Focused ultrasound blood-brain barrier opening reveals a paradoxical remote metabolic response in the primate brain

Low-intensity focused ultrasound (LIFU) is a promising technique for opening the blood-brain barrier (BBB) for drug delivery, but its physiological consequences in remote brain regions remain a major blind spot for clinical safety and efficacy. To address this gap, we performed the quantitative mapping of brain metabolism following a focal LIFU-induced BBB opening in a nonhuman primate model, using quantitative BOLD MRI to measure the oxygen extraction fraction (OEF). We report a paradoxical response: While the targeted striatum showed no significant metabolic changes, we observed a profound and spatially specific increase in OEF in the homologous contralateral striatum, an effect predominantly driven by the putamen. These findings demonstrate that focal BBB opening is not merely a localized vascular event but a potent neuromodulatory intervention that induces metabolic stress in distant, untreated brain regions, a discovery with critical implications for the safe and effective clinical translation of all focal brain therapies.