Structural MRI correlates of PASAT performance in multiple sclerosis.
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ABSTRACT:
SUBMITTER: Matias-Guiu JA
PROVIDER: S-EPMC6300910 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Although diffusion tensor imaging (DTI) and the magnetization transfer ratio (MTR) have been extensively studied in multiple sclerosis (MS), it is still unclear if they are more effective biomarkers of disability than conventional MRI. MRI scans were performed on 117 participants with MS in addition to 26 healthy volunteers. Mean values were obtained for DTI indices and MTR for supratentorial brain and three white matter tracts of interest. DTI and MTR values were tested for correlations with measures of atrophy and lesion volume and were compared with these more conventional indices for prediction of disability. All DTI and MTR values correlated to an equivalent degree with lesion volume and cerebral volume fraction (CVF). Thalamic volumes correlated with all indices in the optic radiations and with mean and perpendicular diffusivity in the corpus callosum. Nested model regression analysis demonstrated that, compared with CVF, DTI indices in the optic radiations were more strongly correlated with Expanded Disability Status Scale and were also more strongly correlated than both CVF and lesion volume with low-contrast visual acuity. Abnormalities in DTI and MTR are equivalently linked with brain atrophy and inflammatory lesion burden, suggesting that for practical purposes they are markers of multiple aspects of MS pathology. Our findings that some DTI and MTR indices are more strongly linked with disability than conventional MRI measures justifies their potential use as targeted, functional system-specific clinical trial outcomes in MS.
| S-EPMC3753185 | biostudies-literature
Project description:Understanding genotype-phenotype relationships or development/validation of biomarkers requires large multicenter cohorts integrated by universal quantification of crucial phenotypical traits, such as central nervous system (CNS) tissue destruction. We hypothesized that mathematical modeling-guided combination of biologically meaningful, semi-quantitative MRI elements characterized by high signal-to-noise ratio will provide such reliable, universal tool for measuring CNS tissue destruction. We retrospectively graded 15 elements in MRI scans performed in 419 untreated subjects with or without neurological diseases, while being blinded to their prospectively acquired clinical scores. We then used 305 subjects for disability-guided mathematical modeling to select and combine MRI elements that had non-redundant contributions to clinical disability, resulting in Combinatorial MRI Scale (COMRIS). We validated our model on the remaining 114 independent subjects. COMRIS requires 5-10 min per scan on average to compute and demonstrates highly significant (p < 0.0001) and validation-consistent Spearman correlation coefficients (0.75, 0.76, and 0.65) for the expanded disability status scale (EDSS), Scripps neurological rating scale (SNRS), and symbol digit modality test (SDMT) measures of neurological disability, respectively. Because COMRIS is not greatly influenced by MRI scanners or protocols and can be computed even in the presence of some motion artifacts, it does not require censoring out patients and it provides comparable results across different cohorts. As such, it represents a broadly available clinical and research tool that can facilitate multicenter research studies and comparative analyses across patient cohorts and research projects.
| S-EPMC4656129 | biostudies-literature
Project description: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 (? perpendicular), parallel diffusivity (?||) 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 ?||. 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, ? perpendicular, ?|| < 0.001; FA = 0.07), vibration sensation threshold (p-values: FA = 0.04; MTR = 0.05; ? perpendicular = 0.06), and Expanded Disability Status Scale scores (p-values: FA = 0.003; MD = 0.03; ? 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.
| S-EPMC4482216 | biostudies-literature
Project description:Diffusion magnetic resonance imaging can reveal quantitative information about the tissue changes in multiple sclerosis. The recently developed multi-compartment spherical mean technique can map different microscopic properties based only on local diffusion signals, and it may provide specific information on the underlying microstructural modifications that arise in multiple sclerosis. Given that the lesions in multiple sclerosis may reflect different degrees of damage, we hypothesized that quantitative diffusion maps may help characterize the severity of lesions "in vivo" and correlate these to an individual's clinical profile. We evaluated this in a cohort of 59 multiple sclerosis patients (62% female, mean age 44.7 years), for whom demographic and disease information was obtained, and who underwent a comprehensive physical and cognitive evaluation. The magnetic resonance imaging protocol included conventional sequences to define focal lesions, and multi-shell diffusion imaging was used with b-values of 1000, 2000 and 3000 s/mm2 in 180 encoding directions. Quantitative diffusion properties on a macro- and micro-scale were used to discriminate distinct types of lesions through a k-means clustering algorithm, and the number and volume of those lesion types were correlated with parameters of the disease. The combination of diffusion tensor imaging metrics (fractional anisotropy and radial diffusivity) and multi-compartment spherical mean technique values (microscopic fractional anisotropy and intra-neurite volume fraction) differentiated two type of lesions, with a prediction strength of 0.931. The B-type lesions had larger diffusion changes compared to the A-type lesions, irrespective of their location (P < 0.001). The number of A and B type lesions was similar, although in juxtacortical areas B-type lesions predominated (60%, P < 0.001). Also, the percentage of B-type lesion volume was higher (64%, P < 0.001), indicating that these lesions were larger. The number and volume of B-type lesions was related to the severity of disease evolution, clinical disability and cognitive decline (P = 0.004, Bonferroni correction). Specifically, more and larger B-type lesions were correlated with a worse Multiple Sclerosis Severity Score, cerebellar function and cognitive performance. Thus, by combining several microscopic and macroscopic diffusion properties, the severity of damage within focal lesions can be characterized, further contributing to our understanding of the mechanisms that drive disease evolution. Accordingly, the classification of lesion types has the potential to permit more specific and better-targeted treatment of patients with multiple sclerosis.
