MRI of peripheral nerve degeneration and regeneration: correlation with electrophysiology and histology

Abstract

Acute axonal nerve lesions cause a hyperintense signal on T2-weighted (T2-w) magnetic resonance imaging (MRI) at the nerve lesion site and distal to it. The aim of this experimental study was to investigate the spatiotemporal evolution and resolution of MR nerve signal changes following denervation and reinnervation, and to relate these findings to electrophysiology and histology. The proximal sciatic nerve of adult rats was ligated by a tight suture that was removed 1 week later to induce complete axotomy and nerve regeneration upon release. Serial electromyography (EMG) and motor nerve conduction studies were performed parallel to MRI at multiple points of time. Moreover, sciatic nerves were taken for quantitative histological evaluation. Nerve hyperintensity on T2-w MRI was present distal to the lesion at thigh level 24 h after denervation preceding the occurrence of spontaneous activity on EMG by 24 h. After 48 h, the entire sciatic nerve and its branches showed an increased signal down to the level of the lower leg. The increased nerve signal regressed with a proximo-distal gradient beginning from week 2 after onset of nerve regeneration in the thigh. On EMG, the first reinnervation potentials were detected at that time at the respective level. Compound muscle action potential (CMAP) in the foot muscle fully recovered 12 weeks after onset of nerve regeneration, that is, 2 weeks after resolution of the hyperintensity along the entire nerve on MRI. Histology revealed axonal degeneration in the acute phase and later nerve oedema parallel to the increased nerve signal on MRI. MR signal alterations occur as early as 24 h after an axonal nerve lesion and correlate with nerve fiber degeneration and later with nerve oedema on histology. MR findings in denervation and reinnervation parallel the electrophysiological changes. Thus, MRI is a promising diagnostic tool for the early detection of acute axonal nerve lesions and monitoring of nerve regeneration.

Introduction

Axonal injury of peripheral nerves caused by axotomy or crush induces a degeneration of the distal nerve fibers called Wallerian degeneration. Determining the site and degree of the nerve lesion is important for patient management especially in the early phase after injury. Electromyography (EMG) and nerve conduction studies are considered as the gold standard in the assessment of peripheral nerve lesions. Nevertheless, the evaluation of the severity of a nerve lesion and assessment of early nerve regeneration by electrophysiology remain difficult. Recently, magnetic resonance imaging (MRI) has been introduced in the diagnosis of peripheral nerve lesions. In experimental studies, axonal nerve injury is characterized by a prolongation of the T2 relaxation time at the lesion site and distal thereof Cudlip et al., 2002, Does and Snyder, 1996, Stanisz et al., 2001, Titelbaum et al., 1989. However, little is known about the pathophysiology and time course of the MR signal changes in denervated nerves, and no data are available corresponding to electrophysiological data. In the present study, nerve signal changes following denervation and reinnervation were studied longitudinally in a rat model using a clinical MR scanner and correlated with quantitative histological and electrophysiological findings.