Functional Ultrasound Imaging Uncovers Vascular Connectivity and Dynamics in Awake Mice During Hyperacute Stroke...

Area of Science:

• Neuroscience
• Vascular Biology
• Medical Imaging

Background:

• Anesthesia in acute ischemic stroke models complicates the study of neurovascular coupling and real-time functional assessments.
• Developing an awake stroke model is crucial for understanding cerebrovascular dynamics without anesthetic interference.

Purpose of the Study:

• To investigate early cerebrovascular dynamics and connectivity changes in an awake mouse model of thromboembolic stroke.
• To assess the predictive value of these early changes for final lesion outcomes.
• To evaluate the efficacy of recombinant tissue-type plasminogen activator (rtPA) in this awake model.

Main Methods:

• An awake mouse model of thromboembolic stroke was established using middle cerebral artery occlusion.
• Multimodal imaging, including ASL MRI, ultrafast Doppler US, and functional ultrasound, was employed to assess blood flow, volume, and neurovascular coupling.
• Mice received rtPA or saline, and outcomes were compared using MRI and ultrasound at various time points.

Main Results:

• rtPA significantly reduced lesion volumes by 36.7% at 24 hours post-stroke.
• Early hypoperfusion (10 minutes) predicted final lesion volume (R²=0.6465, P=0.0016).
• Whisker stimulation revealed abolished ipsilateral responses at 10 minutes, with partial functional recovery observed with rtPA by 24 hours.

Conclusions:

• The awake stroke model with multimodal imaging effectively captures early cerebrovascular changes and connectivity disruptions.
• These early dynamics are sensitive to rtPA treatment and predictive of lesion outcomes.
• This platform offers enhanced translational relevance for testing novel thrombolytics under physiological conditions.