Person:

Neema, M

The objective of this study was to test a new version of the Magnetic Resonance Disease Severity Scale (MRDSS2), incorporating cerebral gray matter (GM) and spinal cord involvement from 3 T MRI, in modeling the relationship between MRI and physical disability or cognitive status in multiple sclerosis (MS). Fifty-five MS patients and 30 normal controls underwent high-resolution 3 T MRI. The patients had an Expanded Disability Status Scale score of 1.6±1.7 (mean±SD). The cerebral normalized GM fraction (GMF), the T2 lesion volume (T2LV), and the ratio of T1 hypointense LV to T2LV (T1/T2) were derived from brain images. Upper cervical spinal cord area (UCCA) was obtained from spinal cord images. A within-subject d-score (difference of MS from normal control) for each MRI component was calculated, equally weighted, and summed to form MRDSS2. With regard to the relationship between physical disability and MRDSS2 or its individual components, MRI–Expanded Disability Status Scale correlations were significant for MRDSS2 (r=0.33, P=0.013) and UCCA (r=−0.33, P=0.015), but not for GMF (P=0.198), T2LV (P=0.707), and T1/T2 (P=0.240). The inclusion of UCCA appeared to drive this MRI–disability relationship in MRDSS2. With regard to cognition, MRDSS2 showed a larger effect size (P=0.035) than its individual components [GMF (P=0.081), T2LV (P=0. 179), T1/T2 (P=0.043), and UCCA (P=0.818)] in comparing cognitively impaired with cognitively preserved patients (defined by the Minimal Assessment of Cognitive Function in MS). Both cerebral lesions (T1/T2) and atrophy (GMF) appeared to drive this relationship. We describe a new version of the MRDSS, which has been expanded to include cerebral GM and spinal cord involvement. MRDSS2 has concurrent validity with clinical status.

Grey matter (GM) damage is a clinically relevant feature of multiple sclerosis (MS) that has been previously assessed with diffusion tensor imaging (DTI). Fractional anisotropy (FA) of the basal ganglia and thalamus might be increased in MS patients, and correlates with disability scores. Despite the established role of the striatum and thalamus in motor control, mood and cognition, the impact of DTI changes within these structures on motor and neuropsychological performance has not yet been specifically addressed in MS. We investigated DTI metrics of deep GM nuclei and their potential association with mobility and neuropsychological function. DTI metrics from 3T MRI were assessed in the caudate, putamen, and thalamus of 30 MS patients and 10 controls. Sixteen of the patients underwent neuropsychological testing. FA of the caudate and putamen was higher in MS patients compared to controls. Caudate FA correlated with Expanded Disability Status Scale score, Ambulation Index, and severity of depressive symptomatology. Putamen and thalamus FA correlated with deficits in memory tests. In contrast, cerebral white matter (WM) lesion burden showed no significant correlation with any of the disability, mobility and psychometric parameters. Our findings support evidence of FA changes in the basal ganglia in MS patients, as well as deep GM involvement in disabling features of MS, including mobility and cognitive impairment. Deep GM FA appears to be a more sensitive correlate of disability than WM lesion burden.

Purpose We tested the validity of a freely available segmentation pipeline to measure compartmental brain volumes from 3T MRI in patients with multiple sclerosis (MS). Our primary focus was methodological to explore the effect of segmentation corrections on the clinical relevance of the output metrics. Methods: Three-dimensional T1-weighted images were acquired to compare 61 MS patients to 30 age- and gender-matched normal controls (NC). We also tested the within patient MRI relationship to disability (eg, expanded disability status scale [EDSS] score) and cognition. Statistical parametric mapping v. 8 (SPM8)-derived gray matter (GMF), white matter (WMF), and total brain parenchyma fractions (BPF) were derived before and after correcting errors from T1 hypointense MS lesions and/or ineffective deep GM contouring. Results: MS patients had lower GMF and BPF as compared to NC (P<.05). Cognitively impaired patients had lower BPF than cognitively preserved patients (P<.05). BPF was related to EDSS; BPF and GMF were related to disease duration (all P<.05). Errors caused bias in GMFs and WMFs but had no discernable influence on BPFs or any MRI-clinical associations. Conclusions: We report the validity of a segmentation pipeline for the detection of MS-related brain atrophy with 3T MRI. Longitudinal studies are warranted to extend these results.

