Updated on 2022/12/01

写真a

 
SHIMADA Hitoshi
 
Organization
Brain Research Institute Center for Integrated Human Brain Science Professor
Title
Professor
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Degree

  • 博士(医学) ( 2009.3 )

Research Interests

  • パーキンソン病

  • レヴィ小体病

  • PET

  • 認知機能

  • tau

  • REM behavior disorder

  • Lewy body diseases

  • fractal analysis

  • Alzheimer's disease

  • Parkinson's disease

  • dementia with Lewy bodies

  • positron emission tomography

  • amyloid

  • acethylcholine

  • voxel-based morphometry

  • 認知症

  • dementia

  • cognition

  • VBM

  • フラクタル解析

  • レム睡眠行動異常症

  • アルツハイマー病

  • レヴィ小体型認知症

  • アセチルコリンエステラーゼ

  • アミロイド

Research Areas

  • Life Science / Neuroscience-general

  • Life Science / Neuroscience-general

  • Life Science / Radiological sciences

  • Life Science / Neurology

Research History (researchmap)

  • National Institutes for Quantum and Radiological Science and Technology   Principal researcher

    2017.7 - 2021.3

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    Country:Japan

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  • 国立研究開発法人放射線医学総合研究所   主任研究員

    2015.4 - 2017.6

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  • National Institutes for Quantum and Radiological Science and Technology   Chief Researcher

    2014.7 - 2015.3

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  • National Institutes for Quantum and Radiological Science and Technology   Researcher

    2010

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  • Chiba University   Hospital

    2007

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  • National Institutes for Quantum and Radiological Science and Technology   Visiting researcher

    2021.4

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  • Niigata University   Brain Research Institute Center for Integrated Human Brain Science Department of Functional Neurology and Neurosurgery   Professor

    2021.4

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Research History

  • Niigata University   Center for Integrated Human Brain Science, Brain Research Institute   Professor

    2021.4

 

Papers

  • High-Contrast Imaging of α-Synuclein Pathologies in Living Patients with Multiple System Atrophy. International journal

    Kiwamu Matsuoka, Maiko Ono, Yuhei Takado, Kosei Hirata, Hironobu Endo, Toshiyuki Ohfusa, Taichi Kojima, Takeshi Yamamoto, Tomohiro Onishi, Asumi Orihara, Kenji Tagai, Keisuke Takahata, Chie Seki, Hitoshi Shinotoh, Kazunori Kawamura, Hiroshi Shimizu, Hitoshi Shimada, Akiyoshi Kakita, Ming-Rong Zhang, Tetsuya Suhara, Makoto Higuchi

    Movement disorders : official journal of the Movement Disorder Society   2022.8

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    Language:English  

    DOI: 10.1002/mds.29186

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  • A Machine Learning-Based Approach to Discrimination of Tauopathies Using [18 F]PM-PBB3 PET Images. International journal

    Hironobu Endo, Kenji Tagai, Maiko Ono, Yoko Ikoma, Asaka Oyama, Kiwamu Matsuoka, Naomi Kokubo, Kosei Hirata, Yasunori Sano, Masaki Oya, Hideki Matsumoto, Shin Kurose, Chie Seki, Hiroshi Shimizu, Akiyoshi Kakita, Keisuke Takahata, Hitoshi Shinotoh, Hitoshi Shimada, Takahiko Tokuda, Kazunori Kawamura, Ming-Rong Zhang, Kenichi Oishi, Susumu Mori, Yuhei Takado, Makoto Higuchi

    Movement disorders : official journal of the Movement Disorder Society   2022.8

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    Language:English   Publishing type:Research paper (scientific journal)  

    BACKGROUND: We recently developed a positron emission tomography (PET) probe, [18 F]PM-PBB3, to detect tau lesions in diverse tauopathies, including mixed three-repeat and four-repeat (3R + 4R) tau fibrils in Alzheimer's disease (AD) and 4R tau aggregates in progressive supranuclear palsy (PSP). For wider availability of this technology for clinical settings, bias-free quantitative evaluation of tau images without a priori disease information is needed. OBJECTIVE: We aimed to establish tau PET pathology indices to characterize PSP and AD using a machine learning approach and test their validity and tracer capabilities. METHODS: Data were obtained from 50 healthy control subjects, 46 patients with PSP Richardson syndrome, and 37 patients on the AD continuum. Tau PET data from 114 regions of interest were subjected to Elastic Net cross-validation linear classification analysis with a one-versus-the-rest multiclass strategy to obtain a linear function that discriminates diseases by maximizing the area under the receiver operating characteristic curve. We defined PSP- and AD-tau scores for each participant as values of the functions optimized for differentiating PSP (4R) and AD (3R + 4R), respectively, from others. RESULTS: The discriminatory ability of PSP- and AD-tau scores assessed as the area under the receiver operating characteristic curve was 0.98 and 1.00, respectively. PSP-tau scores correlated with the PSP rating scale in patients with PSP, and AD-tau scores correlated with Mini-Mental State Examination scores in healthy control-AD continuum patients. The globus pallidus and amygdala were highlighted as regions with high weight coefficients for determining PSP- and AD-tau scores, respectively. CONCLUSIONS: These findings highlight our technology's unbiased capability to identify topologies of 3R + 4R versus 4R tau deposits. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

    DOI: 10.1002/mds.29173

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  • Correction to: First-in-human in vivo imaging and quantification of monoacylglycerol lipase in the brain: a PET study with <sup>18</sup>F-T-401 (European Journal of Nuclear Medicine and Molecular Imaging, (2022), 49, 9, (3150-3161), 10.1007/s00259-021-05671-y)

    Keisuke Takahata, Chie Seki, Yasuyuki Kimura, Manabu Kubota, Masanori Ichise, Yasunori Sano, Yasuharu Yamamoto, Kenji Tagai, Hitoshi Shimada, Soichiro Kitamura, Kiwamu Matsuoka, Hironobu Endo, Hitoshi Shinotoh, Kazunori Kawamura, Ming Rong Zhang, Yuhei Takado, Makoto Higuchi

    European Journal of Nuclear Medicine and Molecular Imaging   49 ( 9 )   3299   2022.7

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    The authors regret that the title that appears in the original article is incorrect. Methods of the assessment of radiometabolites in plasma by high-performance liquid chromatography (HPLC) in the supplementary should also be corrected. The author wrote “An aliquot of the supernatant was analyzed by radio-HPLC (Analytical column: Waters XBridge OST C18 (10 × 50 mm; particle size, 2.5 μm), acetonitrile (90%; A) and ammonium acetate (0.02 M; B) were used as mobile phases (40/60 A/B) at a flow rate of 5.0 mL/min.”. This was incorrect. The correct description is “An aliquot of the supernatant was analyzed by radio-HPLC with a C18 column (Main column: Waters Atlantis T3 OBD Prep, 10 × 150 mm; particle size, 5 μm; guard column: Waters Atlantis T3, 10 × 10 mm; particle size, 5 μm), and the mixture of acetonitrile (A) and water (B) were used as mobile phases (A/B, 40/60) at a flow rate of 4.5 mL/min.” The original article has been corrected.

    DOI: 10.1007/s00259-022-05795-9

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  • PET-based classification of corticobasal syndrome. International journal

    Yoshikazu Nakano, Hitoshi Shimada, Hitoshi Shinotoh, Shigeki Hirano, Kenji Tagai, Yasunori Sano, Yasuharu Yamamoto, Hironobu Endo, Kiwamu Matsuoka, Keisuke Takahata, Manabu Kubota, Yuhei Takado, Yasuyuki Kimura, Masanori Ichise, Maiko Ono, Naruhiko Sahara, Kazunori Kawamura, Ming-Rong Zhang, Satoshi Kuwabara, Tetsuya Suhara, Makoto Higuchi

    Parkinsonism & related disorders   98   92 - 98   2022.4

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    INTRODUCTION: Corticobasal degeneration (CBD) is the most common neuropathological substrate for clinically diagnosed corticobasal syndrome (CBS), while identifying CBD pathology in living individuals has been challenging. This study aimed to examine the capability of positron emission tomography (PET) to detect CBD-type tau depositions and neuropathological classification of CBS. METHODS: Sixteen CBS cases diagnosed by Cambridge's criteria and 12 cognitively healthy controls (HCs) underwent PET scans with 11C-PiB, 11C-PBB3, and 18F-FDG, along with T1-weighted magnetic resonance imaging. Amyloid positivity was assessed by visual inspection of 11C-PiB retentions. Tau positivity was judged by quantitative comparisons of 11C-PBB3 binding to HCs. RESULTS: Sixteen CBS cases consisted of two cases (13%) with amyloid and tau positivities indicative of Alzheimer's disease (AD) pathologies, 11 cases (69%) with amyloid negativity and tau positivity, and three cases (19%) with amyloid and tau negativities. Amyloid(-), tau(+) CBS cases showed increased retentions of 11C-PBB3 in the frontoparietal areas, basal ganglia, and midbrain, and reduced metabolism in the precentral gyrus and thalamus relative to HCs. The enhanced tau probe retentions in the frontal gray and white matters partially overlapped with metabolic deficits and atrophy and correlated with Clinical Dementia Rating scores. CONCLUSIONS: PET-based classification of CBS was in accordance with previous neuropathological reports on the prevalences of AD, non-AD tauopathies, and others in CBS. The current work suggests that 11C-PBB3-PET may assist the biological classification of CBS and understanding of links between CBD-type tau depositions and neuronal deteriorations leading to cognitive declines.

    DOI: 10.1016/j.parkreldis.2022.04.015

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  • First-in-human in vivo undefined imaging and quantification of monoacylglycerol lipase in the brain: a PET study with 18F-T-401

    Keisuke Takahata, Chie Seki, Yasuyuki Kimura, Manabu Kubota, Masanori Ichise, Yasunori Sano, Yasuharu Yamamoto, Kenji Tagai, Hitoshi Shimada, Soichiro Kitamura, Kiwamu Matsuoka, Hironobu Endo, Hitoshi Shinotoh, Kazunori Kawamura, Ming-Rong Zhang, Yuhei Takado, Makoto Higuchi

    European Journal of Nuclear Medicine and Molecular Imaging   2022.1

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    Publishing type:Research paper (scientific journal)   Publisher:Springer Science and Business Media LLC  

    DOI: 10.1007/s00259-021-05671-y

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    Other Link: https://link.springer.com/article/10.1007/s00259-021-05671-y/fulltext.html

  • タウPETを用いた機械学習に基づく非アルツハイマー型認知症の自動診断法開発

    遠藤 浩信, 互 健二, 松岡 究, 平田 浩聖, 小久保 奈緒美, 生駒 洋子, 高畑 圭輔, 関 千江, 小野 麻衣子, 河村 和紀, 張 明栄, 篠遠 仁, 徳田 隆彦, 島田 斉, 大石 健一, 森 進, 高堂 裕平, 樋口 真人

    Dementia Japan   35 ( 4 )   612 - 612   2021.10

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    Language:Japanese   Publisher:(一社)日本認知症学会  

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  • A first-in-human study of 11C-MTP38, a novel PET ligand for phosphodiesterase 7. International journal

    Manabu Kubota, Chie Seki, Yasuyuki Kimura, Keisuke Takahata, Hitoshi Shimada, Yuhei Takado, Kiwamu Matsuoka, Kenji Tagai, Yasunori Sano, Yasuharu Yamamoto, Maki Okada, Tatsuya Kikuchi, Masanori Ichise, Kazunori Kawamura, Ming-Rong Zhang, Makoto Higuchi

    European journal of nuclear medicine and molecular imaging   48 ( 9 )   2846 - 2855   2021.8

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    PURPOSE: Phosphodiesterase 7 (PDE7) is an enzyme that selectively hydrolyses cyclic adenosine monophosphate, and its dysfunction is implicated in neuropsychiatric diseases. However, in vivo visualization of PDE7 in human brains has hitherto not been possible. Using the novel PET ligand 11C-MTP38, which we recently developed, we aimed to image and quantify PDE7 in living human brains. METHODS: Seven healthy males underwent a 90-min PET scan after injection of 11C-MTP38. We performed arterial blood sampling and metabolite analysis of plasma in six subjects to obtain a metabolite-corrected input function. Regional total distribution volumes (VTs) were estimated using compartment models, and Logan plot and Ichise multilinear analysis (MA1). We further quantified the specific radioligand binding using the original multilinear reference tissue model (MRTMO) and standardized uptake value ratio (SUVR) method with the cerebellar cortex as reference. RESULTS: PET images with 11C-MTP38 showed relatively high retentions in several brain regions, including in the striatum, globus pallidus, and thalamus, as well as fast washout from the cerebellar cortex, in agreement with the known distribution of PDE7. VT values were robustly estimated by two-tissue compartment model analysis (mean VT = 4.2 for the pallidum), Logan plot, and MA1, all in excellent agreement with each other, suggesting the reversibility of 11C-MTP38 binding. Furthermore, there were good agreements between binding values estimated by indirect method and those estimated by both MRTMO and SUVR, indicating that these methods could be useful for reliable quantification of PDE7. Because MRTMO and SUVR do not require arterial blood sampling, they are the most practical for the clinical use of 11C-MTP38-PET. CONCLUSION: We have provided the first demonstration of PET visualization of PDE7 in human brains. 11C-MTP38 is a promising novel PET ligand for the quantitative investigation of central PDE7.

    DOI: 10.1007/s00259-021-05235-0

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  • Dynamic alterations in the central glutamatergic status following food and glucose intake: in vivo multimodal assessments in humans and animal models. International journal

    Manabu Kubota, Yasuyuki Kimura, Masafumi Shimojo, Yuhei Takado, Joao Mn Duarte, Hiroyuki Takuwa, Chie Seki, Hitoshi Shimada, Hitoshi Shinotoh, Keisuke Takahata, Soichiro Kitamura, Sho Moriguchi, Kenji Tagai, Takayuki Obata, Jin Nakahara, Yutaka Tomita, Masaki Tokunaga, Jun Maeda, Kazunori Kawamura, Ming-Rong Zhang, Masanori Ichise, Tetsuya Suhara, Makoto Higuchi

    Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism   41 ( 11 )   271678X211004150 - 2943   2021.5

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    Fluctuations of neuronal activities in the brain may underlie relatively slow components of neurofunctional alterations, which can be modulated by food intake and related systemic metabolic statuses. Glutamatergic neurotransmission plays a major role in the regulation of excitatory tones in the central nervous system, although just how dietary elements contribute to the tuning of this system remains elusive. Here, we provide the first demonstration by bimodal positron emission tomography (PET) and magnetic resonance spectroscopy (MRS) that metabotropic glutamate receptor subtype 5 (mGluR5) ligand binding and glutamate levels in human brains are dynamically altered in a manner dependent on food intake and consequent changes in plasma glucose levels. The brain-wide modulations of central mGluR5 ligand binding and glutamate levels and profound neuronal activations following systemic glucose administration were further proven by PET, MRS, and intravital two-photon microscopy, respectively, in living rodents. The present findings consistently support the notion that food-associated glucose intake is mechanistically linked to glutamatergic tones in the brain, which are translationally accessible in vivo by bimodal PET and MRS measurements in both clinical and non-clinical settings.

    DOI: 10.1177/0271678X211004150

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  • 【タウPET:その足跡と今】非アルツハイマー病性タウオパチーのタウPETイメージング

    互 健二, 島田 斉

    臨床放射線   66 ( 4 )   335 - 341   2021.4

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    Language:Japanese   Publisher:金原出版(株)  

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  • High-Contrast In Vivo Imaging of Tau Pathologies in Alzheimer's and Non-Alzheimer's Disease Tauopathies. International journal

    Kenji Tagai, Maiko Ono, Manabu Kubota, Soichiro Kitamura, Keisuke Takahata, Chie Seki, Yuhei Takado, Hitoshi Shinotoh, Yasunori Sano, Yasuharu Yamamoto, Kiwamu Matsuoka, Hiroyuki Takuwa, Masafumi Shimojo, Manami Takahashi, Kazunori Kawamura, Tatsuya Kikuchi, Maki Okada, Haruhiko Akiyama, Hisaomi Suzuki, Mitsumoto Onaya, Takahiro Takeda, Kimihito Arai, Nobutaka Arai, Nobuyuki Araki, Yuko Saito, John Q Trojanowski, Virginia M Y Lee, Sushil K Mishra, Yoshiki Yamaguchi, Yasuyuki Kimura, Masanori Ichise, Yutaka Tomita, Ming-Rong Zhang, Tetsuya Suhara, Masahiro Shigeta, Naruhiko Sahara, Makoto Higuchi, Hitoshi Shimada

    Neuron   109 ( 1 )   42 - 58   2021.1

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    A panel of radiochemicals has enabled in vivo positron emission tomography (PET) of tau pathologies in Alzheimer's disease (AD), although sensitive detection of frontotemporal lobar degeneration (FTLD) tau inclusions has been unsuccessful. Here, we generated an imaging probe, PM-PBB3, for capturing diverse tau deposits. In vitro assays demonstrated the reactivity of this compound with tau pathologies in AD and FTLD. We could also utilize PM-PBB3 for optical/PET imaging of a living murine tauopathy model. A subsequent clinical PET study revealed increased binding of 18F-PM-PBB3 in diseased patients, reflecting cortical-dominant AD and subcortical-dominant progressive supranuclear palsy (PSP) tau topologies. Notably, the in vivo reactivity of 18F-PM-PBB3 with FTLD tau inclusion was strongly supported by neuropathological examinations of brains derived from Pick's disease, PSP, and corticobasal degeneration patients who underwent PET scans. Finally, visual inspection of 18F-PM-PBB3-PET images was indicated to facilitate individually based identification of diverse clinical phenotypes of FTLD on a neuropathological basis.

    DOI: 10.1016/j.neuron.2020.09.042

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  • A case of Kii amyotrophic lateral sclerosis/parkinsonism dementia complex presenting as progressive parkinsonism with corresponding tau imaging

    Yasuyuki Ohta, Hitoshi Shimada, Ken Ikegami, Keiichiro Tsunoda, Nozomi Hishikawa, Toru Yamashita, Mami Takemoto, Yoshio Omote, Kenji Tagai, Kiwamu Matsuoka, Makoto Higuchi, Koji Abe

    NEUROLOGY AND CLINICAL NEUROSCIENCE   9 ( 1 )   124 - 126   2021.1

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:WILEY  

    Amyotrophic lateral sclerosis/parkinsonism dementia complex (ALS/PDC), frequently observed in the Kii peninsula of Japan, is pathologically characterized by widespread tau pathology in the cerebrum and brainstem. Here, we report a case of Kii ALS/PDC predominantly presenting progressive parkinsonism. Tau positron emission tomography (PET) imaging with F-18-PM-PBB3 suggested tau deposition in the substantia nigra of the midbrain and subcortical areas, but not in the cerebral cortex, which was similar to progressive supranuclear palsy (PSP), suggesting that parkinsonism-predominant type of Kii ALS/PDC may have a similar area of tau deposition to PSP.

    DOI: 10.1111/ncn3.12463

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  • 前頭側頭葉変性症患者の18F-PM-PBB3 PET定量解析におけるヒストグラムを用いた参照領域の最適化の検討

    互 健二, 遠藤 浩信, Debnath OiendrilaBhowmik, 関 千江, 松岡 究, 高畑 圭輔, 小野 麻衣子, 島田 斉, 生駒 洋子, 高堂 裕平, 樋口 真人

    核医学   58 ( Suppl. )   S223 - S223   2021

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    Language:Japanese   Publisher:(一社)日本核医学会  

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  • Binding of Dopamine D1 Receptor and Noradrenaline Transporter in Individuals with Autism Spectrum Disorder: A PET Study. International journal

    Manabu Kubota, Junya Fujino, Shisei Tei, Keisuke Takahata, Kiwamu Matsuoka, Kenji Tagai, Yasunori Sano, Yasuharu Yamamoto, Hitoshi Shimada, Yuhei Takado, Chie Seki, Takashi Itahashi, Yuta Y Aoki, Haruhisa Ohta, Ryu-Ichiro Hashimoto, Ming-Rong Zhang, Tetsuya Suhara, Motoaki Nakamura, Hidehiko Takahashi, Nobumasa Kato, Makoto Higuchi

    Cerebral cortex (New York, N.Y. : 1991)   30 ( 12 )   6458 - 6468   2020.11

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    Although previous studies have suggested the involvement of dopamine (DA) and noradrenaline (NA) neurotransmissions in the autism spectrum disorder (ASD) pathophysiology, few studies have examined these neurotransmissions in individuals with ASD in vivo. Here, we investigated DA D1 receptor (D1R) and noradrenaline transporter (NAT) binding in adults with ASD (n = 18) and neurotypical controls (n = 20) by utilizing two different PET radioligands, [11C]SCH23390 and (S,S)-[18F]FMeNER-D2, respectively. We found no significant group differences in DA D1R (striatum, anterior cingulate cortex, and temporal cortex) or NAT (thalamus and pons) binding. However, in the ASD group, there were significant negative correlations between DA D1R binding (striatum, anterior cingulate cortex and temporal cortex) and the "attention to detail" subscale score of the Autism Spectrum Quotient. Further, there was a significant positive correlation between DA D1R binding (temporal cortex) and emotion perception ability assessed by the neurocognitive battery. Associations of NAT binding with empathic abilities and executive function were found in controls, but were absent in the ASD group. Although a lack of significant group differences in binding might be partly due to the heterogeneity of ASD, our results indicate that central DA and NA function might play certain roles in the clinical characteristics of ASD.

    DOI: 10.1093/cercor/bhaa211

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  • 微小出血を有するアルツハイマー病における臨床および髄液バイオマーカーの特徴

    木戸 雄介, 平野 成樹, 潮平 俊哉, 仲野 義和, 櫻井 透, 島田 斉, 柏戸 孝一, 吉山 容正, 杉山 淳比古, 横田 元, 桑原 聡

    臨床神経学   60 ( Suppl. )   S539 - S539   2020.11

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  • 進行性核上性麻痺における前部帯状回の乳酸高値は前頭葉機能障害と関連する

    高堂 裕平, 互 健二, 松岡 究, 篠遠 仁, 佐野 康徳, 高畑 圭輔, 久保田 学, 小野 麻衣子, 佐原 成彦, 小畠 隆行, 河村 和紀, 張 明栄, 須原 哲也, 島田 斉, 樋口 真人

    臨床神経学   60 ( Suppl. )   S338 - S338   2020.11

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  • 認知症CPC「認知症にかかわる医師のための臨床神経病理カンファレンス」 急速に運動・認知機能障害が進行し、もの忘れ外来受診後経過3年で死亡した83歳女性剖検例

    金田 大太, 松原 知康, 石井 賢二, 徳丸 阿耶, 島田 斉, 佐原 成彦, 須原 哲也, 村山 繁雄, 齊藤 祐子

    Dementia Japan   34 ( 4 )   470 - 470   2020.10

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  • 自閉スペクトラム症者における脳内ドーパミンD1受容体およびノルアドレナリントランスポーター結合についてのPET研究(Binding of dopamine D1 receptor and noradrenaline transporter in individuals with autism spectrum disorder: A PET study)

    久保田 学, 藤野 純也, 鄭 志誠, 高畑 圭輔, 松岡 究, 互 健二, 佐野 康徳, 山本 保天, 島田 斉, 高堂 裕平, 関 千江, 板橋 貴史, 青木 悠太, 太田 晴久, 橋本 龍一郎, 張 明栄, 中村 元昭, 高橋 英彦, 加藤 進昌, 樋口 真人

    日本神経精神薬理学会年会・日本生物学的精神医学会年会・日本精神薬学会総会・学術集会合同年会プログラム・抄録集   50回・42回・4回   216 - 216   2020.8

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    Language:English   Publisher:日本神経精神薬理学会・日本生物学的精神医学会・日本精神薬学会  

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  • Excess tau PET ligand retention in elderly patients with major depressive disorder. International journal

    Sho Moriguchi, Keisuke Takahata, Hitoshi Shimada, Manabu Kubota, Soichiro Kitamura, Yasuyuki Kimura, Kenji Tagai, Ryosuke Tarumi, Hajime Tabuchi, Jeffrey H Meyer, Masaru Mimura, Kazunori Kawamura, Ming-Rong Zhang, Shigeo Murayama, Tetsuya Suhara, Makoto Higuchi

    Molecular psychiatry   2020.7

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    Depression is one of the common psychiatric disorders in old age. Major depressive disorder (MDD) has been identified as a risk factor or prodrome for neurodegenerative dementias, suggesting neuropathological overlaps and a continuum between MDD and neurodegenerative disorders. In this study, we examined tau and amyloid-β (Aβ) accumulations in the brains of MDD and healthy controls using positron emission tomography (PET) to explore pathological substrates of this illness. Twenty MDD and twenty age-matched, healthy controls were examined by PET with a tau radioligand, [11C]PBB3, and an Aβ radioligand, [11C]PiB. Radioligand retentions were quantified as a standardized uptake value ratio (SUVR). We also assessed clinical manifestations of the patients using the 17-item Hamilton Depression Scale, the Geriatric Depression Scale, and psychotic symptoms. Mean cortical [11C]PBB3 SUVRs in MDD patients were significantly higher than those of healthy controls. These values were higher in MDD patients with psychotic symptoms than in those without any. The present findings indicate that tau depositions may underlie MDD, and especially in patients with psychotic symptoms. PET detection of tau accumulations may provide mechanistic insights into neuronal dysfunctions in these cases and could serve as predictions of their clinical consequences.

