MRI and isotope microscopy using 17O-labeled water to elucidate water dynamics in the central nervous system.

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K17256
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52040:Radiological sciences-related
• Research Institution: Hokkaido University
• Principal Investigator: Kameda Hiroyuki 北海道大学, 歯学研究院, 助教 (70829887)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 17O-MRI / glymphatic system / Neurofluids / stable isotope / isotope microscopy

Outline of Final Research Achievements

We established an experimental system that allowed evaluation by indirect 17O-MRI during intrathecal and intravascular administration of 17O-labeled water in rats. We visualized the intrathecal dynamics of 17O-labeled water administered intrathecally to a normal rat. In the 17O arterial infusion model, we traced the spatiotemporal spread of water from the cerebral arterial blood to other water spaces in the cranium. Evaluation during intrathecal injection of 17O-labeled water using the amyotrophic lateral sclerosis (ALS) rat model revealed that 17O-labeled water tended to be distributed within the brain parenchyma in the ALS rat group. To map 17O-labeled water in the brain at the microscopic level, we used a cryo-electron microscopy environment and observed water-containing biological samples. 18O-labeled water was injected directly into the rat brain or intraportally into the rat liver grafts for analyses, enabling the microimaging of its anatomical distribution.

Free Research Field

Radiology

Academic Significance and Societal Importance of the Research Achievements

脳リンパ系を含む脳内水循環の仕組みや疾患への関与が少しずつ明らかになりつつある。本研究で発展したイメージング技術は、生体の水分子をマルチスケールで直接追跡するものであり、脳リンパ系の生理的な役割や病態形成への関与を明らかにし、この分野の研究のさらなる進歩に役立てることができる。また、本研究で扱った筋萎縮性側索硬化症や、認知症、その他の神経疾患の病態解明が進み、これまでにない早期画像診断や治療戦略につながることが期待される。