Clinically Feasible Microstructural MRI to Quantify Cervical Spinal Cord Tissue Injury Using DTI, MT, and T2*-Weighted Imaging: Assessment of Normative Data and Reliability

Abstract

BACKGROUND AND PURPOSE: DTI, magnetization transfer, T2*-weighted imaging, and cross-sectional area can quantify aspects of spinal cord microstructure. However, clinical adoption remains elusive due to complex acquisitions, cumbersome analysis, limited reliability, and wide ranges of normal values. We propose a simple multiparametric protocol with automated analysis and report normative data, analysis of confounding variables, and reliability.

A Novel MRI Biomarker of Spinal Cord White Matter Injury: T2*-Weighted White Matter to Gray Matter Signal Intensity Ratio

“…19,20 We hypothesized that T2*WI hyperintensity is a general phenomenon in WM injury, leading to decreased graywhite contrast that can be quantified by normalizing the WM signal intensity within each axial section by that of the GM as a T2*WI WM/GM signal-intensity ratio. Our investigation in 40 healthy subjects established that T2*WI WM/GM has lower intersubject variability compared with CSA, FA, and MTR and superior reliability compared with FA and MTR, 7 though the latter metrics showed acceptable results, in keeping with prior reports. 11,[21][22][23][24][25] These encouraging findings prompted the current study in degenerative cervical myelopathy (DCM), a common condition involving degeneration of the discs, ligaments, and vertebrae, resulting in cervical spinal cord compression and functional impairment (Fig 1).…”

“…T2*WI WM/GM also shows better reliability, compared with FA and MTR, with our techniques. 7 In comparison with DTI and MT techniques, T2*WI had fewer excluded sections, required less imaging time, and involved less postprocessing, suggesting that this biomarker is well-suited for clinical use. Unfortunately, all qMRI metrics failed to show diagnostic accuracy (AUC) of Ͼ90% and provided only moderate clinical correlations, indicating somewhat limited utility when used individually.…”

“…7 Metrics included CSA from T2WI, FA, MTR, and T2*WI WM/GM signalintensity ratio extracted from the rostral uncompressed SC (C1-C3); the maximally compressed level (MCL); and the caudal un- compressed cord (C6 -C7). For MCL metrics, CSA was extracted from a single section, whereas FA, MTR, and T2*WI WM/GM were averaged over 3 sections centered at the compressed level.…”

“…7 The multiecho recombined gradient-echo sequence uses 3 echoes that are magnitude-reconstructed and combined with a sum-of-squares algorithm. Total imaging time was approximately 30 -35 minutes, including subject positioning, section prescription, and second-order localized shimming.…”

“…3 The strongest results include cross-sectional area (CSA) as a measure of spinal cord atrophy, the DTI metric fractional anisotropy (FA) to evaluate axonal integrity, and the magnetization transfer ratio (MTR) as a measure of demyelination. 3 Spinal cord CSA has shown moderate-to-strong correlation with disability in MS [4][5][6] but is a nonspecific measure of tissue injury and shows high intersubject variability in healthy subjects, 7,8 somewhat limiting its utility. FA has demonstrated moderate correlation with global and focal disability in dozens of studies involving various pathologies 3,[9][10][11][12][13][14] but has yet to achieve clinical uptake due to a lack of standardized/portable acquisition methods and cumbersome analysis techniques.…”