Theranostics 2020; 10(17):7480-7491. doi:10.7150/thno.44233

Research Paper

Early Ultrafast Ultrasound Imaging of Cerebral Perfusion correlates with Ischemic Stroke outcomes and responses to treatment in Mice

Vincent Hingot1†, Camille Brodin2†, Florent Lebrun2,5, Baptiste Heiles1, Audrey Chagnot2, Mervé Yetim2, Maxime Gauberti3, Cyrille Orset2, Mickael Tanter1, Olivier Couture1, Thomas Deffieux1‡, Denis Vivien2,4‡✉

1. Institute Physics for Medicine Paris, Inserm U1273, ESPCI Paris, CNRS FRE 2031, PSL University.
2. Normandie Univ, UNICAEN, INSERM, GIP Cyceron, Institut Blood and Brain @Caen-Normandie (BB@C), UMR-S U1237, Physiopathology and Imaging of Neurological Disorders (PhIND), Caen, France.
3. CHU Caen, Department of radiology, Caen University Hospital, Avenue de la Côte de Nacre, Caen, France.
4. CHU Caen, Department of Clinical Research, Caen University Hospital, Avenue de la Côte de Nacre, Caen, France.
5. STROK@LLIANCE, ETAP-Lab, 2 rue des Rochambelles, Caen, France
These co-first authors equally contributed to this work.
These co-last authors equally contributed to this work.

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Citation:
Hingot V, Brodin C, Lebrun F, Heiles B, Chagnot A, Yetim M, Gauberti M, Orset C, Tanter M, Couture O, Deffieux T, Vivien D. Early Ultrafast Ultrasound Imaging of Cerebral Perfusion correlates with Ischemic Stroke outcomes and responses to treatment in Mice. Theranostics 2020; 10(17):7480-7491. doi:10.7150/thno.44233. Available from http://www.thno.org/v10p7480.htm

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Abstract

In the field of ischemic cerebral injury, precise characterization of neurovascular hemodynamic is required to select candidates for reperfusion treatments. It is thus admitted that advanced imaging-based approaches would be able to better diagnose and prognose those patients and would contribute to better clinical care. Current imaging modalities like MRI allow a precise diagnostic of cerebral injury but suffer from limited availability and transportability. The recently developed ultrafast ultrasound could be a powerful tool to perform emergency imaging and long term follow-up of cerebral perfusion, which could, in combination with MRI, improve imaging solutions for neuroradiologists.

Methods: In this study, in a model of in situ thromboembolic stroke in mice, we compared a control group of non-treated mice (N=10) with a group receiving the gold standard pharmacological stroke therapy (N=9). We combined the established tool of magnetic resonance imaging (7T MRI) with two innovative ultrafast ultrasound methods, ultrafast Doppler and Ultrasound Localization Microscopy, to image the cerebral blood volumes at early and late times after stroke onset and compare with the formation of ischemic lesions.

Results: Our study shows that ultrafast ultrasound can be used through the mouse skull to monitor cerebral perfusion during ischemic stroke. In our data, the monitoring of the reperfusion following thrombolytic within the first 2 h post stroke onset matches ischemic lesions measured 24 h. Moreover, similar results can be made with Ultrasound Localization Microscopy which could make it applicable to human patients in the future.

Conclusion: We thus provide the proof of concept that in a mouse model of thromboembolic stroke with an intact skull, early ultrafast ultrasound can be indicative of responses to treatment and cerebral tissue fates following stroke. It brings new tools to study ischemic stroke in preclinical models and is the first step prior translation to the clinical settings.

Keywords: Ischemic stroke, Thrombolysis, Ultrasound Imaging, Ultrasound Localization Microscopy, Outcome