PDF(Pubmed)
Abstract：
In acute ischemic stroke, even when successful recanalization is obtained, downstream microcirculation may still be obstructed by microvascular thrombosis, which is associated with compromised brain reperfusion and cognitive decline. Identifying these microthrombi through non-invasive methods remains challenging. We developed the PHySIOMIC (Polydopamine Hybridized Self-assembled Iron Oxide Mussel Inspired Clusters), a MRI-based contrast agent that unmasks these microthrombi. In a mouse model of thromboembolic ischemic stroke, our findings demonstrate that the PHySIOMIC generate a distinct hypointense signal on T2*-weighted MRI in the presence of microthrombi, that correlates with the lesion areas observed 24 hours post-stroke. Our microfluidic studies reveal the role of fibrinogen in the protein corona for the thrombosis targeting properties. Finally, we observe the biodegradation and biocompatibility of these particles. This work demonstrates that the PHySIOMIC particles offer an innovative and valuable tool for non-invasive in vivo diagnosis and monitoring of microthrombi, using MRI during ischemic stroke.
摘要：
在急性缺血性中风中，即使获得了成功的再通，下游微循环可能仍然被微血管血栓阻塞，这与受损的大脑再灌注和认知能力下降有关。通过非侵入性方法识别这些微血栓仍然具有挑战性。我们开发了PHYSIOMIC（聚多巴胺杂交自组装氧化铁贻贝启发簇），一种基于MRI的造影剂，可以揭开这些微血栓。在血栓栓塞性缺血性中风的小鼠模型中，我们的发现表明，在存在微血栓的情况下，PHYSIOMIC在T2*加权MRI上产生明显的低信号，这与卒中后24小时观察到的病变区域相关。我们的微流体研究揭示了纤维蛋白原在血栓形成靶向特性的蛋白质冠中的作用。最后,我们观察到这些颗粒的生物降解和生物相容性。这项工作表明，PHYSIOMIC颗粒为微血栓的非侵入性体内诊断和监测提供了一种创新和有价值的工具，在缺血性卒中期间使用MRI。
