Longitudinal changes in DTI parameters of specific spinal white matter tracts correlate with behavior following spinal cord injury in monkeys

Abstract

This study aims to evaluate how parameters derived from diffusion tensor imaging reflect axonal disruption and demyelination in specific white matter tracts within the spinal cord of squirrel monkeys following traumatic injuries, and their relationships to function and behavior. After a unilateral section of the dorsal white matter tract of the cervical spinal cord, we found that both lesioned dorsal and intact lateral tracts on the lesion side exhibited prominent disruptions in fiber orientation, integrity and myelination. The degrees of pathological changes were significantly more severe in segments below the lesion than above. The lateral tract on the opposite (non-injured) side was minimally affected by the injury. Over time, RD, FA, and AD values of the dorsal and lateral tracts on the injured side closely tracked measurements of the behavioral recovery. This unilateral section of the dorsal spinal tract provides a realistic model in which axonal disruption and demyelination occur together in the cord. Our data show that specific tract and segmental FA and RD values are sensitive to the effects of injury and reflect specific behavioral changes, indicating their potential as relevant indicators of recovery or for assessing treatment outcomes. These observations have translational value for guiding future studies of human subjects with spinal cord injuries.

Cerebral White Matter Myelination and Relations to Age, Gender, and Cognition: A Selective Review

“…Also, age-related decrease in myelination in these fibers is delayed ( Lebel et al, 2012 ). Myelination of the SC is mainly studied in animal and clinical studies ( Tu et al, 2013 ; Antherieu et al, 2019 ; Mishra et al, 2020 ). Cervical SC microstructural properties are vulnerable to aging, as FA in this subdivision shows strong negative correlation with age ( Agosta et al, 2007 ) and it dramatically decreases after the age of 55 years ( Vedantam et al, 2013 ).…”

Harmonization of Longitudinal Diffusion Tensor Imaging Data of the Pediatric Cervical and Thoracic Spinal Cord at 3T Using Longitudinal ComBat

“…Diffusion tensor imaging (DTI) has emerged as a powerful modality for examining microstructural alterations within the spinal cord, offering invaluable insights into various neurological conditions such as traumatic and non-traumatic spinal cord injury, degenerative diseases, and tumors [1][2][3]. DTI parameters including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), apparent diffusion coe cient (ADC), and relative anisotropy (RA) have been demonstrated to be good indicators of normative white matter microstructure and potential predictors of demyelination in pathological states in human and animal studies [3,[9][10][11][12][13].…”

Sensitivity and specificity of CEST and NOE MRI in injured spinal cord in monkeys

“…Non-invasive, multi-parametric, magnetic resonance imaging (mpMRI) methods allow detection and monitoring of the injury itself as well as injury-associated structural, functional and molecular changes over time ( Stroman et al, 2014 , Wheeler-Kingshott et al, 2014 , Chen et al, 2015 , Wang et al, 2015 , Wang et al, 2016b , Wang et al, 2018b , Wang et al, 2019 , Yang et al, 2015 , Wu et al, 2020 ). In previous studies, we have studied injured spinal cords of non-human primates (NHPs) using a mpMRI protocol, including chemical exchange saturation transfer (CEST) ( Wang et al, 2015 , Wang et al, 2018b ), relayed nuclear Overhauser enhancement (NOE) ( Wang et al, 2015 , Wang et al, 2018b ), diffusion tensor imaging (DTI) ( Wang et al, 2015 , Mishra et al, 2020 ), quantitative magnetization transfer (qMT) ( Wang et al, 2016b , Wang et al, 2019 ), and functional MRI (fMRI) ( Chen et al, 2015 , Yang et al, 2015 ). These advanced quantitative MRI methods have allowed us to delineate the damage to injured spinal cord at the compartment level and across several spinal segments around the injury site for up to 6 months post injury ( Chen et al, 2015 , Wang et al, 2015 , Wang et al, 2016b , Wang et al, 2018b , Wang et al, 2019 , Wu et al, 2019 ).…”