Activatable Fluorescence Imaging of Macrophages in Cerebral Aneurysms Using Iron Oxide Nanoparticles Conjugated With Indocyanine Green

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08992
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56010:Neurosurgery-related
• Research Institution: Kyoto University
• Principal Investigator: Ishii Akira 京都大学, 医学研究科, 特定准教授 (30467469)
• Co-Investigator(Kenkyū-buntansha): 青木 友浩 国立研究開発法人国立循環器病研究センター, 研究所, 室長 (40633144)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: macrophage / inflammation / cerebral aneurysm / iron oxide / nanoparticles / fluorescent imaging / indocyanine green

Outline of Final Research Achievements

Chronic inflammation is involved in the formation and enlargement of cerebral aneurysms (CAs), with macrophages playing a key role in the process. Iron oxide nanoparticles (IONPs) conjugated with indocyanine green (ICG) was intravenously administered to 15-week-old CA model rats, and ex vivo near-infrared fluorescence (NIRF) imaging and histological assessment of exposed CAs and cerebral arteries were performed. ICG-derived NIRF signals were detected in the CA and at the site of hemodynamic stress in the left posterior cerebral artery. Histologically, NIRF signals correlated strongly with macrophage localization. Based on the results of this study, NIRF imaging using an IONP-ICG probe is feasible for detecting the macrophage-rich regions in CAs and the cerebral artery wall, which is considered an early lesion in the process of CA formation.

Free Research Field

脳動脈瘤

Academic Significance and Societal Importance of the Research Achievements

インドシアニングリーン標識酸化鉄ナノ粒子を用いた近赤外蛍光イメージングは、3次元的なマクロファージの発現様式を可視化できるため、動脈瘤壁への血行力学的ストレスとの関連性を評価することで、更なる基礎研究の発展に繋がる可能性がある。生体で使用できれば、リアルタイムにマクロファージを標的とした慢性炎症の局在を検出することが可能となる。そのため、脳動脈瘤に対する開頭クリッピング術中に脳動脈瘤と脳血管の慢性炎症を検出して、手術支援と脳動脈瘤根治率の向上に寄与する可能性がある。