Personalized tremor control targeting for MR-guided focused ultrasound using tractography

Magnetic Resonance guided Focused Ultrasound Surgery (MRgFUS) is a non-invasive, innovative technology that induces a thermal lesion to treat tremor in medication-resistant patients diagnosed with essential tremor or Parkinson's disease. The ventral intermediate nucleus of the thalamus (VIM) is a well-established neuromodulation target for tremor reduction. The standard VIM detection method is based on anatomical landmarks, specifically the anterior and posterior commissure. However, it is correlated with suboptimal tremor control up to 20%, inconsistency of the treatment's outcome, leading to longer procedures with excessive amounts of sonications and adverse events. The use of tractography as a targeting tool is gaining momentum. However, validation and implementation are needed to establish tractography as a superior VIM targeting method. This study suggests a novel personalized targeting approach for treatment, leading to superior clinical outcomes. Pre- and postoperative magnetic resonance imaging scans were obtained from 81 patients who underwent MRgFUS between 2014 and 2021. Using preoperative diffusion tensor imaging, three tracts (pyramidal tract, medial lemniscus, and dentatorubrothalamic tract [DRT]) were identified for each patient using tractography. The postoperative T1 weighted images were used for segmentation, volumetric lesion evaluation, and correlation to the tracts. Clinical outcome was evaluated up to 2 years postoperatively and correlated to each patient's lesion characterization. Retrospective analysis of lesion location relative to a personalized DRT-based coordinate system has shown that successful lesions are consistently located in the anterolateral region of the DRT, whereas failed-treatment lesions encircle them. A linear regression model using tract features predicted optimal target locations with high accuracy (R ² = 0.84). In addition, a specific circular region of the tract in which at least 85% of the success lesions overlap was detected, while a 'critical area' of maximum success-fail difference was observed in its posterior-lateral margins. Using normalized 'sweet spot' DRT coordinates can distinguish successful from failed lesions with a P-value < 0.0001. Other factors, such as lesion volume and area at the anterior and posterior commissure plane, lesioned DRT volume and area, and anatomical coordinates, showed no correlation with treatment outcome, underscoring the importance of lesioning the specific part of the DRT for successful long-term tremor control. These results reveal an innovative personalized tool for optimal targeting of tremor control treatment, while further investigation should examine the targeting approach outcome superiority.