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- ss 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.

Automated summary

Cerebral amyloid angiopathy (CAA) is a cerebrovascular disease characterized by amyloid-β deposition in small arteries of the brain, leading to cognitive decline and intracerebral hemorrhage. A new marker for assessing CAA progression is cortical superficial siderosis (cSS) on MRI. Current evaluation of cSS using a qualitative score has limitations, thus a more quantitative measurement is needed. This study proposes a semi-automated method to quantify cSS burden on MRI and demonstrates its feasibility and repeatability in 20 CAA patients. The method has potential for tracking disease progression and can be used for further studies in CAA cohorts.