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类生物或病理功能、癌症的基因表达/治疗、药物开发研究和通过定位肿瘤来改善临床诊断的研究，从而提高分期和治疗计划的准确性。根据飞行时间(TOF)时间分辨率的不同，飞行时间(TOF)PET技术有可能将有效的PET检测灵敏度提高数倍。据报道，目前临床上使用L(Y)SO闪烁晶体的正电子发射计算机断层扫描的TOF分辨率为650-1200ps，有可能将有效正电子发射计算机断层扫描的灵敏度提高2-3倍。我们的初步研究表明，TOF时间分辨率为300-350 ps是可以实现的，从而潜在地将有效的PET灵敏度提高了4-6倍，因此全身扫描可以在5分钟内完成，而不是30分钟，脑/心脏扫描只需1分钟。利用光电倍增管象限共享(PQS)探测器设计，我们成功地开发了具有2.4 mm空间分辨率的人类PET探测器，同时将光电倍增管(PMT)成本降低了75%，而目前临床PET的分辨率为4-6.5 mm，使用4倍以上的PMT。PMT是PET的一项主要成本。我们还发现，我们探测器的内部结构提供了比当前探测器设计更多的光输出，这可能会将TOF时间分辨率从当前的650-1200ps提高到320-350ps，从而潜在地将PET的有效检测灵敏度提高4-6倍。其次，我们构思了一种简单的电子方法，可以在像PET这样的大系统中工作，这可能会将临床PET的分辨率提高到1.6-2 mm，或者解码两层探测器中的相互作用深度。由于我们团队或其他人未来将开发潜在更好的TOF时间分辨率的探测器，需要更好、更快的TOF探测器电子设备来充分实现这些更好的探测器的未来TOF时间分辨率；因此，我们还建议开发更好的TOF-PET电子设备。我们还将采用为建立TOF-PET测试平台而开发的探测器生产技术，使用本项目中开发的技术，以量化TOF成像对病变检测的有效性，作为患者大小、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，用于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，以改善患者舒适度，减少PET图像中的患者运动伪影，并减少由于患者运动而导致的PET和CT图像之间的配准错误，(C)降低TOF-PET的高昂成本并大幅增加患者吞吐量，以降低临床PET扫描的高昂成本，从而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日益增长的成本，以及(D)超高分辨率和1分钟脑或其他区域扫描，从而打开新的窗口，了解脑功能、心理和神经元反应、动态癌症示踪和多示踪癌症成像。与公共卫生相关：该项目是为了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)探测/电子系统，这将导致低成本、更高分辨率(1.6-2 mm)和更高图像质量的PET和PET-CT。我们将在当前资金期间开发的光电倍增管象限共享(PQS)探测技术的基础上开发这项飞行时间探测技术。我们还将研究飞行时间技术的总体成像优势和在本项目中开发的特定飞行时间技术。其目标是显著提高癌症早期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，以改善患者舒适度，减少PET图像中的患者运动伪影，(C)降低TOF-PET系统的高成本，并显著增加患者吞吐量，以降低临床PET手术的高成本，从而提高患者和我们的社会的负担能力。

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.