Functional Neuroimaging Feedback for Focused Ultrasound Thalamotomy

Functional Neuroimaging Feedback for Focused Ultrasound Thalamotomy for Tremor Surgery

Focused ultrasound for Essential Tremor is an FDA approved treatment performed by neurosurgeons at the Ohio State Center for Neuromodulation that utilizes ultrasound technology to create a lesion in the thalamus of Essential Tremor patients. In order to improve long term effectiveness and reduce potential for side effects, brain imaging may be used to examine the functional connectivity of certain brain networks during the procedure. In order to investigate functional connectivity changes with these long term goals in mind, in this study neuroimaging will be taken immediately before, immediately after, and 24 hours after the focused ultrasound procedure for 10 Essential Tremor patients. One series of neuroimaging will also be conducted for 20 healthy control subjects to serve as a comparison. This study will not introduce any risks above standard of care, and may lead to improved long term outcomes of patients undergoing the Focused Ultrasound procedure.

Study Overview

• Status: Unknown
• Conditions: Essential Tremor
• Intervention / Treatment: Device: multi-modality neuroimaging

Detailed Description

To calculate the connectivity correlates of tremor (CCT) by analyzing and comparing functional connectivity in the tremor network in ET patients and healthy controls. The fMRI data will be acquired in two separate conditions: t-fMRI and rs-fMRI. a. For t-fMRI, patients will perform simple repetitive tasks (e.g. finger tapping, hand grasping) to identify activation clusters within tremor network. Functional connectivity between the clusters will be calculated by creating cross-correlation matrices. A sensitivity analysis will then be performed to determine an optimal value of CCT to distinguish ET patients from controls. b. For rs-fMRI the hubs within tremor network will be identified with a state-of-the-art multimodality atlas. Cross-correlation matrices will be created to calculate measures of functional connectivity. A sensitivity analysis will then be performed to determine an optimal value of CCT to distinguish ET patients from controls. 2. To study changes in functional connectivity in the tremor network before, immediate postoperative and and 24-hours after FUS-T in ET patients. a. The CCT will be calculated and compared between baseline, immediate postoperative and 24-hours post-operative conditions to determine the effect of FUS-T. For this sub-aim the connectivity data will be separately analyzed for t-fMRI and for rs-fMRI. b. The CCT in immediate postoperative and 24-hours post-operative condition among ET patients will be compared to healthy controls to determine whether FUS-T restored the abnormal connectivity in tremor network. For this sub-aim the connectivity data will be separately analyzed for t-fMRI and rs-fMRI.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• The tremor diagnosis, disability and medically refractory status are agreed upon by at least two movement disorder trained physicians (neurologists and/or neurosurgeons).
• The patient is deemed suitable for surgical therapy for tremor with VIM targeting.
• The patient is willing to participate in the study and provides written informed consent.
• The patient is able to clearly communicate clinical findings with the clinical team.
• The patient is willing to participate in at least one follow-up visit at 3 or 6 months.
• In order to maintain uniformity of image acquisition only patients undergoing imaging with the 3T MRI at The Ohio State University Wexner Medical Center will be included.

Exclusion Criteria:

• Medically unstable - uncontrolled hypertension, coronary artery disease, significant pulmonary problems, active history of bleeding disorders or anticoagulation.
• Other diagnoses of tremor like Parkinson's disease, traumatic tremor, dystonic tremor, and/or tremor associated with multiple sclerosis
• Unwilling or unable to undergo awake tremor surgery.
• Tremor patients undergoing surgery with targets other than the VIM.
• Significant motion artifact in imaging.
• Unable to undergo 3T MRI imaging.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: ET cohort; Ten adults with refractory ET (ET cohort) will undergo multi-modality neuroimaging (structural imaging, diffusion tensor imaging (DTI), task-based functional MRI (t-fMRI), and resting state functional MRI (rs-fMRI)). In addition the ET cohort will also undergo imaging with the identical protocol immediately after and 24 hours after FUS-T.	Device: multi-modality neuroimaging; multi-modality neuroimaging consists of structural imaging, diffusion tensor imaging (DTI), task-based functional MRI (t-fMRI), and resting state functional MRI (rs-fMRI).
EXPERIMENTAL: control cohort; Twenty adult healthy controls (control cohort) will undergo multi-modality neuroimaging (structural imaging, diffusion tensor imaging (DTI), task-based functional MRI (t-fMRI), and resting state functional MRI (rs-fMRI)).	Device: multi-modality neuroimaging; multi-modality neuroimaging consists of structural imaging, diffusion tensor imaging (DTI), task-based functional MRI (t-fMRI), and resting state functional MRI (rs-fMRI).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
connectivity correlates of tremor (CCT)	CCT will be calculated by analyzing and comparing functional connectivity in the tremor network in ET patients and healthy controls. The fMRI data will be acquired in two separate conditions: t-fMRI and rs-fMRI. Both t-fMRI and rs-MRI will be calculated based upon functional connectivity between the dentate nucleus, ventral intermediate nucleus, globus pallidus, motor and premotor cortex sensitivity analysis will then be performed to determine an optimal value of CCT to distinguish ET patients from controls.	during the surgical procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
changes in functional connectivity	2. To study changes in functional connectivity in the tremor network before, immediate postoperative and and 24-hours after FUS-T in ET patients.; The CCT will be calculated and compared between baseline, immediate postoperative and 24-hours post-operative conditions to determine the effect of FUS-T. For this sub-aim the connectivity data will be separately analyzed for t-fMRI and for rs-fMRI.; The CCT in immediate postoperative and 24-hours post-operative condition among ET patients will be compared to healthy controls to determine whether FUS-T restored the abnormal connectivity in tremor network. For this sub-aim the connectivity data will be separately analyzed for t-fMRI and rs-fMRI.	immediately post-operative and 24-hours after surgery for ET patients

Collaborators and Investigators

• Sponsor: Vibhor Krishna
• Collaborators: National Institutes of Health (NIH); Focused Ultrasound Foundation

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 1, 2018
• Primary Completion (ANTICIPATED): December 31, 2021
• Study Completion (ANTICIPATED): December 31, 2021

Study Registration Dates

• First Submitted: June 6, 2018
• First Submitted That Met QC Criteria: June 6, 2018
• First Posted (ACTUAL): June 18, 2018

Study Record Updates

• Last Update Posted (ACTUAL): February 24, 2021
• Last Update Submitted That Met QC Criteria: February 23, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: fMRI; focused ultrasound
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Movement Disorders; Dyskinesias; Tremor; Essential Tremor
• Other Study ID Numbers: 2018H0035

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes