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A quantitative postmortem MRI design sensitive to white matter hyperintensity differences and their relationship with underlying pathology.

ABSTRACT: White matter hyperintensities (WMHs) associate with both cognitive slowing and motor dysfunction in the neurologically normal elderly. A full understanding of the pathology underlying this clinicoradiologic finding is currently lacking in autopsy-confirmed normal brains. To determine the histopathologic basis of WMH seen on magnetic resonance imaging, we studied the relationship between postmortem fluid-attenuated inversion recovery (FLAIR) intensity and neuropathologic markers of WM lesions (WMLs) that correspond to WMH in cognitively normal aging brains. Samples of periventricular (n = 24), subcortical (n = 26), and normal-appearing WM (NAWM, n = 31) from 4clinically and pathologically confirmed normal cases were examined. The FLAIR intensity, vacuolation, and myelin basic protein immunoreactivity loss were significantly higher in periventricular WML versus subcortical WML; both were higher than in NAWM. The subcortical WML and NAWM had significantly less axonal loss, astrocytic burden, microglial density, and oligodendrocyte loss than those of the periventricular WML. Thus, vacuolation, myelin density, and small vessel density contribute to the rarefaction of WM, whereas axonal density, oligodendrocyte density, astroglial burden, and microglial density did not. These data suggest that the age-related loss of myelin basic protein and the decrease in small vessel density may contribute to vacuolation of WM. Vacuolation enables interstitial fluid to accumulate, which contributes to the prolonged T2 relaxation and elevated FLAIR intensity in the WM.

SUBMITTER: Murray ME

PROVIDER: S-EPMC3511604 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

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A quantitative postmortem MRI design sensitive to white matter hyperintensity differences and their relationship with underlying pathology.

Murray Melissa E ME Vemuri Prashanthi P Preboske Greg M GM Murphy Matthew C MC Schweitzer Katherine J KJ Parisi Joseph E JE Jack Clifford R CR Dickson Dennis W DW

Journal of neuropathology and experimental neurology 20121201 12

White matter hyperintensities (WMHs) associate with both cognitive slowing and motor dysfunction in the neurologically normal elderly. A full understanding of the pathology underlying this clinicoradiologic finding is currently lacking in autopsy-confirmed normal brains. To determine the histopathologic basis of WMH seen on magnetic resonance imaging, we studied the relationship between postmortem fluid-attenuated inversion recovery (FLAIR) intensity and neuropathologic markers of WM lesions (WM ...[more]

PMID: 23147507

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Project description:IntroductionSubtle inhomogeneities in the scanner's magnetic fields (B0 and B1) alter the intensity levels of the structural magnetic resonance imaging (MRI) affecting the volumetric assessment of WMH changes. Here, we investigate the influence that (1) correcting the images for the B1 inhomogeneities (i.e. bias field correction (BFC)) and (2) selection of the WMH change assessment method can have on longitudinal analyses of WMH progression and discuss possible solutions.MethodsWe used brain structural MRI from 46 mild stroke patients scanned at stroke onset and 3 years later. We tested three BFC approaches: FSL-FAST, N4 and exponentially entropy-driven homomorphic unsharp masking (E(2)D-HUM) and analysed their effect on the measured WMH change. Separately, we tested two methods to assess WMH changes: measuring WMH volumes independently at both time points semi-automatically (MCMxxxVI) and subtracting intensity-normalised FLAIR images at both time points following image gamma correction. We then combined the BFC with the computational method that performed best across the whole sample to assess WMH changes.ResultsAnalysis of the difference in the variance-to-mean intensity ratio in normal tissue between BFC and uncorrected images and visual inspection showed that all BFC methods altered the WMH appearance and distribution, but FSL-FAST in general performed more consistently across the sample and MRI modalities. The WMH volume change over 3 years obtained with MCMxxxVI with vs. without FSL-FAST BFC did not significantly differ (medians(IQR)(with BFC) = 3.2(6.3) vs. 2.9(7.4)ml (without BFC), p = 0.5), but both differed significantly from the WMH volume change obtained from subtracting post-processed FLAIR images (without BFC)(7.6(8.2)ml, p < 0.001). This latter method considerably inflated the WMH volume change as subtle WMH at baseline that became more intense at follow-up were counted as increase in the volumetric change.ConclusionsMeasurement of WMH volume change remains challenging. Although the overall volumetric change was not significantly affected by the application of BFC, these methods distorted the image intensity distribution affecting subtle WMH. Subtracting the FLAIR images at both time points following gamma correction seems a promising technique but is adversely affected by subtle WMH. It is important to take into account not only the changes in volume but also in the signal intensity.

Dataset Information

A quantitative postmortem MRI design sensitive to white matter hyperintensity differences and their relationship with underlying pathology.

Publications

A quantitative postmortem MRI design sensitive to white matter hyperintensity differences and their relationship with underlying pathology.

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