KINDAI UNIVERSITY


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KIMURA Yuichi

Profile

FacultyDepartment of Computational Systems Biology / Graduate School of Biology-Oriented Science and Technology
PositionProfessor
Degree
Commentator Guidehttps://www.kindai.ac.jp/meikan/565-kimura-yuuichi.html
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Last Updated :2020/09/30

Education and Career

Education

  • Waseda University
  • Graduate School of Waseda University
  •   1980 04  - 1984 03 , Waseda University, School of Science and Engineering
  •   1984 04  - 1989 03 , Waseda University, Graduate School of Science and Engineering

Academic & Professional Experience

  •   2017 10 ,  - 現在, Yokohama City University
  •   2013 04 ,  - 現在, Professor, Department of Computational Systems Biology, Faculty of Biology-Oriented Science and Technology, Kindai University
  •   2007 04 ,  - 2013 03 , National Institute of Radiological Sciences
  •   1999 02 ,  - 1999 08 , Tokyo Medical and Dental University
  •   1994 08 ,  - 1999 01 , Tokyo Medical and Dental University
  •   1991 04 ,  - 1994 07 , College of Industrial Technology, Nihon University
  •   1988 04 ,  - 1991 03 , School of Science and Engineering, Waseda University
  • Nihon University
  • Waseda University
  •   1999 , Senior research scientist, Tokyo Metropolitan
  •   1999 , Associate Professor, Institute for Medical and
  •   1994 , Research associate, Institute for Medical and
  •   1991 , Research associate, School of Industrial Engineering,
  •   1988 , Research associate, School of Science and Engineering,
  • Institute of Gerontology
  • Dental Engineering, Tokyo Medical and Denial University
  • Dental Engineering, Tokyo Medical and Dental University

Research Activities

Research Areas

  • Life sciences, Radiology
  • Manufacturing technology (mechanical, electrical/electronic, chemical engineering), Measurement engineering
  • Life sciences, Medical systems
  • Life sciences, Biomaterials
  • Life sciences, Biomedical engineering

Research Interests

  • kinetics analysis, molecular imaging, positron emission tomography, nuclear medicine

