153 Hemodynamic Imaging in Brain Metastases: ASL vs. Hypercapnic BOLD were used to divide brain into regions of vascular steal versus no vascular steal. In this study, steal was conceptualized as voxels containing negative CVR values (i.e. regions in which BOLD signal intensity decreased with increase in PetCO2; Figure 2.4). The data provided by steps 1-4 were used in the subsequent comparative analyses. First the previously generated masks were used to subdivide the brain into GM, WM, edema and brain metastases regions (Figure 2.A). Next, for steal and nonsteal regions separately, the mean value per brain regions was calculated for each hemodynamic parameter map. Kruskal-Walis H-tests were performed to compare the mean hemodynamic values between tissue types. To reduce the false discovery rate due to multiple testing, alpha’s were corrected according to the BenjaminiHochberg method.34 Additionally, Spearman’s correlation analyses were performed between the mean values of the different parameter maps within each tissue type. For a second comparative analysis, the AAT data was sorted based on ascending values. The sorted AAT’s were then subdivided into 20 bins, each containing 5 percent of the data. Using the boundaries of these ‘5%-bins’, the AAT map was divided into ROIs. Thereby, each ROI contained 5 percent of the AAT data, where the lowest bin value represented the 5 percent lowest AAT values and the highest bin value the 5 percent highest AAT values (Figure 2.B). For each hemodynamic parameter, the mean value for each of these binned ROIs was calculated and used in the subsequent correlation analysis to assess whether the hemodynamic parameters in each AAT bin correlate with other hemodynamic parameters. In order to compare CBF values to the CVR metrics as well, this process was repeated using the CBF maps to bin the data. As this binning resulted in 20 mean values per individual (i.e. for each binned ROI), a repeated-measures correlation was chosen to account for the within-individual variance between these values. The ‘rmcorr’ package implemented in RStudio (Version 2021.9.1.372) was used to perform this repeated-measures correlation.35 This analysis estimates the common regression slope for repeated measures. Lastly, a Pearson’s correlation coefficient was calculated for the voxelwise association between the ASL and CVR metrics for each individual. This correlation was performed separately for non-vascular steal and vascular steal regions. Next, we performed a nonparametric Wilcoxon-signed rank-test to assess whether the correlation values significantly differed from zero on the group-level (Supplementary Materials). For all statistical tests a p-value of 0.05 was deemed significant. 6
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