Quantitative measurement of cortical superficial siderosis in cerebral amyloid angiopathy

Cerebral amyloid angiopathy (CAA) is a cerebrovascular disease affecting the small arteries in the brain with hallmark depositions of amyloid-β in the vessel wall, leading to cognitive decline and intracerebral hemorrhage (ICH). An emerging MRI marker for CAA is cortical superficial siderosis (cSS) as it is strongly related to the risk of (recurrent) ICH. Current assessment of cSS is mainly done on T2*- weighted MRI using a qualitative score consisting of 5 categories of severity which is hampered by ceiling effects. Therefore, the need for a more quantitative measurement is warranted to better map disease progression for prognosis and future therapeutic trials. We propose a semi-automated method to quantify cSS burden on MRI and investigated it in 20 patients with CAA and cSS. The method showed excellent inter-observer (Pearson's 0.991, P < 0.001) and intra-observer reproducibility (ICC 0.995, P < 0.001). Furthermore, in the highest category of the multifocality scale a large spread in the quantitative score is observed, demonstrating the ceiling effect in the traditional score. We observed a quantitative increase in cSS volume in two of the 5 patients who had a 1 year follow up, while the traditional qualitative method failed to identify an increase because these patients were already in the highest category. The proposed method could therefore potentially be a better way of tracking progression. In conclusion, semi-automated segmenting and quantifying cSS is feasible and repeatable and may be used for further studies in CAA cohorts.