Longitudinal analysis of structural changes following unilateral focused ultrasound thalamotomy.
Authors: Sammartino F, Yeh FC, Krishna V
Focused ultrasound thalamotomy is an emerging treatment for essential tremor, and it is ideal for studying reorganization in the human brain after acute injury because it creates a controlled thalamic ablation without breaching the cortex. However, there is not yet a metric capable of detecting microstructural changes in the presence of acute phase edema with good sensitivity in the chronic phase, when the lesion boundaries become inconspicuous. We prospectively studied microstructural changes at the lesion site using generalized q-sampling imaging with restricted diffusion imaging. We obtained diffusion-weighted MRI scans preoperatively, 1 day after (n = 18), and 1 year after (n = 9) focused ultrasound thalamotomy. The restricted diffusion imaging maps were compared at the group level, controlling for improvement in contralateral hand tremor. The restricted diffusion imaging metric significantly increased in the 1 day post images, and the area with restricted diffusivity extended beyond the lesion boundaries identified on T2-weighted imaging. Two distinct zones of microstructural changes were identified, and the lesion area was identifiable at 1 year. The anterior and medial aspects of the lesion had a significant changes in RDI at 1 year, potentially signifying reorganization. The voxels with significant changes in restricted diffusion imaging values extend beyond the VIM into the surrounding white matter. Correcting for free water contamination with restricted diffusion imaging allowed us to study microstructural changes after focused ultrasound thalamotomy. We observed statistically significant changes in RDI in the anterior and medial aspect of the lesion at 1 year. Whether these changes represent tissue reorganization remains to be confirmed in future studies. These findings may support performing additional ablations antero-medially for durable efficacy.
Introduction
Purpose
Thermal ablation
Study Objective
To prospectively evaluate microstructural changes at the thalamic lesion site after focused ultrasound thalamotomy using generalized q-sampling imaging with restricted diffusion imaging (RDI) at 1 day and 1 year post-treatment.
Animal model / Human subject
Homo sapiens (human patients with essential tremor), strain: N/A, age: not reported, sex: not reported (n=18; 1-year follow-up n=9)
Disease model
Essential tremor
MRI or image guidance method
MRI guided
Targeted brain region(s)
Thalamus
Outcomes and Safety
Summary of Outcomes
Focused ultrasound thalamotomy produced acute increases in restricted diffusion imaging (RDI) at the lesion site (mean +54.6% at 1 day) forming two concentric microstructural zones that extended beyond T2 lesion boundaries, with persistent RDI changes—especially in the anterior and medial lesion aspects—and decreased streamline counts in the core at 1 year; clinically patients showed substantial contralateral hand tremor improvement (~61% at 3 months, ~58% at 1 year). The study did not test multiple focused ultrasound delivery parameters for comparison.
Duration of biological effect
1 year
Safety-related matter
The paper notes significant acute edema after focused ultrasound thalamotomy and that procedures are performed with triple monitoring (clinical, thermography, and anatomical); no specific adverse clinical events or other safety complications are reported in this cohort.
Brain Region
Ultrasound Parameters
Ultrasound instrument
ExAblate 4000 transducer (Insightec)
Focal Characteristics
Focal depth: None; Focal length: None; Aperture size: None
Treatment frequency
single session
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