Scintillating balloon-enabled fiber-optic system for radionuclide imaging of atherosclerotic plaques

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 ¹⁸F-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 ¹⁸F- 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 ¹⁸F-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-foldhigher radioluminescence signal from the ligated left carotid artery than the nonligated right carotid: 1.63 × 10² ± 4.01 × 10¹ vs. 4.21 × 10¹ ± 2.09 × 10⁰ (photon counts), P = 0.006. We found no significant benefit to adding a scintillating crystal to the balloon: 1.65 × 10² ± 4.07 × 10¹ vs. 4.44 × 10¹ ± 2.17 × 10⁰ (photon counts), P = 0.005. Both external optical imaging and autoradiography confirmed the high signal from the ¹⁸F-FDG in carotid plaques versus controls. Conclusion: This SBRI system provides high-resolution and sensitive detection of ¹⁸F-FDG uptake by murine atherosclerotic plaques.