Physicians rely on self-reports to monitor and evaluate the functional outcome in patients with spinal cord injury during their rehabilitation. These clinical and outcome measurements can be subjective and sometimes impractical if patients have cognitive difficulty. Traditional clinical MRI scans can provide doctors more objective information but they are not sensitive to detect the progression or repair during patient’s recovery. In this study, we investigated the sensitivity of DTI technique in detecting SCI injury and its progression or recovery over the course of rehabilitation in the individuals with SCI.
Introduction
Today, the International Standards for the Neurological Classification of Spinal Cord Injury (ISNSCI), and Spinal Cord Independence Measure (SCIM) are the gold standards for neurological classification of spinal cord injury (SCI)1,2. However, 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 below the neurological level3. Magnetic resonance imaging (MRI) has been proposed as a more objective tool to help clinicians make prognosis. However, study showed that conventional clinical MRI does not correlate well with scores measured with ISNSCI4. Diffusion Tensor Imaging (DTI) is an advanced MRI tool capable of probing white matter integrity through measuring directional diffusion of water molecules, thus may providing more microscopic details. In this study, we investigated the sensitivity of DTI in detecting SCI injury and its progression or recovery over the course of rehabilitation.Participants: Five acute SCI patients (age=22 to 56, Female/Male=3/2, AIS grade=B to D) and three healthy controls (age = 23 to 55, Female/Male=2/1) have participated the study. All the participants went through five visits including imaging and outcome measurement sessions over the course of the first-year post injury (baseline, 2 weeks, 1 month, 3 months, and 6 months after the commencement of rehabilitative treatment). The outcome measurements including ISNSCI, Modified Ashworth Scale (MAS) and Spinal Cord Independence Measure III (SCIM III) were performed at each visit for the patient group.
Image Acquisition: All MRIs were acquired at a 3T Siemens scanner with a 20-channel head/neck coil and a 32-channel spine coil. A high resolution T2-weighted spin echo sequence were used to collect anatomical spine images on sagittal plane. The axial DTI covering the entire cervical and thoracic sections of the cord was acquired with the following parameters: TE=97ms, TR=3600ms, Flip angle=90º; in-plane resolution=132x132mm2, thickness = 3mm, 30 directions with b=1000s/mm2. Another anatomical scan using T2*-weighted Multi-Echo Data Image Combination (MEDIC) sequence matching the DTI slice location was acquired.
Data Analysis: The raw DTI data were corrected for eddy current distortion and motion using FSL then further processed using Diffusion Toolkit. DTI indices including FA, MD, AD, and RD were computed for each voxel. ROIs at each disk and midlevel locations were carefully drawn from C2 to T12 level on the FA map, with the guide of T2* images. Virtual nerve fibers were reconstructed using the fiber assignment through line propagation approach based on 2nd order Runge Kutta algorithm. For each ROI, we compared the measured DTI indices along the entire cord using along-tract-stats toolbox.
Results
Fig 1 shows the results from a representative health subject. All levels of spine can be clearly identified from the scan (Fig 1A). The T2* weighted axial image of cervical spine shows a superb contrast between white matter and gray matter within SC (Fig 1B). Fig 1C shows a 3D fiber tractography. SC fiber tracts and spinal nerves branching out from and going into the SC are clearly visible from tractography. Fig 2 shows the tractography of the cervical spine of one healthy subject (A) and one SCI patient (B). Continuous and longer fibers (blue tracks) can be observed on the healthy subject, indicating the intact integrity of the white matter fibers. On the other hand, shorter and thinner fibers are seen on the SCI patient, suggesting the damaged white matter fibers. A signal drop off is observed on the SCI T2 image (Fig 2B, yellow circled area), which matches the implanted hardware located at T4 level on this patient. The DTI indices on the HCs are significantly greater than those on the SCIs across all the five time points (paired t-test, p < 0.01) except for RD (Fig 3). SCIM scores additionally improved over time (p < 0.05), with higher scores at the six month period than at baseline (p < 0.05; mean = 69.0 and 81.25, respectively). However, DTI indices did not show significant correlation with SCIM totals.
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