Comparison of the pathology of cerebral white matter with post‐mortem magnetic resonance imaging (MRI) in the elderly brain

Abstract

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.

Classification of White Matter Lesions on Magnetic Resonance Imaging in Elderly Persons

“…FLAIR sensitivity and specificity reported for PVWMLs was 95% (87-99%) and 71% (44-90%), and those for DWMLs were 86% (79-93%) and 80% (72-88%). (82).…”

Age-related changes in human and non-human primate white matter: from myelination disturbances to cognitive decline

“…Chronic hypoperfusion due to damaged small blood vessels has been implicated in age-related WM damage (reviewed by Iadecola 2010). A variety of conditions that reduce cerebral blood flow, including reduced angiogenesis, tortuous arterioles, and hypoxia-induced loss of capillaries, may each result in WM damage in the elderly (Fernando et al 2004;Brown and Thore 2011). The finding that myelin-and axon-associated free radical injury, as assessed by measurements of distinct isoprostanes, inversely correlated with FA in vascular brain injury independent of AD (Back et al 2011) support a model whereby vascular changes cause age-related WM damage through oxidative stress.…”

Heterogeneity in age-related white matter changes

“…Early studies claimed that postmortem MRI reliably detects white matter lesions with some problems occurring with small punctate foci [20]. Fernando et al [23] compared postmortem MRI of white matter lesions in fixed brain slices with pathology in 33 brains and described that MRI detection of lesions was less sensitive than pathology. A sensitivity of 95% and a specificity of 71% were reported for periventricular abnormalities, for deep/subcortical white matter changes the sensitivity was 86% and the specificity was 80%.…”