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）是一种标准的护理，以分子特征的癌症和心脏病。 它也是一种常用的研究工具，用于可视化和量化神经系统疾病的分子途径。 紊乱我们建议开发一种超材料，为飞行时间（ToF）PET创建一个“超级闪烁体”。如果 如果成功，这项技术将大大提高PET的图像质量和定量准确性， 为该模式在疾病管理中发挥新的作用。PET采用放射性标记的分子对比 被注射到病人体内以探测疾病的生物机制的试剂。这种示踪剂在 表达某些分子特征的细胞，使三维可视化和定量的 疾病生物标志物。示踪剂分子由正电子发射体标记，对于每次衰变， 发射两个方向相反的511千电子伏（keV）湮灭光子。ToF-PET使用到达 以更精确地定位发射位置沿着 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强相关的图像质量度量。越精确 这种时间差测量，称为符合时间分辨率（CTR），RISNR越好。任何 RISNR中的增强也可以用于减少注入的放射性剂量或扫描持续时间， 患者安全或诊所的吞吐量。拟议的新闪烁的长期目标 该技术的CTR <10皮秒（ps），这是20倍以上的最佳CTR（214 ps）实现了一个 最先进的临床ToF-PET系统，可实现约5倍的RISNR或约25倍的注射剂量或扫描 与这个系统相比。如果成功，这种能力将使PET的新应用成为可能。项当前宠兽 系统采用闪烁晶体，闪烁晶体是在晶体中转换511 keV光子相互作用的材料 变成可见光的闪光。我们建议使用纳米光子技术来创建一个超材料“超级” 具有比所有已知PET闪烁器短得多的上升时间和衰减时间以及更大的光输出的闪烁器， 使得所提出的CTR降低>20倍。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提供了对内部电磁场的相当大的控制。 领域，使高度不寻常的光学性能没有发现在标准材料。这项令人兴奋的调查将 通过将一种新技术，超材料，引入生物医学成像领域， 通过在PET成像方面实现突破性的性能水平，如果成功，将大大扩展PET的 这将有助于提高PET在疾病诊断中的能力，并使PET在疾病管理中发挥新的作用。

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.