Jasmin Annica Kuhn-Keller

116 Chapter 6 6.3.4 Brain MRI markers The brain MRI markers included to determine the brain MRI phenotypes were brain tissue volumes for the estimation of brain atrophy, WMH volumes, WMH shape markers, brain infarcts, microbleeds, and enlarged perivascular spaces. Gray matter, white matter, CSF, and WMH were segmented automatically with a modified algorithm based on the Montreal Neurological Institute pipeline.12 Intracranial volume was calculated by adding gray matter, white matter, CSF, and WMH volumes.13 Brain parenchymal fraction, white matter fraction, gray matter fraction, and lateral ventricle fraction were calculated by expressing the volumes as a fraction of intracranial volume. Volumes of periventricular/confluent, deep, and total WMH were determined automatically using an in-house developed pipeline.14 Moreover, volumes of deep and periventricular WMH per lobe were calculated using a mask to delineate the lobes. WMH shape markers (fractal dimension, solidity, convexity, concavity index, and eccentricity15) were calculated, as previously described.14 A description of the shape markers, as well as their corresponding formulas, can be found in supplementary table S.6.8.1. and supplementary figure S.6.8.1. links.lww.com/WNL/D459). Brain infarcts (subcortical, cerebellar, and cortical infarcts), microbleeds, and enlarged perivascular spaces were visually scored.9 Microbleeds were first scored by neuroradiologists and then by trained radiographers.11 Infarcts were defined as parenchymal defects with a signal intensity that is isointense to that of CSF on all MRI sequences (i.e., FLAIR, T2-weighted, proton density-weighted).9 Cortical infarcts were defined as infarcts involving or limited to the cortical gray matter and surrounded by a high signal intensity area on FLAIR images. Subcortical infarcts were categorized as such when they do not extend into the cortex and are surrounded by a high signal intensity area on FLAIR images of ≥4 mm in diameter. Parenchymal defects in the subcortical area without a rim or area of high signal intensity on FLAIR images and without evidence of hemosiderin on the T2*-weighted scan were scored as enlarged perivascular spaces. Enlarged perivascular spaces were excluded from the definition of subcortical infarcts. Enlarged perivascular spaces were documented separately in the whole brain and in the basal ganglia. Cerebellar infarcts were scored without any size criteria. Infarcts covering 2 of the mentioned areas were attributed to the location in which the largest measured diameter was located (in millimeters).9

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