Scintillating Balloon-Enabled Fiber-Optic System for Radionuclide Imaging of Atherosclerotic Plaques

UNLABELLED: Atherosclerosis underlies coronary artery disease, the leading cause of death in the United States and worldwide. Detection of coronary plaque inflammation remains challenging. In this study, we developed a scintillating balloon-enabled fiber-optic radionuclide imaging (SBRI) system to improve the sensitivity and resolution of plaque imaging using (18)F-FDG, a marker of vascular inflammation, and tested it in a murine model. METHODS: The fiber-optic system uses a Complementary Metal-Oxide Silicon (CMOS) camera with a distal ferrule terminated with a wide-angle lens. The novelty of this system is a scintillating balloon in the front of the wide-angle lens to image light from the decay of (18)F-FDG emission signal. To identify the optimal scintillating materials with respect to resolution, we calculated the modulation transfer function of yttrium-aluminum-garnet doped with cerium, anthracene, and calcium fluoride doped with europium (CaF2:Eu) phosphors using an edge pattern and a thin-line optical phantom. The scintillating balloon was then fabricated from 10 mL of silicone RTV catalyst mixed with 1 mL of base and 50 mg of CaF2:Eu per mL. The addition of a lutetium oxyorthosilicate scintillating crystal (500 μm thick) to the balloon was also investigated. The SBRI system was tested in a murine atherosclerosis model: carotid-ligated mice (n = 5) were injected with (18)F-FDG, followed by ex vivo imaging of the macrophage-rich carotid plaques and nonligated controls. Confirmatory imaging of carotid plaques and controls was also performed by an external optical imaging system and autoradiography. RESULTS: Analyses of the different phosphors showed that CaF2:Eu enabled the best resolution of 1.2 μm. The SBRI system detected almost a 4-fold-higher radioluminescence signal from the ligated left carotid artery than the nonligated right carotid: 1.63 × 10(2) ± 4.01 × 10(1) vs. 4.21 × 10(1) ± 2.09 × 10(0) (photon counts), P = 0.006. We found no significant benefit to adding a scintillating crystal to the balloon: 1.65 × 10(2) ± 4.07 × 10(1) vs. 4.44 × 10(1) ± 2.17 × 10(0) (photon counts), P = 0.005. Both external optical imaging and autoradiography confirmed the high signal from the (18)F-FDG in carotid plaques versus controls. CONCLUSION: This SBRI system provides high-resolution and sensitive detection of (18)F-FDG uptake by murine atherosclerotic plaques.