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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 Human (age: 50–90 years, sex: 15 male, 2 female)
Disease model essential tremor
MRI or image guidance method MRI, 3 T Discovery 750, (General Electric Healthcare, Waukesha, WI, USA)
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.
Duration of biological effect 3 months

Brain Region

Ultrasound Parameters

Ultrasound instrument ExAblate 4000 (InSightec, Haifa, Israel); transducer aperture/diameter: None
Treatment frequency Single

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