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ex vivo imaging of cerebral amyloid angiopathy and its associated lesions using micro-MRI

Research Project

Project/Area Number 16K15246
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Human pathology
Research InstitutionMie University

Principal Investigator

Tomimoto Hidekazu  三重大学, 医学系研究科, 教授 (80324648)

Research Collaborator Hashizume Yoshio  
Niwa Atsushi  
Shindo Akihiro  
Ishikawa Hidehiro  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
KeywordsマイクロMRI / 脳アミロイド血管症 / 剖検脳 / アミロイドβ / 毛細血管
Outline of Final Research Achievements

Amyloid β is a protein causing Alzheimer’s disease, and deposits not only in the neuropil but also in the blood vessels which leads to cerebral amyloid angiopathy (CAA). As a result of vascular amyloid β deposit, various microvascular lesions such as microbleeds and microinfarctions may occur, but the exact pathomechanism of lesion development remained uncertain. In the present study, we applied micro-MRI technique to autopsied brains which enabled us to obtain radiological images of microvascular lesion due to CAA, and further delineated the pathological aspects of these images. In addition, we delineated contribution of neuroinflammation to the loss of vascular integrity, because in the sites of microvascular lesions, there was marked accumulation of inflammatory molecules including complement proteins.

Academic Significance and Societal Importance of the Research Achievements

脳アミロイド血管症は高率にアルツハイマー病に合併するが、それ自体も認知症の原因となる。従来の診断技術では脳アミロイド血管症を臨床的に診断するためには脳生検が必要であったが、本研究の結果から、脳アミロイド血管症を示唆する画像所見に対応する病理変化が明らかになった。この結果、必ずしも脳生検を行わなくてもMRIの画像所見から脳アミロイド血管症を診断する新たな診断技術の可能性が示された。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (31 results)

All 2019 2018 2017 2016

All Journal Article (13 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 13 results,  Open Access: 10 results) Presentation (17 results) (of which Int'l Joint Research: 4 results,  Invited: 14 results) Book (1 results)

  • [Journal Article] Chronic cerebral hypoperfusion upregulates leptin receptor expression in astrocytes and tau phosphorylation in tau transgenic mice.2019

    • Author(s)
      Shimada T, Shindo A, Matsuyama H, Yata K, Niwa A, Sasaki R, Ayaki T, Maki T, Wakita H, Tomimoto H.
    • Journal Title

      Neuroscience Letters

      Volume: 704 Pages: 133-140

    • DOI

      10.1016/j.neulet.2019.04.009

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comparison of Premortem Magnetic Resonance Imaging and Postmortem Autopsy Findings of a Cortical Microinfarct2018

    • Author(s)
      Ishikawa Hidehiro、Ii Yuichiro、Niwa Atsushi、Shindo Akihiro、Ito Ai、Matsuura Keita、Sasaki Ryogen、Uno Kenichiro、Maeda Masayuki、Tomimoto Hidekazu
    • Journal Title

      Journal of Stroke and Cerebrovascular Diseases

      Volume: 27 Issue: 10 Pages: 2623-2626

    • DOI

      10.1016/j.jstrokecerebrovasdis.2018.05.037

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Diffusion tensor imaging and magnetic resonance spectroscopy in a patient with adult onset tuberous sclerosis complex2018

    • Author(s)
      Ishikawa Hidehiro、Niwa Atsushi、Asahi Masaru、Matsuura Keita、Masuzugawa Satoshi、Niida Yo、Maeda Masayuki、Kondo Mineo、Tomimoto Hidekazu
    • Journal Title

      J Clin Neurosci

      Volume: 48 Pages: 108-110

    • DOI

      10.1016/j.jocn.2017.10.072

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comparative Analysis of Cortical Microinfarcts and Microbleeds using 3.0-Tesla Postmortem Magnetic Resonance Images and Histopathology.2017

    • Author(s)
      Niwa A, Ii Y, Shindo A, Matsuo K, Ishikawa H, Taniguchi A, Takase S, Maeda M, Sakuma H, Akatsu H, Hashizume Y, Tomimoto H.
    • Journal Title

      J Alzheimers Dis.

      Volume: 59 Issue: 3 Pages: 951-959

    • DOI

      10.3233/jad-161242

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Double-seropositive myasthenia gravis with acetylcholine receptor and low-density lipoprotein receptor-related protein 4 antibodies associated with invasive thymoma.2017

    • Author(s)
      3.Ishikawa H, Taniguchi A, Ii Y, Higuchi O, Matsuo H, Nakane S, Asahi M, Niwa A, Tomimoto H.
    • Journal Title

      Neuromuscul Disord.