    DOI: 10.1038/s41380-020-0766-9

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  • 脳循環代謝イメージングを再考する Reviewed

    島田 斉, 互 健二, 久保田 学, 高畑 圭輔, 高堂 裕平, 樋口 真人, 篠遠 仁, 平野 成樹

    千葉医学雑誌   96 ( 2 )   42 - 42   2020.4

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    Language:Japanese   Publisher:千葉医学会  

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  • 【脳画像解析による精神疾患の診断・評価の可能性】神経認知障害群の脳画像解析 画像診断の進歩 Reviewed

    互 健二, 内海 智博, 小高 文聰, 繁田 雅弘, 島田 斉

    臨床精神医学   49 ( 4 )   519 - 525   2020.4

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    Language:Japanese   Publisher:(株)アークメディア  

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  • 脳循環代謝イメージングを再考する

    島田 斉, 互 健二, 久保田 学, 高畑 圭輔, 高堂 裕平, 樋口 真人, 篠遠 仁, 平野 成樹

    千葉医学雑誌   96 ( 2 )   42 - 42   2020.4

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  • 本年の動向 非アルツハイマー病タウオパチーにおけるtau-PET

    互 健二, 島田 斉

    Annual Review神経   2020   111 - 116   2020.4

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  • 【老年精神医学分野の疾患における画像診断のいまとこれから】アルツハイマー病におけるPETを中心とした技術の発展

    互 健二, 繁田 雅弘, 島田 斉

    老年精神医学雑誌   31 ( 3 )   227 - 232   2020.3

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    ポジトロン放出断層撮影(PET)はもとより研究用ツールとして開発され発展してきた経緯をもつが、[18F]fluorodeoxyglucose-PET(FDG-PET)などで得られた知見は今日の認知症診断に利用され、他の臨床検査にも応用されている。また近年では、アミロイドやタウといった異常蓄積タンパク質を可視化する神経病理イメージングが隆盛を迎え、さまざまなPET診断薬が開発されている。神経病理イメージングはアルツハイマー病(AD)の発症前診断を可能とする一方で、根本的治療薬のない現在、画像診断のもたらす心理的影響についても配慮する必要がある。本稿では、ADを対象とするPETを中心とした技術の発展について概説した。(著者抄録)

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    Other Link: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J02464&link_issn=&doc_id=20200420130002&doc_link_id=%2Faj2rsizd%2F2020%2F003103%2F003%2F0227-0232%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Faj2rsizd%2F2020%2F003103%2F003%2F0227-0232%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

  • Relationship between person with dementia and adolescents: A preliminary survey of the Association Between Children and Dementia Elders (ABCDE) Project

    Shigeki Hirano, Keisuke Shimizu, Noriko Murayama, Moeno Ishikawa, Shogo Furukawa, Kazuho Kojima, Ai Ishikawa, Hitoshi Shimada, Hitoshi Shinotoh, Koichi Kashiwado, Tsuyoshi Sasaki, Masaomi Iyo, Satoshi Kuwabara

    Nursing and Palliative Care   5 ( 1 )   2020

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    DOI: 10.15761/npc.1000211

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  • The Neuropsychological Correlates of Brain Perfusion and Gray Matter Volume in Alzheimer's Disease. International journal

    Hong Tai, Shigeki Hirano, Toru Sakurai, Yoshikazu Nakano, Ai Ishikawa, Kazuho Kojima, Hongliang Li, Hitoshi Shimada, Koichi Kashiwado, Hiroki Mukai, Takuro Horikoshi, Atsuhiko Sugiyama, Takashi Uno, Satoshi Kuwabara

    Journal of Alzheimer's disease : JAD   78 ( 4 )   1639 - 1652   2020

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    BACKGROUND: Neuropsychological tests, structural neuroimaging, and functional neuroimaging are employed as diagnostic and monitoring biomarkers of patients with Alzheimer's disease (AD)Objective:We aimed to elucidate the similarities and differences in neuropsychological tests and neuroimaging with the use of the Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog), structural magnetic resonance image (MRI), and perfusion single photon emission computed tomography (SPECT), and parametric image analyses to understand its role in AD. METHODS: Clinically-diagnosed AD patients (n = 155) were scanned with three-dimensional T1-weighted MRI and N-isopropyl-p-[123I] iodoamphetamine SPECT. Statistical parametric mapping 12 was used for preprocessing images, statistical analyses, and voxel-based morphometry for gray matter volume analyses. Group comparison (AD versus healthy controls), multiple regression analyses with MMSE, ADAS-cog total score, and ADAS-cog subscores as variables, were performed. RESULTS: The AD group showed bilateral hippocampal volume reduction and hypoperfusion in the bilateral temporo-parietal lobe and posterior midline structures. Worse MMSE and ADAS-cog total score were associated with bilateral temporo-parietal volume loss and hypoperfusion. MMSE, but not ADAS-cog, was associated with the posterior midline structures. The ADAS-cog subscores were associated with the temporal volume, while perfusion analyses were linked to the left temporo-parietal region with the language function and right analogous region with the constructional praxis subscore. CONCLUSION: MMSE and ADAS-cog are associated with temporo-parietal regions, both in volume and perfusion. The MMSE score is associated with posterior midline structures and linked to an abnormal diagnostic AD pattern. Perfusion image analyses better represents the cognitive function in AD patients.

    DOI: 10.3233/JAD-200676

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  • Amyloid PET陽性皮質基底核症候群における臨床的特徴の検討

    初鹿野 悦子, 平野 成樹, 櫻井 透, 李 洪亮, 仲野 義和, 島田 斉, 飯森 隆志, 堀越 琢郎, 宇野 隆, 桑原 聡

    臨床神経学   59 ( Suppl. )   S464 - S464   2019.11

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  • 軽度認知障害と軽度アルツハイマー病におけるACEIIIを用いた神経心理評価研究

    清水 啓介, 平野 成樹, 柏戸 孝一, 島田 斉, 小島 一歩, 石川 愛, 仲野 義和, 櫻井 透, 鈴木 政秀, 村山 紀子, 石川 萌乃, 焼山 正嗣, 澁谷 和幹, 伊豫 雅臣, 桑原 聡

    臨床神経学   59 ( Suppl. )   S448 - S448   2019.11

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  • 筋萎縮性側索硬化症の運動皮質磁化率変化は上位運動ニューロン障害の指標となり得る

    遠藤 浩信, 関口 兼司, 島田 斉, 上田 健博, 濱口 浩敏, 古和 久朋, 苅田 典生, 戸田 達史

    臨床神経学   59 ( Suppl. )   S333 - S333   2019.11

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  • PET-detectable tau pathology correlates with long-term neuropsychiatric outcomes in patients with traumatic brain injury Reviewed International journal

    Keisuke Takahata, Yasuyuki Kimura, Naruhiko Sahara, Shunsuke Koga, Hitoshi Shimada, Masanori Ichise, Fumie Saito, Sho Moriguchi, Soichiro Kitamura, Manabu Kubota, Satoshi Umeda, Fumitoshi Niwa, Jin Mizushima, Yoko Morimoto, Michitaka Funayama, Hajime Tabuchi, Kevin F Bieniek, Kazunori Kawamura, Ming-Rong Zhang, Dennis W Dickson, Masaru Mimura, Motoichiro Kato, Tetsuya Suhara, Makoto Higuchi

    Brain   142 ( 10 )   3265 - 3279   2019.10

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    Tau deposits is a core feature of neurodegenerative disorder following traumatic brain injury (TBI). Despite ample evidence from post-mortem studies demonstrating exposure to both mild-repetitive and severe TBIs are linked to tau depositions, associations of topology of tau lesions with late-onset psychiatric symptoms due to TBI have not been explored. To address this issue, we assessed tau deposits in long-term survivors of TBI by PET with 11C-PBB3, and evaluated those associations with late-life neuropsychiatric outcomes. PET data were acquired from 27 subjects in the chronic stage following mild-repetitive or severe TBI and 15 healthy control subjects. Among the TBI patients, 14 were diagnosed as having late-onset symptoms based on the criteria of traumatic encephalopathy syndrome. For quantification of tau burden in TBI brains, we calculated 11C-PBB3 binding capacity (cm3), which is a summed voxel value of binding potentials (BP*ND) multiplied by voxel volume. Main outcomes of the present study were differences in 11C-PBB3 binding capacity between groups, and the association of regional 11C-PBB3 binding capacity with neuropsychiatric symptoms. To confirm 11C-PBB3 binding to tau deposits in TBI brains, we conducted in vitro PBB3 fluorescence and phospho-tau antibody immunofluorescence labelling of brain sections of chronic traumatic encephalopathy obtained from the Brain Bank. Our results showed that patients with TBI had higher 11C-PBB3 binding capacities in the neocortical grey and white matter segments than healthy control subjects. Furthermore, TBI patients with traumatic encephalopathy syndrome showed higher 11C-PBB3 binding capacity in the white matter segment than those without traumatic encephalopathy syndrome, and regional assessments revealed that subgroup difference was also significant in the frontal white matter. 11C-PBB3 binding capacity in the white matter segment correlated with the severity of psychosis. In vitro assays demonstrated PBB3-positive tau inclusions at the depth of neocortical sulci, confirming 11C-PBB3 binding to tau lesions. In conclusion, increased 11C-PBB3 binding capacity is associated with late-onset neuropsychiatric symptoms following TBI, and a close correlation was found between psychosis and 11C-PBB3 binding capacity in the white matter.

    DOI: 10.1093/brain/awz238

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  • レビー小体病におけるアルツハイマー病理は認知機能障害、萎縮、糖代謝障害に影響する

    互 健二, 島田 斉, 高畑 圭輔, 久保田 学, 佐野 康徳, 山本 保天, 篠遠 仁, 仲野 義和, 高堂 裕平, 北村 聡一郎, 繁田 雅弘, 須原 哲也, 樋口 真人

    Dementia Japan   33 ( 4 )   527 - 527   2019.10

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  • 軽度認知障害と軽度アルツハイマー病におけるACEIIIを用いた神経心理評価研究

    清水 啓介, 平野 成樹, 柏戸 孝一, 島田 斉, 仲野 義和, 櫻井 透, 鈴木 政秀, 石川 萌乃, 焼山 正嗣, 伊豫 雅臣, 桑原 聡

    Dementia Japan   33 ( 4 )   534 - 534   2019.10

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  • In vivo direct relation of tau pathology with neuroinflammation in early Alzheimer's disease. International journal

    Tatsuhiro Terada, Masamichi Yokokura, Tomokazu Obi, Tomoyasu Bunai, Etsuji Yoshikawa, Ichiro Ando, Hitoshi Shimada, Tetsuya Suhara, Makoto Higuchi, Yasuomi Ouchi

    Journal of neurology   266 ( 9 )   2186 - 2196   2019.9

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    OBJECTIVE: Neuronal damage and neuroinflammation are important events occurring in the brain of Alzheimer's disease (AD). The purpose of this study was to clarify in vivo mutual relationships among abnormal tau deposition, neuroinflammation and cognitive impairment in patients with early AD using positron emission tomography (PET) with [11C]PBB3 and [11C]DPA713. METHODS: Twenty patients with early AD and 20 age-matched normal control (NC) subjects underwent a series of PET measurements with [11C]PBB3 for tau aggregation and [11C]DPA713 for microglial activation (neuroinflammation). Inter- and intrasubject comparisons were performed regarding the levels of [11C]PBB3 binding potential (BPND) and [11C]DPA713 BPND in the light of cognitive functions using statistical parametric mapping (SPM) and regions of interest (ROIs) method. RESULTS: The [11C]PBB3 BPND was greater in the temporo-parietal regions of AD patents than NC subjects, and a similar increasing pattern of [11C]DPA713 BPND was observed in the same patients. Correlation analyses within the AD group showed a positive direct correlation between [11C]PBB3 BPND and [11C]DPA713 BPND in the parahippocampus. Pass analysis revealed that cognitive impairment was more likely linked to the level of the parahippocampal [11C]PBB3 BPND than that of [11C]DPA713 BPND. CONCLUSIONS: The pattern of abnormal tau deposition was very similar to that of neuroinflammation in patients with early-stage AD. Specifically, the direct positive correlation of tau pathology with neuroinflammation in the parahippocampus suggests that neuronal damage in this region is closely associated with microglial activation. Consistently, tau aggregation in this region matters more than neuroinflammation regarding the cognitive deterioration in AD.

    DOI: 10.1007/s00415-019-09400-2

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  • 18F-PM-PBB3 PETは発症前駆期より4リピートタウオパチーの脳病理を捕捉し得る

    島田 斉, 互 健二, 小野 麻衣子, 久保田 学, 高畑 圭輔, 高堂 裕平, 篠遠 仁, 山本 保天, 佐野 康徳, 関 千江, 平野 成樹, 木村 泰之, 市瀬 正則, 関 大成, 河村 和紀, 張 明栄, 桑原 聡, 服部 信孝, 須原 哲也, 樋口 真人

    パーキンソン病・運動障害疾患コングレスプログラム・抄録集   13回   129 - 129   2019.7

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  • PETを用いた大脳皮質基底核症候群の背景病理推定に関する検討

    仲野 義和, 島田 斉, 篠遠 仁, 平野 成樹, 木村 泰之, 市瀬 正則, 関 千江, 高堂 裕平, 高畑 圭輔, 久保田 学, 互 健二, 河村 和紀, 張 明栄, 須原 哲也, 桑原 聡, 樋口 真人

    パーキンソン病・運動障害疾患コングレスプログラム・抄録集   13回   79 - 79   2019.7

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  • In vivo binding of a tau imaging probe, [C-11]PBB3, in patients with progressive supranuclear palsy Reviewed

    Endo Hironobu, Shimada Hitoshi, Sahara Naruhiko, Ono Maiko, Koga Shunsuke, Kitamura Soichiro, Niwa Fumitoshi, Hirano Shigeki, Kimura Yasuyuki, Ichise Masanori, Shinotoh Hitoshi, Zhang Ming Rong, Kuwabara Satoshi, Dickson Dennis W, Toda Tatsushi, Suhara Tetsuya, Higuchi Makoto

    MOVEMENT DISORDERS   34 ( 5 )   744 - 754   2019.5

  • Clinical heterogeneity of frontotemporal dementia and Parkinsonism linked to chromosome 17 caused by MAPT N279K mutation in relation to tau positron emission tomography features Reviewed International journal

    Ikeda Aya, Shimada Hitoshi, Nishioka Kenya, Takanashi Masashi, Hayashida Arisa, Li Yuanzhe, Yoshino Hiroyo, Funayama Manabu, Ueno Yuji, Hatano Taku, Sahara Naruhiko, Suhara Tetsuya, Higuchi Makoto, Hattori Nobutaka

    MOVEMENT DISORDERS   34 ( 4 )   568 - 574   2019.4

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    BACKGROUND: While mechanistic links between tau abnormalities and neurodegeneration have been proven in frontotemporal dementia and parkinsonism linked to chromosome 17 caused by MAPT mutations, variability of the tau pathogenesis and its relation to clinical progressions in the same MAPT mutation carriers are yet to be clarified. OBJECTIVES: The present study aimed to analyze clinical profiles, tau accumulations, and their correlations in 3 kindreds with frontotemporal dementia and parkinsonism linked to chromosome 17 attributed to the MAPT N279K mutation. METHODS: Four patients with N279K mutant frontotemporal dementia and parkinsonism linked to chromosome 17/MAPT underwent [11 C]PBB3-PET to estimate regional tau loads. RESULTS: Haplotype assays revealed that these kindreds originated from a single founder. Despite homogeneity of the disease-causing MAPT allele, clinical progression was more rapid in 2 kindreds than in the other. The kindred with slow progression showed mild tau depositions, mostly confined to the midbrain and medial temporal areas. In contrast, kindreds with rapid progression showed profoundly increased [11 C]PBB3 binding in widespread regions from an early disease stage. CONCLUSIONS: [11 C]PBB3-PET can capture four-repeat tau pathologies characteristic of N279K mutant frontotemporal dementia and parkinsonism linked to chromosome 17/MAPT. Our findings indicate that, in addition to the mutated MAPT allele, genetic and/or epigenetic modifiers of tau pathologies lead to heterogeneous clinicopathological features. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

    DOI: 10.1002/mds.27623

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  • 18F-PM-PBB3 PETによる4リピートタウオパチーのタウイメージング

    島田 斉, 互 健二, 久保田 学, 高畑 圭輔, 高堂 裕平, 市瀬 正則, 須原 哲也, 樋口 真人, 篠遠 仁, 平野 成樹, 木村 泰之

    千葉医学雑誌   95 ( 2 )   57 - 57   2019.4

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  • Amyloid-Negative Dementia in the Elderly is Associated with High Accumulation of Tau in the Temporal Lobes Reviewed

    Takeuchi J, Kikukawa T, Saito H, Hasegawa I, Takeda A, Hatsuta H, Kawabe J, Wada Y, Mawatari A, Igesaka A, Doi H, Watanabe Y, Shimada H, Kitamura S, Higuchi M, Suhara T, Itoh Y

    The Open Biomedical Engineering Journal   13   55 - 66   2019.3

  • Tau imaging detects distinctive distribution of tau pathology in ALS/PDC on the Kii Peninsula Reviewed International journal

    Shinotoh Hitoshi, Shimada Hitoshi, Kokubo Yasumasa, Tagai Kenji, Niwa Fumitoshi, Kitamura Soichiro, Endo Hironobu, Ono Maiko, Kimura Yasuyuki, Hirano Shigeki, Mimuro Maya, Ichise Masanori, Sahara Naruhiko, Zhang Ming-Rong, Suhara Tetsuya, Higuchi Makoto

    NEUROLOGY   92 ( 2 )   E136 - E147   2019.1

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    OBJECTIVE: To characterize the distribution of tau pathology in patients with amyotrophic lateral sclerosis/parkinsonism dementia complex on the Kii Peninsula (Kii ALS/PDC) by tau PET using [11C]PBB3 as ligand. METHODS: This is a cross-sectional study of 5 patients with ALS/PDC and one asymptomatic participant with a dense family history of ALS/PDC from the Kii Peninsula who took part in this study. All were men, and their age was 76 ± 8 (mean ± SD) years. Thirteen healthy men (69 ± 6 years) participated as healthy controls (HCs). Dynamic PET scans were performed following injection of [11C]PBB3, and parametric PET images were generated by voxel-by-voxel calculation of binding potential (BP* ND) using a multilinear reference tissue model. [11C] Pittsburgh compound B (PiB) PET, MRI, and cognitive tests were also performed. RESULTS: A voxel-based comparison of [11C]PBB3 BP* ND illustrated PET-detectable tau deposition in the cerebral cortex and white matter, and pontine basis including the corticospinal tract in Kii ALS/PDC patients compared with HCs (uncorrected p < 0.05). Group-wise volume of interest analysis of [11C]PBB3 BP* ND images showed increased BP* ND in the hippocampus and in frontal and parietal white matters of Kii ALS/PDC patients relative to HCs (p < 0.05, Holm-Sidak multiple comparisons test). BP* ND in frontal, temporal, and parietal gray matters correlated with Mini-Mental State Examination scores in Kii ALS/PDC patients (p < 0.05). All Kii ALS/PDC patients were negative for [11C]PiB (β-amyloid) except one with marginal positivity. CONCLUSION: [11C]PBB3 PET visualized the characteristic topography of tau pathology in Kii ALS/PDC, corresponding to clinical phenotypes of this disease.

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  • Classification of Clinically Diagnosed Alzheimer's Disease Associated with Diabetes Based on Amyloid and Tau PET Results. International journal

    Naoto Takenoshita, Soichiro Shimizu, Hidekazu Kanetaka, Hirofumi Sakurai, Ryo Suzuki, Takashi Miwa, Masato Odawara, Kenji Ishii, Hitoshi Shimada, Makoto Higuchi, Tetsuya Suhara, Haruo Hanyu

    Journal of Alzheimer's disease : JAD   71 ( 1 )   261 - 271   2019

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    BACKGROUND/OBJECTIVE: Although type 2 diabetes mellitus (DM) is a risk factor for the development of dementia, the underlying brain pathologies and mechanisms vary among patients. In this study, we classified patients with clinically diagnosed Alzheimer's disease (AD) associated with DM into subgroups based on their amyloid and tau accumulation patterns on positron emission tomography (PET), and analyzed the differences in clinical features and brain imaging findings between the subgroups. METHODS: Sixty-four patients with probable or possible AD associated with DM were classified using PiB (detects amyloid, A) and PBB3 (detects tau, T) PET studies. Patients were classified into the A+/T+ group (n = 35, AD pathology), the A- /T+ group (n = 19, tauopathy), and the A- /T- group (n = 10, non-amyloid/non-tau neuronal damage). RESULTS: Compared with the A+/T+ group, the A- /T+ group showed less-well controlled glycemia, longer duration of diabetes, more glucose variability, higher frequency of insulin therapy and biochemical hypoglycemia, and greater impairment of frontal lobe function, slower progression of cognitive decline, fewer APOE4 carriers, less severe medial temporal lobe atrophy, and lower frequency of posterior cerebral hypoperfusion. This subgroup showed different clinical and radiological features from AD. CONCLUSION: Among patients with clinically diagnosed AD with DM, there are subgroups with neuronal damage independent of AD pathology. A subgroup of dementia patients suspected of having tauopathy is strongly associated with DM-related metabolic abnormalities. This study highlights the identification of a novel dementia subgroup (diabetes-related dementia), which is important for considering appropriate therapies and care in clinical practice.

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  • 若年性認知症の人に対するサービス課題調査 若年性認知症カフェ開設の試み

    清水 啓介, 平野 成樹, 柏戸 孝一, 島田 斉, 小島 一歩, 石川 愛, 仲野 義和, 櫻井 透, 村山 紀子, 石川 萌乃, 中島 梓, 伊豫 雅臣, 桑原 聡

    臨床神経学   58 ( Suppl. )   S440 - S440   2018.12

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  • 紀伊半島から移住して73年後に発症し、タウPETで陽性であった紀伊ALS/PDC疑いの1例

    角田 慶一郎, 山下 徹, 島田 斉, 野村 恵美, 高橋 義秋, 商 敬偉, 佐藤 恒太, 武本 真美, 菱川 望, 太田 康之, 樋口 真人, 須原 哲也, 小久保 康昌, 葛原 茂樹, 阿部 康二

    日本難病医療ネットワーク学会機関誌   6 ( 1 )   148 - 148   2018.11

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  • Tau-induced focal neurotoxicity and network disruption related to apathy in Alzheimer's disease. Reviewed International journal

    Soichiro Kitamura, Hitoshi Shimada, Fumitoshi Niwa, Hironobu Endo, Hitoshi Shinotoh, Keisuke Takahata, Manabu Kubota, Yuhei Takado, Shigeki Hirano, Yasuyuki Kimura, Ming-Rong Zhang, Satoshi Kuwabara, Tetsuya Suhara, Makoto Higuchi

    Journal of neurology, neurosurgery, and psychiatry   89 ( 11 )   1208 - 1214   2018.11

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    OBJECTIVE: Apathy is a common neuropsychological symptom in Alzheimer's disease (AD), and previous studies demonstrated that neuronal loss and network disruption in some brain regions play pivotal roles in the pathogenesis of apathy. However, contributions of tau and amyloid-β (Aβ) depositions, pathological hallmarks of AD, to the manifestation of apathy remain elusive. METHODS: Seventeen patients with AD underwent positron emission tomography (PET) with 11C-pyridinyl-butadienyl-benzothiazole 3 (11C-PBB3) and 11C-Pittsburgh compound-B (11C-PiB) to estimate tau and Aβ accumulations using standardised uptake value ratio (SUVR) images. 11C-PBB3 and 11C-PiB SUVR were compared between AD patients with high and low Apathy Scale (AS) scores. Additionally, volumetric and diffusion tensor MRI was performed in those areas where any significant difference was observed in PET analyses. Correlation and path analyses among AS and estimated imaging parameters were also conducted. RESULTS: AD patients with high AS scores showed higher 11C-PBB3 SUVR in the orbitofrontal cortex (OFC) than those with low AS scores, while 11C-PiB SUVR in any brain regions did not differ between them. Elevated 11C-PBB3 SUVR in OFC, decreased OFC thickness and decreased fractional anisotropy (FA) in the uncinate fasciculus (UNC), which is structurally connected to OFC, correlated significantly with increased scores of the AS. Path analysis indicated that increased 11C-PBB3 SUVR in OFC affects apathy directly and through reduction of OFC thickness and subsequent decrease of FA in UNC. CONCLUSIONS: The present findings suggested that tau pathology in OFC may provoke focal neurotoxicity in OFC and the following disruption of the OFC-UNC network, leading to the emergence and progression of apathy in AD.

