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In recent studies, measures of whole brain atrophy were strongly correlated with neuropsychologic... more In recent studies, measures of whole brain atrophy were strongly correlated with neuropsychological testing, explaining more variance than measures of lesion burden in patients with multiple sclerosis. The relationship between regional lobar atrophy and cognitive impairment is yet to be examined. We endeavored to assess the clinical significance of regional lobar atrophy in multiple sclerosis.

Archives of Neurology, 2004

Cognition and magnetic resonance imaging correlations are well established in patients with multi... more Cognition and magnetic resonance imaging correlations are well established in patients with multiple sclerosis (MS), but it is unclear whether lesion burden or atrophy accounts for most of the predictive variance. These indices have been directly compared in only a few studies. No such study included measurement of the third ventricle, which was strongly predictive of neuropsychological competence in the early literature. Furthermore, few studies accounted for the influence of age, premorbid intelligence, or depression. To determine if conventional measures of lesion burden or atrophy predict cognitive dysfunction in MS while accounting for age, premorbid intelligence, and depression. We studied 37 patients with MS and 27 controls matched according to demographic variables. Correlations between neuropsychological tests and the following magnetic resonance imaging indices were considered: T1 hypointense lesion volume, fluid-attenuated inversion recovery hyperintense lesion volume, third ventricle width, bicaudate ratio, and brain parenchymal fraction. Regression models predicting neuropsychological performance controlled for the effects of age, premorbid intelligence, and depression. We included only those tests discriminating patients with MS from controls. In each regression model, third ventricle width was the sole magnetic resonance imaging measure retained. When this variable was removed from consideration, brain parenchymal fraction was retained in all analyses. Brain atrophy accounts for more variance than lesion burden in predicting cognitive impairment in MS, and central atrophy in particular is strongly associated with neuropsychological morbidity. This finding may be explained in part by atrophy of the thalamus, a deep gray matter structure that mediates cognitive function via cortical and subcortical pathways. Enthusiasm for the clinical utility of third ventricle width is tempered by modest intraobserver and interobserver reliability.

BACKGROUND AND PURPOSE: Semiautomated and automated methods are used to measure whole-brain atrop... more BACKGROUND AND PURPOSE: Semiautomated and automated methods are used to measure whole-brain atrophy in multiple sclerosis (MS), but their comparative reliability, sensitivity, and validity are unknown.

Neuroimage, 2005

We used SPM99 to obtain normalized whole brain volumes of gray matter, white matter, and total pa... more We used SPM99 to obtain normalized whole brain volumes of gray matter, white matter, and total parenchyma in patients with multiple sclerosis (MS) (n = 41) and age-/sex-matched normal controls (n = 18). As SPM99's automated gray/white matter volumes were significantly influenced by tissue compartment misclassification due to the effect of MS-related brain lesions, we corrected these automated volumes for misclassification before performing our primary analyses. For MS patients (disease duration = 9.5 T 6.3 years; EDSS score = 3.2 T 1.8; 25FTW = 6.6 T 3.1 s), we also measured lesion load total T1 hypointense [T1LV] and FLAIR hyperintense lesion volume [FLLV]), central brain atrophy (third ventricular width [TVW] and bicaudate ratio [BCR]), and clinical status (Expanded Disability Status Scale [EDSS] and 25-ft timed walk [25FTW]

Neurology, 2007

Diseases Chemicals OBJECTIVES: Recent studies have indicated that brain atrophy is more closely a... more Diseases Chemicals OBJECTIVES: Recent studies have indicated that brain atrophy is more closely associated with cognitive impairment in multiple sclerosis (MS) than are conventional MRI lesion measures. Enlargement of the third ventricle shows a particularly strong correlation with cognitive impairment, suggesting clinical relevance of damage to surrounding structures, such as the thalamus. Previous imaging and pathology studies have demonstrated thalamic involvement in MS. In this study, we tested the hypothesis that thalamic volume is lower in MS than in normal subjects, and that thalamic atrophy in MS correlates with cognitive function.

Journal of The Neurological Sciences, 2003

Brain atrophy is a proposed MRI marker of irreversible pathologic damage in multiple sclerosis (M... more Brain atrophy is a proposed MRI marker of irreversible pathologic damage in multiple sclerosis (MS). The brain parenchymal fraction (BPF) is the ratio of brain parenchymal volume to the total volume within the surface contour. We developed a semiautomated measure of BPF using commercially available edge-finding and thresholding software (30-min analysis time per patient). We measured BPF in 78 patients with MS and 17 healthy controls. BPF was lower in a cohort of patients with MS (n = 50) (0.843 F 0.042, range 0.743 -0.906) agematched to controls (0.877 F 0.020, range 0.835 -0.901) ( p < 0.001). BPF correlated inversely with third ventricular width (r = À 0.785, p < 0.001), and total T1 hypointense lesion volume (r = À 0.347, p = 0.011), but not with total T2 hyperintense lesion volume (r = À 0.213, p = 0.13). BPF correlated negatively with expanded disability status scale (EDSS) score (r = À 0.391, p = 0.0006) and disease duration (r = À 0.281, p = 0.01). Stepwise regression compared the relative abilities of MRI variables to predict clinical data. By regression of age, BPF, third ventricular width, T2 lesions, and T1 lesions, BPF was the best predictor of disability score (R 2 = 0.204, p < 0.001). Third ventricular width was the best predictor of disease duration (R 2 = 0.316, p < 0.001). None of the MRI variables differed between relapsingremitting (RR) (n = 60) and secondary progressive (SP) (n = 18) disease course ( p>0.05). The intrarater, interrater, and scan -rescan BPF variability (COV) was 0.31%, 0.34%, and 0.41% and the accuracy against a phantom was 99.1%. We conclude that whole-brain atrophy in MS can be reliably and readily quantified by a semiautomated approach. Longitudinal studies are warranted to determine if this method provides a sensitive biologic marker of the MS disease process. D

Journal of Neuroimaging, 2003