White Matter Lesion Assessment in Patients with Cognitive Impairment and Healthy Controls: Reliability Comparisons between Visual Rating, a Manual, and an Automatic Volumetrical MRI Method—The Gothenburg MCI Study
Age-related white matter lesions (WML) are a risk factor for stroke, cognitive decline, and dementia. Different requirements are imposed on methods for the assessment of WML in clinical settings and for research purposes, but reliability analysis is of major importance. In this study, WML assessment with three different methods was evaluated. In the Gothenburg mild cognitive impairment study, MRI scans from 152 participants were used to assess WML with the Fazekas visual rating scale on T2 images, a manual volumetric method on FLAIR images, and FreeSurfer volumetry on T1 images. Reliability was acceptable for all three methods. For low WML volumes (2/3 of the patients), reliability was overall lower and nonsignificant for the manual volumetric method. Unreliability in the assessment of patients with low WML with manual volumetry may mainly be due to intensity variation in the FLAIR sequence used; hence, intensity standardization and normalization methods must be used for more accurate assessments. The FreeSurfer segmentations resulted in smaller WML volumes than the volumes acquired with the manual method and showed deviations from visible hypointensities in the T1 images, which quite likely reduces validity. 1. Introduction Age-related white matter lesions (WML) mainly affect information processing speed and executive function [1] and entail an increased risk for cognitive decline and disability [2]. In a meta-analytic study, high hazard ratios were also reported for incident stroke (3.3) and dementia (1.9) [3], but results from studies on WML association to dementia subtypes are inconclusive [4–6]. The prevalence of WML increases with age, and in a population study, 51% of randomly selected healthy subjects aged 44–48 had WML [7]. For the age range 60–64, all had WML, and 49% of these had at least one large (>12？mm) WML region [8]. In magnetic resonance (MR) imaging, white matter hypointensities in T1 weighted images, and white matter hyperintensities in T2 weighted and FLAIR images are regarded as visualizations of WML. The conditions for demarcation of WML are enhanced in FLAIR images due to suppression of the signal from free fluid. In contrast to T2 and T1 weighted images, this suppression causes fluid filled cavities in FLAIR images to be hypointensive and excluded from WML by the intensity definition. However, the intensity suppression in the FLAIR sequence entails incident imaging artifacts in the border region between WML and free fluid, for example, in the periventricular region [9]. WML visible in MR imaging reflect demyelinization, axonal
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