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  • 紀伊半島の筋萎縮性側索硬化症/パーキンソン認知症複合における末梢神経軸索興奮性変化

    網野 寛, 澁谷 和幹, 三澤 園子, 関口 縁, 水地 智基, 常山 篤子, 鈴木 陽一, 島田 斉, 小久保 康昌, 桑原 聡

    臨床神経生理学   46 ( 5 )   532 - 532   2018.10

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  • Dual tracer tau PET imaging reveals different molecular targets for<sup>11</sup>C-THK5351 and<sup>11</sup>C-PBB3 in the Alzheimer brain

    Konstantinos Chiotis, Per Stenkrona, Ove Almkvist, Ove Almkvist, Ove Almkvist, Vladimir Stepanov, Daniel Ferreira, Ryosuke Arakawa, Akihiro Takano, Eric Westman, Andrea Varrone, Nobuyuki Okamura, Nobuyuki Okamura, Hitoshi Shimada, Makoto Higuchi, Christer Halldin, Agneta Nordberg, Agneta Nordberg

    European Journal of Nuclear Medicine and Molecular Imaging   45   1605 - 1617   2018.7

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    © 2018, The Author(s). Purpose: Several tau PET tracers have been developed, but it remains unclear whether they bind to the same molecular target on the heterogeneous tau pathology. In this study we evaluated the binding of two chemically different tau-specific PET tracers (11C-THK5351 and11C-PBB3) in a head-to-head, in vivo, multimodal design. Methods: Nine patients with a diagnosis of mild cognitive impairment or probable Alzheimer’s disease and cerebrospinal fluid biomarker evidence supportive of the presence of Alzheimer’s disease brain pathology were recruited after thorough clinical assessment. All patients underwent imaging with the tau-specific PET tracers11C-THK5351 and11C-PBB3 on the same day, as well as imaging with the amyloid-beta-specific tracer11C-AZD2184, a T1-MRI sequence, and neuropsychological assessment. Results: The load and regional distribution of binding differed between11C-THK5351 and11C-PBB3 with no statistically significant regional correlations observed between the tracers. The binding pattern of11C-PBB3, but not that of11C-THK5351, in the temporal lobe resembled that of11C-AZD2184, with strong correlations detected between11C-PBB3 and11C-AZD2184 in the temporal and occipital lobes. Global cognition correlated more closely with11C-THK5351 than with11C-PBB3 binding. Similarly, cerebrospinal fluid tau measures and entorhinal cortex thickness were more closely correlated with11C-THK5351 than with11C-PBB3 binding. Conclusion: This research suggests different molecular targets for these tracers; while11C-PBB3 appeared to preferentially bind to tau deposits with a close spatial relationship to amyloid-beta, the binding pattern of11C-THK5351 fitted the expected distribution of tau pathology in Alzheimer’s disease better and was more closely related to downstream disease markers.

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  • Low signal intensity in motor cortex on susceptibility-weighted MR imaging is correlated with clinical signs of amyotrophic lateral sclerosis: a pilot study. International journal

    Hironobu Endo, Kenji Sekiguchi, Hitoshi Shimada, Takehiro Ueda, Hisatomo Kowa, Fumio Kanda, Tatsushi Toda

    Journal of neurology   265 ( 3 )   552 - 561   2018.3

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    There is no reliable objective indicator for upper motor neuron dysfunction in amyotrophic lateral sclerosis (ALS). To determine the clinical significance and potential utility of magnetic resonance (MR) signals, we investigated the relationship between clinical symptoms and susceptibility changes in the motor cortex measured using susceptibility-weighted MR imaging taken by readily available 3-T MRI in clinical practice. Twenty-four ALS patients and 14 control subjects underwent 3-T MR T1-weighted imaging and susceptibility-weighted MR imaging with the principles of echo-shifting with a train of observations (PRESTO) sequence. We analysed relationships between relative susceptibility changes in the motor cortex assessed using voxel-based analysis (VBA) and clinical scores, including upper motor neuron score, ALS functional rating scale revised score, and Medical Research Council sum score on physical examination. Patients with ALS exhibited significantly lower signal intensity in the precentral gyrus on susceptibility-weighted MR imaging compared with controls. Clinical scores were significantly correlated with susceptibility changes. Importantly, the extent of the susceptibility changes in the bilateral precentral gyri was significantly correlated with upper motor neuron scores. The results of our pilot study using VBA indicated that low signal intensity in motor cortex on susceptibility-weighted MR imaging may correspond to clinical symptoms, particularly upper motor neuron dysfunction. Susceptibility-weighted MR imaging may be a useful diagnostic tool as an objective indicator of upper motor neuron dysfunction.

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  • Voxel-Based Acetylcholinesterase PET Study in Early and Late Onset Alzheimer's Disease

    Shigeki Hirano, Hitoshi Shinotoh, Hitoshi Shimada, Tsuneyoshi Ota, Koichi Sato, Noriko Tanaka, Ming Rong Zhang, Makoto Higuchi, Kiyoshi Fukushi, Toshiaki Irie, Satoshi Kuwabara, Tetsuya Suhara

    Journal of Alzheimer's Disease   62 ( 4 )   1539 - 1548   2018

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    © 2018 - IOS Press and the authors. All rights reserved. Background: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by chronic progressive cognitive decline and displays underlying brain cholinergic dysfunction, providing a rationale for treatment with cholinomimetic medication. The clinical presentations and courses of AD patients may differ by age of onset. Objective: The objective of the present study was to illustrate the regional differences of brain acetylcholinesterase (AChE) activity as quantified by N-[11C]methylpiperidinyl-4-acetate ([11C]MP4A) and PET using parametric whole brain analysis and clarify those differences as a function of age. Methods: 22 early onset AD (EOAD) with age at onset under 65, the remaining 26 as late onset AD (LOAD), and 16 healthy controls (HC) were enrolled. Voxel-based AChE activity estimation of [11C]MP4A PET images was conducted by arterial input and unconstrained nonlinear least-squares method with subsequent parametrical analyses. Statistical threshold was set as Family Wise Error corrected, p-value <0.05 on cluster-level and cluster extent over 30 voxels. Results: Voxel-based group comparison showed that, compared to HC, both EOAD and LOAD showed cortical AChE decrement in parietal, temporal, and occipital cortices, with wider and stringent cortical involvement in the EOAD group, most prominently demonstrated in the temporal region. There was no significant correlation between age and regional cerebral AChE activity except for a small left superior temporal region in the AD group (Brodmann's area 22, Zmax = 5.13, 396 voxels), whereas no significant cluster was found in the HC counterpart. Conclusion: Difference in cortical cholinergic dysfunction between EOAD and LOAD may shed some light on the cholinomimetic drug efficacy in AD.

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  • Voxel-Based Acetylcholinesterase PET Study in Early and Late Onset Alzheimer's Disease. International journal

    Shigeki Hirano, Hitoshi Shinotoh, Hitoshi Shimada, Tsuneyoshi Ota, Koichi Sato, Noriko Tanaka, Ming-Rong Zhang, Makoto Higuchi, Kiyoshi Fukushi, Toshiaki Irie, Satoshi Kuwabara, Tetsuya Suhara

    Journal of Alzheimer's disease : JAD   62 ( 4 )   1539 - 1548   2018

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    BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by chronic progressive cognitive decline and displays underlying brain cholinergic dysfunction, providing a rationale for treatment with cholinomimetic medication. The clinical presentations and courses of AD patients may differ by age of onset. OBJECTIVE: The objective of the present study was to illustrate the regional differences of brain acetylcholinesterase (AChE) activity as quantified by N-[11C]methylpiperidinyl-4-acetate ([11C]MP4A) and PET using parametric whole brain analysis and clarify those differences as a function of age. METHODS: 22 early onset AD (EOAD) with age at onset under 65, the remaining 26 as late onset AD (LOAD), and 16 healthy controls (HC) were enrolled. Voxel-based AChE activity estimation of [11C]MP4A PET images was conducted by arterial input and unconstrained nonlinear least-squares method with subsequent parametrical analyses. Statistical threshold was set as Family Wise Error corrected, p-value <0.05 on cluster-level and cluster extent over 30 voxels. RESULTS: Voxel-based group comparison showed that, compared to HC, both EOAD and LOAD showed cortical AChE decrement in parietal, temporal, and occipital cortices, with wider and stringent cortical involvement in the EOAD group, most prominently demonstrated in the temporal region. There was no significant correlation between age and regional cerebral AChE activity except for a small left superior temporal region in the AD group (Brodmann's area 22, Zmax = 5.13, 396 voxels), whereas no significant cluster was found in the HC counterpart. CONCLUSION: Difference in cortical cholinergic dysfunction between EOAD and LOAD may shed some light on the cholinomimetic drug efficacy in AD.

    DOI: 10.3233/JAD-170749

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  • Voxel-Based Acetylcholinesterase PET Study in Early and Late Onset Alzheimer's Disease

    Shigeki Hirano, Hitoshi Shinotoh, Hitoshi Shimada, Tsuneyoshi Ota, Koichi Sato, Noriko Tanaka, Ming-Rong Zhang, Makoto Higuchi, Kiyoshi Fukushi, Toshiaki Irie, Satoshi Kuwabara, Tetsuya Suhara

    JOURNAL OF ALZHEIMERS DISEASE   62 ( 4 )   1539 - 1548   2018

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    Background: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by chronic progressive cognitive decline and displays underlying brain cholinergic dysfunction, providing a rationale for treatment with cholinomimetic medication. The clinical presentations and courses of AD patients may differ by age of onset.Objective: The objective of the present study was to illustrate the regional differences of brain acetylcholinesterase (AChE) activity as quantified by N-[C-11] methylpiperidinyl-4-acetate ([C-11] MP4A) and PET using parametric whole brain analysis and clarify those differences as a function of age.Methods: 22 early onset AD (EOAD) with age at onset under 65, the remaining 26 as late onset AD (LOAD), and 16 healthy controls (HC) were enrolled. Voxel-based AChE activity estimation of [C-11] MP4A PET images was conducted by arterial input and unconstrained nonlinear least-squares method with subsequent parametrical analyses. Statistical threshold was set as Family Wise Error corrected, p-value < 0.05 on cluster-level and cluster extent over 30 voxels.Results: Voxel-based group comparison showed that, compared to HC, both EOAD and LOAD showed cortical AChE decrement in parietal, temporal, and occipital cortices, with wider and stringent cortical involvement in the EOAD group, most prominently demonstrated in the temporal region. There was no significant correlation between age and regional cerebral AChE activity except for a small left superior temporal region in the AD group (Brodmann's area 22, Z(max) = 5.13, 396 voxels), whereas no significant cluster was found in the HC counterpart.Conclusion: Difference in cortical cholinergic dysfunction between EOAD and LOAD may shed some light on the cholinomimetic drug efficacy in AD.

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  • Amyloid and Tau Positron Emission Tomography in Suggested Diabetesrelated Dementia. International journal

    Naoto Takenoshita, Raita Fukasawa, Yusuke Ogawa, Soichiro Shimizu, Takahiko Umahara, Kenji Ishii, Hitoshi Shimada, Makoto Higuchi, Tetsuya Suhara, Haruo Hanyu

    Current Alzheimer research   15 ( 11 )   1062 - 1069   2018

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    BACKGROUND: Type 2 diabetes mellitus (DM) has been shown to increase the risk for cognitive decline and dementia, such as Alzheimer disease (AD) and vascular dementia (VaD). In addition to AD and VaD, there may be a dementia subgroup associated with specific DM-related metabolic abnormalities rather than AD pathology or cerebrovascular disease, referred to as diabetes-related dementia (DrD). METHOD: We studied 11C-PiB and 11C-PBB3 positron emission tomography (PET) in 31 subjects with DrD and 5 subjects with AD associated with DM to assess amyloid and tau deposits in the brain. RESULTS: All subjects with AD showed both positive PiB and PBB3. However, only 12 out of 31 subjects (39%) with DrD showed positive PiB, whereas 17 out of 21 subjects (81%) who underwent PBB3 PET showed positive PBB3. Depending on the positivity of PiB and PBB3, we classified 21 subjects into a negative PiB and a positive PBB3 pattern (11 cases, 52%), indicating tauopathy, a positive PiB and a positive PBB3 pattern (6 cases, 29%), indicating AD pathology, or a negative PiB and a negative PBB3 pattern (4 cases, 19%). Among 11 subjects showing a negative PiB and a positive PBB3 pattern, there were 2 PBB3 deposit patterns, including the medial temporal lobe only and extensive neocortex beyond the medial temporal lobe. CONCLUSION: DrD showed variable amyloid and tau accumulation patterns in the brain. DrD may be associated predominantly with tau pathology, in addition to AD pathology and non-amyloid/non-tau neuronal damage due to DM-related metabolic abnormalities.

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  • Occupancy of Norepinephrine Transporter by Duloxetine in Human Brains Measured by Positron Emission Tomography with (S,S)-[18F]FMeNER-D2 Reviewed

    Sho Moriguchi, Harumasa Takano, Yasuyuki Kimura, Tomohisa Nagashima, Keisuke Takahata, Manabu Kubota, Soichiro Kitamura, Tatsuya Ishii, Masanori Ichise, Ming-Rong Zhang, Hitoshi Shimada, Masaru Mimura, Jeffrey H Meyer, Makoto Higuchi, Tetsuya Suhara

    International Journal of Neuropsychopharmacology   20 ( 12 )   957 - 962   2017.12

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  • A migration case of Kii amyotrophic lateral sclerosis/parkinsonism dementia complex with the shortest stay in the endemic area and the longest incubation to develop the disease Reviewed

    Keiichiro Tsunoda, Toru Yamashita, Hitoshi Shimada, Emi Nomura, Yoshiaki Takahashi, Jingwei Shang, Kota Sato, Mami Takemoto, Nozomi Hishikawa, Yasuyuki Ohta, Makoto Higuchi, Tetsuya Suhara, Yasumasa Kokubo, Shigeki Kuzuhara, Koji Abe

    JOURNAL OF CLINICAL NEUROSCIENCE   46   64 - 67   2017.12

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    Amyotrophic lateral sclerosis/parkinsonism dementia complex (ALS/PDC) is an endemic disease observed in the Kii peninsula, Guam, and Papua. We report a case of a 76-year old man with ALS/PDC of the Kii peninsula of Japan (Kii ALS/PDC). The patient was born and grew up in the Kii peninsula. He moved out at age three, and developed symptoms 73 years later. He showed pyramidal sign, parkinsonian symptoms, and mildly impaired cognitive function. I-131-metaiodobenzylguanidine myocardial scintigraphy showed decreased cardiac sympathetic nerve function, and dopamine transporter single photon emission computed tomography imaging showed decreased I-123-N-omega-fluoropropy1-2 beta-carbomethoxy3 beta-(4-iodo phenyl) nortropane accumulation. Cerebral blood flow showed hypoperfusion. Positron emission tomography showed widespread tau deposition in his brain. This is a migration case of Kii ALS/PDC with the shortest stay in the endemic area and the longest delay to develop the disease, indicating a genetic factor for the disease development in a considerable degree. (C) 2017 Elsevier Ltd. All rights reserved.

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  • Normative data of dopaminergic neurotransmission functions in substantia nigra measured with MRI and PET: Neuromelanin, dopamine synthesis, dopamine transporters, and dopamine D-2 receptors Reviewed

    Ito Hiroshi, Kawaguchi Hiroshi, Kodaka Fumitoshi, Takuwa Hiroyuki, Ikoma Yoko, Shimada Hitoshi, Kimura Yasuyuki, Seki Chie, Kubo Hitoshi, Ishii Shiro, Takano Harumasa, Suhara Tetsuya

    NEUROIMAGE   158   12 - 17   2017.9

  • Increased Pet-Detectable Tau Pathologies in Late-Life Depression with Psychosis Reviewed

    Sho Moriguchi, Keisuke Takahata, Hitoshi Shimada, Yasuyuki Kimura, Manabu Kubota, Soichiro Kitamura, Tatsuya Ishii, Yuhei Takado, Kenji Tagai, Shinichiro Nakajima, Ryosuke Tarumi, Hajime Tabuchi, Masaru Mimura, Tetsuya Suhara, Makoto Higuchi

    BIOLOGICAL PSYCHIATRY   81 ( 10 )   S384 - S385   2017.5

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  • Delayed-Onset Psychosis following TBI is Associated with Tau Depositions in the Neocortex but Not with beta-Amyloid Depositions: A Pet Study with [11C] PBB3 and [11C]PiB Reviewed

    Keisuke Takahata, Yasuyuki Kimura, Hitoshi Shimada, Masanori Ichise, Hajime Tabuchi, Soichiro Kitamura, Manabu Kubota, Sho Moriguchi, Tatsuya Ishii, Fumitoshi Nina, Hironobu End, Yoko Morimoto, Michitaka Funayama, Matsumoto Onaya, Naruhiko Sahara, Satoshi Umeda, Masaru Mimura, Makoto Higuchi, Tetsuya Suhara

    BIOLOGICAL PSYCHIATRY   81 ( 10 )   S295 - S296   2017.5

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  • Association between Aβ and tau accumulations and their influence on clinical features in aging and Alzheimer's disease spectrum brains: A [11C]PBB3-PET study Reviewed

    Hitoshi Shimada, Soichiro Kitamura, Hitoshi Shinotoh, Hironobu Endo, Fumitoshi Niwa, Shigeki Hirano, Yasuyuki Kimura, Ming-Rong Zhang, Satoshi Kuwabara, Tetsuya Suhara, Makoto Higuchi

    Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring   6   11 - 20   2017

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    Introduction Amyloid-β (Aβ) and tau accumulations may occur independently and concurrently as exemplified by primary age-related tauopathy and Alzheimer's disease (AD), respectively. Interactions between Aβ and tau accumulations and their influence on clinical features, however, are still unclear. Methods Associations among clinical symptoms, gray-matter volume, regional tau, and Aβ deposition assessed by positron emission tomography with [11C]pyridinyl-butadienyl-benzothiazole 3 (PBB3) and [11C]Pittsburgh compound-B (PiB), were evaluated in 17 AD, 9 mild cognitive impairment due to AD, and 28 PiB(−)-cognitive healthy controls (HCs). Results High tau burden was associated with aging and low-level education in PiB(−)-HC and AD-spectrum groups, and with high Aβ burden and low-level education in all subjects. It was not Aβ but tau accumulation that showed significant associations with cognitive performance even in PiB(−)-HC. Discussion The present study indicated aging and low-level education after Aβ would be enhancers for tau pathology, associated with neurodegeneration and cognitive impairment in healthy and diseased elderly individuals.

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  • Impact of spillover from white matter by partial volume effect on quantification of amyloid deposition with [C-11]PiB PET Reviewed

    Keisuke Matsubara, Masanobu Ibaraki, Hitoshi Shimada, Yoko Ikoma, Tetsuya Suhara, Toshibumi Kinoshita, Hiroshi Itco

    NEUROIMAGE   143   316 - 324   2016.12

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    High non-specific uptake of [C-11]Pittsburgh compound B ([C-11]PiB) in white matter and signal spillover from white matter, due to partial volume effects, confound radioactivity measured in positron emission tomography (PET) with [C-11]PiB. We aimed to reveal the partial volume effect in absolute values of kinetic parameters for [C-11]PiB, in terms of spillover from white matter. Dynamic data acquired in [C-11]PiB PET scans with five healthy volunteers and eight patients with Alzheimer's disease were corrected with region-based and voxel-based partial volume corrections. Binding potential (BPND) was estimated using the two-tissue compartment model analysis with a plasma input function. Partial volume corrections significantly decreased cortical BPND values. The degree of decrease in healthy volunteers (-52.7 +/- 5.8%) was larger than that in Alzheimer's disease patients (-11.9 +/- 4.2%). The simulation demonstrated that white matter spillover signals due to the partial volume effect resulted in an overestimation of cortical BPND, with a greater degree of overestimation for lower BPND values. Thus, an overestimation due to partial volume effects is more severe in healthy volunteers than in Alzheimer's disease patients. Partial volume corrections may be useful for accurately quantifying A beta deposition in cortical regions. (C) 2016 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license.

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  • 学齢期の子ども達による子ども達用認知症教育パンフレット製作の試み

    石川 萌乃, 平野 成樹, 清水 啓介, 村山 紀子, 吉山 容正, 柏戸 孝一, 島田 斉, 古川 彰吾, 荒木 信之, 小島 一歩, 石川 愛, 篠遠 仁, 佐々木 剛, 富田 薫, 桑原 聡, 伊豫 雅臣

    臨床神経学   56 ( Suppl. )   S241 - S241   2016.12

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  • アルツハイマー病患者でのMMSE下位項目と脳血流の関連

    小島 一歩, 平野 成樹, たい 虹, 李 洪亮, 清水 啓介, 石川 愛, 古川 彰吾, 島田 斉, 柏戸 孝一, 吉山 容正, 堀越 琢郎, 宇野 隆, 桑原 聡

    臨床神経学   56 ( Suppl. )   S399 - S399   2016.12

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  • 認知症の人と孫との関係に関する疫学研究 千葉市認知症こども力プロジェクト

    清水 啓介, 平野 成樹, 村山 紀子, 石川 萌乃, 吉山 容正, 柏戸 孝一, 島田 斉, 古川 彰吾, 荒木 信之, 小島 一歩, 石川 愛, 篠遠 仁, 佐々木 剛, 富田 薫, 桑原 聡, 伊豫 雅臣

    臨床神経学   56 ( Suppl. )   S241 - S241   2016.12

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  • 糖尿病性認知症のアミロイド、タウPET

    羽生 春夫, 清水 聰一郎, 平尾 健太郎, 金高 秀和, 石井 賢二, 島田 斉, 樋口 真人, 須原 哲也

    核医学   53 ( Suppl. )   S277 - S277   2016.10

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  • 紀伊半島の筋萎縮性側索硬化症/パーキンソン認知症複合のタウイメージング

    篠遠 仁, 島田 斉, 小久保 康昌, 丹羽 文俊, 佐々木 良元, 森本 悟, 平野 成樹, 饗場 郁子, 葛原 茂樹, 樋口 真人, 須原 哲也

    核医学   53 ( Suppl. )   S286 - S286   2016.10

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  • PET measurement of brain acetylcholinesterase activities in cortex and subcortical areas Reviewed

    Hitoshi Shimada, Shigeki Hirano, Hitoshi Shinotoh, Toshiaki Irie, Tetsuya Suhara

    INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY   31 ( 8 )   952 - 953   2016.8

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  • イメージングバイオマーカーを用いた高齢者の精神神経疾患の評価 タウ・アミロイドPETを用いた老年期精神障害の背景病理に関する検討

    高畑 圭輔, 森口 翔, 田渕 肇, 島田 斉, 篠遠 仁, 木村 泰之, 北村 聡一郎, 三村 將, 樋口 真人, 須原 哲也

    精神神経学雑誌   ( 2016特別号 )   S287 - S287   2016.6

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  • Principal Component Analysis of Multimodal Neuromelanin MRI and Dopamine Transporter PET Data Provides a Specific Metric for the Nigral Dopaminergic Neuronal Density Reviewed

    Hiroshi Kawaguchi, Hitoshi Shimada, Fumitoshi Kodaka, Masayuki Suzuki, Hitoshi Shinotoh, Shigeki Hirano, Jeff Kershaw, Yuichi Inoue, Masaki Nakamura, Taeko Sasai, Mina Kobayashi, Tetsuya Suhara, Hiroshi Ito

    PLOS ONE   11 ( 3 )   e0151191   2016.3

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    The loss of dopaminergic (DA) neurons in the substantia nigra (SN) is a major pathophysiological feature of patients with Parkinson's disease (PD). As nigral DA neurons contain both neuromelanin (NM) and dopamine transporter (DAT), decreased intensities in both NM-sensitive MRI and DAT PET reflect decreased DA neuronal density. This study demonstrates that a more specific metric for the nigral DA neuronal density can be derived with multimodal MRI and PET. Participants were 11 clinically diagnosed PD patients and 10 age and gender matched healthy controls (HCs). Two quantities, the NM-related index (R-NM) and the binding potential of the radiotracer [F-18] FE-PE2I to DAT (BPND) in SN, were measured for each subject using MRI and PET, respectively. Principal component analysis (PCA) was applied to the multimodal data set to estimate principal components. One of the components, PCP, corresponds to a basis vector oriented in a direction where both BPND and R-NM increase. The ability of BPND, R-NM and PCP to discriminate between HC and PD groups was compared. Correlation analyses between the motor score of the unified Parkinson's disease rating scale and each metric were also performed. PCP, BPND and R-NM for PD patients were significantly lower than those for HCs (F = 16.26, P&lt;0.001; F = 6.05, P = 0.008; F = 7.31, P = 0.034, respectively). The differential diagnostic performance between the HC and PD groups as assessed by the area under the receiver-operating characteristic curve was best for PCP (0.94, 95% CI: 0.66-1.00). A significant negative correlation was found between the motor severity score and PCp (R = -0.70, P&lt;0.001) and R-NM (R = -0.52, P = 0.015), but not for BPND (R = -0.36, P = 0.110). PCA of multimodal NM-sensitive MRI and DAT PET data provides a metric for nigral DA neuronal density that will help illuminate the pathophysiology of PD in SN. Further studies are required to explore whether PCA is useful for other parkinsonian syndromes.