| S-EPMC7502564 | biostudies-literature
Project description:Although cognitive impairment (CI) is frequently observed in people with multiple sclerosis (pwMS), its pathogenesis is still controversial. Conflicting results emerged concerning the role of microstructural gray matter (GM) damage especially when involving the deep GM structures. In this study, we aimed at evaluating whether differences in cortical and deep GM structures between apparently cognitively normal (ACN) and CI pwMS (36 subjects in total) are present, using an extensive set of diffusion MRI (dMRI) indices and conventional morphometry measures. The results revealed increased anisotropy and restriction over several deep GM structures in CI compared with ACN pwMS, while no changes in volume were present in the same areas. Conversely, reduced anisotropy/restriction values were detected in cortical regions, mostly the pericalcarine cortex and precuneus, combined with reduced thickness of the superior frontal gyrus and insula. Most of the dMRI metrics but none of the morphometric indices correlated with the Symbol Digit Modality Test. These results suggest that deep GM microstructural damage can be a strong anatomical substrate of CI in pwMS and might allow identifying pwMS at higher risk of developing CI.
| S-EPMC8234586 | biostudies-literature
Project description:ObjectivesTo explore in vivo innate immune cell activation as a function of the distance from ventricular CSF in patients with multiple sclerosis (MS) using [18F]-DPA714 PET and to investigate its relationship with periventricular microstructural damage, evaluated by magnetization transfer ratio (MTR), and with trajectories of disability worsening.MethodsThirty-seven patients with MS and 19 healthy controls underwent MRI and [18F]-DPA714 TSPO dynamic PET, from which individual maps of voxels characterized by innate immune cell activation (DPA+) were generated. White matter (WM) was divided in 3-mm-thick concentric rings radiating from the ventricular surface toward the cortex, and the percentage of DPA+ voxels and mean MTR were extracted from each ring. Two-year trajectories of disability worsening were collected to identify patients with and without recent disability worsening.ResultsThe percentage of DPA+ voxels was higher in patients compared to controls in the periventricular WM (p = 6.10e-6) and declined with increasing distance from ventricular surface, with a steeper gradient in patients compared to controls (p = 0.001). This gradient was found in both periventricular lesions and normal-appearing WM. In the total WM, it correlated with a gradient of microstructural tissue damage measured by MTR (r s = -0.65, p = 1.0e-3). Compared to clinically stable patients, patients with disability worsening were characterized by a higher percentage of DPA+ voxels in the periventricular normal-appearing WM (p = 0.025).ConclusionsOur results demonstrate that in MS the innate immune cell activation predominates in periventricular regions and is associated with microstructural damage and disability worsening. This could result from the diffusion of proinflammatory CSF-derived factors into surrounding tissues.
| S-EPMC8105971 | biostudies-literature
Project description:Multiple Sclerosis (MS) is a chronic inflammatory/demyelinating and neurodegenerative disease of the central nervous system (CNS). Most patients experience a relapsing-remitting (RR) course, while about 15-20% of patients experience a primary progressive (PP) course. Cognitive impairment affects approximately 40-70% of all MS patients and differences in cognitive impairment between RR-MS and PP-MS have been found. We aimed to compare RR-MS and PP-MS patients in terms of cognitive performance, and to investigate the MRI correlates of cognitive impairment in the two groups using measures of brain volumes and cortical thickness. Fifty-seven patients (42 RR-MS, 15 PP-MS) and thirty-eight matched controls underwent neuropsychological (NP) testing and MRI. PP-MS patients scored lower than RR-MS patients on most of the NP tests in absence of any specific pattern. PP-MS patients showed significantly lower caudate volume. There was no significant difference in MRI correlates of cognitive impairment between the two groups except for a prevalent association with MRI measures of cortical GM injury in RR-MS patients and with MRI measures of subcortical GM injury in PP-MS patients. This suggests that although cognitive impairment results from several factors, cortical and subcortical GM injury may play a different role depending on the disease course.
