Relaxation-compensated chemical exchange saturation transfer MRI in the cervical spinal cord at 3T: An application in multiple sclerosis

Multiple sclerosis (MS) is an autoimmune disease affecting the central nervous system, characterized by demyelination. Exploring pathological changes in the spinal cord could improve our understanding of the mechanisms that cause neurological dysfunction and clinical symptoms; however, conventional MRI is not sensitive to molecular changes within the tissue. Chemical exchange saturation transfer (CEST) can probe tissue biochemistry with high resolution and sensitivity, without exogenous contrasts. However, CEST measurements in vivo are contaminated by concurrent effects including semi-solid magnetization transfer (MT), direct water saturation, and T1-relaxation, which can be altered in MS and need to be removed to accurately quantify changes. Fifty-three people with relapsing-remitting MS (pwRRMS) and 45 healthy controls (HCs) were imaged at 3 T to quantify amide and nuclear Overhauser enhancement (NOE) CEST effects in the cervical spinal cord. Using Lorentzian fitting, confounding effects were removed, and the apparent exchange-dependent relaxation (AREX) contrast was calculated. Uncorrected and corrected AREX amide and NOE contrasts were compared across groups and tissue types. In pwRRMS, AREX NOE was significantly different in lesions compared to normal-appearing white matter. Greater heterogeneity in both CEST contrasts was observed in pwRRMS compared to the HCs. In a sub-analysis of pwRRMS separated by neurological disability, AREX amide was significantly different between pwRRMS with and without disability. The correction of confounding factors in this study highlights the importance of isolating CEST effects in the cervical spinal cord for more specific characterization and to better understand changes in tissue pathology and relationship to disease severity.