Neuroimaging Markers of Cerebrovascular Disease

All MRIs were assessed blinded to clinical information by one experienced neuroradiologist for the presence, location, and size of the recent symptomatic infarct and any other vascular lesions. A recent infarct was defined as a hyperintense area on DWI with corresponding reduced signal on the apparent diffusion coefficient image, with or without increased signal on FLAIR or T2-weighted imaging, that corresponded with a typical vascular territory.¹⁸ Recent small subcortical (lacunar) infarcts were defined as rounded or ovoid lesions with signal characteristics as above, >3- but <20-mm diameter, in the basal ganglia, internal capsule, centrum semiovale, or brainstem and carefully distinguished from WMH.^{1 (link)} Cortical infarcts were defined as infarcts involving cortical ± adjacent subcortical tissue, or large (>2-cm) striatocapsular/subcortical lesions.^{14 (link)} Lacunes were defined as rounded or ovoid lesions, >3- and <20-mm diameter, in the basal ganglia, internal capsule, centrum semiovale, or brainstem, of CSF signal intensity on T2 and FLAIR, generally with a hyperintense rim on FLAIR and no increased signal on DWI.^{14 (link)} Microbleeds were defined as small (<5 mm), homogeneous, round foci of low signal intensity on gradient echo images in cerebellum, brainstem, basal ganglia, white matter, or cortico-subcortical junction, differentiated from vessel flow voids and mineral depositions in the globi pallidi.^{14 (link)} Deep and periventricular WMH were both coded according to the Fazekas scale from 0 to 3.^{19 (link)} We defined PVS as small (<3 mm) punctate (if perpendicular) and linear (if longitudinal to the plane of scan) hyperintensities on T2 images in the basal ganglia or centrum semiovale, and they were rated on a previously described, validated semiquantitative scale from 0 to 4.^{7 (link)} Cerebral atrophy was classified for both deep (enlargement of the ventricles) and superficial (enlargement of the sulci) components on a 4-point scale (absent, mild, moderate, severe) in study 1, and on a modified 6-point version of the same scale in study 2.^{20 (link)} The atrophy grade is determined by comparison with templates indicating normal to atrophied brains obtained in research into normal subjects on our scanner.^{20 (link)} To merge the data from both studies, we condensed study 2's version to 4 categories (1 absent, 2–3 mild, 4 moderate, 5–6 severe). The intraclass correlation coefficient for WMH intraobserver rating (100 scans) was 0.96. The intrarater κ for PVS (50 scans) was 0.80 to 0.90 (unpublished data), for lacunes was 0.85 (unpublished data), and for microbleeds was 0.68 to 0.78.^{21 (link)}