Early Detection of Neuroinflammation and White Matter Damage Following Dorsal Spinal Nerve Root Sectioning in a Nonhuman Primate Model.

Abstract

PURPOSE: Dorsal rhizotomy, or spinal dorsal nerve root lesioning, is a surgical procedure used to treat intractable nerve pain by selectively severing sensory afferent nerve roots. This study aimed to evaluate whether multiparametric MRI, including diffusion tensor imaging (DTI), quantitative magnetization transfer (qMT), chemical exchange saturation transfer (CEST), and relayed nuclear Overhauser enhancement (rNOE), can sensitively detect structural and biochemical changes in the intact spinal cord following a focal dorsal nerve root section in a nonhuman primate model. METHODS: In four squirrel monkeys, unilateral dorsal nerve roots at cervical segments C4 and C5 were surgically transected. MRI data were collected using a 9.4 T scanner with a custom saddle-shaped transmit-receive quadrature coil before and 1 week after lesioning. DTI-derived fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD); qMT-derived pool size ratio (PSR); and CEST and rNOE effects extracted from five-pool Lorentzian fitting of Z-spectrum, were quantified across seven regions of interest. RESULTS: At the lesioned dorsal nerve root bundles, FA, PSR, and rNOE (-1.6 ppm) values decreased, while RD and CEST (3.5 ppm) increased, consistent with fiber degeneration, demyelination, and inflammation. Similar, though less pronounced, changes were observed in the dorsal root entry zone, particularly within the first week post-lesion. CONCLUSION: Multiparametric MRI enables region-specific detection of spinal cord pathology, including axonal degeneration, demyelination, and possible neuroinflammation, as early as 1 week after dorsal nerve root injury. These results demonstrate its promise for noninvasive monitoring of post-injury pathology and for evaluating therapeutic efficacy.