Exploring concepts in nanophotonics and metamaterials to create a 'super-scintillator' for time-of-flight positron emission tomography

摘要 正电子发射断层扫描 (PET) 是从分子角度表征癌症和心脏病的护理标准。 它也是一种常用的研究工具，可可视化和量化神经系统疾病的分子途径 失调。我们建议开发一种超材料来为飞行时间 (ToF) PET 创建“超级闪烁体”。如果 该技术的成功，将大幅提高 PET 和 PET 的图像质量和定量精度。 为疾病管理方式开辟新的角色。 PET 采用放射性标记分子对比 将药剂注射到患者体内以探究疾病的生物学机制。该示踪剂累积在 表达某些分子特征的细胞，可实现 3 维可视化和量化 疾病生物标志物。示踪分子由正电子发射器标记，每次衰变都会产生 发射两个方向相反的 511 千电子伏 (keV) 湮灭光子。 ToF-PET应用到 每对中两个光子之间的时间差，可以更准确地定位发射位置 PET 系统探测器响应线，增强重建图像信噪比 (RISNR)。 RISNR 是与病变检测灵敏度和准确性密切相关的图像质量指标。越精确 这种时间差测量，称为符合时间分辨率（CTR），RISNR 越好。任意 RISNR 的增强还可用于减少注射放射性剂量或扫描持续时间，从而增加 分别是患者安全或诊所的吞吐量。拟议的新闪烁的长期目标 技术的 CTR <10 皮秒 (ps)，比最佳 CTR (214 ps) 好 20 倍以上 最先进的临床 ToF-PET 系统，可实现约 5 倍的 RISNR 提高或约 25 倍的注射剂量或扫描降低 与该系统相比的时间。如果成功，这一能力将为 PET 带来新的应用。当前PET 系统采用闪烁晶体，这种材料可以在晶体中转换 511 keV 光子相互作用 变成可见光的闪光。我们建议使用纳米光子技术来创建超材料“超级” 与所有已知的 PET 闪烁体相比，闪烁体具有更短的上升时间和衰减时间以及更高的光输出， 使建议的点击率降低 20 倍以上。纳米光子学和超材料的出现 彻底改变了光子学。纳米结构材料对内部电磁提供了相当大的控制 领域，实现标准材料中不存在的非常不寻常的光学特性。这项激动人心的调查将 通过将超材料这一新技术引入生物医学成像领域，产生了巨大的影响， 通过在 PET 成像领域实现突破性的性能水平，如果成功，将大大扩展 PET 的应用范围 描述疾病特征的能力，以及使 PET 在疾病管理中发挥新作用。

Abstract Positron emission tomography (PET) is a standard of care to molecularly characterize cancer and heart disease. It is also a well-used research tool to visualize and quantify molecular pathways of disease in neurological disorders. We propose to develop a metamaterial to create a “super-scintillator” for time-of-flight (ToF) PET. If successful, this technology will substantially enhance the image quality and quantitative accuracy of PET and open new roles for the modality in the management of disease. PET employs a radiolabeled molecular contrast agent that is injected into the patient to probe the biological mechanisms of disease. This tracer accumulates in the cells that express certain molecular signatures, enabling 3-dimensional visualization and quantification of disease biomarkers. The tracer molecule is labeled by a positron emitter that for every decay results in the emission of two oppositely directed 511 kilo-electron-volt (keV) annihilation photons. ToF-PET uses the arrival time difference between the two photons in each pair to more accurately position the emission location along PET system detector response lines, enhancing the reconstructed image signal-to-noise ratio (RISNR). RISNR is an image quality metric that strongly correlates with lesion detection sensitivity and accuracy. The more precise this time difference measurement, known as the coincidence time resolution (CTR), the better the RISNR. Any boosts in RISNR can also be employed to reduce injected radioactive dose or scanning duration, increasing patient safety or throughput in the clinic, respectively. The long-term goal for the proposed new scintillation technology is <10 picosecond (ps) CTR, which is over 20-fold better than the best CTR (214 ps) achieved for a state-of-the-art clinical ToF-PET system, enabling ~5-fold higher RISNR or ~25-fold lower injected dose or scan time compared to that system. If successful, this capability would enable new applications for PET. Current PET systems employ scintillation crystals, which are materials that convert 511 keV photon interactions in the crystal into flashes of visible light. We propose to use nanophotonic techniques to create a metamaterial “super” scintillator with vastly shorter rise time and decay time and greater light yield than all known PET scintillators, enabling the >20-fold reduction in CTR proposed. The emergence of nanophotonics and metamaterials has revolutionized photonics. Nanostructured materials provide considerable control over internal electromagnetic fields, enabling highly unusual optical properties not found in standard materials. This exciting investigation will have tremendous impact by both introducing a new technology, metamaterials, to the field of biomedical imaging, and by achieving breakthrough performance levels in PET imaging, that, if successful, will greatly expand PET’s capabilities for characterizing disease, as well as enable new roles for PET in disease management.