Abstract

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. 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. 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. 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.

Highlights

  • BACKGROUND AND PURPOSEDTI, magnetization transfer, T2*-weighted imaging, and cross-sectional area can quantify aspects of spinal cord microstructure

  • 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, with T2*WI WM/GM comparing favorably with fractional anisotropy and magnetization transfer ratio

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Summary

MATERIALS AND METHODS

Study Design and Subjects This study received approval from the University Health Network (Toronto, Ontario, Canada), and written informed consent was obtained from all participants. Relationships between MR imaging metrics (averaged from C1–C7) and patient characteristics (age, sex, height, weight, cervical cord length) were assessed with Pearson correlation coefficients and backward stepwise linear regression to determine significant independent relationships and their coefficients. Reliability was assessed by using testretest coefficient of variation, and differences between healthy subjects and those with DCM were assessed with Welch t tests, as were pair-wise comparisons between techniques at each rostrocaudal level. Univariate relationships between MR imaging metrics and subject characteristics included the following: CSA increased with cervical cord length (P ϭ 8 ϫ 10Ϫ4), weight (P ϭ .03), and male sex (P ϭ .03); FA decreased with age (P ϭ .009); and MTR decreased with height (P ϭ .008), weight (P ϭ .01), and male sex (P ϭ .006) (Table 3). Cord length (␤ ϭ ϩ5.3690); FA, with age (␤ ϭ Ϫ0.0012053); and MTR, with height (␤ ϭ Ϫ0.17410, P ϭ .001) and age (␤ ϭ Ϫ0.074131, P ϭ .01), while T2*WI WM/GM did not require nor-

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