Jacqmarcq Charlène, Picot Audrey, Flon Jules, Lebrun Florent, Martinez de Lizarrondo Sara, Naveau Mikaël, Bernay Benoît, Goux Didier, Rubio Marina, Malzert-Fréon Aurélie, Michel Anita, Proamer Fabienne, Mangin Pierre, Gauberti Maxime, Vivien Denis, Bonnard Thomas
Normandie University, UNICAEN, Université Caen Normandie, INSERM UMR-S U1237, Physiopathology and Imaging of Neurological Disorders (PhIND), GIP Cyceron, Institute Blood and Brain @ Caen-Normandie (BB@C), Caen, France.
Normandie University, UNICAEN, Université Caen Normandie, CNRS UMS 3408, Caen, France.
Nat Commun. 2024 Jun 13;15(1):5070. doi: 10.1038/s41467-024-49480-x.
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 T*-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.
在急性缺血性卒中中,即使成功实现再灌注,下游微循环仍可能被微血管血栓阻塞,这与脑再灌注受损和认知功能下降有关。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,可揭示这些微血栓。在血栓栓塞性缺血性卒中的小鼠模型中,我们的研究结果表明,PHySIOMIC在存在微血栓的情况下,在T*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蛋白质冠层中对血栓靶向特性的作用。最后,我们观察了这些颗粒的生物降解和生物相容性。这项工作表明,PHySIOMIC颗粒为在缺血性卒中期间使用MRI对微血栓进行非侵入性体内诊断和监测提供了一种创新且有价值的工具。