ICH, PHE and IVH volumes were determined by two independent raters (S.U. and D.W.G.) using Analyze 11.0 (AnalyzeDirect, Overland Park, KS, USA) (Figures I–VII Online Supplement). The raters were blinded to clinical data and to each other’s measurements. Measurements were performed by outlining the hemorrhage and rim of PHE on axial slices in the software’s Region of Interest (ROI) module with a semi-automated edge detection tool. This tool calculates boundaries for each lesion based on Hounsfield Units in the area selected by the rater, the most optimal of which is selected by the rater. Next, boundaries were adjusted after inspection of the three orthogonal planes in the software’s Volume Edit module, which allows for better assessment of the location and distribution of each lesion beyond the two-dimensional axial plane. The three-dimensional view is especially helpful to visualize the extent of PHE throughout the brain in large hemorrhages. To delineate PHE the additional principles that it should be (a) more hypodense than the corresponding region in the contralateral hemisphere and (b) most hypodense immediately surrounding the hemorrhage were employed. The rationale for the latter is that following ICH, transendothelial water flux from the intravascular to the interstitial compartments, both before and after frank blood-brain barrier disruption, occurs initially immediately adjacent to the hematoma.13 (link) Therefore, if a less hypodense area adjacent to the hematoma is followed by a more hypodense area further outward, the latter could represent another entity like an old infarct. Measurements were repeated by one rater (S.U.) after a four-month interval to determine intrarater reliability. All measurements were reviewed by two stroke neurologists (L.A.B. and K.N.S.). Figures 1 depicts a representative example of a subject’s ICH and PHE measurements. PHE volumes were determined on MRI (fluid-attenuated inversion recovery sequence, FLAIR) using the semi-automated edge detection tool to delineate the peri-hematomal hyperintensity.