      Volume: 27 Issue: 10 Pages: 914-914

    • DOI

      10.1016/j.nmd.2017.06.001

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Background and distribution of lobar microbleeds in cognitive dysfunction.2017

    • Author(s)
      Matsuyama H, Ii Y, Maeda M, Umino M, Ueda Y, Tabei KI, Kida H, Satoh M, Shindo A, Taniguchi A, Takahashi R, Tomimoto H1
    • Journal Title

      Brain Behav.

      Volume: 7 Issue: 11

    • DOI

      10.1002/brb3.856

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Complement Activation in Capillary Cerebral Amyloid Angiopathy2017

    • Author(s)
      Matsuo Ko、Shindo Akihiro、Niwa Atsushi、Tabei Ken-ichi、Akatsu Hiroyasu、Hashizume Yoshio、Akiyama Haruhiko、Ayaki Takashi、Maki Takakuni、Sawamoto Nobukatsu、Takahashi Ryosuke、Oikawa Shinji、Tomimoto Hidekazu
    • Journal Title

      Dement Geriatr Cogn Disord

      Volume: 44 Issue: 5-6 Pages: 343-353

    • DOI

      10.1159/000486091

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Detection of cerebral amyloid angiopathy by 3-T magnetic resonance imaging and amyloid positron emission tomography in a patient with subcortical ischaemic vascular dementia2017

    • Author(s)
      Kida H, Satoh M, Ii Y, Fukuyama H, Maeda M, Tomimoto H.
    • Journal Title

      Psychogeriatrics

      Volume: 17 Issue: 1 Pages: 70-72

    • DOI

      10.1111/psyg.12187

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Subcortical ischemic vascular disease: roles of oligodendrocyte function in experimental models of subcortical white-matter injury.2016

    • Author(s)
      Shindo A, Liang AC, Maki T, Miyamoto N, Tomimoto H, Lo EH, Arai K.
    • Journal Title

      J Cereb Blood Flow Metab.

      Volume: 36 Pages: 187-98

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Neuropsychological features of microbleeds and cortical microinfarct detected by high resolution magnetic resonance imaging.2016

    • Author(s)
      Ueda Y, Satoh M, Tabei K, Kida H, Ii Y, Asahi M, Maeda M, Sakuma H, Tomimoto H
    • Journal Title

      J Alzheimers Dis.

      Volume: 53 Issue: 1 Pages: 315-25

    • DOI

      10.3233/jad-151008

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Astrocyte-Derived Pentraxin 3 Supports Blood-Brain Barrier Integrity Under Acute Phase of Stroke2016

    • Author(s)
      Shindo A, Maki T, Mandeville ET, Liang AC, Egawa N, Itoh K, Itoh N, Borlongan M, Holder JC, Chuang TT, McNeish JD, Tomimoto H, Lok J, Lo EH, Arai K.
    • Journal Title

      Stroke

      Volume: 47 Issue: 4 Pages: 1094-100

    • DOI

      10.1161/strokeaha.115.012133

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A longitudinal study of neuromelanin-sensitive magnetic resonance imaging in Parkinson’s disease.2016

    • Author(s)
      Matsuura K, Maeda M, Tabei K, Umino M, Kajikawa H, Satoh M, Kida H, Tomimoto H.
    • Journal Title

      Neuroscience Letters

      Volume: 633 Pages: 112-17

    • DOI

      10.1016/j.neulet.2016.09.011

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Detection of Low-Signal Pulvinar Areas Using Diffusion-Weighted Imaging in Patients with Dementia Experiencing Visual Hallucinations.2016

    • Author(s)
      Sugiura M, Satoh M, Tabei KI, Saito T, Mori M, Abe M, Kida H, Maeda M, Sakuma H, Tomimoto H.
    • Journal Title

      Dement Geriatr Cogn Dis Extra

      Volume: 6 Pages: 458-464

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Differentiation of cortical microinfarctions due to cerebral amyloid angiopathy from those caused by microembolism on 3T MRI2019

