Essential tremor (ET) is a common neurological disorder and a leading cause of functional and psychological
disabilities that can be difficult to suppress with oral medications, many of which have considerable side effects
limiting adequate dosing. As a result, up to 20% of ET patients cannot achieve satisfactory control of their
symptoms and must consider interventional options. Focused ultrasound ablation (FUSA) of the ventral
intermediate nucleus (Vim) is an FDA-approved and Medicare-reimbursed procedure for ET resistant to
medications that can selectively ablate the brain area associated with tremor without the need for surgical
incisions or anesthesia. The success of Vim-FUSA depends on the ability to accurately ablate 70% of the Vim
volume without lesioning neighboring structures, a goal that is complicated by technical challenges in three
critical phases of the procedure: planning (identifying the Vim location and extension); delivery (ablating the Vim
volume with adequate accuracy); and monitoring (confirming Vim ablation with reliable intraoperative imaging).
We propose to advance Vim-FUSA with the support of 3-D tractography, a neuroimaging technique to visually
represent nerve tracts within the brain. We hypothesize that 3-D tractography Vim-FUSA will improve the Vim
ablation compared to standard Vim-FUSA and prove safe and feasible in the clinical setting. We also hypothesize
that intraoperative magnetic resonance (i-MR) monitoring will differentiate ablated tissue from immediate
perilesional edema and accurately predict the Vim-FUSA clinical outcomes.
Aim 1. Estimate and characterize the improvement in Vim ablation achieved with 3-D tractography
Vim-FUSA vs. standard Vim-FUSA in an experimental controlled animal study. Through an experimental
animal study, we will characterize the Vim ablation delivered with 3-D tractography Vim-FUSA in one hemisphere
(experimental group) vs. standard Vim-FUSA in the opposite hemisphere (control group).
Aim 2. Test safety, feasibility, and preliminary efficacy, and estimate effect size of 3-D tractography
Vim-FUSA in a phase-II, two-groups, pre-post interventional human study. In a human study, we will test
the safety and feasibility of ablating 70% of the Vim volume while checking for side effects with intraoperative
clinical testing. Tremor assessments will be videotaped at baseline and 12 weeks and compared, in a blinded
fashion, with age-sex matched controls randomly selected from the video repository of the two FDA-regulated
studies of standard Vim-FUSA at baseline and 12 weeks.
Aim 3 (Exploratory). Assess the accuracy of i-MR in differentiating tissue ablation from immediate
perilesional edema and its utility in predicting Vim-FUSA clinical outcomes. In the experimental animal
study, we will estimate and compare the accuracy of conventional and non-conventional i-MR in differentiating
tissue necrosis from perilesional edema. In the interventional human study, we will evaluate the utility of i-MR in
predicting Vim-FUSA clinical outcomes.