Published Papers

  • Dynamic PET Image Reconstruction Using Nonnegative Matrix Factorization Incorporated with Deep Image Prior, Tatsuya Yokota, Kazuya Kawai, Muneyuki Sakata, Yuichi Kimura, Hidekata Hontani, International Conference on Computer Vision, International Conference on Computer Vision, Oct. 27 2019 , Refereed
  • Micro-Liter Order Automatic Blood Sampling System for Fully Quantitative Analysis of Small Animal PET, Akinori Takenaka, Yoshitaka Inui, Yuichi Kimura, Chikara Miyake, Yoichi Fujiyama, Takashi Yamada, obuya Hashizume, Takashi Kato, Kengo Ito, Hiroshi Toyama, Annals of Nuclear Medicine, Annals of Nuclear Medicine, 33(8), 586 - 593, Aug. 2019 , Refereed
  • Quantitative Cosmetic Evaluation of Long-Lasting Foundation Using Multispectral Imaging, NAGAOKA Takashi, KIMURA Yuichi, Skin Research Technology, Skin Research Technology, 25(3), 318 - 324, Dec. 2018 , Refereed
  • Simultaneous PET Image reconstruction and Feature Extraction Method Using Non-negative, Smooth, and Sparse Matrix Factorization, K. Kawai, H. Hontani, T. Yokota, M. Sakata, Y. Kimura, Proceedings of APSIPA-ASC 2018, Proceedings of APSIPA-ASC 2018, Nov. 2018 , Refereed
  • A Robust PET Image Reconstruction using Constrained Non-negative Matrix Factorization, K. Kawai, J. Yamada, H. Hontani, T. Yokota, M. Sakata, Y. Kimura, Proceedings of the Asia-Pacific Signal and Information Processing Association Annual Summit and Conference (APSIPA ASC), Proceedings of the Asia-Pacific Signal and Information Processing Association Annual Summit and Conference (APSIPA ASC), Dec. 15 2017 , Refereed
  • Full quantification of CMRGlc of small animals with arterial blood sampling using the new system of CD-Well, Kimura Yuichi, Yamada Takashi, Hashizume Nobuya, Nomura Masahiko, Ota Seiichiro, Kitamura Keishi, Toyama Hiroshi, JOURNAL OF NUCLEAR MEDICINE, JOURNAL OF NUCLEAR MEDICINE, 55(22), 7889 - 7903, May 2014 , Refereed
  • Validation of a First Block-Iterative Spatio-Temporal Reconstruction Algorithm with Small Animal Dynamic PET Data, Tatsuya Kon, Takashi Obi, Muneyuki Sakata, Nagaaki Ohyama, Yuichi Kimura, Adv Biomed Eng, Adv Biomed Eng, 3, 7 - 13, 2014 , Refereed
  • Guidelines for clinical use of FDG PET, PET/CT 2012, 細野 眞, 佐賀 恒夫, 伊藤 健吾, 汲田 伸一郎, 佐々木 雅之, 千田 道雄, 畑澤 順, 渡邉 浩, 伊藤 浩, 金谷 信一, 木村 裕一, 佐治 英郎, 陣之内 正史, 福喜多 博義, 村上 康二, 絹谷 清剛, 山崎 純一, 内山 眞幸, 宇野 公一, 加藤 克彦, 川野 剛, 日下部 きよ子, 窪田 和雄, 戸川 貴史, 本田 憲業, 丸野 廣大, 吉村 真奈, 宍戸 文男, 井上 登美夫, 福田 寛, 中村 佳代子, Jpn J Nucl Med (Kaku Igaku), Jpn J Nucl Med (Kaku Igaku), 49(4), 391 - 401, Nov. 30 2012
  • Differential effects of age on human striatal adenosine A1 and A2A receptors, Masahiro Mishina, Yuichi Kimura, Mika Naganawa, Kenji Ishii, Keiichi Oda, Muneyuki Sakata, Jun Toyohara, Shiro Kobayashi, Yasuo Katayama, Kiichi Ishiwata, SYNAPSE, SYNAPSE, 66(9), 832 - 839, Sep. 2012 , Refereed
    Summary:The aim of this study was to investigate the effect of age on the distribution of adenosine A1 receptors (A1Rs) and adenosine A2A receptors (A2ARs) in the striatum of healthy subjects using PET imaging with 8-dicyclopropylmethyl-1-[11C]methyl-3-propylxanthine ([11C]MPDX) and [7-methyl-11C]-(E)-8-(3,4,5-trimethoxystyryl)-1,3,7-trimethylxanthine ([11C]TMSX), respectively. We recruited 8 young (22.0 +/- 1.7 years) and 10 elderly (65.4 +/- 7.6 years) volunteers to undergo [11C]MPDX PET scanning, and 11 young (22.7 +/- 2.7 years) and six elderly (60.7 +/- 8.5 years) volunteers to undergo [11C]TMSX PET scanning. A dynamic series of decay-corrected PET scans was performed for 60 min following injection of [11C]MPDX or [11C]TMSX. We calculated the binding potential (BPND) of [11C]MPDX and distribution volume ratio (DVR) of [11C]TMSX in the striatum. The BPND of [11C]MPDX was significantly lower in elderly than in young subjects, both in the putamen and head of the caudate nucleus. The BPND was negatively correlated with age in both the putamen and the head of the caudate nucleus. However, no difference was found between the DVR of [11C]TMSX in the striata of young and elderly subjects, nor was there a correlation between age and the DVR of [11C]TMSX. The effect of age on the distribution of A1Rs in the human striatum described herein is similar to previous reports of age-related decreases in dopamine D1 and D2 receptors. Unlike A1Rs, however, this study suggests that the distribution of A2ARs does not change with age. Synapse 66:832839, 2012. (c) 2012 Wiley Periodicals, Inc.
  • Striatal and extrastriatal dopamine D-2 receptor occupancy by the partial agonist antipsychotic drug aripiprazole in the human brain: a positron emission tomography study with [C-11]raclopride and [C-11]FLB457, Keisuke Takahata, Hiroshi Ito, Harumasa Takano, Ryosuke Arakawa, Hironobu Fujiwara, Yasuyuki Kimura, Fumitoshi Kodaka, Takeshi Sasaki, Tsuyoshi Nogami, Masayuki Suzuki, Tomohisa Nagashima, Hitoshi Shimada, Motoichiro Kato, Masaru Mimura, Tetsuya Suhara, PSYCHOPHARMACOLOGY, PSYCHOPHARMACOLOGY, 222(1), 165 - 172, Jul. 2012 , Refereed
    Summary:Second-generation antipsychotics demonstrate clinical efficacy with fewer extrapyramidal side effects compared with first-generation antipsychotics. One of the proposed explanations is the hypothesis of preferential extrastriatal dopamine D-2 receptor occupancy (limbic selectivity) by antipsychotics. In the present study, we focused on aripiprazole, which has a unique pharmacological profile with partial agonism at dopamine D-2 receptors and the minimal risk of extrapyramidal side effects. Previous positron emission tomography (PET) studies using high-affinity radioligands for dopamine D-2 receptors have reported inconsistent results regarding regional differences of dopamine D-2 receptor occupancy by aripiprazole. To test the hypothesis of preferential binding to extrastriatal dopamine D-2 receptors by aripiprazole, we investigated its regional dopamine D-2 receptor occupancies in healthy young subjects. Using PET and two radioligands with different affinities for dopamine D-2 receptors, [C-11]raclopride and [C-11]FLB457, striatal and extrastriatal dopamine D-2 receptor bindings at baseline and after oral administration of 6 mg aripiprazole were measured in 11 male healthy subjects. Our data showed that dopamine D-2 receptor occupancies in the striatum measured with [C-11]raclopride were 70.1% and 74.1%, with the corresponding values for the extrastriatal regions measured with [C-11]FLB457 ranging from 46.6% to 58.4%. In the present study, preferential extrastriatal dopamine D-2 receptor occupancy by aripiprazole was not observed. Our data suggest partial agonism at dopamine D-2 receptors is the most likely explanation for the minimal risk of extrapyramidal side effects in the treatment by aripiprazole.
  • MAP-Based Denoising of Dynamic PET Data for Quantitative Receptor Imaging, N. Hoshino, H. Hontani, K. Sakaguchi, M. Sakata, K. Ishiwata, Y. Kimura, SPIE Medical Imaging Conference, SPIE Medical Imaging Conference, Feb. 04 2011 , Refereed
  • Denoising for PET Dynamic Data using Parametric Eigenspace, N. Hoshino, H. Hontani, K. Sakaguchi, M. Sakata, K. Ishiwata, Y. Kimura, 28(5), 362 - 370, Nov. 2010 , Refereed
  • [11C]BF-227を用いた脳内アミロイド蓄積に関する動脈採血データを用いた定量解析, 田代学, 岡村信行, 熊谷和明, 古本祥三, 船木善仁, 木村裕一, 岩田錬, 工藤幸司, 渡部浩司, 荒井啓行, 谷内一彦, 核医学, 核医学, 46(3), 262 - 262, Sep. 2009
  • PET pharmacokinetic analysis to estimate boron concentration in tumor and brain as a guide to plan BNCT for malignant cerebral glioma., Tadashi Nariai, Kiichi Ishiwata, Yuichi Kimura, Motoki Inaji, Toshiya Momose, Tetsuya Yamamoto, Akira Matsumura, Kenji Ishii, Kikuo Ohno, Appl Radiat Isot, Appl Radiat Isot, 67(7-8 Suppl), S348 - S350, Jul. 2009
    Summary:To plan the optimal BNCT for patients with malignant cerebral glioma, estimation of the ratio of boron concentration in tumor tissue against that in the surrounding normal brain (T/N ratio of boron) is important. We report a positron emission tomography (PET) imaging method to estimate T/N ratio of tissue boron concentration based on pharmacokinetic analysis of amino acid probes.
    Twelve patients with cerebral malignant glioma underwent 60 min dynamic PET scanning of brain after bolus injection of (18)F-borono-phenyl-alanine (FBPA) with timed arterial blood sampling. Using kinetic parameter obtained by this scan, T/N ratio of boron concentration elicited by one-hour constant infusion of BPA, as performed in BNCT, was simulated on Runge-Kutta algorithm. (11)C-methionine (MET) PET scan, which is commonly used in worldwide PET center as brain tumor imaging tool, was also performed on the same day to compare the image characteristics of FBPA and that of MET.
    PET glioma images obtained with FBPA and MET are almost identical in all patients by visual inspection. Estimated T/N ratio of tissue boron concentration after one-hour constant infusion of BPA, T/N ratio of FBPA on static condition
  • DPAA等有機ヒ素化合物ばく露者における脳ポジトロンCT(PET)の解析に関する研究, 石井賢二, 織田圭一, 木村裕一, 石渡喜一, 川崎敬一, 斎藤陽子, 石井一弘, 平成17年度ジフェニルアルシン酸等の健康影響に関する調査研究」研究報告, 平成17年度ジフェニルアルシン酸等の健康影響に関する調査研究」研究報告, 81-85, Jan. 2006 , Refereed
  • Imaging detailed glucose metabolism in the brain using MAP estimation in Positron Emission Tomography., Kimura Y, Naganawa M, Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference, Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference, 5, 4477 - 4479, 2005 , Refereed
  • Regional differences in blood flow and oxygen consumption in exercised muscle and their relationship curing recovery from exhausive exercise, Masaki Mizuno, Yuichi Kimura, Takashi Iwakawa, Keiichi Oda, Kenji Ishii, Kiichi Ishiwata, Yoshio Nakamura, Isao Muraoka, J. of. Appl Physiol, J. of. Appl Physiol, 53, 467 - 470, 2003
  • [Three-dimensional projection display of striatum dopamine function measured by PET]., Oda K, Ishii K, Kimura Y, Ishiwata K, Nihon Hoshasen Gijutsu Gakkai zasshi, Nihon Hoshasen Gijutsu Gakkai zasshi, 58(12), 1573 - 1578, Dec. 2002 , Refereed
  • Generation of Fractal Dimension Images and its Application to Automatic Edge Detection in Brain MRI, Kouji Uemura, Hinako Toyama, Shigeyuki Baba, Yuichi Kimura, Michio Senda, Akihiko Uchiyama, Comp Med Image Graph, Comp Med Image Graph, 24(73), 85, 2000 , Refereed
  • Assesment of Glucose Metabolism in Exercised Muscle with Positron Emission Tomography, Kazunobu Ohmori, Shin-ya Kuno, Yuichi Kimura, Masaki Mizuno, Yoshio Nakamura, Isao Muraoka, Fukio Ohta, Masahiro Mishina, Hinako Toyama, Michio Senda, Adv Exerc Sports Physiol, Adv Exerc Sports Physiol, 6(3), 81 - 84, 2000 , Refereed
  • 一様吸収体における2 次元PET 画像の統計ノイズ特性に関す る分析, 14(1), 107 - 114, 1996 , Refereed
  • Detection of Respiratory Sinus Arrhythmia by Using Adaptive Filter, Tosiaki Yamanouchi, Akihiko Uchiyama, Yuichi Kimura, Yosio Nakamura, Japanese journal of medical electronics and biological engineering, Japanese journal of medical electronics and biological engineering, 31(1), 18 - 24, 1993 , Refereed
    Summary:A method for detecting respiratory sinus arrhythmia (RSA) by using an adaptive filter is proposed. RSA is a correlative component to breath which is comprised in a heart rate fluctuation. Since the spectrum of the breath changes with respiratory rate, methods that assume statistical stationarity, e.g. FFT, cannot detect RSA precisely under free breath. So we have adopted an adaptive filter which has two inputs. One is a primary input to which an interval between successive R-wave in ECG is applied. The other is a reference input to which a respiratory signal, such as chest movement or respiratory flow rate, is applied. This filter extracts correlated component to the reference signal in the primary input. A remarkable merit of an adaptive filter is a tracking capability, such as the characteristics are followed to input signal, even if power spectrum of the signal changes slowly with time. In this paper, a least mean square algorithm is used to control the filter because of its simplicity. There are two parameters to be decided for the adaptive filter. One is dimension n, and the other is convergent parameter µ. These parameters must be optimized, because they affect to tracking speed and error. A small µ causes slow tracking characteristics with small error. A large µ brings fast tracking speed with large error. As a result of simulation, we can conclude that the optimal µl is obtained by 1/(‘power of reference input’ x70x w). To test the filter characteristics, change of RSA during exercise of bicycle ergometer and that with posture characteristics were measured under free breath. The results of experiments have shown that the proposed method is effective for the estimation of RSA. © 1993, Japanese Society for Medical and Biological Engineering. All rights reserved.
  • Regional Gray-Matter-Dedicated SUVR with 3D-MRI Detects Positive Amyloid Deposits in Equivocal Amyloid PET Images, Kazunari Ishii, Takahiro Yamada, Kohei Hanaoka, Hayato Kaida, Koichi Miyazaki, Masami Ueda, Kazushi Hanada, Kazumasa Saigoh, Julia Sauerbeck, Axel Rominger, Peter Bartenstein, Yuichi Kimura, Annals of Nuclear Medicine, Annals of Nuclear Medicine, 34(10), 0 - 0, Sep. 2020 , Refereed
    Summary:in press. Accepted on July 27, 2020.
  • AI approach of cycle-consistent generative adversarial networks to synthesize PET images to train computer-aided diagnosis algorithm for dementia., Yuichi Kimura, Aya Watanabe, Takahiro Yamada, Shogo Watanabe, Takashi Nagaoka, Mitsutaka Nemoto, Koichi Miyazaki, Kohei Hanaoka, Hayato Kaida, Kazunari Ishii, Annals of nuclear medicine, Annals of nuclear medicine, 34(7), 512 - 515, Jul. 2020 , Refereed
    Summary:OBJECTIVE: An artificial intelligence (AI)-based algorithm typically requires a considerable amount of training data; however, few training images are available for dementia with Lewy bodies and frontotemporal lobar degeneration. Therefore, this study aims to present the potential of cycle-consistent generative adversarial networks (CycleGAN) to obtain enough number of training images for AI-based computer-aided diagnosis (CAD) algorithms for diagnosing dementia. METHODS: We trained CycleGAN using 43 amyloid-negative and 45 positive images in slice-by-slice. RESULTS: The CycleGAN can be used to synthesize reasonable amyloid-positive images, and the continuity of slices was preserved. DISCUSSION: Our results show that CycleGAN has the potential to generate a sufficient number of training images for CAD of dementia.
  • Automatic Diagnosis of melanoma using Hyperspectral data and GoogLeNet, Ginji Hirano, Mitsutaka Nemoto, Yuichi Kimura, Yoshio Kiyohara, Hiroshi Koga, Naoya Yamazaki, Gustav Christensen, Christian Ingvar, Kari Nielsen, Atsushi Nakamura, Takayuki Sota, Takashi Nagaoka, Skin Research and Technology, Skin Research and Technology, Jun. 2020 , Refereed
    Summary:Published online 2020/6/25.
  • A strategy to account for noise in the X-variable to reduce underestimation in Logan graphical analysis for quantifying receptor density in positron emission tomography., Paulus K Shigwedha, Takahiro Yamada, Kohei Hanaoka, Kazunari Ishii, Yuichi Kimura, Yutaka Fukuoka, BMC medical imaging, BMC medical imaging, 20(1), 15 - 15, Feb. 10 2020 , Refereed
    Summary:BACKGROUND: The Logan graphical analysis (LGA) algorithm is widely used to quantify receptor density for parametric imaging in positron emission tomography (PET). Estimating receptor density, in terms of the non-displaceable binding potential (BPND), from the LGA using the ordinary least-squares (OLS) method has been found to be negatively biased owing to noise in PET data. This is because OLS does not consider errors in the X-variable (predictor variable). Existing bias reduction methods can either only reduce the bias slightly or reduce the bias accompanied by increased variation in the estimates. In this study, we addressed the bias reduction problem by applying a different regression method. METHODS: We employed least-squares cubic (LSC) linear regression, which accounts for errors in both variables as well as the correlation of these errors. Noise-free PET data were simulated, for 11C-carfentanil kinetics, with known BPND values. Statistical noise was added to these data and the BPNDs were re-estimated from the noisy data by three methods, conventional LGA, multilinear reference tissue model 2 (MRTM2), and LSC-based LGA; the results were compared. The three methods were also compared in terms of beta amyloid (A β) quantification of 11C-Pittsburgh compound B brain PET data for two patients with Alzheimer's disease and differing A β depositions. RESULTS: Amongst the three methods, for both synthetic and actual data, LSC was the least biased, followed by MRTM2, and then the conventional LGA, which was the most biased. Variations in the LSC estimates were smaller than those in the MRTM2 estimates. LSC also required a shorter computational time than MRTM2. CONCLUSIONS: The results suggest that LSC provides a better trade-off between the bias and variability than the other two methods. In particular, LSC performed better than MRTM2 in all aspects; bias, variability, and computational time. This makes LSC a promising method for BPND parametric imaging in PET studies.
  • Automatic delineation algorithm of reference region for amyloid imaging based on kinetics., Takahiro Yamada, Shogo Watanabe, Takashi Nagaoka, Mitsutaka Nemoto, Kohei Hanaoka, Hayato Kaida, Kazunari Ishii, Yuichi Kimura, Annals of nuclear medicine, Annals of nuclear medicine, 34(2), 102 - 107, Feb. 2020 , Refereed
    Summary:OBJECTIVE: This study aims to develop an algorithm named AutoRef to delineate a reference region for quantitative PET amyloid imaging. METHODS: AutoRef sets the reference region automatically using a distinguishing feature in the kinetics of reference region. This is reflected in the shapes of the tissue time activity curve. A statistical shape recognition algorithm of the gaussian mixture model is applied with considering spatial and temporal information on a reference region. We evaluate the BPND with manually set reference region and AutoRef using 86 cases (43 positive cases, 10 equivocal cases, and 33 negative cases) of dynamically scanned 11C-Pittsburgh Compound-B. RESULTS: From the Bland-Altman plot, the difference between two BPND is 0.099 ± 0.21 as standard deviation, and no significant systematic error is observed between the BPND with AutoRef and with manual definition of a reference region. Although a proportional error is detected, it is smaller than the 95% limits of agreement. Therefore, the proportional error is negligibly small. CONCLUSIONS: AutoRef presents the same performance as the manual definition of the reference region. Further, since AutoRef is more algorithmic than the ordinary manual definition of the reference region, there are few operator-oriented uncertainties in AutoRef. We thus conclude that AutoRef can be applied as an automatic delineating algorithm for the reference region in amyloid imaging.
  • Visualization of AMPA receptors in living human brain with positron emission tomography., Tomoyuki Miyazaki, Waki Nakajima, Mai Hatano, Yusuke Shibata, Yoko Kuroki, Tetsu Arisawa, Asami Serizawa, Akane Sano, Sayaka Kogami, Tomomi Yamanoue, Kimito Kimura, Yushi Hirata, Yuuki Takada, Yoshinobu Ishiwata, Masaki Sonoda, Masaki Tokunaga, Chie Seki, Yuji Nagai, Takafumi Minamimoto, Kazunori Kawamura, Ming-Rong Zhang, Naoki Ikegaya, Masaki Iwasaki, Naoto Kunii, Yuichi Kimura, Fumio Yamashita, Masataka Taguri, Hideaki Tani, Nobuhiro Nagai, Teruki Koizumi, Shinichiro Nakajima, Masaru Mimura, Michisuke Yuzaki, Hiroki Kato, Makoto Higuchi, Hiroyuki Uchida, Takuya Takahashi, Nature medicine, Nature medicine, 26(2), 281 - 288, Feb. 2020 , Refereed
    Summary:Although aberrations in the number and function of glutamate AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors are thought to underlie neuropsychiatric disorders, no methods are currently available for visualizing AMPA receptors in the living human brain. Here we developed a positron emission tomography (PET) tracer for AMPA receptors. A derivative of 4-[2-(phenylsulfonylamino)ethylthio]-2,6-difluoro-phenoxyacetamide radiolabeled with 11C ([11C]K-2) showed specific binding to AMPA receptors. Our clinical trial with healthy human participants confirmed reversible binding of [11C]K-2 in the brain according to Logan graphical analysis (UMIN000020975; study design: non-randomized, single arm; primary outcome: dynamics and distribution volumes of [11C]K-2 in the brain; secondary outcome: adverse events of [11C]K-2 during the 4-10 d following dosing; this trial met prespecified endpoints). In an exploratory clinical study including patients with epilepsy, we detected increased [11C]K-2 uptake in the epileptogenic focus of patients with mesial temporal lobe epilepsy, which was closely correlated with the local AMPA receptor protein distribution in surgical specimens from the same individuals (UMIN000025090; study design: non-randomized, single arm; primary outcome: correlation between [11C]K-2 uptake measured with PET before surgery and AMPA receptor protein density examined by biochemical study after surgery; secondary outcome: adverse events during the 7 d following PET scan; this trial met prespecified endpoints). Thus, [11C]K-2 is a potent PET tracer for AMPA receptors, potentially providing a tool to examine the involvement of AMPA receptors in neuropsychiatric disorders.
  • Performance Improvement of Automated Melanoma Diagnosis System by Data Augumentation, Kana Kato, Mitsutaka Nemoto, Yuichi Kimura, Yoshio Kiyohara, Hiroshi Koga, Naoya Yamazaki, Gustav Christensen, Christian Ingvar, Kari Nielsen, Atsushi Nakamura, Takayuki Sota, Takashi Nagaoka, Advanced Biomedical Engineering, Advanced Biomedical Engineering, 9, 62 - 70, Jan. 2020 , Refereed
  • Age-Related Decrease in Male Extra-Striatal Adenosine A(1) Receptors Measured Using C-11-MPDX PET, Masahiro Mishina, Yuichi Kimura, Muneyuki Sakata, Kenji Ishii, Keiichi Oda, Jun Toyohara, Kazumi Kimura, Kiichi Ishiwata, FRONTIERS IN PHARMACOLOGY, FRONTIERS IN PHARMACOLOGY, 8(903), Dec. 2017 , Refereed
    Summary:Adenosine A(1) receptors (A(1)Rs) are widely distributed throughout the entire human brain, while adenosine A(2A) receptors (A(2A)Rs) are present in dopamine-rich areas of the brain, such as the basal ganglia. A past study using autoradiography reported a reduced binding ability of A(1)R in the striatum of old rats. We developed positron emission tomography (PET) ligands for mapping the adenosine receptors and we successfully visualized the A(1)Rs using 8-dicyclopropylmethyl-1-C-11-methyl-3-propylxanthine (C-11-MPDX). We previously reported that the density of A(1)Rs decreased with age in the human striatum, although we could not observe an age-related change in A(2A)Rs. The aim of this study was to investigate the age-related change of the density of A(1)Rs in the thalamus and cerebral cortices of healthy participants using C-11-MPDX PET. We recruited eight young (22.0 +/- 1.7 years) and nine elderly healthy male volunteers (65.7 +/- 8.0 years). A dynamic series of decay-corrected PET scans was performed for 60 min starting with the injection of C-11-MPDX. We placed the circular regions of interest of 10 mm in diameter in C-11-MPDX PET images. The values for the binding potential (BPND) of C-11-MPDX in the thalamus, and frontal, temporal, occipital, and parietal cortices were calculated using a graphical analysis, wherein the reference region was the cerebellum. BPND of C-11-MPDX was significantly lower in elderly participants than young participants in the thalamus, and frontal, temporal, occipital, and parietal cortices. In the human brain, we could observe the age-related decrease in the distribution of A(1)Rs.
  • Parametric PET Image Reconstruction via Regional Spatial Bases and Pharmacokinetic Time Activity Model, Naoki Kawamura, Tatsuya Yokota, Hidekata Hontani, Muneyuki Sakata, Yuichi Kimura, ENTROPY, ENTROPY, 19(11), 629, Nov. 2017 , Refereed
    Summary:It is known that the process of reconstruction of a Positron Emission Tomography (PET) image from sinogram data is very sensitive to measurement noises; it is still an important research topic to reconstruct PET images with high signal-to-noise ratios. In this paper, we propose a new reconstruction method for a temporal series of PET images from a temporal series of sinogram data. In the proposed method, PET images are reconstructed by minimizing the Kullback-Leibler divergence between the observed sinogram data and sinogram data derived from a parametric model of PET images. The contributions of the proposition include the following: (1) regions of targets in images are explicitly expressed using a set of spatial bases in order to ignore the noises in the background; (2) a parametric time activity model of PET images is explicitly introduced as a constraint; and (3) an algorithm for solving the optimization problem is clearly described. To demonstrate the advantages of the proposed method, quantitative evaluations are performed using both synthetic and clinical data of human brains.
  • Adenosine A(1) receptors measured with C-11-MPDX PET in early Parkinson's disease, Masahiro Mishina, Kenji Ishii, Yuichi Kimura, Masahiko Suzuki, Shin Kitamura, Kenji Ishibashi, Muneyuki Sakata, Keiichi Oda, Shiro Kobayashi, Kazumi Kimura, Kiichi Ishiwata, SYNAPSE, SYNAPSE, 71(8), Aug. 2017 , Refereed
    Summary:Adenosine A(1) receptors (A(1)Rs) interact negatively with dopamine D-1 receptors (D(1)Rs) in neurons of the basal ganglia's direct pathway, while adenosine A(2A) receptors (A(2A)Rs) negatively interact with dopamine D-2 receptors (D(2)Rs) in indirect-pathway neurons. The aim of this study was to investigate the cerebral density of A(1)Rs in Parkinson's disease (PD) in its early stages, using PET scans with the radioligand 8-dicyclopropylmethyl-1-C-11-methyl-3-propylxanthine (C-11-MPDX). We studied 10 drug-naive patients with early PD. Each patient was also examined for dopamine transporters (DATs) and D(2)Rs by PET using C-11-2--carbomethoxy-3--(4-fluorophenyl)-tropane (C-11-CFT) and C-11-raclopride (C-11-RAC), respectively. Ten elderly, healthy volunteers were recruited as controls for C-11-MPDX PET scanning and eight elderly volunteers were recruited as controls for C-11-CFT and C-11-RAC PET scanning. The PET scans revealed a decrease in the uptake ratio index (URI) of C-11-CFT and an increase in the URI of C-11-RAC in patients. In the temporal lobe, the binding potential for C-11-MPDX was higher in the patient group than in healthy subjects, but not in the other regions examined, including the striatum. In patients, we observed motor-symptom asymmetry and a relationship between parkinsonism and the striatal density of DATs, but not A(1)R density. In the putamen of early PD, asymmetrical down-regulation of A(2A)Rs is likely a compensatory mechanism in response to a decrease in dopamine. However, our study suggests that A(1)Rs are unaltered in the putamen of early PD.
  • [C-11]TASP457, a novel PET ligand for histamine H-3 receptors in human brain, Yasuyuki Kimura, Chie Seki, Yoko Ikoma, Masanori Ichise, Kazunori Kawamura, Keisuke Takahata, Sho Moriguchi, Tomohisa Nagashima, Tatsuya Ishii, Soichiro Kitamura, Fumitoshi Niwa, Hironobu Endo, Makiko Yamada, Makoto Higuchi, Ming-Rong Zhang, Tetsuya Suhara, EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, 43(9), 1653 - 1663, Aug. 2016 , Refereed
    Summary:Purpose The histamine H-3 receptors are presynaptic neuroreceptors that inhibit the release of histamine and other neurotransmitters. The receptors are considered a drug target for sleep disorders and neuropsychiatric disorders with cognitive decline. We developed a novel PET ligand for the H3 receptors, [C-11]TASP0410457 ([C-11]TASP457), with high affinity, selectivity and favorable kinetic properties in the monkey, and evaluated its kinetics and radiation safety profile for quantifying the H3 receptors in human brain. Methods Ten healthy men were scanned for 120 min with a PET scanner for brain quantification and three healthy men were scanned for radiation dosimetry after injection of 386 +/- 6.2 MBq and 190 +/- 7.5 MBq of [C-11] TASP457, respectively. For brain quantification, arterial blood sampling and metabolite analysis were performed using high-performance liquid chromatography. Distribution volumes (V-T) in brain regions were determined by compartment and graphical analyses using the Logan plot and Ichise multilinear analysis (MA1). For dosimetry, radiation absorbed doses were estimated using the Medical Internal Radiation Dose scheme. Results [C-11] TASP457 PET showed high uptake (standardized uptake values in the range of about 3-6) in the brain and fast washout in cortical regions and slow washout in the pallidum. The two-tissue compartment model and graphical analyses estimated VT with excellent identification using 60 min scan data (about 16 mL/cm(3) in the pallidum, 9-14 in the basal ganglia, 6-9 in cortical regions, and 5 in the pons), which represents the known distribution of histamine H-3 receptors. For parametric imaging, MA1 is recommended because of minimal underestimation with small intersubject variability. The organs with the highest radiation doses were the pancreas, kidneys, and liver. The effective dose delivered by [C-11] TASP457 was 6.9 mu Sv/MBq. Conclusion [C-11] TASP457 is a useful novel PET ligand for the investigation of the density of histamine H3 receptors in human brain.
  • Performance of C-11-Pittsburgh Compound B PET Binding Potential Images in the Detection of Amyloid Deposits on Equivocal Static Images, Chisa Hosokawa, Kazunari Ishii, Yuichi Kimura, Tomoko Hyodo, Makoto Hosono, Kenta Sakaguchi, Kimio Usami, Kenji Shimamoto, Yuzuru Yamazoe, Takamichi Murakami, JOURNAL OF NUCLEAR MEDICINE, JOURNAL OF NUCLEAR MEDICINE, 56(12), 1910 - 1915, Dec. 2015 , Refereed
    Summary:The goal of this study was to clarify whether binding potential (BP) images using C-11-Pittsburgh compound B (C-11-PiB) and dynamic PET can reliably detect cortical amyloid deposits for patients whose C-11-PiB PET static images are ambiguous and whether visual ratings are affected by white matter retention. Methods: Static and BP images were constructed for 85 consecutive patients with cognitive impairment after C-11-PiB dynamic PET. Cortical uptake was visually assessed as positive, negative, or equivocal for both types of images. Quantitatively, the standardized uptake value ratio (SUVR) from the static image, the nondisplaceable BP from the dynamic image for mean gray matter uptake, and the ratio of gray matter uptake to white matter retention were compared among C-11-PiB-positive, C-11-PiB-equivocal, and C-11-PiB-negative groups. Results: Forty-three scans were visually assessed as C-11-PiB-positive in both the static and the BP images. Ten scans were C-11-PiB-equivocal in the static images. In 8 of them, the BP images were C-11-PiB-positive, whereas the other 2 were C-11-PiB-equivocal. Thirty-two scans were assessed as C-11-PiB-negative in the static images. In the BP images, 4 were C-11-PiB-positive and 2 were C-11-PiB-equivocal. The mean gray matter uptake of C-11-PiB in SUVR and nondisplaceable BP, respectively, showed statistically significant differences among the C-11-PiB-positive, C-11-PiB-equivocal, and C-11-PiB-negative groups. The ratio of gray matter uptake to white matter retention was lower in the BP images than static images from the C-11-PiB-negative and C-11-PiB-equivocal groups, whereas it was higher in the C-11-PiB-positive group. Conclusion: C-11-PiB PET BP images can clarify visual interpretation of clinical static C-11-PiB-equivocal images by reducing the interference of nonspecific white matter retention. We conclude that C-11-PiB-equivocal PET findings on static images reflect cortical amyloid deposits, which can be verified using BP images. Furthermore, quantitative assessments, such as SUVR and nondisplaceable BP, are of no use for correctly rating equivocal visual findings.
  • Clinical practice guideline for dedicated breast PET, Makoto Hosono, Tsuneo Saga, Kengo Ito, Shinichiro Kumita, Masayuki Sasaki, Michio Senda, Jun Hatazawa, Hiroshi Watanabe, Hiroshi Ito, Shinichi Kanaya, Yuichi Kimura, Hideo Saji, Seishi Jinnouchi, Hiroyoshi Fukukita, Koji Murakami, Seigo Kinuya, Junichi Yamazaki, Mayuki Uchiyama, Koichi Uno, Katsuhiko Kato, Tsuyoshi Kawano, Kazuo Kubota, Takashi Togawa, Norinari Honda, Hirotaka Maruno, Mana Yoshimura, Masami Kawamoto, Yukihiko Ozawa, ANNALS OF NUCLEAR MEDICINE, ANNALS OF NUCLEAR MEDICINE, 28(6), 597 - 602, Jul. 2014 , Refereed
  • Comparison between SUV and BP images acquired using 11C-PIB PET: Questionable PIB accumulation in SUV images, Chisa Hosokawa, Kazunari Ishii, Yuichi Kimura, Kenta Sakaguchi, Makoto Hosono, Takamichi Murakami, JOURNAL OF NUCLEAR MEDICINE, JOURNAL OF NUCLEAR MEDICINE, 55, May 2014 , Refereed
  • Assessment of participant compliance with a Web-based home healthcare system for promoting specific health checkups, Toshiyo Tamura, Sohichi Maeno, Takumu Hattori, Yutaka Kimura, Yuichi Kimura, Masaki Yoshida, Kotaro Minato, BIOCYBERNETICS AND BIOMEDICAL ENGINEERING, BIOCYBERNETICS AND BIOMEDICAL ENGINEERING, 34(1), 63 - 69, 2014 , Refereed
    Summary:We investigated the effectiveness of a Web-based healthcare system that allows participants to record measurements of blood pressure, body weight, and the number of steps walked per day. After receiving a medical examination, participants were registered on the Web-based system and encouraged to record data. A total of 223 participants initiated contact with the system; however, only 27 monitored their blood pressure on more than 60 days during the 3-month period. Furthermore, only 46 participants monitored their body weight, and 79 monitored the number of steps taken per day. Although specific health checkups are important to prevent diseases, we conclude that existing health checkup monitoring is not sufficient, and we should develop a new Web-based health checkup and monitoring system that is more familiar to the participants. (C) 2013 Nalecz Institute of Biocybernetics and Biomedical Engineering. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.
  • A gait abnormality measure based on root mean square of trunk acceleration, Masaki Sekine, Toshiyo Tamura, Masaki Yoshida, Yuki Suda, Yuichi Kimura, Hiroaki Miyoshi, Yoshifumi Kijima, Yuji Higashi, Toshiro Fujimoto, JOURNAL OF NEUROENGINEERING AND REHABILITATION, JOURNAL OF NEUROENGINEERING AND REHABILITATION, 10, 118, Dec. 2013 , Refereed
    Summary:Background: Root mean square (RMS) of trunk acceleration is seen frequently in gait analysis research. However, many studies have reported that the RMS value was related to walking speed. Therefore, the relationship between the RMS value and walking speed should be considered when the RMS value is used to assess gait abnormality. We hypothesized that the RMS values in three sensing axes exhibit common proportions for healthy people if they walk at their own preferred speed and that the RMS proportions in abnormal gait deviate from the common proportions. In this study, we proposed the RMS ratio (RMSR) as a gait abnormality measure and verified its ability to discriminate abnormal gait. Methods: Forty-seven healthy male subjects (24-49 years) were recruited to examine the relationship between walking speed and the RMSR. To verify its ability to discriminate abnormal gait, twenty age-matched male hemiplegic patients (30-48 years) participated as typical subjects with gait abnormality. A tri-axial accelerometer was attached to their lower back, and they walked along a corridor at their own preferred speed. We defined the RMSR as the ratio between RMS in each direction and the RMS vector magnitude. Results: In the healthy subjects, the RMS in all directions related to preferred walking speed. In contrast, RMSR in the mediolateral (ML) direction did not correlate with preferred walking speed (rs = -0.10, p = 0.54) and represented the similar value among the healthy subjects. Moreover, the RMSR in the ML direction for the hemiplegic patients was significantly higher than that for the healthy subjects (p < 0.01). Conclusions: These results suggest that the RMSR in the ML direction exhibits a common value when healthy subjects walk at their own preferred speed, even if their preferred walking speed were different. For subjects with gait abnormality, the RMSR in the ML direction deviates from the common value of healthy subjects. The RMSR in the ML direction may potentially be a quantitative measure of gait abnormality.
  • A gait abnormality measure based on root mean square of trunk acceleration, Masaki Sekine, Toshiyo Tamura, Masaki Yoshida, Yuki Suda, Yuichi Kimura, Hiroaki Miyoshi, Yoshifumi Kijima, Yuji Higashi, Toshiro Fujimoto, JOURNAL OF NEUROENGINEERING AND REHABILITATION, JOURNAL OF NEUROENGINEERING AND REHABILITATION, 10(118), 1 - 7, Dec. 2013 , Refereed
    Summary:Background: Root mean square (RMS) of trunk acceleration is seen frequently in gait analysis research. However, many studies have reported that the RMS value was related to walking speed. Therefore, the relationship between the RMS value and walking speed should be considered when the RMS value is used to assess gait abnormality. We hypothesized that the RMS values in three sensing axes exhibit common proportions for healthy people if they walk at their own preferred speed and that the RMS proportions in abnormal gait deviate from the common proportions. In this study, we proposed the RMS ratio (RMSR) as a gait abnormality measure and verified its ability to discriminate abnormal gait. Methods: Forty-seven healthy male subjects (24-49 years) were recruited to examine the relationship between walking speed and the RMSR. To verify its ability to discriminate abnormal gait, twenty age-matched male hemiplegic patients (30-48 years) participated as typical subjects with gait abnormality. A tri-axial accelerometer was attached to their lower back, and they walked along a corridor at their own preferred speed. We defined the RMSR as the ratio between RMS in each direction and the RMS vector magnitude. Results: In the healthy subjects, the RMS in all directions related to preferred walking speed. In contrast, RMSR in the mediolateral (ML) direction did not correlate with preferred walking speed (rs = -0.10, p = 0.54) and represented the similar value among the healthy subjects. Moreover, the RMSR in the ML direction for the hemiplegic patients was significantly higher than that for the healthy subjects (p < 0.01). Conclusions: These results suggest that the RMSR in the ML direction exhibits a common value when healthy subjects walk at their own preferred speed, even if their preferred walking speed were different. For subjects with gait abnormality, the RMSR in the ML direction deviates from the common value of healthy subjects. The RMSR in the ML direction may potentially be a quantitative measure of gait abnormality.
  • Novel system using microliter order sample volume for measuring arterial radioactivity concentrations in whole blood and plasma for mouse PET dynamic study, Yuichi Kimura, Chie Seki, Nobuya Hashizume, Takashi Yamada, Hidekatsu Wakizaka, Takahiro Nishimoto, Kentaro Hatano, Keishi Kitamura, Hiroshi Toyama, Iwao Kanno, PHYSICS IN MEDICINE AND BIOLOGY, PHYSICS IN MEDICINE AND BIOLOGY, 58(22), 7889 - 7903, Nov. 2013 , Refereed
    Summary:This study aimed to develop a new system, named CD-Well, for mouse PET dynamic study. CD-Well allows the determination of time-activity curves (TACs) for arterial whole blood and plasma using 2-3 mu L of blood per sample; the minute sample size is ideal for studies in small animals. The system has the following merits: (1) measures volume and radioactivity of whole blood and plasma separately; (2) allows measurements at 10 s intervals to capture initial rapid changes in the TAC; and (3) is compact and easy to handle, minimizes blood loss from sampling, and delay and dispersion of the TAC. CD-Well has 36 U-shaped channels. A drop of blood is sampled into the opening of the channel and stored there. After serial sampling is completed, CD-Well is centrifuged and scanned using a flatbed scanner to define the regions of plasma and blood cells. The length measured is converted to volume because the channels have a precise and uniform cross section. Then, CD-Well is exposed to an imaging plate to measure radioactivity. Finally, radioactivity concentrations are computed. We evaluated the performance of CD-Well in in vitro measurement and in vivo F-18-fluorodeoxyglucose and [C-11] 2-carbomethoxy-3 beta-(4-fluorophenyl) tropane studies. In in vitro evaluation, per cent differences (mean +/- SE) from manual measurement were 4.4 +/- 3.6% for whole blood and 4.0 +/- 3.5% for plasma across the typical range of radioactivity measured in mouse dynamic study. In in vivo studies, reasonable TACs were obtained. The peaks were captured well, and the time courses coincided well with the TAC derived from PET imaging of the heart chamber. The total blood loss was less than 200 mu L, which had no physiological effect on the mice. CD-Well demonstrates satisfactory performance, and is useful for mouse PET dynamic study.
  • Test-retest reproducibility of dopamine D-2/3 receptor binding in human brain measured by PET with [C-11]MNPA and [C-11]raclopride, Fumitoshi Kodaka, Hiroshi Ito, Yasuyuki Kimura, Saori Fujie, Harumasa Takano, Hironobu Fujiwara, Takeshi Sasaki, Kazuhiko Nakayama, Christer Halldin, Lars Farde, Tetsuya Suhara, EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, 40(4), 574 - 579, Apr. 2013 , Refereed
    Summary:Dopamine D-2/3 receptors (D(2/3)Rs) have two affinity states for endogenous dopamine, referred to as high-affinity state (D-2/3 (HIGH)), which has a high affinity for endogenous dopamine, and low-affinity state (D-2/3 (LOW)). The density of D-2/3 (HIGH) can be measured with (R)-2-(CH3O)-C-11-N-n-propylnorapomorphine ([C-11]MNPA), while total density of D-2/3 (HIGH) and D-2/3 (LOW) (D(2/3)Rs) can be measured with [C-11]raclopride using positron emission tomography (PET). Thus, the ratio of the binding potential (BP) of [C-11]MNPA to that of [C-11]raclopride ([C-11]MNPA/[C-11]raclopride) may reflect the proportion of the density of D-2/3 (HIGH) to that of D(2/3)Rs. In the caudate and putamen, [C-11]MNPA/[C-11]raclopride reflects the proportion of the density of D-2 (HIGH) to that of D(2)Rs. To evaluate the reliability of the PET paradigm with [C-11]MNPA and [C-11]raclopride, we investigated the test-retest reproducibility of non-displaceable BP (BP (ND)) measured with [C-11]MNPA and of [C-11]MNPA/[C-11]raclopride in healthy humans. Eleven healthy male volunteers underwent two sets of PET studies on separate days that each included [C-11]MNPA and [C-11]raclopride scans. BP (ND) values in the caudate and putamen were calculated. Test-retest reproducibility of BP (ND) of [C-11]MNPA and [C-11]MNPA/[C-11]raclopride was assessed by intra-subject variability (absolute variability) and test-retest reliability (intraclass correlation coefficient: ICC). The absolute variability of [C-11]MNPA BP (ND) was 5.30 +/- 3.96 % and 12.3 +/- 7.95 % and the ICC values of [C-11]MNPA BP (ND) were 0.72 and 0.82 in the caudate and putamen, respectively. The absolute variability of [C-11]MNPA/[C-11]raclopride was 6.11 +/- 3.68 % and 11.60 +/- 5.70 % and the ICC values of [C-11]MNPA/[C-11]raclopride were 0.79 and 0.80 in the caudate and putamen, respectively. In the present preliminary study, the test-retest reproducibility of BP (ND) of [C-11]MNPA and of [C-11]MNPA/[C-11]raclopride was reliable in the caudate and putamen.
  • Superiority illusion arises from resting-state brain networks modulated by dopamine, Makiko Yamada, Lucina Q. Uddin, Hidehiko Takahashi, Yasuyuki Kimura, Keisuke Takahata, Ririko Kousa, Yoko Ikoma, Yoko Eguchi, Harumasa Takano, Hiroshi Ito, Makoto Higuchi, Tetsuya Suhara, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 110(11), 4363 - 4367, Mar. 2013 , Refereed
