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

探索纳米光子学和超材料概念，创建用于飞行时间正电子发射断层扫描的“超级闪烁体”

• 批准号: 10509318
• 负责人: CRAIG S LEVIN
• 金额: $ 23.61万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-17 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10509318
• 关键词: Adopted; Biodistribution; Biological; Biological Markers; Biology; Bismuth; Caliber; Cell physiology; Cells; Chemicals; Chemistry; Clinic; Clinical; Contrast Media; Crystallization; Databases; Detection; Diagnostic Neoplasm Staging; Disease; Disease Management; Disease Pathway; Dose; Electromagnetic Energy; Electromagnetic Fields; Electromagnetics; Electrons; Elements; Enhancing Lesion; Event; Fluorides; Geometry; Goals; Heart Diseases; Image; Image Enhancement; Imaging technology; Investigation; Label; Lesion; Light; Location; Malignant Neoplasms; Measurement; Measures; Medical Imaging; Methods; Modality; Molecular; Molecular Profiling; Monitor; Nanostructures; Noise; Operative Surgical Procedures; Optics; Patients; Performance; Photons; Planet Earth; Positioning Attribute; Positron; Positron-Emission Tomography; Procedures; Property; Publishing; Radiation; Radiation therapy; Radioactive; Radioisotopes; Radiolabeled; Recurrence; Research; Resolution; Role; Scanning; Shapes; Signal Transduction; System; Techniques; Technology; Three-Dimensional Image; Time; Tracer; Visible Radiation; Visualization; Work; absorption; alkalinity; base; biomedical imaging; cancer therapy; cost; crystallinity; design; detection sensitivity; detector; image reconstruction; improved; multidisciplinary; nanocomposite; nanofabrication; nanomaterials; nanoparticle; nanophotonic; nervous system disorder; new technology; novel; novel diagnostics; novel therapeutics; patient safety; photon-counting detector; photonics; response; simulation; standard of care; three-dimensional visualization; tool; transmission process; two-photon

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.

摘要 正电子发射断层扫描(PET)是诊断癌症和心脏病的分子特征的标准检查方法。 它也是一种常用的研究工具，用于可视化和量化神经病学疾病的分子途径 精神错乱。我们建议开发一种超材料来创建用于飞行时间(ToF)正电子发射计算机断层扫描(TOF)的“超级闪烁体”。如果 这项技术的成功将大大提高PET的图像质量和定量精度 为该模式在疾病管理中发挥新的作用。PET使用放射性标记的分子对比度 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，使三维可视化和量化 疾病生物标志物。示踪剂分子由正电子发射器标记，每一次衰变都会导致 发射两个方向相反的511千电子伏特(Kev)湮没光子。TOF-PET使用到达 每对中的两个光子之间的时间差，以更准确地沿 PET系统探测器响应线，提高了重建图像的信噪比(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。任何 RISNR中的助推器也可以用来减少注入的放射性剂量或扫描持续时间，增加 患者的安全或诊所的吞吐量。提议的新闪烁体的长期目标 技术的CTR为&lt；10皮秒(Ps)，比最好的CTR(214 Ps)高20倍以上 最先进的临床ToF-PET系统，使RISNR提高约5倍或注射剂量或扫描减少约25倍 与那个系统相比的时间。如果成功，这一能力将使PET的新应用成为可能。当前的PET 系统使用闪烁晶体，这种晶体是在晶体中转换511kev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造一种超材料“超级” 闪烁体具有比所有已知的PET闪烁体更短的上升时间和衰减时间以及更大的光产额， 使建议的CTR降低20倍。纳米光子学和超材料的出现 革命性的光子学。纳米材料提供了对内部电磁的相当大的控制 场，实现了标准材料中没有的极不寻常的光学特性。这项令人兴奋的调查将 通过将超材料这一新技术引入生物医学成像领域， 通过在PET成像方面实现突破性的性能水平，如果成功，这将极大地扩展PET的 能够表征疾病，并使PET在疾病管理中发挥新的作用。