Background/Purpose: To assess correlation between brain lesions and clinical status with 1.5T and 3T magnetic resonance imaging (MRI). Methods: Brain MRI fluid-attenuated inversion-recovery (FLAIR) sequences were performed in 32 multiple sclerosis (MS) patients. Expanded Disability Status Scale (EDSS) score (mean ± standard deviation) was 2 ± 2.0 (range 0-8), disease duration 9.3 ± 8.0 (range .8-29) years. Results: FLAIR lesion volume (FLLV) at 3T was higher than at 1.5T (P= .01). Correlation between 1.5T FLLV and EDSS score was poor, while 3T FLLV correlated moderately and significantly (rs= .39, P= .03). When controlling for age and depression, correlations between FLLV and cognitive measures were significant at 1.5T for the Judgment of Line Orientation test (JLO) (rs=−.44, P= .05), the Symbol Digit Modalities Test (SDMT) (rs=−.49, P= .02), and the California Verbal Learning Test Delayed Free Recall (CVLT DR) (rs=−.44, P= .04). Correlations at 3T were also significant for these tests, but of greater magnitude: JLO (rs=−.70, P= .0005), SDMT (rs=−.73, P= .0001), CVLT DR (rs=−.061, P= .003). Additional significant correlations obtained only at 3T included the 2 second-paced auditory serial addition test (rs=−.55, P= .01), the Brief Visuospatial Memory Test-Delayed Free Recall (rs=−.56, P= .007), and the California Verbal Learning Test Total Recall (rs=−.42, P= .05). Conclusion: MRI at 3T may boost sensitivity and improve validity in MS brain lesion assessment.

Background and Purpose: Fluid attenuated inversion recovery (FLAIR) MR imaging of the brain has become a routine tool for assessing lesions in patients with suspected neurologic disorders. There is growing interest in 3T brain FLAIR MR imaging but little normative data are available. The purpose of this study was to evaluate the frequency and topography of cerebral hyperintensities seen with FLAIR MR imaging of the brain at 3T in a normal population and compare those findings to 1.5T.Materials and Methods: Whole-brain 2D FLAIR MR imaging was performed in 22 healthy controls (mean age, 44 ± 8 years; range, 30–53 years) at 3T. Fifteen of these subjects also underwent 2D FLAIR at 1.5T, with similar optimized parameters and voxel size. Cerebral hyperintense areas, including discrete foci, anterior and posterior periventricular capping, diffuse parenchymal hyperintensity, septal hyperintensity, corticospinal tract hyperintensity, and CSF flow artifacts were assessed. The Spearman rank test assessed the correlation between discrete hyperintense foci and age. The Wilcoxon signed rank test compared foci detectability at 3T versus 1.5T. Results: FLAIR at 3T commonly showed hyperintensities such as discrete foci (mean, 10.68 per subject; at least 1 present in 68% of subjects), anterior and posterior periventricular capping, diffuse posterior white matter hyperintensity, septal hyperintensity, corticospinal tract hyperintensity, and ventricular CSF flow artifacts. FLAIR at 3T showed a higher hyperintense foci volume (170 ± 243 versus 93 ± 152 mm3, P < .01) and number (9.4 ± 13 versus 5.5 ± 9.2, P < .01) than at 1.5T. No significant differences (P = .68) in the length/diameter of individual discrete hyperintense foci were seen between 3T and 1.5T. Discrete foci volume (r = 0.72 at 3T, r = 0.70 at 1.5T) and number (r = 0.74 at 3T; r = 0.69 at 1.5T) correlated with age to a similar degree on both platforms. All discrete foci were confined to the noncallosal supratentorial white matter. The other nonfocal hyperintensities (anterior and posterior periventricular capping, diffuse parenchymal hyperintensity, septal hyperintensity, corticospinal tract hyperintensity, and CSF flow artifacts) were generally more common and prominent at 3T than at 1.5T. Conclusions: Discrete and diffuse parenchymal brain white matter FLAIR hyperintensities are more common and prominent at 3T than at 1.5T in healthy volunteers.

Background: Whole brain atrophy is a putative outcome measure in monitoring relapsing-remitting multiple sclerosis (RRMS). With the ongoing MRI transformation from 1.5T to 3T, there is an unmet need to calibrate this change. We evaluated brain parenchymal volumes (BPVs) from 1.5T versus 3T in MS and normal controls (NC). Methods: We studied MS [n = 26, age (mean, range) 43 (21-55), 22 (85%) RRMS, Expanded Disability Status Scale (EDSS) 1.98 (0-6.5), timed 25 foot walk (T25FW) 5.95 (3.2-33.0 seconds)] and NC [n = 9, age 45 (31-53)]. Subjects underwent 1.5T (Phillips) and 3T (GE) 3-dimensional T1-weighted scans to derive normalized BPV from an automated SIENAX pipeline. Neuropsychological testing was according to consensus panel recommendations. Results: BPV-1.5T was higher than BPV-3T [mean (95% CI) + 45.7 mL (+35.3, +56.1), P < .00001], most likely due to improved tissue-CSF contrast at 3T. BPV-3T showed a larger volume decrease and larger effect size in detecting brain atrophy in MS versus NC [-74.5 mL (-126.5, -22.5), P = .006, d = .92] when compared to BPV-1.5T [-51.3.1 mL (-99.8, -2.8), P = .04, d = .67]. Correlations between BPV-1.5T and EDSS (r = -.43, P = .027) and BPV-3T and EDSS (r = -.49, P = .011) and between BPV-1.5T and T25FW (r = -.46, P = .018) and BPV-3T and T25FW (r = -.56, P = .003) slightly favored 3T. BPV-cognition correlations were significant (P < .05) for 6 of 11 subscales to a similar degree at 1.5T (r range = .44-.58) and 3T (r range = .43-.53). Conclusions: Field strength may impact whole brain volume measurements in patients with MS though the differences are not too divergent between 1.5T and 3T.

