Clinically feasible MTR is sensitive to cortical demyelination in MS.
ABSTRACT OBJECTIVE: Presently there is no clinically feasible imaging modality that can effectively detect cortical demyelination in patients with multiple sclerosis (MS). The objective of this study is to determine if clinically feasible magnetization transfer ratio (MTR) imaging is sensitive to cortical demyelination in MS. METHODS: MRI were acquired in situ on 7 recently deceased patients with MS using clinically feasible sequences at 3 T, including relatively high-resolution T1-weighted and proton density-weighted images with/without a magnetization transfer pulse for calculation of MTR. The brains were rapidly removed and placed in fixative. Multiple cortical regions from each brain were immunostained for myelin proteolipid protein and classified as mostly myelinated (MM(ctx)), mostly demyelinated (MD(ctx)), or intermediately demyelinated (ID(ctx)). MRIs were registered with the cortical sections so that the cortex corresponding to each cortical section could be identified, along with adjacent subcortical white matter (WM). Mean cortical MTR normalized to mean WM MTR was calculated for each cortical region. Linear mixed-effects models were used to test if mean normalized cortical MTR was significantly lower in demyelinated cortex. RESULTS: We found that mean normalized cortical MTR was significantly lower in cortical tissue with any demyelination (ID(ctx) or MD(ctx)) compared to MM(ctx) (demyelinated cortex: least-squares mean [LSM] = 0.797, SE = 0.007; MM(ctx): LSM = 0.837, SE = 0.006; p = 0.01, n = 89). CONCLUSIONS: This result demonstrates that clinically feasible MTR imaging is sensitive to cortical demyelination and suggests that MTR will be a useful tool to help detect MS cortical lesions in living patients with MS.
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ABSTRACT: Magnetization transfer imaging (MTI) can detect microstructural brain tissue changes and may be helpful in determining age-related cerebral damage. We investigated the association between the magnetization transfer ratio (MTR) in gray and white matter (WM) and cognitive functioning in 355 participants of the Austrian stroke prevention family study (ASPS-Fam) aged 38-86 years. MTR maps were generated for the neocortex, deep gray matter structures, WM hyperintensities, and normal appearing WM (NAWM). Adjusted mixed models determined whole brain and lobar cortical MTR to be directly and significantly related to performance on tests of memory, executive function, and motor skills. There existed an almost linear dose-effect relationship. MTR of deep gray matter structures and NAWM correlated to executive functioning. All associations were independent of demographics, vascular risk factors, focal brain lesions, and cortex volume. Further research is needed to understand the basis of this association at the tissue level, and to determine the role of MTR in predicting cognitive decline and dementia.Frontiers in Aging Neuroscience 09/2014; 6:263. DOI:10.3389/fnagi.2014.00263 · 2.84 Impact Factor
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ABSTRACT: Neuropathological studies in multiple sclerosis have suggested that meningeal inflammation in the brain may be linked to disease progression. Inflammation in the spinal cord meninges has been associated with axonal loss, a pathological substrate for disability. Quantitative magnetic resonance imaging facilitates the investigation of spinal cord microstructure by approximating histopathological changes. We acquired structural and quantitative imaging of the cervical spinal cord from which we calculated magnetization transfer ratio in the outer spinal cord-an area corresponding to the expected location of the pia mater and subpial region-and in spinal cord white and grey matter. We studied 26 healthy controls, 22 people with a clinically isolated syndrome, 29 with relapsing-remitting, 28 with secondary-progressive and 28 with primary-progressive multiple sclerosis. Magnetization transfer ratio values in the outermost region of the spinal cord were higher than the white matter in controls and patients: controls (51.35 ± 1.29 versus 49.87 ± 1.45, P < 0.01), clinically isolated syndrome (50.46 ± 1.39 versus 49.13 ± 1.19, P < 0.01), relapsing-remitting (48.86 ± 2.89 versus 47.44 ± 2.70, P < 0.01), secondary-progressive (46.33 ± 2.84 versus 44.75 ± 3.10, P < 0.01) and primary-progressive multiple sclerosis (46.99 ± 3.78 versus 45.62 ± 3.40, P < 0.01). In linear regression models controlling for cord area and age, higher outer spinal cord magnetization transfer ratio values were seen in controls than all patient groups: clinically isolated syndrome (coefficient = -0.32, P = 0.03), relapsing-remitting (coefficient = -0.48, P < 0.01), secondary-progressive (coefficient = -0.51, P < 0.01) and primary-progressive multiple sclerosis (coefficient = -0.38, P < 0.01). In a regression analysis correcting for age and cord area, magnetization transfer ratio values in the outer cord were lower in relapsing-remitting multiple sclerosis compared with clinically isolated syndrome (coefficient = -0.28, P = 0.02), and both primary and secondary-progressive compared to relapsing-remitting multiple sclerosis (coefficients = -0.29 and -0.24, respectively, P = 0.02 for both). In the clinically isolated syndrome and relapsing-remitting multiple sclerosis groups, outer cord magnetization transfer ratio was decreased in the absence of significant cord atrophy. In a multivariate regression analysis an independent association was seen between outer cord magnetization transfer ratio and cord atrophy (coefficient = 0.40, P < 0.01). Our in vivo imaging observations suggest that abnormalities in a region involving the pia mater and subpial cord occur early in the course of multiple sclerosis and are more marked in those with a progressive course.Brain 06/2014; DOI:10.1093/brain/awu171 · 10.23 Impact Factor
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ABSTRACT: To investigate whether spinal cord (SC) lesion load, when quantified on axial images with high in-plane resolution, is associated with disability in multiple sclerosis (MS). Twenty-eight healthy controls and 92 people with MS had cervical SC 3T MRI with axial phase sensitive inversion recovery, T2, and magnetization transfer (MT) sequences. We outlined all visible focal lesions from C2 to C4 to obtain lesion load and also measured upper cervical cord area. We measured MT ratio in normal-appearing cord tissue and in lesions. Disability was recorded using the Expanded Disability Status Scale (EDSS) and MS Functional Composite. We used linear regression models to determine associations with disability. SC lesion load was significantly higher in both secondary progressive MS (SPMS) (p = 0.008) and primary progressive MS (PPMS) (p = 0.02) compared to relapsing-remitting MS (RRMS); in each comparison, adjustment was made for age, sex, and brain volume. These differences were not evident when EDSS was added as a covariate. SC area was significantly lower in both SPMS (p < 0.001) and PPMS (p = 0.009) compared to RRMS. In a multiple regression model, cord lesion load (p < 0.001), cord area (p = 0.003), age (p < 0.001), and sex (p = 0.001) were independently associated with EDSS (R(2) = 0.58). Cord lesion load (p = 0.003), cord area (p = 0.034), and brain parenchymal fraction (p = 0.007) were independently associated with the 9-hole peg test (R(2) = 0.42). When quantified on axial MRI with high in-plane resolution, upper cervical cord lesion load is significantly and independently correlated with physical disability and is higher in progressive forms of MS than RRMS. © 2014 American Academy of Neurology.Neurology 12/2014; DOI:10.1212/WNL.0000000000001186 · 8.30 Impact Factor