Zaman Raiyan T, Kosuge Hisanori, Carpenter Colin, Sun Conroy, McConnell Michael V, Xing Lei
Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California Division of Radiation Physics, Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California; and
Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California.
J Nucl Med. 2015 May;56(5):771-7. doi: 10.2967/jnumed.114.153239. Epub 2015 Apr 9.
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.
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.
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.
This SBRI system provides high-resolution and sensitive detection of (18)F-FDG uptake by murine atherosclerotic plaques.
动脉粥样硬化是冠心病的基础，而冠心病是美国及全球范围内的首要死因。检测冠状动脉斑块炎症仍然具有挑战性。在本研究中，我们开发了一种基于闪烁球囊的光纤放射性核素成像（SBRI）系统，以提高使用（18）F-FDG（一种血管炎症标志物）进行斑块成像的灵敏度和分辨率，并在小鼠模型中对其进行了测试。
该光纤系统使用一台互补金属氧化物半导体（CMOS）相机，其远端插芯端接有一个广角镜头。该系统的新颖之处在于在广角镜头前方有一个闪烁球囊，用于对（18）F-FDG发射信号衰变产生的光进行成像。为了确定分辨率方面的最佳闪烁材料，我们使用边缘图案和细线光学体模计算了掺杂铈的钇铝石榴石、蒽以及掺杂铕的氟化钙（CaF2:Eu）磷光体的调制传递函数。然后，将10 mL硅橡胶室温硫化催化剂与1 mL基料以及每毫升50 mg的CaF2:Eu混合制成闪烁球囊。还研究了向球囊中添加厚度为500μm的正硅酸镥闪烁晶体的情况。SBRI系统在小鼠动脉粥样硬化模型中进行了测试：对颈动脉结扎的小鼠（n = 5）注射（18）F-FDG，随后对富含巨噬细胞的颈动脉斑块和未结扎的对照进行离体成像。还通过外部光学成像系统和放射自显影对颈动脉斑块和对照进行了确证成像。
对不同磷光体的分析表明，CaF2:Eu实现了最佳分辨率，为1.2μm。SBRI系统检测到结扎的左颈动脉发出的放射发光信号几乎是非结扎的右颈动脉的4倍：1.63×10(2)±4.01×10(1)对4.21×10(1)±2.09×10(0)（光子计数），P = 0.006。我们发现向球囊中添加闪烁晶体没有显著益处：1.65×10(2)±4.07×10(1)对4.44×10(1)±2.17×10(0)（光子计数），P = 0.005。外部光学成像和放射自显影均证实颈动脉斑块中（18）F-FDG的信号高于对照。
该SBRI系统能够高分辨率且灵敏地检测小鼠动脉粥样硬化斑块对（18）F-FDG的摄取。
