Visualising superfine cerebrovasculature in MRI using supramolecular self-assembly
| Project/Area Number |
22K20520
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Multi-year Fund |
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| Review Section |
0403:Biomedical engineering and related fields
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| Research Institution | National Cardiovascular Center Research Institute |
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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)
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| Project Period (FY) |
2022-08-31 – 2024-03-31
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| Project Status |
Granted (Fiscal Year 2022)
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| 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)
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| Keywords | Fluorescein / 4 arm PEG / Fe3O4 / Supramolecular assembly / MRI contrast agent / Cerebrovasculature / 8 arms-PEG |
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| 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.
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| Outline of Annual Research Achievements |
Iron oxide nanoparticles (IONPs) are promising contrast agents in terms of their high T1/T2 relaxation time and biocompatibility. However, IONPs easily accumulate in the liver and possess shorter circulation time. Therefore, microvessel imaging is not possible with them. Nanoparticles size between ~100 to 200 nm should be optimal to achieve maximum stability and longer circulation time. Firstly, we have synthesized fluorescein/Fe3O4 conjugated PEG that can form supramolecular self-assemble structure by the fluorescein groups stacked with one another. We have performed different characterization test as FTIR, UV-spectra and XPS to confirm the synthesis. Dynamic light scattering (DLS) analysis has been performed to confirm the change in hydrodynamic radius. Further we have evaluated self-assemble structure stability with different time, pH and temperature. Fluorescein conjugation enhance stability of self-assembly structure at normal pH, and the structure get disintegrated in alkaline pH. Moreover, blood circulation test and organ accumulation analysis have performed on small animal. These results were presented at 44th annual meeting of Japanese Society of Biomaterials (JSB), and 72nd annual meeting of Society of Polymer Science Japan (SPSJ).
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
The research is progress well and on the time. We have successfully synthesized fluorescein/Fe3O4 conjugated PEG that can form supramolecular self-assemble structure. Moreover, we have observed disintegration behavior of supramolecular structure at alkaline ph. This phenomenon is very important for urinary track excretion during in-vivo experiments. We are analyzing in-vivo behavior of supramolecular self-assemble structure.
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| Strategy for Future Research Activity |
For the next stage, we will synthesis fluorescein/Fe3O4 conjugated PEG with different structure and molecular weight as liner, 4-arm and 8-arm with 10kDa, and 20kDa. We will inject them in rat to analyze blood circulation, organ accumulation and urinary track excretion. H&E staining and Prussian blue staining will be performed to examine impact and accumulation of the contrast agent in different organs. Finally, we will perform rat cerebrovascular imaging using 7T MRI. Based on the findings in the first year, the applicant is going to write and publish a paper in an international journal. Also, the applicant expects to present the new findings this year at an international conference.
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Report
(1 results)
Research Products
(5 results)
