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Identification of ALS-related brain networks and development of a diagnostic/monitoring system

Research Project

Project/Area Number 20K12670
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 90130:Medical systems-related
Research InstitutionJuntendo University (2021-2022)
The University of Tokushima (2020)

Principal Investigator

Sako Wataru  順天堂大学, 医学部, 准教授 (60581155)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords筋萎縮性側索硬化症 / バイオマーカー / MRI / fMRI / MRS / 一次運動野 / 補足運動野 / 感覚運動ネットワーク / ALS / 安静時機能的MRI / 構造的MRI / 診療支援システム / 診断支援システム / グルタミン酸 / N-アセチルアスパラギン酸 / NAA / ネットワーク
Outline of Research at the Start

筋萎縮性側索硬化症の正確な早期診断と客観的モニタリングは、実際の臨床のみならず、信頼性の高い臨床試験の遂行においても重要であり、それをサポートするシステムが必要とされている。新たな筋萎縮性側索硬化症診断・モニタリング支援システム構築を目指して、以下の研究項目を予定している。
①安静時脳機能MRIを用いた筋萎縮性側索硬化症に関連する病的な脳機能ネットワークの同定。
②その他のMRIバイオマーカー(大脳皮質の厚さ、apparent diffusion coefficient値、b0画像の信号強度、皮質脊髄路の仮想線維数)の診断・モニタリング能力の評価。
③上記方法を統合した筋萎縮性側索硬化症診断・モニタリング支援システム構築。

Outline of Final Research Achievements

The objective diagnosis and monitoring system is important to perform clinical trials for amyotrophic lateral sclerosis (ALS). We hypothesized that brain networks-related alterations in MRI, MR spectroscopy, and protein biomarkers could contribute to building a new diagnostic and monitoring system. Increased glutamate and decreased N-acetyl aspartate concentrations were reported in the supplementary motor cortex, and serum neurofilament light chain concentrations were found to be excellent for ALS diagnosis even in the early stages. MRI can detect reduced volume of the primary motor cortex in cases that do not meet diagnostic criteria of ALS but actually have ALS, and is expected to help the diagnosis. We also found that atrophy of the primary motor cortex was associated with hyperactivity of the sensory-motor network.

Academic Significance and Societal Importance of the Research Achievements

筋萎縮性側索硬化症 (ALS)における補足運動野のグルタミン酸/N-アセチルアスパラギン酸 (NAA)比の上昇は、ALSの神経興奮毒性仮説に矛盾しないグルタミン酸の上昇、神経細胞減少と関連するNAA減少を統合したバイオマーカーとなりうる可能性がある。進行期だけではなく、早期のALSでも血清神経フィラメント軽鎖濃度減少が診断に有用なことも証明でき、早期診断のバイオマーカーとしてのエビデンス構築にも寄与できた。一次運動野容量の減少、全灰白質容量の経時的減少も報告でき、上記報告と併せALS診断・モニタリングシステム構築へ近づくことができた。

Report

(3 results)
  • 2022 Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (13 results)

All 2022 2021 2020

All Journal Article (7 results) (of which Peer Reviewed: 7 results,  Open Access: 2 results) Presentation (6 results) (of which Invited: 4 results)

  • [Journal Article] Serum NfL and CHI3L1 for ALS and parkinsonian disorders in the process of diagnosis2022

    • Author(s)
      Shotaro Haji, Wataru Sako, Nagahisa Murakami, Yusuke Osaki, Yuishin Izumi
    • Journal Title

      J Neural Transm

      Volume: 129 Issue: 3 Pages: 301-309

    • DOI

      10.1007/s00702-022-02470-z

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] The cerebellum is a common key for visuospatial execution and attention in Parkinson’s disease2021

    • Author(s)
      Wataru Sako, Takashi Abe, Yuki Matsumoto, Kazumi Nakamura, Shotaro Haji, Yusuke Osaki, Masafumi Harada, Yuishin Izumi
    • Journal Title