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  • A new method to quantify tau pathologies with C-11-PBB3 PET using reference tissue voxels extracted from brain cortical gray matter Reviewed

    Yasuyuki Kimura, Hironobu Endo, Masanori Ichise, Hitoshi Shimada, Chie Seki, Yoko Ikoma, Hitoshi Shinotoh, Makiko Yamada, Makoto Higuchi, Ming-Rong Zhang, Tetsuya Suhara

    EJNMMI RESEARCH   6 ( 1 )   24   2016.3

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    Background: Quantitative in vivo imaging of tau pathologies potentially improves diagnostic accuracy of neurodegenerative tauopathies and would facilitate evaluation of disease-modifying drugs targeting tau lesions in these diseases. Tau pathology can be quantified by reference tissue models without arterial blood sampling when reference tissue devoid of target binding sites is available. The cerebellar cortex has been used as a reference region in analyses of tau positron emission tomography (PET) data in Alzheimer's disease (AD). However, in a significant subset of tauopathies such as progressive supranuclear palsy and corticobasal degeneration, tau accumulation may occur in diverse brain regions including the cerebellar cortex. This hampers selection of a distinctive reference region lacking binding sites for a tau PET ligand. The purpose of this study was to develop a new method to quantify specific binding of a PET radioligand, C-11-PBB3, to tau deposits using reference voxels extracted from cortical gray matter, which have a low likelihood of containing tau accumulations.
    Methods: We reanalyzed C-11-PBB3 PET data of seven mild AD patients (ADs) and seven elderly healthy control subjects (HCs) acquired in a previous study. As a standard method, parametric images of binding potential (BPND*) were initially generated using reference tissue manually defined on the cerebellar cortex. We then constructed a frequency histogram of BPND* values in these parametric images and selected cortical gray matter voxels contained in a certain range of the histogram with a low likelihood of having C-11-PBB3 binding sites. Finally, these reference voxels were used for generating new BPND* parametric images.
    Results: Reference tissue voxels defined by the histogram analysis spread throughout the cortical gray matter of AD and HC brains. The BPND* values determined by our new method correlated very well with those estimated by the standard method (r(2) = 0.94), although the binding estimates by the current method were slightly higher by similar to 0.14 than those by the standard method.
    Conclusions: We developed and validated a new method enabling quantification of tau lesions that can accumulate in the cerebellum and other extensive brain areas. This method may be applicable to all tauopathy subtypes and various tau PET ligands besides C-11-PBB3.

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  • The Role of Tau PET Imaging in the Diagnosis of Dementia

    NIWA Fumitoshi, SHIMADA Hitoshi

    Medical Imaging Technology   34 ( 1 )   22 - 25   2016

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    On the clinical management of neurodegenerative dementia including Alzheimer's disease (AD), molecular imaging using positron emission topography (PET), which makes it possible to detect in vivo pathological modification in the brain, have been developed. While amyloid PET imaging implies an important role for diagnosis of AD, tau PET imaging also would be useful as a biomarker to diagnose tauopathies including non-AD dementia as well as to evaluate disease severity.

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  • アルツハイマー病での脳血流と高血圧の関連

    小島 一歩, 平野 成樹, たい 虹, 李 洪亮, 吉山 容正, 柏戸 孝一, 島田 斉, 古川 彰吾, 石川 愛, 清水 啓介, 堀越 琢郎, 宇野 隆, 桑原 聡

    臨床神経学   55 ( Suppl. )   S248 - S248   2015.12

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  • Dementia with Lewy bodies can be well-differentiated from Alzheimer's disease by measurement of brain acetylcholinesterase activity - A [<sup>11</sup>C]MP4A PET study

    H. Shimada, S. Hirano, H. Sinotoh, T. Ota, N. Tanaka, K. Sato, M. Yamada, K. Fukushi, T. Irie, M. R. Zhang, M. Higuchi, S. Kuwabara, T. Suhara

    International Journal of Geriatric Psychiatry   30 ( 11 )   1105 - 1113   2015.11

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    Copyright © 2015 John Wiley & Sons, Ltd. Objective To investigate the diagnostic performance of brain acetylcholinesterase (AChE) activity measurement using N-[11C]-methyl-4-piperidyl acetate (MP4A) and PET in patients with dementia with Lewy bodies (DLB) and Alzheimer's disease (AD). Methods Participants were 14 DLB patients, 25 AD patients and 18 age-matched healthy controls (HC). All subjects underwent PET scans and MP4A to measure regional brain AChE activity. We performed anatomical standardization of each brain image, and k3 values, an index of AChE activity, in each voxel were estimated by nonlinear least squares analysis. Volumes of interest (VOIs) were identified on parametric k3 images in frontal, temporal, parietal and occipital cortices, and in anterior and posterior cingulate gyri (ACG and PCG). In each VOI, the differential diagnostic performance between AD and DLB of k3 values was assessed by area under the curve (AUC) of the receiver-operating characteristic. Voxel-based statistical analyses were also performed. Results Mean cortical AChE activities in AD patients (-8.2% compared with normal mean) and DLB patients (-27.8%) were lower than HCs (p-<-0.05, p-<-0.001, respectively). There was a significant difference in mean cortical AChE activities between AD and DLB patients (p-<-0.001). All regional brain AChE activities of defined VOIs except ACG were able to well discriminate DLB from AD, and notably performance was the most significant in PCG (AUC-=-0.989, 95% CI: 0.965-1.000). Conclusions Brain cholinergic deficit is consistently prominent in DLB compared with AD. PET measurement of brain AChE activity may be useful for the differential diagnosis between DLB and AD.

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  • PET Quantification of Tau Pathology in Human Brain with C-11-PBB3 Reviewed

    Yasuyuki Kimura, Masanori Ichise, Hiroshi Ito, Hitoshi Shimada, Yoko Ikoma, Chie Seki, Harumasa Takano, Soichiro Kitamura, Hitoshi Shinotoh, Kazunori Kawamura, Ming-Rong Zhang, Naruhiko Sahara, Tetsuya Suhara, Makoto Higuchi

    JOURNAL OF NUCLEAR MEDICINE   56 ( 9 )   1359 - 1365   2015.9

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    Tau accumulation in the brain is a pathologic hallmark of Alzheimer disease and other tauopathies. Quantitative visualization of tau pathology in humans can be a powerful method as a diagnostic aid and for monitoring potential therapeutic interventions. We established methods of PET quantification of tau pathology with C-11-PBB3 (2-((1E,3E)-4-(6-(C-11-methylamino)pyridin-3-yl)buta-1,3-dienyl) benzo[d]thiazol-6-ol), considering its radiometabolite entering the brain. Methods: Seven Alzheimer disease patients and 7 healthy subjects underwent dynamic 11C-PBB3 PET scanning. Arterial blood was sampled to obtain the parent and metabolite input functions. Quantification of C-11-PBB3 binding was performed using dual-input models that take the brain metabolite activity into consideration, traditional single-input models without such considerations, and the reference tissue model (MRTMO) and standardized uptake value ratio (SUVR). The cerebellar cortex was used as the reference tissue for all methods. Results: The dual-input graphical models estimated binding parameter (BPND*) stably (similar to 0.36 in high-binding regions). The MRTMO BPND* matched the corresponding BPND* by the dual-input graphical model (r(2) = 1.00). SUVR minus 1 correlated well with MRTMO BPND* (r(2) &gt; 0.97). However, BPND by the single-input models did not correlate with BPND* by the dual-input graphical model (r(2) = 0.04). Conclusion: The dual-input graphical model BPND* is consistent with the reference tissue BPND* and SUVR-1, suggesting that these parameters can accurately quantify binding of C-11-PBB3 despite the entry of its radiometabolites into the brain.

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  • 11C-PBB3を用いたタウ病変のPET定量解析 Reviewed

    木村 泰之, 市瀬 正則, 伊藤 浩, 島田 斉, 生駒 洋子, 関 千江, 高野 晴成, 北村 聡一郎, 篠遠 仁, 須原 哲也, 樋口 真人

    核医学   52 ( 3 )   260 - 260   2015.9

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  • Reconstruction magnetic resonance neurography in chronic inflammatory demyelinating polyneuropathy. International journal

    Kazumoto Shibuya, Atsuhiko Sugiyama, Sho-ichi Ito, Sonoko Misawa, Yukari Sekiguchi, Satsuki Mitsuma, Yuta Iwai, Keisuke Watanabe, Hitoshi Shimada, Hiroshi Kawaguchi, Tetsuya Suhara, Hajime Yokota, Hiroshi Matsumoto, Satoshi Kuwabara

    Annals of neurology   77 ( 2 )   333 - 7   2015.2

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    To study distribution and patterns of nerve hypertrophy in chronic inflammatory demyelinating polyneuropathy (CIDP), magnetic resonance neurography with 3-dimensional reconstruction of short tau inversion recovery images was performed in 33 patients. This technique clearly showed longitudinal morphological changes from the cervical roots to the nerve trunks in the proximal arm. Nerve enlargement was detected in 88% of the patients. According to the clinical subtype of CIDP, typical CIDP patients showed symmetric and root-dominant hypertrophy, whereas Lewis-Sumner syndrome patients had multifocal fusiform hypertrophy in the nerve trunks. The patterns of nerve hypertrophy presumably reflect the different pathophysiology of each CIDP subtype.

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  • Amyloid beta Accumulation Assessed with C-11-Pittsburgh Compound B PET and Postmortem Neuropathology Reviewed

    Hiroyuki Hatsuta, Masaki Takao, Kenji Ishii, Kiichi Ishiwata, Yuko Saito, Kazutomi Kanemaru, Tomio Arai, Tetsuya Suhara, Hitoshi Shimada, Hitoshi Shinotoh, Akira Tamaoka, Shigeo Murayama

    CURRENT ALZHEIMER RESEARCH   12 ( 3 )   278 - 286   2015

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    C-11-Pittsburgh compound B (PiB) uptake in PET images is frequently used to analyze beta amyloid (A beta) deposition in living individuals, but its correlation with histologically determined A beta has not been examined. Six individuals with dementia underwent PiB-PET imaging, and their brains were analyzed neuropathologically (mean interval between imaging and death: 816 days; PiB positive: negative, 3: 3; male: female, 3: 3; mean age: 84.0 years). PiB uptake (reported as standardized uptake value ratio [SUVR]) was analyzed in 11 cortical regions and 10 subcortical grey matter areas and compared with the A beta load (% area [the percentage of total area positive for A beta] and number of neuritic plaques) seen with immunohistochemical staining with an anti-A beta 11-28 antibody. Two PiB-positive subjects had abundant neuritic plaques and were diagnosed with Alzheimer's disease (AD). SUVR and % area were strongly correlated in the cortical regions of these subjects (subject 1: r = 0.65, p = 0.03; subject 2: r = 0.80, p = 0.003). The other PiB-positive subject (subject 3) showed focal PiB uptake. In subject 3 and the 3 PiB-negative subjects (subjects 4-6), there was no correlation between regional SUVR and % area or neuritic plaques. PiB uptake was not correlated with A beta deposition in subcortical regions. High PiB positivity in the cerebral cortex suggests the presence of substantial A beta deposition and neuritic plaques associated with the pathologic changes of AD. Our results suggest that high cortical SUVR is a reliable marker of AD. Subcortical PiB positivity must be interpreted more carefully.

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  • [C-11]PBB3による脳内タウ病変の定量測定 Reviewed

    伊藤 浩, 島田 斉, 生駒 洋子, 関 千江, 木村 泰之, 高野 晴成, 篠遠 仁, 張 明栄, 須原 哲也, 樋口 真人

    核医学   51 ( 3 )   309 - 309   2014.9

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  • Quantitative Analysis of Amyloid Deposition in Alzheimer Disease Using PET and the Radiotracer C-11-AZD2184 Reviewed

    Hiroshi Ito, Hitoshi Shimada, Hitoshi Shinotoh, Harumasa Takano, Takeshi Sasaki, Tsuyoshi Nogami, Masayuki Suzuki, Tomohisa Nagashima, Keisuke Takahata, Chie Seki, Fumitoshi Kodaka, Yoko Eguchi, Hironobu Fujiwara, Yasuyuki Kimura, Shigeki Hirano, Yoko Ikoma, Makoto Higuchi, Kazunori Kawamura, Toshimitsu Fukumura, Eva Lindstrom Boo, Lars Farde, Tetsuya Suhara

    JOURNAL OF NUCLEAR MEDICINE   55 ( 6 )   932 - 938   2014.6

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    Characteristic neuropathologic changes in Alzheimer disease (AD) are amyloid-p deposits and neurofibrillary tangles. Recently, a new radioligand for amyloid senile plaques, C-11-labeled 5-(6-{[tertbutyl(dimethyl)sily]oxy}-1,3-benzothiazol-2-yl)pyridin-2-amine (C-11-AZD2184), was developed, and it was reported to show rapid brain uptake followed by rapid washout. In this study, C-11-AZD2184 binding in control subjects and AD patients was examined in more detail by compartment model analysis using a metabolite-corrected arterial input function. The accuracy of simplified quantitative methods using a reference brain region was also evaluated. Methods: After intravenous bolus injection of C-11-AZD2184, a dynamic PET scan was obtained for 90 min in 6 control subjects and 8 AD patients. To obtain the arterial input function, arterial blood sampling and high-performance liquid chromatography analysis were performed. Results: Time activity curves in all brain regions could be described using the standard 2-tissue-compartment model. The total distribution volume ratios to reference region (DVR) in cerebral cortical regions were significantly higher in AD patients than in control subjects. Although there was no conspicuous accumulation of radioactivity in white matter as compared with other amyloid radioligands, DVR values in the centrum semiovale were more than 1 for both control subjects and AD patients, suggesting binding to myelin. The standardized uptake value ratio calculated from integrated time activity curves in brain regions and the reference region was statistically in good agreement with DVR. Conclusion: Although the white matter binding of C-11-AZD2184 may have some effect on cortical measurement, it can be concluded that the kinetic behavior of C-11-AZD2184 is suitable for quantitative analysis. The standardized uptake value ratio can be used as a validated measure of C-11-AZD2184 binding in clinical examinations without arterial input function.

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  • Quantitative Analysis of Amyloid Deposition in Alzheimer Disease Using PET and the Radiotracer ¹¹C-AZD2184.

    Ito Hiroshi, Shimada Hitoshi, Shinotoh Hitoshi, Takano Harumasa, Sasaki Takeshi, Nogami Tsuyoshi, Suzuki Masayuki, Nagashima Tomohisa, Takahata Keisuke, Seki Chie, Kodaka Fumitoshi, Eguchi Yoko, Fujiwara Hironobu, Kimura Yasuyuki, Hirano Shigeki, Ikoma Yoko, Higuchi Makoto, Kawamura Kazunori, Fukumura Toshimitsu, Böö Éva Lindström, Farde Lars, Suhara Tetsuya

    Journal of nuclear medicine : official publication, Society of Nuclear Medicine   55 ( 6 )   932 - 8   2014.6

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    Characteristic neuropathologic changes in Alzheimer disease (AD) are amyloid-β deposits and neurofibrillary tangles. Recently, a new radioligand for amyloid senile plaques, (11)C-labeled 5-(6-{[tert-butyl(dimethyl)silyl]oxy}-1,3-benzothiazol-2-yl)pyridin-2-amine ((11)C-AZD2184), was developed, and it was reported to show rapid brain uptake followed by rapid washout. In this study, (11)C-AZD2184 binding in control subjects and AD patients was examined in more detail by compartment model analysis using a metabolite-corrected arterial input function. The accuracy of simplified quantitative methods using a reference brain region was also evaluated.After intravenous bolus injection of (11)C-AZD2184, a dynamic PET scan was obtained for 90 min in 6 control subjects and 8 AD patients. To obtain the arterial input function, arterial blood sampling and high-performance liquid chromatography analysis were performed.Time-activity curves in all brain regions could be described using the standard 2-tissue-compartment model. The total distribution volume ratios to reference region (DVR) in cerebral cortical regions were significantly higher in AD patients than in control subjects. Although there

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  • In vivo tau PET imaging using [11C]PBB3 in Alzheimer's disease and non-Alzheimer's disease tauopathies

    Suhara, Tetsuya, Shimada, Hitoshi, Shinotoh, Hitoshi, Hirano, Shigeki, Eguchi, Yoko, Takahata, Keisuke, Kimura, Yasuyuki, Yamada, Makiko, Ito, Hiroshi, Higuchi, Makoto

    JOURNAL OF NUCLEAR MEDICINE   55   72 - 78   2014.5

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  • Imaging of amyloid deposition in human brain using positron emission tomography and [F-18]FACT: comparison with [C-11] PIB Reviewed

    Hiroshi Ito, Hitoshi Shinotoh, Hitoshi Shimada, Michie Miyoshi, Kazuhiko Yanai, Nobuyuki Okamura, Harumasa Takano, Hidehiko Takahashi, Ryosuke Arakawa, Fumitoshi Kodaka, Maiko Ono, Yoko Eguchi, Makoto Higuchi, Toshimitsu Fukumura, Tetsuya Suhara

    EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING   41 ( 4 )   745 - 754   2014.4

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    Purpose The characteristic neuropathological changes in Alzheimer's disease (AD) are deposition of amyloid senile plaques and neurofibrillary tangles. The F-18-labeled amyloid tracer, [F-18]2-[(2-{(E)-2-[2-(dimethylamino)-1,3-thiazol-5-yl]vinyl}-1,3-benzoxazol-6-yl)oxy]-3-fluoropropan-1-ol (FACT), one of the benzoxazole derivatives, was recently developed. In the present study, deposition of amyloid senile plaques was measured by positron emission tomography (PET) with both [C-11]Pittsburgh compound B (PIB) and [F-18]FACT in the same subjects, and the regional uptakes of both radiotracers were directly compared.
    Methods Two PET scans, one of each with [C-11]PIB and [F-18]FACT, were performed sequentially on six normal control subjects, two mild cognitive impairment (MCI) patients, and six AD patients. The standardized uptake value ratio of brain regions to the cerebellum was calculated with partial volume correction using magnetic resonance (MR) images to remove the effects of white matter accumulation.
    Results No significant differences in the cerebral cortical uptake were observed between normal control subjects and AD patients in [F-18]FACT studies without partial volume correction, while significant differences were observed in [C-11]PIB. After partial volume correction, the cerebral cortical uptake was significantly larger in AD patients than in normal control subjects for [F-18]FACT studies as well as [C-11]PIB. Relatively lower uptakes of [C-11]PIB in distribution were observed in the medial side of the temporal cortex and in the occipital cortex as compared with [F-18]FACT. Relatively higher uptake of [C-11]PIB in distribution was observed in the frontal and parietal cortices.
    Conclusion Since [F-18]FACT might bind more preferentially to dense-cored amyloid deposition, regional differences in cerebral cortical uptake between [C-11]PIB and [F-18]FACT might be due to differences in regional distribution between diffuse and dense-cored amyloid plaque shown in the autoradiographic and histochemical assays of postmortem AD brain sections.

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  • Apathy correlates with prefrontal amyloid β deposition in Alzheimer's disease. International journal

    Takaaki Mori, Hitoshi Shimada, Hitoshi Shinotoh, Shigeki Hirano, Yoko Eguchi, Makiko Yamada, Ryuji Fukuhara, Satoshi Tanimukai, Ming-Rong Zhang, Satoshi Kuwabara, Shu-Ichi Ueno, Tetsuya Suhara

    Journal of neurology, neurosurgery, and psychiatry   85 ( 4 )   449 - 55   2014.4

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    OBJECTIVE: Neuropsychiatric symptoms affect many patients with Alzheimer's disease (AD). ((11)C)Pittsburgh Compound-B (PIB) positron emission tomography (PET) has enabled the in vivo visualisation of brain amyloid-β (Aβ) deposition. This study exploratively investigated the correlation between brain Aβ deposition measured by ((11)C)PIB PET and neuropsychiatric symptoms in AD. METHODS: Participants were 28 patients (15 women, 13 men) with PIB-positive AD. Clinical assessments included Mini-Mental State Examination, Clinical Dementia Rating scale, neuropsychiatry inventory (NPI) and frontal assessment battery. All patients underwent three-dimensional T1-weighted MRI and ((11)C)PIB PET. The distribution volume ratio (DVR), an index of ((11)C)PIB retention and, thus, Aβ deposition, was estimated voxel by voxel from ((11)C)PIB PET data with partial volume correction. Voxel-based correlation analysis was performed to assess the relationships between DVR and each NPI subscale. Additionally, voxel-based analysis of covariance (ANCOVA) of the DVR images was performed between Patients with AD with and without each neuropsychiatric symptom. Voxel-based morphometry analysis of MRI was also performed. RESULTS: Apathy subscale was correlated with ((11)C)PIB retention in the bilateral frontal and right anterior cingulate. ((11)C)PIB retention was greater in the bilateral frontal cortex of patients with AD with apathy than those of without apathy. Overlapping areas between the two analyses were the bilateral orbitofrontal gyrus and left superior frontal gyrus. Other NPI subscales were not correlated with ((11)C)PIB retention. Voxel-based morphometry analysis of MRI showed no significant cluster of correlation between grey matter volume and NPI subscales. CONCLUSIONS: This study revealed that prefrontal Aβ deposition correlates with apathy.

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  • Norepinephrine transporter occupancy by nortriptyline in patients with depression: a positron emission tomography study with (S,S)-[¹⁸F]FMeNER-D₂. International journal

    Harumasa Takano, Ryosuke Arakawa, Tsuyoshi Nogami, Masayuki Suzuki, Tomohisa Nagashima, Hironobu Fujiwara, Yasuyuki Kimura, Fumitoshi Kodaka, Keisuke Takahata, Hitoshi Shimada, Yoshitaka Murakami, Amane Tateno, Makiko Yamada, Hiroshi Ito, Kazunori Kawamura, Ming-Rong Zhang, Hidehiko Takahashi, Motoichiro Kato, Yoshiro Okubo, Tetsuya Suhara

    The international journal of neuropsychopharmacology   17 ( 4 )   553 - 60   2014.4

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    Norepinephrine transporter (NET) plays important roles in the treatment of various neuropsychiatric disorders, such as depression and attention deficit hyperactivity disorder (ADHD). Nortriptyline is a NET-selective tricyclic antidepressant (TCAs) that has been widely used for the treatment of depression. Previous positron emission tomography (PET) studies have reported over 80% serotonin transporter occupancy with clinical doses of selective serotonin reuptake inhibitors (SSRIs), but there has been no report of NET occupancy in patients treated with relatively NET-selective antidepressants. In the present study, we used PET and (S,S)-[18¹⁸F]FMeNER-D₂ to investigate NET occupancies in the thalamus in 10 patients with major depressive disorder taking various doses of nortriptyline, who were considered to be responders to the treatment. Reference data for the calculation of occupancy were derived from age-matched healthy controls. The result showed approximately 50-70% NET occupancies in the brain as a result of the administration of 75-200 mg/d of nortriptyline. The estimated effective dose (ED₅₀) and concentration (EC₅₀) required to induce 50% occupancy was 65.9 mg/d and 79.8 ng/ml, respectively. Furthermore, as the minimum therapeutic level of plasma nortriptyline for the treatment of depression has been reported to be 70 ng/ml, our data indicate that this plasma nortriptyline concentration corresponds to approximately 50% NET occupancy measured with PET, suggesting that more than 50% of central NET occupancy would be appropriate for the nortriptyline treatment of patients with depression.

