Quantifying Brain Microbleeds and Hemorrhages

Ratings of microbleeds and intracranial hemorrhages and estimation of R2* were performed for specific brain regions. Microbleeds were classified as well-defined, circular hyperintensities with diameters ranging from 2–10 mm on R2* map^{28 (link)}. Only definite microbleeds in seven anatomic regions (i.e., frontal, parietal, temporal, occipital, insula, deep white matter, and cerebellar regions) were counted and converted to the scale of 0–4, using cut-points (< 1, 1–4, 5–9, 10–19, ≥ 20)^{28 (link),49} . Microbleeds rating of the cerebral cortex was then computed as the average rating of the frontal, parietal, temporal, occipital, and insular regions. We also counted total brain regions showing intracranial hemorrhages^{50 (link),51 (link)} according to the following anatomical division: frontal, parietal, temporal, occipital, and cerebellar regions. Rating of hyperintensities on T2-weighted scans followed Fazekas method^{52 (link)} in the following regions: anterior, posterior, and inferior periventricular white matter; frontal, parietal, temporal, and occipital deep white matter; MCP/cerebellar white matter; globus pallidus; brainstem; and the genu and splenium of the corpus callosum. Periventricular WMHs were rated as 0 (absence), 1 (“caps” or pencil-thin lining), 2 (smooth “halo”), and 3 (irregular hyperintensities extending into the deep white matter) whereas hyperintensities in the remaining brain regions were rated as 0 (absence), 1 (punctate foci), 2 (beginning confluence of foci), and 3 (large confluent areas). For the five whole brain specimens, number of microbleeds and anatomic volume were estimated in both hemispheres and then divided by two. For hyperintensities, the higher ratings among the two hemispheres were utilized. Missing/incomplete brain regions were excluded from the analysis (Table 1). All ratings were performed after intra-rater reliability assessed using Cohen’s kappa reached 0.80 or above (almost perfect).