Microstructural, Morphological, and Metabolic Changes Following Magnetic Resonance-Guided Focused Ultrasound...

Magnetic resonance-guided focused ultrasound anterior capsulotomy (MRgFUS-AC) is an experimental, incisionless intervention for refractory obsessive-compulsive disorder (OCD) and major depressive disorder (MDD). Although its clinical efficacy has been demonstrated, the longitudinal structural and microstructural brain changes that it induces remain incompletely characterized.

A total of 33 patients with treatment-resistant OCD (n = 14) or MDD (n = 19) underwent MRgFUS-AC targeting the ventral anterior limb of the internal capsule. Diffusion and structural magnetic resonance imaging were acquired preoperatively and at follow-up. White matter integrity was evaluated using probabilistic tractography, and cortical and subcortical volumes were quantified using the FreeSurfer longitudinal pipeline. Longitudinal changes were assessed with linear mixed effects models.

MRgFUS-AC produced small lesions (∼117 mm³) that regressed by over 80% within 3 months. Despite this, significant reductions in fractional anisotropy were observed along multiple corticothalamic and corticostriatal tracts. Volume loss was detected in both cortical (medial orbitofrontal, inferior temporal, fusiform) and subcortical (bilateral caudate) regions, with more widespread effects in OCD. A smaller preoperative volume of the left pars triangularis predicted greater clinical improvement.

MRgFUS-AC induces measurable white matter and gray matter changes within fronto-striatal-thalamic circuits, even with small, regressing lesions. Structural effects were more pronounced in OCD than in MDD. Preoperative imaging features may aid in stratifying response and optimizing individualized targeting strategies for psychiatric neurosurgery.