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  • Biodistribution and radiation dosimetry in humans of [C-11]FLB 457, a positron emission tomography ligand for the extrastriatal dopamine D-2 receptor Reviewed

    Yasuyuki Kimura, Hiroshi Ito, Takahiro Shiraishi, Hironobu Fujiwara, Fumitoshi Kodaka, Harumasa Takano, Hitoshi Shimada, Iwao Kanno, Tetsuya Suhara

    NUCLEAR MEDICINE AND BIOLOGY   41 ( 1 )   102 - 105   2014.1

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    Purpose: [C-11]FLB 457, a radioligand with very high affinity and selectivity for dopamine D-2/3 receptors, is used to measure receptor binding in extrastriatal regions showing low density of the receptors. The purpose of this study was to estimate the whole-body biodistribution of radioactivity and the radiation absorbed doses to organs after intravenous injection of [C-11]FLB 457 in healthy human subjects.
    Methods: Whole-body images were acquired for 2 h after an injection of [C-11]FLB 457 in six healthy humans. Radiation absorbed doses were estimated by the MIRD scheme implemented in OLINDA/EXM 1.1 software.
    Results: Organs with the longest residence time were the liver, lungs, and brain. The organs with the highest radiation doses were the kidneys, liver, and pancreas. The effective dose delivered by [C-11]FLB 457 is 5.9 mu Sv/MBq, similar to those of other C-11-labeled tracers.
    Conclusions: This effective dose would allow multiple scans in the same individual based on prevailing maximum recommended-dose guidelines in the USA and Europe. (C) 2014 Elsevier Inc. All rights reserved.

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  • Tau PET Imaging of Neurocognitive Disorders Using Newly Developed Tau Ligand [11C]PBB3 Reviewed

    Suhara Tetsuya, Shimada Hitoshi, Maruyama Masahiro, Shinotoh Hitoshi, Ji Bin, Maeda Jun, Takano Harumasa, Sahara Naruhiko, Zhang Ming-Rong, Ito Hiroshi, Higuchi Makoto

    NEUROPSYCHOPHARMACOLOGY   38   S159 - S160   2013.12

  • パーキンソン病患者における視床下核脳深部刺激療法による脳血流変化

    古川 彰吾, 平野 成樹, 内山 智之, 樋口 佳則, 山本 達也, 朝比奈 正人, 山中 義崇, 宇治 百合子, 阿部 翠, 風間 俊基, 島田 斉, 篠遠 仁, 桑原 聡

    臨床神経学   53 ( 12 )   1434 - 1434   2013.12

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  • PiB PET集積とアミロイドβ免疫染色とチオフラビンS染色の剖検例における検討

    初田 裕幸, 高尾 昌樹, 新井 冨生, 須原 哲也, 島田 斉, 篠遠 仁, 石渡 喜一, 石井 賢二, 村山 繁雄

    Dementia Japan   27 ( 4 )   505 - 505   2013.10

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  • Imaging of Tau Pathology in a Tauopathy Mouse Model and in Alzheimer Patients Compared to Normal Controls Reviewed

    Masahiro Maruyama, Hitoshi Shimada, Tetsuya Suhara, Hitoshi Shinotoh, Bin Ji, Jun Maeda, Ming-Rong Zhang, John Q. Trojanowski, Virginia M. -Y. Lee, Maiko Ono, Kazuto Masamoto, Harumasa Takano, Naruhiko Sahara, Nobuhisa Iwata, Nobuyuki Okamura, Shozo Furumoto, Yukitsuka Kudo, Qing Chang, Takaomi C. Saido, Akihiko Takashima, Jada Lewis, Ming-Kuei Jang, Ichio Aoki, Hiroshi Ito, Makoto Higuchi

    NEURON   79 ( 6 )   1094 - 1108   2013.9

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    Accumulation of intracellular tau fibrils has been the focus of research on the mechanisms of neurodegeneration in Alzheimer's disease (AD) and related tauopathies. Here, we have developed a class of tau ligands, phenyl/pyridinyl-butadienyl-benzothiazoles/benzothiazoliums (PBBs), for visualizing diverse tau inclusions in brains of living patients with AD or non-AD tauopathies and animal models of these disorders. In vivo optical and positron emission tomographic (PET) imaging of a transgenic mouse model demonstrated sensitive detection of tau inclusions by PBBs. A pyridinated PBB, [C-11]PBB3, was next applied in a clinical PET study, and its robust signal in the AD hippocampus wherein tau pathology is enriched contrasted strikingly with that of a senile plaque radioligand, [C-11]Pittsburgh Compound-B ([C-11]PIB. [C-11]PBB3-PET data were also consistent with the spreading of tau pathology with AD progression. Furthermore, increased [C-11]PBB3 signals were found in a corticobasal syndrome patient negative for [C-11]PIB-PET.

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  • [11C]PBB3 PETによるタウイメージング

    島田 斉, 篠遠 仁, 平野 成樹, 江口 洋子, 木村 泰之, 高畑 圭輔, 小高 文聰, 高野 晴成, 伊藤 浩, 樋口 誠人, 須原 哲也

    核医学   50 ( 3 )   S181 - S181   2013.9

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  • [C-11]AZD2184による脳内アミロイド蓄積の定量測定

    伊藤 浩, 島田 斉, 篠遠 仁, 高野 晴成, 小高 文聰, 木村 泰之, 生駒 洋子, 関 千江, 福村 利光, 須原 哲也

    核医学   50 ( 3 )   S180 - S180   2013.9

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  • Occupancy of serotonin and norepinephrine transporter by milnacipran in patients with major depressive disorder: a positron emission tomography study with [C-11]DASB and (S,S)-[F-18]FMeNER-D-2 Reviewed

    Tsuyoshi Nogami, Harumasa Takano, Ryosuke Arakawa, Tetsuya Ichimiya, Hironobu Fujiwara, Yasuyuki Kimura, Fumitoshi Kodaka, Takeshi Sasaki, Keisuke Takahata, Masayuki Suzuki, Tomohisa Nagashima, Takaaki Mori, Hitoshi Shimada, Hajime Fukuda, Mizuho Sekine, Amane Tateno, Hidehiko Takahashi, Hiroshi Ito, Yoshiro Okubo, Tetsuya Suhara

    INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY   16 ( 5 )   937 - 943   2013.6

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    Antidepressants used for treatment of depression exert their efficacy by blocking reuptake at serotonin transporters (5-HTT) and/or norepinephrine transporters (NET). Recent studies suggest that serotonin and norepinephrine reuptake inhibitors that block both 5-HTT and NET have better tolerability than tricyclic antidepressants and may have higher efficacy compared to selective serotonin reuptake inhibitors. Previous positron emission tomography (PET) studies have reported &gt;80% 5-HTT occupancy with clinical doses of antidepressants, but there has been no report of NET occupancy in patients treated with antidepressants. In the present study, we investigated both 5-HTT and NET occupancies by PET using radioligands [C-11]DASB and (S,S)-[F-18]FMeNER-D-2, in six patients, each with major depressive disorder (MDD), using various doses of milnacipran. Our data show that mean 5-HTT occupancy in the thalamus was 33.0% at 50 mg, 38.6% at 100 mg, 60.0% at 150 mg and 61.5% at 200 mg. Mean NET occupancy in the thalamus was 25.3% at 25 mg, 40.0% at 100 mg, 47.3% at 125 mg and 49.9% at 200 mg. Estimated ED50 was 122.5 mg with the dose for 5-HTT and 149.9 mg for NET. Both 5-HTT and NET occupancies were observed in a dose-dependent manner. Both 5-HTT and NET occupancies were about 40% by milnacipran at 100 mg, the dose most commonly administered to MDD patients.

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  • Occupancy of serotonin and norepinephrine transporter by milnacipran in patients with major depressive disorder: a positron emission tomography study with [(11)C]DASB and (S,S)-[(18)F]FMeNER-D(2).

    Nogami Tsuyoshi, Takano Harumasa, Arakawa Ryosuke, Ichimiya Tetsuya, Fujiwara Hironobu, Kimura Yasuyuki, Kodaka Fumitoshi, Sasaki Takeshi, Takahata Keisuke, Suzuki Masayuki, Nagashima Tomohisa, Mori Takaaki, Shimada Hitoshi, Fukuda Hajime, Sekine Mizuho, Tateno Amane, Takahashi Hidehiko, Ito Hiroshi, Okubo Yoshiro, Suhara Tetsuya

    The international journal of neuropsychopharmacology   16 ( 5 )   937 - 43   2013.6

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    Antidepressants used for treatment of depression exert their efficacy by blocking reuptake at serotonin transporters (5-HTT) and/or norepinephrine transporters (NET). Recent studies suggest that serotonin and norepinephrine reuptake inhibitors that block both 5-HTT and NET have better tolerability than tricyclic antidepressants and may have higher efficacy compared to selective serotonin reuptake inhibitors. Previous positron emission tomography (PET) studies have reported &gt;80% 5-HTT occupancy with clinical doses of antidepressants, but there has been no report of NET occupancy in patients treated with antidepressants. In the present study, we investigated both 5-HTT and NET occupancies by PET using radioligands [(11)C]DASB and (S,S)-[(18)F]FMeNER-D(2), in six patients, each with major depressive disorder (MDD), using various doses of milnacipran. Our data show that mean 5-HTT occupancy in the thalamus was 33.0% at 50 mg, 38.6% at 100 mg, 60.0% at 150 mg and 61.5% at 200 mg. Mean NET occupancy in the thalamus was 25.3% at 25 mg, 40.0% at 100 mg, 47.3% at 125 mg and 49.9% at 200 mg. Estimated ED(50) was 122.5 mg with the dose for 5-HTT and 149.9 mg for NET. Both 5-HTT and NET occupa

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  • β-Amyloid in Lewy body disease is related to Alzheimer's disease-like atrophy. International journal

    Hitoshi Shimada, Hitoshi Shinotoh, Shigeki Hirano, Michie Miyoshi, Koichi Sato, Noriko Tanaka, Tsuneyoshi Ota, Kiyoshi Fukushi, Toshiaki Irie, Hiroshi Ito, Makoto Higuchi, Satoshi Kuwabara, Tetsuya Suhara

    Movement disorders : official journal of the Movement Disorder Society   28 ( 2 )   169 - 75   2013.2

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    The aim of this study was to investigate whether amyloid deposition is associated with Alzheimer's disease (AD)-like cortical atrophy in Lewy body (LB) disease (LBD). Participants included 15 LBD with dementia patients (8 with dementia with Lewy bodies [DLB] and 7 with Parkinson's disease [PD] with dementia [PDD]), 13 AD patients, and 17 healthy controls. Age, gender, and Mini-Mental State Examination scores were matched between patient groups. All subjects underwent PET scans with [(11)C]Pittsburgh Compound B to measure brain amyloid deposition as well as three-dimensional T1-weighted MRI. Gray-matter volumes (GMVs) were estimated by voxel-based morphometry. Volumes-of-interest analyses were also performed. Forty percent of the 15 DLB/PDD patients were amyloid positive, whereas all AD patients and none of the healthy controls were amyloid positive. Amyloid-positive DLB/PDD and AD patients showed very similar patterns of cortical atrophy in the parahippocampal area and lateral temporal and parietal cortices, with 95.2% of cortical atrophy distribution being overlapped. In contrast, amyloid-negative DLB/PDD patients had no significant cortical atrophy. Compared to healthy controls, parahippocampal GMVs were reduced by 26% in both the amyloid-positive DLB/PDD and AD groups and by 10% in the amyloid-negative DLB/PDD group. The results suggest that amyloid deposition is associated with AD-like atrophy in DLB/PDD patients. Early intervention against amyloid may prevent or delay AD-like atrophy in DLB/PDD patients with amyloid deposition.

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  • 精神・神経疾患治療薬の脳内標的部位のPETイメージング

    森口 翔, 島田 斉, 須原 哲也

    ファルマシア   49 ( 7 )   650 - 654   2013

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    DOI: 10.14894/faruawpsj.49.7_650

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  • Noninvasive k3 estimation method for slow dissociation PET ligands: Application to [11C] Pittsburgh compound B Reviewed

    Koichi Sato, Kiyoshi Fukushi, Hitoshi Shinotoh, Hitoshi Shimada, Shigeki Hirano, Noriko Tanaka, Tetsuya Suhara, Toshiaki Irie, Hiroshi Ito

    EJNMMI Research   3 ( 1 )   1 - 10   2013

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    Background: Recently, we reported an information density theory and an analysis of three-parameter plus shorter scan than conventional method (3P+) for the amyloid-binding ligand [11C]Pittsburgh compound B (PIB) as an example of a non-highly reversible positron emission tomography (PET) ligand. This article describes an extension of 3P + analysis to noninvasive '3P++' analysis (3P + plus use of a reference tissue for input function). Methods: In 3P++ analysis for [11C]PIB, the cerebellum was used as a reference tissue (negligible specific binding). Fifteen healthy subjects (NC) and fifteen Alzheimer's disease (AD) patients participated. The k3 (index of receptor density) values were estimated with 40-min PET data and three-parameter reference tissue model and were compared with that in 40-min 3P + analysis as well as standard 90-min four-parameter (4P) analysis with arterial input function. Simulation studies were performed to explain k3 biases observed in 3P++ analysis. Results: Good model fits of 40-min PET data were observed in both reference and target regions-of-interest (ROIs). High linear intra-subject (inter-15 ROI) correlations of k3 between 3P++ (Y-axis) and 3P + (X-axis) analyses were shown in one NC (r2 = 0.972 and slope = 0.845) and in one AD (r2 = 0.982, slope = 0.655), whereas inter-subject k3 correlations in a target region (left lateral temporal cortex) from 30 subjects (15 NC + 15 AD) were somewhat lower (r2 = 0.739 and slope = 0.461). Similar results were shown between 3P++ and 4P analyses: r2 = 0.953 for intra-subject k3 in NC, r2 = 0.907 for that in AD and r2 = 0.711 for inter-30 subject k3. Simulation studies showed that such lower inter-subject k3 correlations and significant negative k3 biases were not due to unstableness of 3P++ analysis but rather to inter-subject variation of both k2 (index of brain-to-blood transport) and k3 (not completely negligible) in the reference region. Conclusions: In [11C]PIB, the applicability of 3P++ analysis may be restricted to intra-subject comparison such as follow-up studies. The 3P++ method itself is thought to be robust and may be more applicable to other non-highly reversible PET ligands with ideal reference tissue. © 2013 Sato et al.

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  • Human Brain Imaging of Dopamine D&lt;inf&gt;1&lt;/inf&gt; Receptors Reviewed

    Hironobu Fujiwara, Hidehiko Takahashi, Hitoshi Shimada, Yoshiro Okubo, Tetsuya Suhara

    Imaging of the Human Brain in Health and Disease   187 - 202   2013

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    Recent functional imaging studies with neuropsychological measures suggest that several brain regions, which are related to dopamine (DA) neurotransmission, would be included among candidates of the major neural underpinnings of affective and cognitive functions such as pleasure and reward processing. Furthermore, evidence suggests the association of the pathophysiologies of neuropsychiatric illnesses such as schizophrenia and Parkinson's disease with the dysregulation of DA-related neurotransmission in these brain regions. Positron emission tomography (PET) is a non-invasive in-vivo imaging tool for measuring DA neurotransmission. We hereby review the evidence of human D1R function, focusing on its associations with cognitive functions including working memory, emotional processing and decision-making, as well as the pathologies of psychiatric illnesses, while introducing our D1R PET imaging studies. Although D1R dysfunction would not always be regarded as a direct cause of the disorders, that is to say, it would not be disease-specific, it might be related to the pathophysiologies by influencing cognitive functions of the individuals. In this sense, the evidence in D1R dysfunction might provide a new insight into the mechanisms of the symptoms of neuropsychiatric disorders and lead to the development of new ways of their dimensional classifications. © 2014 Elsevier Inc. All rights reserved.

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  • 10年以上の純粋自律神経不全の経過後に認知症とパーキンソン症状を呈した3例の臨床的解析

    朝比奈 正人, 平野 成樹, 山中 義崇, 島田 斉, 藤沼 克好, 片桐 明, Anupama Poudel, 岡 尚省, 桑原 聡

    臨床神経学   52 ( 12 )   1423 - 1423   2012.12

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  • Striatal and extrastriatal dopamine D₂ receptor occupancy by the partial agonist antipsychotic drug aripiprazole in the human brain: a positron emission tomography study with [¹¹C]raclopride and [¹¹C]FLB457.

    Takahata Keisuke, Ito Hiroshi, Takano Harumasa, Arakawa Ryosuke, Fujiwara Hironobu, Kimura Yasuyuki, Kodaka Fumitoshi, Sasaki Takeshi, Nogami Tsuyoshi, Suzuki Masayuki, Nagashima Tomohisa, Shimada Hitoshi, Kato Motoichiro, Mimura Masaru, Suhara Tetsuya

    Psychopharmacology   222 ( 1 )   165 - 72   2012.7

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    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 D₂ 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 D₂ receptors and the minimal risk of extrapyramidal side effects. Previous positron emission tomography (PET) studies using high-affinity radioligands for dopamine D₂ receptors have reported inconsistent results regarding regional differences of dopamine D₂ receptor occupancy by aripiprazole.To test the hypothesis of preferential binding to extrastriatal dopamine D₂ receptors by aripiprazole, we investigated its regional dopamine D₂ receptor occupancies in healthy young subjects.Using PET and two radioligands with different affinities for dopamine D₂ receptors, [¹¹C]raclopride and [¹¹C]FLB457, striatal and extrastriatal dopamine D₂ receptor bindings at baseline and after oral administration of 6 mg aripiprazole were measured in 11 male healthy

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  • 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 Reviewed

    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   222 ( 1 )   165 - 172   2012.7

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    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.

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  • Molecular imaging of dementia Reviewed

    Takaaki Mori, Jun Maeda, Hitoshi Shimada, Makoto Higuchi, Hitoshi Shinotoh, Shu-ichi Ueno, Tetsuya Suhara

    PSYCHOGERIATRICS   12 ( 2 )   106 - 114   2012.6

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    Diagnosis and treatment strategies for dementia are based on the sensitive and specific detection of the incipient neuropathological characteristics, combined with emerging treatments that counteract molecular processes in its pathogenesis. Positron emission tomography (PET) is used for diverse clinical and basic studies on dementia with a wide range of radiotracers. Approaches to visualize amyloid deposition in human brains non-invasively with PET depend on imaging agents reacting with amyloid fibrils. The most widely used tracer is [11C]-6-OH-BTA-1, also known as Pittsburgh Compound-B, which has a high affinity to amyloid beta peptide (A beta) aggregates. Some 18F-labeled amyloid ligands with a longer radioactive half-life have also been developed for broader clinical applications. In addition, there have been demonstrated advantages of tracers with high specific radioactivity in the sensitive detection of amyloid, which have indicated the significance of A beta-N3-pyroglutamate as a new diagnostic and therapeutic target. Furthermore, beneficial outcomes of A beta and tau immunization in humans and mouse models have highlighted crucial roles of immunocompetent glia in the protection of neurons against amyloid toxicities. The utility of PET with a radioligand for translocator protein as a biomarker for tau-triggered toxicity, and as a complement to amyloid and tau imaging for diagnostic assessment of tauopathies with and without A beta pathologies, has also been demonstrated. Meanwhile, brain cholinergic function can be estimated by measuring acetylcholinesterase activity in the brain with PET and radiolabeled acetylcholine analogues. It has been reported that patients with early Parkinson's disease exhibit a reduction in acetylcholinesterase activity in the cerebral cortex, and this decline is more profound in patients with Parkinson's disease with dementia and dementia with Lewy bodies than in patients with Parkinson's disease without dementia. The Alzheimer's Disease Neuroimaging Initiative was a multicentre research project conducted over 6 years that studied changes in cognition, brain structure, and biomarkers in healthy elderly controls and subjects with mild cognitive impairment and Alzheimer's disease. An international workgroup of the National Institute on Aging-Alzheimer's Association has suggested that Alzheimer's disease would be optimally treated before significant cognitive impairment, defined as a presymptomatic or preclinical stage. Therefore, PET will be of technical importance for both clinical and basic research aimed at prodromal pathologies of Alzheimer's disease.

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  • Levy小体型認知症はPETによる脳アセチルコリンエステラーゼの測定によってアルツハイマー病から明確に鑑別できる(Dementia with Lewy bodies can be well-differentiated from Alzheimer's disease by measurement of brain acetylcholinesterase activity by PET)

    島田 斉, 平野 成樹, 篠遠 仁, 佐藤 康一, 田中 典子, 伊藤 浩, 須原 哲也, 福士 清, 入江 俊章, 黄田 常嘉, 朝比奈 正人, 桑原 聡, 青墳 章代

    千葉医学雑誌   88 ( 1 )   59 - 60   2012.2

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  • Lewy小体型痴呆はPETによる脳内アセチルコリンエステラーゼ活性測定により、アルツハイマー病との鑑別に有用である(Dementia with Lewy bodies can be well-differentiated from Alzheimer's disease by measurement of brain acetylcholinesterase activity by PET)

    島田 斉, 平野 成樹, 篠遠 仁, 佐藤 康一, 田中 典子, 黄田 常嘉, 朝比奈 正人, 青墳 章代, 伊藤 浩, 福士 清, 桑原 聡, 入江 俊章, 須原 哲也

    臨床神経学   51 ( 12 )   1220 - 1220   2011.12

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  • 11C-Pittsburg Compound B(PIB)PET集積と、病理学的アミロイドβ沈着の、解剖学的部位別検討 6剖検例における検討

    初田 裕幸, 石井 賢二, 高尾 昌樹, 齊藤 祐子, 新井 冨生, 須原 哲也, 島田 斉, 篠遠 仁, 村山 繁雄

    Dementia Japan   25 ( 3 )   340 - 340   2011.10

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  • [11C]AZD2184 PETによるアミロイドイメージング

    島田 斉, 篠遠 仁, 平野 成樹, 森 崇明, 江口 洋子, 田中 典子, 佐藤 康一, 小高 文聰, 藤原 広臨, 木村 泰之, 桑原 聡, 高野 晴成, 伊藤 浩, 須原 哲也

    Dementia Japan   25 ( 3 )   336 - 336   2011.10

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  • Relation between Presynaptic and Postsynaptic Dopaminergic Functions Measured by Positron Emission Tomography: Implication of Dopaminergic Tone Reviewed

    Hiroshi Ito, Fumitoshi Kodaka, Hidehiko Takahashi, Harumasa Takano, Ryosuke Arakawa, Hitoshi Shimada, Tetsuya Suhara

    JOURNAL OF NEUROSCIENCE   31 ( 21 )   7886 - 7890   2011.5

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    Both presynaptic and postsynaptic dopaminergic functions can be estimated by positron emission tomography (PET). While both presynaptic and postsynaptic dopaminergic functions would be regulated by corresponding genes and related to personality traits, the relation between presynaptic and postsynaptic functions in terms of interindividual variation has hardly been investigated. In the present study, both striatal dopamine D(2) receptor binding and endogenous dopamine synthesis rate were measured in the same healthy subjects using PET with [(11)C]raclopride and L-[beta-(11)C]DOPA, respectively, and these two parameters were compared. Two PET studies with [(11)C] raclopride and L-[beta-(11)C] DOPA were performed sequentially at rest condition on 14 healthy men. For [(11)C] raclopride PET, the binding potential was calculated by the reference tissue model method. For L-[beta-(11)C]DOPAPET, the endogenous dopamine synthesis rate was estimated by graphical analysis. A significant negative correlation was observed between the binding potential of dopamine D(2) receptors and endogenous dopamine synthesis rate (r = -0.66, p &lt; 0.05). Although the interindividual variation of binding potential of [(11)C] raclopride would be due to both the interindividual difference in the receptor density and that in the concentration of endogenous dopamine in the synaptic cleft, the negative correlation between parameters for both presynaptic and postsynaptic functions might indicate a compensative relation between the two functions.

