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Neuroimaging is the new “spatial omic”: multi-omic approaches to neuro-inflammation and immuno-thrombosis in acute ischemic stroke

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Abstract

Ischemic stroke (IS) is the leading cause of acquired disability and the second leading cause of dementia and mortality. Current treatments for IS are primarily focused on revascularization of the occluded artery. However, only 10% of patients are eligible for revascularization and 50% of revascularized patients remain disabled at 3 months. Accumulating evidence highlight the prognostic significance of the neuro- and thrombo-inflammatory response after IS. However, several randomized trials of promising immunosuppressive or immunomodulatory drugs failed to show positive results. Insufficient understanding of inter-patient variability in the cellular, functional, and spatial organization of the inflammatory response to IS likely contributed to the failure to translate preclinical findings into successful clinical trials. The inflammatory response to IS involves complex interactions between neuronal, glial, and immune cell subsets across multiple immunological compartments, including the blood-brain barrier, the meningeal lymphatic vessels, the choroid plexus, and the skull bone marrow. Here, we review the neuro- and thrombo-inflammatory responses to IS. We discuss how clinical imaging and single-cell omic technologies have refined our understanding of the spatial organization of pathobiological processes driving clinical outcomes in patients with an IS. We also introduce recent developments in machine learning statistical methods for the integration of multi-omic data (biological and radiological) to identify patient-specific inflammatory states predictive of IS clinical outcomes.

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Abbreviations

AIS:

Acute ischemic stroke

ASL:

Arterial spin labeling

BBB:

Blood-brain barrier

CNS:

Central nervous system

CSF:

Cerebrospinal fluid

ChP:

Choroid plexus

EVT:

Endovascular therapy

FLAIR:

Fluid attenuated inversion recovery

HARM:

Hyperintense acute reperfusion marker

ICH:

Intracranial hemorrhage

IL:

Interleukin

IVT:

Intravenous thrombolysis

mLVs:

Meningeal lymphatic vessels

MS:

Multiple sclerosis

MRI:

Magnetic resonance imaging

NMOSD:

Neuromyelitis optica spectrum disorders

PET:

Positron emission tomography

SDF-1:

Stroma cell-derived factor 1

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Acknowledgements

We thank Dyani Gaudilliere for providing her scientific input and editing the manuscript.

Funding

This work was supported in part by the National Institute of Health (NIH) R35GM137936, P01HD106414 (BG), the Precision Health and Integrated Diagnosis Center, and the Center for Human Systems Immunology at Stanford (BG). This work was also supported by INSERM and by public grants overseen by the French National Research Agency (ANR) as part of the Investments for the Future program (PIA) under grant agreement No. ANR-18-RHUS-0001 (RHU Booster) and ANR-ETHERISCH.

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Author notes

  1. Benjamin Maïer, Amy S. Tsai, Mikael Mazighi and Brice Gaudillière contributed equally to this work.

Authors and Affiliations

  1. Interventional Neuroradiology Department, Hôpital Fondation A. de Rothschild, Paris, France

    Benjamin Maïer, Jean-Philippe Desilles & Mikael Mazighi

  2. Neurology Department, Hôpital Saint-Joseph, Paris, France

    Benjamin Maïer

  3. Université Paris-Cité and Université Sorbonne Paris Nord, INSERM, LVTS, F-75018, Paris, France

    Benjamin Maïer, Jean-Philippe Desilles, Benoît Ho-Tin-Noé & Mikael Mazighi

  4. FHU NeuroVasc, Paris, France

    Benjamin Maïer, Jean-Philippe Desilles & Mikael Mazighi

  5. Department of Anesthesiology, Perioperative and Pain Medicine, Stanford School of Medicine, 300 Pasteur Drive, Room S238, Stanford, CA, 94305-5117, USA

    Amy S. Tsai, Jakob F. Einhaus & Brice Gaudillière

  6. CHRU-Nancy, Department of Diagnostic and Therapeutic Neuroradiology, Université de Lorraine, F-54000, Nancy, France

    Benjamin Gory

  7. Bakar Computational Health Sciences Institute, University of California San Francisco, San Francisco, CA, USA

    Marina Sirota

  8. Department of Pediatrics, University of California San Francisco, San Francisco, CA, USA

    Marina Sirota

  9. Department of Neurology, Johns Hopkins University, Baltimore, MD, USA

    Richard Leigh

  10. Department of Neurology, University Hospitals Leuven, Leuven, Belgium

    Robin Lemmens

  11. Department of Neurosciences Division of Experimental Neurology, KU Leuven-University of Leuven, Leuven, Belgium

    Robin Lemmens

  12. VIB, Centre for Brain and Disease Research, Laboratory of Neurobiology, Leuven, Belgium

    Robin Lemmens

  13. Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA

    Gregory Albers

  14. Vascular Neurology Department, University Hospital of Toulouse, Toulouse, France

    Jean-Marc Olivot

  15. Neurology Department, Lariboisière Hospital, Université Paris-Cité, Paris, France

    Mikael Mazighi

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  1. Benjamin Maïer
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Correspondence to Mikael Mazighi or Brice Gaudillière.

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Conflict of interest

MM declares institutional fees for teaching presentations from Boerhinger Ingelheim, Medtronic, Amgen, and consulting fees from Boerhinger Ingelheim, Acticor Biotech, and Air liquide. MM received a grant from the French National Research Agency (ANR) as part of the Investments for the future program (PIA) (grant agreement no. ANR-18-RHUS-0001) for the BOOSTER (Brain clOt persOnalized therapeutic Strategies for sTroke Emergent Reperfusion) consortium. BG declares consulting fees from Surge2surgery. JMO declares institutional fees for teaching presentation for Boehringer Ingelheim and Bristol Myers Squibb; Consulting fees from Abbvie, Acticor, and Bioxodes.

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This article is a contribution to the special issue on: Single-cell and spatial multi-omics in clinical outcomes studies - Guest Editor: Brice Gaudillière

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Maïer, B., Tsai, A.S., Einhaus, J.F. et al. Neuroimaging is the new “spatial omic”: multi-omic approaches to neuro-inflammation and immuno-thrombosis in acute ischemic stroke. Semin Immunopathol 45, 125–143 (2023). https://doi.org/10.1007/s00281-023-00984-6

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