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Visualising superfine cerebrovasculature in MRI using supramolecular self-assembly

Research Project

Project/Area Number 22K20520
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeMulti-year Fund
Review Section 0403:Biomedical engineering and related fields
Research InstitutionNational Cardiovascular Center Research Institute

Principal Investigator

SONI RAGHAV  国立研究開発法人国立循環器病研究センター, 研究所, リサーチフェロー (10967863)

Project Period (FY) 2022-08-31 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2023: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
KeywordsNanoparticles / Fluorescein / PEG / Self-assembly / MRI contrast / self-assembly / 4-arm PEG / 4 arm PEG / Fe3O4 / Supramolecular assembly / MRI contrast agent / Cerebrovasculature / 8 arms-PEG
Outline of Research at the Start

MRI is a powerful, non-invasive tool for evaluating and diagnosing cerebral vasculature. However, MR techniques are limited only for the cerebral vessels larger than 1mm because of weak signal. Currently, clinically available contrast agents are lower molecular weight; therefore, higher diffusion across the vascular endothelium causes poor contrast quality. Herein, we propose developing a supramolecular self-assemble polymer-based contrast agent that minimizes the signal in the intravascular space, circulates stably in the blood, and excretion thoroughly to visualize the cerebral vasculature.

Outline of Final Research Achievements

In this study, we created a self-assembled iron oxide nanoparticle-based contrast agent for high-resolution imaging of the cerebrovasculature. The branched polyethylene glycols having approximately 10 kDa of molecular weight are conjugated with iron oxide nanoparticles and fluorescein. The self-assembled fiber structure is concentration-dependent and formed by electrostatic interaction. Self-assembly fibers measuring 120 nm in length and 50 nm in width are detected at 25 mg/ml. Furthermore, self-assembly contrast administered intravenously in a rat model revealed a more significant cerebral microvascular network than conventional MRI imaging. The research result was presented at several domestic conferences and published in an international journal.

Academic Significance and Societal Importance of the Research Achievements

This study demonstrated that self-assemble contrast, when delivered into the circulation, can visualize microvascular networks that conventional MRI imaging cannot, making it an effective new imaging tool for diagnosing cerebral atherosclerosis and stroke.

Report

(3 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • Research Products

    (10 results)

All 2023 2022 Other

All Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results) Presentation (8 results) (of which Int'l Joint Research: 6 results) Remarks (1 results)

  • [Journal Article] In vivo MR imaging for tumor-associated initial neovascularization by supramolecular contrast agents2023

    • Author(s)
      Atsushi Mahara, Keigo Shima, Raghav Soni, Ryutaro Onishi, Yoshiaki Hirano, Shigeyoshi Saito, Tetsuji Yamaoka
    • Journal Title

      Colloids and Surfaces B: Biointerfaces

      Volume: 230 Pages: 113525-113525

    • DOI

      10.1016/j.colsurfb.2023.113525

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Self-assemble iron-oxide nanocluster with improved pharmacokinetics2023

    • Author(s)
      Raghav Soni, Tetsuji Yamaoka, and Atsushi Mahara
    • Organizer
      45th annual meeting of the Japanese society for biomaterials
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Self-assemble iron-oxide nanocluster for MR contrast agent2023

    • Author(s)
      Raghav Soni
    • Organizer
      18th Young Researcher Presentation Meeting JSB Kansai Block
    • Related Report
      2023 Annual Research Report
  • [Presentation] Self-assemble iron-oxide nanocluster for superfine cerebrovasculature MR imaging2023

    • Author(s)
      Raghav Soni
    • Organizer
      1st annual NCVC symposium
    • Related Report
      2023 Annual Research Report
  • [Presentation] Synthesis of fluorescein conjugated iron-oxide nanocluster for MR contrast agent2023

    • Author(s)
      Raghav Soni, Tetsuji Yamaoka, Atsushi Mahara
    • Organizer
      72nd Society of Polymer Science Japan annual meeting (SPSJ)
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] Supramolecular MR contrast agents for visualizing cancer angiogenesis2023

    • Author(s)
      Atsushi Mahara, Raghav Soni, Shigeyoshi Saito, Tetsuji Yamaoka
    • Organizer
      72nd Society of Polymer Science Japan annual meeting (SPSJ)
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] Synthesis of fluorescein/Fe3O4 nanoparticle-conjugated polyethylene glycol for self-assemble MR contrast agent2022

    • Author(s)
      Raghav Soni, Atsushi Mahara, Tetsuji Yamaoka
    • Organizer
      44th annual meeting of Japanese Society of Biomaterials (JSB)
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] Self-assembled formation of fluorescein/Gd-chelate-conjugated polyethylene glycol for microvasculature MR imaging2022

    • Author(s)
      Atsushi Mahara, Raghav Soni, Shigeyoshi Saito, Tetsuji Yamaoka
    • Organizer
      44th annual meeting of Japanese Society of Biomaterials (JSB)
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] Self-assembled formation of fluorescein/Gd-chelate-conjugated polyethylene glycol for microvasculature MR imaging2022

    • Author(s)
      Atsushi Mahara, Raghav Soni, Shigeyoshi Saito, Tetsuji Yamaoka
    • Organizer
      71th symposium on macromolecules
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Remarks] 高分子/鉄ナノ微粒子の“弱い”複合体が拓く新たな MRI 診断プローブ~安全性・画像精度の向上

    • URL

      https://main.spsj.or.jp/koho/72n.pdf

    • Related Report
      2023 Annual Research Report

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Published: 2022-09-01   Modified: 2025-01-30  

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