This review highlights MRI-guided high-intensity focused ultrasound (MRgHIFU) as a noninvasive, tract-based neuromodulation approach using patient-specific diffusion MRI and advanced sequences to directly target pathological white-matter tracts (e.g., dentatorubrothalamic in ET, pallidothalamic in…

Provides a clinically actionable, translational pathway for personalized, incisionless treatment of PD motor circuits that could expand therapeutic options and target selection (including AI-assisted planning), though it does not address molecular disease-modifying mechanisms.

MRI-guided high-intensity focused ultrasound (MRgHIFU) has emerged as an alternative to other neuromodulatory interventions for patients with medically refractory movement disorders, including open surgery, radiosurgery, and deep brain stimulation. Microelectrode recordings permit refinement of indirect targets during open procedures for movement disorders. However, their use is not possible during incisionless procedures including MRgHIFU. Traditional MRgHIFU employing indirect targets yields limited efficacy or adverse effects from anatomic or functional variability. Furthermore, the clinical efficacy associated with indirect targeting of subcortical gray-matter structures is increasingly recognized to result from circuit-wide neuromodulation distributed along white matter pathways. Additionally, diffusion tensor imaging tractography and white matter-nulled sequences (e.g., fast gray matter acquisition T1 inversion recovery) now enable patient-specific targeting of pathologic brain circuits. These developments are prompting growing interest in MRgHIFU for direct targeting of disease-specific white matter tracts. In essential tremor, dentatorubrothalamic tract targeting by MRgHIFU has demonstrated high tremor suppression with few adverse effects; in Parkinson disease, pallidothalamic tract targeting has likewise emerged as a promising intervention. These tract-based approaches can leverage patient-specific targeting to improve precision, efficacy, and safety. Future developments, including artificial-intelligence-driven approaches, are expected to enhance MRgHIFU targeting and broaden its role in personalized movement disorder therapy.