    Summary:The majority of individuals evaluate themselves as superior to average. This is a cognitive bias known as the "superiority illusion." This illusion helps us to have hope for the future and is deep-rooted in the process of human evolution. In this study, we examined the default states of neural and molecular systems that generate this illusion, using resting-state functional MRI and PET. Resting-state functional connectivity between the frontal cortex and striatum regulated by inhibitory dopaminergic neurotransmission determines individual levels of the superiority illusion. Our findings help elucidate how this key aspect of the human mind is biologically determined, and identify potential molecular and neural targets for treatment for depressive realism.
  • A wearable motion sensor for evaluating walking performance in Parkinson’s disease with treatments, Toshiyo Tamura, Yuki Suda, Masaki Sekine, Yuichi Kimura, Tomoyuki Uchiyama, Biosystems and Biorobotics, Biosystems and Biorobotics, 1, 717 - 720, 2013 , Refereed
    Summary:A new treatment, deep brain stimulation (DBS), is available for the management Parkinson’s disease. However, the assessment of its efficacy is limited by the inadequacies of current methods. The present study was performed to develop and validate a portable device capable of objectively measuring the performance and therapeutic efficiency of Parkinson’s disease by walking performance. The developed wearable motion sensor with accelerometer and gyro sensor was used to measure walking performance under DBS-off, DBS-on, and medication conditions. The root mean square (RMS) and coefficient of variations (CV) of acceleration signals were compared between controls and patients with medication. The results indicated significantly improved walking balance after medication. DBS-on improved performance but the effect was not statistically significant.
  • Human Brain Imaging of Adenosine Receptors, Masahiro Mishina, Yuichi Kimura, Kiich Ishiwata, Imaging of the Human Brain in Health and Disease, Imaging of the Human Brain in Health and Disease, 161 - 186, 2013 , Refereed
    Summary:Adenosine is an endogenous modulator of various physiological functions mediated by adenosine receptors (ARs). Advances in radiotracer chemistry have led to the development of novel imaging probes for ARs, especially adenosine A< inf> 1< /inf> and A< inf> 2A< /inf> receptors. In this review, we discuss (1) functions of adenosine and ARs in the central nervous system (2) brain imaging for ARs, including postmortem studies and positron emission tomography (3) comparison of radioligands for AR imaging in health and diseases and (4) kinetic analysis for quantitative AR imaging. © 2014 Elsevier Inc. All rights reserved.
  • Application of a pedometer in a clinical setting: is the number of walking steps predictive of changes in blood pressure?, Toshiyo Tammura, Soichi Maeno, Yutaka Kimira, Takumu Hattori, Yuichi Kimura, Kotaro Minato, 2013 IEEE INTERNATIONAL CONFERENCE ON BODY SENSOR NETWORKS (BSN), 2013 IEEE INTERNATIONAL CONFERENCE ON BODY SENSOR NETWORKS (BSN), 1 - 4, 2013 , Refereed
    Summary:A pedometer is a popular wearable sensor used to enumerate walking steps taken per day and in this way determines the approximate distance traveled. In this study, we used blood pressure and walking step data, obtained from 48 patients in a home healthcare system, to investigate the effectiveness of the pedometer in a clinical setting. Changes in blood pressure and walking steps per day were compared. Our results indicate that walking, as a regular form of exercise, contributed to lowering of blood pressure. Thus the pedometer is useful for improving the quality of life of patients in the home healthcare setting
  • Feedback-controlled bolus plus infusion (FC-B/I) method for quantitative drug assessment in living brain with PET, Hiroyuki Ohba, Norihiro Harada, Shingo Nishiyama, Takeharu Kakiuchi, Yuichi Kimura, Hideo Tsukada, JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 33(1), 85 - 90, Jan. 2013 , Refereed
    Summary:We have developed a feedback-controlled bolus plus infusion (FC-B/I) method for monitoring the interaction between positron emission tomography (PET) ligands and their specific target molecules with PET. The usefulness of the FC-B/I method was evaluated by the direct interaction between [C-11]raclopride, a dopamine D-2 receptor (D2R) ligand, and cold raclopride (10 and 100 mu g/kg) in the brains of conscious monkeys. The present results demonstrated that the FC-B/I method could achieve the equilibrium state of [C-11]raclopride in the striatum of monkey brain, and also that the cold raclopride-induced reduction of [C-11]raclopride binding to D2R was observed in a dose-dependent manner. Good correlations of distribution volume ratio of the striatum to cerebellum between the conventional bolus plus infusion (B/I) method and the FC-B/I method as well as between the conventional bolus injection method and the FC-B/I method were observed. These results indicated that the system could be a useful tool for the evaluation of interaction between drug candidates and their target molecules like enzymes, receptors, and transporters by using of their specific PET ligands. Journal of Cerebral Blood Flow & Metabolism (2013) 33, 85-90; doi:10.1038/jcbfm.2012.134; published online 12 September 2012
  • Increased Adenosine A(1) Receptor Levels in Hemianopia Patients After Cerebral Injury An Application of PET Using C-11-8-Dicyclopropylmethyl-1-Methyl-3-Propylxanthine, Yukihisa Suzuki, Tadashi Nariai, Motohiro Kiyosawa, Manabu Mochizuki, Yuichi Kimura, Keiichi Oda, Kenji Ishii, Kiich Ishiwata, CLINICAL NUCLEAR MEDICINE, CLINICAL NUCLEAR MEDICINE, 37(12), 1146 - 1151, Dec. 2012 , Refereed
    Summary:Purpose: The aim of this study was to apply positron emission tomography (PET) with C-11-8-dicyclopropylmethyl-1-methyl-3-propylxanthine (MPDX), a radioligand for adenosine A(1) receptor (A1R), to patients with hemianopia caused by brain injury to study neurorepair mechanisms in the brain. Patients and Methods: Four patients with homonymous hemianopia and 15 healthy subjects were examined using PET to measure cerebral glucose metabolism, C-11-flumazenil (FMZ) binding to the central benzodiazepine receptor, and MPDX binding to A1R. Left and right regions of interest (ROIs) were selected, and semiquantitative data on the 3 kinds of PET examinations were obtained. The ROIs were referenced using the data for homologous regions in the contralateral hemisphere [ipsilateral/contralateral (I/C) ratio]. Results: The I/C ratios for cerebral glucose metabolism and FMZ binding were low in the primary visual cortex (PVC) and visual association cortex in all the patients, whereas MPDX binding increased in the PVC in patients 1 and 2. Patients 1 and 2 experienced improvement in their visual field after 1 year. However, the other 2 patients showed no changes. We observed an increase in MPDX binding to A1R in the injured portion of the PVC in the patients who recovered. Conclusions: Evaluation of A1R by MPDX-PET may be useful for predicting prognosis and understanding the compensatory and reorganization processes in hemianopia caused by organic brain damage.
  • Association between Striatal Subregions and Extrastriatal Regions in Dopamine D-1 Receptor Expression: A Positron Emission Tomography Study, Hironobu Fujiwara, Hiroshi Ito, Fumitoshi Kodaka, Yasuyuki Kimura, Harumasa Takano, Tetsuya Suhara, PLOS ONE, PLOS ONE, 7(11), e49775, Nov. 2012 , Refereed
    Summary:The mesencephalic dopamine (DA) system is the main DA system related to affective and cognitive functions. The system consists of two different cell groups, A9 and A10, which originate from different regions of the midbrain. The striatum is the main input from the midbrain, and is functionally organized into associative, sensorimotor and limbic subdivisions. At present, there have been few studies investigating the associations of DA functions between striatal subdivisions and extrastriatal regions. The aim of this study was to investigate the relationship of DA D-1 receptor (D1R) expression between striatal subdivisions and extrastriatal regions in humans using positron emission tomography (PET) with voxel-by-voxel whole brain analysis. The PET study was performed on 30 healthy subjects using [C-11]SCH23390 to measure D1R expression. Parametric images of binding potentials (BPND) were created using the simplified reference tissue model. Regions of interest were defined for striatal subdivisions. Multiple regression analysis was undertaken to determine extrastriatal regions that were associated with each striatal subdivision in BPND using statistical parametric mapping 5. The BPND values of associative, sensorimotor and limbic subdivisions were similarly correlated with those of multiple brain regions. Regarding the interrelationships among striatal subdivisions, mutual correlations were found among associative, sensorimotor and limbic subdivisions in BPND as well. The relationships in BPND between striatal subdivisions and extra-striatal regions suggest that differential striatal subdivisions and extrastriatal regions have a similar biological basis of D1R expression. Different DA projections from the midbrain did not explain the associations between striatal subdivisions and extrastriatal regions in D1R expression, and the DA-related neural networks among the midbrain, striatum and the other regions would contribute to a similar D1R expression pattern throughout the whole brain.
  • Estimation of the linearity point in graphical analysis, R. Todd Ogden, Yuichi Kimura, JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 32, S33 - S34, Aug. 2012 , Refereed
  • Quantification of Dopamine Transporter in Human Brain Using PET with F-18-FE-PE2I, Takeshi Sasaki, Hiroshi Ito, Yasuyuki Kimura, Ryosuke Arakawa, Harumasa Takano, Chie Seki, Fumitoshi Kodaka, Saori Fujie, Keisuke Takahata, Tsuyoshi Nogami, Masayuki Suzuki, Hironobu Fujiwara, Hidehiko Takahashi, Ryuji Nakao, Toshimitsu Fukumura, Andrea Varrone, Christer Halldin, Toru Nishikawa, Tetsuya Suhara, JOURNAL OF NUCLEAR MEDICINE, JOURNAL OF NUCLEAR MEDICINE, 53(7), 1065 - 1073, Jul. 2012 , Refereed
    Summary:F-18-(E)-N-(3-iodoprop-2E-enyl)-2 beta-carbofluoroethoxy-3 beta-(4-methylphenyl)nortropane (F-18-FE-PE2I) is a new PET radioligand with a high affinity and selectivity for the dopamine transporter (DAT). In nonhuman primates, F-18-FE-PE2I showed faster kinetics and less production of radiometabolites that could potentially permeate the blood-brain barrier than did C-11-PE2I. The aims of this study were to examine the quantification of DAT using F-18-FE-PE2I and to assess the effect of radiometabolites of F-18-FE-PE2I on the quantification in healthy humans. Methods: A 90-min dynamic PET scan was obtained for 10 healthy men after intravenous injection of F-18-FE-PE2I. Kinetic compartment model analysis with a metabolite-corrected arterial input function was performed. The effect of radiometabolites on the quantification was evaluated by time-stability analyses. The simplified reference tissue model (SRTM) method with the cerebellum as a reference region was evaluated as a noninvasive method of quantification. Results: After the injection of F-18-FE-PE2I, the whole-brain radioactivity showed a high peak (similar to 3-5 standardized uptake value) and fast washout. The radioactive uptake of F-18-FE-PE2I in the brain was according to the relative density of the DAT (striatum > midbrain > thalamus). The cerebellum showed the lowest uptake. Tissue time-activity curves were well described by the 2-tissue-compartment model (TCM), as compared with the 1-TCM, for all subjects in all regions. Time stability analysis showed stable estimation of total distribution volume with 60-min or longer scan durations, indicating the small effect of radiometabolites. Binding potentials in the striatum and midbrain were well estimated by the SRTM method, with modest intersubject variability. Although the SRTM method yielded a slight underestimation and overestimation in regions with high and low DAT densities, respectively, binding potentials by the SRTM method were well correlated to the estimates by the indirect kinetic method with 2-TCM. Conclusion: F-18-FE-PE2I is a promising PET radioligand for quantifying DAT. The binding potentials could be reliably estimated in both the striatum and midbrain using both the indirect kinetic and SRTM methods with a scan duration of 60 min. Although radiometabolites of F-18-FE-PE2I in plasma possibly introduced some effects on the radioactivity in the brain, the effects on estimated binding potential were likely to be small.
  • Quantitative measurement of changes in calcium channel activity in vivo utilizing dynamic manganese-enhanced MRI (dMEMRI), Christoph Leuze, Yuichi Kimura, Jeff Kershaw, Sayaka Shibata, Tsuneo Saga, Kai-Hsiang Chuang, Ichiro Shimoyama, Ichio Aoki, NEUROIMAGE, NEUROIMAGE, 60(1), 392 - 399, Mar. 2012 , Refereed
    Summary:The ability of manganese ions (Mn2+) to enter cells through calcium ion (Ca2+) channels has been used for depolarization dependent brain functional imaging with manganese-enhanced MRI (MEMRI). The purpose of this study was to quantify changes to Mn2+ uptake in rat brain using a dynamic manganese-enhanced MRI (dMEMRI) scanning protocol with the Patlak and Logan graphical analysis methods. The graphical analysis was based on a three-compartment model describing the tissue and plasma concentration of Mn. Mn2+ uptake was characterized by the total distribution volume of manganese (Mn) inside tissue (V-T) and the unidirectional influx constant of Mn2+ from plasma to tissue (K-i). The measurements were performed on the anterior (APit) and posterior (PPit) parts of the pituitary gland, a region with an incomplete blood brain barrier. Modulation of Ca2+ channel activity was performed by administration of the stimulant glutamate and the inhibitor verapamil. It was found that the APit and PPit showed different Mn2+ uptake characteristics. While the influx of Mn2+ into the PPit was reversible, Mn2+ was found to be irreversibly trapped in the APit during the course of the experiment. In the PPit, an increase of Mn2+ uptake led to an increase in V-T (from 2.8 +/- 0.3 ml/cm(3) to 4.6 +/- 1.2 ml/cm(3)) while a decrease of Mn2+ uptake corresponded to a decrease in V-T (from 2.8 0.3 ml/cm(3) to 1.4 +/- 0.3 ml/cm(3)). In the APit, an increase of Mn2+ uptake led to an increase in K-i (from 0.034 +/- 0.009 min(-1) to 0.049 +/- 0.012 min(-1)) while a decrease of Mn2+ uptake corresponded to a decrease in K-i (from 0.034 0.009 min(-1) to 0.019 +/- 0.003 min(-1)). This work demonstrates that graphical analysis applied to dMEMRI data can quantitatively measure changes to Mn2+ uptake following modulation of neural activity. (C) 2011 Elsevier Inc. All rights reserved.
  • Quantification of metabotropic glutamate subtype 5 receptors in the brain by an equilibrium method using F-18-SP203, Yasuyuki Kimura, Fabrice G. Simeon, Sami S. Zoghbi, Yi Zhang, Jun Hatazawa, Victor W. Pike, Robert B. Innis, Masahiro Fujita, NEUROIMAGE, NEUROIMAGE, 59(3), 2124 - 2130, Feb. 2012 , Refereed
    Summary:A new PET ligand, 3-fluoro-5-(2-(2-F-18-(fluoromethyl)-thiazol-4-yl)ethynyl)benzonitrile (F-18-SP203) can quantify metabotropic glutamate subtype 5 receptors (mGluR5) in human brain by a bolus injection and kinetic modeling. As an alternative approach to a bolus injection, binding can simply be measured as a ratio of tissue to metabolite-corrected plasma at a single time point under equilibrium conditions achieved by administering the radioligand with a bolus injection followed by a constant infusion. The purpose of this study was to validate the equilibrium method as an alternative to the standard kinetic method for measuring F-18-SP203 binding in the brain. Nine healthy subjects were injected with F-18-SP203 using a bolus plus constant infusion for 300 min. A single ratio of bolus-to-constant infusion (the activity of bolus equaled to that of infusion over 219 min) was applied to all subjects to achieve equilibrium in approximately 120 min. Ass measure of ligand binding, we compared total distribution volume (V-T) calculated by the equilibrium and kinetic methods in each scan. The equilibrium method calculated V-T by the ratio of radioactivity in the brain to the concentration of F-18-SP203 in arterial plasma at 120 min, and the kinetic method calculated V-T by a two-tissue compartment model using brain and plasma dynamic data from 0 to 120 min. V-T obtained via the equilibrium method was highly correlated with V-T obtained via kinetic modeling. Inter-subject variability of V-T obtained via the equilibrium method was slightly smaller than V-T obtained via the kinetic method. V-T obtained via the equilibrium method was -10% higher than V-T obtained via the kinetic method, indicating a small difference between the measurements. Taken together, the results of this study show that using the equilibrium method is an acceptable alternative to the standard kinetic method when using F-18-SP203 to measure mGluR5. Although small differences in the measurements obtained via the equilibrium and kinetic methods exist, both methods consistently measured mGluR5 as indicated by the highly correlated V-T values; the equilibrium method was slightly more precise, as indirectly measured by the smaller coefficient of variability across subjects. In addition, when using F-18-SP203, the equilibrium method is more efficient because it requires much less data. (C) 2011 Published by Elsevier Inc.
  • PET study using [C-11]FTIMD with ultra-high specific activity to evaluate I-2-imidazoline receptors binding in rat brains, Kazunori Kawamura, Yuichi Kimura, Joji Yui, Hidekatsu Wakizaka, Tomoteru Yamasaki, Akiko Hatori, Katsushi Kumata, Masayuki Fujinaga, Yuichiro Yoshida, Masanao Ogawa, Nobuki Nengaki, Toshimitsu Fukumura, Ming-Rong Zhang, NUCLEAR MEDICINE AND BIOLOGY, NUCLEAR MEDICINE AND BIOLOGY, 39(2), 199 - 206, Feb. 2012 , Refereed
    Summary:Introduction: We recently developed a selective C-11-labeled I-2-imidazoline receptor (I2R) ligand, 2-(3-fluoro-4[C-11]tolyl)-4,5-dihydro-1H-imidazole ([C-11]FTIMD). [C-11]FTIMD showed specific binding to I(2)Rs in rat brains having a high density of I2R, as well as to I(2)Rs those in monkey brains, as illustrated by positron emission tomography (PET) and autoradiography. However, [C-11]FTIMD also showed moderate non-specific binding in rat brains. In order to increase the specificity for 1,2 in rat brains, we synthesized [C-11]FTIMD with ultra-high specific activity and evaluated its binding. Methods: [C-11)FTIMD with ultra-high specific activity was prepared by a palladium-promoted cross-coupling reaction of the tributylstannyl precursor and [C-11]methyl iodide, which was produced by iodination of [C-11]methane using the single-pass method. Dynamic PET scans were conducted in rats, and the kinetic parameters were estimated. Results: [C-11]FTIMD with ultra-high specific activity was successfully synthesized with an appropriate level of radioactivity and ultra-high specific activity (4470 +/- 1660 GBq/mu mol at end of synthesis, n=11) for injection. In the PET study, distribution volume (V-T) values in all the brain regions investigated whether I2R expression was greatly reduced in BU224-pretreatead rats compared with control rats (29-45% decrease). Differences in V-T values between control and BU224-pretreated rats using [C-11]FTIMD with ultra-high specific activity were greater than those using [C-11]FTIMD with normal specific activity (17-34% decrease) in all brain regions investigated. Conclusion: Quantitative PET using [C-11]FTIMD with ultra-high specific activity can contribute to the detection of small changes in I2R expression in the brain. (C) 2012 Elsevier Inc. All rights reserved.
  • Monitoring and Evaluation of Blood Pressure Changes With a Home Healthcare System, Toshiyo Tamura, Isao Mizukura, Masaki Sekine, Yutaka Kimura, IEEE TRANSACTIONS ON INFORMATION TECHNOLOGY IN BIOMEDICINE, IEEE TRANSACTIONS ON INFORMATION TECHNOLOGY IN BIOMEDICINE, 15(4), 602 - 607, Jul. 2011 , Refereed
    Summary:We investigated changes in blood pressure with exercise, including walking and ergometer training, sleep, and body weight. Blood pressure was monitored over a period of about 1 year in 61 subjects in Osaka, Japan. The morning systolic blood pressures were analyzed using multivariate regression analysis, and the correlations between systolic blood pressure and the above parameters were determined. The systolic blood pressure distribution was classified into improved, stable, and ingravescence groups. In the improved group, exercise intensity and total calories were important factors controlling the systolic blood pressure. More than 300 kcal per day was needed to improve the systolic blood pressure. In the stable and ingravescence groups, body weight control was also an important factor in maintaining blood pressure. An increase of 1 kg in body weight was associated with systolic blood pressure increases of 3 and 6 mm Hg in the stable and ingravescence groups, respectively. The long-term repeated use of home blood pressure testing may be a good self-care strategy for monitoring daily health.
  • Relationship between whole body oxygen consumption and skeletal muscle glucose metabolism during walking in older adults: FDG PET study, Hiroyuki Shimada, Daina Sturnieks, Yosuke Endo, Yuichi Kimura, Takao Suzuki, Keiichi Oda, Kenji Ishii, Kiichi Ishiwata, AGING CLINICAL AND EXPERIMENTAL RESEARCH, AGING CLINICAL AND EXPERIMENTAL RESEARCH, 23(3), 175 - 182, Jun. 2011 , Refereed
    Summary:Background and aims: The purpose of this study was to determine the relationship between whole body energy metabolism measured as oxygen consumption (VO(2)) and local muscle activity measured by positron emission tomography (PET) and [(18)F]fluorodeoxyglucose (FDG). Methods: Ten community-dwelling older women (73-83 yrs) had FDG PET and VO(2) measured while walking at a comfortable speed. Results: A significant positive correlation was found between VO(2) and FDG uptake in the biceps femoris (r=0.83), gluteus minimus (r=0.67), gluteus medius (r=0.77) and pelvis section muscles (r=0.76). The subjects who showed high FDG uptake in the hip muscle group had significantly higher VO(2) while walking, compared with subjects without high FDG uptake in the hip muscles. Conclusions: These results indicate that FDG PET provides an index which reflects whole body energy metabolism during walking, and revealed that excess muscle activity in the hip muscles during walking plays a key role in increasing VO(2) in older adults. (Aging Clin Exp Res 2011; 23:175-182) (c) 2011, Editrice Kurtis
  • Evaluation of Limiting Brain Penetration Related to P-glycoprotein and Breast Cancer Resistance Protein Using [C-11]GF120918 by PET in Mice, Kazunori Kawamura, Tomoteru Yamasaki, Fujiko Konno, Joji Yui, Akiko Hatori, Kazuhiko Yanamoto, Hidekatsu Wakizaka, Makoto Takei, Yuichi Kimura, Toshimitsu Fukumura, Ming-Rong Zhang, MOLECULAR IMAGING AND BIOLOGY, MOLECULAR IMAGING AND BIOLOGY, 13(1), 152 - 160, Feb. 2011 , Refereed
    Summary:GF120918 has a high inhibitory effect on P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP). We developed [C-11]GF120918 as a positron emission tomography (PET) probe to assess if dual modulation of P-gp and BCRP is useful to evaluate brain penetration. PET studies using [C-11]GF120918 were conducted on P-gp and/or Bcrp knockout mice as well as wild-type mice. In PET studies, the AUC(brain) ([0-60 min]) and K (1) value in P-gp/Bcrp knockout mice were nine- and 26-fold higher than that in wild-type mice, respectively. These results suggest that brain penetration of [C-11]GF120918 is related to modulation of P-gp and BCRP and is limited by two transporters working together. PET using [C-11]GF120918 may be useful for evaluating the function of P-gp and BCRP. PET using P-gp/Bcrp knockout mice may be an effective method to understand the overall contributions the functions of P-gp and BCRP.
  • Adenosine A(2A) Receptors Measured with [C-11]TMSX PET in the Striata of Parkinson's Disease Patients, Masahiro Mishina, Kiichi Ishiwata, Mika Naganawa, Yuichi Kimura, Shin Kitamura, Masahiko Suzuki, Masaya Hashimoto, Kenji Ishibashi, Keiichi Oda, Muneyuki Sakata, Makoto Hamamoto, Shiro Kobayashi, Yasuo Katayama, Kenji Ishii, PLOS ONE, PLOS ONE, 6(2), e17338, Feb. 2011 , Refereed
    Summary:Adenosine A(2A) receptors (A2ARs) are thought to interact negatively with the dopamine D2 receptor (D2R), so selective A2AR antagonists have attracted attention as novel treatments for Parkinson's disease (PD). However, no information about the receptor in living patients with PD is available. The purpose of this study was to investigate the relationship between A2ARs and the dopaminergic system in the striata of drug-naive PD patients and PD patients with dyskinesia, and alteration of these receptors after antiparkinsonian therapy. We measured binding ability of striatal A2ARs using positron emission tomography (PET) with [7-methyl-C-11]-(E)-8-(3,4,5-trimethoxystyryl)-1,3,7-trimethylxanthine ([C-11]TMSX) in nine drug-naive patients with PD, seven PD patients with mild dyskinesia and six elderly control subjects using PET. The patients and eight normal control subjects were also examined for binding ability of dopamine transporters and D2Rs. Seven of the drug-naive patients underwent a second series of PET scans following therapy. We found that the distribution volume ratio of A2ARs in the putamen were larger in the dyskinesic patients than in the control subjects (p < 0.05, Tukey-Kramer post hoc test). In the drug-naive patients, the binding ability of the A2ARs in the putamen, but not in the head of caudate nucleus, was significantly lower on the more affected side than on the less affected side (p < 0.05, paired t-test). In addition, the A2ARs were significantly increased after antiparkinsonian therapy in the bilateral putamen of the drug-naive patients (p < 0.05, paired t-test) but not in the bilateral head of caudate nucleus. Our study demonstrated that the A2ARs in the putamen were increased in the PD patients with dyskinesia, and also suggest that the A2ARs in the putamen compensate for the asymmetrical decrease of dopamine in drug-naive PD patients and that antiparkinsonian therapy increases the A2ARs in the putamen. The A2ARs may play an important role in regulation of parkinsonism in PD.
  • Biodistribution and radiation dosimetry of a positron emission tomographic ligand, F-18-SP203, to image metabotropic glutamate subtype 5 receptors in humans, Yasuyuki Kimura, Fabrice G. Simeon, Jun Hatazawa, P. David Mozley, Victor W. Pike, Robert B. Innis, Masahiro Fujita, EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, 37(10), 1943 - 1949, Oct. 2010 , Refereed
    Summary:A new PET ligand, 3-fluoro-5-(2-(2-F-18-(fluoromethyl)-thiazol-4-yl)ethynyl)benzonitrile (F-18-SP203), is a positron emission tomographic radioligand selective for metabotropic glutamate subtype 5 receptors. The purposes of this study were to estimate the radiation-absorbed doses of F-18-SP203 in humans and to determine from the distribution of radioactivity in bone structures with various proportions of bone and red marrow whether F-18-SP203 undergoes defluorination. Whole-body images were acquired for 5 h after injecting F-18-SP203 in seven healthy humans. Urine was collected at various time points. Radiation-absorbed doses were estimated by the Medical Internal Radiation Dose scheme. After injecting F-18-SP203, the two organs with highest radiation exposure were urinary bladder wall and gallbladder wall, consistent with both urinary and fecal excretion. In the skeleton, most of the radioactivity was in bone structures that contain red marrow and not in those without red marrow. Although the dose to red marrow (30.9 mu Sv/MBq) was unusually high, the effective dose (17.8 mu Sv/MBq) of F-18-SP203 was typical of that of other F-18 radiotracers. F-18-SP203 causes an effective dose in humans typical of several other F-18 radioligands and undergoes little defluorination.
  • Automatic controlled bolus plus infusion method for reliable quantitative drug assessment, Hiroyuki Ohba, Shingo Nishiyama, Takeharu Kakiuchi, Norihiro Harada, Yuichi Kimura, Hideo Tsukada, NEUROIMAGE, NEUROIMAGE, 52, S28 - S28, Aug. 2010 , Refereed
  • Imaging of I-2-imidazoline receptors by small-animal PET using 2-(3-fluoro-[4-C-11]tolyl)-4,5-dihydro-1H-imidazole ([C-11]FTIMD), Kazunori Kawamura, Mika Naganawa, Fujiko Konno, Joji Yui, Hidekatsu Wakizaka, Tomoteru Yamasaki, Kazuhiko Yanamoto, Akiko Hatori, Makoto Takei, Yuichiro Yoshida, Kazuya Sakaguchi, Toshimitsu Fukumura, Yuichi Kimura, Ming-Rong Zhang, NUCLEAR MEDICINE AND BIOLOGY, NUCLEAR MEDICINE AND BIOLOGY, 37(5), 625 - 635, Jul. 2010 , Refereed
    Summary:Introduction: Imidazoline receptors (IRs) have been established as distinct receptors, and have been categorized into at least two subtypes (I1R and I2R). I(2)Rs are associated with depression, Alzheimer's disease, Huntington's disease and Parkinson's disease. A few positron emission tomography (PET) probes for I(2)Rs have been synthesized, but a selective PET probe has not been evaluated for the imaging of I(2)Rs by PET. We labeled a selective I2R ligand 2-(3-fluoro-4-tolyl)-4,5-dihydro-1H-imidazole (FTIMD) with C-11 and performed the first imaging of I(2)Rs by PET using 2-(3-fluoro-[4-C-11]tolyl)-4,5-dihydro-1H-imidazole ([C-11]FTIMD). Methods: [C-11]FTIMD was prepared by a palladium-promoted cross-coupling reaction of the tributylstannyl precursor and [C-11]methyl iodide in the presence of tris(dibenzylideneacetone)dipalladium(0) and tri(o-tol)phosphine. Biodistribution was investigated in rats by tissue dissection. [C-11]FTIMD metabolites were measured in brain tissues and plasma. Dynamic PET scans were acquired in rats, and the kinetic parameters estimated. Results: [C-11]FTIMD was successfully synthesized with a suitable radioactivity for the injection. Co-injection with 0.1 mg/kg of cold FTIMD and BU224 induced a significant reduction in the brain-to-blood ratio 15 and 30 mm after the injection. In metabolite analysis, unchanged [C-11]FTIMD in the brain was high (98%) 30 min after the injection. In PET studies, high radioactivity levels were observed in regions with a high density of I2R. The radioactivity levels and V-T values in the brain regions were prominently reduced by 1.0 mg/kg of BU224 pretreatment as compared with control. Conclusion: [C-11]FTIMD showed specific binding to I(2)Rs in rat brains with a high density of I2R. (C) 2010 Elsevier Inc. All rights reserved.
  • A small animal holding fixture system with positional reproducibility for longitudinal multimodal imaging, Daisuke Kokuryo, Yuichi Kimura, Takayuki Obata, Taiga Yamaya, Kazunori Kawamura, Ming-Rong Zhang, Iwao Kanno, Ichio Aoki, PHYSICS IN MEDICINE AND BIOLOGY, PHYSICS IN MEDICINE AND BIOLOGY, 55(14), 4119 - 4130, Jul. 2010 , Refereed
    Summary:This study presents a combined small animal holding fixture system, termed a 'bridge capsule', which provides for small animal re-fixation with positional reproducibility. This system comprises separate holding fixtures for the head and lower body and a connecting part to a gas anesthesia system. A mouse is fixed in place by the combination of a head fixture with a movable part made from polyacetal resin, a lower body fixture made from vinyl-silicone and a holder for the legs and tail. For re-fixation, a similar posture could be maintained by the same holding fixtures and a constant distance between the head and lower body fixtures is maintained. Artifacts caused by the bridge capsule system were not observed on magnetic resonance (MRI) and positron emission tomography (PET) images. The average position differences of the spinal column and the iliac body before and after re-fixation for the same modality were approximately 1.1 mm. The difference between the MRI and PET images was approximately 1.8 mm for the lower body fixture after image registration using fiducial markers. This system would be useful for longitudinal, repeated and multimodal imaging experiments requiring similar animal postures.
  • Development of PET radiopharmaceuticals and their clinical applications at the Positron Medical Center, Kiichi Ishiwata, Yuichi Kimura, Keiichi Oda, Kenji Ishii, Muneyuki Sakata, Keiichi Kawasaki, Tadashi Nariai, Yukihisa Suzuki, Kenji Ishibashi, Masahiro Mishina, Masaya Hashimoto, Masatomo Ishikawa, Jun Toyohara, GERIATRICS & GERONTOLOGY INTERNATIONAL, GERIATRICS & GERONTOLOGY INTERNATIONAL, 10, S180 - S196, Jul. 2010 , Refereed
    Summary:The Positron Medical Center has developed a large number of radiopharmaceuticals and 36 radiopharmaceuticals have been approved for clinical use for studying aging and geriatric diseases, especially brain functions. Positron emission tomography (PET) has been used to provide a highly advanced PET-based diagnosis. The current status of the development of radiopharmaceuticals, and representative clinical and methodological results are reviewed. Geriatr Gerontol Int 2010; 10 (Suppl. 1): S180-S196.
  • Quantitative analysis of dopamine transporters in human brain using [C-11]PE2I and positron emission tomography: evaluation of reference tissue models, Chie Seki, Hiroshi Ito, Tetsuya Ichimiya, Ryosuke Arakawa, Yoko Ikoma, Miho Shidahara, Jun Maeda, Akihiro Takano, Hidehiko Takahashi, Yuichi Kimura, Kazutoshi Suzuki, Iwao Kanno, Tetsuya Suhara, ANNALS OF NUCLEAR MEDICINE, ANNALS OF NUCLEAR MEDICINE, 24(4), 249 - 260, May 2010 , Refereed
    Summary:Dopamine transporter (DAT) is a reuptake carrier of dopamine at presynapse that regulates dopaminergic neural transmission. [C-11]PE2I is a cocaine analog developed as a potent positron emission tomography (PET) ligand for DAT with high selectivity. The aim of this study was to evaluate the applicability of quantification methods using reference tissue models for [C-11]PE2I. Dynamic PET scans were performed in 6 young healthy male volunteers after an intravenous bolus injection of [C-11]PE2I. Metabolite-corrected arterial plasma-input functions were obtained. Compartment model analysis and plasma-input Logan analysis were performed to determine the kinetic parameters and distribution volume (V (T)). The distribution volume ratio (DVR) was calculated as the ratio of V (T) in the cerebral region to that in the cerebellum. DVRs were also determined by the original multilinear reference tissue model method (MRTMo) and the simplified reference tissue model method (SRTM), comparing the results with those obtained from graphical analysis using arterial input function. To estimate errors in DVR calculated using the reference tissue model, a simulation study that focused on cerebellar kinetics and scan duration was performed. The highest [C-11]PE2I binding was observed in the striatum, followed by the midbrain and thalamus. The 2-tissue model was preferable to the 1-tissue model for describing the [C-11]PE2I kinetics in the cerebellum. Both the measured and 90-min simulated data showed that reference tissue models caused an underestimation of DVR in the striatum. The simulation showed that 90-min scan duration was insufficient when cerebellar kinetics was described as a 1-tissue model. Nevertheless, DVR values determined by MRTMo and SRTM were in good agreement with those by the graphical approach in other lower binding regions. Due to the [C-11]PE2I kinetics in the cerebellum and limited scan duration for C-11, MRTMo and SRTM underestimated the striatal DVR. Despite this limitation, the present study demonstrated the applicability of reference tissue models. Since DAT in the midbrain and thalamus is of interest in the pathophysiology of neuropsychiatric disease, this noninvasive quantitative analysis will be useful for clinical investigations.
  • Biodistribution and Radiation Dosimetry in Humans of a New PET Ligand, F-18-PBR06, to Image Translocator Protein (18 kDa), Yota Fujimura, Yasuyuki Kimura, Fabrice G. Simeon, Leah P. Dickstein, Victor W. Pike, Robert B. Innis, Masahiro Fujita, JOURNAL OF NUCLEAR MEDICINE, JOURNAL OF NUCLEAR MEDICINE, 51(1), 145 - 149, Jan. 2010 , Refereed
    Summary:As a PET biomarker for inflammation, translocator protein (18 kDa) (TSPO) can be measured with an F-18-labeled aryloxyanilide, F-18-N-fluoroacetyl-N-(2,5-dimethoxybenzyl)-2-phenoxyaniline (F-18-PBR06), in the human brain. The objective of this study was to estimate the radiation absorbed doses of F-18-PBR06 based on biodistribution data in humans. Methods: After the injection of F-18-PBR06, images were acquired from head to thigh in 7 healthy humans. Urine was collected at various time points. Radiation absorbed doses were estimated by the MIRD scheme. Results: Moderate to high levels of radioactivity were observed in organs with high densities of TSPO and in organs of metabolism and excretion. Bone had low levels of radioactivity. The effective dose was 18.5 mu Sv/MBq. Conclusion: The effective dose of F-18-PBR06, compared with other F-18 radioligands, was moderate. This radioligand had negligible defluorination, as indirectly assessed by bone radioactivity. Doses to the gallbladder wall and spleen may limit the amount of permissible injected radioactivity.
  • Measurement error analysis for the determination of dopamine D-2 receptor occupancy using the agonist radioligand [C-11]MNPA, Miho Shidahara, Hiroshi Ito, Tatsui Otsuka, Yoko Ikoma, Ryosuke Arakawa, Fumitoshi Kodaka, Chie Seki, Harumasa Takano, Hidehiko Takahashi, Federico E. Turkheimer, Yuichi Kimura, Iwao Kanno, Tetsuya Suhara, JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 30(1), 187 - 195, Jan. 2010 , Refereed
    Summary:The purpose of this study is to investigate errors in quantitative analysis for estimating dopamine D-2 receptor occupancy of antipsychotics with agonist radioligand [C-11]MNPA by numerical simulation, with particular attention to the validity of a quantitative approach based on the use of a reference region. Synthetic data were validated using clinical data combined with a bootstrap approach. Time-activity curves (TACs) of [C-11]MNPA were simulated, and the reliability of binding potential (BPND) and occupancy estimated by nonlinear least square (NLS) fitting and a simplified reference tissue model (SRTM) were investigated for various noise levels and scan durations. In the human positron emission tomography (PET) study with and without antipsychotic, risperidone, the uncertainty of BPND and occupancy estimated by SRTM was investigated using resampled TACs based on bootstrap approach with weighted residual errors of fitting. For both NLS and SRTM, it was possible to have < 3% of bias in occupancy estimates of [C-11]MNPA by 60 mins. However, shortened scan duration degrades the quantification of very small binding potentials, especially in case of SRTM. Observations were replicated on the clinical data. Results showed that dopamine D-2 receptor occupancy by antipsychotics can be estimated precisely in region of interest analysis by SRTM with a longer than 60-min [C-11]MNPA PET scan duration. Journal of Cerebral Blood Flow & Metabolism (2010) 30, 187-195; doi: 10.1038/jcbfm.2009.193; published online 16 September 2009
  • A new graphic plot analysis for determination of neuroreceptor binding in positron emission tomography studies, Hiroshi Ito, Takashi Yokoi, Yoko Ikoma, Miho Shidahara, Chie Seki, Mika Naganawa, Hidehiko Takahashi, Harumasa Takano, Yuichi Kimura, Masanori Ichise, Tetsuya Suhara, NEUROIMAGE, NEUROIMAGE, 49(1), 578 - 586, Jan. 2010 , Refereed
    Summary:In positron emission tomography (PET) studies with radioligands for neuroreceptors, tracer kinetics have been described by the standard two-tissue compartment model that includes the compartments of nondisplaceable binding and specific binding to receptors. In the present Study, we have developed a new graphic plot analysis to determine the total distribution volume (V(T)) and nondisplaceable distribution volume (V(ND)) independently, and therefore the binding potential (BP(ND)). In this plot, Y(t) is the ratio of brain tissue activity to time-integrated arterial input function, and X(t) is the ratio of time-integrated brain tissue activity to time-integrated arterial input function. The x-intercept of linear regression of the plots for early phase represents V(ND), and the x-intercept of linear regression of the plots for delayed phase after the equilibrium time represents V(T). BP(ND) can be calculated by BP(ND) = V(T)/V(ND) - 1. Dynamic PET scanning with measurement of arterial input function was performed on six healthy men after intravenous rapid bolus injection of [(11)C]FLB457. The plot yielded a curve in regions with specific binding while it yielded a straight line through all plot data in regions with no specific binding. V(ND), V(T), and BP(ND) values calculated by the present method were in good agreement with those by conventional non-linear least-squares fitting procedure. This method can be used to distinguish graphically whether the radioligand binding includes specific binding or not. (C) 2009 Elsevier Inc. All rights reserved.
  • Effects of a robotic walking exercise on walking performance in community-dwelling elderly adults, Hiroyuki Shimada, Takashi Hirata, Yuichi Kimura, Takako Naka, Keishiro Kikuchi, Keiichi Oda, Kenji Ishii, Kiichi Ishiwata, Takao Suzuki, GERIATRICS & GERONTOLOGY INTERNATIONAL, GERIATRICS & GERONTOLOGY INTERNATIONAL, 9(4), 372 - 381, Dec. 2009 , Refereed
    Summary:Background: Reduced gait speed and stride length are characteristic of gait in elderly people and increase their dependency on assistance. We developed a robotic stride assistance system (SAS) to automatically control the walk ratio during walking. Our aim was to quantify the effects of a walking exercise with the SAS on walking performance and glucose metabolism during walking in community-dwelling elderly adults. Methods: For 3 months, 15 women (72-85 years old) performed the walking exercise twice weekly for 90 min/session. We assessed walking for 5 m at a comfortable speed before and after the intervention. Positron emission tomography with [18F]fluorodeoxyglucose (FDG) was used to assess muscle activity during an unassisted 50-min walk. Results: Walking speed was improved by the intervention and FDG uptake by the gluteus minimus, gluteus medius and rectus femoris, and pelvic muscles (iliacus and gluteus muscles) were reduced. Conclusion: These results suggest that a walking intervention program using an applied robotic system is useful for improving the walking ability and the efficiency of muscle activities during walking in the elderly.
  • High occupancy of sigma(1) receptors in the human brain after single oral administration of donepezil: a positron emission tomography study using [C-11]SA4503, Masatomo Ishikawa, Muneyuki Sakata, Kenji Ishii, Yuichi Kimura, Keiichi Oda, Jun Toyohara, Jin Wu, Kiichi Ishiwata, Masaomi Iyo, Kenji Hashimoto, INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY, INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY, 12(8), 1127 - 1131, Sep. 2009 , Refereed
    Summary:The acetylcholinesterase (AChE) inhibitor donepezil is also a sigma(1) receptor agonist. We examined whether donepezil binds to a, receptors in the living human brain after a single oral administration. Dynamic positron emission tomography (PET) data acquisition using the selective sigma(1) receptor ligand [C-11]SA4503 was performed to evaluate quantitatively the binding of [C-11]SA4503 to at receptors in eight healthy male volunteers. Each subject had a PET scan before and after receiving a single dose of donepezil (5 or 10 mg). The binding potential of [C-11]SA4503 was calculated. Doses of 5 mg and 10 mg donepezil bound to a, receptors in the human brain with occupancies of similar to 60% and similar to 75%, respectively, in a dose-dependent manner. This study demonstrated that donepezil binds to sigma(1) receptors in the Living human brain at therapeutic doses. Therefore, sigma(1) receptors may be implicated in the pharmacological mechanism of donepezil in the human brain.
  • PET pharmacokinetic analysis to estimate boron concentration in tumor and brain as a guide to plan BNCT for malignant cerebral glioma, Tadashi Nariai, Kiichi Ishiwata, Yuichi Kimura, Motoki Inaji, Toshiya Momose, Tetsuya Yamamoto, Akira Matsumura, Kenji Ishii, Kikuo Ohno, APPLIED RADIATION AND ISOTOPES, APPLIED RADIATION AND ISOTOPES, 67(7-8), S348 - S350, Jul. 2009 , Refereed
