MRI-based microthrombi detection in stroke with polydopamine iron oxide
Charlène Jacqmarcq, Audrey Picot, Jules Flon, Florent Lebrun, Sara Martínez de Lizarrondo, Mikaël Naveau, Benoı̂t Bernay, Didier Goux, Marina Rubio, Aurélie Malzert‐Fréon, Anita Michel, Fabienne Proamer, Pierre Mangin, Maxime Gauberti, Denis Vivien, Thomas Bonnard
Abstract
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 T 2 *-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.