Investigation of Brain Functional MRI as an Early Biomarker of Recovery in Individuals With Spinal Cord Injury
Condition: Spinal Cord Injuries
MeSH terms: Spinal Cord Injuries; Wounds and Injuries
Study type: Interventional

Summary: 
      Early detection of response to therapeutic intervention is vital, as it will enable early
      termination of intervention in non-responding patients, prevent unnecessary financial burden,
      and allow for early changes to the intervention program. Previous functional MRI (fMRI)
      studies have shown that changes in brain functional network in spinal cord injury (SCI)
      patients can occur after as little as one week of intervention. Resting state fMRI (rsfMRI)
      is a type of fMRI that does not require performance of explicit motor tasks, which makes the
      method especially suitable for SCI patient population. In this project, the investigators
      propose that rsfMRI outcome measures can be used to detect early brain functional network
      changes that occur during intervention, and that the changes will be predictive of recovery
      in chronic SCI patients.
    

Detailed description: 
      Early detection of response to spinal cord injury (SCI) therapeutic intervention programs is
      vital, as it will enable early termination of intervention in non-responding patients,
      prevent unnecessary financial burden, and allow for early changes of the programs. In this
      project, the investigators propose that resting state functional MRI (rsfMRI) can be used to
      detect early brain functional network changes that occur during intervention, and that the
      changes will be predictive of recovery in chronic SCI patients. The long-term goal of this
      study is to establish rsfMRI as a new imaging biomarker that is predictive of progress
      towards recovery in response to therapy. International Standard of Neurological
      Classification for Spinal Cord Injury (ISNCSCI) scoring system is the most widely used
      clinical classification system of SCI that describes neurological injury level and degree of
      functional preservation. It is also used to monitor the progress and response to
      interventions such as functional electrical stimulation (FES) therapy. However, monitoring
      responses using ISNSCI is challenging, because its ability to describe the degree of
      functional loss is limited. Therefore, there is a need in the field of SCI for a biomarker
      that is more sensitive to changes in function. The investigators will recruit 2 groups of 24
      chronic SCI patients. In one group, the investigators will characterize the baseline time
      profile of rsfMRI outcome measures acquired during a 4-weeks passive cycling program, where
      movement is driven only by the cycle's motor (no electric stimulation). RsfMRI data of the
      patients acquired at weeks 0, 2, and 4 will be used perform functional parcellation of the
      sensorimotor cortex using independent component analysis (ICA) and spectral clustering
      analysis (SCA) approaches. BNC will be calculated between pairs of sensory and motor brain
      parcels. Sensory and motor ISNCSCI scores will also be measured at weeks 0, 2, and 4. The
      investigators will then test the hypothesis that the investigators will observe stable
      baseline measures of sensory and motor cortex BNC and ISNCSCI scores of the patients during
      the 4-week passive cycling program, with minimal to no change in values. In the second group,
      the investigators will characterize the time profile of the cortical reorganization in
      chronic SCI patients that occurs during the four-week FES cycling. Specifically, the
      investigators predict that the investigators will observe early functional network changes in
      the sensorimotor cortex of SCI patients (measured using BNC) at week 2 of the four-week FES
      cycling program, which will be predictive of changes in ISNSCI scores (neurological outcomes)
      at week 4. Finally, the longitudinal intra-subject reproducibility of the two parcellation
      methods will be investigated. If successful, the study will: 1) provide a new and effective
      clinical tool to study plastic cortical changes that occur after SCI, 2) provide a new
      non-invasive imaging biomarker that is predictive of progress towards recovery in response to
      therapy, and 3) extend our knowledge about the functional reorganization that takes place
      during and after therapeutic intervention.
    

Intervention name(s): Functional Electric Stimulation cycling; Passive cycling
Intervention type(s): Device; Device
Intervention description(s): The Functional Electrical Stimulation (FES) cycling group will use RT300 ergometer (Restorative Therapies, Inc). Bilateral glutei, quadriceps and hamstrings will be stimulated. The stimulation parameters will be set as follows: waveform biphasic, charged balanced; phase duration of 250 microseconds; pulse rate 33-45 pps. The stimulus intensity will be adjusted for individual patients and muscle group so that a tolerable stimulation is provided that will generate a cycling action. Target cycling speed is 50 RPM. Resistance will be automatically adjusted by the FES bike according to the subject's performance. When fatigue occurs, participants will continue cycling with electrical stimulation and motor support. FES therapy will be administered for one hour per session 3 times a week.; The passive cycling group will use the same RT300 ergometer however during this period stimulation will not be turned on. Instead, continuous motor support will be activated resulting in passive cycling. Target cycling speed is 50 RPM. Participants assigned to passive cycling will be required to have one hour of passive therapy 3 times a week for the entire duration of treatment assignment.
Other intervention name(s): RT300 ergometer; RT300 ergometer
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: The study will be performed as a randomized, parallel group trial to determine if the amount of changes in brain functional connectivity outcome measures (i.e., between network connectivity) is significantly different between the group of patients that perform FES cycling and another group of patients that perform passive (sham) cycling.
Official screening will be performed after participants consent by signing the study's consent form. Participants will be randomized into 2 groups: FES cycling (Group 1; n=24) and passive cycling (Group 2; n=24). The participants will undergo either an FES cycling or a passive cycling sessions for 4 weeks, 3 times a week. MRI will be performed on all participants at the beginning (prior to cycling sessions) and at the end of the 2nd and 4th weeks of the intervention program. ISNCSCI evaluations will be performed to coincide with the dates of MRI acquisitions, to determine the neurological level and the degree of sensory and motor impairments.
Masking: Double (Participant, Care Provider)
Primary purpose: Basic Science
Keywords: Spinal Cord Injuries; MRI, Functional; Rehabilitation; Neuronal Plasticity