Background and aims: Diffusion tensor imaging (DTI) has the advantage in revealing subtle pathology of damaged spinal cord more clearly and comprehensively. However, no study to date has elucidated the correlation between motor function recovery and dynamic changes of DTI parameters involving the whole spinal cord after repeated subarachnoid administrations of human umbilical cord mesenchymal stem cells (hUC-MSCs) in canine model of spinal cord injury (SCI). This study aimed to clarify it to quantitatively investigate DTI metrics as potential prognostic indicators for functional recovery of locomotion.

Materials and methods: Eight female beagle canines were subjected to thoracolumbar SCI, and then they received four times of intrathecal transplantation of hUC-MSCs from Week 2 (W2) to W5 (once per week). During the 15-week observation period, motor function of pelvic limb was assessed by using OIby score system at each week. At W1, W8 and W15, DTI scanning rostrally, centrally and caudally within the lesion site was performed and then, multiple radiological parameters, including fractional anisotropy (FA), average diffusion coefficient (ADC), axial diffusivity (AD), radial diffusivity (RD), mean diffusivity (MD), were collected.

Results: Significant improvement of OIby score was observed at the latest ten time points when compared with that at W1. FA rostrally, centrally and caudally within the lesion site revealed the decrease tendency, while all the other radiological indicators at these three regions had the N-shaped trend that showed initial increase and subsequent decrease. Except the comparisons between W15 and W1 regarding cranial MD, cranial RD and caudal RD, the remaining comparisons of radiological data between W15 and W1 and all the DTI metrics between W8 and W1 demonstrated statistical significance. Pearson correlation analysis found that cranial FA (r = 0.723, P = 0.043) at W8, as well as both cranial AD (r = -0.761, P = 0.028) and MD (r = -0.728, P = 0.041) at W15 correlated with the final OIby score. Simple regression model (y = 26.178 - 4.176x, y: OIby score, x: cranial AD value) uncovered a negative linear correlation between rostral AD and locomotion performance both at W15 (R² = 0.578, β=-0.761, P=0.028).

Conclusions: For the first time, our work demonstrates that in canine model of SCI receiving repeated intrathecal transplantation of hUC-MSCs, cranial FA at 3 weeks post-cytotherapy, as well as both cranial AD and MD at 10 weeks after hUC-MSCs administrations were associated with final regaining of motor function, and rostral AD seems a feasible predictor of behavioral recovery. This study provides DTI clues in predicting sensorimotor function restoration in humans with SCI after repeated subarachnoid transplantation of hUC-MSCs.