Alteration of water exchange rates following focused ultrasound-mediated BBB opening in the dorsal striatum of non-human primates: A diffusion-prepared pCASL study

This study applied diffusion-prepared pseudo-continuous arterial spin labeling (DP-pCASL) to quantify cerebral blood flow (CBF), arterial transit time (ATT), and blood-brain barrier (BBB) water exchange rate (K_w) before and after focused ultrasound (FUS)-mediated blood-brain barrier opening (BBBO) in the dorsal striatum of four non-human primates. Six baseline and seven BBBO sessions were performed. DP-pCASL was acquired approximately 45 min after FUS sonication combined with intravenous microbubbles, and contrast-enhanced T1-weighted imaging was subsequently used to confirm the BBBO region. Whole-brain analyses revealed no significant changes in CBF or ATT following BBBO (permutation p > 0.05). Region-of-interest analysis within the sonicated caudate demonstrated a significant localized decrease in K_w, with median (IQR) values of 45.0 (40.6 - 55.6) min⁻¹ at the BBBO site versus 61.6 (58.3 - 70.4) min⁻¹ in the contralateral control region (p < 0.05), confirming spatially specific suppression of transendothelial water flux. In contrast, whole-brain K_w increased significantly following BBBO, with median (IQR) values of 49.8 (46.3 - 55.9) min⁻¹ in non-BBBO sessions versus 59.4 (56.6 - 66.3) min⁻¹ in BBBO sessions (p < 0.01), indicating a diffuse enhancement of water exchange across the brain. These findings establish DP-pCASL-derived K_w as a sensitive, non-contrast biomarker for both local and global BBB permeability changes induced by focused ultrasound, supporting its potential for longitudinal monitoring in preclinical and clinical neurotherapeutic applications.