    Summary:Introduction: To plan the optimal BNCT for patients with malignant cerebral glioma, estimation of the ratio of boron concentration in tumor tissue against that in the surrounding normal brain (T/N ratio of boron) is important. We report a positron emission tomography (PET) imaging method to estimate T/N ratio of tissue boron concentration based on pharmacokinetic analysis of amino acid probes. Methods: Twelve patients with cerebral malignant glioma underwent 60 min dynamic PET scanning of brain after bolus injection of (18)F-borono-phenyl-alanine (FBPA) with timed arterial blood sampling. Using kinetic parameter obtained by this scan, T/N ratio of boron concentration elicited by one-hour constant infusion of BPA, as performed in BNCT, was simulated on Runge-Kutta algorithm. (11)C-methionine (MET) PET scan, which is commonly used in worldwide PET center as brain tumor imaging tool, was also performed on the same day to compare the image characteristics of FBPA and that of MET. Result: PET glioma images obtained with FBPA and MET are almost identical in all patients by visual inspection. Estimated T/N ratio of tissue boron concentration after one-hour constant infusion of BPA, T/N ratio of FBPA on static condition, and T/N ratio of MET on static condition showed significant linear correlation between each other. Conclusion: T/N ratio of boron concentration that is obtained by constant infusion of BPA during BNCT can be estimated by FBPA PET scan. This ratio can also be estimated by MET-PET imaging. As MET-PET study is available in many clinical PET center, selection of candidates for BNCT may be possible by MET-PET images. Accurate planning of BNCT may be performed by static images of FBPA PET. Use of PET imaging with amino acid probes may contribute very much to establish an appropriate application of BNCT for patients with malignant glioma. (C) 2009 Elsevier Ltd. All rights reserved.
  • A statistical clustering approach to visualizing the relationship between early and delayed images in whole-body FDG-PET, Keiichi Oda, Hinako Toyama, Yasuoki Mashima, Kenji Ishii, Toru Kosaka, Yuichi Kimura, Masahiro Fukushi, Kiichi Ishiwata, Radiological Physics and Technology, Radiological Physics and Technology, 2(2), 145 - 150, Jul. 2009 , Refereed
    Summary:We propose a new method for diagnostic assistance in oncology, [fluorine-18]-2-fluoro-2-deoxy-d-glucose (FDG)-positron emission tomography (PET). Early and delayed scans were performed on 10 patients with lung cancer by use of an ECAT EXACT 47 PET scanner, and standardized-uptake-value (SUV) images were created. Three segmentation (S1, S2, and S3) maps were created from the early and delayed SUV images according to various thresholds (SUV threshold = 2.0, 2.5, and 3.0) based on the early image and the percentage change defined as (SUVdelayed - SUVearly) × 100/SUVearly. Voxels that had larger voxel values in their early images than the SUVthreshold were clustered into three classes: S1 if the percentage change was larger than 10, S2 if the percentage change was between 0 and 10, and S3 if the percentage change was negative. The S1 segments showed malignant lesions clearly however, the S2 segments showed an SUV that had decreased from the S1 areas due to the partial volume effect or misalignment between the early and delayed scans. The S3 areas showed benignity or physiologic accumulation. The segmented images, S1, S2, and S3, were useful for clinical diagnosis with dual-phase FDG-PET scans and offer an easy way of exploring the longitudinal alteration in the SUV. © 2009 Japanese Society of Radiological Technology and Japan Society of Medical Physics.
  • Comparison of regional lower limb glucose metabolism in older adults during walking, H. Shimada, Y. Kimura, S. R. Lord, K. Oda, K. Ishii, T. Suzuki, K. Ishiwata, SCANDINAVIAN JOURNAL OF MEDICINE & SCIENCE IN SPORTS, SCANDINAVIAN JOURNAL OF MEDICINE & SCIENCE IN SPORTS, 19(3), 389 - 397, Jun. 2009 , Refereed
    Summary:Glucose metabolism in lower limb muscles during walking has an important role in gait efficiency and endurance. The purpose of this study was to identify differences in muscle activity during walking between healthy young and older adults using positron emission tomography (PET) and [(18)F]fluorodeoxyglucose (FDG). Ten healthy young men (24 +/- 2 years) and 10 healthy older men (76 +/- 2 years) participated in this study. An FDG PET assessment of each subject was conducted after 50 min of treadmill walking. The images of glucose metabolism in 18 regions of interest were estimated from the standardized uptake value (SUV). The older adults showed a significantly higher FDG uptake in the semitendinosus, biceps femoris, iliacus, gluteus minimus, gluteus medius, and gluteus maximus muscles than the young adults: FDG uptake ratios of SUV in the old to SUV in the young were 3.02, 3.19, 1.66, 1.64, 3.68, and 3.05, respectively. During walking, the FDG uptake in older adults was higher in hamstrings and deep layer hip muscles than that in young adults. These results suggest that intervention to facilitate efficient muscle activity during walking should be practiced to improve gait endurance in older adults with impaired walking patterns.
  • Improvement of likelihood estimation in Logan graphical analysis using maximum a posteriori for neuroreceptor PET imaging, Miho Shidahara, Chie Seki, Mika Naganawa, Muneyuki Sakata, Masatomo Ishikawa, Hiroshi Ito, Iwao Kanno, Kiichi Ishiwata, Yuichi Kimura, ANNALS OF NUCLEAR MEDICINE, ANNALS OF NUCLEAR MEDICINE, 23(2), 163 - 171, Feb. 2009 , Refereed
    Summary:To reduce variance of the total volume of distribution (V (T)) image, we improved likelihood estimation in graphical analysis (LEGA) for dynamic positron emission tomography (PET) images using maximum a posteriori (MAP). In our proposed MAP estimation in graphical analysis (MEGA), a set of time-activity curves (TACs) was formed with V (T) varying in physiological range as a template, and then the most similar TAC was sought out for a given measured TAC in a feature space. In simulation, MEGA was compared with other three methods, Logan graphical analysis (GA), multilinear analysis (MA1), and LEGA using 500 noisy TACs, under each of seven physiological conditions (from 9.9 to 61.5 of V (T)). PET studies of [(11)C]SA4503 were performed in three healthy volunteers. In clinical studies, the V (T) images estimated from MEGA were compared with region of interest (ROI) estimates from a nonlinear least square (NLS) fitting over four brain regions. In the simulation study, the estimated V (T) by GA had a large underestimation (y = 0.27x + 8.72, r (2) = 0.87). Applying the other methods (MA1, LEGA, and MEGA), these noise-induced biases were improved (y = 0.80x + 4.04, r (2) = 0.98; y = 0.85x + 3.05, r (2) = 0.99; y = 0.96x + 1.21, r (2) = 0.99, respectively). MA1 and LEGA produced increased variance of the estimated V (T) in clinical studies. However, MEGA improved signal-to-noise ratio (SNR) in V (T) images with linear correlations between ROI estimates with NLS (y = 0.87x + 5.1, r (2) = 0.96). MEGA was validated as an alternative strategy of LEGA to improve estimates of V (T) in clinical PET imaging.
  • Adenosine A(1) receptors using 8-dicyclopropylmethyl-1-[C-11]methyl-3-propylxanthine PET in Alzheimer's disease, Nobuyoshi Fukumitsu, Kenji Ishii, Yuichi Kimura, Keiichi Oda, Masaya Hashimoto, Masahiko Suzuki, Kiichi Ishiwata, ANNALS OF NUCLEAR MEDICINE, ANNALS OF NUCLEAR MEDICINE, 22(10), 841 - 847, Dec. 2008 , Refereed
    Summary:Adenosine is an endogenous modulator of synaptic functions in the central nervous system. The effects of adenosine are mediated by at least four adenosine receptor subtypes. Decreased density of adenosine A1 receptors, which is a major subtype adenosine receptor in the hippocampus, has been reported in vitro in Alzheimer's disease. We evaluated adenosine A1 receptor in the brain of elderly normal subjects and patients with Alzheimer's disease (n = 8 and 6, respectively), using positron emission tomography (PET) and 8- dicyclopropylmethyl-1-[C-11]methyl-3-propylxanthine ([C-11]MPDX). A 60-min PET scan with [C-11]MPDX was performed. The patients with Alzheimer's disease also underwent PET with [F-18]fluorodeoxyglucose (FDG). The binding potential of [11C]MPDX was quantitatively calculated in the regions of interest (ROIs) placed on the frontal, medial frontal, temporal, medial temporal, parietal, and occipital cortices, striatum, thalamus, cerebellum, and pons. Statistical parametric mapping (SPM2) was used for analysis of [C-11]MPDX and FDG-PET. In the ROI-based analysis, the binding potential of [C-11]MPDX in patients with Alzheimer's disease was significantly lower in the temporal and medial temporal cortices and thalamus than that in elderly normal subjects (P = 0.038, 0.028, and 0.039, respectively). SPM analysis also showed significant decreased binding potential in the temporal and medial temporal cortices and thalamus in patients with Alzheimer's disease. FDG uptake was significantly decreased in the temporoparietal cortex and posterior cingulate gyrus. Decreased binding of [C-11]MPDX in patients with Alzheimer's disease was detected in temporal and medial temporal cortices and thalamus. This pattern possibly differed from the hypometabolism pattern of FDG. [C-11]MPDX PET is valuable for the detection of degeneration in the temporal and medial temporal cortices and corticothalamic transmission, and may provide a different diagnostic tool from FDG-PET in brain disorders such as Alzheimer's disease.
  • Effects of an automated stride assistance system on walking parameters and muscular glucose metabolism in elderly adults, H. Shimada, T. Suzuki, Y. Kimura, T. Hirata, M. Sugiura, Y. Endo, K. Yasuhara, K. Shimada, K. Kikuchi, K. Oda, K. Ishii, K. Ishiwata, BRITISH JOURNAL OF SPORTS MEDICINE, BRITISH JOURNAL OF SPORTS MEDICINE, 42(11), 922 - 929, Nov. 2008 , Refereed
    Summary:Objective: To identify the effects of an automated stride assistance system (SAS) on walking scores and muscle activities in the lower extremities of elderly people. Methods: Seven healthy elderly men (73 -81 years) participated in this study. Subjects walked continuously at a constant speed for 50 min on a treadmill with and without the SAS, which is a device to control the walk ratio (step length/cadence) and to add support power to the thigh during walking. A step counter equipped with an infrared device was used to record walking data. The average speeds during treadmill walking were 2.89 -3.82 km/h without the SAS and 3.03-4.03 km/h with the SAS. Positron emission tomography (PET) and [(18)F] fluorodeoxyglucose (FDG) evaluation of glucose metabolism were conducted on each subject twice after walking with and without the SAS. Results: Walk ratio, walking speed and step length were significantly improved in all subjects by the SAS, while cadence was significantly decreased by the SAS in all subjects except one. The SAS did not have a significant effect on glucose metabolism of the muscles of the lower extremities. There were no significant correlations between change in walking speed and change in glucose metabolism in each muscle without the SAS and with the SAS. In contrast, significant correlations between walking speed and glucose metabolism were shown in gluteus minimus (r= -0.929), hip-related muscles (r= -0.862), soleus (r= -0.907), and medial gastrocnemius (r= -0.952) without the SAS. With the SAS, there were significant correlations in gluteus medius (r= -0.899), hip-related muscles (r= -0.819), and medial gastrocnemius (r= -0.817) in the elderly subjects. Conclusions: The SAS increases walking scores in elderly people without increasing energy consumption of lower-extremity muscles. The elderly subjects with low walking speed showed higher glucose metabolism in hiprelated muscles and triceps surae. Thus, this association suggested that decreased walking speed in elderly adults has a higher metabolic cost in these muscle regions.
  • Error analysis for PET measurement of dopamine D(2) receptor occupancy by antipsychotics with [(11)C]raclopride and [(11)C]FLB 457, Yoko Ikoma, Hiroshi Ito, Ryosuke Arakawa, Masaki Okumura, Chie Seki, Miho Shidahara, Hidehiko Takahashi, Yuichi Kimura, Iwao Kanno, Tetsuya Suhara, NEUROIMAGE, NEUROIMAGE, 42(4), 1285 - 1294, Oct. 2008 , Refereed
    Summary:Dopamine D(2) receptor occupancy by antipsychotic drugs has been measured with positron emission tomography (PET) by comparing the binding potential (BP) values before and after drug administration. This occupancy has been found to be related to clinical effects and side effects. in this study, we evaluated the in simulation and human studies of [(11)C]raclopride and for the high affinity ligand [(11)C]FLB 457. Time-activity curves of [(11)C]raclopride and [(11)C]FLB 457 were simulated, and the reliability of BP estimated by a simplified reference tissue model and the calculated Occupancy were investigated for various noise levels, BP values, and scan durations. Then, in the human PET study with and without antipsychotics, the uncertainty of BP and occupancy estimates and the scan duration required for a reliable estimation were investigated by a bootstrap approach. Reliable and unbiased estimates of [(11)C]raclopride BP(ND) could be obtained with recording as short as 32 min, with the relative standard deviation (SD) of the striatal occupancy remaining less than 10%. Conversely, in [(11)C]FLB 457 Studies, the mean value increased and SD of the temporal cortex and thalamus exceeded 10% when the scan duration was shorter than 60 min. These results demonstrated that dopamine D(2) receptor occupancy by antipsychotics can be estimated precisely with an optimal scan duration with [(11)C]raclopride and [(11)C]FLB 457. (C) 2008 Elsevier Inc. All rights reserved.
  • Successive positron emission tomography measurement of cerebral blood flow and neuroreceptors in the human brain: an (11)C-SA4503 study, Kiichi Ishiwata, Kenji Ishii, Yuichi Kimura, Kazunori Kawamura, Keiichi Oda, Toru Sasaki, Muneyuki Sakata, Michio Senda, ANNALS OF NUCLEAR MEDICINE, ANNALS OF NUCLEAR MEDICINE, 22(5), 411 - 416, Jun. 2008 , Refereed
    Summary:For evaluating a newly developed radioligand for positron emission tomography (PET), successive measurements of regional cerebral blood flow (rCBF) and the kinetics of the radioligand in the same subject are preferable in the first clinical trial. In this study, we demonstrate an example for the study of (11)C-labeled 1-(3,4-dimethoxyphenethyl)-4-(3-phenylprophyl) piperazine ((11)C-SA4503) for mapping sigma(1) receptors in the human brain. Five healthy male subjects underwent two successive PET scans with (15)O-H(2)O to measure the rCBF and with (11)C-SA4503 (dynamic 60-min scan). The brain kinetics of (11)C-SA4503 was evaluated using the time-activity curve (TAC) of tissue in each of the 11 regions of the brain and the metabolite-corrected TAC of plasma on the basis of a two-tissue compartment fourparameter model. The estimated parameters were four rate constants: K (1), influx from plasma to brain tissue; k (2), efflux from tissue to plasma; k (3), association between tracer and receptors; and k (4), dissociation of tracer-receptor complex, and the binding potential (BP), k (3)/k (4). (11)CSA4503 was distributed all over the brain, and the TACs exhibited an accumulation pattern in all the 11 regions. K (1) of (11)C-SA4503 correlated with rCBF, but the other three rate constant parameters and BP did not. The regional difference in the BP of (11)C-SA4503 is compatible with those of sigma(1) receptors. In conclusion, successive PET measurements of rCBF and the brain kinetics of radioligand-neuroreceptor binding are useful for the first clinical trial of a newly developed radioligand for mapping neuroreceptors, and the protocol is applicable to pathophysiological studies of brain disorders.
  • Measurement of the C-11-flumazenil binding in the visual cortex predicts the prognosis of hemianopia, Yukihisa Suzuki, Chiharu Horie, Motohiro Kiyosawa, Tadashi Nariai, Manabu Mochizuki, Keiichi Oda, Yuichi Kimura, Kiich Ishiwata, Kenji Ishii, JOURNAL OF THE NEUROLOGICAL SCIENCES, JOURNAL OF THE NEUROLOGICAL SCIENCES, 268(1-2), 102 - 107, May 2008 , Refereed
    Summary:In order to determine whether functional neuroimaging studies can predict the prognosis of hemianopia due to organic cerebral disorders, we studied 8 patients (6 men and 2 women; age, 56.0 +/- 8.6 years) with homonymous hemianopia and compared them with 15 normal subjects (6 men and 9 women; age, 54.3 +/- 4.4 years). The cerebral glucose metabolism and C-11-flumazenil (FMZ) binding were measured by positron emission tomography, more than I month after the onset of the condition. Bilateral regions of interest (ROIs) were selected in the striate cortex, extrastriate cortex, cuneus and thalamus. Further, semi-quantitative data on the cerebral glucose metabolism and FMZ binding were obtained for the ROIs and compared with the data obtained for homologous regions in the contralateral hemisphere by calculating the ipsilateral/ contralateral (I/C) ratio. The I/C ratios for the cerebral glucose metabolism and FMZ binding in the striate cortex were significantly low in the patients (glucose metabolism, P<0.0005; FMZ binding, P<0.005), while the ratio for the FMZ binding in the cuneus increased (P<0.0005). We observed that 5 patients, whose I/C ratio for the FMZ binding in the striate cortex was >0.850, experienced an improvement in their visual field, while that 3 patients with lower PC ratios did not. The FMZ-PET may be useful to predict the prognosis of hemianopia in the chronic phase. (C) 2007 Elsevier B.V. All rights reserved.
  • Low density of sigma(1) receptors in early Alzheimer's disease, Masahiro Mishina, Masashi Ohyama, Kenji Ishii, Shin Kitamura, Yuichi Kimura, Kei-ichi Oda, Kazunori Kawamura, Toru Sasaki, Shiro Kobayashi, Yasuo Katayama, Kiichi Ishiwata, ANNALS OF NUCLEAR MEDICINE, ANNALS OF NUCLEAR MEDICINE, 22(3), 151 - 156, Apr. 2008 , Refereed
    Summary:Objective The sigma, receptor is considered to be involved in cognitive function. A postmortem study reported that the sigma, receptors were reduced in the hippocampus in Alzheimer's disease (AD). However, in vivo imaging of sigma, receptors in the brain of AD patients has not been reported. The aim of this study is to investigate the mapping of sigma, receptors in AD using [(11)C]SA4503 positron emission tomography (PET). Methods We studied five AD patients and, seven elderly volunteers. A dynamic series of decay-corrected PET data acquisition was performed for 90 min starting at the time of the injection of 500 MBq of [(11)C]SA4503. A two-tissue three-compartment model was used to estimate K(1), k(2), k(3), k(4), and the delay between metabolite-corrected plasma and tissue time activity using a Gauss-Newton algorithm. The ratio of k(3) to k(4) was computed as the binding potential (BP), which is linearly related to the density of sigma, receptors. Unpaired t tests were used to compare K(1) and BP in patients with AD and normal subjects. Results As compared with normals, BP in the AD was significantly lower in the frontal, temporal, and occipital lobe, cerebellum and thalamus, whereas K(1) was significantly lower in the parietal lobe. Conclusions [(11)C]SA4503 PET can demonstrate that the density of cerebral and cerebellar sigma, receptors is reduced in early AD.
  • Influence of mild hyperglycemia on cerebral FDG distribution patterns calculated by statistical parametric mapping, Keiichi Kawasaki, Kenji Ishii, Yoko Saito, Keiichi Oda, Yuichi Kimura, Kiichi Ishiwata, ANNALS OF NUCLEAR MEDICINE, ANNALS OF NUCLEAR MEDICINE, 22(3), 191 - 200, Apr. 2008 , Refereed
    Summary:Objective In clinical cerebral 2-[(18)F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) studies, we sometimes encounter hyperglycemic patients with diabetes mellitus or patients who have not adhered to the fasting requirement. The objective of this study was to investigate the influence of mild hyperglycemia (plasma glucose range 110-160 mg/dl) on the cerebral FDG distribution patterns calculated by statistical parametric mapping (SPM). Methods We studied 19 healthy subjects (mean age 66.2 years). First, all the subjects underwent FDG-PET scans in the fasting condition. Then, 9 of the 19 subjects (mean age 64.3 years) underwent the second FDG-PET scans in the mild hyperglycemic condition. The alterations in the FDG-PET scans were investigated using SPM- and region of interest (ROT)-based analyses. We used three reference regions: (1) SPM global brain (SPMgb) used for SPM global mean calculation, (2) the gray and white matter region computed from magnetic resonance image (MRIgw), and (3) the cerebellar cortex (Cbll). Results The FDG uptake calculated as the standardized uptake value (average) in SPMgb, MRIgw, and Cbll regions in the mild hyperglycemic condition was 42.7%, 41.3%, and 40.0%, respectively, of that observed in the fasting condition. In SPM analysis, the mild hyperglycemia was found to affect the cerebral distribution patterns of FDG. The FDG uptake was relatively decreased in the gray matter, mainly in the frontal, temporal, and parietal association cortices, posterior cingulate, and precuneus in both SPMgb- and MRIgw-reference-based analyses. When Cbll was adopted as the reference region, those decrease patterns disappeared. The FDG uptake was relatively increased in the white matter, mainly in the centrum semiovale in all the reference-based analyses. Conclusions It is noteworthy that the FDG distribution patterns were altered under mild hyperglycemia in SPM analysis. The decreased uptake patterns in SPMgb(SPM default) and MRIgw-reference-based analyses resembled those observed in Alzheimer's disease. Under mild hyperglycemia, we can recommend Cbll as the reference region to detect decreased uptake patterns. We should pay special attention to controlling the diet condition, monitoring hyperglycemia, and optimizing the reference region in SPM analysis, particularly in the diagnosis of early Alzheimer's disease in clinical FDG-PET.
  • Robust estimation of the arterial input function for Logan plots using an intersectional searching algorithm and clustering in positron emission tomography for neuroreceptor imaging, Mika Naganawa, Yuichi Kimura, Junichi Yano, Masahiro Mishina, Masao Yanagisawa, Kenji Ishii, Kelichi Oda, Klichi Ishiwata, NEUROIMAGE, NEUROIMAGE, 40(1), 26 - 34, Mar. 2008 , Refereed
    Summary:The Logan plot is a powerful algorithm used to generate binding-potential images from dynamic positron emission tomography (PET) images in neuroreceptor studies. However, it requires arterial blood sampling and metabolite correction to provide an input function, and clinically it is preferable that this need for arterial blood sampling be obviated. Estimation of the input function with metabolite correction using an intersectional searching algorithm (ISA) has been proposed. The ISA seeks the input function from the intersection between the planes spanned by measured radioactivity curves in tissue and their cumulative integrals in data space. However, the ISA is sensitive to noise included in measured curves, and it often fails to estimate the input function. In this paper, we propose a robust estimation of the cumulative integral of the plasma time-activity curve (pTAC) using ISA (robust EPISA) to overcome noise issues. The EPISA reduces noise in the measured PET data using averaging and clustering that gathers radioactivity curves with similar kinetic parameters. We confirmed that a little noise made the estimation of the input function extremely difficult in the simulation. The robust EPISA was validated by application to eight real dynamic [(11)C]TMSX PET data sets used to visualize adenosine A(2A) receptors and four real dynamic [(11)C]PIB PET data sets used to visualize amyloid-beta plaque. Peripherally, the latter showed faster metabolism than the former. The clustering operation improved the signal-to-noise ratio for the PET data sufficiently to estimate the input function, and the calculated neuroreceptor images had a quality equivalent to that using measured pTACs after metabolite correction. Our proposed method noninvasively yields an alternative input function for Logan plots, allowing the Logan plot to be more useful in neuroreceptor studies. (c) 2007 Elsevier Inc. All rights reserved.
  • Wavelet denoising for voxel-based compartmental analysis of peripheral benzodiazepine receptors with F-18-FEDAA1106, Miho Shidahara, Yoko Ikoma, Chie Seki, Yota Fujimura, Mika Naganawa, Hiroshi Ito, Tetsuya Suhara, Iwao Kanno, Yuichi Kimura, EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, 35(2), 416 - 423, Feb. 2008 , Refereed
    Summary:Purpose We evaluated the noise reduction capability of wavelet denoising for estimated binding potential (BP) images (k(3)/k (4)) of the peripheral benzodiazepine receptor using F-18-FEDAA1106 and nonlinear least-square fitting. Methods Wavelet denoising within a three-dimensional discrete dual-tree complex wavelet transform was applied to simulate data and clinical dynamic positron emission tomography images of F-18-FEDAA1106. To eliminate noise components in wavelet coefficients, real and imaginary coefficients for each subband were thresholded individually using NormalShrink. A simulated dynamic brain image of F-18-FEDAA1106 was generated and Gaussian noise was added to mimic PET dynamic scan. The derived BP images were compared with true images using 156 rectangular regions of interest. Wavelet denoising was also applied to data derived from seven young normal volunteers. Results In the simulations, estimated BP by denoised image showed better correlation with the true BP values (Y=0.83X+0.94, r=0.80), although no correlation was observed in the estimates between noise-added and true images (Y=1.2X+0.78, r=0.49). For clinical data, there were visual improvements in the signal-to-noise ratio for estimated BP images. Conclusions Wavelet denoising improved the bias and reduced the variation of pharmacokinetic parameters for BP.
  • Shortened protocol in practical [(11)C]SA4503-PET studies for sigma(1) receptor quantification, Muneyuki Sakata, Yuichi Kimura, Mika Naganawa, Masatomo Ishikawa, Keiichi Oda, Kenji Ishii, Kenji Hashimoto, Kunihiro Chihara, Kiichi Ishiwata, ANNALS OF NUCLEAR MEDICINE, ANNALS OF NUCLEAR MEDICINE, 22(2), 143 - 146, Feb. 2008 , Refereed
    Summary:In practical positron emission tomography (PET) diagnosis, a shortened protocol is preferred for patients with brain disorders. In this study, the applicability of a shortened protocol as an alternative to the 90-min PET scan with [(11)C]SA4503 for quantitative sigma(1) receptor measurement was investigated. Tissue time-activity curves of 288 regions of interest in the brain from 32 [(11)C]SA4503-PET scans of 16 healthy subjects prior to and following administration of a selective serotonin reuptake inhibitor (fluvoxamine or paroxetine) were applied to two algorithms of quantitative analysis; binding potential (BP) was derived from compartmental analysis based on nonlinear estimation, and total distribution volume (tDV) was derived from Logan plot analysis. As a result, although both BP and tDV tended to be underestimated by the shortened method, the estimates from the shortened protocol had good linear relationships with those of the full-length protocol. In conclusion, if approximately 10% differences in the estimated results are acceptable for a specific purpose, then a 60-min measurement protocol is capable of providing reliable results.
  • Evaluation of k(2) imaging algorithm with C-11-verapamil using clustering-based kinetic approach, Yuichi Kimura, M. Naganawa, K. Oda, K. Ishii, I. Leir, K. Ishiwata, NEUROIMAGE, NEUROIMAGE, 41, T68 - T68, 2008 , Refereed
  • Presynaptic and postsynaptic nigrostriatal dopaminergic functions in multiple system atrophy, Masaya Hashimoto, Keiichi Kawasaki, Masahiko Suzuki, Kazuko Mitania, Shigeo Murayama, Masahiro Mishina, Keiichi Oda, Yuichi Kimura, Kiichi Ishiwata, Kenji Ishiia, Kiyoharu Inoue, NEUROREPORT, NEUROREPORT, 19(2), 145 - 150, Jan. 2008 , Refereed
    Summary:A simultaneous evaluation of presynaptic and postsynaptic dopaminergic positron emission tomography markers, the dopamine transporters and the dopamine D-2-like receptors, was performed in eight patients with parkinsonian phenotype of multiple system atrophy. Both presynaptic and postsynaptic markers were revealed to have declined in such a manner that they kept strong positive correlation throughout the striatum of all patients, suggesting that the degeneration process in the striatum may involve the entire structure of the dopaminergic synapse. In two L-3,4,dihydroxyphenyl-alanine-responsive cases, the balance of decline in two markers was relatively shifted to presynaptic dominant side. Correlative positron emission tomography study of presynaptic and postsynaptic dopaminergic function may be useful for the diagnosis of multiple system atrophy and to understand the mechanisms of its temporal L-3,4,dihydroxyphenyl-alanine responsiveness.
  • Distribution volume as an alternative to the binding potential for sigma(1) receptor imaging, Yuichi Kimura, Mika Naganawa, Muneyuki Sakata, Masatomo Ishikawa, Masahiro Mishina, Keiichi Oda, Kenji Ishii, Kiichi Ishiwata, ANNALS OF NUCLEAR MEDICINE, ANNALS OF NUCLEAR MEDICINE, 21(9), 533 - 535, Nov. 2007 , Refereed
    Summary:yThe applicability of total distribution volume (DVt) as an alternative to binding potential (BP) was investigated for neuroreceptor mapping by positron emission tomography (PET). BP is defined as a representative quantity of receptor density. However, for making parametric images of BP, a reference region where an aimed receptor has a very low density is assumed to exist in a target region such as the brain. Thus, if the kinetics of a radioligand for target receptors does not permit an appropriate reference region, BP imaging is unattainable. In this study, [C-11]SA4503 PET is taken to be considered which has a high affinity to the sigma(1) receptors. Through a clinical investigation using wide ranges of physiological situations, ages, sex, diseases, and selective drug-loading conditions, DVt has a good linear relationship with BP, and the images can be used as a spatial distribution of sigma(1) density.
  • High occupancy of sigma-1 receptors in the human brain after single oral administration of fluvoxamine: A positron emission tomography study using [C-11]SA4503, Masatomo Ishikawa, Kiichi Ishiwata, Kenji Ishii, Yuichi Kimura, Muneyuki Sakata, Mika Naganawa, Keiichi Oda, Ryousuke Miyatake, Mihisa Fujisaki, Eiji Shimizu, Yukihiko Shirayama, Masaomi Iyo, Kenji Hashimoto, BIOLOGICAL PSYCHIATRY, BIOLOGICAL PSYCHIATRY, 62(8), 878 - 883, Oct. 2007 , Refereed
    Summary:Background: Sigma-1 receptors might be implicated in the pathophysiology of psychiatric diseases, as well as in the mechanisms of action of some selective serotonin reuptake inhibitors (SSRIs). Among the several SSRIs, fluvoxamine has the highest affinity for sigma-1 receptors (Ki = 36 nM), whereas paroxetine shows low affinity (Ki = 1893 nM). The present study was undertaken to examine whether fluvoxamine binds to sigma-1 receptors in living human brain. Methods: A dynamic positron emission tomography (PET) data acquisition using the selective sigma-1 receptor ligand [C-11]SA4503 was performed with arterial blood sampling to evaluate quantitatively the binding of [C-11]SA4503 to sigma-1 receptors in 15 healthy male volunteers. Each subject had two PET scans before and after randomly receiving a single dose of either fluvoxa mine (50,100,150, or 200 mg) or paroxetine (20 mg). The binding potential of [C-11]SA4503 in 9 regions of the brain was calculated by a 2-tissue 3-compartment model. In addition, we examined the effects of functional polymorphisms of the sigma-1 receptor (SIGMARI) gene on the binding potential of [C-11]SA4503. Results: Fluvoxamine bound to sigma-1 receptors in all brain regions in a dose-dependent manner, whereas paroxetine did not bind to sigma-1 receptors. However, there was no association between the SIGMAR1 gene polymorphism GC-241-240TT and binding potential. Conclusions: The study demonstrated that fluvoxamine bound to sigma-1 receptors in living human brain at therapeutic doses. These findings suggest that sigma-1 receptors may play an important role in the mechanism of action of fluvoxamine.
  • Evaluation of distribution of adenosine A(2A) receptors in normal human brain measured with [(11)C]TMSX PET, Masahiro Mishina, Kiichi Ishiwata, Yuichi Kimura, Mika Naganawa, Keiichi Oda, Shiro Kobayashi, Yasuo Katayama, Kenji Ishii, SYNAPSE, SYNAPSE, 61(9), 778 - 784, Sep. 2007 , Refereed
    Summary:Adenosine A(2A) receptor (A2AR) is thought to interact with dopamine D(2) receptor. Selective A2AR antagonists have attracted attention as the treatment of Parkinson's disease. In this study, we investigated the distribution of the A2ARs in the living human brain using positron emission tomography (PET) and [7-methyl-(11)C]-(E)-8-(3,4,5-trimethoxystyryl)-1,3,7-trimethylxanthine ([(11)C]TMSX). We recruited five normal male subjects. A dynamic series of PET scans was performed for 60 min, and the arterial blood was sampled during the scan to measure radioactivity of the parent compound and labeled metabolites. Circular regions of interest of 10-mm diameter were placed in the PET images over the cerebellum, brainstem, thalamus, head of caudate nucleus, anterior and posterior putamen, frontal lobe, temporal lobe, parietal lobe, occipital lobe, and posterior cingulate gyrus for each subject. A two-tissue, three-compartment model was used to estimate K(1), k(2), k(3), and k(4) between metabolite-corrected plasma and tissue time activity of [(11)C]TMSX. The binding potential (BP) was the largest in the anterior (1.25) and posterior putamen (1.20), was next largest in the head of caudate nucleus (1.05) and thalamus (1.03), and was small in the cerebral cortex, especially frontal lobe (0.46). [(11)C]TMSX PET showed the largest BP in the striatum in which A2ARs were enriched as in postmortem and nonhuman studies reported, but that the binding of [(11)C]TMSX was relatively larger in the thalamus to compare with other mammals. To date, [(11)C]TMSX is the only promising PET ligand, which is available to clinical use for mapping the A2ARs in the living human brain. (c) 2007 Wiley-Liss, Inc.
  • Temporal and spatial blood information estimation using Bayesian ICA in dynamic cerebral positron emission tomography, Mika Naganawa, Yuichi Kimura, Kenji Ishii, Keiichi Oda, Kiichi Ishiwata, DIGITAL SIGNAL PROCESSING, DIGITAL SIGNAL PROCESSING, 17(5), 979 - 993, Sep. 2007 , Refereed
    Summary:Positron emission tomography (PET) is a nuclear medicine technique that provides tomographic images of the distribution of positron-emitting radiopharmaceuticals. We have previously proposed a method for estimating an input blood curve based on a standard independent component analysis using a specially designed cost function and a preprocessing scheme. While the input blood curve was successfully extracted, the voxels with a negative sign remained in the estimated blood volume image. They should be positive because of its physiological meaning. In this study, ensemble learning introduces a nonnegative constraint to correctly estimate temporal and spatial blood information from dynamic cerebral PET images. The rectified Gaussian distribution and exponential distribution were adopted as nonnegative priors on the elements of the time curves and the source images, respectively. The proposed method (extraction of the plasma time-activity curve using ensemble learning, EPEL) was applied to human brain PET studies with three kinds of radiopharmaceuticals for investigating its validity. The results implied that the EPEL-estimated blood curve was similar to the measured curve, and that the estimated blood volume correlated well with that measured clinically. We concluded that EPEL is a valid method for estimating the blood curve and the blood volume image in a noninvasive way. (C) 2007 Elsevier Inc. All rights reserved.
  • The use of positron emission tomography and [F-18] fluorodeoxyglucose for functional imaging of muscular activity during exercise with a stride assistance system, Hiroyuki Shimada, Yuichi Kimura, Takao Suzuki, Takashi Hirata, Miho Sugiura, Yosuke Endo, Ken Yasuhara, Kei Shimada, Keishiro Kikuchi, Masaya Hashimoto, Masatomo Ishikawa, Keiichi Oda, Kenji Ishii, Kiichi Ishiwata, IEEE TRANSACTIONS ON NEURAL SYSTEMS AND REHABILITATION ENGINEERING, IEEE TRANSACTIONS ON NEURAL SYSTEMS AND REHABILITATION ENGINEERING, 15(3), 442 - 448, Sep. 2007 , Refereed
    Summary:The aim of this study was to investigate the use of [F-18] fluorodeoxyglucose and positron emission tomography(FDG PET) for quantitative evaluation of glucose metabolism in skeletal muscle during walking. Ten young males underwent FDG PET twice during walks, which were done with or without an automated stride assistance system (SAS). Walk ratios were significantly increased by the SAS in seven subjects. Regional glucose metabolism in muscles between the crista iliaca: and the planta was clearly visualized in all ten subjects. Glucose utilization increased significantly in the tibialis posterior and medial gastrocnemius muscles of the seven subjects in whom walk ratios were increased by the SAS. FDG PET is useful for analysis of muscle activity during exercise and rehabilitation.
  • Synthesis and evaluation of fluorine-18-labeled SA4503 as a selective sigma(1) receptor ligand for positron emission tomography, Kazunori Kawamura, Hideo Tsukada, Kazuhiro Shiba, Chieko Tsuji, Norihiro Harada, Yuichi Kimura, Klichi Ishlwata, NUCLEAR MEDICINE AND BIOLOGY, NUCLEAR MEDICINE AND BIOLOGY, 34(5), 571 - 577, Jul. 2007 , Refereed
    Summary:The [F-18]fluoromethyl analog of the sigma, selective ligand 1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine dihydrochloride (SA4503) ([F-18]FM-SA4503) was prepared and its potential evaluated for the in vivo measurement of sigma, receptors with positron emission tomography (PET). FM-SA4503 had selective affinity for the sigma, receptor (K-i for sigma, receptor, 6.4 nM; Ki for sigma(2) receptor, 250 nM) that was compatible with the affinity of SA4503 (K-i for sigma, receptor, 4.4 nM; Ki for sigma2 receptor, 242 nM). [F-18]FM-SA4503 was synthesized by F-18-fluoromethylation of O-demethyl SA4503 in the radiochemical yield of 2.9-16.6% at the end of bombardment with a specific activity of 37.8-283 TBq/mmol at the end of synthesis. In mice, the uptake of [F-18]FM-SA4503 in the brain was gradually increased for 30 min after injection, and then decreased. In the blocking study, brain uptake was significantly decreased by coinjection of haloperidol to 32% of control, and FM-SA4503 to 52% of control. In PET study of the monkey brain, high uptake was found in the cerebral cortex, thalamus and striatum. The radioactivity level of [F-18]FM-SA4503 in the brain regions gradually increased over a period of 120 min after injection, followed by a stable plateau phase until 180 min after injection. In pretreatment with haloperidol measurement of the monkey brain, the radioactivity level was 22-32% and 11-25% of the baseline at 60 and 180 min, respectively, after injection, suggesting high receptor-specific binding. [F-18]FM-SA4503 showed specific binding to sigma, receptors in mice and monkeys;, therefore, [F-18]FMSA4503 has the potential for mapping sigma, receptors in the brain. (c) 2007 Elsevier Inc. All rights reserved.
  • Quantification of adenosine A(2A) receptors in the human brain using [C-11]TMSX and positron emission tomography, Mika Naganawa, Yuichi Kimura, Masahiro Mishina, Yoshitsugu Manabe, Kunihiro Chihara, Keiichi Oda, Kenji Ishii, Kiichi Ishiwata, EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, 34(5), 679 - 687, May 2007 , Refereed
    Summary:Purpose [7-methyl-C-11]-(E)-8-(3,4,5-trimethoxystyryl)-1,3,7-trimethylxanthine ([C-11]TMSX) is a positron-emitting adenosine A(2A) receptor (A2AR) antagonist for visualisation of A2AR distribution by positron emission tomography (PET). The aims of this paper were to use a kinetic model to analyse the behaviour of [C-11]TMSX in the brain and to examine the applicability of the Logan plot. We also studied the applicability of a simplified Logan plot by omitting metabolite correction and arterial blood sampling. Methods The centrum semiovale was used as a reference region on the basis of a post-mortem study showing that it has a negligibly low density of A2ARs. Compartmental analysis was performed in five normal subjects. Parametric images of A2AR binding potential (BP) were also generated using a Logan plot with or without metabolite correction and with or without arterial blood sampling. To omit arterial blood sampling, we applied a method to extract the plasma-related information using independent component analysis (EPICA). Results The estimated K-1/k(2) was confirmed to be common in the centrum semiovale and main cortices. The three-compartment model was well fitted to the other regions using the fixed value of K-1/k(2) estimated from the centrum semiovale. The estimated BPs using the Logan plot matched those derived from compartment analysis. Without the metabolite correction, the estimate of BP underestimated the true value by 5%. The estimated BPs agreed regardless of arterial blood sampling. Conclusion A three-compartment model with a reference region, the centrum semiovale, describes the kinetic behaviour of [C-11]TMSX PET images. A2ARs in the human brain can be visualised as a BP image using [C-11]TMSX PET without arterial blood sampling.
  • Mapping of human cerebral sigma, receptors using positron emission tomography and [C-11]SA4503, Muneyuki Sakata, Yuichi Kimura, Mika Naganawa, Kelichi Oda, Kenji Ishii, Kunihiro Chihara, Kiichi Ishiwata, NEUROIMAGE, NEUROIMAGE, 35(1), 1 - 8, Mar. 2007 , Refereed
    Summary:The objective of this study was to establish the kinetic analysis for mapping sigma, receptors (cFIRs) in the human brain by positron emission tomography (PET) with [C-11]SA4503. The crlRs are considered to be involved in various neurological and psychiatric diseases. [C-11]SA4503 is a recently developed radioligand with high and selective affinity for cFIRs, and we have first applied it to clinical studies. Nine healthy male subjects each underwent a dynamic 90-min PET scan after injection of [C-11]SA4503. In addition to the baseline measurement, three of the nine subjects underwent a second [C-11] SA4503-PET after partial blockade of sigma IRs by oral administration of haloperidol, a sigma receptor antagonist. Full kinetic analysis using two times nonlinear estimations was applied for fitting a two-tissue three-compartment model to determine the binding potential (BP) and total distribution volume (tDV) of [C-11]SA4503. Graphical analysis with a Logan plot was also applied for estimations of tDV. The regional distribution patterns of BP and tDV in 11 regions were compatible with those of previously reported crlRs in vitro. The reduced binding sites of sigma IRs by haloperidol were appropriately evaluated. The tDVs derived from the two methods matched each other well. The Logan plot offered images of the tDV, which reflected sigma 1R densities, and the tDV in the images decreased after haloperidol loading. Moreover, comparison of BPs calculated with and without metabolite correction for plasma input function indicated that the metabolite correction could be omitted. We concluded that this method enables the quantitative analysis of sigma 1Rs in the human brain. (c) 2006 Elsevier Inc. All rights reserved.