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  • Central nervous system drug evaluation using positron emission tomography.

    Sekine Mizuho, Maeda Jun, Shimada Hitoshi, Nogami Tsuyoshi, Arakawa Ryosuke, Takano Harumasa, Higuchi Makoto, Ito Hiroshi, Okubo Yoshiro, Suhara Tetsuya

    Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology   9 ( 1 )   9 - 16   2011.4

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    In conventional pharmacological research in the field of mental disorders, pharmacological effect and dose have been estimated by ethological approach and in vitro data of affinity to the site of action. In addition, the frequency of administration has been estimated from drug kinetics in blood. However, there is a problem regarding an objective index of drug effects in the living body. Furthermore, the possibility that the concentration of drug in blood does not necessarily reflect the drug kinetics in target organs has been pointed out. Positron emission tomography (PET) techniques have made progress for more than 20 years, and made it possible to measure the distribution and kinetics of small molecule components in living brain. In this article, we focused on rational drug dosing using receptor occupancy and proof-of-concept of drugs in the drug development process using PET.

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  • [11C]PIB PETの定量解析 新規定量解析法(TPESS法)による経時的変化の検討

    三好 美智恵, 篠遠 仁, 島田 斉, 平野 成樹, 佐藤 康一, 田中 典子, 黄田 常嘉, 福士 清, 入江 俊章, 伊藤 浩, 松本 昌泰, 須原 哲也

    臨床神経学   50 ( 12 )   1229 - 1229   2010.12

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  • [11C]PIB PETの定量解析 新規定量解析法(TPESS法)によるParametric Imaging

    島田 斉, 福士 清, 篠遠 仁, 佐藤 康一, 田中 典子, 三好 美智恵, 平野 成樹, 黄田 常嘉, 長縄 美香, 伊藤 浩, 桑原 聡, 入江 俊章, 須原 哲也

    臨床神経学   50 ( 12 )   1229 - 1229   2010.12

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  • 咽頭・頸部・上腕型ギラン・バレー症候群(PCB-GBS)に体位性頻脈症候群(POTS)を合併した47歳女性例

    藤沼 好克, 朝比奈 正人, 島田 斉, 山中 義崇, 桑原 聡

    日本自律神経学会総会プログラム・抄録集   63回   173 - 173   2010.10

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  • アミロイド沈着は認知症を伴うレヴィ小体病の海馬傍回萎縮を促進する

    島田 斉, 篠遠 仁, 三好 美智恵, 平野 成樹, 佐藤 康一, 田中 典子, 黄田 常嘉, 桑原 聡, 福士 清, 入江 俊章, 伊藤 浩, 須原 哲也

    Dementia Japan   24 ( 3 )   320 - 320   2010.9

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  • 時間短縮、無採血によるPIB-PET k3の測定

    田中 典子, 佐藤 康一, 福士 清, 篠遠 仁, 平野 成樹, 島田 斉, 三好 美智恵, 黄田 常嘉, 伊藤 浩, 須原 哲也, 入江 俊章

    核医学   47 ( 3 )   414 - 414   2010.9

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  • レヴィ小体病における脳内アセチルコリンエステラーゼ活性測定(Mapping of brain acetylcholinesterase alterations in Lewy body disease by PET)

    島田 斉, 平野 成樹, 篠遠 仁, 青墳 章代, 佐藤 康一, 田中 典子, 黄田 常嘉, 朝比奈 正人, 福士 清, 入江 俊章, 須原 哲也

    神経化学   49 ( 2-3 )   582 - 582   2010.8

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  • In vivo detection of neuropathologic changes in presymptomatic MAPT mutation carriers: A PET and MRI study Reviewed

    Michie Miyoshi, Hitoshi Shinotoh, Zbigniew K. Wszolek, Audrey J. Strongosky, Hitoshi Shimada, Ryosuke Arakawa, Makoto Higuchi, Yoko Ikoma, Fumihiko Yasuno, Kiyoshi Fukushi, Toshiaki Irie, Hiroshi Ito, Tetsuya Suhara

    PARKINSONISM & RELATED DISORDERS   16 ( 6 )   404 - 408   2010.7

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    Background: Microglial activation and disrupted neurotransmissions may herald symptomatic manifestations in neurodegenerative tauopathies.
    Methods: We investigated microglial activation with [(11)C]DAA1106 positron emission tomography (PET), striatal dopaminergic function with L-[beta-(11)C]dopa PET, acetylcholinesterase (AChE) activity with [(11)C]N-methylpiperidin-4-yl acetate PET, and morphologic brain changes with MRI in three persons (aged 38-41 years) with frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17), who were presymptomatic gene carriers (PGCs) from an American kindred with pallidopontonigral degeneration. The results from these 3 PGCs were compared with [(11)C]DAA1106 PET results from age-matched 9 healthy volunteers (HV), and with L-[beta-(11)C]dopa and [(11)C]MP4A PET results from 10 HV. Values considered significant were more than 2 SDs greater or less than the normal control mean, as the number of subjects was small for group comparisons.
    Results: Glial activities were increased in the frontal cortex of one PGC, the occipital cortex of two PGCs, and the posterior cingulate cortex of one PGC, although none of the PGCs showed overt glial activation in the brain. Only one of the PGCs showed reduced AChE activity in the temporo-parietal cortex. Three PGCs showed low dopamine synthesis rates in the putamen. Hippocampal atrophy was observed in two PGCs.
    Conclusions: Hippocampal atrophy and striatal dopaminergic dysfunction may be early disease processes in the pathogenesis of FTDP-17. Neuroinflammation may also be an in vivo signature of tau pathology at a prodromal stage, although current PET techniques may not constantly reveal it as the earliest neuroimaging abnormality. (C) 2010 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.parkreldis.2010.04.004

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  • Cholinergic imaging in corticobasal syndrome, progressive supranuclear palsy and frontotemporal dementia Reviewed

    Shigeki Hirano, Hitoshi Shinotoh, Hitoshi Shimada, Akiyo Aotsuka, Noriko Tanaka, Tsuneyoshi Ota, Koichi Sato, Hiroshi Ito, Satoshi Kuwabara, Kiyoshi Fukushi, Toshiaki Irie, Tetsuya Suhara

    BRAIN   133 ( Pt 7 )   2058 - 2068   2010.7

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    Corticobasal syndrome, progressive supranuclear palsy and frontotemporal dementia are all part of a disease spectrum that includes common cognitive impairment and movement disorders. The aim of this study was to characterize brain cholinergic deficits in these disorders. We measured brain acetylcholinesterase activity by [(11)C] N-methylpiperidin-4-yl acetate and positron emission tomography in seven patients with corticobasal syndrome (67.6 +/- 5.9 years), 12 with progressive supranuclear palsy (68.5 +/- 4.1 years), eight with frontotemporal dementia (59.8 +/- 6.9 years) and 16 healthy controls (61.2 +/- 8.5 years). Two-tissue compartment three-parameter model and non-linear least squares analysis with arterial input function were performed. k(3) value, an index of acetylcholinesterase activity, was calculated voxel-by-voxel in the brain of each subject. The k(3) images in each disease group were compared with the control group by using Statistical Parametric Mapping 2. Volume of interest analysis was performed on spatially normalized k(3) images. The corticobasal syndrome group showed decreased acetylcholinesterase activity (k(3) values) in the paracentral region, frontal, parietal and occipital cortices (P &lt; 0.05, cluster corrected). The group with progressive supranuclear palsy had reduced acetylcholinesterase activity in the paracentral region and thalamus (P &lt; 0.05, cluster corrected). The frontotemporal dementia group showed no significant differences in acetylcholinesterase activity. Volume of interest analysis showed mean cortical acetylcholinesterase activity to be reduced by 17.5% in corticobasal syndrome (P &lt; 0.001), 9.4% in progressive supranuclear palsy (P &lt; 0.05) and 4.4% in frontotemporal dementia (non-significant), when compared with the control group. Thalamic acetylcholinesterase activity was reduced by 6.4% in corticobasal syndrome (non-significant), 24.0% in progressive supranuclear palsy (P &lt; 0.03) and increased by 3.3% in frontotemporal dementia (non-significant). Both corticobasal syndrome and progressive supranuclear palsy showed brain cholinergic deficits, but their distribution differed somewhat. Significant brain cholinergic deficits were not seen in frontotemporal dementia, which may explain the unresponsiveness of this condition to cholinergic modulation therapy.

    DOI: 10.1093/brain/awq120

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  • レヴィ小体病における脳内アセチルコリンエステラーゼ活性測定

    島田 斉, 平野 成樹, 篠遠 仁, 佐藤 康一, 田中 典子, 黄田 常嘉, 朝比奈 正人, 福士 清, 入江 俊章, 須原 哲也

    認知神経科学   12 ( 2 )   111 - 111   2010.7

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  • Estimation of Plasma IC50 of Donepezil for Cerebral Acetylcholinesterase Inhibition in Patients With Alzheimer Disease Using Positron Emission Tomography Reviewed

    Tsuneyoshi Ota, Hitoshi Shinotoh, Kiyoshi Fukushi, Tatsuya Kikuchi, Koichi Sato, Noriko Tanaka, Hitoshi Shimada, Shigeki Hirano, Michie Miyoshi, Heii Arai, Tetsuya Suhara, Toshiaki Irie

    CLINICAL NEUROPHARMACOLOGY   33 ( 2 )   74 - 78   2010.3

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    Objectives: Estimate the value of in vivo plasma IC50 of donepezil, the concentration of donepezil in plasma that inhibits brain acetylcholinesterase (AChE) activity by 50% at the steady-state conditions of donepezil between the plasma and the brain.
    Methods: N-[C-11] methylpiperidin-4-yl acetate ([C-11]MP4A) positron emission tomography was performed in 16 patients with probable Alzheimer disease (AD) before and during the treatment of donepezil (5 mg/day) with a mean interval of 5.3 months. The plasma IC50 value of donepezil was estimated from plasma donepezil concentrations and cerebral cortical mean AChE inhibition rates measured by positron emission tomography, using one-parameter model.
    Results: Donepezil reduced AChE activity uniformly in the cerebral cortex compared with the baseline in each AD patient, and the mean reduction rate in the cerebral cortex was 34.6%. The donepezil concentrations in the plasma ranged from 18.5 to 43.9 ng/mL with a mean of 28.9 +/- 7.3 ng/mL. The plasma IC50 value was estimated to be 53.6 +/- 4.0 ng/mL.
    Conclusions: Once the plasma IC50 of donepezil is determined, the brain AChE inhibition rate could be estimated from the plasma concentration of donepezil in each subject based on the plasma IC50. Now that the mean donepezil concentrations in the plasma, when the patients took 5 mg/day, remained 28.9 ng/mL, approximately half of the plasma IC50, higher dose of donepezil might provide further benefits for patients with AD. This technique can be also applied to measure the in vivo plasma IC50 of other cholinesterase inhibitors such as rivastigmine and galantamine.

    DOI: 10.1097/WNF.0b013e3181c71be9

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  • 認知症を伴うレヴィ小体病におけるアミロイドイメージング

    島田 斉, 篠遠 仁, 三好 美智恵, 平野 成樹, 佐藤 康一, 田中 典子, 黄田 常嘉, 伊藤 浩, 福士 清, 入江 俊章, 須原 哲也

    臨床神経学   49 ( 12 )   1060 - 1060   2009.12

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  • [11C]PIB PETによる脳内アミロイド沈着の経時的変化の検討(第二報)

    三好 美智恵, 篠遠 仁, 島田 斉, 佐藤 康一, 田中 典子, 黄田 常嘉, 福士 清, 伊藤 浩, 松本 昌泰, 入江 俊章, 須原 哲也

    臨床神経学   49 ( 12 )   1136 - 1136   2009.12

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  • 平衡型PETトレーサーのk3推定 TACのセグメント化と単純化モデルの適用

    田中 典子, 佐藤 康一, 福士 清, 篠遠 仁, 島田 斉, 平野 成樹, 黄田 常嘉, 三好 美智恵, 大矢 智幸, 入江 俊章

    核医学   46 ( 3 )   248 - 248   2009.9

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  • 認知症を伴うレヴィ小体病におけるアミロイドイメージング

    島田 斉, 篠遠 仁, 三好 美智恵, 平野 成樹, 佐藤 康一, 田中 典子, 黄田 常嘉, 福士 清, 入江 俊章, 伊藤 浩, 須原 哲也

    核医学   46 ( 3 )   262 - 262   2009.9

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  • 大脳皮質基底核変性症、進行性核上性麻痺、前頭側頭型認知症における脳内コリン神経パラメトリック画像

    平野 成樹, 島田 斉, 篠遠 仁, 青墳 章代, 田中 典子, 黄田 常嘉, 佐藤 康一, 伊藤 浩, 須原 哲也, 福士 清, 入江 俊章

    核医学   46 ( 3 )   310 - 310   2009.9

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  • PIB-PETの定量解析法の新しい試み 3パラメータ法と4パラメータ法の比較

    田中 典子, 佐藤 康一, 福士 清, 篠遠 仁, 島田 斉, 三好 美智恵, 黄田 常嘉, 入江 俊章, 伊藤 浩, 須原 哲也

    核医学   46 ( 3 )   248 - 249   2009.9

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  • Reduced perfusion in the anterior cingulate cortex of patients with pure autonomic failure: An<sup>123</sup>I-IMP SPECT study Reviewed

    S. Hirano, M. Asahina, Y. Uchida, H. Shimada, R. Sakakibara, H. Shinotoh, T. Hattori

    Journal of Neurology, Neurosurgery and Psychiatry   80 ( 9 )   1053 - 1055   2009.9

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    Background: Pure autonomic failure (PAF) is a selective peripheral disorder in which Lewy bodies form within the autonomic ganglia. Patients with this disorder usually have no central lesions; however, chronic autonomic failure may secondarily affect the central nervous system. This study evaluated brain perfusion in patients with PAF by using N-isopropyl-p-123I iodoamphetamine (123I-IMP) single photon emission computed tomography (SPECT). Methods: Six patients with PAF (all men; mean (SD) age 68±5 years) who had experienced autonomic symptoms for more than 5 years and six age-matched healthy control subjects (all men; mean (SD) age 67±5 years) were included in this study. The regions of interest (ROI) on spacially normalized 123I-IMP SPECT images were automatically computed for both groups. Results: Perfusion of the dorsal anterior cingulate cortex was decreased in the PAF group compared with the healthy control group (0.93 vs 1.01; p<0.001). In the other brain regions measured, there was no significant difference in regional perfusion between the two groups. Conclusions: The dorsal anterior cingulate cortex is poorly perfused andmay be functionally altered in patients with PAF. The reduced perfusion in such individuals may be a secondary change that results from chronic autonomic failure.

    DOI: 10.1136/jnnp.2008.152678

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  • 脳内コリン神経系の障害はアルツハイマー病よりも認知症を伴うレヴィ小体病で重度である

    島田 斉, 篠遠 仁, 平野 成樹, 三好 美智恵, 佐藤 康一, 田中 典子, 黄田 常嘉, 朝比奈 正人, 青墳 章代, 伊藤 浩, 福士 清, 桑原 聡, 入江 俊章, 須原 哲也

    Dementia Japan   23 ( 2 )   162 - 162   2009.8

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  • Mapping of brain acetylcholinesterase alterations in Lewy body disease by PET

    H. Shimada, S. Hirano, H. Shinotoh, A. Aotsuka, K. Sato, N. Tanaka, T. Ota, M. Asahina, K. Fukushi, S. Kuwabara, T. Hattori, T. Suhara, T. Irie

    Neurology   73 ( 4 )   273 - 278   2009.7

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    OBJECTIVE: To characterize brain cholinergic deficits in Parkinson disease (PD), PD with dementia (PDD), and dementia with Lewy bodies (DLB). METHODS: Participants included 18 patients with PD, 21 patients with PDD/DLB, and 26 healthy controls. The PD group consisted of nine patients with early PD, each with a disease duration of less than 3 years, five of whom were de novo PD patients, and nine patients with advanced PD, each with a disease duration greater than or equal to 3 years. The PDD/DLB group consisted of 10 patients with PDD and 11 patients with DLB. All subjects underwent PET scans with N-[C]-methyl-4-piperidyl acetate to measure brain acetylcholinesterase (AChE) activity. Brain AChE activity levels were estimated voxel-by-voxel in a three-compartment analysis using the arterial input function, and compared among our subject groups through both voxel-based analysis using the statistical parametric mapping software SPM5 and volume-of-interest analysis. RESULTS: Among patients with PD, AChE activity was significantly decreased in the cerebral cortex and especially in the medial occipital cortex (% reduction compared with the normal mean = -12%) (false discovery rate-corrected p value <0.01). Patients with PDD/DLB, however, had even lower AChE activity in the cerebral cortex (% reduction = -27%) (p < 0.01). There was no significant difference between early PD and advanced PD groups or between DLB and PDD groups in the amount by which regional AChE activity in the brain was reduced. CONCLUSIONS: Brain cholinergic dysfunction occurs in the cerebral cortex, especially in the medial occipital cortex. It begins in early Parkinson disease, and is more widespread and profound in both Parkinson disease with dementia and dementia with Lewy bodies. © 2009 AAN Enterprises, Inc.

    DOI: 10.1212/WNL.0b013e3181ab2b58

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  • [11C]PIB PETによる脳内アミロイド沈着の経時的変化の検討

    三好 美智恵, 篠遠 仁, 島田 斉, 佐藤 康一, 田中 典子, 黄田 常嘉, 福士 清, 伊藤 浩, 松本 昌康, 入江 俊章, 須原 哲也

    臨床神経学   48 ( 12 )   1044 - 1044   2008.12

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  • 早期発症および晩期発症のアルツハイマー病における脳内アミロイドの沈着

    篠遠 仁, 島田 斉, 三好 美智恵, 福士 清, 田中 典子, 黄田 常嘉, 佐藤 康一, 入江 俊章, 伊藤 浩, 須原 哲也

    臨床神経学   48 ( 12 )   1215 - 1215   2008.12

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  • [11C]PIB PETによる脳内アミロイド沈着と認知機能の経時変化

    三好 美智恵, 篠遠 仁, 島田 斉, 佐藤 康一, 田中 典子, 黄田 常嘉, 福士 清, 伊藤 浩, 松本 昌泰, 入江 俊章, 須原 哲也

    脳循環代謝   20 ( 1 )   113 - 113   2008.11

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  • 早期発症と晩期発症アルツハイマー病における脳内アミロイド沈着 [11C]PIB PETによる測定

    篠遠 仁, 島田 斉, 三好 美智恵, 田中 典子, 黄田 常嘉, 佐藤 康一, 福士 清, 伊藤 浩, 入江 俊章, 須原 哲也

    核医学   45 ( 3 )   S180 - S181   2008.9

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  • [11C]PIB PETを用いた脳内アミロイド沈着の経時的変化の定量的検討

    三好 美智恵, 篠遠 仁, 島田 斉, 佐藤 康一, 田中 典子, 黄田 常嘉, 福士 清, 伊藤 浩, 松本 昌泰, 入江 俊章, 須原 哲也

    核医学   45 ( 3 )   S195 - S196   2008.9

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  • 一般高齢者における脳内アミロイド沈着 小金原地域調査研究

    篠遠 仁, 島田 斉, 三好 美智恵, 田中 典子, 黄田 常嘉, 佐藤 康一, 福士 清, 伊藤 浩, 入江 俊章, 須原 哲也

    核医学   45 ( 3 )   S181 - S181   2008.9

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  • [11C]MP4P/PETの内部標準参照法におけるk3値測定精度向上の試み 内部標準ROIの自動抽出

    佐藤 康一, 福士 清, 篠遠 仁, 田中 典子, 黄田 常嘉, 島田 斉, 三好 美智恵, 伊藤 浩, 須原 哲也, 入江 俊章

    核医学   45 ( 3 )   S236 - S237   2008.9

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  • アルツハイマー病と軽度認知障害における大脳皮質アミロイド沈着と傍海馬領域の萎縮の関係

    島田 斉, 篠遠 仁, 三好 美智恵, 田中 典子, 黄田 常嘉, 佐藤 康一, 福士 清, 伊藤 浩, 入江 俊章, 須原 徹也

    核医学   45 ( 3 )   S181 - S181   2008.9

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  • Potassium channel antibody-associated encephalitis with hypothalamic lesions and intestinal pseudo-obstruction Reviewed

    Yukari Sekiguchi, Hirokatsu Takahashi, Masahiro Mori, Shoichi Ito, Hitoshi Shimada, Takamichi Hattori, Satoshi Kuwabara

    JOURNAL OF THE NEUROLOGICAL SCIENCES   269 ( 1-2 )   176 - 179   2008.6

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    A subgroup of limbic encephalitis is associated with antibodies against voltage-gated potassium channels (VGKC), and responds well to immuno-modulating therapies. Anti-VGKC antibodies are also found in Isaacs' syndrome and Morvan's syndrome, both of which are sometimes complicated by thymoma. We describe a 52-years-old man with limbic encephalitis, thymoma, and anti-VGKC antibodies, who presented with autonomic dysfunctions such as severe intestinal pseudo-obstruction, hyperhidrosis and hypertension. Thymectomy and corticosteroid therapy remarkably improved his symptoms. Brain magnetic resonance imaging showed hypothalamic lesions, in addition to the bilateral involvement of the medial temporal lobes. This patient had severe autonomic dysfunctions resembling those of Morvan's syndrome. This case may represent a subgroup of VGKC-antibody associated syndromes with a wide spectrum of symptoms, including Isaacs' syndrome, Morvan's syndrome, and limbic encephalitis. (C) 2008 Published by Elsevier B.V.

