Multimodal imaging of murine cerebrovascular dynamics induced by transcranial pulse stimulation
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2025-02
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Journal Article
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Abstract
INTRODUCTION: Transcranial pulse stimulation (TPS) is increasingly being investigated as a promising potential treatment for Alzheimer's disease (AD). Although the safety and preliminary clinical efficacy of TPS short pulses have been supported by neuropsychological scores in treated AD patients, its fundamental mechanisms are uncharted. METHODS: Herein, we used a multi-modal preclinical imaging platform combining real-time volumetric optoacoustic tomography, contrast-enhanced magnetic resonance imaging, and ex vivo immunofluorescence to comprehensively analyze structural and hemodynamic effects induced by TPS. Cohorts of healthy and AD transgenic mice were imaged during and after TPS exposure at various per-pulse energy levels. RESULTS: TPS enhanced the microvascular network, whereas the blood-brain barrier remained intact following the procedure. Notably, higher pulse energies were necessary to induce hemodynamic changes in AD mice, arguably due to their impacted vessels. DISCUSSION: These findings shed light on cerebrovascular dynamics induced by TPS treatment, and hence are expected to assist improving safety and therapeutic outcomes. Highlights center dot Transcranial pulse stimulation (TPS) facilitates transcranial wave propagation using short pulses to avoid tissue heating. center dot Preclinical multi-modal imaging combines real-time volumetric optoacoustic (OA) tomography, contrast-enhanced magnetic resonance imaging (CE-MRI), and ex vivo immunofluorescence to comprehensively analyze structural and hemodynamic effects induced by TPS. center dot Blood volume enhancement in microvascular networks was reproducibly observed with real-time OA imaging during TPS stimulation. center dot CE-MRI and gross pathology further confirmed that the brain architecture was maintained intact without blood-brain barrier (BBB) opening after TPS exposure, thus validating the safety of the procedure. center dot Higher pulse energies were necessary to induce hemodynamic changes in AD compared to wild-type animals, arguably due to their pathological vessels.
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21 (2)
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Wiley
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Subject
Alzheimer's disease; blood-brain barrier; brain hemodynamics; magnetic resonance imaging; mouse models; optoacoustic imaging; therapeutic ultrasound; transcranial pulsed stimulation
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09648 - Razansky, Daniel / Razansky, Daniel