  • Inter-crystal scatter identification for a depth-sensitive detector using support vector machine for small animal positron emission tomography, Eiji Yoshida, Kelshi Kitamura, Yuichi Kimura, Fumihiko Nishikido, Kengo Shibuya, Taiga Yamaya, Hideo Murayama, NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH SECTION A-ACCELERATORS SPECTROMETERS DETECTORS AND ASSOCIATED EQUIPMENT, NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH SECTION A-ACCELERATORS SPECTROMETERS DETECTORS AND ASSOCIATED EQUIPMENT, 571(1-2), 243 - 246, Feb. 2007 , Refereed
    Summary:In a conventional positron emission tomography (PET) detector, detected events are projected onto a 2D position histogram by an Anger calculation for crystal identification. However, the measured histogram is affected by inter-crystal scatterings (ICS) which occur in the entire detector. Peaks which are projected for each crystal in the histogram are blurred, and this causes ICS mispositioning. A depth-of-interaction (DOI) detector has been developed for the small animal PET scanner jPET-RD. This DOI detector uses 32 x 32 crystals with four layers and a 256-channel multi-anode flat panel photomultiplier tube (FP-PMT) which was developed by Hamamatsu Photonics K.K. Each crystal element is 1.45 x 1.45 x 4.5 mm(3). The FP-PMT has a large detective area (49 x 49 mm(2)) and a small anode pitch (3.04 mm). Therefore, the FP-PMT can extensively trace the behavior of incident gamma rays in the crystals including ICS event. We, therefore, propose a novel method for ICS estimation using a statistical pattern recognition algorithm based on a support vector machine (SVM). In this study, we applied the SVM for discriminating photoelectric events from ICS events generated from multiple-anode outputs. The SVM was trained by uniform irradiation events generated from a detector simulator using a Monte Carlo calculation. The success rate for ICS event identification is about 78% for non-training data. The SVM can achieve a true subtraction of ICS events from measured events. and it is also useful for random correction in PET. (c) 2006 Elsevier B.V. All rights reserved.
  • Omission of serial arterial blood sampling for quantitative analysis of monkey PET data using independent component analysis-based method, Mika Naganawa, Hideo Tsukada, Hiroyuki Ohba, Kiichi Ishiwata, Chie Seki, Miho Shidahara, Yuichi Kimura, IEEE Nuclear Science Symposium Conference Record, IEEE Nuclear Science Symposium Conference Record, 6, 4510 - 4512, 2007 , Refereed
    Summary:Serial arterial blood sampling is required to measure a blood input function in quantitative estimation of physiological parameters in dynamic positron emission tomography (PET) studies. However, blood sampling is problematic for animal PET study due to limited amount of blood allowed. Therefore, it is of interest to obviate arterial blood sampling. We have previously proposed a method for estimating a blood input curve based on independent component analysis in human study. In this paper, we applied the method to monkey [18F]fluorodeoxyglucose studies, and validated its applicability by comparing the estimated regional cerebral metabolic rates of glucose using the estimated and the measured blood input function. Experimental results suggest that the proposed method enables quantitative analysis in PET without serial arterial blood sampling not only in human data but also in monkey data. ©2007 IEEE.
  • Inter-crystal scatter identification for a depth-sensitive detector using multi-anode outputs, Eiji Yoshida, Keishi Kitamura, Yuichi Kimura, Fumihiko Nishikido, Kengo Shibuya, Taiga Yamaya, Hideo Murayama, IEEE Nuclear Science Symposium Conference Record, IEEE Nuclear Science Symposium Conference Record, 3, 1860 - 1864, 2007 , Refereed
    Summary:In conventional PET detectors, detected events are projected to a 2D position histogram using the Anger calculation for crystal identification. Inter-crystal scatter (ICS) events cause mispositioned identification of crystals because peaks projected by each crystal in the histogram are blurred. A depth-of-interaction (DOI) detector has been developed for the small animal PET scanner: jPET-RD. This DOI detector uses four-layered arrays of 32 × 32 crystals and a 256-channel multi-anode flat panel photomultiplier tube (FP-PMT). Each crystal is 1.45 mm × 1.45 mm × 4.5 mm. The FP-PMT has a large detective area and small anode pitch. We think that the FP-PMT has a good potential for tracing the scattered gamma rays in the crystals. In this study, we therefore propose a novel method for ICS event identification using the principle component analysis (PCA). The PCA is applied to multiple-anode outputs in order to discriminate photoelectric events from ICS events. The first principle component depends on the number of anode outputs deposited energy through preprocessing. Numerical simulation results show that the rate of the ICS identification by the proposed method is about 77.6 % at a 511 keV uniform irradiation. Also, by incorporating the PCA technique in our method we can identify only events which have large effect on spatial resolution in the ICS events. Our method can archive a true subtraction of ICS events from measured events. © 2006 IEEE.
  • Omission of serial arterial blood sampling for quantitative analysis of monkey PET data using independent component analysis-based method, Mika Naganawa, Hideo Tsukada, Hiroyuki Ohba, Kiichi Ishiwata, Chie Seki, Miho Shidahara, Yuichi Kimura, 2007 IEEE NUCLEAR SCIENCE SYMPOSIUM CONFERENCE RECORD, VOLS 1-11, 2007 IEEE NUCLEAR SCIENCE SYMPOSIUM CONFERENCE RECORD, VOLS 1-11, 4510 - +, 2007 , Refereed
    Summary:Serial arterial blood sampling is required to measure a blood input function in quantitative estimation of physiological parameters in dynamic positron emission tomography (PET) studies. However, blood sampling is problematic for animal PET study due to limited amount of blood allowed. Therefore, it is of interest to obviate arterial blood sampling. We have previously proposed a method for estimating a blood input curve based on independent component analysis in human study. In this paper, we applied the method to monkey [F-18]fluorodeoxyglucose studies, and validated its applicability by comparing the estimated regional cerebral metabolic rates of glucose using the estimated and the measured blood input function. Experimental results suggest that the proposed method enables quantitative analysis in PET without serial arterial blood sampling not only in human data but also in monkey data.
  • A feasibility study of [C-11]SA4503-PET for evaluating sigma(1) receptor occupancy by neuroleptics: the binding of haloperidol to sigma(1) and dopamine D-2-like receptors, Kiichi Ishiwata, Kenji Oda, Muneyuki Sakata, Yuichi Kimura, Kazunori Kawamura, Keiichi Oda, Toru Sasaki, Mika Naganawa, Kunihiro Chihara, Yoshiro Okubo, Kenji Ishii, ANNALS OF NUCLEAR MEDICINE, ANNALS OF NUCLEAR MEDICINE, 20(8), 569 - 573, Oct. 2006 , Refereed
    Summary:We investigated feasibility of positron emission tomography (PET) with [C-11]SA4503 for evaluating the sigma(1) receptor occupancy rate by neuroleptics. Haloperidol, which is well known to bind dopamine D-2-like receptor (D2R) as well as to be a representative non-selective antagonist for sigma I receptor (at R), was selected as a model drug. Three healthy male subjects underwent 60-min [C-11]raclopride-PET and 90-min [C-11]SA4503-PET scans successively at a 120-min interval twice in a day for baseline measurement and on another day for haloperidol-loading measurement 16 hours after peroral administration of 3 mg of halopefidol. Binding potential (BP) of [C-11]raclopfide and [C-11]SA4503 was quantitatively evaluated and the sigma 1R and D2R occupancy rates were determined. D2R occupancy rates by haloperidol were 64% and 62% in the caudate and putamen, respectively, 16 h after the administration, while at R occupancy rates were approximately 80% in all seven regions investigated including the caudate, putamen and cerebellum 18 h after the administration, suggesting that the at R receptor occupancy rate by haloperidol was slightly larger than the D2R receptor occupancy rate. We concluded that [C-11]SA4503-PET can be used for evaluating the sigma lR occupancy rates by neuroleptics or other drugs.
  • MAP-based kinetic analysis for voxel-by-voxel compartment model estimation: Detailed imaging of the cerebral glucose metabolism using FDG, Y Kimura, M Naganawa, J Yamaguchi, Y Takabayashi, A Uchiyama, K Oda, K Ishii, K Ishiwata, NEUROIMAGE, NEUROIMAGE, 29(4), 1203 - 1211, Feb. 2006 , Refereed
    Summary:We propose a novel algorithm for voxel-by-voxel compartment model analysis based on a maximum a posteriori (MAP) algorithm. Voxel-by-voxel compartment model analysis can derive functional images of living tissues, but it suffers from high noise statistics in voxel-based PET data and extended calculation times. We initially set up a feature space of the target radiopharmaceutical composed of a measured plasma time activity curve and a set of compartment model parameters, and measured the noise distribution of the PET data. The dynamic PET data were projected onto the feature space, and then clustered using the Mahalanobis distance. Our method was validated using simulation studies, and compared with ROI-based ordinary kinetic analysis for FDG. The parametric images exhibited an acceptable linear relation with the simulations and the ROI-based results, and the calculation time took about 10 min. We therefore concluded that our proposed MAP-based algorithm is practical. (c) 2005 Elsevier Inc. All rights reserved.
  • Inter-crystal scatter identification for a depth-sensitive detector using multi-anode outputs, Eiji Yoshida, Keishi Kitamura, Yuichi Kimura, Fumihiko Nishikido, Kengo Shibuya, Taiga Yamaya, Hideo Murayama, 2006 IEEE NUCLEAR SCIENCE SYMPOSIUM CONFERENCE RECORD, VOL 1-6, 2006 IEEE NUCLEAR SCIENCE SYMPOSIUM CONFERENCE RECORD, VOL 1-6, 1860 - 1864, 2006 , Refereed
    Summary:In conventional PET detectors, detected events are projected to a 2D position histogram using the Anger calculation for crystal identification. Inter-crystal scatter (ICS) events cause mispositioned identification of crystals because peaks projected by each crystal in the histogram are blurred. A depth-of-interaction (DOI) detector has been developed for the small animal PET scanner: jPET-RD. This DOI detector uses four-layered arrays of 32 x 32 crystals and a 256-channel multi-anode flat panel photomultiplier tube (FP-PMT). Each crystal is 1.45 mm x 1.45 mm x 4.5 mm. The FP-PMT has a large detective area and small anode pitch. We think that the FP-PMT has a good potential for tracing the scattered gamma rays in the crystals. In this study, we therefore propose a novel method for ICS event identification using the principle component analysis (PCA). The PCA is applied to multiple-anode outputs in order to discriminate photoelectric events from ICS events. The first principle component depends on the number of anode outputs deposited energy through preprocessing. Numerical simulation results show that the rate of the ICS identification by the proposed method is about 77.6 % at a 511 keV uniform irradiation. Also, by incorporating the PCA technique in our method we can identify only events which have large effect on spatial resolution in the ICS events. Our method can archive a true subtraction of ICS events from measured events.
  • Use of reference tissue models for quantification of histamine H-1 receptors in human brain by using positron emission tomography and [C-11]doxepin, Atsuro Suzuki, Keizo Ishii, Manabu Tashiro, Yuichi Kimura, Kenji Ishii, Kiichi Ishiwata, Hideki Mochizuki, Kazuhiko Yanai, Miroshi Watabe, FUTURE MEDICAL ENGINEERING BASED ON BIONANOTECHNOLOGY, PROCEEDINGS, FUTURE MEDICAL ENGINEERING BASED ON BIONANOTECHNOLOGY, PROCEEDINGS, 817 - +, 2006 , Refereed
    Summary:The aim of the present study is to evaluate the validity of the Simplified Reference Tissue Model (SRTM) and of Logan Graphical Analysis with Reference Tissue (LGAR) for quantification of histamine H-1 receptors (H1Rs) by using positron emission tomography (PET) with [C-11]doxepin. These model-based analytic methods (SRTM and LGAR) are compared to Logan Graphical Analysis (LGA) and to the one-tissue model (1TM), using complete datasets obtained from 5 healthy volunteers. Since H1R concentration in the cerebellum can be regarded as negligibly small, the cerebellum was used as a reference tissue in the present study. The comparison of binding potential (BP) values estimated by LGAR and 1TM showed good agreement, on the other hand, SRTM was unstable concerning parameter estimation in several regions of the brain. By including the results of noise analysis, LGAR became a reliable method for parameter estimation of [C-11]doxepin data in the cortical regions.
  • Brain histamine H-1 receptor occupancy of orally administered antihistamines measured by positron emission tomography with C-11-doxepin in a placebo-controlled crossover study design in healthy subjects: a comparison of olopatadine and ketotifen, M Tashiro, H Mochizuki, Y Sakurada, K Ishii, K Oda, Y Kimura, T Sasaki, K Ishiwata, K Yanai, BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 61(1), 16 - 26, Jan. 2006 , Refereed
    Summary:Aims The strength of sedation due to antihistamines can be evaluated by using positron emission tomography (PET). The purpose of the present study is to measure histamine H-1 receptor (H1R) occupancy due to olopatadine, a new second-generation antihistamine and to compare it with that of ketotifen. Methods Eight healthy males (mean age 23.5 years-old) were studied following single oral administration of olopatadine 5 mg or ketotifen 1 mg using PET with C-11-doxepin in a placebo-controlled crossover study design. Binding potential ratio and H1R occupancy were calculated and were compared between olopatadine and ketotifen in the medial prefrontal (MPFC), dorsolateral prefrontal (DLPFC), anterior cingulate (ACC), insular (IC), temporal (TC), parietal (PC), occipital cortices (OC). Plasma drug concentration was measured, and correlation of AUC to H1R occupancy was examined. Results H1R occupancy after olopatadine treatment was significantly lower than that after ketotifen treatment in the all cortical regions (P < 0.001). Mean H1R occupancies for olopatadine and ketotifen were, respectively: MPFC, 16.7 vs. 77.7; DLPFC, 14.1 vs. 85.9; ACC, 14.7 vs. 76.1; IC, 12.8 vs. 69.7; TC, 12.5 vs. 66.5; PC, 13.9 vs. 65.8; and OC, 19.5 vs. 60.6. Overall cortical mean H1R occupancy of olopatadine and ketotifen were 15% and 72%, respectively. H1R occupancy of both drugs correlated well with their respective drug plasma concentrations (P < 0.001). Conclusion It is suggested that 5 mg oral olopatadine, with its low H1R occupancy and thus minimal sedation, could safely be used an antiallergic treatment for various allergic disorders.
  • Greater adenosine A(2A) receptor densities in cardiac and skeletal muscle in endurance-trained men: a [C-11]TMSX PET study, M Mizuno, Y Kimura, K Tokizawa, K Ishii, K Oda, T Sasaki, Y Nakamura, Muraoka, I, K Ishiwata, NUCLEAR MEDICINE AND BIOLOGY, NUCLEAR MEDICINE AND BIOLOGY, 32(8), 831 - 836, Nov. 2005 , Refereed
    Summary:We examined the densities of adenosine A(2A) receptors in cardiac and skeletal muscles between untrained and endurance-trained subjects using positron emission tomography (PET) and [7-methyl-C-11]-(E)-8-(3,4,5-trimethoxystyryl)-1,3,7-trimethylxanthine ([C-11]TMSX), a newly developed radioligand for mapping adenosine A(2A) receptors. Five untrained and five endurance-trained subjects participated in this study. The density of adenosine A(2A) receptors was evaluated as the distribution volume of [C-11]TMSX in cardiac and triceps brachii muscles in the resting state using PET. The distribution volume of [C-11]TMSX in the myocardium was significantly greater than in the triceps brachii muscle in both groups. Further, distribution volumes [C-11]TMSX in the trained subjects were significantly grater than those in untrained subjects (myocardium, 3.6 +/- 0.3 vs. 3.1 +/- 0.4 ml g(-1); triceps brachii muscle, 1.7 +/- 0.3 vs. 1.2 +/- 0.2 ml g(-1), respectively). These results indicate that the densities of adenosine A(2A) receptors in the cardiac and skeletal muscles are greater in the endurance-trained men than in the untrained men. (c) 2005 Elsevier Inc. All rights reserved.
  • Use of reference tissue models for quantification of histamine H-1 receptors in human brain by using positron emission tomography and [C-11]doxepin, A Suzuki, M Tashiro, Y Kimura, H Mochizuki, K Ishii, H Watabe, K Yanai, K Ishiwata, K Ishii, ANNALS OF NUCLEAR MEDICINE, ANNALS OF NUCLEAR MEDICINE, 19(6), 425 - 433, Sep. 2005 , Refereed
    Summary:The aim of the present study is to evaluate the validity of the simplified reference tissue model (SRTM) and of Logan graphical analysis with reference tissue (LGAR) for quantification of histamine H-1 receptors (H1Rs) by using positron emission tomography (PET) with [C-11]doxepin. These model-based analytic methods (SRTM and LGAR) are compared to Logan graphical analysis (LGA) and to the one-tissue model (1TM), using complete datasets obtained from 5 healthy volunteers. Since H1R concentration in the cerebellum can be regarded as negligibly small, the cerebellum was selected as the reference tissue in the present study. The comparison of binding potential (BP) values estimated by LGAR and 1TM showed good agreement; on the other hand, SRTM turned out to be unstable concerning parameter estimation in several regions of the brain. By including the results of noise analysis, LGAR became a reliable method for parameter estimation of [C-11]doxepin data in the cortical regions.
  • Function of sigma(1) receptors in Parkinson's disease, M Mishina, K Ishiwata, K Ishii, S Kitamura, Y Kimura, K Kawamura, K Oda, T Sasaki, O Sakayori, M Hamamoto, S Kobayashi, Y Katayama, ACTA NEUROLOGICA SCANDINAVICA, ACTA NEUROLOGICA SCANDINAVICA, 112(2), 103 - 107, Aug. 2005 , Refereed
    Summary:Objective - The objective of this study was to investigate the mapping of sigma(1) receptors in Parkinson's disease (PD) using [C-11]SA4503 and positron emission tomography (PET), and to assess whether sigma1 receptors are involved in the damaged dopaminergic system in PD patients. Materials and methods - We studied seven normal volunteers and six PD patients. The low density of dopamine transporters and the normal or high density of dopamine receptors were confirmed in the putamen of all patients using [C-11]CFT and [C-11] RAC PET. A dynamic series of PET data acquisition was performed with arterial blood sampling. We computed the binding potential (BP) of [C-11]SA4503. Results - In PD patients, the BP was significantly lower on the more affected than the less affected side of the anterior putamen, although there was no significant difference with respect to the BP between patients and controls. Conclusions - Release of dopamine is reduced asymmetrically in the putamen of early PD. [C-11]SA4503 PET is an indicator of presynaptic dopaminergic damage in PD.
  • Omission of serial arterial blood sampling in neuroreceptor imaging with independent component analysis, M Naganawa, Y Kimura, T Nariai, K Ishii, K Oda, Y Manabe, K Chihara, K Ishiwata, NEUROIMAGE, NEUROIMAGE, 26(3), 885 - 890, Jul. 2005 , Refereed
    Summary:We have previously proposed a statistical method for extracting a plasma time-activity curve (pTAC) from dynamic PET images, named EPICA, for kinetic analysis of cerebral glucose metabolism. We assumed that the dynamic PET images consist of a blood-related component and a tissue-related component which are spatially independent in a statistical sense. The aim of this study is to investigate the utility of EPICA in imaging total distribution volume (DVt) and binding potential (BP) with Logan plots in a neuroreceptor mapping study. We applied EPICA to dynamic [C-11]MPDX PET images in 25 subjects, including healthy subjects and patients with brain diseases, and validated the estimated pTACs. [C-11]MPDX is a newly developed radiopharmaceutical for mapping cerebral adenosine A, receptors. EPICA successfully extracted pTAC for all 25 subjects. Parametric images of DVts were estimated by applying Logan plots with the EPICA-estimated pTAC and then used to define a reference region. The BPs estimated using EPICA were evaluated in 18 subjects by ROI-based comparison with those obtained using the nonlinear least squares method (NLSM). The calculated BPs were identical to the estimates using NLSM in each subject. We conclude that EPICA is a promising technique that generates parametric images of DVt and BP in neuroreceptor mapping without requiring arterial blood sampling. (c) 2005 Elsevier Inc. All rights reserved.
  • Preclinical and clinical evaluation of O-[C-11]methyl-L-tyrosine for tumor imaging by positron emission tomography, K Ishiwata, H Tsukada, K Kubota, T Nariai, N Harada, K Kawamura, Y Kimura, K Oda, R Iwata, K Ishii, NUCLEAR MEDICINE AND BIOLOGY, NUCLEAR MEDICINE AND BIOLOGY, 32(3), 253 - 262, Apr. 2005 , Refereed
    Summary:We performed preclinical and clinical studies of O-[C-11]methyl-L-tyrosine, a potential tracer for imaging amino acid transport Of tumors by positron emission tomography (PET). Examinations of the radiation-absorbed dose by O-[C-11]methyl-L-tyrosine and the acute toxicity and mutagenicity of O-methyl-L-tyrosine showed suitability of the tracer for clinical use. The whole-body imaging of monkeys and healthy humans by PET showed low uptake of O-[C-11]methyl-L-tyrosine in all normal organs except for the urinary track and bladder, suggesting that the O-[C-11]methyl-L-tyrosine PET has the potential for tumor imaging in the whole-body. Finally, the brain tumor imaging was preliminarily demonstrated. (c) 2005 Elsevier Inc. All rights reserved.
  • First visualization of adenosine A(2A) receptors in the human brain by positron emission tomography with [C-11]TMSX, K Ishiwata, M Mishina, Y Kimura, K Oda, T Sasaki, K Ishii, SYNAPSE, SYNAPSE, 55(2), 133 - 136, Feb. 2005 , Refereed
    Summary:[C-11]TMSX is a new positron emission tomography (PET) radioligand that provides visualization of adenosine A(2A) receptors (A(2A)Rs) in the brain, heart and skeletal muscle. Here we report on the first visualization of the A(2A)Rs in the human brain by PET and [C-11]TMSX in a male healthy volunteer, compared with the adenosine A, receptors (A(1)Rs) and dopamine D-2 receptors (D(2)Rs) which were measured by PET with [C-11]MPDX and [C-11]raclopride, respectively. The distribution volume (DV) of [C-11]TMSX in the baseline was relatively high in the head of caudate nucleus, putamen, and thalamus and relatively low in the cortical regions. Infusion of theophylline, a nonselective A(2A)R antagonist (K for A(2A)Rs = 16000 nM for theophylline vs 5.9 nM for TMSX), slightly reduced the DVs in the head of caudate nucleus (8.0% reduction) and putamen (4.5% reduction), but not in the other regions having much lower levels of A(2A)Rs, demonstrating the A(2A)R-specific binding of [C-11]TMSX. On the other hand, the A(1)Rs were widely distributed in the whole brain except for the cerebellum, while the binding potential of [C-11]raclopride was predominantly high in the striatum. We concluded that [C-11]TMSX is an applicable PET ligand for mapping the A(2A)Rs in the caudate nucleus and putamen in clinical studies because of no availability of other radioligands until now. The [C-11]TMSX PET is of great interest for studying the pathophysiology of neurological and psychiatric disorders together with the [C-11]raclopride PET for D(2)Rs evaluation and/or the [C-11]MPDX PET for A(1)Rs evaluation. (C) 2004 Wiley-Liss, Inc.
  • Extraction of a plasma time-activity curve from dynamic brain PET images based on independent component analysis, M Naganawa, Y Kimura, K Ishii, K Oda, K Ishiwata, A Matani, IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING, IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING, 52(2), 201 - 210, Feb. 2005 , Refereed
    Summary:A compartment model has been used for kinetic analysis of dynamic positron emission tomography (PET) data [e.g., 2-deoxy-2-F-18-fluoro-D-glucose (FDG)]. The input function of the model [the plasma time-activity curve (pTAC)] was obtained by serial arterial blood sampling. It is of clinical interest to develop a method for PET studies that estimates the pTAC without needing serial arterial blood sampling. For this purpose, we propose a new method to extract the pTAC from the dynamic brain PET images using a modified independent component analysis [extraction of the pTAC using independent component analysis (EPICA). Source codes of EPICA are freely available at http://www5f.biglobe.ne.jp/-ukimura/Software/top.html]. EPICA performs the appropriate preprocessing and independent component analysis (ICA) using an objective function that takes the various properties of the pTAC into account. After validation of EPICA by computer simulation, EPICA was applied to human brain FDG-PET studies. The results imply that the EPICA-estimated pTAC was similar to the actual measured pTAC, and that the estimated blood volume image was highly correlated with the blood volume image measured using O-15-CO inhalation. These results demonstrated that EPICA is useful for extracting the pTAC from dynamic PET images without the necessity of serial arterial blood sampling.
  • Extraction of a plasma time-activity curve from dynamic brain PET images based on independent component analysis, M Naganawa, Y Kimura, K Ishii, K Oda, K Ishiwata, A Matani, IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING, IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING, 52(2), 201 - 210, Feb. 2005
    Summary:A compartment model has been used for kinetic analysis of dynamic positron emission tomography (PET) data [e.g., 2-deoxy-2-F-18-fluoro-D-glucose (FDG)]. The input function of the model [the plasma time-activity curve (pTAC)] was obtained by serial arterial blood sampling. It is of clinical interest to develop a method for PET studies that estimates the pTAC without needing serial arterial blood sampling. For this purpose, we propose a new method to extract the pTAC from the dynamic brain PET images using a modified independent component analysis [extraction of the pTAC using independent component analysis (EPICA). Source codes of EPICA are freely available at http://www5f.biglobe.ne.jp/-ukimura/Software/top.html]. EPICA performs the appropriate preprocessing and independent component analysis (ICA) using an objective function that takes the various properties of the pTAC into account. After validation of EPICA by computer simulation, EPICA was applied to human brain FDG-PET studies. The results imply that the EPICA-estimated pTAC was similar to the actual measured pTAC, and that the estimated blood volume image was highly correlated with the blood volume image measured using O-15-CO inhalation. These results demonstrated that EPICA is useful for extracting the pTAC from dynamic PET images without the necessity of serial arterial blood sampling.
  • Event-by-event random and scatter estimator based on support vector machine using multi-anode outputs, Eiji Yoshida, Yuichi Kimura, Keishi Kitamura, Fumihiko Nishikido, Taiga Yamaya, Hideo Murayama, IEEE Nuclear Science Symposium Conference Record, IEEE Nuclear Science Symposium Conference Record, 3, 1800 - 1803, 2005 , Refereed
    Summary:In PET, the incident angle of gamma rays is estimated from coincidence information, but coincidence events are contaminated with random and scatter components. The mean contribution to the image from these components can be measured or estimated, but the noise resulting from the statistical variations in the detected events still remains and decreases noise equivalent count rates (NECR). Theoretically, incident angle to detectors or other related information can be used to discriminate random and scatter events from true events for increasing the NECR. This information can be delineated from spatial distributions of deposited energies on multi-anode photomultiplier tubes (PMTs), which arise from inter-crystal scattering and vary with the coincidence event type (true or random/scatter). In this work, a novel method for random and scatter subtraction has been developed using the support vector machine (SVM), a recently developed and widely used statistical pattern recognition scheme. SVM input data are s a pair of spatial distributions of 256 outputs of multi-anode PMTs from coincidence detectors. The SVM is trained by coincidence events generated from a detector simulator using Monte Carlo calculation. True and random coincidence events are simulated and the results show that the proposed method is applicable for event-by-event estimation of random coincidence. © 2005 IEEE.
  • Imaging detailed glucose metabolism in the brain using MAP estimation in Positron Emission Tomography, Yuichi Kimura, Mika Naganawa, 2005 27th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, Vols 1-7, 2005 27th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, Vols 1-7, 4477 - 4479, 2005 , Refereed
    Summary:In this study, maximize a posterior approach (MAP) was applied for detailed imaging of the glucose metabolism in the brain using PET and F-18-FDG. FDG is a glucose analog and it can investigate a glucose metabolism. In PET studies, glucose metabolism can be measured to estimate a compartment model which describes the behavior of glucose in the brain. We applied the MAP approach to a voxel-by-voxel compartment model estimation in order to visualize a net amount of glucose, glucose transportation, and glucose phosphorylation because a MAP approach is advantageous for robust model estimation against noise existence. When the algorithm was applied to Alzheimer patients, the images had different patterns depending on severity of the disease. We conclude that the proposed MAP-based algorithm is useful for detail imaging of glucose metabolism in the brain.
  • Practical consideration about cost functions of spatial independent component analysis in medical image processing, M. Naganawa, Y. Kimura, Y. Manabe, K. Chihara, 2005 27th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, Vols 1-7, 2005 27th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, Vols 1-7, 1120 - 1122, 2005 , Refereed
    Summary:Independent component analysis (ICA) is widely used for signal separation in various fields. However, low signal to noise ratio (SNR) of data sometimes causes failures in component estimation. We have proposed a spatial ICA-based method for extracting a blood-related component from medical images measured with positron emission tomography (PET) to omit arterial blood sampling, in which a cost function was designed in consideration of statistical properties of components. In this study, spatial ICA with the proposed cost function or kurtosis, a conventional cost function, was applied to real PET images measured with three kinds of radiopharmaceuticals, and the estimation results were compared. The proposed cost function fails to estimate components from the PET data with low SNR because it is sensitive to outliers. Experimental results suggest that a cost function should be selected depending on SNR of data.
  • Event-by-event random and scatter estimator based on support vector machine using multi-anode outputs, Eiji Yoshida, Yuichi Kimura, Keishi Kitamura, Fumihiko Nishikido, Taiga Yamaya, Hideo Murayama, 2005 IEEE Nuclear Science Symposium Conference Record, Vols 1-5, 2005 IEEE Nuclear Science Symposium Conference Record, Vols 1-5, 1800 - 1803, 2005 , Refereed
    Summary:In PET, the incident angle of gamma rays is estimated from coincidence information, but coincidence events are contaminated with random and scatter components. The mean contribution to the image from these components can be measured or estimated, but the noise resulting from the statistical variations in the detected events still remains and decreases noise equivalent count rates (NECR). Theoretically, incident angle to detectors or other related information can be used to discriminate random and scatter events from true events for increasing the NECR. This information can be delineated from spatial distributions of deposited energies on multi-anode photomultiplier tubes (PMTs), which arise from inter-crystal scattering and vary with the coincidence event type (true or random/scatter). In this work, a novel method for random and scatter subtraction has been developed using the support vector machine (SVM), a recently developed and widely used statistical pattern recognition scheme. SVM input data are s a pair of spatial distributions of 256 outputs of multi-anode PMTs from coincidence detectors. The SVM is trained by coincidence events generated from a detector simulator using Monte Carlo calculation. True and random coincidence events are simulated and the results show that the proposed method is applicable for event-by-event estimation of random coincidence.
  • Adenosine A(1) receptor mapping of the human brain by PET with 8-dicyclopropylmethyl-1-C-11-methyl-3-propylxanthine, N Fukumitsu, K Ishii, Y Kimura, K Oda, T Sasaki, Y Mori, K Ishiwata, JOURNAL OF NUCLEAR MEDICINE, JOURNAL OF NUCLEAR MEDICINE, 46(1), 32 - 37, Jan. 2005 , Refereed
    Summary:Adenosine is an enclogenous modulator of synaptic functions in the central nervous system. To investigate the physiologic and pathologic roles of the adenosine receptors in the human brain, PET is a powerful in vivo technique. In this study, we quantitatively evaluated the distribution of a major subtype A(1) adenosine receptor in the human brain by PET with a newly developed radioligand, 8-dicyclopropylmethyl-1-C-11-methyl-3-propylxanthine (C-11-MPDX). Methods: In 5 healthy volunteers, after PET measurement of the regional cerebral blood flow (rCBF) with O-15-H2O, a 60-min PET scan with C-11-MPDX was performed. The distribution volume (DV) of C-11-MPDX was quantitatively evaluated by Logan's graphical analysis. Results: C-11-MPDX was taken up at a high level, reaching a peak at 2-2.5 min, followed by a rapid decrease. The unchanged form of C-11-MPDX in plasma was 75% at 60 min after injection. The DV of C-11-MPDX was large in the striaturn and thalamus, moderate in the cerebral cortices and pons, and small in the cerebellum. The distribution pattern of C-11-MPDX in the brain was coincident with that of adenosine A(1) receptors in vitro, reported previously, but discretely different from that of rCBF. Conclusion: C-11-MPDX PET has the potential for mapping adenosine A(1) receptors in the human brain.
  • Simplified PET measurement for evaluating histamine H-1 receptors in human brains using [C-11]doxepin, H Mochizuki, Y Kimura, K Ishii, K Oda, T Sasaki, M Tashiro, K Yanai, K Ishiwata, NUCLEAR MEDICINE AND BIOLOGY, NUCLEAR MEDICINE AND BIOLOGY, 31(8), 1005 - 1011, Nov. 2004 , Refereed
    Summary:The aim of this study was to develop simplified positron emission tomography measurement using [C-11]doxepin ([C-11]DOX) to evaluate histamine H-1 receptors (H1Rs) in human brains. We evaluated the correlation between the distribution volume (DV) of [C-11]DOX, estimated quantitatively with a two-compartment model, and the [C-11]DOX uptake obtained at various time intervals and normalized using the metabolite-corrected plasma radioactivity. We found that the static 70- to 90-min images normalized using the plasma radioactivity at 10 min postinjection reflected the DV of [C-11]DOX-H1R binding. (C) 2004 Elsevier Inc. All rights reserved.
  • Quantitative analysis of adenosine A(1) receptors in human brain using positron emission tomography and [1-methyl-C-11]8-dicyclopropylmethyl-1-methyl-3-propylxanthine, Y Kimura, K Ishii, N Fukumitsu, K Oda, T Sasakia, K Kawamura, K Ishiwata, NUCLEAR MEDICINE AND BIOLOGY, NUCLEAR MEDICINE AND BIOLOGY, 31(8), 975 - 981, Nov. 2004 , Refereed
    Summary:Fully quantitative analysis of the adenosine A(1) receptor (A1R) in the brain with C-11-MPDX and positron emission tomography is reported. The kinetics is described using a two-tissue three-compartment model, and estimated binding potentials correspond well with the estimates made by Logan plot. The image of the binding potential of the MPDX is physiologically reasonable. We conclude that MPDX is applicable to the visualization of the A1Rs in the brain with Logan plot. (C) 2004 Elsevier Inc. All rights reserved.
  • Potential of [C-11]TMSX for the evaluation of adenosine A(2A) receptors in the skeletal muscle by positron emission tomography, K Ishiwata, M Mizuno, Y Kimura, K Kawamura, K Oda, T Sasaki, Y Nakamura, Muraoka, I, K Ishii, NUCLEAR MEDICINE AND BIOLOGY, NUCLEAR MEDICINE AND BIOLOGY, 31(7), 949 - 956, Oct. 2004 , Refereed
    Summary:We examined the potential of [7-methyl-C-11]-(E)-8-(3,4,5-trimethoxystyryl)-1,3,7-trimethylxanthine ([C-11]TMSX) for the assessment of adenosine A(2A) receptors in muscle. In rodents, specific binding of [C-11]TMSX was observed in muscle and heart by blockade with A(2A)-selective CSC and non-selective theophylline, but not with A(1)-selective DPCPX. Swimming exercise fluctuated radioligand-receptor binding in these tissues. In a PET study of two subjects, theophylline-infusion slightly deceased the distribution volume of [C-11]TMSX in the heart (20% reduction) and muscle (10% reduction), which suggested the specific binding. (C) 2004 Elsevier Inc. All rights reserved.
  • Calibration procedure for a DOI detector of high resolution PET through a Gaussian mixture model, E Yoshida, Y Kimura, K Kitamura, H Murayama, IEEE TRANSACTIONS ON NUCLEAR SCIENCE, IEEE TRANSACTIONS ON NUCLEAR SCIENCE, 51(5), 2543 - 2549, Oct. 2004
    Summary:A depth of interaction detector is developed for the next generation of positron emission tomography (PET) scanners. The detector unit consists of 8 x 8 crystal blocks with four layers of 2 x 2 Gd2SiO5:Ce arrays coupled to a 52 mm square position sensitive photomultiplier tube (PS-PMT). Each scintillation event is mapped in a two-dimensional (2-D) position histogram through the relative ratio of the output signals of the PS-PMT. To facilitate high spatial resolution imaging, accurate crystal identification is needed. A statistical model based on the approach-of a Gaussian mixture model (GMM) is introduced for crystal identification. In the GMM, a cluster center and range attributed to individual peaks in the 2-D position histogram are defined. GMM can simultaneously estimate overlapping regions projected each crystal element. After block separation of 8 x 8 on the 2-D distribution, the crystal element regions are identified by the GMM in each block. The GMM method is applied two times, once for the cluster centers and once for determination of the range. These results are used to generate a look-up-table (LUT). This method successfully identified all crystal elements in the clustering area. By Monte Carlo simulation, we also proved that GMM method could choose LUT patterns to high resolution or high sensitivity with one parameter.
  • Evaluation of in vivo selective binding of [C-11]doxepin to histamine H-1 receptors in five animal species, K Ishiwata, K Kawamura, WF Wang, H Tsukada, N Harada, H Mochizuki, Y Kimura, K Ishii, R Iwata, K Yanai, NUCLEAR MEDICINE AND BIOLOGY, NUCLEAR MEDICINE AND BIOLOGY, 31(4), 493 - 502, May 2004 , Refereed
    Summary:The specific binding of [C-11]doxepin, which has been used as a radioligand for mapping histamine H-1 receptors in human brain by positron emission tomography, was evaluated in five animal species. In mice the [C-11]doxepin uptake was reduced by treatment with cold doxepin and two H-1 receptor antagonists, but not with H-2/H-3 antagonists. The specific binding evaluated with treatment with (+)-chlorpheniramine (H-1 antagonist) was in the range of 10-30% in mouse, rat, rabbit, and monkey, but was not detected in guinea pig. (C) 2004 Elsevier Inc. All rights reserved.
  • Evaluation of [F-18]fluorinated sigma receptor ligands in the conscious monkey brain, PH Elsinga, H Tsukada, N Harada, T Kakiuchi, K Kawamura, W Vaalburg, Y Kimura, T Kobayashi, K Ishiwata, SYNAPSE, SYNAPSE, 52(1), 29 - 37, Apr. 2004 , Refereed
    Summary:PET-imaging of the sigma receptors is very helpful to understand processes, e.g., several central nervous system (CNS)-diseases in which the sigma receptors are involved. The [F-18]fluoroethylated analogs of SA4503 and SA5845 ([F-18]FE-SA4503 and [F-18]FE-SA5845) were evaluated in conscious monkeys to estimate its suitability for human application for PET. Conscious monkeys (Macaca Mulatta) were either scanned with [F-18]FE-SA4503 or [F-18]FE-SA5845 (n = 3 for both groups, 220 - 802 MBq). After a dynamic study of 120 min, radioactivity was displaced by intravenous (i.v.) injection of haloperidol (1 mg/kg). One month later the same set of three monkeys were scanned with [F-18]FE-SA4503 for 120 min and "cold" SA4503 (1 mg/kg) was infused to displace the radioactivity, and the other three monkeys were pretreated with haloperidol (1 mg/kg) before the 120-min PET-scan with [F-18]FE-SA5845. Cortical areas (cingulate, frontal, occipital, parietal, temporal), striatum, and thalamus showed high radioactivity uptake. Infusion of haloperidol displaced the radioactivity levels of the two radioligands. The same effect was found for [18F]FE-SA4503 after SA4503 displacement. Pretreatment with haloperidol blocked the [F-18]FE-SA5845 binding to give PET-images with low and uniform uptake in the brain. The findings demonstrated the reversible binding of the two radioligands. Metabolite analysis showed that 14% and 23% parent compound of [F-18]FE-SA5845 and [F-18]FE-SA4503, respectively, at 120 min postinjection was present in plasma. Kinetic analysis showed that the binding potential of [F-18]FE-SA5845 was higher in all brain regions than that of [F-18]FE-SA4503 (4.75-8.79 vs. 1.65-4.04). The highest binding potential was found in the hippocampus, followed by the cortical regions, thalamus, cerebellar hemisphere, striatum and vermis. Both [F-18]FE-SA compounds bound specifically to cerebral sigma receptors of the monkey and have potential for mapping sigma receptors in the human brain. (C) 2004 Wiley-Liss, Inc.
  • Quantitative measurement of histamine H-1 receptors in human brains by PET and [C-11]doxepin, H Mochizuki, Y Kimura, K Ishii, K Oda, T Sasaki, M Tashiro, K Yanai, K Ishiwata, NUCLEAR MEDICINE AND BIOLOGY, NUCLEAR MEDICINE AND BIOLOGY, 31(2), 165 - 171, Feb. 2004 , Refereed
    Summary:The aim of this stud), is to establish a method for quantitative measurement of histamine H-1 receptor (H1R) in human brain by PET and ([C-11]doxepin ([C-11]DOX). The estimated parameters with a two-compartment model were stable for the initial values for parameter estimation but those with a three-compartment model were not. This finding suggests that the HIR measured by the [C-11]DOX and PET can be evaluated with a two-compartment model. (C) 2004 Elsevier Inc. All rights reserved.
  • Supervised clustering approach to form functional images in positron emission tomography, Y Kimura, Y Takabayashi, J Yamaguchi, PROCEEDINGS OF THE 26TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-7, PROCEEDINGS OF THE 26TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-7, 26, 1896 - 1898, 2004 , Refereed
    Summary:The aim of this study is to investigate the availability of supervised statistical clustering algorithm for image-based model analysis in positron emission tomography or nuclear medicine to form a functional image. Voxel-by-voxel model analysis can derive functional images, but bad statistic property in voxel-based PET data and huge number of voxels prevent to realize practical algorithm to form parametric images. In this study, supervised clustering is applied to categorized PET data. The shape of tTAC is projected in multidimensional feature space, and noise propagation is modeled as multivariate Gaussian in the space. Simulation study shows that the estimates by the proposed algorithm was identical to the true values. And a clinical image of has physiologically acceptable aspect. We can conclude that supervised clustering sachem has potential to realize practical algorithm for voxel-based model analysis in PET.
