Diffusion Magnetic Resonance Imaging Predicts Peripheral Nerve Recovery in a Rat Sciatic Nerve Injury Model

Abstract

Background: Nerve regeneration after an injury should occur in a timely fashion for function to be restored. Current methods cannot monitor regeneration prior to muscle reinnervation. Diffusion tensor imaging has been previously shown to provide quantitative indices after nerve recovery. The goal of this study was to validate the use of this technology following nerve injury via a series of rat sciatic nerve injury/repair studies. Methods: Sprague-Dawley rats were prospectively divided by procedure (sham, crush, or cut/repair) and time points (1, 2, 4, and 12 weeks after surgery). At the appropriate time point, each animal was euthanized and the sciatic nerve was harvested and fixed. Data were obtained using a 7-Tesla magnetic resonance imaging system. For validation, findings were compared to behavioral testing (foot fault asymmetry and sciatic function index) and cross-sectional axonal counting of toluidine blue–stained sections examined under light microscopy. Results: Sixty-three rats were divided into three treatment groups (sham, n = 21; crush, n = 23; and cut/repair, n = 19). Fractional anisotropy was able to differentiate between recovery following sham, crush, and cut/repair injuries as early as 2 weeks (p < 0.05), with more accurate differentiation thereafter. More importantly, the difference in anisotropy between distal and proximal regions recognized animals with successful and failed recoveries according to behavioral analysis, especially at 12 weeks. In addition, diffusion tension imaging–based tractography provided a visual representation of nerve continuity in all treatment groups. Conclusions: Diffuse tensor imaging is an objective and noninvasive tool for monitoring nerve regeneration. Its use could facilitate earlier detection of failed repairs to potentially help improve outcomes.

Performance of Single-Shot Echo-Planar Imaging in Diffusion Tensor Imaging in Rat Sciatic Nerve Compared With Readout-Segmented Echo-Planar Imaging

“…FA and RD values are the most stable and sensitive biomarkers among the DTI metrics to evaluate peripheral nerve regeneration ( Naraghi et al, 2015 ; Chen et al, 2017 ). Previous studies on peripheral nerve repair have shown that the density and integrity of myelin increase during the process of nerve fiber regeneration, thereby resulting in higher FA and lower RD values ( Chen et al, 2017 ; Farinas et al, 2020 ; Zheng et al, 2021 ). Conversely, nerve anisotropy (FA) values decrease, and RD values increase during peripheral nerve degeneration in healthy older individuals or individuals with peripheral nerve disease because of decreased number of myelinated fibers ( Jeon et al, 2018 ; Lichtenstein et al, 2021 ).…”

“…DTI is also routinely used to assess the integrity of the peripheral nerves, especially in experimental animal studies of nerve injury. Several preclinical and animal studies have shown that DTI parameters such as fractional anisotropy (FA) and radial diffusivity (RD) are associated with axon density and myelin abnormalities ( Chen et al, 2017 ; Farinas et al, 2020 ; Zheng et al, 2021 ). Therefore, DTI parameters such as FA and RD are highly sensitive biomarkers for the early detection of peripheral nerve dysfunction and monitoring the progression of peripheral nerve degeneration and regeneration ( Chen et al, 2017 ; Farinas et al, 2020 ; Zheng et al, 2021 ).…”

Assessment of Rat Sciatic Nerve Using Diffusion-Tensor Imaging With Readout-Segmented Echo Planar Imaging

“…At the same time, RD quantifies the diffusion perpendicular to the axonal orientation and is supposed to reflect myelin-related information ( Jeon et al, 2018 ). Previously, peripheral nerve repair-related studies have shown that in the process of nerve fiber regeneration, with the density and integrality of myelin increases, FA value increases while RD value decreases ( Chen et al, 2017 ; Farinas et al, 2020 ; Zheng et al, 2021 ). Similarly, in the peripheral nerve degeneration process of healthy aging people, nerve anisotropy (FA) decreases and RD increases with the decrease of the number of myelinated fibers ( Jeon et al, 2018 ).…”

“…Many preclinical and animal studies have proven that DTI is one of the most valuable functional sequences in evaluating peripheral nerve injury repair and function ( Guggenberger et al, 2012 ; Jeon et al, 2018 ; Zheng et al, 2021 ). Parameters such as FA and RD derived from DTI are strongly correlated with myelin-related pathological parameters and are considered to be the sensitive biomarkers for detecting early peripheral nerve dysfunction, degeneration, and regeneration ( Chen et al, 2017 ; Farinas et al, 2020 ; Zheng et al, 2021 ).…”

Functional, morphological and molecular characteristics in a novel rat model of spinal sacral nerve injury-surgical approach, pathological process and clinical relevance

“…Peripheral nerve injury has always been the focus of clinical studies and basic medicine 31 , 32 . However, regarding basic medicine research, most previous studies have focused on peripheral nerves such as the sciatic nerve 33 , brachial plexus 34 and facial nerve 35 . Animal models of peripheral nerve injury and evaluation methods are mature 36 , 37 .…”