Probabilistic Assessment of Nerve Regeneration with Diffusion MRI in Rat Models of Peripheral Nerve Trauma

Abstract

Nerve regeneration after injury must occur in a timely fashion to restore function. Unfortunately, current methods (e.g., electrophysiology) provide limited information following trauma, resulting in delayed management and suboptimal outcomes. Herein, we evaluated the ability of diffusion MRI to monitor nerve regeneration after injury/repair. Sprague-Dawley rats were divided into three treatment groups (sham = 21, crush = 23, cut/repair = 19) and ex vivo diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI) was performed 1–12 weeks post-surgery. Behavioral data showed a distinction between crush and cut/repair nerves at 4 weeks. This was consistent with DTI, which found that thresholds based on the ratio of radial and axial diffusivities (RD/AD = 0.40 ± 0.02) and fractional anisotropy (FA = 0.53 ± 0.01) differentiated crush from cut/repair injuries. By the 12th week, cut/repair nerves whose behavioral data indicated a partial recovery were below the RD/AD threshold (and above the FA threshold), while nerves that did not recover were on the opposite side of each threshold. Additional morphometric analysis indicated that DTI-derived normalized scalar indices report on axon density (RD/AD: r = −0.54, p < 1e-3; FA: r = 0.56, p < 1e-3). Interestingly, higher-order DKI analyses did not improve our ability classify recovery. These findings suggest that DTI may provide promising biomarkers for distinguishing successful/unsuccessful nerve repairs and potentially identify cases that require reoperation.

Initial findings in traumatic peripheral nerve injury and repair with diffusion tensor imaging

“…However, it is difficult to separate axonal regeneration from remyelination using measures of RD alone, and a more myelin‐specific measure, like magnetization transfer MRI, 40 could further improve specificity. For AD, previous animal studies have shown that AD is sensitive to axonal regeneration in the first two weeks after injury 41 . However, we acquired MRI data later within our cohort (i.e., after Wallerian degeneration), potentially explaining why we did not observe any significant differences for AD between injured and contralateral, healthy nerves ( P = 0.250).…”

Multiparametric Quantitative MRI of Peripheral Nerves in the Leg: A Reliability Study

“…It has also been reported that the RD is more sensitive to axonal loss and is modulated by demyelination in ex vivo nerve crushing models on rats. 27 Clinical studies have reported consistently reduced FA, but generally heterogeneous results on MD, AD, and RD in neuropathies and nerve trauma. 9,[28][29][30][31][32][33] On the other hand, MRI-based morphological quantification shows nerve hypertrophy in demyelinating polyneuropathies such as CMT type-1A and CIDP.…”

Feasibility of in vivo multi-parametric quantitative magnetic resonance imaging of the healthy sciatic nerve with a unified signal readout protocol

“…In terms of the standard DTI metrics, the mean values obtained in this study seem to follow a similar trend and appear to be in agreement with the results of previous studies examining the sciatic nerve in healthy controls 9 , 11 , although differences in technical and demographic factors do not permit a direct comparison. The potential value and feasibility of DKI measurements in the PNS has previously been explored in animal models 55 , but has only recently been addressed in vivo 56 . Therefore, more studies will be required in the future to understand the additional information related to tissue composition and microstructure that can potentially be obtained in pathological conditions affecting the PNS.…”