Mapping the Target for the MRgFUS Treatment of Tremor

MRI-guided Personalized Targeting of the Ventral Intermediate Nucleus (VIM)/Dentato-rubro-thalamic Tract (DRT) for the MRgFUS Tremor Treatment

The purpose of this investigation is to determine the optimal DRT/VIM target location and its safety margins based on MR-SISET imaging features by comparing with postoperative lesions and clinical outcomes in patients with tremor who will undergo the MRgFUS tremor therapy.

Study Overview

• Status: Completed
• Conditions: Parkinson's Disease; Tremor, Essential
• Intervention / Treatment: Other: Automatic DRT/VIM target-recognition method using MR-SISET and ML approaches; Other: Routine clinical MRI protocol

Detailed Description

Magnetic susceptibility is an important source of contrast in MRI, which arises from the subtle field perturbations generated by inter-molecular interaction in response to an external magnetic field. The DRT tract consists mainly of axon fibers covered by myelin sheaths that cause magnetic susceptibility variations. In addition, magnetic susceptibility of fiber bundle is in fact anisotropic. Such distinctive features of the DRT can generate a unique type of susceptibility contrast with respect to its neighboring thalamic tissues, yet clinically practical protocols are lacking. This study will utilize a novel MR susceptibility-based method, termed 'MR Susceptibility Imaging with Short Echo Time (MR-SISET)' which leverages short echo times to realize high contrast for direct and individualized DRT targeting. Combined with machine learning (ML) approaches, an automatic, operator-independent DRT-recognition will be achieved. This could provide a valid support to operators in the surgical planning and significantly improve the current operative methodology.

MR imaging will be done on a 3T MRI Magnet at the NYU Langone Health. All patients will undergo a routine clinical preoperative MRI of the brain under general anesthesia to reduce movement artifacts. The proposed sequence (<15 minutes) will be added as a supplementary sequence only for the preoperative imaging for subjects who agree to participate. The operator/clinician will be blinded to the results of this study for the MRgFUS treatment. A routine clinical postoperative MRI will be performed prior to discharge by the clinician, typically the following day of the MRgFUS treatment. The severity of tremor will be assessed before and after the treatment (~6 weeks). Postoperative clinical data will be retrieved to get a surgical target lesion and clinical outcome after treatment in order to confirm our method.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10016
      • NYU Langone

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female
• 18 years of age or older
• Any ethnic background
• History of a primary diagnosis of essential tremor or Parkinson's disease
• Present for the MRgFUS tremor treatment
• Ability to understand and agree to informed consent as determined by referring physician

Exclusion Criteria:

• Inability to give informed consent

• Contraindications for MRI, including

  1. Intracranial clips
  2. Metal implants
  3. External metallic devices/objects/clips within 10 mm of the head
  4. Suspected or confirmed metal in eyes (history of welding or similar activity)
  5. Cardiac pacemaker
  6. Pregnant or potentially pregnant - pregnancy tests will be offered to women of childbearing age at no cost to the patient. (A SOC pregnancy test (Urine test) will be done for women of child bearing age if requested/required at the time of check-in at Tisch.This will be billed to the research study). The result of the test (if performed) will be added to the patient's chart in EPIC.
  7. No vulnerable populations will be enrolled.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Investigational Scan; The proposed sequence (<15 minutes) will be added as a supplementary sequence only for the preoperative imaging if subjects agree to participate.	Other: Automatic DRT/VIM target-recognition method using MR-SISET and ML approaches; The proposed sequence (<15 minutes) will be added as a supplementary sequence only for the preoperative imaging for subjects who agree to participate: a 3D multi-echo GRE sequence will be performed during a preoperative MR imaging, using the following parameters: field of view = 220x170x75 mm3, matrix = 176x136x60, 1.25-mm isotropic resolution, flip angle = 22 degrees, TR = 92 ms, 20 TEs = 1.90 - 45.98 ms with echo spacing of 2.32 ms, bandwidth = 840 Hz/pixel.
ACTIVE_COMPARATOR: Current Clinical Practice; All patients will undergo a routine clinical preoperative MRI of the brain under general anesthesia to reduce movement artifacts.	Other: Routine clinical MRI protocol; MRI will be performed using 3T scanner (Skyra, Siemens, Erlangen, Germany). All patients will undergo preoperative MRI of the brain including routine clinical MRI protocol (T1-/T2-weighted and diffusion imaging) under general anesthesia to reduce movement artifacts.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tremor improvement	A routine clinical follow-up will be performed to assess the severity of tremor after the treatment (~ 6 weeks) by the clinician. Patients will be categorized into three groups based on their outcome: a good clinical outcome (>65% tremor improvement), a moderate outcome (>33%, but <66% tremor improvement) and a poor outcome (<33% tremor improvement).	6 weeks

Collaborators and Investigators

• Sponsor: NYU Langone Health
• Investigators: Principal Investigator: Sohae Chung, MD, NYU Langone; Principal Investigator: Timothy Shepherd, MD, NYU Langone

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 10, 2020
• Primary Completion (ACTUAL): June 15, 2022
• Study Completion (ACTUAL): June 15, 2022

Study Registration Dates

• First Submitted: December 3, 2020
• First Submitted That Met QC Criteria: December 3, 2020
• First Posted (ACTUAL): December 10, 2020

Study Record Updates

• Last Update Posted (ACTUAL): August 15, 2022
• Last Update Submitted That Met QC Criteria: August 12, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: Parkinson's Disease; Tremor; MRgFUS; magnetic resonance-guided focused ultrasound
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Dyskinesias; Parkinson Disease; Tremor; Essential Tremor
• Other Study ID Numbers: 20-00981

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The de-identified participant data from the final research dataset used in the published manuscript will be shared upon reasonable request beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research provided the investigator who proposes to use the data executes a data use agreement with NYU Langone Health. Requests may be directed to sohae.chung@nyulangone.org. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
• IPD Sharing Time Frame: beginning 9 months and ending 36 months following article publication
• IPD Sharing Access Criteria: Requests may be directed to sohae.chung@nyulangone.org.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

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