  • Calibration procedure for a DOI detector of high resolution PET through mixture Gaussian model, E Yoshida, Y Kimura, K Kitamura, H Murayama, 2003 IEEE NUCLEAR SCIENCE SYMPOSIUM, CONFERENCE RECORD, VOLS 1-5, 2003 IEEE NUCLEAR SCIENCE SYMPOSIUM, CONFERENCE RECORD, VOLS 1-5, 2491 - 2495, 2004 , Refereed
    Summary:A depth of interaction (DOI) detector is developed for the next generation of PET scanners. The detector unit consists of 8x8 crystal blocks with 4 layers of 2x2 Gd2SiO5:Ce (GSO) arrays coupled to a 52 mm square position sensitive photomultiplier tube (PS-PMT). Each scintillation event is mapped in a two-dimensional (2D) distribution through the relative ratio of the output signals of the PS-PMT. To facilitate high spatial resolution imaging, accurate crystal identification is needed. A statistical model based on the approach of a mixture Gaussian model (MGM) is introduced for crystal identification. In the MGM, a cluster center and range attributed to individual peaks in the 2D distribution are defined. The MGM method is applied two times, once for the cluster centers and once for determination of the range. These results are used to generate a Look-Up-Table (LUT). This method successfully identifies 288 crystal elements composing 36 crystal blocks.
  • Regional differences in blood flow and oxygen consumption in resting muscle and their relationship during recovery from exhaustive exercise, M Mizuno, Y Kimura, T Iwakawa, K Oda, K Ishii, K Ishiwata, Y Nakamura, Muraoka, I, JOURNAL OF APPLIED PHYSIOLOGY, JOURNAL OF APPLIED PHYSIOLOGY, 95(6), 2204 - 2210, Dec. 2003 , Refereed
    Summary:This investigation evaluated regional differences in blood flow and oxygen consumption and their relationship in exercised muscle during recovery from exhaustive exercise. Five healthy men performed exhaustive one-legged cycling exercise. Positron emission tomography was used to measure blood flow, oxygen uptake, and oxygen extraction in the quadriceps femoris muscle before and after exercise. Regions of interest included five areas of the muscle (two proximal, one central, and two distal), which were evenly spaced across the muscle. Before exercise, blood flow and oxygen consumption decreased Significantly (P < 0.05) in the direction from the proximal to the distal portions; blood flow declined from 2.0 +/- 0.5 to 1.4 +/- 0.3 ml center dot 100 g(-1) center dot min(-1), and oxygen consumption decreased from 0.21 +/- 0.04 to 0.17 +/- 0.02 ml center dot 100 g(-1) center dot min(-1). In contrast, these gradients in blood flow and oxygen consumption diminished during recovery after exercise. Consequently, there was a positive relationship between changes in blood flow and oxygen consumption in an exercised muscle during recovery after exercise (r = 0.963, P < 0.01). These changes became larger in the direction from proximal to distal portions: blood flow increased from 2.9 +/- 0.7 to 3.9 +/- 0.8 and oxygen consumption from 1.4 +/- 0.1 to 1.8 +/- 0.4 times resting values. These results suggest that hemodynamic variables are heterogeneous within a muscle both at rest and during recovery from exercise and that there is a systematic difference in these variables in the direction from proximal to distal regions within the quadriceps femoris muscle.
  • Regional differences in blood volume and blood transit time in resting skeletal muscle, M Mizuno, Y Kimura, T Iwakawa, K Oda, K Ishii, K Ishiwata, Y Nakamura, Muraoka, I, JAPANESE JOURNAL OF PHYSIOLOGY, JAPANESE JOURNAL OF PHYSIOLOGY, 53(6), 467 - 470, Dec. 2003 , Refereed
    Summary:We examined regional differences in blood volume and transit time along the length of a resting skeletal muscle by positron emission tomography. In contrast, blood volume didn't change. The blood transit time increased significantly from proximal to distal portions, suggesting that blood flow velocity slows even though there are no changes in blood volume.
  • Regional differences in blood volume and blood transit time in resting skeletal muscle, M Mizuno, Y Kimura, T Iwakawa, K Oda, K Ishii, K Ishiwata, Y Nakamura, Muraoka, I, JAPANESE JOURNAL OF PHYSIOLOGY, JAPANESE JOURNAL OF PHYSIOLOGY, 53(6), 467 - 470, Dec. 2003
    Summary:We examined regional differences in blood volume and transit time along the length of a resting skeletal muscle by positron emission tomography. In contrast, blood volume didn't change. The blood transit time increased significantly from proximal to distal portions, suggesting that blood flow velocity slows even though there are no changes in blood volume.
  • An increase of sigma(1) receptors in the aged monkey brain, K Kawamura, Y Kimura, H Tsukada, T Kobayashi, S Nishiyama, T Kakiuchi, H Ohba, N Harada, K Matsuno, K Ishii, K Ishiwata, NEUROBIOLOGY OF AGING, NEUROBIOLOGY OF AGING, 24(5), 745 - 752, Sep. 2003 , Refereed
    Summary:We evaluated in vivo the effect of aging on the sigma, receptors in the monkey brain by the quantitative analysis of the binding of [C-11]SA4503 to sigma, receptors with positron emission tomography. Based on a three-compartment model, the influx rate constant K-1 of [C-11]SA4503 from plasma to brain across the blood-brain barrier in all 10 regions investigated became smaller in the aged monkeys (20-28 years old, n = 5) than in the young adult monkeys (4-8 years old, it = 5), but the reduction was not significant due to the individual differences. On the other hand, the binding potential, which was calculated as the ratio of the association rate constant k(3) to the dissociation rate constant k(4) for the binding of [C-11]SA4503 to sigma, receptors in the brain, significantly increased in nine of the brain regions of the aged monkeys to the 160-210% levels of the young monkeys. We concluded that the sigma, receptor binding sites increased in the aging process of the monkey brain. (C) 2002 Elsevier Science Inc. All rights reserved.
  • Potential of an adenosine A(2A) receptor antagonist [C-11]TMSX for myocardial imaging by positron emission tomography: a first human study, K Ishiwata, K Kawamura, Y Kimura, K Oda, K Ishii, ANNALS OF NUCLEAR MEDICINE, ANNALS OF NUCLEAR MEDICINE, 17(6), 457 - 462, Sep. 2003 , Refereed
    Summary:In previous in vivo studies with mice, rats, cats and monkeys, we have demonstrated that [7-methyl-C-11]-(E)-8-(3,4,5-trimethoxystyryl)-1,3,7-trimethylxanthine ([C-11]TMSX) is a potential radioligand for mapping adenosine A(2A) receptors of the brain by positron emission tomography (PET). In the present study, we studied the potential of [C-11]TMSX for myocardial imaging. Uptake of radioactivity by the heart was high and gradually decreased after an intravenous injection of [C-11]TMSX into mice. In metabolite analysis, 54% and 76% of the radioactivity in plasma and heart, respectively, were present as the unchanged form of [C-11]TMSX 60 min postinjection. The myocardial uptake was reduced by carrier-loading and by co-injection of an adenosine A(2A) antagonist CSC, but not by co-injection of an adenosine A(1) antagonist DPCPX. Pretreatment with a high dose of a non-selective antagonist theophylline also reduced the myocardial uptake of [C-11]TMSX. These findings demonstrate the specific binding of [C-11]TMSX to adenosine A(2A) receptors in the heart. Finally we successfully performed the myocardial imaging by PET with [C-11]TMSX in a normal volunteer. A graphical analysis by Logan plot supported the receptor-mediated uptake of [C-11]TMSX. Peripherally [C-11]TMSX was very stable in human: >90% of the radioactivity in plasma was detected as the unchanged form in a 60-min study. We concluded that [C-11]TMSX PET has the potential for myocardial imaging.
  • Imaging of adenosine A(1) receptors in the human brain by positron emission tomography with [C-11]MPDX, N Fukumitsu, K Ishii, Y Kimura, K Oda, T Sasaki, Y Mori, K Ishiwata, ANNALS OF NUCLEAR MEDICINE, ANNALS OF NUCLEAR MEDICINE, 17(6), 511 - 515, Sep. 2003 , Refereed
    Summary:We report the first clinical PET study using [1-methyl-C-11]8-dicyclopropylmethyl-1-methyl-3-propylxanthine ([C-11]MPDX) for imaging adenosine A(1) receptors in the human brain. The binding of [C-11]MPDX evaluated quantitatively as the distribution volume by a graphical analysis was high in the striatum and thalamus, and low in the cerebellum. The distribution pattern of [C-11]MPDX was coincident with that of adenosine A(1) receptors in vitro reported previously, and was different from those of blood flow and [F-18]FDG. The [C-11]MPDX PET has the potential for mapping adenosine A(1) receptors in the human brain.
  • Increased regional cerebral blood flow but normal distribution of GABA(A) receptor in the visual cortex of subjects with early-onset blindness, M Mishina, M Senda, M Kiyosawa, K Ishiwata, AG De Volder, H Nakano, H Toyama, K Oda, Y Kimura, K Ishii, T Sasaki, M Ohyama, Y Komaba, S Kobayashi, S Kitamura, Y Katayama, NEUROIMAGE, NEUROIMAGE, 19(1), 125 - 131, May 2003 , Refereed
    Summary:Before the completion of visual development, visual deprivation impairs synaptic elimination in the visual cortex. The purpose of this study was to determine whether the distribution of central benzodiazepine receptor (BZR) is also altered in the visual cortex in subjects with early-onset blindness. Positron emission tomography was carried out with [O-15]water and [C-11]flumazenil on six blind subjects and seven sighted controls at rest. We found that the CBF was significantly higher in the visual cortex for the early-onset blind subjects than for the sighted control subjects. However, there was no significant difference in the BZR distribution in the visual cortex for the subject with early-onset blindness than for the sighted control subjects. These results demonstrated that early visual deprivation does not affect the distribution of GABA(A) receptors in the visual cortex with the sensitivity of our measurements. Synaptic elimination may be independent of visual experience in the GABAergic system of the human visual cortex during visual development. (C) 2003 Elsevier Science (USA). All rights reserved.
  • Preclinical studies on [C-11]TMSX for mapping adenosine A(2A) receptors by positron emission tomography, K Ishiwata, WF Wang, Y Kimura, K Kawamura, K Ishii, ANNALS OF NUCLEAR MEDICINE, ANNALS OF NUCLEAR MEDICINE, 17(3), 205 - 211, May 2003 , Refereed
    Summary:In previous in vivo studies with mice, rats and monkeys, we have demonstrated that [C-11]TMSX ([7-methyl-C-11]-(E)-8-(3,4,5-trimethoxystyryl)-1,3,7-trimethylxanthine) is a potential radioligand for mapping adenosine A(2A) receptors of the brain by positron emission tomography (PET). In the present study, we performed a preclinical study. A suitable preparation method for [C-11]TMSX injection was established. The radiation absorbed-dose by [C-11]TMSX in humans estimated from the tissue distribution in mice was low enough for clinical use, and the acute toxicity and mutagenicity of TMSX were not found. The striatal uptake of [C-11]TMSX in mice was reduced by pretreatment with,theophylline at the dose of 10 and 100 mg/kg, suggesting that the [C-11]TMSX PET should be carefully performed in the patients received with theophylline. We have concluded that [C-11]TMSX is-suitable for mapping adenosine A(2A) receptors in the human brain by PET.
  • Punctional image on glucose metabolism in brain using PET with short time scan, Y Kimura, Y Takabayashi, K Oda, K Ishii, K Ishiwata, PROCEEDINGS OF THE 25TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-4, PROCEEDINGS OF THE 25TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-4, 25, 967 - 970, 2003 , Refereed
    Summary:Dynamic scan in PET has powerful capability to visualize various functionalities in a living tissue. But a dynamic scan requires long scan duration, and it is not practical for routine use. In this study, a shortened scan protocol is investigated in case of imaging of glucose metabolism in brain using F-18-FDG. In ordinary protocol of dynamic PET scan, more than 45 minutes is required. It is found that the first 30 minutes after FDG injection is enough to form a parametric image on glucose metabolism if a statistical clustering algorithm is incorporate to composed the parametric images.
  • Simplified measurement of histamine H-1 receptor in human brains with PET, H Mochizuki, Y Kimura, K Ishii, K Oda, T Sasaki, M Tashiro, K Yanai, K Ishiwata, IEEE EMBS APBME 2003, IEEE EMBS APBME 2003, 198 - 199, 2003 , Refereed
    Summary:present study, we developed a simplified positron emission tomography (PET) measurement to evaluate histamine H, receptor (HIR). Our findings demonstrated that brain images reflecting H1R can be obtained with static PET scan started from 70 min after injection of [C-11]doxepin.
  • Implementation of statistical clustering for voxel-based kinetic analysis in PET, Y Kimura, Y Noshi, K Ishii, K Oda, 2002 IEEE NUCLEAR SCIENCE SYMPOSIUM, CONFERENCE RECORD, VOLS 1-3, 2002 IEEE NUCLEAR SCIENCE SYMPOSIUM, CONFERENCE RECORD, VOLS 1-3, 1322 - 1324, 2003 , Refereed
    Summary:Voxel-based kinetic analysis to a dynamic data derived from PET has a potential capability to visualize some functionality of living tissue. But bad noisy statistic in voxel-vased PET data and a huge number of calculation time make it impractical to apply an ordinal ROI-based kinetic analysis to voxel-by-voxel. The novel method for voxel-based kinetic analysis is proposed, clustering analysys for kinetics (CAKS). In CAKS, voxels are clustered by its time history, and parameter estimation is applied in this cluster. As the result, CAKS can derive physiologically acceptable parametric images in 20 minutes. We can conclude that CAKS is a practical method to realize voxel-based linetic analysis.
  • Regional difference in blood flow and oxygen consumption in exercise muscle and their relationship during recovery fron exhausive exercise, J Appl Physiolo, J Appl Physiolo, 95, 2204-2210, 2003
  • Preclinical studies on [C-11]MPDX for mapping adenosine A(1) receptors by positron emission tomography, K Ishiwata, T Nariai, Y Kimura, K Oda, K Kawamura, K Ishii, M Senda, S Wakabayashi, J Shimada, ANNALS OF NUCLEAR MEDICINE, ANNALS OF NUCLEAR MEDICINE, 16(6), 377 - 382, Sep. 2002 , Refereed
    Summary:In previous in vivo studies with mice, rats and cats, we have demonstrated that [C-11]MPDX ([1-methyl- C-11]8-dicyclopropylmethyl-1-methyl-3-propylxanthine) is a potential radioligand for mapping adenosine A(1) receptors of the brain by positron emission tomography (PET). In the present study, we performed a preclinical study. The radiation absorbed-dose by [C-11]MPDX in humans estimated from the tissue distribution in mice was low enough for clinical use, and the acute toxicity and mutagenicity of MPDX were not found. The monkey brain was clearly visualized by PET with [C-11]MPDX. We have concluded that [C-11]MPDX is suitable for mapping adenosine A(1) receptors in the human brain by PET.
  • Fast formation of statistically reliable FDG parametric images based on clustering and principal components, Y Kimura, M Senda, NM Alpert, PHYSICS IN MEDICINE AND BIOLOGY, PHYSICS IN MEDICINE AND BIOLOGY, 47(3), 455 - 468, Feb. 2002 , Refereed
    Summary:Formation of parametric images requires voxel-by-voxel estimation of fate constants, a process sensitive to noise and computationally demanding. A model-based clustering method for a two-parameter model (CAKS) was extended to the FDG three-parameter model. The concept was to average voxels with similar kinetic signatures to reduce noise. Voxel kinetics were categorized by the first two principal components of the tissue time-activity curves for all voxels. k(2) and k(3) were estimated cluster-by-cluster, and K-1 was estimated voxel-by-voxel within clusters. When CAKS was applied to simulated images with noise levels similar to brain FDG scans, estimation bias was well suppressed, and estimation errors were substantially smaller-1.3 times for K-i and 1.5 times for k(3)-than those of conventional voxel-based estimation. The statistical reliability of voxel-level estimation by CAKS was comparable with ROI analysis including 100 voxels. CAKS was applied to clinical cases with Alzheimer's disease (ALZ) and cortico basal degeneration (CBD). In ALZ, the affected regions had low K-i(K(1)k(3)/(k(2) + k(3))) and k(3). In CBD, K-i was low, but k(3) was preserved. These results were consistent with ROI-based kinetic analysis. Because CAKS decreased (lie number of invoked estimations, the calculation time was reduced substantially. In conclusion, CAKS has been extended to allow parametric imaging of a three-compartment model. The method is computationally efficient, with low bias and excellent noise properties.
  • Fully automated segmentation of MRI brain image, using mixture Gaussian model and three-dimensional morphological filter, M Okano, Y Kimura, K Ishii, A Uchiyama, K Ishiwata, SECOND JOINT EMBS-BMES CONFERENCE 2002, VOLS 1-3, CONFERENCE PROCEEDINGS, SECOND JOINT EMBS-BMES CONFERENCE 2002, VOLS 1-3, CONFERENCE PROCEEDINGS, 997 - 998, 2002 , Refereed
    Summary:The method to segment a human brain of a magnetic resonance image is proposed in which tissue characteristic and structure are considered using two algorithms, one is mixture Gaussian model and the other is three-dimensional morphological filter. First, the image is segmented into five clusters of background, cerebro-spinal fluid, gray matter, white matter and others by mixture Gaussian model applied to a histogram of voxel values. Next, a three-dimensional morphological filter is invoked to modify missclustered voxels. All of steps can be done in automatically. The brain structures are segmented well in derived results and the proposed algorithm has a potential possibility for clinical applications.
  • Statistical model-based scatter correction for 3D PET, Y Chiba, Y Kimura, K Kitamura, K Oda, A Uchiyama, K Ishiwata, SECOND JOINT EMBS-BMES CONFERENCE 2002, VOLS 1-3, CONFERENCE PROCEEDINGS, SECOND JOINT EMBS-BMES CONFERENCE 2002, VOLS 1-3, CONFERENCE PROCEEDINGS, 965 - 966, 2002 , Refereed
    Summary:The aim of this study is to propose a scatter correction method based on a statistical model of mixture Gaussian Model (MGM) that has robust capability for information. extraction and can make smaller in size of PET data stored. Clustering algorithm based on MGM is applied to extract scatter component. MGM assumed that measure data are sum of unknown components that statistical characteristic is Gaussian. MGM was applied to three different implementations of one-, two-, and three-dimensional projection data. Good extraction performance and reduction of the amount of data are archived.
  • Imaging glucose metabolism of brain using PET with clustering analysis for kinetics, Y Noshi, Y Kimura, K Ishii, A Uchiyama, K Oda, K Kitamura, K Ishiwata, SECOND JOINT EMBS-BMES CONFERENCE 2002, VOLS 1-3, CONFERENCE PROCEEDINGS, SECOND JOINT EMBS-BMES CONFERENCE 2002, VOLS 1-3, CONFERENCE PROCEEDINGS, 951 - 952, 2002 , Refereed
    Summary:The aim of this study is to visualize glucose metabolism in a brain using PET dynamic data and the proposed clustering analysis (CAKS). PET can give glucose metabolism using F-18-FDG. Voxel-based analysis is not practical because of bad noisy property In voxel-based PET data and a large number of voxels. In CAKS, PET data are clustered to Improve reliability In estimation and calculation speed. In CAKS voxels whose concentration history in tissue time activity are similar are gathered before parameter estimation using a statistical clustering algorithm based on mixture Gaussian model, then averaged time course is used for parameter estimation. As results, physiologically acceptable Images on glucose metabolism were obtained in ten minutes.
  • Application of visual evoked potentials for preoperative estimation of visual function in eyes with dense cataract, H Mori, K Momose, N Nemoto, F Okuyama, Y Kimura, M Kiyosawa, M Mochizuki, GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY, GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY, 239(12), 915 - 922, Dec. 2001 , Refereed
    Summary:Purpose: To determine whether the temporal frequency characteristics of the visual system as determined by visually evoked potentials (VEP) can be used for a preoperative estimation of the visual function in eyes with cataracts. Methods: Light stimuli driven by a pseudorandom binary sequence (PRBS) of 40950 ms duration were presented and EEG recordings were made from 13 control and 20 patients with cataracts preoperatively and 1 week after cataract operation. The first kernel of the PRBS-VEP was obtained as the first-order cross-correlation function between PRBS and PRBS-VER The Fourier transform of this function was used as the temporal frequency characteristic (TFC). Results: The mean +/- standard deviation of the latency and amplitude of the VEP in normal controls were 110.8 +/- 4.3 ms and 2.01 +/- 0.67 muV, respectively. A high correlation (r > 0.7) between the pre- and postoperative VEP waveform was obtained in 13 eyes (65%), and 14 eyes (70%) in the VEP-TFC curves. The sensitivity of the examination was 73%, 27%, and 91% for the latency, amplitude and TFC of the VEP, respectively. The specificity of the examination was 67%, 100%, and 89% for the same measures. Eleven of 12 eyes with abnormal TFC preoperatively showed retinal or optic nerve lesions postoperatively. False-negative results were seen in cases with delayed corneal edema. Conclusion: Postoperative visual function of patients with cataracts can be predicted by preoperative measurement of the TFC obtained by PRBS-VEP.
  • Comparison of parametric FBP and OS-EM reconstruction algorithm images for PET dynamic study, K Oda, H Toyama, K Uemura, Y Ikoma, Y Kimura, M Senda, ANNALS OF NUCLEAR MEDICINE, ANNALS OF NUCLEAR MEDICINE, 15(5), 417 - 423, Oct. 2001 , Refereed
    Summary:An ordered subsets expectation maximization (OS-EM) algorithm is used for image reconstruction to suppress image noise and to make non-negative value images. We have applied OS-EM to a digital brain phantom and to human brain F-18-FDG PET kinetic studies to generate parametric images. A 45 min dynamic scan was performed starting injection of FDG with a 2D PET scanner. The images were reconstructed with OS-EM (6 iterations, 16 subsets) and with filtered backprojection (FBP), and K1, k2 and k3 images were created by the Marquardt non-linear least squares method based on the 3-parameter kinetic model. Although the OS-EM activity images correlated fairly well with those obtained by FBP, the pixel correlations were poor for the k2 and k3 parametric images, but the plots were scattered along the line of identity and the mean values for K1, k2 and k3 obtained by OS-EM were almost equal to those by FBP. The kinetic fitting error for OS-EM was no smaller than that for FBP. The results suggest that OS-EM is not necessarily superior to FBP for creating, parametric images.
  • Auditory triggered mental imagery of shape involves visual association areas in early blind humans, AG De Volder, H Toyama, Y Kimura, M Kiyosawa, H Nakano, A Vanlierde, MC Wanet-Defalque, M Mishina, K Oda, K Ishiwata, M Senda, NEUROIMAGE, NEUROIMAGE, 14(1), 129 - 139, Jul. 2001 , Refereed
    Summary:Previous neuroimaging studies identified a large network of cortical areas involved in visual imagery in the human brain, which includes occipitotemporal and visual associative areas. Here we test whether the same processes can be elicited by tactile and auditory experiences in subjects who became blind early in life. Using positron emission tomography, regional cerebral blood flow was assessed in six right-handed early blind and six age-matched control volunteers during three conditions: resting state, passive listening to noise sounds, and mental imagery task (imagery of object shape) triggered by the sound of familiar objects. Activation foci were found in occipitotemporal and visual association areas, particularly in the left fusiform gyrus (Brodmann areas 19-37), during mental imagery of shape by both groups. Since shape imagery by early blind subjects does involve similar visual structures as controls at an adult age, it indicates their developmental crossmodal reorganization to allow perceptual representation in the absence of vision. (C) 2001 Academic Press.
  • Mapping of CNS sigma(1) receptors in the conscious monkey: Preliminary PET study with [C-11]SA4503, K Ishiwata, H Tsukada, K Kawamura, Y Kimura, S Nishiyama, T Kobayashi, K Matsuno, M Senda, SYNAPSE, SYNAPSE, 40(3), 235 - 237, Jun. 2001 , Refereed
  • Extraction of vessel-related information from pet images without continuous blood sampling using modified independent component analysis, M Naganawa, A Matani, Y Kimura, PROCEEDINGS OF THE 23RD ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-4, PROCEEDINGS OF THE 23RD ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-4, 23, 2744 - 2747, 2001 , Refereed
    Summary:Quantitative positron emission tomography (PET) analysis with a compartment model requires a plasma time-activity curve (pTAC). In the analysis, continuous blood sampling via an inserted catheter in the brachial artery is widely used to obtain pTAC. However, this continuous blood sampling encounters some difficulties. Therefore, it is of clinical interest to develop a method that does not involve continuous blood sampling. We proposed a method for extracting pTAC from dynamic PET image sequences using a modified independent component analysis (ICA). To improve the, mismatch between properties of the dynamic PET image structure and assumptions of ICA, two preprocessings were proposed: (1) appending negative images and (2) standardization. This proposed method was applied to simulated data and clinical data for evaluation. The extracted pTAC obtained using the proposed method was nonnegative and the distribution of the pTAC image was similar to that of blood volume data. In contrast, the extracted pTAC obtained by conventional ICA included negative values. It was concluded that the proposed method is useful for extracting pTAC.
  • Formation of parametric images in positron emission tomography using a clustering-based kinetic analysis with statistical clustering, Y Kimura, Y Noshi, K Oda, K Ishii, PROCEEDINGS OF THE 23RD ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-4, PROCEEDINGS OF THE 23RD ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-4, 23, 2763 - 2765, 2001 , Refereed
    Summary:A method is proposed for forming parametric images in positron emission tomography, using clustering kinetic analysis. To overcome the dual problems experienced in voxel-based data, of signal noise and the very long computational time, the data are clustered before parameter estimation, and then an estimation procedure is applied to the averaged data in eac: hcluster. Using this algorithm, PET data are optimally clustered, depending on the noise that is present, by hierarchically applying a statistical-clustering algorithm based on Mixed Gaussian model. In a computer simulation, the proposed method correctly clustered noise-contaminated data. Applying the proposed algorithm to F-18-FDG clinical data, physiologically acceptable parametric images of glucose metabolism in a brain were obtained in a practical calculation time.
  • Preclinical evaluation of [C-11]SA4503: radiation dosimetry, in vivo selectivity and PET imaging of sigma(1) receptors in the cat brain, K Kawamura, K Ishiwata, Y Shimada, Y Kimura, T Kobayashi, K Matsuno, Y Homma, M Senda, ANNALS OF NUCLEAR MEDICINE, ANNALS OF NUCLEAR MEDICINE, 14(4), 285 - 292, Aug. 2000 , Refereed
    Summary:Our previous in vivo study with rats has demonstrated that C-11-labeled 1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine ([C-11]SA4503) is a potential radioligand for mapping CNS sigma(1) receptors by positron emission tomography (PET). In the present study, we further characterized this ligand. The radiation absorbed-dose of [C-11]SA4503 in humans estimated with the tissue distribution in mice, was higher in the liver, kidney and pancreas than in other organs studied, but was low enough for clinical use. The brain uptake of [(11)]SA4503 in mice was reduced to approximately 60-70% by co-injection of carrier SA4S03 and haloperidol, but not by co-injection of any of six ligands for sigma(2) or other receptors, for which SA4503 showed in vitro >100 times weaker affinity than for sigma(1) receptor. In. the cat brain, the uptake in the cortex was higher than that in the cerebellum. The radioactivity in the cortex and cerebellum accumulated for the first 10 min and then gradually decreased until 81.5 min in the baseline measurement, but rapidly decreased in the carrier-loading condition. The receptor-mediated uptake was estimated to be approximately 60-65% of the total radioactivity in. the cortex and cerebellum at 76 min after tracer injection. We have concluded that [C-11]SA4S03 has she potential for mapping sigma(1) receptor by PET.
  • Intrasubject correlation between static scan and distribution volume images for [C-11]flumazenil PET, M Mishina, M Senda, Y Kimura, H Toyama, K Ishiwata, M Ohyama, T Nariai, K Ishii, K Oda, T Sasaki, S Kitamura, Y Katayama, ANNALS OF NUCLEAR MEDICINE, ANNALS OF NUCLEAR MEDICINE, 14(3), 193 - 198, Jun. 2000 , Refereed
    Summary:Accumulation of [C-11]flumazenil (FMZ) reflects central nervous system benzodiazepine receptor (BZR). We searched for the optimal time for a static PET scan with FMZ as semi-quantitative imaging of BZR distribution. In 10 normal subjects, a dynamic series of decay-corrected PET scans was performed for 60 minutes, and the arterial blood was sampled during the scan to measure radioactivity and labeled metabolites. We generated 13 kinds of "static scan" images from the dynamic scan in each subject, and analyzed the pixel correlation for these images versus distribution volume (DV) images. We also analyzed the time for the [C-11]FMZ in plasma and tissue to reach the equilibrium. The intra-subject pixel correlation demonstrated that the "static scan" images for the period centering around 30 minutes post-injection had the strongest linear correlation with the DV image. The ratio of radioactivity in the cortex to that in the plasma reached a peak at 40 minutes after injection. Considering the physical decay and patient burden, we conclude that the decay corrected static scan for [C-11]FMZ PET as semi-quantitative imaging of BZR distribution is to be optimally acquired from 20 to 40 minutes after injection.
  • Generation of fractal dimension images and its application to automatic edge detection in brain MRI, K Uemura, H Toyama, S Baba, Y Kimura, M Senda, A Uchiyama, COMPUTERIZED MEDICAL IMAGING AND GRAPHICS, COMPUTERIZED MEDICAL IMAGING AND GRAPHICS, 24(2), 73 - 85, Mar. 2000 , Refereed
    Summary:We have developed four methods to generate a fractal dimension image and have applied them to the brain MRI. We have adopted four types of scanning methods, "CONVENTIONAL", "OVERLAPPING", "SYMMETRIC" and "FOLDED" to estimate the fractal dimension. The first three methods show almost the same fractal dimension images and their values were between two and three. In the "FOLDED" method, we were able to obtain the images in which the edge of a narrow region including dura and scalp surrounding the brain was selectively enhanced in the T1-weighted MRI, This is found to be a new edge-enhancing filter. We could remove the surrounding structure of the brain by using these filtered images and detect the edge of the brain surface automatically. The brain surface data can be used for various applications such as three-dimensional surface display and registration of inter-modal brain images. (C) 2000 Elsevier Science Ltd. All rights reserved.
  • Improved signal-to-noise ratio in parametric images by cluster analysis, Y Kimura, H Hsu, H Toyama, M Senda, NM Alpert, NEUROIMAGE, NEUROIMAGE, 9(5), 554 - 561, May 1999 , Refereed
    Summary:Parametric images are formed by analyzing the concentration history of every voxel in PET data sets. Because PET concentration data at the voxel level are rather noisy, noise propagation into the parametric image is often quite noticeable. To address this problem, a model-based clustering method has been developed to generate parametric images. The basic idea of the clustering method is to average over voxels whose concentration histories have the same shape. We applied the method to a two-parameter (K-1, k(2)) compartment model of local cerebral blood flow. The statistic R = integral tC(t) dtl integral C(t) df = integral te(-k2t) x C-a(t) dtl integral e(-k2t) x C-a(t) dt classifies curves in terms of k(2), where C(t) and C,(t) denote the tissue and blood concentration histories, respectively, and x is the convolution operator. Simulation studies of noise propagation in the clustering statistic showed that 30% voxel noise yielded a 2% standard deviation in R. Parametric images of blood flow and partition coefficient were computed for an O-15 study, with and without clustering. Cluster size affected bias, statistical precision, and computation time. With clusters of 400 voxels, the variance of the flow parameter was around 1/50 smaller with clustering, with negligible bias and a computation time of 30 s on a 64-MHz workstation for 15 x 128 x 128 images with MATLAB 5.1. (C) 1999 Academic Press.
  • A comparison between cyclists and noncyclists of joint torque of the lower extremities during pedaling, Hidetoshi Hoshikawa, Keiichi Tamaki, Hiroshi Fujimoto, Yuichi Kimura, Hirokazu Saito, Yoshiro Satoh, Yoshio Nakamura, Isao Muraoka, Japanese Journal of Physical Fitness and Sports Medicine, Japanese Journal of Physical Fitness and Sports Medicine, 48(5), 547 - 558, 1999 , Refereed
    Summary:The purpose of this study was to compare the effect between cyclists and noncyclists of pedal rates on ankle, knee, and hip joint torque during pedaling exercises. Six male cyclists (CY) and seven male noncyclists (NC) pedaled at 40, 60, 90 and 120 rpm with a power output of 200 W. The lower limb was modeled as three rigid segment links constrained to plane motion. Based on the Newton-Euler method, the equation for each segment was constructed and solved on a computer using pedal force, pedal, crank, and lower limb position data to calculate torque at the ankle, knee, and hip joints. The average planter flexor torque decreased with increasing pedal rates in both groups. The average knee extensor torque for CY decreased up to 90 rpm, and then leveled off at 120 rpm. These results were similar to NC. The average knee flexor torque in both groups remained steady over all pedal rates. The average hip extensor torque for CY decreased significantly up to 90 rpm where it showed the lowest value, but increased at 120 rpm. For NC, the average hip extensor torque did not decrease at 90 rpm compared with 60 rpm, and was significantly higher than CY at 120 rpm (CY : 28.1 ± 9.0 Nm, NC : 38.6 ± 6.7 Nm, p < 0.05). The average hip flexsor torque for NC at 120 rpm increased significanly from 90 rpm, and was significantly higher than CY (CY : 11.6 ± 2.9 Nm, NC : 22.6 ± 11.8 Nm, p < 0.05). These results suggest that it would be better for cyclists to select a pedal rate of between 90 to 110 rpm to minimize joint torque, and, as a result, reduce peripheral muscle fatigue.
  • Improving signal-to-noise ratio in FDG parametric images by cluster analysis, Y Kimura, M Senda, NM Alpert, 1999 IEEE NUCLEAR SCIENCE SYMPOSIUM - CONFERENCE RECORD, VOLS 1-3, 1999 IEEE NUCLEAR SCIENCE SYMPOSIUM - CONFERENCE RECORD, VOLS 1-3, 1269 - 1271, 1999 , Refereed
    Summary:The problems associated with forming parametric images from a positron emission tomography (PET) kinetic study are large noise levels in the voxel-based tissue time-activity curve (tTAC), and huge calculation times. A clustering based kinetics method is proposed for addressing these problems. In this method, voxels with the same shape are gathered and averaged before parameter estimation. Compared with an ordinal regions of interest (ROT) based non-linear parameter estimation method, parametric images with almost the same statistical reliability are obtained. In addition, the calculation time is very short (two minutes).
  • Effect of reconstruction algorithm on parametric images in PET dynamic study: Comparison between FBP and OS-EM, K Oda, H Toyama, K Uemura, Y Ikoma, Y Kimura, M Senda, 1999 IEEE NUCLEAR SCIENCE SYMPOSIUM - CONFERENCE RECORD, VOLS 1-3, 1999 IEEE NUCLEAR SCIENCE SYMPOSIUM - CONFERENCE RECORD, VOLS 1-3, 1542 - 1545, 1999 , Refereed
    Summary:Ordered subset expectation maximization (OS-EM) algorithm is used for image reconstruction to suppress image noise and to make non-negative value images. We have applied OS-EM to a digital phantom and to an F-18-FDG PET kinetic study to generate parametric images. A 45min dynamic scan was performed starting injection of 86-223MBq of FDG using a 2D PET scanner. The Images were reconstructed with OS-EM (6 iterations, 16 subsets) and with filtered backprojection (FBP), and K1,k2 and k3 images were created with Marquardt method. The activity images by OS-EM correlated fairly well with those by FBP. Although the mean values of K1, k2 and k3 for OS-EM were almost equal to those for FBP, the pixel correlation between OS-EM and FBP showed an offset from the line of identity in parametric images, possibly due to different noise characteristics. The kinetic fitting error far OS-EM was no smaller than that for FBP. The results suggest that OS-EM is not necessarily superior to FBP for creating parametric images.
  • Visual temporal frequency characteristics determined by pseudorandom stimuli, K Momose, M Kiyosawa, N Nemoto, Y Kimura, F Okuyama, M Senda, INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 40(1), 50 - 54, Jan. 1999 , Refereed
    Summary:PURPOSE. TO investigate whether a rapid and practical determination of the temporal frequency characteristic (TFC) of the visual system can be obtained by using the visually evoked potentials (VEPs) elicited by pseudorandom binary sequence (PRBS) stimulation. METHODS. VEPs were recorded from eight volunteers. For the conventional steady state VEPs (S-VEP), the eye was stimulated with five stimulus frequencies. To acquire the PRBS-VEPs, the eye was stimulated with a PRBS stimulus for 40 seconds. The TFC for the S-VEP was calculated from the root mean squared amplitude for each frequency using Fourier transform. For the PRBS stimulus, a cross-correlation function between PRBS (x[t]) and PRBS-VEP (y[t]) was calculated to obtain the TFC. RESULTS. The TFCs obtained by the PRBS and S-VEP methods were highly correlated (P < 0.05), and the TFC curves resembled those in the literature. Most important, the data necessary to determine the TFCs using the PRBS stimulus could be obtained in 4 minutes, whereas that for the S-VEP required 60 minutes for the two eyes. CONCLUSIONS. The high correlation between the TFCs obtained by the two methods indicated that the PRBS technique gives a good measure of the TFC of the human visual system. The significantly shorter time required for this method demonstrated that it is a practical method for determining the linear (and nonlinear) property of the visual system and that it may be useful in clinical applications.
  • Mapping visual field with positron emission tomography by mathematical modeling of the retinotopic organization in the calcarine cortex, S Endo, H Toyama, Y Kimura, K Ishii, M Senda, M Kiyosawa, A Uchiyama, IEEE TRANSACTIONS ON MEDICAL IMAGING, IEEE TRANSACTIONS ON MEDICAL IMAGING, 16(3), 252 - 260, Jun. 1997 , Refereed
    Summary:We developed an objective and quantitative method of mapping the human visual field with positron emission tomography (PET) and magnetic resonance image (MRI). The regional cerebral blood flow (rCBF) images were acquired with H-2(15)}O- PET under visual fixation as well as under visual stimulation with flickering diodes arranged along the ring at 0 degrees, 3 degrees, 7 degrees, 14 degrees, 21 degrees, or 29 degrees from the fixation point, After coregistration of PET and MR images, we extracted the surface of the calcarine cortex from the MR images and unfolded it to a two-dimensional (2-D) elliptic plane, on which the activated PET images were superimposed. Then we transformed the unfolded calcarine cortex into the visual field coordinates using the complex logarithmic function proposed by Schwartz. A large individual variation was observed in the retinotopical organization as well as in the morphology of the calcarine cortex. The formula was valid only within 15 degrees from the center of the visual field. The constant parameter in the formula was estimated to be 1.5. The cortical linear magnification factor was 12.1, 2.8, and 1.6 at 0, 5, and 10 degrees, respectively, The areas of the central 10 degrees and 40 degrees in the visual field correspond to 50% and 81% of the calcarine surface, respectively.
  • Basic study on relationship between estimated rate constants and noise in FDG kinetic analysis, Yuichi Kimura, Hinako Toyama, Michio Senda, Kakuigaku, Kakuigaku, 33(2), 107 - 114, 1996 , Refereed
    Summary:For accurate estimation of the rate constants in 18F-FDG dynamic study, the shape of the estimation function (Φ) is crucial. In this investigation, the relationship between the noise level in tissue time activity curve and the shape of the least squared estimation function which is the sum of squarred error between a function of model parameters and a measured data is calculated in 3 parameter model of 18F-FDG. In the first simulation, by using actual plasma time activity curve, the true tissue curve was generated from known sets of rate constants ranging 0.05 ≤ k 1 ≤ 0.15, 0.1 ≤ k 2 ≤ 0.2 and 0.01 ≤ k 3 ≤ 0.1 in 0.01 step. This procedure was repeated under various noise levels in the tissue time activity curve from 1 to 8% of the maximum value in the tissue activity. In the second simulation, plasma and tissue time activity curves from clinical 18F-FDG dynamic study were used to calculate the Φ. Results are: (1) In the noise-free case, because the global minima is separated from neighboring local minimums, it was easy to find out the optimum point. However, with increasing noise level, the optimum point was buried in many neighboring local minima. Making it difficult to find out the optimum point. (2) The optimum point was found within 20% of the convergence point by standard non-linear optimization method. (3) The shape of Φ for the clinical data was similar to that with the noise level of 3 or 5% in the first simulation. Therefore direct search within the area extending 20% from the result of usual non-linear curve fitting procedure is recommended for accurate estimation of the constants.
  • Power spectrum of heart rate fluctuations during incremental cycle exercise, Yoshio Nakamura, Keiichi Tamaki, Minoru Shinohara, Yuichi Kimura, Isao Muraoka, Japanese Journal of Physical Fitness and Sports Medicine, Japanese Journal of Physical Fitness and Sports Medicine, 38(5), 208 - 214, 1989 , Refereed
    Summary:Spectral analysis was applied to investigate whether the system for control of heart rate (HR) is influenced by exercise intensity. Five healthy males performed incremental exercise on an electrically braked cycle ergometer until exhaustion. The work rate was increased at 12 W/min following 2 min of exercise at a constant load of 20 W. HR was measured every second from R-R intervals. The power spectrum was calculated every 10 s using the FFT method for 64 consecutive data points. Power spectra during 20 W exercise showed a similar pattern to those in previous reports on resting HR perturbations. Although interindividual differences were observed for the spectrum patterns related to exercise intensity, there was a characteristic pattern revealing dissipation of the spectral power above a frequency of 0.2 Hz for all subjects. This pattern was not maintained for more than 1 min in any of the subjects, and was followed by a semirandom pattern whose magnitude varied among the subjects. These results support the hypothesis that the cardiac pacemaker is influenced by exercise intensity, presumably due to sympatho-vagal interaction with the respiratory control system. © 1989, The Japanese Society of Physical Fitness and Sports Medicine. All rights reserved.

