Establishing orbital and cranial vessel wall MRI enhancement as an imaging biomarker in giant cell arteritis - PROJECT SUMMARY/ABSTRACT The as complication and disease glucocorticoids there unvalidated, biomarker improve vascular cranial MRI goal of this project is to establish orbital and cranial vessel wall magnetic resonance imaging (oVW-MRI) an imaging tool that assesses disease activity in giant cell arteritis (GCA), including the most feared of ocular involvement. GCA is a relapsing systemic vasculitis which frequently involves the orbital cranial arteries. Due to the fear of blindness, high rates of relapse, and lack of a reliable biomarker of ocular in GCA, all patients with GCA regardless of visual symptoms receive high doses and long duration of resulting in significant treatment-related adverse events. To minimize glucocorticoid exposure, are now an unprecedented number of t herapeutic trials in GCA. However, these trials all rely on poorly standardized, and subjective outcome measures. There is a critical need for an objective of disease activity, particularly ocular involvement, which can inform treatment decision-making and t he conduct of clinical trials in GCA. oVW-MRI has the potential to address this need by visualizing inflammation of multiple arteries in a single 35-minute scan . Prior studies of MRI in GCA f ocused on vessel wall imaging but little is known about the utility of adding dedicated orbital imaging to vessel wall to better assess orbital pathology in GCA.We hypothesize that combining orbital MRI with cranial vessel wall MRI (oVW-MRI) enables detection of orbital activity even in the absence of visual symptoms and can be used to longitudinally monitor disease activity in GCA. The premise of this study is supported by our preliminary data which found that oVW-MRI enhancement has a negative predictive value of 97% for ocular GCA, detects orbital disease in patients with and without visual symptoms, significantly decreases with treatment, and has additive value over existing measures of disease activity. We will now perform a multi-center prospective observational study which aims to: (1) and validate oVW-MRI enhancement as a diagnostic biomarker of ocular GCA, (2) determine the responsiveness and convergent validity of oVW-MRI enhancement in GCA. Patients with suspected GCA will be recruited from four sites with excellent track records in recruitment for GCA studies and expertise in vessel wall MRI. The study will leverage the clinical research infrastructure of the Vasculitis Clinical Research Consortium which has performed numerous multi-center, international studies in vasculitis. At completion a and will the f the proposed study, we will have the components needed for clinical t rials of oVW-MRI including validated and refined MRI score for GCA and ocular GCA, tandardized imaging and clinical data collection, data for power calculations. We anticipate that oVW-MRI will be additive to current clinical measures and provide a more quantitative and precise measurement of disease activity. o s Our long-term goals are to: (1) perform a clinical trial which definitively demonstrates that incorporation of MRI into treatment decision-making in GCA reduces both disease- and treatment-related morbidity; and (2) utilize MRI as a surrogate outcome measure in therapeutic trials of GCA. This proposal is fully responsive to the NIAMS FOA PAR-24-036.
