Lesion probability maps of white matter hyperintensities in elderly individuals: results of the Austrian stroke prevention study.
ABSTRACT White matter hyperintensities (WMH) are common on brain MRI of the elderly. Their size ranges from punctate to early confluent to confluent lesions. While this increase in extension is frequently seen as evidence for a continuum of changes, histological data and clinical follow-up suggest differences in underlying pathology and their progression.
We tested this hypothesis by exploring the distributions of punctuate and confluent lesions using lesion probability maps (LPM) generated from MRI scans of 189 participants (mean age 60.8+/-6.2 years) in the Austrian Stroke Prevention Study. We dichotomised WMH according to the classification by Fazekas et al. [punctate (n=143) vs. early confluent and confluent (n=33)] to run voxel-based t-tests using permutation-based nonparametric inference. To test alternative hypotheses, we created similar LPM for age and arterial hypertension.
We observed significant differences in the spatial distribution of lesions for the two WMH groups (p<0.01). Punctate lesions were more diffusely distributed throughout the cerebral white matter (peak probability approximately 5%) relative to confluent lesions (peak probability 45%). Confluent lesions had greatest likelihood of being found in perfusion "watershed" regions. These differences in distribution could not be explained by differences in age or hypertension only, as both greater age and the diagnosis of hypertension were associated with WMH abutting the occipital horns.
Punctate and early confluent to confluent WMH show distinguishable differences in their spatial distribution within a normal elderly population. The pattern of punctate WMH is probably a consequence of mixed etiologies. Preferential localization of the more confluent WMH with arterial watershed areas implies a stronger ischemic component in their development.
Article: An automated procedure for the assessment of white matter hyperintensities by multispectral (T1, T2, PD) MRI and an evaluation of its between-centre reproducibility based on two large community databases.[show abstract] [hide abstract]
ABSTRACT: An automated procedure for the detection, quantification, localization and statistical mapping of white matter hyperintensities (WMH) on T2-weighted magnetic resonance (MR) images is presented and validated based on the results of a between-centre reproducibility study. The first step is the identification of white matter (WM) tissue using a multispectral (T1, T2, PD) segmentation. In a second step, WMH are identified within the WM tissue by segmenting T2 images, isolating two different classes of WMH voxels - low- and high-contrast WMH voxels, respectively. The reliability of the whole procedure was assessed by applying it to the analysis of two large MR imaging databases (n = 650 and n= 710, respectively) of healthy elderly subjects matched for demographic characteristics. Average overall WMH load and spatial distribution were found to be similar in the two samples, (1.81 and 1.79% of the WM volume, respectively). White matter hyperintensity load was found to be significantly associated with both age and high blood pressure, with similar effects in both samples. With specific reference to the 650 subject cohort, we also found that WMH load provided by this automated procedure was significantly associated with visual grading of the severity of WMH, as assessed by a trained neurologist. The results show that this method is sensitive, well correlated with semi-quantitative visual rating and highly reproducible.Neuroradiology 02/2008; 50(1):31-42. · 2.82 Impact Factor
Article: Volume of white matter hyperintensities in healthy adults: contribution of age, vascular risk factors, and inflammation-related genetic variants.[show abstract] [hide abstract]
ABSTRACT: Aging is associated with appearance of white matter hyperintensities (WMH) on MRI scans. Vascular risk and inflammation, which increase with age, may contribute to white matter deterioration and proliferation of WMH. We investigated whether circulating biomarkers and genetic variants associated with elevated vascular risk and inflammation are associated with WMH volume in healthy adults (144 volunteers, 44-77 years of age). We examined association of WMH volume with age, sex, hypertension, circulating levels of total plasma homocysteine (tHcy), cholesterol (low-density lipoprotein), and C-reactive protein (CRP), and four polymorphisms related to vascular risk and inflammation: Apolipoprotein ε (ApoE ε2,3,4), Angiotensin-Converting Enzyme insertion/deletion (ACE I/D), methylenetetrahydrofolate reductase (MTHFR) C677T, C-reactive protein (CRP)-286C>A>T, and interleukin-1β (IL-1β) C-511T. We found that larger WMH volume was associated with advanced age, hypertension, and elevated levels of homocysteine and CRP but not with low-density lipoprotein levels. Homozygotes for IL-1β-511T allele and carriers of CRP-286T allele that are associated with increased inflammatory response had larger WMH than the other allelic combinations. Carriers of the APOE ε2 allele had larger frontal WMH than ε3 homozygotes and ε4 carriers did. Thus, in healthy adults, who are free of neurological and vascular disease, genetic variants that promote inflammation and elevated levels of vascular risk biomarkers can contribute to brain abnormalities. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease.Biochimica et Biophysica Acta 08/2011; 1822(3):361-9. · 4.66 Impact Factor