Abstract 2036: In Vivo Imaging of Protease Activity in Atherosclerosis Using A Near-Infrared Fluorescence Intravascular Catheter
Introduction: Augmented protease activity is a defining feature of vulnerable plaques. Here we demonstrate feasibility of imaging proteolytic activity in atherosclerosis using a custom-built intravascular near-infrared fluorescence (NIRF) catheter in concert with a protease-activatable NIRF imaging agent.
Methods: The catheter consists of an optical fiber (0.014“ floppy tip, 0.018” shaft) with laser excitation (2.0 mW) tuned to the NIR (excitation 746 nm). Cholesterol-fed rabbits underwent balloon injury of the aortoiliac arteries. Eight weeks later rabbits were intravenously injected with the imaging agent (n=5, Prosense 600 nmol/kg, VisEn Medical) or saline (n=2). After 24 hours, the catheter was percutaneously advanced beyond angiographically-visible iliac plaques. In vivo NIRF signal measurements were recorded through blood during a 30 second manual pullback. Resected vessels then underwent NIRF imaging and histopathological analysis.
Results: In the Prosense group, catheter pullback revealed focal NIRF signal in vivo in iliac plaques (Figure 1⇓). No flushing of blood was performed. Ex vivo NIRF imaging confirmed strong signal in atheromata (Figure 1⇓). Microscopy revealed focal NIRF signal in plaque sections that colocalized with macrophages and cathepsin B. No significant NIRF signal was evident in the saline group (p<0.05).
Conclusions: Augmented protease activity in atherosclerosis can be rapidly imaged in vivo in coronary-sized vessels using a novel intravascular NIRF catheter and a protease-activatable NIRF sensor. These experiments potentially provide a new framework for intracoronary imaging of inflammation in atheroscle-rotic plaques.