## 4 Discussion  
In this study, we confirmed that the PIRAMID scoring system is helpful in predicting current or past neurological symptomatology. We evaluated not only the ICA territories, as proposed by [PERSON] et al., but also the ACA and MCA territories separately regarding past or current neurological symptoms and thereby obtained comparable results (AUC PIRAMID score 0.749 vs. 0.784, AUC PIRAMID grade 0.724 vs. 0.745). The AUC in our study was lower than in the study of [PERSON] et al. (PIRAMID score 0.749 vs. 0.860, PIRAMID grade 0.724 vs. 0.845). Additionally, we intended to evaluated the PIRAMID scoring system with regard to the prediction of a severe CPR impairment on [15O]water PET. Certainly, patients' past and current neurological symptomatology should be considered before the indication of neurosurgical revascularization. The aim of surgical intervention, however, is to prevent these ischemic events (ideally, in still asymptomatic patients), so the previous or current symptoms are not the best target values for the assessment of the risk of stroke. Additionally, silent strokes can be missed and will elude this evaluation. We therefore considered a CPR impairment on [15O]water PET to be the most important outcome, as it is already validated as a surrogate parameter for the risk of stroke [14]. Our second aim was to propose a new, entirely MRI-based classification system called MARS-MMA, which was optimized based on the [15O]water PET CPR impairment. For statistical reasons, we calculated an adapted PIRAMID score (i.e., we optimized the weights of the predefined components of the PIRAMID score on our data) to avoid an unequal comparison between the MARS-MMA score, which was fitted to the current data, and the PIRAMID score. Both scoring systems revealed a strong ability to predict a severe CPR impairment, while the MARS-MMA scoring system predicted a CPR impairment slightly better than the PRIAMID scoring system (AUC 0.859 vs. 0.827), even after considering the inclusion of additional information (AIC = 140 vs. 146) in the model. We determined three grades with low (MARS-MMA grade 1), intermediate (MARS-MMA grade 2), and high (MARS-MMA grade 3) risks of stroke. The analysis of the MARS-MMA grading revealed a strong ability to predict a severe CPR impairment (AUC 0.860), with high negative predictive value for MARS-MMA grade 1 (97.7%) and positive predictive value for MARS-MMA grade 3 (78.4%). A dedicated analysis of the territories  
Figure 4: Bar graph showing MARS-MMA grade versus cerebral perfusion reserve (CPR) impairment on [15O]water PET. The negative predictive value impairment of MARS-MMA grade 1 was 97.7% and the positive predictive value of MARS-MMA grade 3 was 78.4%. with MARS-MMA grade 3 despite the \"absence of a severely impaired\" CPR indicated that, in 9 of 11 of the territories, surgical revascularization was indicated. This supports the usefulness of the MARS-MMA scoring system, which is intended to predict the risk of stroke and the indication for surgical revascularization. It should be considered that the four-point CPR rating and its subsequent binarization in this study were arbitrary and used for simplification, and this is not the gold standard for clinical decision-making. The results suggest that, for territories with MARS-MMA grade 1 and MARS-MMA grade 3, the reliable selection of patients with a very low and very high risk of stroke is possible with MR imaging alone. In territories with MARS-MMA grade 2 and an intermediate risk of stroke, we would recommend a [15O]water PET examination or early MRI examinations to reevaluate the MARS-MMA score and grade. The MARS-MMA scoring system consists of the parameters of reduced CVR obtained from bh-fMRI, arterial vessel wall contrast enhancement and the presence of the Ivy sign on FLAIR images. Interestingly, the regression analysis showed no improvement in the prediction of CPR impairment with the additional evaluation of angiographic findings.