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MRI-based microthrombi detection in stroke with polydopamine iron oxide

Author

Listed:
  • 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)
    Department of Diagnostic Imaging and Interventional Radiology)

  • Denis Vivien

    (Institute Blood and Brain @ Caen-Normandie (BB@C)
    Department of Clinical Research)

  • Thomas Bonnard

    (Institute Blood and Brain @ Caen-Normandie (BB@C))

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.

Suggested Citation

  • 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 & Fabi, 2024. "MRI-based microthrombi detection in stroke with polydopamine iron oxide," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49480-x
    DOI: 10.1038/s41467-024-49480-x
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    1. Francisco Perez-Balderas & Sander I. van Kasteren & Alaa A. A. Aljabali & Kim Wals & Sébastien Serres & Andrew Jefferson & Manuel Sarmiento Soto & Alexandre A. Khrapitchev & James R Larkin & Claire Br, 2017. "Covalent assembly of nanoparticles as a peptidase-degradable platform for molecular MRI," Nature Communications, Nature, vol. 8(1), pages 1-10, April.
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