| S-EPMC4616346 | biostudies-other
Project description:Upper and lower limb impairments are common in people with multiple sclerosis (pwMS), yet difficult to clinically identify in early stages of disease progression. Tasks involving complex motor control can potentially reveal more subtle deficits in early stages, and can be performed during functional MRI (fMRI) acquisition, to investigate underlying neural mechanisms, providing markers for early motor progression. We investigated brain activation during visually guided force matching of hand or foot in 28 minimally disabled pwMS (Expanded Disability Status Scale (EDSS) < 4 and pyramidal and cerebellar Kurtzke Functional Systems Scores ≤ 2) and 17 healthy controls (HC) using ultra-high field 7-Tesla fMRI, allowing us to visualise sensorimotor network activity in high detail. Task activations and performance (tracking lag and error) were compared between groups, and correlations were performed. PwMS showed delayed (+124 s, p = .002) and more erroneous (+0.15 N, p = .001) lower limb tracking, together with lower cerebellar, occipital and superior parietal cortical activation compared to HC. Lower activity within these regions correlated with worse EDSS (p = .034), lower force error (p = .006) and higher lesion load (p < .05). Despite no differences in upper limb task performance, pwMS displayed lower inferior occipital cortical activation. These results demonstrate that ultra-high field fMRI during complex hand and foot tracking can identify subtle impairments in lower limb movements and upper and lower limb brain activity, and differentiates upper and lower limb impairments in minimally disabled pwMS.
| S-EPMC8090767 | biostudies-literature
Project description:Background:Secondary progressive multiple sclerosis (SPMS) is characterized by worsening of postural control and brain atrophy. However, little is known about postural deficits and their neuroanatomical correlates in this population. We aimed to determine the neuroanatomical correlates of postural deficits in people with SPMS and whether posture control deteriorates concomitantly with the brain and spinal cord atrophy in 2 years in SPMS. Methods:This study is a post hoc analysis of data from 27 people with SPMS (mean ± SE age, 58.6 ± 1.1 years). Participants had magnetic resonance imaging (MRI) of the brain and cervical spinal cord followed by sway testing using inertial sensors during standing with eyes open (EO) and eyes closed without (EC) and with (ECC) a cognitive task. Partial correlations investigated relationships between postural control and MRI measures at baseline and 2 years. Results:At baseline, sway measures were inversely related to cortical thickness and cord cross-sectional area (CSA) during the EO task but only to cord CSA with EC (P < .05). After 2 years, the percentage change in sway amplitude and dispersion during EO tasks significantly related to the percentage decline in cord CSA (P < .01). Conclusions:Cortical and spinal cord inputs are essential for regulation of postural control during standing with EO in SPMS. Without visual input, people with SPMS preferentially rely on somatosensory inputs from the spinal cord for maintaining postural control. Postural deficits related to cord atrophy over 2 years, suggesting that postural control may be a surrogate marker of disease progression in people with SPMS.
| S-EPMC7307870 | biostudies-literature
Project description:BACKGROUND: B cells and humoral immune responses play an important role in the pathogenesis and diagnosis of multiple sclerosis (MS). A characteristic finding in patients with MS is a polyspecific intrathecal B cell response against neurotropic viruses, specifically against measles virus, rubella virus, and varicella zoster virus, also known as an MRZ reaction (MRZR). Here, we correlated from the routine clinical diagnostics individual IgG antibody indices (AIs) of MRZR with magnetic resonance imaging (MRI) findings in patients with first MS diagnosis. METHODS/RESULTS: MRZR was determined in 68 patients with a clinically isolated syndrome (CIS) or early relapsing-remitting MS (RRMS). Absolute AI values for measles virus, rubella virus, and varicella zoster virus were correlated with T2 lesion load and gadolinium enhancing lesions on cerebral MRI (cMRI) and cMRI combined with spinal MRI (sMRI). Measles virus AI correlated significantly with T2 lesion load on cMRI (p?=?0.0312, Mann-Whitney U test) and the sum of lesions on cMRI and sMRI (p?=?0.0413). Varicella zoster virus AI also showed a correlation with T2 lesion load on cMRI but did not reach statistical significance (p?=?0.2893). CONCLUSION: The results confirm MRZR as part of the polyspecific immune reaction in MS with possible prognostic impact on MRI and clinical parameters. Furthermore, the data indicate that intrathecal measles virus IgG production correlates with disease activity on cMRI and sMRI in patients with early MS.
| S-EPMC3261854 | biostudies-other