    DOI: 10.1016/j.jns.2007.12.019

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  • [11C]-PIB PETによるアルツハイマー病の脳内アミロイドイメージング

    島田 斉, 篠遠 仁, 平野 成樹, 佐藤 康一, 田中 典子, 黄田 常嘉, 福士 清, 須原 哲也, 服部 孝道, 入江 俊章

    臨床神経学   47 ( 12 )   1055 - 1055   2007.12

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  • 加齢による脳内アミロイドの沈着 [11C]PIB-PETによる測定

    篠遠 仁, 島田 斉, 平野 成樹, 福士 清, 田中 典子, 黄田 常嘉, 佐藤 康一, 須原 哲也, 入江 俊章

    臨床神経学   47 ( 12 )   1055 - 1055   2007.12

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  • 脳梁の拡散テンソル解析によるパーキンソン病と進行性核上性麻痺の鑑別 Reviewed

    伊藤 彰一, 白井 和佳子, 島田 斉, 服部 孝道

    臨床神経学   47 ( 12 )   1154 - 1154   2007.12

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  • アルツハイマー病と軽度認知機能障害における大脳皮質アミロイドの沈着と海馬傍回の萎縮について

    篠遠 仁, 島田 斉, 福士 清, 田中 典子, 黄田 常嘉, 佐藤 康一, 伊藤 浩, 須原 哲也, 入江 俊章

    核医学   44 ( 3 )   301 - 301   2007.10

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  • PIB-PETにおけるアルツハイマー病診断感度 NLS法とLogan plot法の比較

    田中 典子, 福士 清, 篠遠 仁, 黄田 常嘉, 佐藤 康一, 島田 斉, 入江 俊章, 須原 哲也, 伊藤 浩

    核医学   44 ( 3 )   323 - 323   2007.10

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  • アルツハイマー病の進行に伴う脳内アセチルコリンエステラーゼ活性と脳血流の障害に関する検討

    黄田 常嘉, 篠遠 仁, 福士 清, 田中 典子, 佐藤 康一, 島田 斉, 伊藤 浩, 須原 哲也, 新井 平伊, 入江 俊章

    核医学   44 ( 3 )   322 - 322   2007.10

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  • レヴィ小体型認知症及び認知症を伴うParkinson病における脳内アセチルコリンエステラーゼ活性測定

    島田 斉, 平野 成樹, 篠遠 仁, 朝比奈 正人, 佐藤 康一, 田中 典子, 黄田 常嘉, 福士 清, 須原 哲也, 服部 孝道, 入江 俊章

    核医学   44 ( 3 )   322 - 322   2007.10

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  • [11C]MP4A/PETのパラメータ画像作成における簡便解析法の検討

    佐藤 康一, 福士 清, 篠遠 仁, 田中 典子, 黄田 常嘉, 島田 斉, 伊藤 浩, 須原 哲也, 入江 俊章

    核医学   44 ( 3 )   314 - 314   2007.10

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  • [11C]6-OH BTA-1-PETによるアミロイドイメージング

    篠遠 仁, 平野 成樹, 島田 斉, 福士 清, 田中 典子, 黄田 常嘉, 佐藤 康一, 棚田 修二, 入江 俊章

    臨床神経学   46 ( 12 )   978 - 978   2006.12

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  • 早期パーキンソン病の11C MP4APETを用いたIn Vivo脳内アセチルコリンエステラーゼ測定

    島田 斉, 平野 成樹, 篠遠 仁, 田中 典子, 黄田 常嘉, 福士 清, 朝比奈 正人, 棚田 修二, 須原 哲也, 服部 孝道, 入江 俊章

    核医学   43 ( 3 )   228 - 228   2006.10

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  • アルツハイマー病に対するドネペジルによる脳内アセチルコリンエステラーゼ活性阻害率の部位差に関する検討

    黄田 常嘉, 篠遠 仁, 福士 清, 田中 典子, 平野 成樹, 佐藤 康一, 島田 斉, 新井 平伊, 須原 哲也, 棚田 修二, 入江 俊章

    核医学   43 ( 3 )   270 - 270   2006.10

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  • アルツハイマー病と軽度認知機能障害における脳内アミロイドイメージング

    篠遠 仁, 福士 清, 平野 成樹, 黄田 常嘉, 田中 典子, 島田 斉, 佐藤 康一, 棚田 修二, 入江 俊章

    老年精神医学雑誌   17 ( 増刊I )   159 - 159   2006.6

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MISC

  • 本年の動向 非アルツハイマー病タウオパチーにおけるtau-PET

    互 健二, 島田 斉

    Annual Review神経   2020   111 - 116   2020.4

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  • 急速に運動・認知機能障害が進行し,もの忘れ外来受診後経過3年で死亡した83歳女性剖検例

    金田大太, 松原知康, 石井賢二, 徳丸阿耶, 島田斉, 佐原成彦, 須原哲也, 須原哲也, 村山繁雄, 村山繁雄, 齊藤祐子

    Dementia Japan   34 ( 4 )   2020

  • 筋萎縮性側索硬化症の運動皮質磁化率変化は上位運動ニューロン障害の指標となり得る Reviewed

    遠藤 浩信, 関口 兼司, 島田 斉, 上田 健博, 濱口 浩敏, 古和 久朋, 苅田 典生, 戸田 達史

    臨床神経学   59 ( Suppl. )   S333 - S333   2019.11

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  • レビー小体病におけるアルツハイマー病理は認知機能障害、萎縮、糖代謝障害に影響する

    互 健二, 島田 斉, 高畑 圭輔, 久保田 学, 佐野 康徳, 山本 保天, 篠遠 仁, 仲野 義和, 高堂 裕平, 北村 聡一郎, 繁田 雅弘, 須原 哲也, 樋口 真人

    Dementia Japan   33 ( 4 )   527 - 527   2019.10

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  • 双極性障害では線条体におけるホスホジエステラーゼ10Aの密度が低下する

    佐野 康徳, 高畑 圭輔, 久保田 学, 山本 保天, 島田 斉, 高堂 裕平, 互 健二, 関 千江, 黒瀬 心, 鈴木 寿臣, 田渕 肇, 垂水 良介, 高橋 希衣, 大川原 浩, 竹内 啓善, 坂村 敦子, 河村 和紀, 張 明栄, 三村 將, 樋口 真人

    日本臨床精神神経薬理学会・日本神経精神薬理学会合同年会プログラム・抄録集   29回・49回   253 - 253   2019.10

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  • ドーパミン生成能と、ドーパミン再取り込み機能およびドーパミンD2受容体密度との関連性に関する検討

    山本 保天, 高畑 圭輔, 久保田 学, 佐野 康徳, 島田 斉, 高堂 裕平, 関 千江, 木村 泰之, 高野 晴成, 互 健二, 黒瀬 心, 竹内 啓善, 河村 和紀, 張 明栄, 三村 將, 樋口 真人

    日本臨床精神神経薬理学会・日本神経精神薬理学会合同年会プログラム・抄録集   29回・49回   250 - 250   2019.10

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  • PETを用いた大脳皮質基底核症候群の背景病理推定に関する検討

    仲野 義和, 島田 斉, 篠遠 仁, 平野 成樹, 木村 泰之, 市瀬 正則, 関 千江, 高堂 裕平, 高畑 圭輔, 久保田 学, 互 健二, 河村 和紀, 張 明栄, 須原 哲也, 桑原 聡, 樋口 真人

    パーキンソン病・運動障害疾患コングレスプログラム・抄録集   13回   79 - 79   2019.7

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  • 18F-PM-PBB3 PETは発症前駆期より4リピートタウオパチーの脳病理を捕捉し得る

    島田 斉, 互 健二, 小野 麻衣子, 久保田 学, 高畑 圭輔, 高堂 裕平, 篠遠 仁, 山本 保天, 佐野 康徳, 関 千江, 平野 成樹, 木村 泰之, 市瀬 正則, 関 大成, 河村 和紀, 張 明栄, 桑原 聡, 服部 信孝, 須原 哲也, 樋口 真人

    パーキンソン病・運動障害疾患コングレスプログラム・抄録集   13回   129 - 129   2019.7

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  • 18F-PM-PBB3 PETによる4リピートタウオパチーのタウイメージング

    島田 斉, 互 健二, 久保田 学, 高畑 圭輔, 高堂 裕平, 市瀬 正則, 須原 哲也, 樋口 真人, 篠遠 仁, 平野 成樹, 木村 泰之

    千葉医学雑誌   95 ( 2 )   57 - 57   2019.4

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  • Amyloid PET陽性皮質基底核症候群における臨床的特徴の検討

    初鹿野悦子, 平野成樹, 櫻井透, 李洪亮, 仲野義和, 島田斉, 飯森隆志, 堀越琢郎, 宇野隆, 桑原聡

    日本神経学会学術大会プログラム・抄録集   60th   2019

  • うつ病・うつ状態のプレシジョンメディシン ポストGWAS時代に進むべき道 ニューロイメージングバイオマーカーを用いた創薬とプレシジョン・メティシンの現況

    高畑 圭輔, 堀口 隆司, 島田 斉, 樋口 真人, 須原 哲也

    日本臨床精神神経薬理学会・日本神経精神薬理学会合同年会プログラム・抄録集   28回・48回   101 - 101   2018.11

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  • 前頭側頭葉変性症における脳内タウ蓄積および代謝型グルタミン酸受容体5型の変化に関するPET研究

    久保田 学, 島田 斉, 高畑 圭輔, 互 健二, 関 千江, 佐野 康徳, 山本 保天, 高堂 裕平, 篠遠 仁, 本井 ゆみ子, 鈴木 寿臣, 女屋 光基, 河村 和紀, 張 明栄, 須原 哲也, 樋口 真人

    日本臨床精神神経薬理学会・日本神経精神薬理学会合同年会プログラム・抄録集   28回・48回   177 - 177   2018.11

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  • 糖尿病性認知症の定量的アミロイド/タウPET集積パターンの検討

    竹野下 尚仁, 深澤 雷太, 廣瀬 大輔, 清水 聰一郎, 馬原 孝彦, 櫻井 博文, 羽生 春夫, 石井 賢二, 島田 斉, 樋口 真人, 須原 哲也

    核医学   55 ( Suppl. )   S168 - S168   2018.11

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  • Alzheimer病における側頭葉内側タウ蓄積は後部帯状回を含む投射先脳領域の糖代謝低下と関連する

    島田 斉, 互 健二, 高畑 圭輔, 久保田 学, 山本 保天, 佐野 康徳, 高堂 裕平, 平野 成樹, 篠遠 仁, 須原 哲也, 樋口 真人

    脳循環代謝   30 ( 1 )   131 - 131   2018.10

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  • Alzheimer病における側頭葉内側タウ蓄積は後部帯状回を含む投射先脳領域の糖代謝低下と関連する

    島田 斉, 互 健二, 高畑 圭輔, 久保田 学, 山本 保天, 佐野 康徳, 高堂 裕平, 平野 成樹, 篠遠 仁, 須原 哲也, 樋口 真人

    脳循環代謝   30 ( 1 )   131 - 131   2018.10

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  • 糖尿病性認知症の定量的アミロイド/タウPET信頼パターンの検討

    竹野下 尚仁, 深澤 雷太, 廣瀬 大輔, 清水 聰一郎, 馬原 孝彦, 羽生 春夫, 石井 賢二, 島田 斉, 樋口 真人, 須原 哲也

    Dementia Japan   32 ( 3 )   465 - 465   2018.9

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  • 18F-PM-PBB3 PETは多様なタウオパチー疾患を視覚評価で弁別可能である

    互 健二, 島田 斉, 北村 聡一郎, 久保田 学, 高畑 圭輔, 佐野 康徳, 山本 保天, 篠遠 仁, 高堂 裕平, 仲野 義和, 小野 麻衣子, 木村 泰之, 市瀬 正則, 繁田 雅弘, 須原 哲也, 樋口 真人

    Dementia Japan   32 ( 3 )   469 - 469   2018.9

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  • 18F-PM-PBB3 PETは多様なタウオパチー疾患を視覚評価で弁別可能である

    互 健二, 島田 斉, 北村 聡一郎, 久保田 学, 高畑 圭輔, 佐野 康徳, 山本 保天, 篠遠 仁, 高堂 裕平, 仲野 義和, 小野 麻衣子, 木村 泰之, 市瀬 正則, 繁田 雅弘, 須原 哲也, 樋口 真人

    Dementia Japan   32 ( 3 )   469 - 469   2018.9

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  • 性格変化・行動異常にて発症し、顕著なすくみ足が出現した60歳女性例

    大内 翔悟, 冨所 康志, 清水 眸, 石井 賢二, 樋口 真人, 島田 斉, 須原 哲也, 玉岡 晃

    臨床神経学   58 ( 8 )   523 - 523   2018.8

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  • 糖尿病関連認知症におけるアミロイドとタウのPET(Amyloid and tau positron emission tomography in diabetes-related dementia)

    竹野下 尚仁, 深澤 雷太, 小川 裕介, 清水 聰一郎, 馬原 孝彦, 羽生 春夫, 石井 賢二, 島田 斉, 樋口 真人, 須原 哲也

    東京医科大学雑誌   76 ( 3 )   282 - 282   2018.7

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  • 18F-PM-PBB3 PETにて脳幹・小脳にタウ蓄積が示唆されたprogressive ataxia and palatal tremorの一例

    関 守信, 高橋 愼一, 大山 宗徳, 島田 斉, 高畑 圭輔, 互 健二, 樋口 真人, 武田 英孝, 鈴木 則宏

    パーキンソン病・運動障害疾患コングレスプログラム・抄録集   12回   93 - 93   2018.7

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  • 18F-PM-PBB3 PETにて脳幹・小脳にタウ蓄積が示唆されたprogressive ataxia and palatal tremorの一例

    関 守信, 高橋 愼一, 大山 宗徳, 島田 斉, 高畑 圭輔, 互 健二, 樋口 真人, 武田 英孝, 鈴木 則宏

    パーキンソン病・運動障害疾患コングレスプログラム・抄録集   12回   93 - 93   2018.7

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  • Alzheimer病における側頭葉内側タウ蓄積は後部帯状回を含む投射先脳領域の糖代謝低下と関連する

    島田斉, 互健二, 高畑圭輔, 久保田学, 山本保天, 佐野康徳, 高堂裕平, 平野成樹, 平野成樹, 篠遠仁, 篠遠仁, 須原哲也, 樋口真人

    脳循環代謝(Web)   30 ( 1 )   131   2018

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    J-GLOBAL

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  • 紀伊半島の筋萎縮性側索硬化症/パーキンソン認知症複合における末梢神経軸索興奮性変化

    網野寛, 澁谷和幹, 三澤園子, 関口縁, 水地智基, 常山篤子, 鈴木陽一, 島田斉, 小久保康昌, 桑原聡

    臨床神経生理学(Web)   46 ( 5 )   2018

  • 発症前Alzheimer病スペクトラム患者におけるタウ病変の縦断的PET評価

    互 健二, 島田 斉, 北村 聡一郎, 高畑 圭輔, 久保田 学, 篠遠 仁, 高堂 裕平, 仲野 義和, 石井 辰弥, 平野 成樹, 繁田 雅弘, 須原 哲也, 樋口 真人

    Dementia Japan   31 ( 4 )   556 - 556   2017.10

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  • 糖尿病性認知症におけるタウ集積パターンの解析

    竹野下 尚仁, 深澤 雷太, 廣瀬 大輔, 清水 聰一郎, 馬原 孝彦, 羽生 春夫, 石井 賢二, 島田 斉, 樋口 真人, 須原 哲也

    Dementia Japan   31 ( 4 )   556 - 556   2017.10

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  • 発症前Alzheimer病スペクトラム患者におけるタウ病変の縦断的PET評価

    互 健二, 島田 斉, 北村 聡一郎, 高畑 圭輔, 久保田 学, 篠遠 仁, 高堂 裕平, 仲野 義和, 石井 辰弥, 平野 成樹, 繁田 雅弘, 須原 哲也, 樋口 真人

    Dementia Japan   31 ( 4 )   556 - 556   2017.10

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  • 新しい診断法 : タウPET (特集 認知症1,000万人時代を目前に控えて : 最新の診断,マネジメント,そして分子標的治療へ) -- (認知症医療のブレイクスルー)

    島田 斉

    内科 = Internal medicine : 臨床雑誌   120 ( 2 )   187 - 191   2017.8

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    Other Link: http://search.jamas.or.jp/link/ui/2017338848

  • Alzheimer病におけるアパシー症状とタウ病変の関係性

    北村 聡一郎, 島田 斉, 篠遠 仁, 丹羽 文俊, 遠藤 浩信, 高畑 圭輔, 久保田 学, 高堂 裕平, 平野 成樹, 木村 泰之, 張 明栄, 桑原 聡, 須原 哲也, 樋口 真人

    千葉核医学研究会   33   1 - 4   2017.6

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  • Alzheimer病のアパシー症状とタウ病変の関連性 11C-PBB3 PET研究

    北村 聡一郎, 島田 斉, 篠遠 仁, 平野 成樹, 丹羽 文俊, 遠藤 浩信, 久保田 学, 高畑 圭輔, 森口 翔, 木村 泰之, 張 明栄, 須原 哲也, 樋口 真人

    老年精神医学雑誌   28 ( 増刊II )   191 - 191   2017.6

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  • Impact of spillover from white matter by partial volume effect on quantification of amyloid deposition with [C-11]PiB PET (vol 143, pg 316, 2016)

    Keisuke Matsubara, Masanobu Ibaraki, Hitoshi Shimada, Yoko Ikoma, Tetsuya Suhara, Toshibumi Kinoshita, Hiroshi Ito

    NEUROIMAGE   153   411 - 411   2017.6

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    DOI: 10.1016/j.neuroimage.2017.04.042

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  • 分子脳イメージングによる糖尿病性認知症の病態解析

    竹野下 尚仁, 深澤 雷太, 清水 聰一郎, 馬原 孝彦, 櫻井 博文, 石井 賢二, 島田 斉, 樋口 真人, 須原 哲也, 羽生 春夫

    日本老年医学会雑誌   54 ( Suppl. )   219 - 219   2017.5

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  • 認知症の脳機能画像 認知症のタウイメージング

    互健二, 島田斉, 須原哲也, 樋口真人

    月刊神経内科   86 ( 4 )   432‐437   2017.4

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  • PET quantification of binding of a novel tau radioligand, F-18-AM-PBB3, in consideration of time-dependent changes in its plasma free fraction

    S. Kitamura, Y. Kimura, M. Ichise, C. Seki, H. Shimada, H. Shinotoh, M. Kubota, K. Takahata, Y. Takado, S. Moriguchi, T. Ishii, M. -R. Zhang, T. Suhara, M. Higuchi

    JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM   37   217 - 218   2017.4

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  • 前頭側頭葉変性症9例における[11C]PBB3 PETを用いた脳内タウ集積の検討

    丹羽 文俊, 島田 斉, 高畑 圭輔, 篠遠 仁, 遠藤 浩信, 北村 聡一郎, 平野 成樹, 木村 泰之, 樋口 真人, 須原 哲也, 肥田 道彦, 田渕 肇, 三村 將

    臨床神経学   56 ( Suppl. )   S279 - S279   2016.12

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  • タウイメージングに期待される認知症診療における役割

    杉山 淳比古, 島田 斉

    Radioisotopes   65 ( 12 )   517 - 522   2016.12

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    わが国では高齢化に伴い認知症患者数が増加している。最も頻度の高い認知症はアルツハイマー病(AD)で、ADの主要な病理所見は、1)アミロイドβ(Aβ)の凝集体である老人斑、2)過剰燐酸タウ蛋白質(TP)の凝集した神経原線維変化の蓄積、3)神経細胞死、である。Aβは主にADで見られるが、TPはADの他に進行性核上麻痺、大脳皮質基底核症候群などでも見られ、神経障害に密接に関与すると考えられ、画像診断ならびに治療の重要な標的と認識されつつある。タウイメージング(TI)用PETリガンド開発の現状、TIの実際、期待される近未来の認知症診断展望について概説した。

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  • 紀伊半島筋萎縮性側索硬化症/パーキンソン認知症複合症例のタウイメージング

    篠遠仁, 島田斉, 小久保康昌, 佐々木良元, 森本悟, 平野成樹, 葛原茂樹, 樋口真人, 須原哲也

    Dementia Japan   30 ( 4 )   584   2016.10

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  • アミロイド、タウPETを用いた糖尿病性認知症の病態解析

    深澤 雷太, 清水 聰一郎, 平尾 健太郎, 櫻井 博文, 石井 賢二, 島田 斉, 樋口 真人, 須原 哲也, 羽生 春夫

    Dementia Japan   30 ( 4 )   569 - 569   2016.10

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  • 最新の機能画像研究 (特集 内科医がおさえておくべきパーキンソン病診療のポイント)

    島田 斉

    内科   118 ( 2 )   265 - 268   2016.8

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  • Tau imaging in patients with ALS/PDC in the Kii Peninsula

    Y. Kokubo, H. Shinotoh, H. Shimada, F. Niwa, R. Sasaki, S. Morimoto, H. Endo, S. Kitamura, S. Hirano, I. Aiba, M. Miyamura, N. Sahara, S. Kuzuhara, M. Higuchi, T. Suhara

    JOURNAL OF NEUROCHEMISTRY   138   373 - 373   2016.8

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  • Recent advances in clinical tau PET imaging with [11C]PBB3

    島田斉, 北村聡一郎, 丹羽文俊, 木村泰之, 市瀬正則, 山田真希子, 佐原成彦, 樋口真人, 須原哲也, 篠遠仁, 篠遠仁, 遠藤浩信, 遠藤浩信, 石川愛, 石川愛, 平野成樹, 平野成樹, 古賀俊介

    千葉医学雑誌   92 ( 3 )   124   2016.6

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  • Neuroimaging-based biomarkers for MCI and preclinical AD and their neuropathological correlates

    樋口 真人, 島田 斉, 須原 哲也

    老年精神医学雑誌   27 ( 6 )   624 - 630   2016.6

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  • In vivo evaluation of tau pathologies in patient with progressive supranuclear palsy and healthy subjects with [C-11]PBB3-PET

    H. Endo, H. Shimada, Y. Kimura, M. Ichise, M. Ono, H. Shinotoh, F. Niwa, S. Kitamura, K. Takahata, S. Hirano, S. Koga, D. W. Dickson, N. Sahara, M. Yamada, M. Higuchi, T. Toda, T. Suhara

    MOVEMENT DISORDERS   31   S383 - S383   2016.6

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  • A potential role of tau PET imaging in diagnosis of dementia

    45 ( 4 )   441 - 445   2016.4

  • CONFORMATIONAL HETEROGENEITY OF TAU LESIONS CAPTURED BY PET AND ITS CLINICAL SIGNIFICANCE

    Makato Higuchi, Hitoshi Shimada, Naruhiko Sahara, Tetsuya Suhara

    NEUROBIOLOGY OF AGING   39   S10 - S11   2016.3

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  • Late-onset neurocognitive deficits following traumatic brain injury: chronic traumatic encephalopathy (CTE) and psychotic disorder following TBI (PDF TBI)

    Takahata Keisuke, Kato Motoichiro, Mimura Masaru, Shimada Hitoshi, Higuchi Makoto, Suhara Tetsuya

    Higher Brain Function Research   35 ( 3 )   276 - 282   2016

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    &amp;ensp;&amp;ensp;Traumatic brain injury (TBI) can cause delayed-onset neurocognitive dysfunctions including such as chronic traumatic encephalopathy (CTE) and psychotic disorder following TBI (PDFTBI) . Initially, CTE was called punch-drunk syndrome since only athletes exposed to recurrent concussions in high-impact sports such as boxing were believed to develop such symptoms. However, it has been revealed that CTE can occur in the wider population including American football players, wrestlers, ice-hockey players and military persons. Pathologically, CTE is characterized by abnormal accumulations of tau proteins and less apparent amyloid-beta proteins, and definitive diagnosis of CTE can be made only at autopsy and no reli able biomarkers of CTE are available. PDFTBI is schizophrenia-like psychosis, which typically occurs several years after single severe TBI. About 3.4-8.9% of single-severe TBI patients develop PDFTBI in later life, and mean onset time after TBI is about 5 years. This temporal interval between onset of psychosis and time of head injury indicates that a neurodegeneration is involved in development of PDFTBI. Al though clinical subtypes associated these post-TBI syndromes are different, evidence suggest that single-severe and mild-repetitive TBI share similar neuropathological features. In this review, we discuss clinical characteristics of CTE and PDFTBI. Next, we describe how novel neuroimaging methods to detect tau and amyloid pathology improve diagnosis and prevention of post-TBI syndromes. Recent development of tau-selective radioligand such as[&lt;sup&gt;11&lt;/sup&gt;C]PBB3 may be a powerful tool to detect tau pathology in the living brain of TBI patients.

