180 Chapter 7 Statistical analysis First, we compared the differences in physiological MRI parameters between various tissue types before SRS. For each physiological MRI map, we calculated the average value per tissue type (GM, WM, edema, and brain metastases) prior to SRS for each patient separately. We used Wilcoxon signed-rank tests to compare the average values across the different tissue types for each physiological MRI map. Secondly, we investigated whether there was a relationship between the extent of edema and the physiological MRI parameters within healthy-appearing brain tissue before SRS. Therefore, we computed the average value within the healthy-appearing brain tissue for each patient and then used Spearman’s rank correlations to assess the correlation between this value and the volume of edema (expressed as a percentage of voxels contained within the (extracted) whole brain mask). Post-radiotherapy changes in the physiological MRI parameters were assessed separately for edematous tissue regions and healthy appearing tissue. Regarding the edematous regions, we divided them into three distinct categories based on their temporal occurrence: 1) regions with edema at either T0 or T1 (i.e. all edema), 2) regions with edema exclusively at T1 (i.e. new edema), and 3) regions with edema exclusively at T0 (i.e. old edema; Figure 1). To evaluate the differences between pre- and post-radiotherapy values for each type of edema and each physiological MRI map, we used Wilcoxon signed-rank tests. For healthy-appearing brain tissue, we calculated the mean values of each physiological parameter separately for pre- and post-radiotherapy MRI scans, for each patient. Subsequently, we used Wilcoxon signed-rank tests to determine whether any changes occurred in the healthyappearing brain tissue after SRS, by comparing the mean pre-radiotherapy values to the mean post-radiotherapy values. Dose-related changes in healthy-appearing brain tissue were assessed using three different methods. First, we calculated the mean value for each physiological parameter map for each dose ROI (i.e. low, medium, high). Next, Wilcoxon signedrank tests were performed to compare each of the ROI’s to assess whether there was a significant difference between regions receiving either low, medium or high dose. For the second method, the radiotherapy dose map was sorted based on ascending values. The sorted dose values were then subdivided into 20 bins, each containing 5 percent of the data. Using the boundaries of these ‘5%-bins’, the dose map was divided into ROIs. Each ROI contained 5 percent of the dose data, where the lowest bin value represented the 5 percent lowest dose values and the highest bin value the 5 percent highest dose values. For each physiological MRI difference map, the mean value for each of these binned ROIs was calculated and used in the
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