Diffusion imaging changes in the treated tract following focused ultrasound thalamotomy for tremor.
Authors: Mazerolle EL, Warwaruk-Rogers R, Romo P, Sankar T, Scott S, Rockel CP, Pichardo S, Martino D, Kiss ZHT, Pike GB
We describe diffusion tensor imaging metrics of brain microstructure changes following magnetic resonance guided focused ultrasound (MRgFUS) ablation of the ventral intermediate nucleus of the thalamus for the treatment of tremor in order to explore the mechanisms of tremor reduction post-MRgFUS. Tractography was performed on pre-treatment images to identify the portion of the dentato-rubro-thalamo-cortical tract (DRTT) intersecting the MRgFUS thalamotomy lesions in 17 essential tremor patients. The resulting tract was divided into regions of interest (ROI), which were then analyzed on pre-, one day post-, and three months post-treatment scans. Fractional anisotropy (FA), and mean, axial, and radial diffusivity (MD, AD, and RD) were computed in each ROI at each time point. At both one day and three months post-treatment, we observed decreased FA and increased MD and RD in the section of the treated tract between the lesion and cortex. At three months post-treatment, we additionally observed increased AD in the section between the lesion and cortex, and decreased FA in the section between the dentate nucleus and the decussation of the superior cerebellar peduncles. Diffusion changes at one day post-treatment may reflect local, acute effects such as inflammation and edema, as opposed to chronic degenerative processes such as axonal degeneration and myelin loss that would be expected at later time points. No significant correlations were detected between diffusion measures and clinical effects, suggesting that microstructural changes in the treated portion of the DRTT alone do not fully explain tremor reduction and motivating additional research using higher spatial resolution diffusion imaging and multimodal approaches such as integrating diffusion and functional magnetic resonance imaging data. Our individualized approach, in which patient-specific lesions are incorporated into the tractography analysis, provided novel insight into both immediate and longer term MRgFUS-related microstructural brain changes.
Introduction
Purpose
Thermal ablation
Study Objective
To determine acute and chronic diffusion MRI–measured microstructural changes in the dentato-rubro-thalamo-cortical tract following MRgFUS thalamotomy for tremor using patient-specific tractography.
Animal model / Human subject
Homo sapiens; strain: N/A; adults aged 50–90 years (mean 73.5 ± 8.8 years); sex: 15 male, 2 female (17 patients)
Disease model
essential tremor
MRI or image guidance method
MRI-guided FUS (MRgFUS) targeting using AC–PC-based coordinates (manufacturer defaults: on the AC‑PC plane, 25% of AC‑PC distance anterior to the PC and 14 mm lateral from midline) with intraoperative neurosurgeon adjustments based on sensory percepts and tremor control (ExAblate 4000, 3 T MRI)
Targeted brain region(s)
Thalamus
Target coordinates
AP: 25% of the AC–PC distance anterior to the posterior commissure; ML: 14 mm lateral from midline; DV: on the AC–PC plane (most sonications placed ~1 mm superior to the AC–PC line)
Outcomes and Safety
Summary of Outcomes
MRgFUS thalamotomy of the ventral intermediate nucleus produced good-to-excellent tremor control (mean CRST total reduction ≈50.5% at 3 months) and was associated with acute and longer-term diffusion changes in the DRTT—specifically decreased FA and increased MD and RD between lesion and cortex at one day and three months, and increased AD plus additional FA decreases in cerebellar portions at three months. The study did not compare multiple focused‑ultrasound parameter settings and therefore did not identify any specific FUS parameter variants as more successful.
Duration of biological effect
3 months
Safety-related matter
No adverse events, complications, or safety concerns are reported in the paper; the text does not mention any treatment-related adverse effects and notes that all patients achieved good-to-excellent tremor control.
Brain Region
Ultrasound Parameters
Ultrasound instrument
ExAblate 4000 (InSightec, Haifa, Israel); transducer aperture/diameter: None
Focal Characteristics
Focal depth: None; Focal length: None; Aperture size: None
Treatment frequency
Single
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