The topography of white matter hyperintensities on brain MRI in healthy 60- to 64-year-old individuals

Abstract

We report the topography of brain white matter hyperintensities (WMHs) on T2-weighted fluid attenuated inversion recovery (FLAIR) magnetic resonance imaging in 477 healthy subjects aged 60–64 years selected randomly from the community. WMHs were delineated by using a computer algorithm. We found that all subjects had periventricular WMHs and 96.6% subjects also had deep WMHs. The mean volume of WMHs was 4.9 ml, comprising 0.83% of the white matter, of which 1.2 ml was severe in intensity. The deep WMHs were distributed throughout the cerebral hemispheres, with the occipital and frontal white matter bearing the greatest burden. The territory of the lenticulostriate arteries had the greatest WMHs. A white matter region of 4 mm adjacent to the cortex was not affected by hyperintensities. The mean (SD) number of discrete WMHs was 19.6 (7.1) per subject, of which 6.1 (4.4) were severe in intensity. Nearly half (48.6%) of the subjects had at least one large WMH (>12 mm diameter) and one eighth (12.5%) of the subjects had at least one large WMH that appeared to be severe in MRI. The overall load of WMHs was similar in men and women, but the latter had a higher proportion of their white matter so affected. This study provides the first detailed topographic analysis of WMHs in a large representative middle-aged sample, emphasizes their high prevalence in mid-adult life and raises issues about their etiology and significance.

Introduction

Foci of high signal intensity on T2-weighted magnetic resonance imaging (MRI) in the white matter are a common finding in the brains of asymptomatic elderly individuals as well as in disease-specific brains Kertesz et al., 1988, Whitman et al., 2001, with reported prevalence in the healthy elderly varying from 10% up to 100% in different studies (De Leeuw et al., 2000). The etiology of white matter hyperintensities (WMHs), sometimes called leuokoaraiosis, is not specific and may relate to ischemia, demyelinating disorders, hydrocephalus, trauma, inflammatory disease, radiation injury, amyloidosis and other causes (Pantoni and Garcia, 1995). Their pathology is similarly varied, with reports of normal findings to complete infarction Fazekas et al., 1993, Liefer et al., 1990, Scheltens et al., 1995, Schmidt et al., 1999, Smith et al., 2000. The volume and number of WMHs have been found to be associated with brain atrophy, reduced cerebral blood flow and focal neurologic signs (DeCarli et al., 1995). WMHs have been noted to be associated with cognitive impairment, with a suggestion that a certain threshold of their extent must be reached before this becomes clinically apparent (Román, 1987). WMHs have also been linked to neuropsychiatric disorders such as major depression, bipolar disorder and schizophrenia (Sachdev and Brodaty, 1999).

Compared to other imaging modalities, T2-weighted MRI is very sensitive to abnormalities in the white matter. Healthy white matter is heavily myelinated and has a high content of long-chain fatty acids and about 12% less water than gray matter. With degradation of myelin, the tissue, due to a higher water content and degeneration of macromolecular structures, dramatically changes its relaxation rates, which is seen as a higher signal on T2-weighted and fluid attenuated inversion recovery (FLAIR) sequence MRI (Bronge, 2001). These signals range from areas of diffuse but mild increase, to punctuate foci of intense signal to areas of confluent patches; rarely, the entire cerebral white matter is so involved. WMHs have therefore been visually graded by radiologists and researchers based on their intensity, focal or diffuse extent, and distribution. Although defining and grading of WMH regions within an image do not directly relate to the existence, type and severity of the pathology of the tissue, neuropathologic studies have shown strong correlations between them (Fazekas et al., 1993). Some studies pointed out that WMH seen in MRI tended to be underestimated in comparison with corresponding histopathological examination Grafton et al., 1991, Munoz et al., 1993, Scarpelli et al., 1994.

The study of WMHs has thus far been limited in many ways. Most studies have used clinic populations or samples of convenience, and their prevalence in healthy, community-dwelling populations has received less attention (Fazekas and Englund, 2002). Previous reports have largely tended to use visual ratings of WMHs, which not only fail to capture the full diversity of the findings and the continuous nature of the data, but also disregard the topography of the lesions. No topographic maps of WMHs have previously been published. Such maps are likely to instruct us on questions such as hemispheric symmetry and gender differences and provide a basis for the examination of the functional relevance of these lesions. Since the development of WMHs is related to age, an examination of individuals in middle age offers the opportunity to determine the distribution of lesions in their early phase and provides a baseline for the examination of the impact of age, hypertension, diabetes and other risk factors on the severity and distribution of WMHs. We report the results of a comprehensive assessment of WMHs in a large representative sample of healthy middle-aged (60–64 years) individuals recruited from the community, selected randomly from the electoral roll and present for the first time topographic maps of WMHs.