The role of diffusion tensor imaging as an objective tool for the assessment of motor function recovery after paraplegia in a naturally-occurring large animal model of spinal cord injury

Abstract

BackgroundTraumatic spinal cord injury (SCI) results in sensory and motor function impairment and may cause a substantial social and economic burden. For the implementation of novel treatment strategies, parallel development of objective tools evaluating spinal cord (SC) integrity during motor function recovery (MFR) is needed. Diffusion tensor imaging (DTI) enables in vivo microstructural assessment of SCI.MethodsIn the current study, temporal evolvement of DTI metrics during MFR were examined; therefore, values of fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were measured in a population of 17 paraplegic dogs with naturally-occurring acute SCI showing MFR within 4 weeks after surgical decompression and compared to 6 control dogs. MRI scans were performed preoperatively and 12 weeks after MFR was observed. DTI metrics were obtained at the lesion epicentre and one SC segment cranially and caudally. Variance analyses were performed to compare values between evaluated localizations in affected dogs and controls and between time points. Correlations between DTI metrics and clinical scores at follow-up examinations were assessed.ResultsBefore surgery, FA values at epicentres were higher than caudally (p = 0.0014) and control values (p = 0.0097); ADC values were lower in the epicentre compared to control values (p = 0.0035) and perilesional (p = 0.0448 cranially and p = 0.0433 caudally). In follow-up examinations, no significant differences could be found between DTI values from dogs showing MFR and control dogs. Lower ADC values at epicentres correlated with neurological deficits at follow-up examinations (r = − 0.705; p = 0.0023).ConclusionsFindings suggest that a tendency to the return of DTI values to the physiological situation after surgical decompression accompanies MFR after SCI in paraplegic dogs. DTI may represent a useful and objective clinical tool for follow-up studies examining in vivo SC recovery in treatment studies.Electronic supplementary materialThe online version of this article (10.1186/s12967-018-1630-4) contains supplementary material, which is available to authorized users.

Diagnostic Imaging in Intervertebral Disc Disease

“…Diffusion tensor imaging has been reported in dogs with experimental injury and various naturally-occurring myelopathies (118,188,(190)(191)(192)(193)(194)(195)(196). Among experimental models, DTI indices have been correlated with specific histologic changes after injury, supporting its potential utility as a non-invasive measure of spinal cord microstructure (193,195,196).…”

Prognostic Factors in Canine Acute Intervertebral Disc Disease

“…A recent study proposed a semiautomated assessment of SC signal changes aiming to minimize interobserver variability (86). Diffusion tensor imaging (DTI) has been used in dogs with naturally occurring spinal cord injury secondary to IVDE (81,(87)(88)(89). The spinal cord, primarily white matter, microstructural changes are captured through quantification using DTI techniques.…”

“…As such DTI is able to detect abnormal SC areas that appear macroscopically normal on T2W sequences. Specific DTI parameters, including tractography, have the potential to serve as prognostic biomarkers, although no specific parameter has been identified (81,(87)(88)(89). More information regarding DTI in IVDE can be found in a companion article entitled Diagnostic imaging in intervertebral disc disease.…”

A Pilot Study on the Safety of a Novel Antioxidant Nanoparticle Delivery System and Its Indirect Effects on Cytokine Levels in Four Dogs

“…Clinical SCI in dogs has been studied as a large animal model for human SCI, with similarities in mechanisms of injury, pathology, and outcome ( 13 – 16 ). An ex vivo evaluation of microglial cells in canine SCI found increased production of ROS from activated microglia in dogs affected by SCI ( 17 ), further supporting their utilization as an intermediate translational model for human secondary SCI.…”