Assessment of Deeper Vascular Structures and Perfusion in Mouse Model of Chemobrain with Functional Ultrasound Imaging

Visualizing deep cerebrovascular structures and blood flow in aging and accelerated aging-related vascular cognitive impairment and dementia (VCID) has been a significant challenge of translational geroscience. Traditional imaging methods face serious limitations due to the dense cranial bone of aging animals, the increasing concentration of fluorescent lipofuscin and the general low penetration of light microscopy, hindering high-resolution imaging and cerebral blood flow (CBF) assessment in deeper brain regions. The rapid advancements in ultrasound imaging, particularly functional ultrasound (fUS), now provide real-time insights into CBF with remarkable spatial-temporal resolution. We applied this advanced imaging approach to investigate chemotherapy-induced cognitive impairment (CICI), commonly known as "chemobrain," a frequent side effect of cancer therapeutic paclitaxel (PTX). In this accelerated aging model, C57BL/6 mice were treated with PTX, and a polymethylpentene window was surgically installed to replace the dorsal cranium for consistent, long-term fUS imaging. Comparing PTX-treated and control animals, our method revealed significant reductions in microvascular density and neurovascular coupling in the chemobrain model, together with reduced cerebral blood flow velocity in the origination of the middle cerebral arteries. These in vivo findings in the deeper brain regions expand our previous results that showed impaired cortical microvascular functions in chemobrain. By demonstrating how PTX further disrupts vascular integrity of deeper brain regions, this study provides critical insights into the mechanisms underlying CICI and establishes a foundation for future therapeutic strategies targeting vascular health in cancer survivors. NIA (R01AG055395, R01AG068295; R01AG070915, K01AG073614, K01AG073613, R03AG070479), NCI (R01CA255840), AHA 24CDA1276505, AHA 916225, AHA CDA941290 This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.