Abstract

Promising treatments are being developed to promote functional recovery after spinal cord injury (SCI). Magnetic resonance imaging, specifically Diffusion Tensor Imaging (DTI) has been shown to non-invasively measure both axonal and myelin integrity following traumatic brain and SCI. A novel data-driven model-selection algorithm known as Diffusion Basis Spectrum Imaging (DBSI) has been proposed to more accurately delineate white matter injury. The objective of this study was to investigate whether DTI/DBSI changes that extend to level of the cerebral peduncle and internal capsule following a SCI could be correlated with clinical function. A prospective non-randomized cohort of 23 patients with chronic spinal cord injuries and 17 control subjects underwent cranial diffusion weighted imaging, followed by whole brain DTI and DBSI computations. Region-based analyses were performed on cerebral peduncle and internal capsule. Three subgroups of patients were included in the region-based analysis. Tract-Based Spatial Statistics (TBSS) was also applied to allow whole-brain white matter analysis between controls and all patients. Functional assessments were made using International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) as modified by the American Spinal Injury Association (ASIA) Scale. Whole brain white matter analysis using TBSS finds no statistical difference between controls and all patients. Only cervical ASIA A/B patients in cerebral peduncle showed differences from controls in DTI and DBSI results with region-based analysis. Cervical ASIA A/B SCI patients had higher levels of axonal injury and edema/tissue loss as measured by DBSI at the level of the cerebral peduncle. DTI Fractional Anisotropy (FA), Axial Diffusivity (AD) and Radial Diffusivity (RD) was able to detect differences in cervical ASIA A/B patients, but were non-specific to pathologies. Increased water fraction indicated by DBSI non-restricted isotropic diffusion fraction in the cerebral peduncle, explains the simultaneously increased DTI AD and DTI RD values. Our results further demonstrate the utility of DTI to detect disruption in axonal integrity in white matter, yet a clear shortcoming in differentiating true axonal injury from inflammation/tissue loss. Our results suggest a preservation of axonal integrity at the cortical level and has implications for future regenerative clinical trials.

Highlights

  • Spinal cord injury (SCI) is a significant public health problem

  • Our results further demonstrate the utility of Diffusion tensor imaging (DTI) to detect disruption in axonal integrity in white matter, yet a clear shortcoming in differentiating true axonal injury from inflammation/tissue loss

  • Fractional Anisotropy (FA) values were significantly lower at the level of cerebral peduncle (CP)

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Summary

Introduction

Spinal cord injury (SCI) is a significant public health problem. Currently, 253,000 people in the United States are living with SCI, while 11,000 Americans are hospitalized for SCI each year [1].Brain Sci. 2017, 7, 21; doi:10.3390/brainsci7020021 www.mdpi.com/journal/brainsciBrain Sci. 2017, 7, 21Annually, $9.7 billion dollars are being spent on SCI research and patient care. Spinal cord injury (SCI) is a significant public health problem. Brain Sci. 2017, 7, 21; doi:10.3390/brainsci7020021 www.mdpi.com/journal/brainsci. $9.7 billion dollars are being spent on SCI research and patient care. A major shortcoming limiting efforts to improve the treatment of SCI is the lack of quantifiable metrics on which to base clinical decisions. Diffusion tensor imaging (DTI) has been demonstrated to noninvasively reflect the progression of white matter tract damage in SCI through characterizing water molecule diffusion [2,3,4,5,6,7,8]. The white matter of the central nervous system is highly ordered and has a coherent structure in which water diffusivity parallel to the fibers (axial diffusivity—AD)

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