Functional connectivity in the dorsal network of the cervical spinal cord is correlated with diffusion tensor imaging indices in relapsing-remitting multiple sclerosis.

Focal lesions may affect functional connectivity (FC) of the ventral and dorsal networks in the cervical spinal cord of people with relapsing-remitting multiple sclerosis (RRMS). Resting-state FC can be measured using functional MRI (fMRI) at 3T. This study sought to determine whether alterations in FC may be related to the degree of damage in the normal-appearing tissue. Tissue integrity and FC in the cervical spinal cord were assessed with diffusion tensor imaging (DTI) and resting-state fMRI, respectively, in a group of 26 RRMS participants with high cervical lesion load, low disability, and minimally impaired sensorimotor function, and healthy controls. Lower fractional anisotropy (FA) and higher radial diffusivity (RD) were observed in the normal-appearing white matter in the RRMS group relative to controls. Average FC in ventral and dorsal networks was similar between groups. Significant associations were found between higher FC in the dorsal sensory network and several DTI markers of pathology in the normal-appearing tissue. In the normal-appearing grey matter, dorsal FC was positively correlated with axial diffusivity (AD) (r = 0.46, p = 0.020) and mean diffusivity (MD) (r = 0.43, p = 0.032). In the normal-appearing white matter, dorsal FC was negatively correlated with FA (r = -0.43, p = 0.028) and positively correlated with RD (r = 0.49, p = 0.012), AD (r = 0.42, p = 0.037) and MD (r = 0.53, p = 0.006). These results suggest that increased connectivity, while remaining within the normal range, may represent a compensatory mechanism in response to structural damage in support of preserved sensory function in RRMS.

Relaxation-Compensated Chemical Exchange Saturation Transfer MRI in the Brain at 7T: Application in Relapsing-Remitting Multiple Sclerosis.

Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) can probe tissue biochemistry in vivo with high resolution and sensitivity without requiring exogenous contrast agents. Applying CEST MRI at ultrahigh field provides advantages of increasing spectral resolution and improving sensitivity to metabolites with faster proton exchange rates such as glutamate, a critical neurotransmitter in the brain. Prior magnetic resonance spectroscopy and CEST MRI studies have revealed altered regulation of glutamate in patients with multiple sclerosis (MS). While CEST imaging facilitates new strategies for investigating the pathology underlying this complex and heterogeneous neurological disease, CEST signals are contaminated or diluted by concurrent effects (e.g., semi-solid magnetization transfer (MT) and direct water saturation) and are scaled by the T1 relaxation time of the free water pool which may also be altered in the context of disease. In this study of 20 relapsing-remitting MS patients and age- and sex-matched healthy volunteers, glutamate-weighted CEST data were acquired at 7.0 T. A Lorentzian fitting procedure was used to remove the asymmetric MT contribution from CEST z-spectra, and the apparent exchange-dependent relaxation (AREX) correction was applied using an R1 map derived from an inversion recovery sequence to further isolate glutamate-weighted CEST signals from concurrent effects. Associations between AREX and cognitive function were examined using the Minimal Assessment of Cognitive Function in MS battery. After isolating CEST effects from MT, direct water saturation, and T1 effects, glutamate-weighted AREX contrast remained higher in gray matter than in white matter, though the difference between these tissues decreased. Glutamate-weighted AREX in normal-appearing gray and white matter in MS patients did not differ from healthy gray and white matter but was significantly elevated in white matter lesions. AREX in some cortical regions and in white matter lesions correlated with disability and measures of cognitive function in MS patients. However, further studies with larger sample sizes are needed to confirm these relationships due to potential confounding effects. The application of MT and AREX corrections in this study demonstrates the importance of isolating CEST signals for more specific characterization of the contribution of metabolic changes to tissue pathology and symptoms in MS.