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: 10685592
• 负责人: CRAIG S LEVIN
• 金额: $ 19.68万
• 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 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10685592
• 关键词: Adopted; Biodistribution; Biological; Biological Markers; Biology; Bismuth; Cell physiology; Cells; Chemicals; Chemistry; Clinic; Clinical; Contrast Media; Databases; Detection; Diagnostic Neoplasm Staging; Diameter; 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 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; biomedical imaging; cancer therapy; cost; crystallinity; design; detection sensitivity; detector; fabrication; 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; self assembly; 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.

抽象的 正电子发射断层扫描（PET）是分子表征癌症和心脏病的护理标准。 它也是一种可视化和量化神经学分子途径的良好研究工具 疾病。我们建议开发一种超材料，以创建一个“超级阶梯”，以制作飞行时间（TOF）宠物。如果 成功，这项技术将大大提高宠物的图像质量和定量准确性 为疾病管理中的方式开放新角色。 PET员工放射标记的分子对比 注射到患者以探测疾病的生物学机制的药物。这个示踪剂积聚在 表达某些分子特征的细胞，实现3维可视化和数量的数量 疾病生物标志物。示踪剂分子被阳性发射极标记，每个衰减都会导致 两次相对指向的511千电子伏特（KEV）歼灭照片的排放。 TOF-PET使用到达 每对两张照片之间的时差，以更准确地定位沿着排放位置 PET系统检测器响应线，增强了重建的图像信噪比（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。更精确 此时间差测量，称为巧合时间分辨率（CTR），RISNR越好。任何 还可以进行RISNR的提升以减少注射的放射性剂量或扫描持续时间，增加 诊所的患者安全或吞吐量。拟议的新闪烁的长期目标 技术<10 picsecond（ps）CTR，比最佳CTR（214 PS）好20倍 最先进的临床TOF-PET系统，使RISNR高约5倍或注射剂量或扫描25倍 与该系统相比。如果成功，此功能将为PET提供新的应用程序。目前的宠物 系统员工闪烁晶体，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学技术来创建超材料的“超级” 比所有已知的宠物闪烁体，闪烁器的上升时间和衰减时间短得多，轻度产量更大， 提出的CTR降低了> 20倍。纳米光子和超材料的出现具有 革命性的光子学。纳米结构材料提供了对内部电子的考虑控制 字段，可以在标准材料中找到高度不寻常的光学特性。这项激动人心的调查将 通过将新技术（超材料）引入生物医学成像领域，具有巨大的影响， 通过在宠物成像中达到突破性的表现水平，如果成功的话，将大大扩展宠物的 表征疾病的能力，并在疾病管理中启用宠物的新作用。