Longitudinal assessment of spinal cord injuries in nonhuman primates with quantitative magnetization transfer

Abstract

Purpose This study aimed to evaluate the reproducibility and specificity of quantitative magnetization transfer (qMT) imaging for monitoring spinal cord injuries (SCIs). Methods MRI scans were performed in anesthetized monkeys at 9.4T, before and serially after a unilateral lesion of the cervical spinal cord. A two-pool fitting model was used to derive qMT parameters. Results qMT measures were reproducible across normal subjects, with an average pool size ratio (PSR) of 0.086 ± 0.003 (Mean ± SD) for gray matter, and 0.120 ± 0.005 for white matter, respectively. Compared to normal gray matter, the PSR of abnormal tissues rostral and caudal to the injury site decreased by 19.5% (p < 0.05), while the PSR of the cyst-like volume decreased drastically weeks after SCI. Strong correlations in cyst-like regions were observed between PSR and other MRI measures including longitudinal relaxation rate (R1), apparent diffusion coefficient (ADC) and fractional anisotropy (FA). Decreased PSR and FA values correlated well with demyelination in abnormal tissues. Conclusion The qMT parameters provide robust and specific information about the molecular and cellular changes produced by SCI. PSR detected demyelination and loss of macromolecules in abnormal tissue regions rostral and caudal to the cyst/lesion sites.

MRI evaluation of regional and longitudinal changes in Z‐spectra of injured spinal cord of monkeys

“…For example, demyelination occurred primarily in spinal cord tissues both rostral and caudal to the lesion sites, and may be reflected in the immobile macromolecular pool VI in Figure f. This observation is consistent with our previous measurements of qMT that were later confirmed with tissue myelin stain . Cysts were formed only on the lesion side and were located next to WM showing dorsal column demyelination.…”

“…Our regional spectral quantifications provide MRI evidence for the presence of complex pathological processes in tissues, which could include inflammation, demyelination , release of neurotransmitter byproducts, and formation of cysts in different regions of spinal tissue surrounding the lesion sites . For example, demyelination occurred primarily in spinal cord tissues both rostral and caudal to the lesion sites, and may be reflected in the immobile macromolecular pool VI in Figure f.…”

“…Differences in T 1 may also affect the magnitudes of CEST effects. Across all abnormal tissue regions, cysts showed the longest T 1 . The amplitude of the Z‐spectrum at different RF offset is a function of the resonance frequency, relaxation rates, exchange rate and concentration.…”

“…CEST imaging revealed dynamic and differential molecular composition alterations within the cyst over a period of weeks to months . Quantitative MT (qMT) imaging identified demyelination of the WM tracts located rostral and dorsal to the injury site .…”

Differential fMRI Activation Patterns to Noxious Heat and Tactile Stimuli in the Primate Spinal Cord

“…Toward this goal, we have developed high-resolution and high-contrast MRI methods in monkeys. The power and potential of such an approach has been well demonstrated in our recent studies on spinal-cord-injured monkeys Wang et al, 2015).…”