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

Abstract

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.

Figure 1

Representative examples of the concordance between brain MRI WMHs and demyelination. (A) Good correlation between radiology and pathology for both periventricular (arrowhead) and deep WM (arrow) lesions; (B) radiological assessment over-estimating periventricular lesions; (C) under-estimating deep WM lesions; (D) over-estimating periventricular lesions and under-estimating deep WM lesions. Radiologic convention, right hemisphere on left hand side. Coronal fluid attenuated inversion recovery (FLAIR) image and corresponding histophatologic slice in Luxol-van Gieson staining with normal WM in green and regions of demyelination in faint green-yellow.

Figure 2

Prominent perivascular spaces evident as radial linear hyperintesities on T2 with additional perivascular confluent WMH in bilateral temporo-occipital WM (A axial T2, B coronal FLAIR). The corresponding histopathology confirms the presence of prominent perivascular spaces, yet there is no significant demyelination around the perivascular spaces, which would correspond to the confluent hyperintense T2/FLAIR signal alteration. Scale bar = 800 micrometers.