White matter lesions (WML) on magnetic resonance imaging (MRI) brain scans are associated with ageing. They are unrelated to specific disorders, and their impact on cognitive and other brain functions is poorly characterized. Pathological studies often omit systematic survey of WML because of the need to study multiple full coronal tissue blocks, and uncertainty over the significance of lesions identified in periventricular and deep subcortical regions. Post-mortem MRI provides a means of mapping WML but the sensitivity and specificity of the method are unresolved. In this study post-mortem MRI of WML in fixed brain slices was compared with pathology in 33 brains donated to the Medical Research Council Cognitive Function and Ageing Study (MRC CFAS). This study shows that MRI detection of WML was less sensitive than pathology: periventricaular lesions (PVL) sensitivity = 95% (87-99%), specificity = 71% (44-90%); deep subcortical lesions (DSCL) sensitivity = 86% (79-93%), specificity = 80% (72-88%). False negative MRI was associated with milder pathology, but lesions detected by myelin attenuation alone showed both microglial and endothelial activation. Therefore post-mortem MRI of formalin-fixed brain slices is a reliable method to obtain systematic data on the severity and distribution of cerebral white matter disease, and appears to detect those WML most likely to have clinical impact.

Background and Purpose-The goal of this study was to determine the efficacy of CT angiography for the characterization of plaque morphology and composition in carotid atherosclerotic disease. Methods-Fifty-five patients undergoing carotid endarterectomy were imaged preoperatively with single-slice spiral CT angiography. One hundred sixty-five endarterectomy sections were examined histologically at selected levels through the distal common and proximal internal carotid arteries. Plaque density was measured (in Hounsfield units) on axial CT sections, and the presence or absence of ulceration was noted. These observations were compared with the histological findings at corresponding levels. Data were analyzed with 2-sample t tests and 1-way analysis of variance (ANOVA). Results-ANOVA testing showed a statistically significant decrease in CT attenuation values with increasing plaque lipid but with a very high standard deviation of values. No other histological factor showed a statistically significant link with CT attenuation. Plaque ulceration was detected by CT with a sensitivity of 60% and a specificity of 74%. Conclusions-Analysis

These findings are consistent with white matter ischemia in the DLPFC and lend support to the 'vascular depression' hypothesis. They implicate the DLPFC as an important site in the pathogenesis of late-life depression and have major implications for the understanding and management of late-life depression and raise the possibility of novel treatments being introduced in the future.

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Overall, we found a decrease in pyramidal neuronal size in the dorsolateral prefrontal cortex in late-life depression.