Multiparametric MRI reveals dynamic changes in molecular signatures of injured spinal cord in monkeys

Abstract

Purpose To monitor the spontaneous recovery of cervical spinal cord injury (SCI) using longitudinal multi-parametric MRI methods. Methods Quantitative MRI imaging including diffusion tensor imaging (DTI), magnetization transfer (MT), and chemical exchange saturation transfer (CEST) was conducted in anesthetized monkeys at 9.4 T. The structural, cellular and molecular features of the spinal cord were examined before and at different time-points after a dorsal column lesion in each monkey. Results Images with MT contrast enhanced visualization of the grey and white matter boundaries and the lesion, and permitted differentiation of core and rim compartments within an abnormal volume (AV). At early weeks after SCI, both core and rim exhibited low cellular density and low protein content, with high levels of exchanging hydroxyl, amine, and amide protons, as evidenced by increased apparent diffusion coefficient (ADC) value, decreased fractional anisotropy (FA), decreased magnetization transfer ratio (MTR), decreased nuclear Overhauser effect (NOE), and large CEST effects. Over time, while cellular density and fiber density increased, amide, amine, and hydroxyl levels dropped significantly, but at differing rates. Histology confirmed the nature of the AV to be a cyst. Conclusion Multi-parametric MRI offers a novel method to quantify the spontaneous changes in structure and cellular and molecular compositions of SC during spontaneous recovery from injury.

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

“…7j). Swollen axonal sheaths and gliosis, and high density of reactivated glia cells were observed (12). Similar features have been reported previously in specimens from SCI patients (49).…”

“…Observed relaxation rate R 1obs and B 1 maps were obtained based on images acquired with two flip angles, whereas data for B 0 mapping were calculated from two gradient echo images (ΔTE = 2 ms). CEST and DTI data were acquired within the same imaging session, and the specific data acqusition and analysis methods are described in the supporting information as well as in our previous report (12). …”

“…To date, simpler metrics such as MTR (32) have been the major approach to assess changes in macromolecular composition in neurological disorders (33,34), neuromuscular diseases (35), liver fibrosis (36), and cancer (37). MTR has also been shown to be sensitive to changes in protein content and has been used previously in studies of SC (12,38,39). The sensitivity and reproducibility of MTR measure can be influenced by various experimental parameters.…”

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

“…a). The correlations between Z‐spectra are affected by changes in CEST, DS, NOE, and/or semisolid MT effects which make them more sensitive for identifying tissue variations than a simple MT ratio . We selected seven regions surrounding the lesion site in one representative SCI subject (SM‐P) 10 weeks after lesion (Fig.…”

“…Extending our previous study that focused on CEST effects at 3 radiofrequency (RF) offsets downfield of water in the Z‐spectra of the rim and core compartments of cysts, as identified by their MT ratio , here we examined whole Z‐spectra to segment distinct abnormal regions around lesion sites based on pixel‐by‐pixel correlations between the Z‐spectra, and simultaneously fit each spectrum to a five‐pool model to derive measurements of tissue molecular constituents. The analysis takes account of direct saturation on free water (DS), NOE (nuclear Overhauser enhancement), and semisolid MT effects in addition to CEST .…”