In vivo imaging of gadolinium-based contrast agent leakage in patients with cerebral amyloid angiopathy

Abstract

Introduction: Blood-brain barrier (BBB) leakage is hypothesized to be an early step in the pathophysiology of cerebral amyloid angiopathy (CAA), possibly preceding vessel wall breakdown and hemorrhage. This study aims (1) to measure BBB leakage in vivo in the parenchyma and at the level of the leptomeningeal blood vessels in patients with CAA without lobar intracerebral hemorrhage compared to controls and (2) to study the relationship between BBB leakage and neuroimaging markers of CAA severity. Methods: To date, 13 participants with probable CAA without prior intracerebral hemorrhage (age 67±9 years, 8 females) and 5 non-CAA controls with mild cognitive impairment (CDR 0.5 or 1) and no microbleeds (age 70±7 years, 1 female) have been included into the study. The 3T MRI protocol included pre- and post-contrast T1-weighted (0.9 × 0.9 × 0.9 mm3) and T2-FLAIR scans (0.9 × 0.9 × 0.9 mm3, TE 500 ms), an SWI (0.6 × 0.6 × 1.4 mm3), and a Dynamic Contrast Enhanced (DCE) scan (0.9 × 0.9 × 3.0 mm3). Participants received (0.2mL/kg) a gadolinium-based contrast agent (Dotarem) intravenously during the DCE scan. DCE scans were analyzed with ROCKETSHIP software to quantify the permeability-surface area product (PS), which represents the rate at which contrast agent leaks from the plasma into the parenchyma. Leptomeningeal CSF enhancement is measured by visually inspecting post-contrast versus pre-contrast T2-FLAIR scans. Preliminary Results: Preliminary analysis revealed higher whole-brain PS in participants with CAA compared to non-CAA controls (Figure 1). Figure 2 shows an example of leptomeningeal CSF enhancement on post-contrast T2-FLAIR (2b) versus pre-contrast T2-FLAIR (2a). Ongoing analyses will compare PS-values in the cortex and white matter and in the occipital and frontal lobe. Furthermore, we aim to study the relationship between parenchymal and leptomeningeal contrast leakage with hemorrhagic neuroimaging markers (i.e. cortical microbleeds and cortical superficial siderosis) on SWI. Discussion: These preliminary results indicate that we can capture BBB leakage in vivo in our cohort, and that parenchymal BBB leakage is higher in patients with CAA compared to controls. Successful completion of this ongoing study will aid our understanding of the role of BBB leakage in the pathophysiology of CAA and the potential added value of BBB imaging as an early disease biomarker in CAA.