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Hubert V, Hristovska I, Karpati S, et al. Multimodal Imaging with NanoGd Reveals Spatiotemporal Features of Neuroinflammation after Experimental Stroke. Adv Sci (Weinh). 2021;8(17):e2101433doi: 10.1002/advs.202101433.
Hubert, V., Hristovska, I., Karpati, S., Benkeder, S., Dey, A., Dumot, C., Amaz, C., Chounlamountri, N., Watrin, C., Comte, J. C., Chauveau, F., Brun, E., Marche, P., Lerouge, F., Parola, S., Berthezène, Y., Vorup-Jensen, T., Pascual, O., & Wiart, M. (2021). Multimodal Imaging with NanoGd Reveals Spatiotemporal Features of Neuroinflammation after Experimental Stroke. Advanced science (Weinheim, Baden-Wurttemberg, Germany), 8(17), e2101433. https://doi.org/10.1002/advs.202101433
Hubert, Violaine, et al. "Multimodal Imaging with NanoGd Reveals Spatiotemporal Features of Neuroinflammation after Experimental Stroke." Advanced science (Weinheim, Baden-Wurttemberg, Germany) vol. 8,17 (2021): e2101433. doi: https://doi.org/10.1002/advs.202101433
Hubert V, Hristovska I, Karpati S, Benkeder S, Dey A, Dumot C, Amaz C, Chounlamountri N, Watrin C, Comte JC, Chauveau F, Brun E, Marche P, Lerouge F, Parola S, Berthezène Y, Vorup-Jensen T, Pascual O, Wiart M. Multimodal Imaging with NanoGd Reveals Spatiotemporal Features of Neuroinflammation after Experimental Stroke. Adv Sci (Weinh). 2021 Sep;8(17):e2101433. doi: 10.1002/advs.202101433. Epub 2021 Jul 01. PMID: 34197055; PMCID: PMC8425862.
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Adv Sci (Weinh). 2021 Sep;8(17):e2101433. doi: 10.1002/advs.202101433. Epub 2021 Jul 01.

Multimodal Imaging with NanoGd Reveals Spatiotemporal Features of Neuroinflammation after Experimental Stroke.

Advanced science (Weinheim, Baden-Wurttemberg, Germany)

Violaine Hubert, Ines Hristovska, Szilvia Karpati, Sarah Benkeder, Arindam Dey, Chloé Dumot, Camille Amaz, Naura Chounlamountri, Chantal Watrin, Jean-Christophe Comte, Fabien Chauveau, Emmanuel Brun, Patrice Marche, Fréderic Lerouge, Stéphane Parola, Yves Berthezène, Thomas Vorup-Jensen, Olivier Pascual, Marlène Wiart

Affiliations

  1. Univ-Lyon, IRIS Team, CarMeN Laboratory, Inserm U1060, INRA U1397, INSA Lyon, Université Claude Bernard Lyon 1, Groupement Hospitalier Est, 59 bd. Pinel, Bron, 69500, France.
  2. SYNATAC Team, Institut NeuroMyoGène, Université Claude Bernard Lyon 1, CNRS UMR 5310, INSERM U1217, Faculté de Médecine et de Pharmacie, 8 avenue Rockefeller, Lyon, 69008, France.
  3. Université de Lyon, École Normale Supérieure de Lyon, CNRS UMR 5182, Université Claude Bernard Lyon 1, Laboratoire de Chimie, Lyon, F69342, France.
  4. Institut pour l'Avancée des Biosciences, Centre de Recherche UGA / Inserm U 1209 / CNRS UMR 5309, Site Santé - Allée des Alpes, La Tronche, 38700, France.
  5. Clinical Investigation Center, Hospices Civils de Lyon, Louis Pradel Hospital, 28 avenue Doyen Lépine, Bron, 69500, France.
  6. FORGETTING Team, Lyon Neuroscience Research Center (CRNL), CNRS UMR5292, INSERM U1028, Université Claude Bernard Lyon 1, Centre Hospitalier Le Vinatier - Bâtiment 462 - Neurocampus Michel Jouvet, 95 boulevard Pinel, Bron, 69675, France.
  7. Université de Lyon, Lyon Neuroscience Research Center (CRNL), CNRS UMR5292, INSERM U1028, Université Claude Bernard Lyon 1, Groupement Hospitalier Est - CERMEP, 59 bd Pinel, Bron Cedex, 69677, France.
  8. Synchrotron Radiation for Biomedical Research (STROBE), UA7 INSERM, Université Grenoble Alpes, Medical Beamline at the European Synchrotron Radiation Facility, 71 Avenue des Martyrs, Grenoble Cedex 9, 38043, France.
  9. Univ-Lyon, Creatis Laboratory, CNRS UMR5220, Inserm U1044, INSA Lyon, Villeurbanne Cedex, 69621, France.
  10. Department of Biomedicine, Biophysical Immunology Laboratory, Aarhus University, Aarhus C, DK-8000, Denmark.

PMID: 34197055 PMCID: PMC8425862 DOI: 10.1002/advs.202101433

Abstract

The purpose of this study is to propose and validate a preclinical in vivo magnetic resonance imaging (MRI) tool to monitor neuroinflammation following ischemic stroke, based on injection of a novel multimodal nanoprobe, NanoGd, specifically designed for internalization by phagocytic cells. First, it is verified that NanoGd is efficiently internalized by microglia in vitro. In vivo MRI coupled with intravenous injection of NanoGd in a permanent middle cerebral artery occlusion mouse model results in hypointense signals in the ischemic lesion. In these mice, longitudinal two-photon intravital microscopy shows NanoGd internalization by activated CX3CR1-GFP/+ cells. Ex vivo analysis, including phase contrast imaging with synchrotron X-ray, histochemistry, and transmission electron microscopy corroborate NanoGd accumulation within the ischemic lesion and uptake by immune phagocytic cells. Taken together, these results confirm the potential of NanoGd-enhanced MRI as an imaging biomarker of neuroinflammation at the subacute stage of ischemic stroke. As far as it is known, this work is the first to decipher the working mechanism of MR signals induced by a nanoparticle passively targeted at phagocytic cells by performing intravital microscopy back-to-back with MRI. Furthermore, using a gadolinium-based rather than an iron-based contrast agent raises future perspectives for the development of molecular imaging with emerging computed tomography technologies.

© 2021 The Authors. Advanced Science published by Wiley-VCH GmbH.

Keywords: intravital two-photon microscopy; magnetic resonance imaging; microglia/macrophage; multimodal nanoprobe; neuroinflammation; stroke

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