Timely Visualization of the Collaterals Formed during Acute Ischemic Stroke with Fe₃ O₄ Nanoparticle-based MR Imaging...

Ischemic stroke is one of the major leading causes for long-term disability and mortality. Collateral vessels provide an alternative pathway to protect the brain against ischemic injury after arterial occlusion. Aiming at visualizing the collaterals occurring during acute ischemic stroke, an integrin α_v β₃ -specific Fe₃ O₄ -Arg-Gly-Asp (RGD) nanoprobe is prepared for magnetic resonance imaging (MRI) of the collaterals. Rat models are constructed by occluding the middle cerebral artery for imaging studies of cerebral ischemia and ischemia-reperfusion on 7.0 Tesla MRI using susceptibility-weighted imaging sequence. To show the binding specificity to the collaterals, the imaging results acquired with the Fe₃ O₄ -RGD nanoprobe and the Fe₃ O₄ mother nanoparticles, respectively, are carefully compared. In addition, an RGD blocking experiment is also carried out to support the excellent binding specificity of the Fe₃ O₄ -RGD nanoprobe. Following the above experiments, cerebral ischemia-reperfusion studies show the collateral dynamics upon reperfusion, which is very important for the prognosis of various revascularization therapies in the clinic. The current study has, for the first time, enabled the direct observation of collaterals in a quasi-real time fashion and further disclosed that the antegrade flow upon reperfusion dominates the blood supply of primary ischemic tissue during the early stage of infarction, which is significantly meaningful for clinical treatment of stroke.