181 Physiological MRI Biomarkers & Cognition after SRS for Brain Metastases subsequent correlation analysis to assess whether the mean change in physiological MRI parameters in each bin-ROI correlated with the mean dose received by the tissue within that bin. As this binning results in 20 mean values per individual (i.e. for each binned ROI), a repeated-measures correlation was chosen to account for the withinindividual variance between these values. The ‘rmcorr’ package47 implemented in RStudio (Version 2021.9.1.372)48 was used to perform this repeated-measures correlation. This analysis estimates the common regression slope for repeated measures. In addition to the two regional dose analyses, voxelwise Spearman’s Rank correlations were calculated between the delivered dose and physiological MRI difference maps for each patient separately. We performed Wilcoxon-signed rank tests to assess whether the correlation values significantly differed from zero on the group level for each physiological MRI parameter. For all statistical tests, a p-value < 0.05 was considered statistically significant, corrected for multiple comparisons when necessary. RESULTS Participants In total 17 patients completed both baseline and follow-up MRI and NCA within the given time period. Of these, 9 patients (4 females) were included for the current analysis (Table 1), most patients were excluded from the analysis due to artefacts in the MRI data (Supplementary Figure 2). Three of the nine patients did not want to perform the breathing challenges during BOLD imaging at follow-up, leading to missing CVR data for those patients. All nine patients received SRS on a Linear Accelerator (Elekta) with conebeam CT imaging guidance, most commonly 21 Gy delivered in 1 fraction. Median age of patients was 66 years and most patients had a primary lung tumor (all non-small cell lung cancer). The median number of brain metastases was 7 (IQR 2-10) and the total volume was median 4 cc. Before SRS edema volume excluding BMs volumes was median 17 cc and three months after SRS 6 cc, with extensive inter-individual variability. Most patients (6/9) had received systemic therapy during the follow-up period. Response to SRS was evaluated approximately three months after treatment completion and the majority (4/9) showed decreased brain metastases volume on follow-up scans, while 2/9 showed growth of new brain metastases. One patient had a mixed response, indicating some brain metastases had grown and others had shrunk. 7
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