Transcranial microbubble-enhanced ultrafast Doppler imaging of ultrasound-induced brain stimulation using a dual-mode...

Ultrafast Doppler imaging enables high-sensitivity detection of slow and microvascular blood flow with high spatiotemporal resolution, allowing real-time visualization of cerebral perfusion dynamics. When combined with high-frequency transducers and singular value decomposition (SVD) clutter filtering, it allows detailed mapping of cerebral microvasculature and facilitates investigations of neural function and hemodynamic alterations associated with neurological disorders. Ultrasound is also increasingly applied in therapeutic applications, including thermal ablation and blood-brain barrier (BBB) opening, highlighting its potential as a unified theranostic modality. However, transcranial imaging with high-frequency ultrasound remains severely limited by skull-induced attenuation. The purpose of this study is to evaluate the feasibility of using a 0.5-MHz dual-mode concave transducer to perform both focused ultrasound (FUS) stimulation and cerebral perfusion imaging through an intact rat skull without the need for a craniotomy. Microbubble (MB)-enhanced ultrafast Doppler further enabled quantitative perfusion analysis using time-intensity curve (TIC) analysis, revealing distinct perfusion dynamics before and after sonication. Perfusion responses were compared across sham, low-dose, and high-dose FUS exposure for BBB opening. Histology and cerebral blood volume (CBV) mapping confirmed successful BBB disruption in the high-dose sonication group. A significant CBV reduction was observed in the treated hemisphere, indicating interhemispheric blood flow redistribution following severe BBB opening. Statistical analysis showed significant differences between the high-dose sonication and sham/ low-dose groups (p < 0.05, n = 3). These findings underscore the capability of low-frequency ultrafast Doppler to evaluate real-time hemodynamic changes induced by FUS-mediated BBB modulation. The dual-functional apparatus, integrating diagnostic and therapeutic capabilities within a single transducer, offers a promising platform for non-invasive neuromodulation and image-guided therapeutic assessment in neuroscience.