Abstract 5463: Dual Channel Hybrid Fluorescence Molecular Tomography/X-ray Computed Tomography (FMT-CT) of Inflammation in Murine Atherosclerotic Plaques
Monocyte/macrophages play a key role in the development and progression of atherosclerotic lesions. Here we present a novel hybrid in vivo imaging approach that simultaneously reports on lesion anatomy, phagocytic activity by uptake of fluorescent nanoparticles and extracellular matrix remodeling with a protease-activatable agent, detectable with hybrid FMT-CT imaging. We co-injected 5 aged apoE deficient and 5 wild type mice with 15mg/kg of macrophage-avid nanoparticle (CLIO-680, emission 700nm) and 2nmol of a cathepsin-activatable protease reporter (Prosense-750, emission 780nm). Mice were imaged using a free space dual channel FMT system inside a cartridge that is optically translucent and has multimodal fiducial markers for image fusion incorporated in its frame. While the immobilized mice were anesthetized with isoflurane, the holding device was transferred for ECG-gated high resolution CT (isotropic resolution 50um). During CT acquisition, iodine contrast was delivered at 65ul/min via tail vein. In vivo, we found strong fluorescent signal for uptake of nanoparticles as well as protease activity (p<0.05 WT vs apoE−/− mice), which was mapped to the proximal aorta on CT. Contrast enhanced CT visualized murine aortic plaques. Ex vivo fluorescence reflectance imaging and fluorescence microscopy corroborated in vivo findings and identified macrophages as target cells. FMT-CT imaging of inflammatory atherosclerosis provides quantifiable 3-dimensional maps of macrophage activity and visualizes murine aortic plaques, providing unprecedented insight into disease progression non-invasively.