MRI-based microthrombi detection in stroke with polydopamine iron oxide

Charlène Jacqmarcq, Audrey Picot, Jules Flon, Florent Lebrun, Sara Martinez de Lizarrondo, Mikaël Naveau, Benoît Bernay, Didier Goux, Marina Rubio, Aurélie Malzert-Fréon, Anita Michel, Fabienne Proamer, Pierre Mangin, Maxime Gauberti, Denis Vivien () and Thomas Bonnard ()
Additional contact information
Charlène Jacqmarcq: Institute Blood and Brain @ Caen-Normandie (BB@C)
Audrey Picot: Institute Blood and Brain @ Caen-Normandie (BB@C)
Jules Flon: Institute Blood and Brain @ Caen-Normandie (BB@C)
Florent Lebrun: Institute Blood and Brain @ Caen-Normandie (BB@C)
Sara Martinez de Lizarrondo: Institute Blood and Brain @ Caen-Normandie (BB@C)
Mikaël Naveau: Université Caen Normandie
Benoît Bernay: Université Caen Normandie
Didier Goux: CMAbio3: Centre de Microscopie Appliquée à la Biologie
Marina Rubio: Institute Blood and Brain @ Caen-Normandie (BB@C)
Aurélie Malzert-Fréon: CERMN: Centre d’études et de recherche sur le médicament de Normandie
Anita Michel: FMTS
Fabienne Proamer: FMTS
Pierre Mangin: FMTS
Maxime Gauberti: Institute Blood and Brain @ Caen-Normandie (BB@C)
Denis Vivien: Institute Blood and Brain @ Caen-Normandie (BB@C)
Thomas Bonnard: Institute Blood and Brain @ Caen-Normandie (BB@C)

Nature Communications, 2024, vol. 15, issue 1, 1-17

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 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.

Date: 2024
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DOI: 10.1038/s41467-024-49480-x

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