## 1 Introduction  
Moyamoya angiopathy (MMA) is a progressive steno-occlusive cerebrovascular disease that predominantly affects the terminal parts of the internal carotid artery (ICA), as well as the proximal branches of the middle cerebral artery (MCA) and the anterior cerebral artery (ACA) [1, 2, 3]. Patients with MMA typically present with transient ischemic attacks (TIA), ischemic or hemorrhagic strokes and headache [2, 3, 4, 5].  
The diagnosis of MMA is based on conventional angiographic imaging [3], where reactively formed collateral vessels surrounding the stenoses appear as a \"puff of smoke\"(Japanese: \"moyamoya\"), which gave the disease its name [2; 6]. Further diagnostic evaluation usually includes different sequences of structural MRI, where ischemic or hemorrhagic lesions can be detected, and MRI-based angiography [6]. The latest studies also propose MRI-based high-resolution arterial vessel wall imaging to identify patients with disease progression [6; 7]. The indication for surgical revascularization to prevent strokes is mainly based on the evaluation of the cerebral perfusion reserve capacity (CPR) [8; 9; 10; 11; 12], which is intended to provide information about the risk of ischemic stroke [13]. The nuclear medicine method [15]Water PET with acetazolamide (ACZ) challenge is the gold standard for the estimation of the CPR [14]. Hypercapnia-triggered BOLD MRI has been used increasingly to evaluate the cerebrovascular reactivity (CVR), which is considered as a surrogate marker of the CPR [8; 10; 14; 15; 16].  
Recently, [PERSON] et al. outlined a multimodal scoring system to classify the severity of MMA, titled _Prior infarcts_, _Reactivity and Angiography in Moyamoya Disease_ (PIRAMD), and proposed it for clinical decision-making and for the evaluation of an intervention response [17]. [PERSON] et al. validated the scoring system in 38 patients with MMA [18]. The PIRAMIO scoring system is based on digital subtraction angiography (DSA), structural MRI and hypercapnia-triggered BOLD MRI and correlates well with the past and current neurological symptomatology [17].  
The first aim of this study was to evaluate the PIRAMIO scoring system in a large number of patients by applying the scoring system to neuroradiological data sets (DSA, structural and functional MRI) and by investigating the capability to predict past and current neurological symptomatology as proposed by [PERSON] et al. We aimed to evaluate the scoring system not only in the ICA territories but also specifically in the ACA and MCA territories separately.  
In our opinion, the indication for revascularization surgery should not mainly be based on patients' past or current neurological symptoms, as the goal is to prevent ischemic events beforehand. Specifically, in (currently) asymptomatic patients, the aim is to avoid ischemic strokes/neurological symptoms. Therefore, therapeutic considerations should rather be based on the evidence of a decreased CPR indicated by [15]Water PET, which plays an important role in clinical decision-making in patients with MMA [9; 10; 14], including those without ischemic symptoms.  
Hence, as the second aim of this study, we intended to validate the PIRAMIO scoring system regarding the capability to predict a reduced CPR. In this context, our aim was to investigate whether a classification system with a stronger ability to predict an impaired CPR on [15]water PET in the ACA and MCA territories can be established with multimodal neuroradiological imaging. Here, we propose an entirely MRI-based scoring system called _MRI-Based Assessment of Risk of Stroke in Moyamoya Angiopathy_ (MARS-MMA).