A Lower Cost High Resolution Time-of-flight PET Detector Development

描述（申请人提供）：PET成像可用于加强对人体生物学或病理功能的研究、癌症的基因表达/治疗、药物开发研究以及通过肿瘤定位提高临床诊断，从而提高分期和治疗计划的准确性。飞行时间（TOF） PET技术具有将有效PET探测灵敏度提高数倍的潜力，这取决于TOF时间分辨率。目前临床使用L(Y)SO闪烁晶体的PET报道TOF分辨率为650-1200 ps，可能将有效PET灵敏度提高2-3倍。我们的初步研究表明，可以实现300-350 ps的TOF时间分辨率，从而有可能将有效PET灵敏度提高4-6倍，因此可以在5分钟内扫描全身，而不是30分钟，在1分钟内扫描大脑/心脏。利用光电倍增管-象限共享（PQS）探测器设计，我们成功开发了2.4 mm空间分辨率的人体PET探测器，同时将光电倍增管（PMT）的成本降低了75%，而目前临床PET的4-6.5 mm分辨率使用了4倍的PMT。PMT是PET的主要成本。我们还发现，我们的探测器的内部结构提供了比现有的探测器设计更多的光输出，这有可能将TOF时间分辨率从目前的650-1200 ps提高到320-350 ps，从而有可能将PET的有效探测灵敏度提高4-6倍。其次，我们设想了一种简单的电子方法，使“phoswich”探测器概念在PET等大型系统中工作，这可能会将临床PET的分辨率提高到1.6- 2mm，或者解码两层探测器的相互作用深度。由于我们或其他人在未来可能开发出更好的TOF时间分辨率的探测器，因此需要更好更快的TOF探测器电子器件来充分实现这些更好的探测器的未来TOF时间分辨率；因此，我们也建议开发更好的TOF-PET电子产品。我们还将采用开发的检测器生产技术，建立TOF- pet检测平台，利用本项目开发的技术，量化TOF成像对病变检测的有效性，并将其作为患者尺寸、TOF分辨率、空间分辨率和不同病变与组织对比度的函数。长期目标是(a)开发成本更低、分辨率更高、灵敏度更高的TOF PET或TOF- PET-CT，以实现更早的癌症检测和更准确的癌症分期；(b)将全身扫描时间从30分钟缩短到5分钟，以提高患者的舒适度，减少PET图像中的患者运动伪影，减少由于患者运动导致的PET和CT图像的错配。(c)降低TOF-PET的高成本，并显著提高患者的处理量，以降低临床PET扫描的高成本，使患者和我们的社会更能负担得起，以减轻医疗保健和高科技药物不断增长的成本；(d)超高分辨率和1分钟脑或其他区域扫描为观察脑功能、心理和神经元反应、动态癌症示踪剂和多示踪剂癌症成像开辟了新的窗口。公共卫生相关性：本项目旨在开发用于正电子发射断层扫描（PET）和PET- ct系统的超高分辨率飞行时间（TOF）检测/电子系统，这将使PET和PET- ct的成本更低，分辨率更高（1.6-2mm），图像质量更高。我们将基于当前资助期开发的光电倍增管-象限共享（PQS）检测技术开发tof检测技术。我们还将研究TOF技术的总体成像优势以及本项目开发的特定TOF技术。目标是显著提高早期癌症检测和更准确的癌症分期，将目前的全身扫描时间从30分钟缩短到5分钟，以提高患者的舒适度，减少PET图像中的患者运动伪影，(c)降低TOF-PET系统的高成本，并显著提高患者的吞吐量，以降低临床PET程序的高成本，使患者和我们的社会更好地负担得起。

DESCRIPTION (provided by applicant): PET imaging can be deployed to enhance research on human biological or pathological functions, gene expression/therapy for cancer, drug-development research and improving clinical diagnosis by localizing tumors, thus improving the accuracy of staging and treatment planning. Time-of-flight (TOF) PET technology has the potential to increase the effective PET detection sensitivity by multiple times, depending on the TOF timing resolution. Current clinical PET with L(Y)SO scintillation crystals reported TOF resolution of 650-1200 ps that potentially increase the effective PET sensitivity by 2-3 times. Our preliminary study shows that a TOF timing resolution of 300-350 ps is achievable, thereby potentially enhancing the effective PET sensitivity by 4-6 times, so wholebody can be scanned in 5 minutes instead of 30 minutes and a brain/heart scan in 1 minute. Using the photomultiplier-quadrant-sharing (PQS) detector design we have successfully developed human PET detectors with 2.4-mm spatial resolution while reducing photomultiplier (PMT) cost by 75% concurrently, compared to the 4-6.5 mm resolution in present clinical PET using 4 times more PMT. PMT is a major cost in PET. We also found that the internal structure of our detector provides more light-output than the current detector designs, which could potentially improve TOF time resolution from the current 650-1200 ps to 320-350 ps, thereby potentially improving PET's effective detection sensitivity by 4-6 times. Secondly, we conceived a simple electronic method to make a "phoswich" detector concept work in a large system such as PET, which may improve resolution of clinical PET to 1.6-2 mm, or to decode the depth-of-interaction in 2-layer detectors. Due to the potentially better TOF time resolution of detectors to be developed by our group or others in the future, better and faster TOF detector electronics are needed to fully realize the future TOF timing resolution of these better detectors; Hence, we also propose to develop better TOF-PET electronics. We will also adopt the detector production technology developed to build a TOF-PET testing platform, using the technology developed in this project, to quantify the effectiveness of TOF imaging for lesion detection as a function of patient sizes, TOF resolution, spatial resolution and different lesion-to-tissue contrast ratios. The long-term goals are (a) to develop lower-cost, higher-resolution, higher-sensitivity TOF PET or TOF- PET-CT for earlier cancer detection and more accurate cancer staging, (b) to shorten wholebody scan time from 30 minutes to 5 minutes to improve patient comfort, to reduce patient-motion artifacts in PET images, and to reduce misregistration between PET and CT images caused by patient motion, (c) to lower the high cost of TOF-PET and to significantly increase patient throughput to reduce the high cost of clinical PET scans for better affordability to patients and our society to alleviate the ever increasing cost of health care and high-tech medicine, and (d) ultrahigh resolution and 1-minute scan of brain or other areas open new windows seeing brain function, psychological and neuronal response, dynamic cancer tracers and multi-tracer cancer imaging. PUBLIC HEALTH RELEVANCE: This project is for the development of ultrahigh resolution time-of-flight (TOF) detection/electronics system for positron emission tomography (PET) and PET-CT systems, which would lead to lower- cost, higher-resolution (1.6-2mm), and higher image quality PET and PET-CT. We will base this TOF-detection technology development on the photomultiplier-quadrant-sharing (PQS) detection technology developed in the current funding period. We will also study the imaging advantage of TOF technology in general and the specific TOF technology developed in this project. The goal is to significantly improve earlier cancer detection and more accurate cancer staging, to shorten the current wholebody scan time from 30 minutes to 5 minutes to improve patient comfort, to reduce patient-motion artifacts in PET images, (c) to lower the high cost of TOF-PET systems and to significantly increase patient throughput to reduce the high cost of clinical PET procedures for better affordability to patients and our society.