Books etc

  • Human Brain Imaging of Adenosine Receptors, Masahiro Mishina, Yuichi Kimura, Kiichi Ishiwata, Joint author, Elsevier,   2013
  • Brain Imaging Using PET, Michio Senda, Yuichi Kimura, Peter Herscovitch, Joint editor, Academic Press,   2002

Conference Activities & Talks

  • Application of Least-Squares Cubic Linear Regression to the Logan Graphical Analysis to Reduce the Underestimation of BPND for Neuroreceptor Parametric Imaging in Positron Emission Tomography Studies, Paulus Kapundja Shigwedha, Takahiro Yamada, Kohei Hanaoka, Kazunari Ishii, Yuichi Kimura, Yutaka Fukuoka,   2019 09 06
  • Automatic Diagnosis of Melanoma Using Hyperspectral Data and GoogLeNet, Ginji Hirano, Mitsutaka Nemoto, Yuichi Kimura, Yoshio Kiyohara, Hiroshi Koga, Naoya Yamazaki, Gustav Christensen, Atsushi Nakamura, Takayuki Sota, Takashi Nagaoka,   2019 09 06
  • Performance Improvement of Automated Melanoma Diagnosis System by Data Augmentation, Kana Kato, Mitsutaka Nemoto, Yuichi Kimura, Yoshio Kiyohara, Hiroshi Koga, Naoya Yamazaki, Gustav Christensen, Atsushi Nakamura, Takayuki Sota, Takashi Nagaoka,   2019 09 06
  • Weighting Function for Kinetics-Based Noise Reduction in PET Amyloid Imaging, Takahiro Yamada, Shogo Watanabe, Takashi Nagaoka, Mitsutaka Nemoto, Kohei Hanaoka, Hayato Kaida, Kazunari Ishii, Yuichi Kimura,   2019 09 06
  • Custering-based data reduction algorithm with simplified reference tissue modelto generate parametric images in amyloid imaging, T.Yamad, Y. Kimura, M. Sakata, T. Nagaoka, M. Nemoto, K. Hanaoka, H. Kaida, K. Ishii, Brain and Brain PET 2019,   2019 07 04
  • Clinical Protocol to Quantify AMPA Receptors Using Novel 11C‐labeled PET Tracer of K2, Yuichi Kimura, Takahiro Yamada, Mai Hatano, Waki Nakajima, Tomoyuki Miyazaki, Takuya Takahashi, 2019 SNMMI Annual Meeting,   2019 06 22 , Society of Nuclear Medicine and Molecular Imaging
  • Quantitative Imaging of AMPA Receptors Using Novel 11C-labeled PET Tracer for AMPA Receptors, KIMURA Yuichi, Annual Congress of the Europian Association of Nuclear Medicine,   2018 10 17
  • Determination of Appropriate Reconstruction Parameters for Each pf 21 PET Scanner Models from 6 Vendors to Meet the Society Phantom Criteria for Brain Amyloid PET Imaging, Yasuhiko Ikari, Keiichi Matsumoto, Goh Akamatsu, Hiroshi Nishida, Yuichi Kimura, Keiichi Oda, Michio Senda, Annual Congress of the Europian Association of Nuclear Medicine,   2018 10 15
  • A Less-Biased Regression Method to Quantify Receptor Density from the Logan Graphical Analysis in Positron Emission Tomography, Paulus Kapundja Shigwedha, Yuichi Kimura, YUtaka Fukuoka, IEEE EMBC18,   2018 07 17
  • Noise Reduction Algorithm for Amyloid Image Preserving Image Resolution --- Quantitative Evaluation Using Clinical Images, KIMURA YuichiTakahiro Yamada, Yuichi Kimura, Kosuke Fuji, Shogo Watanabe, Takashi Nagaoka, Mitsutaka Nemoto, Kohei Hanaoka, Hayato Kaida, Chisa Hosokawa, Kazunari Ishii, Human Amyloid Imaging 2018,   2018 01 17
  • Phantom Test Procedures and Criterion for Standardization of Brain PET Imaging across Different Cameras, Go Akamatsu, Yasuhiro Ikari, Hidekatsu Wakizaka, Taiga Yamaya, Yuichi Kimura, Keiichi Oda, Michio Senda, 2017 IEEE Nuclear Science Symposium and Medical Imaging Conference,   2017 10 12
  • Qualification of PET cameras and imaging sites for 11C-methionine PET on brain tumor in Japan, Kimura Yuichi, Nishida Hiroyuki, Ikari Yasuhiko, Matsumoto Keiichi, Oda Keiichi, Nishio Tomoyuki, Fukukita Hiroyoshi, Inoue Tomio, Senda Michio, JOURNAL OF NUCLEAR MEDICINE,   2014 05
  • Comparison between SUV and BP images acquired using 11C-PIB PET: Questionable PIB accumulation in SUV images, Hosokawa Chisa, Ishii Kazunari, Kimura Yuichi, Sakaguchi Kenta, Hosono Makoto, Murakami Takamichi, JOURNAL OF NUCLEAR MEDICINE,   2014 05

