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

Background: White 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. Results: Inter-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. Conclusions: MRI 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.