Background: While disease categories (i.e. clinical phenotypes) of multiple sclerosis (MS) are established, there remains MRI heterogeneity among patients within those definitions. MRI-defined lesions and atrophy show only moderate inter-correlations, suggesting that they represent partly different processes in MS. We assessed the ability of MRI-based categorization of cerebral lesions and atrophy in individual patients to identify distinct phenotypes. Methods: We studied 175 patients with MS [age (mean ± SD) 42.7 ± 9.1 years, 124 (71%) women, Expanded Disability Status (EDSS) score 2.5 ± 2.3, n = 18 (10%) clinically isolated demyelinating syndrome (CIS), n = 115 (66%) relapsing-remitting (RR), and n = 42 (24%) secondary progressive (SP)]. Brain MRI measures included T2 hyperintense lesion volume (T2LV) and brain parenchymal fraction (to assess whole brain atrophy). Medians were used to create bins for each parameter, with patients assigned a low or high severity score. Results: Four MRI phenotype categories emerged: Type I = low T2LV/mild atrophy [n = 67 (38%); CIS = 14, RR = 47, SP = 6]; Type II = high T2LV/mild atrophy [n = 21 (12%); RR = 19, SP = 2]; Type III = low T2LV/high atrophy [n = 21 (12%); CIS = 4, RR = 16, SP = 1]; and Type IV = high T2LV/high atrophy [n = 66 (38%); RR = 33, SP = 33]. Type IV was the most disabled and was the only group showing a correlation between T2LV vs. BPF and MRI vs. EDSS score (all p < 0.05). Conclusions: We described MRI-categorization based on the relationship between lesions and atrophy in individual patients to identify four phenotypes in MS. Most patients have congruent extremes related to the degree of lesions and atrophy. However, many have a dissociation. Longitudinal studies will help define the stability of these patterns and their role in risk stratification.

Background and Purpose: VBM has been widely used to study GM atrophy in MS. MS lesions lead to segmentation and registration errors that may affect the reliability of VBM results. Improved segmentation and registration have been demonstrated by WM LI before segmentation. DARTEL appears to improve registration versus the USM. Our aim was to compare the performance of VBM-DARTEL versus VBM-USM and the effect of LI in the regional analysis of GM atrophy in MS. Materials and Methods: 3T T1 MR imaging scans were acquired from 26 patients with RRMS and 28 age-matched NC. LI replaced WM lesions with normal-appearing WM intensities before image segmentation. VBM analysis was performed in SPM8 by using DARTEL and USM with and without LI, allowing the comparison of 4 VBM methods (DARTEL + LI, DARTEL − LI, USM + LI, and USM − LI). Accuracy of VBM was assessed by using NMI, CC, and a simulation analysis. Results: Overall, DARTEL + LI yielded the most accurate GM maps among the 4 methods (highest NMI and CC, P < .001). DARTEL + LI showed significant GM loss in the bilateral thalami and caudate nuclei in patients with RRMS versus NC. The other 3 methods overestimated the number of regions of GM loss in RRMS versus NC. LI improved the accuracy of both VBM methods. Simulated data suggested the accuracy of the results provided from patient MR imaging analysis. Conclusions: We introduce a pipeline that shows promise in limiting segmentation and registration errors in VBM analysis in MS.

Background and Purpose: Spinal cord atrophy is a common feature of MS. However, it is unknown which cord levels are most susceptible to atrophy. We performed whole cord imaging to identify the levels most susceptible to atrophy in patients with MS versus controls and also tested for differences among MS clinical phenotypes. Materials and Methods: Thirty-five patients with MS (2 with CIS, 27 with RRMS, 2 with SPMS, and 4 with PPMS phenotypes) and 27 healthy controls underwent whole cord 3T MR imaging. The spinal cord contour was segmented and assigned to bins representing each C1 to T12 vertebral level. Volumes were normalized, and group comparisons were age-adjusted. Results: There was a trend toward decreased spinal cord volume at the upper cervical levels in PPMS/SPMS versus controls. A trend toward increased spinal cord volume throughout the cervical and thoracic cord in RRMS/CIS versus controls reached statistical significance at the T10 vertebral level. A statistically significant decrease was found in spinal cord volume at the upper cervical levels in PPMS/SPMS versus RRMS/CIS. Conclusions: Opposing pathologic factors impact spinal cord volume measures in MS. Patients with PPMS demonstrated a trend toward upper cervical cord atrophy. However patients with RRMS showed a trend toward increased volume at the cervical and thoracic levels, which most likely reflects inflammation or edema-related cord expansion. With the disease causing both expansion and contraction of the cord, the specificity of spinal cord volume measures for neuroprotective therapeutic effect may be limited.