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

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.

Megalencephalic leukoencephalopathy with subcortical cysts is a developmental disorder of the gliovascular unit

“…We had demonstrated previously that PvAPs and the associated neuronal fibers remain attached to vessels during their mechanical purification (Fig. 4e) [22]. Surprisingly, Aqp4 levels were similar in whole brain extracts (which was not certified by peer review) is the author/funder.…”

“…(encoding smooth muscle actin, SMA) in MVs purified from WT and Mlc1 KO whole brain on P5 and P15 and at 2 months [22] (Fig. 2a; Table S1).…”

“…MVs were isolated from whole brain using selection filtration, as described previously [22]. We purified vessels that passed through 100 µm pores but not 20 µm pores [22]. Brain vessels from two animals were pooled for the 2-month sample, with 3 for P15 and 5 for P5.…”

New Opportunities for Diagnosis and Prognosis of Stroke: The Benefits of Across Border Approaches

“…Using fUS/ULM, we have provided data demonstrating that early fUS/ULM imaging (<2 hours after stroke onset or treatments) could be useful to predict final outcomes following stroke (in rodents) including responses to treatments, usually observed only after 24 to 48 hours. 10 We are now working to translate this methodology to the clinical setting.…”

Clinical Application of High- Precision Neuroimaging Methods in Newborns with Brain Injuries

“…Высокое пространственно-временное разрешение и высокая чувствительность методики позволяют получить уникальную информацию не только об анатомических особенностях головного мозга пациента, но и функциональном состоянии различных структур, детально оценить пространственные и временные изменения, происходящие на уровне мелких сосудов в остром периоде болезни и во время лечения [33,38]. Сверхбыстрое допплеровское исследование значительно превосходит функциональную магнитно-резонансную томографию не только по техническим характеристикам, но и возможности использования в неонатологии и педиатрии [31].…”