Misc

  • A pilot study to detect anatomical landmarks using convolutional neural network, 根本 充貴, 渡辺 翔吾, 木村 裕一, 花岡 昇平, 野村 行弘, 吉川 健啓, 林 直人, 電子情報通信学会技術研究報告 = IEICE technical report : 信学技報, 117, 518, 47, 50,   2018 03 19 , http://ci.nii.ac.jp/naid/40021522933
  • Performance Evaluation of Noise Reduction Algorithm for PET Amyloid Imaging Using Clinical Images., Yamada Takahiro, Kimura Yuichi, Fujii kosuke, Watanabe Shogo, Nagaoka Takashi, Nemoto Mitsutaka, Hanaoka Kohei, Kaida Hayato, Ishii Kazunari, Transactions of Japanese Society for Medical and Biological Engineering, 56, 0, S294, S294,   2018 , http://ci.nii.ac.jp/naid/130007483802
    Summary:<p>This study aims to develop a noise reduction algorithm for amyloid PET imaging. A visualization of a small amyloid-β (Aβ) deposit is required for early diagnosis of Alzheimer's disease (AD) pathology, and a noise in amyloid image should be reduced without any loss of spatial resolution. Conventional noise reduction algorithms use spatial averaging, but our proposed algorithm, CAKS, averages pixels that have similar kinetics of administered PET radiopharmaceutical. As a result of CAKS applying to actual clinical images, the noise is reduced and the image quality is improved. The contrast between gray and white matters is significantly improved (p<.05). We concluded that CAKS is applied to clinical amyloid PET imaging is useful for diagnosis of AD pathology. </p>
  • 動態に基づいたアミロイドイメージング雑音除去アルゴリズムの性能評価, 山田 誉大, 木村 裕一, 藤井 康介, 渡辺 翔吾, 永岡 隆, 花岡 宏平, 細川 知紗, 石井 一成, 村上 卓道, 核医学, 54, Suppl., S210, S210,   2017 09
  • 機械学習によるDatSCANのPD・健常の自動鑑別, 渡辺 翔吾, 木村 裕一, 根本 充貴, 山田 誉大, 藤井 康介, 林 俊行, 三品 雅洋, 核医学, 54, Suppl., S210, S210,   2017 09
  • 機械学習を用いた認知症自動鑑別におけるFDG画像とMR画像の比較, 坂田 宗之, 王 小宇, 石井 賢二, 木村 裕一, 我妻 慧, 石橋 賢士, 豊原 潤, 矢田 紀子, 眞鍋 佳嗣, 核医学, 54, Suppl., S187, S187,   2017 09
  • Development of automated delineation algorithm of reference regions for amyloid imaging. - Considering time information and the number of clusters -, Yamada Takahiro, Kimura Yuichi, Nagaoka Takashi, Hanaoka Kohei, Hosokawa Chisa, Ishii Kazunari, Trans. jpn. Soc. Med. Bio. Eng, 55, 4, 281, 281,   2017 , http://ci.nii.ac.jp/naid/130006077023
    Summary:<p>In Alzheimer's disease (AD) amyloid-β (Aβ) depositions disturbs neurons irreversibly, and early treatment before occurrence of dementia is important for AD treatments. This study aims at proposing an automated delineation algorithm for reference regions (AutoRef) for Aβ accumulation quantification. This presentation focuses on merits of a limited temporal information and the increased number clusters. As a result, for 86 clinical data (43 cases of AD, 33 cases of normal and 10 cases of equivocal deposition of Aβ), AutoRef succeeded in delineating the reference region for all the data. There was no significant difference (p < 0.05) between AutoRef and manually delineated reference region by a physician. The standard deviation of the difference between them was smaller than the discrimination threshold of AD used in actual clinical practice. In conclusions, the effectiveness of this study was suggested.</p>
  • 脳FDG画像を用いた認知症鑑別診断における機械学習から得られる画像指標と認知機能との関係, 坂田 宗之, 王 小宇, 石井 賢二, 木村 裕一, 我妻 慧, 石橋 賢士, 豊原 潤, 矢田 紀子, 眞鍋 佳嗣, 核医学, 53, Suppl., S278, S278,   2016 10
  • FDG‐PETを用いた認知症鑑別診断における画像指標と臨床指標の関係, WANG Xiaoyu, WANG Xiaoyu, 坂田宗之, 石井賢二, 木村裕一, 木村裕一, 我妻慧, 石橋賢士, 豊原潤, 矢田紀子, 眞鍋佳嗣, 電子情報通信学会大会講演論文集(CD-ROM), 2016, ROMBUNNO.D‐16‐6,   2016 03 01 , http://jglobal.jst.go.jp/public/201602215501930931
  • 脳FDG画像を用いた認知症鑑別診断における機械学習の可用性の検討, 坂田 宗之, 王 小宇, 石井 賢二, 木村 裕一, 我妻 慧, 石橋 賢士, 豊原 潤, 矢田 紀子, 石渡 喜一, 眞鍋 佳嗣, 核医学, 52, 3, 278, 278,   2015 09
  • D-16-6 A feasibility study of machine learning for differential dementia diagnosis using FDG-PET images, Wang Xiaoyu, Sakata Muneyuki, Ishii Kenji, Kimura Yuichi, Wagatsuma Kei, Ishibashi Kenji, Toyohara Jun, Yata Noriko, Ishiwata Kiichi, Manabe Yoshitugu, Proceedings of the IEICE General Conference, 2015, 2,   2015 02 24 , http://ci.nii.ac.jp/naid/110009946724
  • 線条件アデノシンA1およびA2A受容体とパーキンソン病の振戦・固縮の関係, 三品 雅洋, 石井 賢二, 鈴木 正彦, 橋本 昌也, 木村 裕一, 長縄 美香, 坂田 宗之, 織田 圭一, 豊原 潤, 永山 寛, 石渡 喜一, 片山 泰朗, 臨床神経学, 54, Suppl., S239, S239,   2014 12
  • 脳FDG画像の統計比較に用いるMRI解剖学的標準化の全脳抽出の改良, 坂田 宗之, 江尻 顕浩, 石井 賢二, 木村 裕一, 織田 圭一, 豊原 潤, 矢田 紀子, 石渡 喜一, 眞鍋 佳嗣, 核医学, 51, 3, 328, 328,   2014 09
  • Comparison between a Renormalization Method for Linear Regression and a Bayes Method for Denoising with respect to Imoprovement of Dynamic PET Image Analysis, KOZAWA Takahiro, HONTANI Hidekata, SAKAGUCHI Kazuya, SAKATA Muneyuki, KIMURA Yuichi, IEICE technical report., 113, 410, 285, 290,   2014 01 19 , http://ci.nii.ac.jp/naid/110009821280
    Summary:The tissue time activity curve (tTAC) represents a time variation of radioactivity of ligand in the brain derived from brain PET imaging, and is used for receptor analysis in combination with the time activity curve in arterial plasma. However, it is known that the noises in measured tTAC seriously deteriorates analysis accuracy. In order to improve the performance, we propose two methods: Bayesian approach to denoise tTAC and the renormalization approach for the Logan Graphical Analysis. We found the first method improves the performance better.
  • Employment of MRI anatomical normalization in statistical comparison of brain FDG-PET : Improvement of the whole brain extraction and performance evaluation, EJIRI Akihiro, SAKATA Muneyuki, ISHII Kenji, KIMURA Yuichi, ODA Keiichi, TOYOHARA Jun, YATA Noriko, ISHIWATA Kiichi, MANABE Yoshitsugu, IEICE technical report., 113, 410, 127, 132,   2014 01 19 , http://ci.nii.ac.jp/naid/110009821250
    Summary:Statistical comparisons of brain FDG-PET images have been effectively used for dementia diagnosis or detection of epileptic foci. The performance of the comparison depends on the accuracy of the anatomical normalization. For more accurate normalization of brain PET images, we have previously proposed the method which utilizes the MRI images and the advanced method for MRI anatomical normalizations. The performances of our previously proposed method have been often affected by the errors included at the pre-process of MRI images. This paper describes the improvements of the method by incorporating the brain extraction from the FDG image. In addition, it describes the evaluations of the methods by using the image of healthy subjects and patients with dementia or epilepsy.
  • 未治療パーキンソン病における被殻アデノシンA1受容体密度, 三品 雅洋, 石渡 喜一, 石井 賢二, 木村 裕一, 鈴木 正彦, 橋本 昌也, 坂田 宗之, 織田 圭一, 豊原 潤, 北村 伸, 片山 泰朗, 臨床神経学, 53, 12, 1435, 1435,   2013 12
  • 脳FDG画像の統計比較を用いた認知症診断におけるMRI解剖学的標準化の導入による性能向上, 坂田 宗之, 水野 僚介, 石井 賢二, 織田 圭一, 豊原 潤, 石渡 喜一, 木村 裕一, 核医学, 50, 3, S180, S180,   2013 09
  • パーキンソン病の振戦・固縮とドパミントランスポータ・ドパミンD2受容体・アデノシンA2A受容体の関係, 三品 雅洋, 石井 賢二, 鈴木 正彦, 橋本 昌也, 木村 裕一, 長縄 美香, 坂田 宗之, 織田 圭一, 豊原 潤, 片山 泰朗, 石渡 喜一, 核医学, 50, 3, S241, S241,   2013 09
  • Influence of rate constants as the prior to performance of denoising tissue time activity curves for PET kinetic analysis, KOZAWA Takahiro, HONTANI Hidekata, SAKAGUCHI Kazuya, SAKATA Muneyuki, KIMURA Yuichi, IEICE technical report., 112, 411, 287, 292,   2013 01 24 , http://ci.nii.ac.jp/naid/110009727748
    Summary:A Bayesian approach to de-noise tissue time activity curves (tTAC) is proposed. The proposed method estimate the posterior distribution of the tTAC. A set of noise-free tTAC is simulated based on a compartment model for obtaining the prior distribution of the tTAC, and is used for the computatation of the posterior distribution. We evaluated the performance of the given rate constant as a prior information introduced when obtaining the prior distribution of tTAC by using simulated and clinical PET data.
  • Performance improvements using MRI anatomical normalization in statistical comparison of brain FDG-PET for dementia diagnosis, MIZUNO RYOSUKE, MIZUNO RYOSUKE, SAKATA MUNEYUKI, ISHII KENJI, ODA KEIICHI, TOYOHARA JUN, ISHIWATA KIICHI, KIMURA YUICHI, KIMURA YUICHI, KIMURA YUICHI, 電子情報通信学会技術研究報告, 112, 411(MI2012 62-124), 25, 29,   2013 01 17 , http://jglobal.jst.go.jp/detail.php?from=API&JGLOBAL_ID=201302234626361264
  • 未治療パーキンソン病における被殻アデノシンA1受容体密度, 三品雅洋, 三品雅洋, 石渡喜一, 石井賢二, 木村裕一, 木村裕一, 鈴木正彦, 鈴木正彦, 橋本昌也, 橋本昌也, 坂田宗之, 織田圭一, 豊原潤, 北村伸, 北村伸, 片山泰朗, 日本神経学会学術大会プログラム・抄録集, 54th, 317,   2013 , http://jglobal.jst.go.jp/detail.php?from=API&JGLOBAL_ID=201302287446718985
  • ジスキネジアを呈するパーキンソン病では被殻アデノシンA2A受容体は増加する, 三品 雅洋, 石渡 喜一, 石井 賢二, 北村 伸, 長縄 美香, 木村 裕一, 鈴木 正彦, 橋本 昌也, 石橋 賢士, 坂田 宗之, 織田 圭一, 豊原 潤, 濱本 真, 小林 士郎, 片山 泰朗, 臨床神経学, 52, 12, 1551, 1551,   2012 12
  • ジスキネジアを呈するパーキンソン病における被殻アデノシンA2A受容体密度 [11C]TMSX PETを用いた検討, 三品 雅洋, 鈴木 正彦, 石井 賢二, 北村 伸, 長縄 美香, 木村 裕一, 橋本 昌也, 坂田 宗之, 織田 圭一, 豊原 潤, 小林 士郎, 片山 泰朗, 石渡 喜一, 脳循環代謝, 24, 1, 171, 171,   2012 11
  • [11C]MPDX PETを用いた未治療パーキンソン病における被殻アデノシンA1受容体結合能, 三品 雅洋, 石井 賢二, 鈴木 正彦, 北村 伸, 橋本 昌也, 木村 裕一, 坂田 宗之, 織田 圭一, 豊原 潤, 片山 泰朗, 石渡 喜一, 核医学, 49, 3, S217, S217,   2012 08
  • Bayesian Inference Approach to Visualize Neuroreceptor Density using Positron Emission Tomography without Arterial Blood Sampling, KOZAWA Takahiro, HONTANI Hidekata, SAKAGUCHI Kazuya, SAKATA Muneyuki, KIMURA Yuichi, IEICE technical report., 112, 142, 29, 34,   2012 07 12 , http://ci.nii.ac.jp/naid/110009626678
    Summary:A Bayesian approach to de-noise tissue time activity curves (tTAC) is proposed in order to quantitatively visualize neuroreceptor density. Given the measurements, the method estimates the posterior probability distribution of the de-noised tTAC. No arterial blood sampling is required for the estimation. Instead, the prior probability distribution of the time activity curve in arterial plasma is used derived from population based clinical data set. A set of artificial noise-free tTACs is generated based on a compartment model for obtaining the prior distribution of the tTAC, and is used for the computation of the posterior distribution. In order to improve the confidence of the estimates, the method refers to the information of regions of interests (ROIs) in the measured PET images. The performance of the proposed method is demonstrated by the results of simulation experiments: The residual square error of the estimated tTAC was reduced about 58% by using the information of ROIs.
  • Bayesian Approach for the Denoising to PET Dynamic Data without Arterial Blood Sampling, KOZAWA Takahiro, HONTANI Hidekata, SAKAGUCHI Kazuya, SAKATA Muneyuki, KIMURA Yuichi, IEICE technical report., 111, 389, 11, 16,   2012 01 19 , http://ci.nii.ac.jp/naid/110009481185
    Summary:In this report, we propose a new method for denoising tissue time activity curve (tTAC) measured from brain PET images. tTAC is a curve representing time variation of radioactivity of ligand in the brain and used receptor analysis in combination with the plasma time activity curve (pTAC), which is obtained by drawing arterial blood. Large amount of noise in measured tTAC reduces accuracy of the estimation, so the accuracy of the estimation is improved by denoising tTAC. It is known that noise free tTAC is represented by the observed pTAC and the compartment model, which is derived from the behavior of ligand. The authors have proposed a method for denoising tTAC by using the measured pTAC and the compartment model. The drawback of the method was that it used the pTAC, which is not easy to measure. The proposed method expands the method: it denoises tTACs without using measured pTAC. In this article, we shows some results of fundamental experiments.
  • 被殻アデノシンA1受容体分布の加齢変化 [11C]MPDX PETを用いた検討, 三品 雅洋, 石渡 喜一, 木村 裕一, 坂田 宗之, 織田 圭一, 石井 賢二, 片山 泰朗, 脳循環代謝, 23, 1, 114, 114,   2011 11
  • MAP推定法によるPET動態データの雑音除去アルゴリズム, 木村 裕一, 本谷 秀堅, 坂口 和也, 織田 圭一, 石井 賢二, 坂田 宗之, 石渡 喜一, 核医学, 48, 3, S265, S265,   2011 09
  • 統合失調症患者における脳シグマ-1受容体のPETによる測定, 石川 雅智, 坂田 宗之, 石井 賢二, 織田 圭一, 呉 勁, 豊原 潤, 木村 裕一, 伊豫 雅臣, 石渡 喜一, 橋本 謙二, 精神薬療研究年報, 43, 57, 58,   2011 03
  • 被殻アデノシンA1受容体分布の加齢変化 [C-11]MPDX PETを用いた検討, 三品 雅洋, 石井 賢二, 木村 裕一, 坂田 宗之, 織田 圭一, 小林 士郎, 片山 泰朗, 石渡 喜一, 臨床神経学, 50, 12, 1183, 1183,   2010 12
  • Estimation algorithm using direct search method in PET neuroreceptor quantification, OKANISHI Yosuke, KIMURA Yuichi, SUGA Mikio, IEICE technical report, 109, 407, 53, 56,   2010 01 21 , http://id.ndl.go.jp/bib/10553843
    Summary:In a compartment model analysis using positron emission tomography(PET), some problems arises in non-linear estimation: misconvergence, dependence in estimation results on a initial values and calculation time. This study aimed at investigating a direct search method. In the algorithm, feature space on a time history of radioactivity concentration in tissues was composed using a measured time history in arterial plasma and a set of rate constraints in the model that covered physiologically expected range. The space was fluctuated by the noise observed in ROI-based PET study. The dynamic PET data were projected onto the feature space, and then clustered using the Mahalanobis distance. The method was validated with simulation based on ROI studies for [^<11>C]TMSX. Especially, the kinetic parameter K_1 and a total distribution volume, V_T, were estimated well. If V_T was fixed at this estimate and the algorithm was applied again, a performance in model estimation on a neuroreceptor density was approximately 20% of quartile deviation that was 40% without the constraint.
  • Determination of starting time for graphical analysis using X-square test in PET receptor imaging, OGAKI Hiroto, SAKAGUCHI Kazuya, SUGA Mikio, KIMURA Yuichi, IEICE technical report, 109, 407, 1, 6,   2010 01 21 , http://id.ndl.go.jp/bib/10553705
    Summary:This study aims at developing an algorithm to estimate a starting point, t^*, for Logan Graphical Analysis(LGA)and Multi-linear Analysis 1(MA1). LGA and MA1 are popular graphical methods for quantitative neuroreceptor imaging using PET. These methods should be applied after equilibrium within a tissue and give us a total distribution volume(V_T)that represents density of neuroreceptors. Previously, t^* was determined using ROI averaged PET data. Because the bias and the variability of the estimated V_T in voxel data get worse as the number of measurement points decreased, it's inappropriate to decide t^* using ROI averaged PET data. In this study, we suggest the determination algorithm of t^* for graphical analysis using χ-square test and try to improve the estimate accuracy of V_T. Although the proposed method estimated a suitable t^* based on the S/N ratio of PET data, it didn't lead to improve the accuracy of estimated V_T in a numerical simulation study.
  • A Strategy to Improve PET Neuroreceptor Analysis MA1 Based on Statistics of Measurement Errors, HOSHINO Naoki, HONTANI Hidekata, NAGANAWA Mika, SAKAGUCHI Kazuya, SAKATA Muneyuki, ISHIWATA Kiichi, KIMURA Yuichi, IEICE technical report, 109, 407, 7, 12,   2010 01 21 , http://ci.nii.ac.jp/naid/110007866387
    Summary:In this article, we propose a new method for improving MA1, which estimates total distribution volume V_T, the parameter reflecting a neuroreceptor density. MA1 applies a linear regression analysis to a set of data computed from the tissue time activity curve(tTAC)and the plasma time activity curve(pTAC)to obtain the value of V_T. The problem is that the linear regression is not supported by the statistics of the noise included in the data. Hence, the proposed method de-noises measured tTAC to estimate the corresponding true tTAC by means of MAP estimation. For the MAP estimation, we need the prior distribution of tTAC and the likelihood one on the measured tTAC. The proposed method estimates the former one based on simulations and estimates the latter one from the measurements. We evaluated the performance of MA1 and of the proposed method by using simulated tTACs and by using clinical data considering ^<11>C-SA4503 that is a probe of σ_1 receptors. The evaluation results show that our proposed method improves the variances of the estimates.
  • 3D-PETにおける体幹部用シールドの効果 ファントム実験による検討, 織田 圭一, 坂田 宗之, 石井 賢二, 長縄 美香, 木村 裕一, 石渡 喜一, 核医学, 46, 3, 250, 250,   2009 09
  • アミロイド蓄積は変性の原因か結果か? 非アルツハイマー病変性型認知症における経時観察, 石井 賢二, 織田 圭一, 坂田 宗之, 木村 裕一, 石橋 賢士, 金丸 和富, 村山 繁雄, 石渡 喜一, 核医学, 46, 3, 262, 262,   2009 09
  • PETによる瀰慢性軸索損傷時の高次脳機能障害病態の探求, 成相 直, 尤 郁偉, 日浦 幹夫, 木村 裕一, 石井 賢二, 石渡 喜一, 大野 喜久郎, 核医学, 46, 3, 306, 306,   2009 09
  • PETアミロイドプローベ[11C]PIB及び[11C]BF227の比較検討, 橋本 昌也, 石井 賢二, 木村 裕一, 織田 圭一, 川崎 敬一, 石川 雅智, 石渡 喜一, 岡村 信行, 谷内 一彦, 臨床神経学, 48, 12, 1094, 1094,   2008 12
  • 未治療パーキンソン病におけるアデノシンA2A受容体の治療開始後の変化, 三品 雅洋, 石渡 喜一, 石井 賢二, 北村 伸, 木村 裕一, 長縄 美香, 織田 圭一, 橋本 昌也, 鈴木 正彦, 濱本 真, 小林 士郎, 片山 泰朗, 臨床神経学, 48, 12, 1135, 1135,   2008 12
  • Determination of starting point for Logan graphical analysis using run test to improve PET neuroreceptor quantification, OGAKI Hiroto, KIMURA Yuichi, NAGANAWA Mika, SAKATA Muneyuki, SHIDAHARA Miho, SUGA Mikio, IEICE technical report, 108, 209, 27, 31,   2008 09 10 , http://id.ndl.go.jp/bib/9674228
    Summary:This study aims at developing an algorithm to estimate a starting point, t^*, for Logan Graphical Analysis (LGA). LGA is a popular algorithm for quantitative neuroreceptor imaging using a positron emission tomography, in which a gradient of linear relation between time activity curves in arterial blood and tissues of administrated radiopharmaceutical gives us a density of neuroreceptors. If t^* is given appropriately, signs of residuals of the line estimation becomes a random sequence. Thus, a run test, that is a nonparametric statistical test for randomness, can be expected to be apply for t^* estimation. From simulation, the run-test based algorithm is useful for neuroreceptor imaging with PET.
  • アルツハイマー病における[11C]PIB集積の意義 代謝低下・萎縮・罹病期間との相関, 石井 賢二, 織田 圭一, 川崎 敬一, 木村 裕一, 坂田 宗之, 石川 雅智, 石橋 賢士, 金丸 和富, 村山 繁雄, 石渡 喜一, 核医学, 45, 3, S180, S180,   2008 09
  • アミロイド蓄積は前頭側頭型認知症の臨床像を修飾するか?, 石井 賢二, 織田 圭一, 川崎 敬一, 木村 裕一, 坂田 宗之, 石川 雅智, 石橋 賢士, 金丸 和富, 村山 繁雄, 石渡 喜一, 核医学, 45, 3, S181, S182,   2008 09
  • アミロイドプローベ[11C]PIBと[11C]BF-227の直接比較 FDGとVBMとの相関, 石井 賢二, 橋本 昌也, 木村 裕一, 織田 圭一, 坂田 宗之, 川崎 敬一, 石橋 賢士, 石川 雅智, 石渡 喜一, 岡村 信行, 谷内 一彦, 核医学, 45, 3, S182, S182,   2008 09
  • パーキンソン病における抗パーキンソン病薬投与後のアデノシンA2A受容体分布の変化, 三品 雅洋, 石井 賢二, 北村 伸, 木村 裕一, 長縄 美香, 橋本 昌也, 織田 圭一, 鈴木 正彦, 小林 士郎, 片山 泰朗, 石渡 喜一, 核医学, 45, 3, S183, S183,   2008 09
  • ニコチンα7受容体新規リガンド[11C]CHIBA-1001の健常者におけるPET撮影, 石川 雅智, 石井 賢二, 豊原 潤, 呉 勁, 坂田 宗之, 木村 裕一, 織田 圭一, 伊豫 雅臣, 石渡 喜一, 橋本 謙二, 核医学, 45, 3, S197, S197,   2008 09
  • α7ニコチン受容体リガンド[11C]CHIBA-1001のヒト脳動態解析, 坂田 宗之, 木村 裕一, 石川 雅智, 豊原 潤, 呉 勁, 織田 圭一, 石井 賢二, 橋本 謙二, 石渡 喜一, 核医学, 45, 3, S228, S228,   2008 09
  • [11C]PIBの定量解析における血漿中代謝物分析の影響, 長縄 美香, 木村 裕一, 坂田 宗之, 織田 圭一, 石井 賢二, 石渡 喜一, 核医学, 45, 3, S236, S236,   2008 09
  • 未治療パーキンソン病におけるアデノシンA2A受容体とドパミントランスポータの左右差, 三品 雅洋, 石渡 喜一, 石井 賢二, 北村 伸, 木村 裕一, 長縄 美香, 織田 圭一, 橋本 昌也, 鈴木 雅彦, 小林 士郎, 片山 泰朗, 臨床神経学, 47, 12, 1017, 1017,   2007 12
  • アミロイドプローブPIBとFDG-PETによる認知症の早期鑑別診断, 石井 賢二, 橋本 昌也, 石渡 喜一, 木村 裕一, 織田 圭一, 齊藤 祐子, 徳丸 阿耶, 金丸 和富, 村山 繁雄, 臨床神経学, 47, 12, 1141, 1141,   2007 12
  • Lewy小体型認知症における後頭葉の機能低下に関連する遠隔部位の機能亢進, 橋本 昌也, 川崎 敬一, 鈴木 正彦, 井上 聖啓, 三谷 和子, 金丸 和富, 村山 繁雄, 織田 圭一, 木村 裕一, 石渡 喜一, 石井 賢二, 臨床神経学, 47, 12, 1154, 1154,   2007 12
  • 認知症診断におけるPIB-PETの意義 Voxel Based Morphometryとの比較, 石井 賢二, 橋本 昌也, 木村 裕一, 石川 雅智, 織田 圭一, 川崎 敬一, 齊藤 祐子, 金丸 和富, 徳丸 阿耶, 村山 繁雄, 石渡 喜一, 核医学, 44, 3, 300, 300,   2007 10
  • 認知症診断におけるPIB-PETの意義 FDG-PETとの比較, 石井 賢二, 橋本 昌也, 木村 裕一, 石川 雅智, 織田 圭一, 川崎 敬一, 齊藤 祐子, 金丸 和富, 徳丸 阿耶, 村山 繁雄, 石渡 喜一, 核医学, 44, 3, 300, 300,   2007 10
  • アルツハイマー病脳におけるアミロイドプローベ[11C]PIB及び[11C]BF227の比較検討, 橋本 昌也, 石井 賢二, 木村 裕一, 織田 圭一, 川崎 敬一, 石川 雅智, 石渡 喜一, 岡村 信行, 谷内 一彦, 核医学, 44, 3, 301, 301,   2007 10
  • 悪性神経膠腫の硼素中性子捕捉療法計画に際してのPETアミノ酸イメージの応用, 成相 直, 石渡 喜一, 木村 裕一, 稲次 基希, 百瀬 俊也, 石井 賢二, 大野 喜久郎, 核医学, 44, 3, 309, 309,   2007 10
  • [11C]TMSX PETを用いた被殻アデノシンA2A受容体分布の加齢変化の検討, 三品 雅洋, 石井 賢二, 木村 裕一, 長縄 美香, 織田 圭一, 橋本 昌也, 鈴木 正彦, 小林 士郎, 片山 泰朗, 石渡 喜一, 核医学, 44, 3, 314, 314,   2007 10
  • 11C-Verapamil P糖タンパク機能画像化に対するクラスタリング動態法の適用, 木村 裕一, 長縄 美香, 志田原 美保, 関 千江, 織田 圭一, 石井 賢二, 石渡 喜一, 核医学, 44, 3, 314, 314,   2007 10
  • [11C]SA4503-PETによるシグマ1受容体動態解析における撮影時間の短縮, 坂田 宗之, 木村 裕一, 長縄 美香, 石川 雅智, 織田 圭一, 石井 賢二, 橋本 謙二, 千原 國宏, 石渡 喜一, 核医学, 44, 3, 314, 314,   2007 10
  • ドネペジルによるシグマ1受容体の占拠 [11C]SA4503-PETを用いて, 石川 雅智, 石井 賢二, 木村 裕一, 坂田 宗之, 織田 圭一, 伊豫 雅臣, 橋本 謙二, 石渡 喜一, 核医学, 44, 3, 323, 323,   2007 10
  • microPET Focus220を用いたサルPET検査における吸収補正に関する検討, 志田原美保, 寅松千枝, 岡内隆, 関千江, 長縄美香, 永井裕司, 伊藤浩, 大林茂, 木村裕一, 菅野巖, 核医学, 44, 3, 315, 315,   2007 10 , http://jglobal.jst.go.jp/detail.php?from=API&JGLOBAL_ID=200902294194027643
  • 長時間歩行時の下肢筋の活動状態 [18F]fluorodeoxyglucoseを用いたPositron Emission Tomographyによる検討, 島田 裕之, 平田 崇, 古名 丈人, 及川 清, 木村 裕一, 杉浦 美穂, 石渡 喜一, 鈴木 隆雄, 理学療法学, 34, Suppl.2, 260, 260,   2007 04
  • 多系統萎縮症における黒質線条体ドパミン機能障害の検討, 橋本 昌也, 川崎 敬一, 鈴木 正彦, 井上 聖啓, 三谷 和子, 三品 雅洋, 織田 圭一, 木村 裕一, 石渡 喜一, 石井 賢二, 臨床神経学, 46, 12, 1145, 1145,   2006 12
  • Mutual information法による脳FDG-PETのエミッションとトランスミッションのレジストレーション, 織田 圭一, 石井 賢二, 木村 裕一, 松本 和徳, 福士 政広, 核医学, 43, 3, 210, 210,   2006 10
  • 半盲患者の中枢性ベンゾジアゼピン受容体とアデノシンA1受容体の密度, 鈴木 幸久, 成相 直, 堀江 長春, 石井 賢二, 織田 圭一, 木村 裕一, 石渡 喜一, 核医学, 43, 3, 213, 213,   2006 10
  • 複数のPETアミノ酸プローブを用いた悪性脳腫瘍の集学的治療, 成相 直, 石渡 喜一, 百瀬 俊哉, 稲次 基希, 細田 千尋, 木村 裕一, 織田 圭一, 石井 賢二, 岩田 錬, 大野 喜久郎, 核医学, 43, 3, 216, 216,   2006 10
  • 同時計数検出器型放射能連続モニタによる動脈血時間放射能曲線の測定, 織田 圭一, 石井 賢二, 木村 裕一, 酒井 健也, 長縄 美香, 福士 政広, 石渡 喜一, 核医学, 43, 3, 226, 226,   2006 10
  • FDG脳糖代謝詳細画像の無採血高速作成手法, 木村 裕一, 長縄 美香, 織田 圭一, 石井 賢二, 石渡 喜一, 核医学, 43, 3, 229, 229,   2006 10
  • アミロイドプローベPIBによるアルツハイマー病脳内アミロイド蓄積の検討, 石井 賢二, 石渡 喜一, 木村 裕一, 織田 圭一, 橋本 昌也, William Klunk, Chester Mathis, 金丸 和富, 齊藤 祐子, 村山 繁雄, 核医学, 43, 3, 234, 235,   2006 10
  • ジフェニルアルシン酸暴露者における脳FDG-PET所見, 石井 賢二, 石井 一弘, 川崎 敬一, 織田 圭一, 武田 徹, 塚田 秀夫, 岩崎 信明, 玉岡 晃, 木村 裕一, 石渡 喜一, 核医学, 43, 3, 235, 235,   2006 10
  • [11C]SA4503-PETによるハロペリドールのシグマ1受容体占拠率評価, 石渡 喜一, 織田 健司, 木村 裕一, 坂田 宗之, 織田 圭一, 佐々木 徹, 長縄 美香, 大久保 善朗, 石井 賢二, 核医学, 43, 3, 237, 237,   2006 10
  • [11C]SA4503によるヒト脳σ1受容体のPET動態解析, 坂田 宗之, 木村 裕一, 長縄 美香, 織田 圭一, 石井 賢二, 千原 國宏, 石渡 喜一, 核医学, 43, 3, 237, 237,   2006 10
  • 神経受容体濃度画像化のための平面交差法によるLogan plotの無採血化, 長縄 美香, 矢野 純一, 織田 圭一, 石井 賢二, 石渡 喜一, 木村 裕一, 核医学, 43, 3, 237, 237,   2006 10
  • 脳FDG-PET画像の機種間差補正, 川崎 敬一, 石井 賢二, 織田 圭一, 宮沢 伸彦, 篠原 豊明, 木村 裕一, 石渡 喜一, 核医学, 43, 3, 242, 242,   2006 10
  • Lewy小体型認知症における後頭葉の機能低下に関連する選隔部位の機能亢進, 橋本 昌也, 川崎 敬一, 鈴木 正彦, 井上 聖啓, 三谷 和子, 金丸 和富, 村山 繁雄, 織田 圭一, 木村 裕一, 石渡 喜一, 石井 賢二, 核医学, 43, 3, 271, 271,   2006 10
  • 新規抗ヒスタミン薬オロパタジン内服後の脳内ヒスタミンH1受容体占拠率測定による薬物副作用評価, 田代 学, 望月 秀紀, 石井 賢二, 木村 裕一, 織田 圭一, 佐々木 徹, 石渡 喜一, 谷内 一彦, 核医学, 43, 3, 274, 274,   2006 10
  • 11C-NMSPによるセロトニン受容体描出を用いた中枢性疲労定量評価, 木村 裕一, 藤本 敏彦, 菊地 次郎, 小川 静香, 橋本 昌也, 石川 雅智, 織田 圭一, 石井 賢二, 石渡 喜一, 核医学, 43, 3, 275, 275,   2006 10
  • [11C]TMSX PETを用いた未治療パーキンソン病におけるアデノシンA2A受容体結合能 a preliminary study, 三品 雅洋, 石井 賢二, 北村 伸, 木村 裕一, 長縄 美香, 橋本 昌也, 鈴木 正彦, 織田 圭一, 小林 士郎, 片山 泰朗, 石渡 喜一, 核医学, 43, 3, 275, 275,   2006 10
  • シグマ1受容体に対するフルボキサミンとバロキセチンの占拠率の相違に関する検討, 石川 雅智, 清水 栄司, 伊豫 雅臣, 藤崎 美久, 橋本 謙二, 石井 賢二, 石渡 喜一, 織田 圭一, 木村 裕一, 千葉医学雑誌, 82, 4, 242, 242,   2006 08
  • 糖負荷は連合野のFDG取込みを抑制する(2報), 川崎 敬一, 石井 賢二, 齊藤 陽子, 織田 圭一, 木村 裕一, 石渡 喜一, 核医学, 42, 3, 305, 305,   2005 09
  • 多系統萎縮症における黒質線条体ドパミン節前・節後機能の相関的解析, 橋本 昌也, 川崎 敬一, 鈴木 正彦, 井上 聖啓, 三谷 和子, 三品 雅洋, 織田 圭一, 木村 裕一, 石渡 喜一, 石井 賢二, 核医学, 42, 3, 306, 306,   2005 09
  • 動脈採血省略定量解析法の脳アデノシンA1およびA2A受容体画像化への適用, 長縄 美香, 木村 裕一, 石井 賢二, 織田 圭一, 三品 雅洋, 成相 直, 石渡 喜一, 核医学, 42, 3, 338, 338,   2005 09
  • 事後確率最大化規範による動態解析推定性能の向上と高速化, 木村 裕一, 長縄 美香, 織田 圭一, 石井 賢二, 石渡 喜一, 核医学, 42, 3, 339, 339,   2005 09
  • アルツハイマー病とレビー小体型痴呆症のFDG-PET所見 剖検病理診断確定例における検討, 石井 賢二, 村山 繁雄, 齊藤 祐子, 織田 圭一, 木村 裕一, 石渡 喜一, 核医学, 42, 3, 341, 341,   2005 09
  • アルツハイマー病とレビー小体型痴呆症のFDG-PET所見 軽度認知障害例における検討, 石井 賢二, 川崎 敬一, 齊藤 陽子, 金丸 和富, 三谷 和子, 織田 圭一, 木村 裕一, 石渡 喜一, 核医学, 42, 3, 341, 341,   2005 09
  • 3D PETにおけるemission/transmission同時収集による吸収補正の検討, 織田 圭一, 石井 賢二, 木村 裕一, 石渡 喜一, 核医学, 42, 3, 365, 365,   2005 09
  • 言語性・非言語性の口舌部運動制御に関わる島皮質の機能局在, 齊藤 陽子, 石井 賢二, 織田 圭一, 木村 裕一, 石渡 喜一, 水澤 英洋, 認知神経科学, 7, 2, 145, 145,   2005 07
  • [C-11]TMSX PETを用いた健常者脳内アデノシンA2A受容体分布の測定, 三品 雅洋, 石井 賢二, 石渡 喜一, 木村 裕一, 大山 雅史, 阿部 新, 福地 孝明, 小林 士郎, 片山 泰朗, 臨床神経学, 44, 12, 1116, 1116,   2004 12
  • [11C]MPDX PETの加齢性変化, 福光延吉, 石井賢二, 木村裕一, 織田圭一, 佐々木徹, 石渡喜一, 核医学, 41, 3, 379,   2004 09 20 , http://jglobal.jst.go.jp/public/200902299154432903
  • アルツハイマー病における髄液バイオマーカーと局所脳糖代謝の相関, 石井 賢二, 金丸 和富, 齊藤 陽子, 織田 圭一, 木村 裕一, 河村 和紀, 佐々木 徹, 石渡 喜一, 核医学, 41, 3, 311, 311,   2004 09
  • [11C]TMSX-PETによる骨格筋アデノシンA2A受容体計測の可能性, 石渡 喜一, 水野 正樹, 木村 裕一, 河村 和紀, 織田 圭一, 佐々木 徹, 石井 賢二, 核医学, 41, 3, 314, 314,   2004 09
  • 局所脳血流とベンゾジアゼピン受容体PET画像の相関クラスター分析, 織田 圭一, 石井 賢二, 木村 裕一, 大橋 信一郎, 外山 比南子, 佐々木 敏秋, 核医学, 41, 3, 341, 341,   2004 09
  • PET代謝受容体計測による難治てんかん病態の評価, 成相 直, 尤 郁偉, 前原 健寿, 大野 喜久郎, 織田 圭一, 木村 裕一, 石井 賢二, 石渡 喜一, 清水 浩之, 核医学, 41, 3, 341, 341,   2004 09
  • 参照領域フリーな動脈採血省略法を用いたLogan plotによる脳神経受容体の画像化, 長縄 美香, 木村 裕一, 三品 雅洋, 成相 直, 織田 圭一, 石井 賢二, 石渡 喜一, 核医学, 41, 3, 341, 341,   2004 09
  • 動態モデルに基づいたクラスタリングによるLogan plot神経受容体画像の画質改善, 木村 裕一, 石井 賢二, 塚原 美穂子, 織田 圭一, 河村 和紀, 石渡 喜一, 核医学, 41, 3, 341, 341,   2004 09
  • 糖負荷は連合野皮質のFDG取り込みを抑制する, 石井 賢二, 川崎 敬一, 齊藤 陽子, 織田 敬一, 河村 和紀, 木村 裕一, 佐々木 徹, 石渡 喜一, 核医学, 41, 3, 367, 367,   2004 09
  • [C-11]TMSX PETを用いた健常者脳内アデノシンA2A受容体分布の測定, 三品 雅洋, 石渡 喜一, 石井 賢二, 木村 裕一, 織田 圭一, 佐々木 徹, 河村 和紀, 大山 雅史, 福地 孝明, 小林 士郎, 片山 泰朗, 核医学, 41, 3, 378, 379,   2004 09
  • 脳シグマ受容体を指標にした加齢・神経変性疾患・脳腫瘍の新しいPET診断法, 石渡 喜一, 石井 賢二, 成相 直, 木村 裕一, 河村 和紀, 大山 雅史, 三品 雅洋, INNERVISION, 19, 7, 21, 21,   2004 06
  • PETによる新しい神経受容体計測法の難治側頭葉てんかん患者への臨床応用, 成相 直, 前原 健寿, 太田 禎久, 今江 省吾, 大野 喜久郎, 木村 裕一, 石井 賢二, 石渡 喜一, てんかん研究, 22, 1, 49, 49,   2004 02
  • Regional Correlation of Pre- and Post- Synaptic Dopaminergic Function in the Striatum of Parkinson's Disease : A Novel Voxel Based Analysis, SUZUKI Masahiko, INOUE Kiyoharu, KITAMURA Shin, MISHINA Masahiro, MITANI Kazuko, YAMANOUCHI Hiroshi, ODA Keiichi, KIMURA Yuichi, ISHIWATA Kiichi, ISHII Kenji, CI研究 : progress in computed imaging, 25, 4, 237, 244,   2003 12 30 , http://ci.nii.ac.jp/naid/10015749131
  • 抗ヒスタミン薬オロパタジン及びケトチフェン内服後のヒト脳内ヒスタミンH1受容体占拠率の測定, 田代 学, 望月 秀紀, 櫻田 幽美子, 石井 賢二, 木村 裕一, 織田 圭一, 石渡 喜一, 谷内 一彦, 日本神経精神薬理学雑誌, 23, 6, 235, 235,   2003 12
  • アルツハイマー病におけるシグマ受容体リガンド11C-SA4503と糖代謝の検討, 大山 雅史, 石渡 喜一, 石井 賢二, 三谷 和子, 三品 雅洋, 北村 伸, 織田 圭一, 木村 裕一, 河村 和紀, 佐々木 徹, 片山 泰朗, 臨床神経学, 43, 12, 989, 989,   2003 12
  • ヒトにおける[11C]MPDXによるアデノシンA1受容体画像, 福光延吉, 石井賢二, 木村裕一, 佐々木徹, 織田圭一, 森豊, 石渡喜一, 核医学, 40, 3, 397,   2003 08 20 , http://jglobal.jst.go.jp/public/200902255172546811
  • 脳ドーパミン節前・節後機能の加齢変化, 石井 賢二, 織田 圭一, 木村 裕一, 河村 和紀, 佐々木 徹, 石渡 喜一, 核医学, 40, 3, 317, 317,   2003 08
  • FDG脳糖代謝パラメトリック画像作製のための簡略化プロトコル, 木村 裕一, 長縄 美香, 織田 圭一, 石井 賢二, 石渡 喜一, 核医学, 40, 3, 347, 347,   2003 08
  • アデノシンA2A受容体リガンド[11C]TMSXの心臓イメージング剤としての可能性, 石渡 喜一, 河村 和紀, 木村 裕一, 織田 圭一, 石井 賢二, 核医学, 40, 3, 373, 373,   2003 08
  • 脳糖代謝と灰白質容積の加齢変化, 石井 賢二, 織田 圭一, 木村 裕一, 河村 和紀, 佐々木 徹, 石渡 喜一, 核医学, 40, 3, 380, 380,   2003 08
  • 全身FDG-PETにおける同時収集法と三次元連続収集法の比較, 織田 圭一, 石井 賢二, 木村 裕一, 石渡 喜一, 核医学, 40, 3, 385, 386,   2003 08
  • 脳アデノシンA2A受容体リガンド[11C]TMSXの前臨床研究, 石渡 喜一, 汪 維芳, 木村 裕一, 三品 雅洋, 河村 和紀, 織田 圭一, 佐々木 徹, 石井 賢二, 核医学, 40, 3, 397, 397,   2003 08
  • PETアデノシンA1受容体計測の難治側頭葉てんかん患者への臨床応用, 成相 直, 前原 健寿, 今江 省吾, 大野 喜久郎, 佐々木 徹, 織田 圭一, 木村 裕一, 石井 賢二, 石渡 喜一, 核医学, 40, 3, 398, 398,   2003 08
  • シグマ受容体リガンド11C-SA4503によるアルツハイマー病への臨床応用, 大山 雅史, 石渡 喜一, 石井 賢二, 三谷 和子, 三品 雅洋, 北村 伸, 織田 圭一, 木村 裕一, 河村 和紀, 佐々木 徹, 片山 泰朗, 臨床神経学, 42, 12, 1249, 1249,   2002 12
  • PETによる脳シグマ1受容体分布描出, 石井 賢二, 木村 裕一, 河村 和紀, 織田 圭一, 石渡 喜一, 臨床神経学, 42, 12, 1265, 1265,   2002 12
  • アルツハイマー病におけるシグマ受容体リガンド11C-SA4503と糖代謝の検討, 大山 雅史, 石井 賢二, 三品 雅洋, 三谷 和子, 北村 伸, 織田 圭一, 木村 裕一, 河村 和紀, 佐々木 徹, 片山 泰朗, 石渡 喜一, 核医学, 39, 3, 326, 326,   2002 09
  • ヒスタミンH1受容体のPETスタティック測定, 望月 秀紀, 木村 裕一, 石井 賢二, 織田 圭一, 佐々木 徹, 田代 学, 谷内 一彦, 石渡 喜一, 核医学, 39, 3, 328, 328,   2002 09
  • 脳アデノシンA1受容体リガンド[11C]MPDXの前臨床研究, 石渡 喜一, 成相 直, 木村 裕一, 織田 圭一, 河村 和紀, 石井 賢二, 千田 道雄, 島田 純一, 核医学, 39, 3, 328, 328,   2002 09
  • パーキンソン病における節前・節後ドーパミン機能の相関的解析 voxel based analysis, 石井 賢二, 三品 雅洋, 鈴木 正彦, 三谷 和子, 織田 圭一, 木村 裕一, 河村 和紀, 佐々木 徹, 石渡 喜一, 核医学, 39, 3, 340, 340,   2002 09
  • SPM99を用いた老年変性疾患のFDG PET画像解析における加齢変化の除去 age matchとANCOVA, 三品 雅洋, 大山 雅史, 石井 賢二, 石渡 喜一, 織田 圭一, 河村 和紀, 木村 裕一, 佐々木 徹, 小林 士郎, 北村 伸, 片山 泰朗, 核医学, 39, 3, 341, 341,   2002 09
  • ヒト脳シグマ1受容体分布の正常加齢変化について, 石井 賢二, 木村 裕一, 河村 和紀, 織田 圭一, 佐々木 徹, 石渡 喜一, 核医学, 39, 3, 376, 376,   2002 09
  • 統計的クラスタリング動態解析によるFDGパラメトリック画像, 木村 裕一, 石井 賢二, 織田 圭一, 北村 圭司, 石渡 喜一, 核医学, 39, 3, 388, 388,   2002 09
  • 独立成分分析の適用によるPET動態画像からの血漿放射能曲線の抽出, 長縄 美香, 木村 裕一, 石井 賢二, 織田 圭一, 石渡 喜一, 核医学, 39, 3, 396, 396,   2002 09
  • [C-11]CFTと[C-11]raclopride PET画像の相関クラスター分析, 織田 圭一, 石井 賢二, 大橋 信一郎, 上村 幸司, 外山 比南子, 木村 裕一, 石渡 喜一, 核医学, 39, 3, 397, 397,   2002 09
  • 習熟随意運動施行時における黒質線条体系ドパミンニューロンの役割, 石井 賢二, 木村 裕一, 織田 圭一, 石渡 喜一, 佐々木 徹, 千田 道雄, 臨床神経学, 41, 11, 973, 973,   2001 11
  • 痴呆研究の展望 老人研プロジェクトの取組みから, 安藤 進, 石渡 喜一, 石井 賢二, 木村 裕一, 織田 圭一, 核医学技術, 21, 4, 250, 254,   2001 10
  • 11C-Doxepinによる脳ヒスタミン受容体の解析, 木村 裕一, 望月 秀紀, 石井 賢二, 織田 圭一, 佐々木 徹, 田代 学, 谷内 一彦, 石渡 喜一, 核医学, 38, 5, 594, 594,   2001 09
  • サル脳シグマ1受容体の加齢変化, 河村 和紀, 木村 裕一, 塚田 秀夫, 小林 直之, 松野 聖, 石井 賢二, 石渡 喜一, 核医学, 38, 5, 593, 593,   2001 09
  • ヒト脳におけるシグマ1受容体分布描出, 石井 賢二, 木村 裕一, 河村 和紀, 織田 圭一, 佐々木 徹, 石渡 喜一, 核医学, 38, 5, 593, 593,   2001 09
  • シグマ受容体リガンド11C-SA4503によるアルツハイマー病への臨床応用, 大山 雅史, 石渡 喜一, 石井 賢二, 三谷 和子, 三品 雅洋, 北村 伸, 千田 道雄, 織田 圭一, 木村 裕一, 片山 泰朗, 核医学, 38, 5, 593, 593,   2001 09
  • [11C]RacloprideとPETによる随意運動遂行時の内因性ドパミン放出測定, 石井 賢二, 木村 裕一, 織田 圭一, 石渡 喜一, 佐々木 徹, 千田 道雄, 核医学, 38, 5, 568, 568,   2001 09
  • PET定性測定における検査時間短縮の試み, 織田 圭一, 石井 賢二, 木村 裕一, 核医学, 38, 5, 573, 573,   2001 09
  • 統計的手法を用いたクラスタリング動態解析によるPETパラメトリック画像の生成, 木村 裕一, 石井 賢二, 織田 圭一, 核医学, 38, 5, 575, 575,   2001 09
  • ポジトロンによる痴呆の早期診断と病態生理の研究 ベンゾジアゼピン受容体のイメージングによる痴呆の病態解析, 千田 道雄, 石渡 喜一, 石井 賢二, 織田 圭一, 佐々木 徹, 木村 裕一, 三谷 和子, 三品 雅洋, 大山 雅史, 外山 比南子, 長期特別プロジェクト成果報告書 老人性痴呆に関する総合的研究, 平成12年度, 35, 38,   2001 03
    Summary:11C-フルマゼニル(FMZ)を用いて中枢性ベンゾジアゼピン受容体を測定する為の簡便な方法を考案し,その精度を評価した.更に,痴呆を呈する脳疾患患者にFMZを用いてPET撮影を行い,その病態を解析した.FMZ投与後様々な時間に撮影したスタティックスキャン画像の中では,投与後20〜40分の20分間撮影が,局所放射能とFMZ-DVとの相関が最もよく,しかもほぼ比例することがわかった.デフォルトのCBF用テンプレートに標準化すると,視床・線条体の集積が低い為にうまく行かなかったが,同日に撮影したH2O- CBF画像を標準化し同条件でFMZ-DV画像を変換した.SPM99で正常群とアルツハイマー病群を比較すると,CBFに比べてFMZでは両群の差が少なく,先に論文発表したROI解析の結果を裏付けた
  • SPMにおける異なるtemplateによる解剖学的標準化の検討, 大山 雅史, 三品 雅洋, 千田 道雄, 石井 賢二, 織田 圭一, 木村 裕一, 片山 泰朗, 核医学, 37, 5, 579, 579,   2000 09
  • クラスタリング動態解析によるPETパラメトリック画像の生成, 木村 裕一, 千田 道雄, 石井 賢二, 核医学, 37, 5, 580, 580,   2000 09
  • SPMによる痴呆脳PET診断のための基礎検討 解剖学的標準化法と対照領域について, 石井 賢二, 馬 云川, 木村 裕一, 織田 圭一, 千田 道雄, 核医学, 37, 5, 543, 543,   2000 09
  • 局所脳萎縮を呈する疾患の形態変化と機能変化の相関について, 石井 賢二, 木村 裕一, 織田 圭一, 千田 道雄, 核医学, 37, 5, 542, 542,   2000 09
  • 在宅健康管理のための家庭台所における日常行動検知, 落合嗣郎, 西原美敬, 庄司健, 木村裕一, 斉藤浩一, 小川充洋, 田村俊世, 戸川達男, 土屋喜一, バイオエンジニアリング講演会講演論文集, 12th, 155, 156,   2000 01 05 , https://jglobal.jst.go.jp/detail?JGLOBAL_ID=200902170104359501
  • An attempt of unconstraint heart and respiratory measurement by using photoplethysmograph for home health monitoring, OGAWA Mitsuhiro, TAMURA Toshiyo, SHOUJI Ken, OHTA Manabu, KIMURA Yuichi, TOGAWA Tatsuo, IEICE technical report. ME and bio cybernetics, 99, 83, 37, 40,   1999 05 22 , http://ci.nii.ac.jp/naid/110003287616
    Summary:For obtaining physiological parameters during daily routine, unconstraint measurement of photoplethysmograph (PPG) during bating is attempted in this paper. For unaware measurement of PPG, infrared LEDs were used for light source. The waterproofed probe was attached on the bottom surface of an inner wall of bathtub, PPG signals were obtained when subject was sitting on the probe. Measured PPG signals were filtered by low-pass filter for extracting respiratory components that were included in PPG signals. From PPG signals, heart and respiratory signals can be obtained in 10 healthy male subjects.
  • A study for personal identification on bathtub ECG by using a wavelet transform and a neural network. Effectiveness about wavelet transform., 小川充洋, 木村裕一, 田村俊世, 戸川達男, 生体・生理工学シンポジウム論文集, 11th, 513, 516,   1996 11 , https://jglobal.jst.go.jp/detail?JGLOBAL_ID=200902190200902705
  • Development of automatic monitoring system for home health care., 依田美紀子, 鈴木正宣, 小川充洋, 木村裕一, 田村俊世, 戸川達男, 若松秀俊, 生体・生理工学シンポジウム論文集, 11th, 401, 404,   1996 11 , https://jglobal.jst.go.jp/detail?JGLOBAL_ID=200902190311248222
  • A study for personal identification on bathtub ECG by using a wavelet transform and a neural network., 小川充洋, 依田美紀子, 出井清之, 木村裕一, 田村俊世, 戸川達男, 土屋喜一, 生体・生理工学シンポジウム論文集, 10th, 481, 484,   1995 11 , https://jglobal.jst.go.jp/detail?JGLOBAL_ID=200902164618790520
  • Qualification of PET cameras and imaging sites for 11C-methionine PET on brain tumor in Japan, Yuichi Kimura, Hiroyuki Nishida, Yasuhiko Ikari, Keiichi Matsumoto, Keiichi Oda, Tomoyuki Nishio, Hiroyoshi Fukukita, Tomio Inoue, Michio Senda, JOURNAL OF NUCLEAR MEDICINE, 55,   2014 05
  • Qualification of PET cameras and imaging sites for 11C-methionine PET on brain tumor in Japan, Yuichi Kimura, Hiroyuki Nishida, Yasuhiko Ikari, Keiichi Matsumoto, Keiichi Oda, Tomoyuki Nishio, Hiroyoshi Fukukita, Tomio Inoue, Michio Senda, JOURNAL OF NUCLEAR MEDICINE, 55,   2014 05
  • Full quantification of CMRGlc of small animals with arterial blood sampling using the new system of CD-Well, Yuichi Kimura, Takashi Yamada, Nobuya Hashizume, Masahiko Nomura, Seiichiro Ota, Keishi Kitamura, Hiroshi Toyama, JOURNAL OF NUCLEAR MEDICINE, 55,   2014 05
  • Comparison between SUV and BP images acquired using 11C-PIB PET: Questionable PIB accumulation in SUV images, Chisa Hosokawa, Kazunari Ishii, Yuichi Kimura, Kenta Sakaguchi, Makoto Hosono, Takamichi Murakami, JOURNAL OF NUCLEAR MEDICINE, 55,   2014 05
  • The prediction of blood pressure changes by the habit of walking, Toshiyo Tammura, Soichi Maeno, Yutaka Kimira, Yuichi Kimura, Takumu Hattori, Kotaro Minato, IFMBE Proceedings, 41, 1406, 1408,   2014 , 10.1007/978-3-319-00846-2_348, http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84891281005&origin=inward
    Summary:A number of walking step per day is an important parameter to evaluate daily activities as well as blood pressure control. In this study, we used blood pressure and walking step data, obtained from 48 patients in a home healthcare system, to investigate the effectiveness of the number of walking steps in a clinical setting. Changes in blood pressure and walking steps per day were compared. Our results indicate that walking, as a regular form of exercise, contributed to lowering of blood pressure. Thus the daily walking is useful for improving the quality of life of subjects in the home healthcare setting. © Springer International Publishing Switzerland 2014.
  • Variability in PET quantitation within a multicenter studies in Japan, K. Matsumoto, K. Suzuki, H. Fukukita, Y. Ikari, K. Oda, Y. Kimura, S. Sakamoto, N. Shimada, T. Shiraishi, T. Nishio, H. Nishida, T. Terauchi, M. Senda, EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, 40, S305, S305,   2013 10
  • Relation of striatal density of adenosine A(2A) receptors, dopamine transporter and dopamine D-2 receptor with tremor at rest and rigidity in Parkinson's disease, M. Mishina, K. Ishii, M. Suzuki, H. Nagayama, S. Kitamura, M. Hashimoto, M. Naganawa, Y. Kimura, M. Sakata, K. Oda, J. Toyohara, Y. Katayama, K. Ishiwata, MOVEMENT DISORDERS, 28, S52, S53,   2013 06
  • Evaluation of putaminal adenosine A(1) receptors in drug naive Parkinson's disease measured with [C-11]MPDX PET, M. Mishina, K. Ishii, M. Suzuki, S. Kitamura, M. Hashimoto, Y. Kimura, M. Sakata, K. Oda, J. Toyohara, S. Kobayashi, Y. Katayama, K. Ishiwata, MOVEMENT DISORDERS, 27, S248, S248,   2012 06
  • Unbiased logan graphical analysis using the renormalization method, H. Hontani, N. Hoshino, M. Naganawa, K. Sakaguchi, M. Sakata, K. Ishiwata, Y. Kimura, JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 29, S316, S317,   2009 10
  • Kinetic analysis of a novel radioligand for alpha 7 nicotinic acetylcholine receptor, [C-11]CHIBA-1001 in human brain, M. Sakata, Y. Kimura, M. Ishikawa, J. Toyohara, J. Wu, K. Oda, K. Ishii, K. Hashimoto, K. Ishiwata, JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 29, S371, S372,   2009 10
  • Simplified quantification of adenosine A(1) receptor with [C-11]MPDX and graphical analysis, Y. Kimura, M. Naganawa, M. Mishina, M. Sakata, K. Oda, K. Ishii, K. Ishiwata, JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 29, S326, S326,   2009 10
  • A noise reduction method for graphical analyses with KL-expansion during transient equilibrium condition, K. Sakaguchi, M. Naganawa, M. Sakata, M. Shidahara, C. Seki, K. Ishiwata, Y. Kimura, JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 29, S333, S333,   2009 10
  • Simplified quantification of adenosine A(2A) receptor with [C-11]TMSX PET and graphical analyses, M. Naganawa, M. Mishina, M. Sakata, K. Oda, K. Ishii, K. Ishiwata, Y. Kimura, JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 29, S321, S322,   2009 10
  • Aging effect on adenosine A(2A) receptors in putamen - A C-11-TMSX PET study, M. Mishina, K. Ishiwata, K. Ishii, M. Naganawa, Y. Kimura, M. Sakata, K. Oda, K. Ishibashi, M. Suzuki, S. Kobayashi, Y. Katayama, MOVEMENT DISORDERS, 24, S202, S202,   2009
  • Variations in adenosine A(2A) receptors following anti-Parkinsonian therapy in drug naive Parkinson's disease using (11)C-TMSX PET, M. Hishina, K. Ishii, S. Kitamura, Y. Kimura, M. Naganawa, M. Hashimoto, M. Suzuki, K. Oda, M. Hamamoto, S. Kobayashi, Y. Katayama, K. Ishiwata, MOVEMENT DISORDERS, 23, 1, S68, S68,   2008
  • Reduction of noise-induced underestimation in Logan graphical analysis using scale invariant linear estimation, Muneyuki Sakata, Y. Kimura, M. Naganawa, M. Shidahara, C. Seki, K. Oda, K. Ishii, K. Ishiwata, NEUROIMAGE, 41, T82, T82,   2008 , 10.1016/j.neuroimage.2008.04.051
  • Parametric Imaging of the total volume of distrihution using MAP estimation for logan graphical analysis, Miho Shidahara, Y. Kimura, C. Seki, M. Naganawa, M. Sakata, M. Ishikawa, H. Ito, T. Suhara, K. Ishiwata, I. Kanno, NEUROIMAGE, 41, T83, T83,   2008 , 10.1016/j.neuroimage.2008.04.052
  • PET kinetic analysis: error consideration of quantitative analysis in dynamic studies, Yoko Ikoma, Hiroshi Watabe, Miho Shidahara, Mika Naganawa, Yuichi Kimura, ANNALS OF NUCLEAR MEDICINE, 22, 1, 1, 11,   2008 01 , Refereed, 10.1007/s12149-007-0083-2
    Summary:Positron emission tomography dynamic studies have been performed to quantify several biomedical functions. In a quantitative analysis of these studies, kinetic parameters were estimated by mathematical methods, such as a nonlinear least-squares algorithm with compartmental model and graphical analysis. In this estimation, the uncertainty in the estimated kinetic parameters depends on the signal-to-noise ratio and quantitative analysis method. This review describes the reliability of parameter estimates for various analysis methods in reversible and irreversible models.
  • PET kinetic analysis: wavelet denoising of dynamic PET data with application to parametric imaging, Miho Shidahara, Yoko Ikoma, Jeff Kershaw, Yuichi Kimura, Mika Naganawa, Hiroshi Watabe, ANNALS OF NUCLEAR MEDICINE, 21, 7, 379, 386,   2007 09 , Refereed, 10.1007/s12149-007-0044-9
    Summary:Physiological functions (e.g., cerebral blood flow, glucose metabolism, and neuroreceptor binding) can be investigated as parameters estimated by kinetic modeling using dynamic positron emission tomography (PET) images. Imaging of these physiological parameters, called parametric imaging, can locate the regional distribution of functionalities. However, the most serious technical issue affecting parametric imaging is noise in dynamic PET data. This review describes wavelet denoising of dynamic PET images for improving image quality in estimated parametric images. Wavelet denoising provides significantly improved quality directly to dynamic PET images and indirectly to estimated parametric images. The application of wavelet denoising to radio-ligand and kinetic analysis is still in the development stage, but even so, it is thought that wavelet techniques will have a substantial impact on nuclear medicine in the near future.
  • Consensus nomenclature for in vivo imaging of reversibly binding radioligands, Robert B. Innis, Vincent J. Cunningham, Jacques Delforge, Masahiro Fujita, Albert Giedde, Roger N. Gunn, James Holden, Sylvain Houle, Sung-Cheng Huang, Masanori Ichise, Hidehiro Lida, Hiroshi Ito, Yuichi Kimura, Robert A. Koeppe, Gitte M. Knudsen, Juhani Knuuti, Adriaan A. Lammertsma, Marc Laruelle, Jean Logan, Ralph Paul Maguire, Mark A. Mintun, Evan D. Morris'o, Ramin Parsey, Julie C. Price, Mark Slifstein, Vesna Sossi, Tetsuya Suhara, John R. Votaw, Dean F. Wong, Richard E. Carson, JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 27, 9, 1533, 1539,   2007 09 , Refereed, 10.1038/sj.jcbfm.9600493
    Summary:An international group of experts in pharmacokinetic modeling recommends a nomenclature to describe in vivo molecular imaging of reversibly binding radioligands.
  • PET tracers for mapping adenosine receptors as probes for diagnosis of CNS disorders, Kiichi Ishiwata, Yuichi Kimura, Erik F. J. De Vries, Philip H. Elsinga, Central Nervous System Agents in Medicinal Chemistry, 7, 1, 57, 77,   2007 03 , 10.2174/187152407780059259
    Summary:Adenosine is an endogenous modulator of several physiological functions in the central nervous system (CNS). The effect is mediated by a receptor family that consists of at least four subtypes: A1, A2A, A 2B and A3 receptors. The adenosine receptors play a role in neurological and psychiatric disorders such as Alzheimer's disease, Parkinson's disease, epilepsy and schizophrenia. Knowledge on adenosine receptor densities and status are important for understanding the mechanisms underlying the pathogenesis of diseases and for developing new therapeutics. Positron emission tomography (PET) offers a non-invasive tool to investigate these features in vivo, provided that suitable radiopharmaceuticals are available. As a consequence of the development of xanthine-type adenosine receptor antagonists with high affinity and high selectivity, several PET ligands labeled with carbon-11 (half-life of 20.4 min) and fluorine-18 (half-life of 109.8 min) have been proposed for mapping the adenosine A1 and A2A receptors (A1R and A2AR, respectively) and the adenosine uptake site in the CNS since 1995. Later non-xanthine-type antagonists for A2AR were radiolabeled. So far two tracers for A1R, [ 18F]CPFPX and [11C]MPDX, and a tracer for A2AR, [11C]TMSX (also called [11C]KF18446), have been applied to humans. For the other subtypes and the adenosine uptake site no suitable radioligands have been developed yet. This paper gives an overview of the current status on PET tracers for mapping adenosine receptors and the development of new compounds that may lead to new PET tracers. © 2007 Bentham Science Publishers Ltd.
  • PET kinetic analysis - Pitfalls and a solution for the Logan plot, Yuichi Kimura, Mika Naganawa, Miho Shidahara, Yoko Ikoma, Hiroshi Watabe, ANNALS OF NUCLEAR MEDICINE, 21, 1, 1, 8,   2007 01 , Refereed, 10.1007/BF03033993
    Summary:The Logan plot is a widely used algorithm for the quantitative analysis of neuroreceptors using PET because it is easy to use and simple to implement. The Logan plot is also suitable for receptor imaging because its algorithm is fast. However, use of the Logan plot, and interpretation of the formed receptor images should be regarded with caution, because noise in PET data causes bias in the Logan plot estimates. In this paper, we describe the basic concept of the Logan plot in detail and introduce three algorithms for the Logan plot. By comparing these algorithms, we demonstrate the pitfalls of the Logan plot and discuss the solution.
  • PET kinetic analysis - compartmental model, Hiroshi Watabe, Yoko Ikoma, Yuichi Kimura, Mika Naganawa, Miho Shidahara, ANNALS OF NUCLEAR MEDICINE, 20, 9, 583, 588,   2006 11 , Refereed, 10.1007/BF02984655
    Summary:PET enables not only visualization of the distribution of radiotracer, but also has ability to quantify several biomedical functions. Compartmental model is a basic idea to analyze dynamic PET data. This review describes the principle of the compartmental model and categorizes the techniques and approaches for the compartmental model according to various aspects: model design, experimental design, invasiveness, and mathematical solution. We also discussed advanced applications of the compartmental analysis with PET.
  • Relationship between dopamine D-2 and adenosine A(2A) receptors in drug naive Parkinson's disease using TMSX PET, M. Mishina, K. Ishii, S. Kitamura, Y. Kimura, M. Naganawa, M. Hashimoto, M. Suzuki, K. Oda, M. Hamamoto, S. Kobayashi, Y. Katayama, K. Ishiwata, MOVEMENT DISORDERS, 21, S622, S622,   2006
  • Direct estimation of cumulative integrals of the input function for Logan plot in neuroreceptor imaging using intersection searching algorithm, Mika Naganawa, Y. Kimura, J. Yano, K. Ishiwata, NEUROIMAGE, 31, T89, T90,   2006 , 10.1016/j.neuroimage.2006.04.077
  • Visualized regional imbalance of striatal dopaminergic function in Parkinson's disease, M Suzuki, K Kawasaki, Y Kimura, K Ishiwata, M Urashima, M Mishina, M Hashimoto, K Inoue, K Ishii, JOURNAL OF THE NEUROLOGICAL SCIENCES, 238, S370, S371,   2005 11
  • Effects of endurance training on adenosine A(2A) receptor density in myocardium and skeletal muscle, M Mizuno, Y Kimura, K Ishii, K Oda, T Sasaki, K Kawamura, K Ishiiwata, Muraoka, I, MEDICINE AND SCIENCE IN SPORTS AND EXERCISE, 36, 5, S26, S26,   2004 05
  • Age-related change in presynaptic and postsynaptic dopaminergic function: The rate of decline and regional correlation in the striatum, K Ishii, K Oda, Y Kimura, K Kawamura, T Sasaki, K Ishiwata, NEUROIMAGE, 22, T77, T78,   2004
  • A quantitative neuroreceptor imaging using independent component analysis with neither serial arterial blood sampling nor use of reference tissue: An adenosine A1 receptor mapping study, M Naganawa, Y Kimura, K Ishii, K Ishiwata, NEUROIMAGE, 22, T15, T16,   2004
  • Visualization of activated microglias in Wernicke-Korsakoff syndrome by [11C]PK11195 and PET, M Tsukahara, K Ishii, Y Kimura, S Matsushita, S Higuchi, K Ishiwata, NEUROIMAGE, 22, T196, T197,   2004
  • Sigma1 receptors in Parkinson's disease, M Mishina, K Ishiwata, K Ishii, S Kitamura, Y Kimura, K Kawamura, K Oda, T Sasaki, K Mitani, M Ohyama, T Fukuchi, S Kobayashi, Y Katayama, NEUROIMAGE, 22, T122, T123,   2004
  • [C-11]TMSX PET for mapping of adenosine A2A receptors in human brain, M Mishina, K Ishiwata, K Ishii, Y Kimura, K Kawamura, K Oda, T Sasaki, S Kobayashi, Y Katayama, NEUROIMAGE, 22, T85, T85,   2004
  • Evaluation of [F-18]fluorinated sigma receptor ligands in the conscious monkey brain., PH Elsinga, H Tsukada, N Harada, T Kakiuchi, K Kawamura, Y Kimura, W Vaalburg, T Kobayashi, K Ishiwata, JOURNAL OF NUCLEAR MEDICINE, 44, 5, 70P, 70P,   2003 05
  • Imaging of adenosine Al receptors in the human brain by positron emission tomoraphy with C-11-MPDX., N Fukumitsu, K Ishii, Y Kimura, K Oda, T Sasaki, Y Mori, K Ishiwata, JOURNAL OF NUCLEAR MEDICINE, 44, 5, 69P, 69P,   2003 05
  • Midbrain hypometabolism: An early diagnostic sign for progressive supranuclear palsy., M Mishina, M Ohyama, K Ishii, K Mitani, K Oda, Y Kimura, T Sasaki, K Ishiwata, T Fukuchi, S Kobayashi, S Kitamura, Y Katayama, JOURNAL OF NUCLEAR MEDICINE, 44, 5, 233P, 233P,   2003 05
  • Brain histamine H1 receptor occupancy of olopatadine and ketotifen: A comparative PET study., M Tashiro, H Mochizuki, Y Sakurada, K Ishii, Y Kimura, K Ishiwata, K Yanai, JOURNAL OF PHARMACOLOGICAL SCIENCES, 91, 90P, 90P,   2003
  • Mapping of sigma(1) receptors by C-11-SA4503-distribution and aging effect in normal human brain, K Ishii, Y Kimura, K Kawamura, K Oda, T Sasaki, K Ishiwata, NEUROIMAGE, 16, 3, S31, S31,   2002 07
  • An increase of binding potentials of C-11-SA4503 to sigma, receptors in the aged monkey brain., K Kawamura, Y Kimura, H Tsukada, T Kobayashi, M Ohyama, K Matsuno, K Ishii, K Ishiwata, JOURNAL OF NUCLEAR MEDICINE, 43, 5, 235P, 235P,   2002 05
  • The first evaluation of sigma1 receptors in patients with Alzheimer's disease using PET and a newly developed ligand: C-11 SA4503., M Ohyama, K Ishiwata, K Ishii, M Mishina, S Kitamura, K Kawamura, Y Kimura, T Sasaki, K Oda, K Mitani, Y Katayama, JOURNAL OF NUCLEAR MEDICINE, 43, 5, 243P, 243P,   2002 05
  • Normal distribution of GABA(A) receptor in visual cortex of early onset blindness., M Mishina, M Senda, M Kiyosawa, K Ishiwata, AG De Volder, H Nakano, H Toyama, K Oda, Y Kimura, K Ishii, T Sasaki, M Ohyama, Y Komaba, S Kobayashi, S Kitamura, Y Katayama, JOURNAL OF NUCLEAR MEDICINE, 43, 5, 253P, 253P,   2002 05
  • Mapping of sigma(1) receptors in living human brain, K Ishii, K Ishiwata, Y Kimura, K Kawamura, K Oda, M Senda, NEUROIMAGE, 13, 6, S984, S984,   2001 06
  • Formation of FDG parametric images based on clustering and principal components., Y Kimura, K Ishii, M Senda, NH Alpert, JOURNAL OF NUCLEAR MEDICINE, 41, 5, 100P, 101P,   2000 05
  • Improved signal to noise ratio in parametric images by cluster analysis., Y Kimura, HB Hsu, H Toyama, M Senda, AJ Fischman, NM Alpert, JOURNAL OF NUCLEAR MEDICINE, 40, 5, 288P, 288P,   1999 05
  • Evaluation of pathological heterogeneity in diffuse encephalopathy by mapping fractal dimension on cortical projection images., K Uemura, A Kobayashi, H Toyama, Y Kimura, K Ishii, K Oda, M Senda, A Uchiyama, JOURNAL OF NUCLEAR MEDICINE, 38, 5, 883, 883,   1997 05
  • Correction for partial volume effect in quantitative polar map of the myocardium., T Itou, H Toyama, Y Kimura, K Ishii, K Oda, M Senda, H Satoh, JOURNAL OF NUCLEAR MEDICINE, 37, 5, 671, 671,   1996 05
  • Feasibility of cerebral blood volume estimation and its effect on the rate constants in FDG compartment model analysis., H Toyama, A Taguchi, Y Matsumura, Y Kimura, K Uemura, K Ishii, K Oda, M Senda, JOURNAL OF NUCLEAR MEDICINE, 37, 5, 996, 996,   1996 05
  • Tracer kinetic modeling in nuclear medicine, H. Toyama, Y. Kimura, Kakuigaku, 30, 12, 1497, 1501,   1993
    Summary:For the quantitative measurement of the function of the organs, the data analysis with the modeling has been performed. The basic concepts and assumptions of the modeling in nuclear medicine are described. In the data analysis with tracer kinetic modeling, there are three important factors to be considered. They are the pharmacokinetics of the tracer in the tissue, the conditions of the study such as data acquisition method and study protocol, and the mathematical methods. We mention many effects of these factors on the values and the interpretation of the results of the examination. For the clinical practice, more simplex methods of measurements and mathematical analysis are desired.

Awards & Honors

  •   2011 , Hisada Award, Quantitative Analysis of Dopamine Tranporters in Human Brain Using [11C]PE2I and Positron Emission Tomography: Evaluation of Refernce Tissue Models
  •   2009 , Best Article Award, Effects of a Robotic Walking Exercise on Walking Performance in Community-Dwelling Elderly Adults
  •   2008 , Japanese Society of Nuclear Medicine, Annals of Nuclear Medicine Frequently Cited Paper 2011, 2013, and 2014, Low Density of Sigma1 Receptros in Early Alzheimer's Disease
  •   2001 01 , Article Award, JSNM, \Fast and Reliable Method to Generate FDG Parametric Images by Clustering Voxels Based on Principal Components
  • Medical Imaging
  • Article of the year 1995 in Japanese Society of

Research Grants & Projects

  • Developement of PET instrumentation
  • Application of PET for exercise physiology
  • 1.Forming parametric images in PET kinetics analysis 2.Image processing in PET