Abstract W P158: Permeability as a Biomarker of Cavernous Malformations

Abstract

Introduction: Vascular hyperpermeability in lesions and nonlesional brain is a cardinal feature of cerebral cavernous malformation (CCM) pathogenesis. Thus we implemented a novel magnetic resonance imaging (MRI) technique in order to quantitate vascular permeability in CCMs and non-CCM brain tissue in humans. We hypothesize that permeability of lesions and background brain will differ between familial and sporadic patients and measurements will be consistent between observers and over time. Method: We used a T 1 -weighted dynamic contrast-enhanced quantitative perfusion (DCEQP) protocol in 30 patients (13 sporadic, 12 familial, and 5 non-CCM cases) in conjunction with routine MRI scans. Regions of interest (ROIs) for permeability measurement included the entire lesion and areas of 12.9 mm 2 (16 pixels) of grey and white matter near and far from the lesion. Measurements were repeated by two observers and at two time points on a subset of patients. Results: For each ROI category except white matter near lesions, the mean permeability was higher in the familial than in the sporadic patients with p-values of 0.04, 0.005, 0.05, and 0.007 for CCM lesions, grey matter near, grey matter far (GMF), and white matter far (WMF) from lesions respectively. No difference was seen between sporadic and non-CCM cases, however familial WMF had higher permeability than both those groups (p0.05) except GMF with p=0.04. The intrapatient coefficients of variation between measurements were 0.74 and 0.63 and interpatient coefficients of variation were 1.36 and 1.56 for sporadic and familial cases respectively. Lastly, it was found that 3 of 4 patients with two scans had stable background (WMF) brain permeability over time. Conclusion: Results show the higher lesional and background brain permeability of familial cases, corroborating previous findings in mice. We also demonstrate the feasibility of DCEQP in CCM disease and the potential of permeability as a biomarker of disease activity or response to treatment. It also highlights the need for further investigation into clinical factors that may impact disease activity and permeability measures.