    • Author(s)
      Hidehiro Ishikawa, Yuichiro Ii, Akihiro Shindo, Masayuki Maeda, Ai Ito, Maki Umino, Keita Matsuura, Akira Taniguchi, Hidekazu Tomimoto
    • Organizer
      International Stroke Conference 2019
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 微小塞栓と脳アミロイド血管症による皮質微小梗塞:3T-MRIによる検出と鑑別の試み2019

    • Author(s)
      石川 英洋、 伊井 裕一郎、新堂 晃大、 伊藤 愛、松山 裕文、松浦 慶太、 田部井 賢一、海野 真記、前田 正幸、 冨本 秀和
    • Organizer
      第44回日本脳卒中学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Nosologic considerations on vascular dementia using SPECT and MRI2018

    • Author(s)
      Hidekazu Tomimoto
    • Organizer
      13th annual meeting of Taiwan Stroke Society(TSS)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Role of small vessel disease in the boundaries of large vessel disease and Alzheimer disease2018

    • Author(s)
      Hidekazu Tomimoto
    • Organizer
      19th International Congress of Neuropathology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Comparative analysis of cortical microinfarcts on 3T MRI in patients with cerebral amyloid angiopathy and embolic stroke2018

    • Author(s)
      Hidehiro Ishikawa, Yuichiro Ii, Akihiro Shindo, Ai Ito, Ken-ichi Tabei, Hirofumi Matsuyama, Keita Matsuura, Maki Umino, Masayuki Maeda, Hidekazu Tomimoto
    • Organizer
      16th Asian Oceanian Congress of Neurology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 生活習慣と認知症リスクについて2018

    • Author(s)
      冨本秀和
    • Organizer
      第52回日本成人病(生活習慣病)学術大会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 微小脳血管病と片頭痛2018

    • Author(s)
      冨本秀和
    • Organizer
      第43回日本脳卒中学会学術集会(STROKE2018)
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 脳小血管病と脳卒中の未来地図2018

    • Author(s)
      冨本秀和
    • Organizer
      第43回日本脳卒中学会学術集会(STROKE2018)
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 脳小血管病の病態と診断~日本と欧米の違いも含めて2017

    • Author(s)
      冨本秀和
    • Organizer
      第42回日本脳卒中学会
    • Place of Presentation
      大阪国際会議場(大阪府・大阪市)
    • Year and Date
      2017-03-16
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] 脳小血管病の病理と臨床症状2017

    • Author(s)
      冨本秀和
    • Organizer
      第26回日本脳ドック学会総会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 【認知症医療の最前線】認知症の画像と病理;診断精度の向上のために2017

    • Author(s)
      冨本秀和
    • Organizer
      第59回日本老年医学会学術集会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 血管性認知症 ;revisited2017

    • Author(s)
      冨本秀和
    • Organizer
      第36回日本認知症学会学術集会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 脳アミロイド血管症の診療最前線2017

    • Author(s)
      冨本秀和
    • Organizer
      第8回日本脳血管・認知症学会総会(VAS-COG Japan 2017)
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 血管性認知症診療の新展開2016

    • Author(s)
      冨本秀和
    • Organizer
      第35回日本認知症学会学術集会
    • Place of Presentation
      東京国際フォーラム(東京都・千代田区)
    • Year and Date
      2016-12-01
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] 大脳白質病変は何を反映しているのか;MRI撮像法、評価法の比較による病態の理解2016

    • Author(s)
      冨本秀和
    • Organizer
      第58回日本老年医学会学術集会
    • Place of Presentation
      石川県立音楽堂、ANAクラウンプラザホテル金沢(石川県・金沢市)
    • Year and Date
      2016-06-08
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] 認知症抑制は可能か?2016

    • Author(s)
      冨本秀和
    • Organizer
      第5回臨床高血圧フォーラム
    • Place of Presentation
      ステーションコンファレンス東京(東京都・千代田区)
    • Year and Date
      2016-05-14
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] 脳小血管病の病態と診断2016

    • Author(s)
      冨本秀和
    • Organizer
      第41回日本脳卒中学会総会
    • Place of Presentation
      ロイトン札幌・札幌市教育文化会館(北海道・札幌市)
    • Year and Date
      2016-04-14
    • Related Report
      2016 Research-status Report
    • Invited
  • [Book] 認知症イメージングテキスト2018

    • Author(s)
      冨本 秀和
    • Total Pages
      15
    • Publisher
      医学書院
    • ISBN
      9784260032315
    • Related Report
      2018 Annual Research Report

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Published: 2016-04-21   Modified: 2020-03-30  

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