      Diagnostics

      Volume: 11 Issue: 6 Pages: 1042-1042

    • DOI

      10.3390/diagnostics11061042

    • NAID

      120007178462

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The value of serum uric acid as a potential biomarker in amyotrophic lateral sclerosis: Evidence from a meta-analysis2021

    • Author(s)
      Shotaro Haji, Wataru Sako, Nagahisa Murakami, Yusuke Osaki, Takahiro Furukawa, Yuishin Izumi, Ryuji Kaji
    • Journal Title

      Clinical Neurology and Neurosurgery

      Volume: 203 Pages: 106566-106566

    • DOI

      10.1016/j.clineuro.2021.106566

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] MR tractography exhibiting retrograde degeneration of the corticospinal tract in a patient with a unilateral spinal cord tumor2021

    • Author(s)
      Yusuke Osaki, Wataru Sako, Masafumi Harada, Yuishin Izumi
    • Journal Title

      Brain and Behavior

      Volume: 11 Issue: 4

    • DOI

      10.1002/brb3.2020

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A new quantitative index in the diagnosis of Parkinson syndrome by dopamine transporter single photon emission computed tomography2021

    • Author(s)
      Ryota Bando, Hideki Otsuka, Tamaki Otani, Noritake Matsuda, Shota Azane, Yamato Kunikane, Yoichi Otomi, Wataru Sako, Yuishin Izumi, Masafumi Harada
    • Journal Title

      Annals of Nuclear Medicine

      Volume: 35 Issue: 4 Pages: 504-513

    • DOI

      10.1007/s12149-021-01592-w

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] MR spectroscopy and imaging-derived measurements in the supplementary motor area for biomarkers of amyotrophic lateral sclerosis2021

    • Author(s)
      Wataru Sako, Yuishin Izumi, Takashi Abe, Shotaro Haji, Nagahisa Murakami, Yusuke Osaki, Yuki Matsumoto, Masafumi Harada, Ryuji Kaji
    • Journal Title

      Neurological Sciences

      Volume: - Issue: 10 Pages: 4257-4263

    • DOI

      10.1007/s10072-021-05107-3

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Differences in cerebellar perfusion between Parkinson’s disease and multiple system atrophy2020

    • Author(s)
      Nagahisa Murakami, Wataru Sako, Shotaro Haji, Takahiro Furukawa, Yoichi Otomi, Hideki Otsuka, Yuishin Izumi, Masafumi Harada, Ryuji Kaji
    • Journal Title

      Journal of Neurological Sciences

      Volume: 409 Pages: 116627-116627

    • DOI

      10.1016/j.jns.2019.116627

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Presentation] パーキンソン病鑑別診断に役立つMRI -測定のススメ-2021

    • Author(s)
      佐光 亘、服部信孝
    • Organizer
      第15回パーキンソン病・運動障害疾患コングレス
    • Related Report
      2021 Research-status Report
  • [Presentation] レビー小体型認知症とパーキンソン病のパーキンソニズム2021

    • Author(s)
      佐光 亘、服部信孝
    • Organizer
      第62回日本神経学会学術大会
    • Related Report
      2021 Research-status Report
  • [Presentation] 役に立つ脳画像2021

    • Author(s)
      佐光 亘
    • Organizer
      第14回パーキンソン病・運動障害疾患コングレス
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] 進化するパーキンソン病の構造・機能画像バイオマーカー2020

    • Author(s)
      佐光 亘
    • Organizer
      第61回日本神経病理学会総会学術研究会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] Tractographyの可能性2020

    • Author(s)
      佐光 亘
    • Organizer
      第61回日本神経学会学術大会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] PSP/CBS: 診断における脳画像の役割2020

    • Author(s)
      佐光 亘
    • Organizer
      第61回日本神経学会学術大会
    • Related Report
      2020 Research-status Report
    • Invited

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Published: 2020-04-28   Modified: 2024-01-30  

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