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Abstract
Background and PurposeChronic inflammation is involved in the formation and enlargement of cerebral aneurysms (CAs), with macrophages playing a key role in the process. The present study evaluated visualization of macrophages present in CAs using an activatable fluorescent probe (IONP-ICG) comprising an iron oxide nanoparticles (IONPs) conjugated with indocyanine green (ICG).MethodsIONP-ICG was intravenously administered to 15-week-old CA model rats (n = 8), and ex vivo near-infrared fluorescence (NIRF) imaging and histological assessment of exposed CAs and cerebral arteries were performed 48 h later. Similar evaluations were performed in the control group, which included CA model rats given IONPs or ICG (n = 8 each).ResultsICG-derived NIRF signals were detected in three IONP-ICG group rats but not in IONP or ICG control groups. Among the three rats that exhibited signals, NIRF signal accumulation was observed in the CA of two rats and at the site of hemodynamic stress in the left posterior cerebral artery in one rat. Histologically, NIRF signals correlated strongly with macrophage localization. A total of 13 CAs formed in the IONP-ICG group. The number of macrophages in the CA wall was significantly greater in the two CAs that exhibited NIRF signals compared to the remaining 11 CAs that did not (P = 0.037). Moreover, all 11 CAs that did not exhibit NIRF signals were iron-negative, while the two CAs that exhibited NIRF signals were both iron-positive (P = 0.013).ConclusionNIRF imaging using an activatable 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.
Highlights
Chronic inflammation is involved in the formation and enlargement of cerebral aneurysms (CAs), and macrophages, which are the primary inflammatory cells that accumulate in the aneurysm wall, play an essential role in these processes (Aoki et al, 2007a,b, 2017a; Kanematsu et al, 2011; Kataoka, 2015)
The present study evaluated whether macrophages localized to CAs can be detected using our activatable IONPICG near-infrared fluorescence (NIRF) probe
All saccular CAs formed at the left posterior cerebral artery, with one in the iron oxide nanoparticles (IONPs)-indocyanine green (ICG) group, and three in the IONP-PEG; saccular CAs did not form in the ICG group
Summary
Chronic inflammation is involved in the formation and enlargement of cerebral aneurysms (CAs), and macrophages, which are the primary inflammatory cells that accumulate in the aneurysm wall, play an essential role in these processes (Aoki et al, 2007a,b, 2017a; Kanematsu et al, 2011; Kataoka, 2015). Macrophage Imaging in Cerebral Aneurysms of ruptured CAs compared to unruptured, suggesting an association between macrophages and CA rupture (Frosen et al, 2004) For this reason, macrophage imaging may enable identification of early lesions in the CA formation process as well as prediction of enlargement and rupture. Chronic inflammation is involved in the formation and enlargement of cerebral aneurysms (CAs), with macrophages playing a key role in the process. The present study evaluated visualization of macrophages present in CAs using an activatable fluorescent probe (IONP-ICG) comprising an iron oxide nanoparticles (IONPs) conjugated with indocyanine green (ICG)
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