3-D Tractography FUS Ablation for Essential Tremor

University of North Carolina (UNC)

Status

Enrolling

Conditions

Essential Tremor

Treatments

Device: MR-guided Focused Ultrasound Ablation

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT06331052

23-2431

1R01NS125386-01 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

The investigators propose to advance Vim-FUSA (Ventral Intermediate Nucleus - Focused Ultrasound Ablation) 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.

Full description

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

Enrollment

24 estimated patients

Sex

All

Ages

22+ years old

Volunteers

No Healthy Volunteers

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.