66 Chapter 4 as former smokers, and the last category were current smokers. Body mass index (BMI) was calculated based on the measured participant’s height (cm) and weight (kg). Systolic and diastolic blood pressure were measured with a standard mercury sphygmomanometer, and the mean of two measurements was calculated. Hypertension was defined based on self-report and/or use of antihypertensive medication, and/or measured systolic blood pressure >140 mm Hg and/or diastolic blood pressure >90 mm Hg. Diabetes mellitus was defined based on self-report, use of anti-diabetic medication, or fasting blood glucose level >7.0 mmol/L. Coronary artery disease was defined based on self-report plus the use of nitrates, a history of a bypass operation, and/or evidence of myocardial infarction on electrocardiogram. 4.3.3 MRI acquisition protocol MRI scans were performed on a 1.5 Tesla Signa Twinspeed system (General Electric Medical Systems, Waukesha, Wisconsin). Sequences included in the protocol: a 3D T1-weighted, spoiled-gradient echo sequence (repetition time = 21 ms; time to echo = 8 ms; field of view = 240 mm; slice thickness = 1.5 mm; voxel size = 0.94 × 0.94 × 1.50 mm3) and a fluid attenuated inversion recovery (FLAIR) sequence (repetition time = 8000 ms; time to echo = 100 ms; field of view = 220 mm; 3 mm interleaved slices; voxel size = 0.86 × 0.86 × 3.00 mm3). 4.3.4 WMH markers An in-house developed pipeline was used to calculate WMH shape markers, as described previously.6 In brief, WMH were segmented automatically from FLAIR MRI scans using the LST toolbox9 in SPM12. Lateral ventricles were segmented from T1 scans and these ventricle masks were inflated with 3 and 10 mm. The inflated ventricle masks were used to classify WMHs into periventricular, confluent, or deep WMH (figure 4.1, supplementary figure S.4.9.2). Convexity, solidity, concavity index, and fractal dimensions were determined based on the segmentations of the periventricular/confluent WMHs.6 A lower convexity and solidity, and higher concavity index and fractal dimension indicate more irregular shapes. For deep WMH fractal dimensions and eccentricity were calculated.6 Higher eccentricity indicates a rounder shape, and a higher fractal dimension indicates a more irregular shape of deep WMH. The formulas of the WMH shape markers are shown in figure 4.1. Moreover, total WMH volume, as well as the volumes of periventricular/confluent and deep WMH were calculated.
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