Do brain T2/FLAIR white matter hyperintensities correspond to myelin loss in normal aging? A radiologic-neuropathologic correlation study

Abstract

BackgroundWhite matter hyperintensities (WMH) lesions on T2/FLAIR brain MRI are frequently seen in healthy elderly people. Whether these radiological lesions correspond to irreversible histological changes is still a matter of debate. We report the radiologic-histopathologic concordance between T2/FLAIR WMHs and neuropathologically confirmed demyelination in the periventricular, perivascular and deep white matter (WM) areas.ResultsInter-rater reliability was substantial-almost perfect between neuropathologists (kappa 0.71 - 0.79) and fair-moderate between radiologists (kappa 0.34 - 0.42). Discriminating low versus high lesion scores, radiologic compared to neuropathologic evaluation had sensitivity / specificity of 0.83 / 0.47 for periventricular and 0.44 / 0.88 for deep white matter lesions. T2/FLAIR WMHs overestimate neuropathologically confirmed demyelination in the periventricular (p < 0.001) areas but underestimates it in the deep WM (0 < 0.05). In a subset of 14 cases with prominent perivascular WMH, no corresponding demyelination was found in 12 cases.ConclusionsMRI T2/FLAIR overestimates periventricular and perivascular lesions compared to histopathologically confirmed demyelination. The relatively high concentration of interstitial water in the periventricular / perivascular regions due to increasing blood–brain-barrier permeability and plasma leakage in brain aging may evoke T2/FLAIR WMH despite relatively mild demyelination.

Correlating Cognitive Decline with White Matter Lesion and Brain Atrophy Magnetic Resonance Imaging Measurements in Alzheimer’s Disease

“…White matter lesions are associated with executive impairment and reduced information processing, and the most common histopathologic correlate in the elderly appears to be infarction with demyelination [24]. Our study showed that baseline white matter lesion load was strikingly increased in the frontal lobes of patients with AD compared to the MCI and CN groups.…”

“…A variety of mechanisms have been described for the development of WMHs including wallerian degeneration secondary to neurodegenerative changes, vascular injury, and ischemia. Pathologically, the observed tissue damage range from mild perturbation of the matrix, all the way to demyelination and axonal loss in severe cases [24]. The most common etiology found at the tissue level appears to be infarction [25].…”

Vascular Dysfunction in Leukoaraiosis

“…40 Quantitative T2 values were higher in leukoaraiosis, which is to be expected because this indicates increased water content due to loss in tissue structure. 41 CBF was reduced; this change indicated a reduction in blood supply, 22 CBV was also reduced; this change suggested decreased density of the local microvasculature. 42 Finally, timedependent MR imaging metrics such as time-to-maximum and TTP were prolonged in leukoaraiosis; this finding demonstrates a delay in the blood supply to areas of leukoaraiosis.…”

Pathological Correlates of White Matter Hyperintensities on Magnetic Resonance Imaging

“…Disrupted ependymal lining of the ventricles could result from cerebral atrophy and ventricular dilatation which may be the consequence of neurodegenerative processes rather than small vessel disease [51]. Other proposed mechanisms include blood-brain barrier dysfunction [34, 40, 44, 46, 72, 73], inflammatory processes involving microglial cells [20, 21, 74], altered cerebral blood flow autoregulation, axonal depletion from Wallerian degeneration [75], and intraparenchymal venular disease [76, 77]. All of these potential causes warrant further investigation [14, 49].…”