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.
BACKGROUND: Endovascular thrombectomy has changed the management of ischemic stroke. The reperfusion can however lead to a hemorrhagic transformation (HT). Decompressive craniectomy (DC) is a surgical procedure used for malignant ischemic stroke. However, its efficacy was demonstrated before the era of endovascular thrombectomy trials. Here, we hypothesized that DC for ischemic stroke after thrombectomy could lead to a higher risk of HT. We thus evaluated this hypothesis in a mouse model of stroke induced by occlusion of the middle cerebral artery (MCAO) with or without mechanical reperfusion. METHODS: Ninety mice subjected to MCAO were divided into 6 groups: permanent MCAO with or without DC; MCAO followed by a mechanical reperfusion with or without DC and MCAO with a mechanical reperfusion followed by r-tPA (recombinant tissue-type plasminogen activator)-induced reperfusion with or without DC. Mice were evaluated by magnetic resonance imaging 24 hours after the MCAO to assess ischemic lesion volumes, and the rate, type, and volume of HTs. RESULTS: The ischemic volume was higher in the 2 groups without reperfusion than in the 4 groups with reperfusion independently of r-tPA treatment and DC. The distribution of HT types was different between the 6 groups. The HT volumes and HT scores was smaller in the 2 groups without reperfusion and in the reperfusion group without r-tPA and without DC. In mice having reperfusion, the mean HT score was higher in mice who had DC without r-tPA (HT score 5; P =0.048) or with r-tPA (HT score 8; P =0.02), than in mice without DC (HT score 1). CONCLUSIONS: DC for a malignant stroke, after reperfusion, corresponding to an endovascular thrombectomy failure, increases the risk of severe hemorrhagic transformations in a model of ischemic stroke in mice. This result support the need of clinical studies to evaluate the added value of DC at the era of endovascular thrombectomy.
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