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Elucidation of cerebral circulation by the use of polymeric MRI contrast agents

Research Project

Project/Area Number 20H04536
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 90120:Biomaterials-related
Research InstitutionJikei University School of Medicine

Principal Investigator

Yokoyama Masayuki  東京慈恵会医科大学, 医学部, 教授 (20220577)

Co-Investigator(Kenkyū-buntansha) 白石 貢一  東京慈恵会医科大学, 医学部, 准教授 (40426284)
小松 鉄平  東京慈恵会医科大学, 医学部, 講師 (60723856)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2022: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2021: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2020: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
KeywordsGlymphatic system / アルツハイマー病 / 高分子MRI造影剤 / 低分子MRI造影剤 / Gd蓄積 / MRI / 脳循環 / 脳脊髄液 / Gymphatic system / 高分子造影剤 / 高分子 / Gd造影剤 / MRI造影剤
Outline of Research at the Start

第3の脳体液循環システムとして発見されたGlymphatic system(GLSと略す)は、脳の生理・代謝機能と脳神経疾患病理の理解に不可欠である。しかし、GLS体液循環は定性的な理解に留まっている現状である。一方、低分子MRI造影剤投与で、その成分ガドリニウム(Gd)がGLS経由で脳特定部位に蓄積することが問題となっている。
本研究は、申請者が作製した高分子MRI造影剤を用い、GLS循環および脳蓄積を定量的に測定し、GLSの境界移動における分子量依存性を解明すると共に、Gd脳蓄積リスクの無いMRI造影剤の臨床応用に向けた安全性を証明することを目的とする。

Outline of Final Research Achievements

This study revealed by the used of MRI and MRI-contrast agents that macromolecules transferred from the blood into the cerebrospinal fluid, and that this transfer was site-specific among several cerebrospinal-fluid-containing sites in the brain.
This transfer, in other words, enhancement of the blood-cerebrospinal fluid barrier’s (BCSFB’s) permeability was observed to be enhanced by young ages of mouse and by mannitol pre-injection. Mannitol is known to enhance blood brain barrrier’s (BBB’s) permeability, but the enhancement degree was found to be much higher for BCSFB than for BBB.

Academic Significance and Societal Importance of the Research Achievements

従来測定の対象になっていなかった血液脳脊髄液関門の高分子透過性という、基礎的な生体挙動をMRIの手法でその透過部位も含めて明らかにすることに成功した学術的価値は高いと考えられる。また、その透過性は様々な要因によって亢進し得ることから、脳神経疾患の病理に新しい解明の糸口を与える可能性がある。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • Research Products

    (5 results)

All 2023 2021 2020 Other

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 1 results) Presentation (1 results) Remarks (1 results)

  • [Journal Article] Precipitation of Insoluble Fibrin in the Brains of Alzheimer’s Disease Model Mice.2023

    • Author(s)
      Osman B, Wang Z, Shiraishi K, Yokoyama M, Matsumura Y
    • Journal Title

      Journal of Blood Disorders

      Volume: 10 Pages: 1070-1070

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Single intratracheal administration of cross-linked water-soluble acrylic acid polymer causes acute alveolo-interstitial inflammation and the subsequent fibrotic formation possibly via the TGF-β1 pathway in the lung of rats.2021

    • Author(s)
      Machi Suka, Takamasa Kido, Wataru Yoshioka, Eri Hachisuka, Hiroto Okoshi,Takashi Yamauchi, Hiroshi Hano, Takashi Okano, Masayuki Yokoyama, and Hiroyuki Yanagisawa
    • Journal Title

      Toxicology,

      Volume: 448 Pages: 152647-152647

    • DOI

      10.1016/j.tox.2020.152647

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Stability evaluation of Gd chelates for macromolecular MRI contrast agents.2020

    • Author(s)
      Masayuki Yokoyama, Kouichi Shiraishi
    • Journal Title

      Magnetic Resonance Materials in Physics

      Volume: 3 Issue: 4 Pages: 527-536

    • DOI

      10.1007/s10334-019-00805-8

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Presentation] MRI造影剤のGd蓄積リスクの低減:高分子造影剤の戦略2021

    • Author(s)
      横山昌幸、白石貢一
    • Organizer
      第15回日本分子イメージング学会
    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
  • [Remarks] 医用エンジニアリング研究部

    • URL

      http://www.jikei.ac.jp/academic/course/24_gazou.html

    • Related Report
      2020 Annual Research Report

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

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