    DOI: 10.2496/hbfr.35.276

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  • 神経変性疾患領域における基盤的調査研究 陽電子放出断層撮影による進行性核上性麻痺の客観的重症度指標の確立

    戸田達史, 遠藤浩信, 遠藤浩信, 島田斉, 市瀬正則, 木村泰之, 佐原成彦, 樋口真人, 桑原聡, 須原哲也

    神経変性疾患領域における基盤的調査研究 平成27年度 総括・分担研究報告書   105‐107   2016

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  • 紀伊半島の筋委縮性側索硬化症/パーキンソン認知症複合のタウイメージング

    篠遠仁, 島田斉, 小久保康昌, 丹羽文俊, 佐々木良元, 森本悟, 平野成樹, 饗場郁子, 葛原茂樹, 樋口真人, 須原哲也

    核医学(Web)   53 ( Supplement )   1240(J‐STAGE)   2016

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  • The Role of Tau PET Imaging in the Diagnosis of Dementia

    丹羽文俊, 島田斉

    Medical Imaging Technology (Web)   34 ( 1 )   2016

  • 灰白質ボクセルより参照領域を抽出する<sup>11</sup>C-PBB3 PET定量法

    木村泰之, 遠藤浩信, 遠藤浩信, 市瀬正則, 島田斉, 関千江, 生駒洋子, 篠遠仁, 山田真希子, 樋口真人, 張明栄, 須原哲也

    核医学(Web)   53 ( Supplement )   2016

  • FTDP‐17 MAPT遺伝子変異症例のタウイメージング―[<sup>11</sup>C]PBB3 PET‐による検討―

    SHINOTOO HITOSHI, SAHARA NARUHIKO, SHIMADA HITOSHI, ZOREKKU TSUBIGUNYU, IKEUCHI KEN, HANYU HARUO, ISHII KENJI, NISHIOKA KEN'YA, KOGA SHUNSUKE, HIGUCHI MAKOTO, SUHARA TETSUYA

    核医学   52 ( 3 )   294 - 294   2015.9

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  • [<sup>11</sup>C]PBB3 PETによるMAPT遺伝子変異症例のタウイメージング

    SHINOTOO HITOSHI, SAHARA NARUHIKO, SHIMADA HITOSHI, ZOREKKU TSUBIGUNYU, IKEUCHI KEN, HANYU HARUO, ISHII KENJI, KOGA SHUNSUKE, HIGUCHI MAKOTO, SUHARA TETSUYA

    Dement Jpn   29 ( 3 )   387 - 387   2015.9

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  • マウスモデルを用いた,神経障害に関与するタウ病変の生体内評価系の確立

    ISHIKAWA AI, ISHIKAWA AI, SAHARA NARUHIKO, TOKUNAGA MASAKI, TAGUWA HIROYUKI, SHIMADA HITOSHI, HIRANO SHIGEKI, HIRANO SHIGEKI, SHINOTOO HITOSHI, KUWABARA SATOSHI, SUHARA TETSUYA, HIGUCHI MAKOTO

    Dement Jpn   29 ( 3 )   418   2015.9

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  • Tau Imaging

    70 ( 9 )   1872 - 1876   2015.9

  • Alzheimer病の分子イメージング (特集 ここが知りたい認知症診療) -- (Alzheimer病の診断)

    北村 聡一郎, 島田 斉

    診断と治療   103 ( 7 )   883 - 886,848-849   2015.7

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  • 脳PET定量イメージングにおけるTOFおよびPSF補正の影響

    前田 貴雅, 鶴岡 伊知郎, 白石 貴博, 石井 徳幸, 谷本 克之, 柴山 晃一, 生駒 洋子, 島田 斉, 木村 泰之, 須原 哲也

    千葉核医学研究会   31   1 - 4   2015.6

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  • タウイメージング用PET製剤[<sup>11</sup>C]PBB3を用いた臨床研究の現状と汎用化体開発の展望

    ISHIKAWA AI, FURUKAWA SHOGO, HIRANO SHIGEKI, SHIMADA HITOSHI, SHINOTOO HITOSHI, SAWARA SHIGEHIKO, HIGUCHI MAKOTO, SUHARA TETSUYA

    千葉医学雑誌   91 ( 3 )   149 - 150   2015.6

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  • Quantitative analysis of tau pathology in human brain using PET with [C-11]PBB3

    Hiroshi Ito, Hitoshi Shimada, Yoko Ikoma, Hitoshi Shinotoh, Yasuyuki Kimura, Masanori Ichise, Tetsuya Suhara, Makoto Higuchi

    JOURNAL OF NUCLEAR MEDICINE   56 ( 3 )   2015.5

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  • Imaging of Tau and Amyloid Pathology in Patients With Traumatic Brain Injury: A PET Study Using [11C]PBB3 and [11C]PIB

    Keisuke Takahata, Hitoshi Shimada, Hitoshi Shinotoh, Yasuyuki Kimura, Soichiro Kitamura, Hironobu Endo, Fumitoshi Niwa, Sho Moriguchi, Masanori Ichise, Jin Mizushima, Hajime Tabuchi, Masaru Mimura, Motoichiro Kato, Makiko Yamada, Makoto Higuchi, Tetsuya Suhara

    BIOLOGICAL PSYCHIATRY   77 ( 9 )   364S - 365S   2015.5

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  • Parametric visualisation and quantification of tau pathology in human brain using PET with [C-11]PBB3

    Yasuyuki Kimura, Masanori Ichise, Yoko Ikoma, Hitoshi Shimada, Chie Seki, Soichiro Kitamura, Hitoshi Shinotoh, Hiroshi Ito, Tetsuya Suhara, Makoto Higuchi

    JOURNAL OF NUCLEAR MEDICINE   56 ( 3 )   2015.5

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  • Correction for partial volume effect in quantification of amyloid beta plaque with [C-11]PIB PET.

    Keisuke Matsubara, Yoko Ikoma, Masanobu Ibaraki, Hitoshi Shimada, Tetsuya Suhara, Toshibumi Kinoshita, Hiroshi Ito

    JOURNAL OF NUCLEAR MEDICINE   56 ( 3 )   2015.5

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  • 【認知症の症候学・治療学および予防への展望】アルツハイマー病の診断と鑑別診断 非定型例の検討を中心に初期診断の限界と問題点を考える アミロイドとタウイメージングが診断に有用であった認知症症例

    篠遠 仁, 島田 斉, 平野 成樹, 古川 彰吾, 高畑 圭輔, 加藤 元一郎, 樋口 真人, 須原 哲也

    老年精神医学雑誌   26 ( 増刊I )   68 - 74   2015.3

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    症例1は60歳代女性で、もの忘れとともに左手の使いにくさが徐々に進行し、大脳皮質基底核変性症候群と診断された。[11C]PIB PETにてアミロイド陽性であり、[11C]PBB3 PETでは側頭葉内側を含む大脳皮質にタウタンパクの蓄積がみられ、背景病理はアルツハイマー病(AD)と考えられた。症例2は50歳代後半の男性で行動の脱抑制、常同行為、実行機能の障害があり、前頭側頭型認知症行動バリアントと診断された。PIB陰性であり、[11C]PBB3 PETでは大脳皮質、大脳基底核、脳幹にタウタンパクの蓄積がみられ、タウタンパクの分布から進行性核上性麻痺と考えられた。(著者抄録)

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  • 脳とこころの分子イメージング 分子神経イメージング研究プログラム 脳病態チーム

    須原哲也, 山田真希子, 木村泰之, 島田斉, 高畑圭輔, 伊藤岳人, 北村聡一郎, 丹羽文俊, 篠遠仁, 市瀬正則, 平野成樹

    放射線科学   58 ( 1 )   06 - 17   2015.2

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  • 認知症のタウPET:一個の細胞の病態が全脳へ波及する過程を追う

    HIGUCHI MAKOTO, MARUYAMA MASAHIRO, SHIMADA HITOSHI, SHINOTOO HITOSHI, RI HIN, ONO MAIKO, SAWARA SHIGEHIKO, TAKUWA HIROYUKI, CHO MEIEI, SUHARA TETSUYA

    NIRS-R (Natl Inst Radiol Sci)   ( 68 )   13 - 14   2015.1

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  • Basic Neuroscience 4.画像 1)タウPETイメージング

    島田斉, 石川愛, 北村聡一郎, 樋口真人

    Annual Review 神経   2015   50 - 56   2015.1

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  • The analyze of four pedigrees with MAPT N279K mutation accompanying DAT scan and Tau imaging

    IKEDA AYA, NISHIOKA KEN'YA, RI GENTETSU, TAKANASHI MASASHI, YOSHINO HIROYO, FUNAYAMA MANABU, MATSUSHIMA TAKASHI, UENO SHIN'ICHI, KURITA SHOEI, UENO YUJI, SHIMADA HITOSHI, SAHARA NARUHIKO, HIGUCHI MAKOTO, SUHARA TETSUYA, MOTOI YUMIKO, HATTORI NOBUTAKA

    パーキンソン病・運動障害疾患コングレスプログラム・抄録集   9th   75 - 75   2015

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  • Progressive supranuclear palsy患者における臨床症候と11C-PBB3 PET集積の関係

    遠藤浩信, 島田斉, 篠遠仁, 篠遠仁, 丹羽文俊, 北村聡一郎, 平野成樹, 平野成樹, 古川彰吾, 古川彰吾, 樋口真人, 須原哲也

    日本神経学会学術大会プログラム・抄録集   56th   2015

  • 高血圧症はアルツハイマー型認知症のタウ蓄積に寄与するか?~PET画像を用いた検討~

    丹羽文俊, 丹羽文俊, 島田斉, 篠遠仁, 遠藤浩信, 北村聡一郎, 平野成樹, 古川彰吾, 樋口真人, 須原哲也

    日本神経学会学術大会プログラム・抄録集   56th   2015

  • レム睡眠行動異常症患者の被殻ドーパミントランスポーター結合能の評価

    古川 彰吾, 島田 斉, 篠遠 仁, 平野 成樹, 山田 真希子, 川口 拓之, 伊藤 浩, 西田 慎吾, 小林 美奈, 笹井 妙子, 中村 真樹, 桑原 聡, 井上 雄一, 須原 哲也

    臨床神経学   54 ( Suppl. )   S51 - S51   2014.12

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  • 頭部外傷の分子イメージング―慢性外傷性脳症(CTE)と頭部外傷後精神病性障害(PDFTBI)を中心に

    高畑圭輔, 加藤元一郎, 三村將, 島田斉, 山田真希子, 樋口真人, 須原哲也

    日本高次脳機能障害学会学術総会プログラム・講演抄録   38th   106   2014.10

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  • 認知症タウ病変のイメージング

    HIGUCHI MAKOTO, SHIMADA HITOSHI, MARUYAMA MASAHIRO, SAHARA SHIGEHIKO, SHINOTOO HITOSHI, HIRANO SHIGEKI, ONO MAIKO, CHO MEIEI, SUHARA TETSUYA

    Dement Jpn   28 ( 4 )   446   2014.10

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  • ドパミントランスポータPETとニューロメラニンMRIによる黒質のパーキンソン病態生理の複合解析

    川口拓之, 島田斉, 小高文聰, 鈴木雅之, 篠遠仁, 平野成樹, カーショウ ジェフ, 須原哲也, 伊藤浩

    核医学   51 ( 3 )   308 - 308   2014.9

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  • 進行性核上性麻痺および大脳基底核変性症におけるタウイメージング [11C]PBB3 PETによる検討

    篠遠 仁, 島田 斉, 平野 成樹, 古川 彰吾, 高畑 圭輔, 木村 泰之, 山田 真希子, 伊藤 浩, 樋口 真人, 桑原 聡, 須原 哲也

    核医学   51 ( 3 )   309 - 309   2014.9

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  • [<sup>11</sup>C]PBB3 PETによるタウイメージング

    島田斉, 丸山将浩, 江口洋子, 木村泰之, 山田真希子, 高野晴成, 伊藤浩, 樋口真人, 須原哲也, 篠遠仁, 平野成樹, 古川彰吾

    千葉医学雑誌   90 ( 3 )   112   2014.6

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  • In vivo tau PET imaging using [C-11]PBB3 in patients with progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS)

    H. Shimada, S. Hirano, H. Shinotoh, S. Furukawa, Y. Eguchi, K. Takahata, Y. Kimura, Y. Ikoma, M. Yamada, M. -R. Zhang, H. Ito, M. Higuchi, S. Kuwabara, T. Suhara

    MOVEMENT DISORDERS   29   S95 - S95   2014.5

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  • Quantification of putaminal dopamine transporter in patients with REM sleep behavior disorder and Parkinson's disease

    S. Furukawa, H. Shimada, H. Shinotoh, S. Hirano, M. Yamada, H. Kawaguchi, H. Ito, S. Nishida, M. Kobayashi, T. Sasai, M. Nakamura, S. Kuwabara, Y. Inoue, T. Suhara

    MOVEMENT DISORDERS   29   S291 - S291   2014.5

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  • タウイメージングの開発

    樋口真人, 丸山将浩, 島田斉, 篠遠仁, ZHANG Ming‐Rong, 須原哲也

    老年精神医学雑誌   25   69 - 75   2014.3

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  • 【認知症医療の新展開】 診断学 タウ関連を中心に、最新知識の提供 タウイメージングの開発

    樋口 真人, 丸山 将浩, 島田 斉, 篠遠 仁, 張 明栄, 須原 哲也

    老年精神医学雑誌   25 ( 増刊I )   69 - 75   2014.3

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    アルツハイマー病(AD)をはじめとする多くの認知症で、タウタンパクの線維性凝集体は中核病変として神経細胞ないしはグリア細胞内に蓄積する。タウ病変は神経細胞死と密接に関連し、これを標的とした認知症の診断法および治療法が求められている。放射線医学総合研究所では、生体脳でタウ蓄積を画像化できるポジトロン断層撮影(PET)用薬剤の開発に成功した。このPET薬剤は、AD患者で想定されるタウ病変の分布に一致した脳内集積パターンを示した。描出されたタウ病変の広がりは、認知症の重症度と神経細胞死の程度を反映することがわかり、疾患重症度の客観的指標となることが明らかになった。さらにAD以外の認知症におけるタウ病変の蓄積も生体で画像化され、認知症の鑑別診断や、タウ蓄積部位と症状の相関を解明するのに有用な技術が実現した。(著者抄録)

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  • 認知障害の画像診断をめぐって 認知症診断におけるtau,amyloid imagingの役割

    島田斉, 丸山将浩, 樋口真人, 須原哲也

    臨床画像   30 ( 2 )   177 - 186   2014.2

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  • タウ蛋白病変が見えた!~ヒト生体タウイメージングの実現と認知症研究促進への期待~

    島田斉, 丸山将浩, 樋口真人, 須原哲也

    放射線科学   57 ( 1 )   40 - 41   2014.2

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  • 画像 2)ミクログリアPET

    島田斉, 樋口真人

    Annual Review 神経   2014   51 - 57   2014.1

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  • アルツハイマー病の画像診断 タウイメージングの開発

    樋口真人, 丸山将浩, 島田斉, ZHANG Ming‐Rong, 須原哲也

    Pharma Med   32 ( 1 )   43 - 49   2014.1

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  • 健常高齢者における脳内タウ蛋白の蓄積について―[11C]PBB3 PETによる検討―

    篠遠仁, 島田斉, 平野成樹, 古川彰吾, 高野晴成, 山田真希子, 伊藤浩, 須原哲也, 樋口真人

    日本神経学会学術大会プログラム・抄録集   55th   665   2014

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  • ヒト黒質のPET脳機能画像解析における解剖学的標準化の影響の解析

    川口拓之, 鈴木雅之, 小高文聰, 島田斉, 篠遠仁, 平野成樹, カーショー ジェフ, 生駒洋子, 須原哲也, 伊藤浩

    日本ヒト脳機能マッピング学会プログラム・抄録集   16th   75   2014

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  • [11C]PBB3 PETで推定したタウ蓄積量はアルツハイマー病の認知症重症度を反映する

    SHIMADA HITOSHI, SHINOTOO HITOSHI, HIRANO SHIGEKI, FURUKAWA SHOGO, EGUCHI YOKO, TAKAHATA KEISUKE, KIMURA YASUYUKI, KODAKA FUMITOSHI, MARUYAMA MASAHIRO, TAKANO HARUMASA, SAHARA NARUHIKO, YAMADA MAKIKO, IKOMA YOKO, CHO MEIEI, ITO HIROSHI, HIGUCHI MAKOTO, KUWABARA SATOSHI, SUHARA TETSUYA

    日本神経学会学術大会プログラム・抄録集   55th ( Suppl. )   (JA)455,(EN)457 - S1   2014

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  • TDP‐17の原因遺伝子MAPTの新規挿入変異の同定と生化学解析

    KAWAKAMI HIDESHI, MORINO TOYOYUKI, MATSUDA YUKIKO, OSAWA RYOSUKE, HIRAKI KEIKO, KURASHIGE TSUYOSHI, IZUMI YUISHIN, YAMASAKI YU, TAKAHASHI TETSUYA, TAKASHIMA AKIHIKO, SOEDA YOSHIYUKI, MIYASAKA TOMOHIRO, HIGUCHI MAKOTO, SAWARA SHIGEHIKO, SUHARA TETSUYA, SHIMADA HITOSHI, ITO HIDEFUMI, MARUYAMA HIROFUMI

    日本生物学的精神医学会誌   266   2014

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  • [<sup>11</sup>C]PBB3PETは進行性核上性麻痺および大脳基底核変性症におけるタウ病変を捉える

    篠遠仁, 篠遠仁, 島田斉, 平野成樹, 平野成樹, 古川彰吾, 古川彰吾, 丹羽文俊, 北村聡一郎, 遠藤浩信, 桑原聡, 樋口真人, 須原哲也

    Dementia Japan   28 ( 4 )   2014

  • レヴィ小体病におけるアミロイド沈着はアルツハイマー病様脳萎縮と関連する

    島田 斉, 平野 成樹, 篠遠 仁, 古川 彰吾, 江口 洋子, 高畑 圭輔, 小高 文聰, 藤原 広臨, 木村 泰之, 山田 真希子, 高野 晴成, 伊藤 浩, 樋口 真人, 桑原 聡, 須原 哲也

    臨床神経学   53 ( 12 )   1482 - 1482   2013.12

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  • Molecular imaging of neurodegenerative dementia

    89 ( 6 )   235 - 241   2013.12

  • MRIによる黒質メラニンとPETによる被殻ドパミントランスポーターイメージング Reviewed

    篠遠 仁, 島田 斉, 平野 成樹, 鈴木 雅之, 古川 彰吾, 川口 拓之, 高野 晴成, 伊藤 浩, 桑原 聡, 須原 哲也

    臨床神経学   53 ( 12 )   1616 - 1616   2013.12

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  • [11C]PBB3 PETによるタウイメージング

    島田 斉, 篠遠 仁, 平野 成樹, 江口 洋子, 木村 泰之, 高野 晴成, 伊藤 浩, 樋口 誠人, 桑原 聡, 須原 哲也

    Dementia Japan   27 ( 4 )   506 - 506   2013.10

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  • アミロイド前駆体蛋白遺伝子に新規変異を認めたアルツハイマー病の1家系

    篠遠 仁, 桑野 良三, 島田 斉, 平野 成樹, 江口 洋子, 高野 晴成, 須原 哲也

    Dementia Japan   27 ( 4 )   487 - 487   2013.10

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  • ニューロメラニンMRIとドーパミントランスポーター結合能のヒト黒質における加齢変化についての検討

    川口拓之, 島田斉, 鈴木雅之, 篠遠仁, 平野成樹, カーショー ジェフ, 須原哲也, 伊藤浩

    核医学   50 ( 3 )   211   2013.9

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  • レビ小体病におけるアミロイド沈着はアルツハイマー病様脳萎縮と関連する

    島田斉, 平野成樹, 篠遠仁, 古川彰吾, 江口洋子, 高畑圭輔, 小高文聴, 藤原広臨, 木村泰之, 山田真希子, 高野晴成, 伊藤浩, 樋口真人, 桑原聡, 須原哲也

    日本神経学会学術大会プログラム・抄録集   54th   368   2013

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  • MRIによる黒質メラニンとPETによる被殻ドパミントランスポーターイメージング

    篠遠仁, 島田斉, 平野成樹, 鈴木雅之, 古川彰吾, 川口拓之, 高野晴成, 伊藤浩, 桑原聡, 須原哲也

    日本神経学会学術大会プログラム・抄録集   54th   511   2013

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  • ヒト黒質におけるニューロメラニンMRIとドーパミントランスポーター結合能の加齢変化

    川口拓之, 島田斉, 鈴木雅之, 篠遠仁, 平野成樹, KERSHAW Jeff, 須原哲也, 伊藤浩

    日本神経放射線学会プログラム・抄録集   42nd   114   2013

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  • C-Pittsburg Compound B(PIB)集積と、病理学的アミロイドβ(Aβ)沈着の、解剖学的部位別検討 6剖検例における検討

    初田 裕幸, 石井 賢二, 高尾 昌樹, 金丸 和富, 新井 冨生, 齊藤 祐子, 宮下 哲典, 桑野 良三, 須原 哲也, 島田 斉, 篠遠 仁, 村山 繁雄

    臨床神経学   52 ( 12 )   1401 - 1401   2012.12

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  • [11C]AZD2184PETによるアミロイドイメージング

    島田 斉, 篠遠 仁, 平野 成樹, 森 崇明, 佐藤 康一, 田中 典子, 高野 晴成, 伊藤 浩, 須原 哲也

    臨床神経学   52 ( 12 )   1479 - 1479   2012.12

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  • Neuroimaging Studies of Diabetes and Risk of Alzheimer's Disease

    64 ( 12 )   1411 - 1419   2012.12

  • 前頭前野Aβ蓄積はAlzheimer病患者のアパシーに関連する

    島田 斉, 森 崇明, 篠遠 仁, 平野 成樹, 古川 彰吾, 入江 俊章, 高野 晴成, 伊藤 浩, 桑原 聡, 須原 哲也

    Dementia Japan   26 ( 4 )   484 - 484   2012.10

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  • [11C]racloprideおよび[11C]FLB457によるPET測定の機種間差の比較

    木村泰之, 伊藤浩, 白石貴博, 生駒洋子, 小高文聰, 山田真希子, 高野晴成, 藤原広臨, 島田斉, 菅野巌, 須原哲也

    核医学   49 ( 3 )   280 - S260   2012.8

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  • 黒質の神経メラニンMRIとPETで測定した被殻のドパミントランスポーターとの関係

    島田斉, 篠遠仁, 平野成樹, 森崇明, 川口拓之, 伊藤浩, 須原哲也

    核医学   49 ( 3 )   255   2012.8

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  • 黒質の神経メラニンと被殻のドパミントランスポーターにおける加齢の影響

    篠遠仁, 島田斉, 平野成樹, 鈴木雅之, 森崇明, 川口拓之, 伊藤浩, 須原哲也

    核医学   49 ( 3 )   256   2012.8

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  • ヒト黒質におけるニューロメラニンMRIとドーパミントランスポーター分布密度の比較

    川口拓之, 島田斉, 篠藤仁, 平野成樹, カーショウ ジェフ, 須原哲也, 伊藤浩

    核医学   49 ( 3 )   256   2012.8

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  • Inter-scanner differences in dopamine receptor imaging

    Yasuyuki Kimura, Hiroshi Ito, Takahiro Shiraishi, Makiko Yamada, Fumitoshi Kodaka, Harumasa Takano, Hironobu Fujiwara, Hitoshi Shimada, Iwao Kanno, Tetsuya Suhara

    JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM   32   S190 - S191   2012.8

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  • Comparison between neuromelanin-related MRI signal and dopamine transporter binding measured by PET in humans

    Hiroshi Kawaguchi, Hitoshi Shimada, Masayuki Suzuki, Harumasa Takano, Jeff Kershaw, Tetsuya Suhara, Hiroshi Ito

    JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM   32   S48 - S49   2012.8

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  • PET-認知症 (特集 エキスパートによる脳・頭頸部の臨床に役立つ最新画像診断 : MRI&PET)

    伊藤 浩, 島田 斉

    映像情報medical   44 ( 7 )   674 - 681,626-628   2012.7

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  • ヒト黒質におけるドーパミントランスポーター分布密度とニューロメラニン濃度の解析

    川口 拓之, 島田 斉, Kershaw Jeff

    千葉核医学研究会   28   1 - 3   2012.6

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  • [<sup>18F</sup>FACTによる脳内アミロイド蓄積の測定―A neuritic plaque imaging―

    伊藤浩, 島田斉, 篠遠仁, 関千江, 生駒洋子, 川口拓之, 田桑弘之, 菅野巖, 高野晴成, 須原哲也

    核医学   49 ( 2 )   69   2012.5

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  • Dynamic postural control: Repetitive alternative rotation of the head and thorax

    88 ( 2 )   91 - 91   2012.4

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  • クリスタルキューブ検出器開発(20)サブミリPETへの期待―MRIによる機能情報との比較研究―

    伊藤浩, 川口拓之, 生駒洋子, 青木孝子, 佐野ひろみ, 島田斉, 小高文聰, 木村泰之, 藤原広臨, 高野晴成

    NIRS-R (Natl Inst Radiol Sci)   ( 65 )   56 - 57   2012.3

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  • 黒質におけるニューロメラニン濃度とドーパミントランスポーター分布密度の比較―MRIおよびPETによる検討―

    川口拓之, 島田斉, カーショー ジェフ, 須原哲也, 伊藤浩

    日本神経放射線学会プログラム・抄録集   41st   75   2012

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  • VSRAD次期バージョンの臨床評価

    篠遠 仁, 島田 斉, 平野 成樹, 森 崇明, 江口 洋子, 高野 晴成, 須原 哲也

    Dementia Japan   25 ( 3 )   334 - 334   2011.10

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  • 健常人におけるドーパミンD2/3受容体結合能の脳内局所間での相関について

    小高文聰, 伊藤浩, 藤原広臨, 木村泰之, 高野晴成, 島田斉, 須原哲也

    核医学   48 ( 3 )   346 - 347   2011.9

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  • [F-18]FACTによる脳内アミロイド蓄積の評価 [C-11]PIBとの比較

    伊藤 浩, 島田 斉, 篠遠 仁, 高野 晴成, 小高 文聰, 須原 哲也, 岡村 信行, 谷内 一彦

    核医学   48 ( 3 )   S287 - S287   2011.9

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  • [11C]AZD2184 PETによるアミロイドイメージング

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    脳循環代謝   23 ( 1 )   113   2011

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