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 minutes 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.
Liu et al. (Fri,) studied this question.
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