Longitudinal Assessment of Spinal Cord Structural Plasticity Using DTI in SCI Patients
Condition: Spinal Cord Injuries
MeSH terms: Spinal Cord Injuries
Study type: Observational

Summary: 
      This study will apply novel magnetic resonance imaging (MRI) techniques to investigation of
      spinal cord injury (SCI) to learn how nerve fibers repair and neural cells regain ability to
      control muscle during the rehabilitation. The information gained will be helpful for
      physicians to make more accurate diagnosis of SCI, predict injury recovery and movement
      restoration, and develop more effective treatment plans.
    

Detailed description: 
      Today, the International Standards for the Neurological Classification of Spinal Cord Injury
      (ISNSCI) , which includes tests of motor and cutaneous sensory function, and Spinal Cord
      Independence Measure (SCIM) are the gold standards for neurological classification of spinal
      cord injury (SCI). These standard measures have very important applications in the
      rehabilitation of SCI as primary clinical and outcome measures. Despite the importance and
      usefulness of their applications, these standard measures have their limitations. For
      example, ISNSCI, intended to be a clinical classification system, is subjective and
      relatively insensitive to incremental neurophysiological and functional changes during both
      acute and chronic stages of recovery. Moreover, the ISNSCI cannot evaluate the spinal cord
      (SC) function bellow the neurological level. For some patients such as children and patients
      with concomitant brain injuries, reliable evaluation cannot be completed due to their limited
      cognitive engagement in the evaluation process. Magnetic resonance imaging (MRI) has been
      proposed as a more objective tool to help clinicians make prognosis. However, recent study
      showed that conventional clinical MRI does not correlate well with scores measured with
      ISNSCI.

      Diffusion Tensor Imaging (DTI) is an advanced MRI tool capable of probing white matter
      integrity information through measuring directional diffusion of water molecules, thus
      providing more microscopic details than conventional MRI. Recent findings suggest that DTI is
      a promising, non-invasive and objective tool for evaluating and monitoring structural changes
      within white matter axon pathways after SCI. Our preliminary data showed significant
      deviation of DTI indices from normative values of healthy subjects in a SCI patient whose
      conventional T2 scans appeared to be normal (see preliminary data section). A likely
      explanation for this observed alteration of DTI indices is degeneration and demyelization in
      descending axonal pathways. Although DTI has been used in animal models to measure the
      evolution of the injury in the SC and showed great promise in detection of pathological
      changes in SC, no longitudinal DTI data obtained from human SC are available to indicate
      sensitivity of DTI technique in detecting SCI progression or recovery. Is DTI capable of
      detecting structural changes taking place in the SC over the course of rehabilitation in
      individuals with SCI? Will these measured DTI parameters correlate with ISNSCI-based scores?
      The fundamental hypothesis of the current study is that rehabilitation can facilitate SC
      fiber tract repair along with spontaneous adaptations following the injury to help reconnect
      some of the injured nerve fibers with motoneurons controlling muscles and this will in turn
      improve the motoneuron activity to promote muscular function, and all these changes can be
      detected by the proposed longitudinal DTI protocols and standard clinical tools for motor
      function evaluation. The expected results gained by this longitudinal study would support the
      application of DTI in monitoring plastic changes in the injured SC and the DTI-derived
      measures could potentially aid clinicians make more objective diagnosis of the injury and
      estimate its progression, which are critical in planning targeted therapies. However, it is
      out of the scope of this proposal to distinguish contributions to structural changes
      occurring in the SC between spontaneous and treatment factors. Because it is unethical to not
      treat patients, this limitation cannot be overcome in the current human study. Given the
      primary focus of the study being longitudinal tracking of SC structural changes using
      neuroimaging rather than determining relative contributions to these changes by spontaneous
      recovery and treatment, the limitation should not significantly influence the quality of our
      study. To test the hypothesis, the investigators propose the following Specific Aims.

      Aim 1: Track SC structural changes in patients with incomplete SCI (iSCI) using DTI. Each
      patient in the proposed study will be scanned covering entire cervical region of the SC using
      a DTI sequence at baseline, 2 weeks, 1 month, 3 month and 6 month after start of standard
      rehabilitation intervention. DTI indices (see methods for details) will be quantified and
      compared across all time points. Previous longitudinal brain DTI human and animal studies
      suggest that DTI is sensitive to detect brain whiter matter structural changes 24 hours
      (animal study) and 3 months (unpublished human DTI results by PI's group) after brain injury,
      and 6 month after initial scan in patients with Amyotrophic lateral sclerosis(ALS) (DTI data
      were only available 6 months after initial scan in this study). The investigators hypothesize
      that the proposed DTI protocol will be able to capture structural changes in SCI during its
      recovery course.

      Aim 2: Correlate the SC plasticity manifested by changes in DTI indices with clinical
      assessments of injury and sensorimotor function. Quantitative DTI indices will be correlated
      to clinical diagnoses of SCI and clinical evaluations of upper and lower limb sensorimotor
      function of the patients. It is hypothesized that the DTI index of SCI will significantly be
      correlated with clinical diagnosis and scores of upper and lower sensorimotor function. The
      DTI parameter holds great promise to be a biomarker of SCI and is expected to have prognostic
      value in predicting functional outcome of a rehabilitation program.
    

Intervention name(s): Standard Rehabilitative Treatment
Intervention type(s): Other
Intervention description(s): The patients will participate in standard but comprehensive SCI specific rehabilitation therapy provided by the SCI program at KIR. The therapy consists of 3 hours per day, 5 days a week. Motor function therapy includes standardized procedures for range of motion, passive and active muscle activities, and therapies to improve mobility. The treatment program for the enrolled patients will be standardized by Dr. Kirshblum, Director of the SCI program at KIR and a Co-Investigator of the study. Patients usually receive 4 weeks of rehabilitation treatment; however, if any of them are discharged earlier from KIR, their out-patient treatment activities will be monitored and the patients will be tested based on the planned schedule.
Observational model: Case-Control
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Twelve (12) individuals with iSCI (within 3 weeks post injury) will be recruited from
        Kessler Institute for Rehabilitation (KIR). In addition, we will recruit twelve healthy
        age- and gender-matched controls. All participants will give informed consent. For the SCI
        group the following clinical evaluations will occur at baseline, 2 weeks, 1 month, 3 months
        and 6 months by the study physician or clinician.
      
Keywords: diffusion tensor imaging