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

Overview

1. Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY, USA
2. Department of Psychiatry, Columbia University, New York, NY, USA
3. Department of Radiology, Columbia University, New York, NY, USA
4. Department of Biomedical Engineering, Columbia University, New York, NY, USA
5. Department of Neuroscience, Columbia University, New York, NY, USA

Abstract

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.

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Data

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Data, code, and materials availability

All data and code needed to evaluate and reproduce the results in the paper are present in the paper and/or the Supplementary Materials. The raw MRI datasets supporting the qBOLD analysis have been deposited in a permanent, independent repository and can be accessed at https://doi.org/10.5281/zenodo.19186774. The computational pipeline, consisting of the Jupyter notebooks required to generate the OEF maps and reproduce the statistical analyses, is archived and is available at https://doi.org/10.5281/zenodo.19188809.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 6 authors, 9 MeSH terms, 1 funder, 63 references.

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This paper

Sanatkhani, S., Liu, D., Munoz, F., Grinband, J., Konofagou, E. E., & Ferrera, V. P. (2026). Focused ultrasound blood-brain barrier opening reveals a paradoxical remote metabolic response in the primate brain. Science advances, 12(29), eaed4944. https://doi.org/10.1126/sciadv.aed4944

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