3-D Tractography FUS Ablation for Essential Tremor

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). The investigators propose to advance Vim-FUSA with the support of 3-D tractography, a neuroimaging technique to visually represent nerve tracts within the brain. The investigators 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. The investigators 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, the investigators 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, the investigators 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, the investigators 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, the investigators will evaluate the utility of i-MR in predicting Vim-FUSA clinical outcomes

Inclusion criteria

• Diagnosis of moderate to severe ET agreed upon by at least two movement disorder trained physicians
• Symptoms refractory to at least two medications
• Stable medication regimen for at least 4 weeks prior to screening
• Willing and able to participate in all follow-up visits
• Willing and able to undergo MR imaging.

Exclusion criteria

• Uncontrolled hypertension
• Medically unstable coronary artery disease
• Coagulopathy, anticoagulant therapy, or inability to temporarily stop any antithrombotic medication
• Tremor disorders other than ET
• Unwilling or unable to undergo tremor surgery while awake
• Significant and non-correctible motion artifact in imaging
• Pregnant at the time of enrollment or preoperative evaluation
• Dementia
• History of psychosis
• History of drug or alcohol abuse
• Prior brain surgery such as Vim-FUSA, deep brain stimulation, and gamma knife thalamotomy
• Botulinum toxin injection in the tremor-impacted areas three months prior to the baseline assessment and until 3-months after Vim-FUSA
• Skull density ratio lower than 0.4
• Does not qualify for FDA-approved clinical use based on current FDA labeling
• Any significant issue raised by the neurologist or neurosurgeon that may compromise participant safety or potentially interfere with study interpretation.