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.MATERIALS AND METHODS:Forty healthy subjects underwent T2WI, DTI, magnetization transfer, and T2*WI at 3T in <35 minutes using standard hardware and pulse sequences. Cross-sectional area, fractional anisotropy, magnetization transfer ratio, and T2*WI WM/GM signal intensity ratio were calculated. Relationships between MR imaging metrics and age, sex, height, weight, cervical cord length, and rostrocaudal level were analyzed. Test-retest coefficient of variation measured reliability in 24 DTI, 17 magnetization transfer, and 16 T2*WI datasets. DTI with and without cardiac triggering was compared in 10 subjects.RESULTS:T2*WI WM/GM showed lower intersubject coefficient of variation (3.5%) compared with magnetization transfer ratio (5.8%), fractional anisotropy (6.0%), and cross-sectional area (12.2%). Linear correction of cross-sectional area with cervical cord length, fractional anisotropy with age, and magnetization transfer ratio with age and height led to decreased coefficients of variation (4.8%, 5.4%, and 10.2%, respectively). Acceptable reliability was achieved for all metrics/levels (test-retest coefficient of variation < 5%), with T2*WI WM/GM comparing favorably with fractional anisotropy and magnetization transfer ratio. DTI with and without cardiac triggering showed no significant differences for fractional anisotropy and test-retest coefficient of variation.CONCLUSIONS:Reliable multiparametric assessment of spinal cord microstructure is possible by using clinically suitable methods. These results establish normalization procedures and pave the way for clinical studies, with the potential for improving diagnostics, objectively monitoring disease progression, and predicting outcomes in spinal pathologies.The era of quantitative MR imaging has arrived, allowing in vivo measurement of specific physical properties reflecting spinal cord (SC) microstructure and tissue damage.1,2 Such measures have potential clinical applications, including improved diagnostic tools, objective monitoring for disease progression, and prediction of clinical outcomes.3 However, technical challenges such as artifacts, image distortion, and achieving acceptable SNR have led to limited reliability. Specialized pulse sequences and custom hardware have advanced the field but incur costs of increased complexity and acquisition time while creating barriers to portability and clinical adoption. Furthermore, quantitative MR imaging metrics often show wide ranges of normal values and confounding relationships with subject characteristics such as age,4–8 for which most previous studies have not accounted.3Among the most promising SC quantitative MR imaging techniques are DTI and magnetization transfer (MT).1–3 These provide measures of axonal integrity and myelin quantity that correlate with functional impairment in conditions such as degenerative cervical myelopathy (DCM)5–7,9 and MS,3,9 albeit with limited physiologic specificity (eg, fractional anisotropy [FA] reflects both demyelination and axonal injury).10,11 SC cross-sectional area (CSA) computed from high-resolution anatomic images can measure atrophy (eg, in MS)12 or the degree of SC compression in DCM.13 T2*-weighted imaging at 3T or higher field strengths offers high resolution and sharp contrast between SC WM and GM, allowing segmentation between these structures similar to that in phase-sensitive inversion recovery.14,15 T2*WI also demonstrates hyperintensity in injured WM,16–18 reflecting demyelination, gliosis, and increased calcium and nonheme iron concentrations.19 T2*WI signal intensity is not an absolute quantity, so we normalize its value in WM by the average GM signal intensity in each axial section, creating a novel measure of WM injury: T2*WI WM/GM ratio.20We propose a multiparametric approach to cervical SC quantitative MR imaging with clinically feasible methods, including acceptable acquisition times, standard hardware/pulse sequences, and automated image analysis. Our protocol yields 4 measures of SC tissue injury (CSA, FA, MT ratio [MTR], and T2*WI WM/GM), for which this study establishes normative values in numerous ROIs. We characterize the variation of these metrics with age, sex, height, weight, cervical cord length, and rostrocaudal level and propose normalization methods. Finally, we assess test-retest reliability of FA, MTR, and T2*WI WM/GM and compare our DTI results against those with cardiac triggering. |