## 4 Discussion
As the CVR is known to correlate highly with the CPR, it is not surprising that it became the main component of the scoring system. As opposed to [PERSON] et al. and [PERSON] et al., we applied bh-fMRI instead of hypercapnia-triggered fMRI with the use of the inhalation of CO2-enriched gas. This method requires no complex inhalation and monitoring equipment and therefore benefits from better availability [8; 10; 15]. Undoubtedly, one disadvantage is the need for patients' cooperation and the ability to perform breath-hold tasks [8; 10; 15]. Still, this study indicates that bh-fMRI appears to be suitable for the MARS-MMA system. Furthermore, the validation of the PIRAMID scoring system suggests that bh-fMRI shows comparable results to CO2-inhalation-triggered fMRI when used with the PIRAMID score (AUC = 0.738 (ICA territories) and 0.771 (ACA/MCA territories) vs. 0.716) [17]. Another component of the MARS-MMA scoring system is the presence of the Ivy sign on FLAIR/T2-weighted images. The Ivy sign is considered an indicator of slow or retrograde flow in the cortical vessels [28]. After revascularization, the sign can diminish or temporally become more apparent [28]. Likewise, arterial vessel wall contrast enhancement is considered a sign of disease progression [7] and therefore represents a dynamic parameter likely ending in progredient stenosis with CPR/CVR impairment. One major advantage of the MARS-MMA scoring system over the PIRAMID scoring system is that it is entirely MRI-based. The MARS-MMA scoring system requires no invasive DSA examination and is not accompanied by radiation exposure. For this reason, the evaluation of the MARS-MMA score can be repeated as often as desired based on patients' therapy and symptoms. All components of the MARS-MMA score can be acquired in the same MR imaging session. Another advantage of the MARS-MMA scoring system is that it predicts the risk of reduced CPR and indirectly the risk of stroke in the vascular territories of the ACA and the MCA, and not only of the entire ICA territories. In our opinion, this is important as, at our center and other moyamoya centers, not only the MCA territories but also the ACA (and PCA) territories are revascularized if required. Therefore, the evaluation of the risk of stroke for all individual vascular territories is of high clinical relevance. However, the PCA territories were excluded in this analysis as their involvement and need for revascularization is only seen in less than 10% of cases. Since, in this study, we found that the PIRAMID score provided comparable accuracy in the neurological assessment of the ACA/MCA territories and ICA territories, we recommend the more detailed ACA/MCA evaluation for future use. The aim of the MARS-MMA score and especially of the MARS-MMA grading is to simplify clinical diagnostics by pre-selecting patients for future treatment decisions (see Figure 5). MARS-MMA grade 1: At this stage of the disease, there is likely only mild perfusion restriction with a near to normal cerebrovascular reserve capacity and only little or no risk of short-term deterioration. We recommend follow-up with breath-hold fMRI and the re-evaluation of the MARS-MMA score in 12-24 months. MARS-MMA grade 2: The impairment of the cerebrovascular reserve capacity and a decline in the near future are possible. Depending on the clinical presentation, we recommend an additional [15O]water PET scan or a short-term bh-fMRI follow-up in 6 months. If the clinical presentation and the imaging findings are conclusive, revascularization surgery may be indicated. MARS-MMA grade 3: MARS-MMA grade 3 is suggestive of severe CVR impairment with a high risk of subsequent stroke. Revascularization may be indicated. In the case of inconclusive clinical and/or imaging findings, timely [15O]water PET scanning is recommended to assess the need for revascularization. With this approach, we aim to avoid unnecessary MRI and [15O]water PET examinations and enable the best possible treatment for patients.