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Assessing spinal cord structure changes using diffusion tensor imaging in patients with incomplete traumatic spinal cord injury
Bing Yao1,2, Hannah Ovadia1, Zhiguo Jiang1, Sarah Wood1, Gail Forrest3, and Steven Kirshblum4

1Rocco Ortenzio Neuroimaging Center, Kessler Foundation, West Orange, NJ, United States, 2Department of Physical Medicine and Rehabilitation, Rutgers University, Newark, NJ, United States, 3Human Performance Engineering Research, Kessler Foundation, West Orange, NJ, United States, 4Kessler Institute for Rehablitation, West Orange, NJ, United States

Synopsis

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.

Methods and Materials

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.

Conclusion and Discussion

The DTI has been widely used in studying human brain. Our study on the spinal cord shows DTI is a sensitive tool to detect SC fiber abnormalities too. These findings support the hypothesis that DTI can detect the reduced nerve fiber structure quality in SCI. DTI thus might be able to detect longitudinal changes in SC white matter structure during the course of rehabilitation in patients with incomplete SCI even below the neurological injury level. It could also potentially provide different neurophysiological information than traditional self-reports. More longitudinal data is being collected to further investigate the detection of spinal cord recovery status using this technique.

Acknowledgements

This study is supported by grants NIH/NINDS R21 NS085456 and New Jersey Commission on Spinal Cord Research CSCR15ERG013.

References

[1] S. C. Kirshblum, W. Waring, F. Biering-Sorensen, S. P. Burns, M. Johansen, M. Schmidt-Read, W. Donovan, D. Graves, A. Jha, L. Jones, M. J. Mulcahey, and A. Krassioukov, “Reference for the 2011 revision of the International Standards for Neurological Classification of Spinal Cord Injury.,” J. Spinal Cord Med., vol. 34, no. 6, pp. 547–54, Nov. 2011.

[2] R. J. Marino and D. E. Graves, “Metric properties of the ASIA motor score: Subscales improve correlation with functional activities,” Arch. Phys. Med. Rehabil., vol. 85, no. 11, pp. 1804–1810, Nov. 2004.

[3] M. J. Mulcahey, A. F. Samdani, J. P. Gaughan, N. Barakat, S. Faro, P. Shah, R. R. Betz, and F. B. Mohamed, “Diagnostic accuracy of diffusion tensor imaging for pediatric cervical spinal cord injury,” Spinal Cord, no. October 2012, pp. 1–6, 2013.

[4] Y. Chang, T. Jung, D. S. Yoo, and J. K. Hyun, “Diffusion Tensor Imaging and Fiber Tractography of Patients with Cervical Spinal Cord Injury,” J. Neurot, vol. 27, no. November, pp. 2033–2040, 2010.

Figures

Fig 1 (A) T2 weighted whole spine image from a representative male healthy volunteer (age=42); (B) Example of T2* weighted MEDIC image; (C) Example of spine DTI tractography. Only the cervical region was displayed. Fiber direction is color coded in RGB. Red=right/left; green=anterior/posterior; blue=inferior-superior.

Fig 2 shows the tractography of the cervical spine of one healthy subject (A) and one SCI patient (B). The yellow circle indicates a significant signal dropout at the T4 level, which matches the location of the implanted hardware in this SCI patient.

Fig 3 shows the comparison of the whole spine averaged DTI indices (AD, MD, FA, and RD) between the healthy control (HC) and patient (SCI) groups.

Proc. Intl. Soc. Mag. Reson. Med. 27 (2019)
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