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Background: Assessing the degree of myelin injury in patients with multiple sclerosis (MS) is challenging due to the lack of magnetic resonance imaging (MRI) methods specific to myelin quantity. By measuring distinct tissue parameters from a two-pool model of the magnetization transfer (MT) effect, quantitative magnetization transfer (qMT) may yield these indices. However, due to long scan times, qMT has not been translated clinically., Objectives: We aim to assess the clinical feasibility of a recently optimized selective inversion recovery (SIR) qMT and to test the hypothesis that SIR-qMT-derived metrics are informative of radiological and clinical disease-related changes in MS., Methods: A total of 18 MS patients and 9 age- and sex-matched healthy controls (HCs) underwent a 3.0 Tesla (3 T) brain MRI, including clinical scans and an optimized SIR-qMT protocol. Four subjects were re-scanned at a 2-week interval to determine inter-scan variability., Results: SIR-qMT measures differed between lesional and non-lesional tissue ( p  < 0.0001) and between normal-appearing white matter (NAWM) of patients with more advanced disability and normal white matter (WM) of HCs ( p  < 0.05). SIR-qMT measures were associated with lesion volumes, disease duration, and disability scores ( p  ⩽ 0.002)., Conclusion: SIR-qMT at 3 T is clinically feasible and predicts both radiological and clinical disease severity in MS.

Background: Cognitive impairment (CI) profoundly impacts quality of life for patients with multiple sclerosis (MS). Dysfunctional regulation of glutamate in gray matter (GM) has been implicated in the pathogenesis of MS by post-mortem pathological studies and in CI by in vivo magnetic resonance spectroscopy, yet GM pathology is subtle and difficult to detect using conventional T 1 - and T 2 -weighted magnetic resonance imaging (MRI). There is a need for high-resolution, clinically accessible imaging techniques that probe molecular changes in GM., Objective: To study cortical GM pathology related to CI in MS using glutamate-sensitive chemical exchange saturation transfer (GluCEST) MRI at 7.0 Tesla (7T)., Methods: A total of 20 patients with relapsing-remitting MS and 20 healthy controls underwent cognitive testing, anatomical imaging, and GluCEST imaging. Glutamate-sensitive image contrast was quantified for cortical GM, compared between cohorts, and correlated with clinical measures of CI., Results and Conclusion: Glutamate-sensitive contrast was significantly increased in the prefrontal cortex of MS patients with accumulated disability ( p  < 0.05). In addition, glutamate-sensitive contrast in the prefrontal cortex was significantly correlated with symbol digit modality test ( r S  = -0.814) and choice reaction time ( r S  = 0.772) scores in patients ( p  < 0.05), suggesting that GluCEST MRI may have utility as a marker for GM pathology and CI.

Background: The clinical course of multiple sclerosis (MS) is mainly attributable to cervical and upper thoracic spinal cord dysfunction. High-resolution, 7T anatomical imaging of the cervical spinal cord is presented. Image contrast between gray/white matter and lesions surpasses conventional, clinical T1- and T2-weighted sequences at lower field strengths., Objective: To study the spinal cord of healthy controls and patients with MS using magnetic resonance imaging at 7T., Methods: Axial (C2-C5) T1- and T2*-weighted and sagittal T2*-/spin-density-weighted images were acquired at 7T in 13 healthy volunteers (age 22-40 years), and 15 clinically diagnosed MS patients (age 19-53 years, Extended Disability Status Scale, (EDSS) 0-3) in addition to clinical 3T scans. In healthy volunteers, a high-resolution multi-echo gradient echo scan was obtained over the same geometry at 3T. Evaluation included signal and contrast to noise ratios and lesion counts for healthy and patient volunteers, respectively., Results/conclusion: High-resolution images at 7T exceeded resolutions reported at lower field strengths. Gray and white matter were sharply demarcated and MS lesions were more readily visualized at 7T compared to clinical acquisitions, with lesions apparent at both fields. Nerve roots were clearly visualized. White matter lesion counts averaged 4.7 vs 3.1 (52% increase) per patient at 7T vs 3T, respectively (p=0.05)., (© The Author(s), 2015.)

Background: Spinal cord (SC) pathology is a major contributor to clinical disability in multiple sclerosis (MS). Conventional magnetic resonance imaging (MRI), specifically SC-MRI lesion load measures that include lesion count and volume, demonstrate only a modest relationship with the clinical status of MS patients. Although SC cross-sectional area (CSA) correlates better with clinical dysfunction than MRI lesion count, SC atrophy likely signifies irreversible tissue loss. Using quantitative MRI indices sensitive to early and late microstructural changes in the spinal cord, we searched for the presence of better correlations between MRI measures and clinical status in MS., Objectives: We investigated whether diffusion-tensor imaging indices and the magnetization-transfer ratio (MTR) were better associated with the clinical status of MS patients than conventional SC-MRI measures., Methods: A total of 129 MS patients underwent 3-tesla cervical SC-MRI and quantitative sensorimotor function testing, using the Vibratron-II and dynamometer. Regions-of-interest circumscribed the SC on axial slices between C3-C4. We calculated SC-CSA, fractional anisotropy (FA), mean diffusivity (MD), perpendicular diffusivity (λ perpendicular), parallel diffusivity (λ||) and MTR. We used multivariable linear regression to determine if there were any associations between MRI indices and clinical measures of dysfunction., Results: All MRI indices were significantly different in subjects with MS versus healthy controls, and between the progressive versus relapsing MS subtypes, with the exception of λ||. In multivariable regression models that were adjusted for age, sex, brain parenchymal fraction, and SC-CSA, the MRI indices independently explained variability in hip flexion strength (p-values: MD, λ perpendicular, λ|| < 0.001; FA = 0.07), vibration sensation threshold (p-values: FA = 0.04; MTR = 0.05; λ perpendicular = 0.06), and Expanded Disability Status Scale scores (p-values: FA = 0.003; MD = 0.03; λ perpendicular = 0.005; MTR = 0.02)., Conclusions: In a large, heterogeneous MS sample, quantitative SC-MRI indices demonstrated independent associations with system-specific and global clinical dysfunction. Our findings suggest that the indices studied may provide important information about microstructural SC changes and the substrates of limb disability in MS. The identified structure-function relationships underpin the potential utility of these measures in assessments of therapeutic efficacy.