Exploring the Benefits of Time-of-Flight PET

描述（由申请人提供）：简单的理论预测，增加飞行时间（TOF）信息可降低PET图像中的噪声。这种降噪可以提高图像质量，减少成像时间，减少注射剂量，或实现这些益处的组合。对转化医学的潜在影响是巨大的，特别是对于大患者的肿瘤学研究，迫切需要改进。因此，随着TOF PET相机在过去五年中的商业化，飞行时间PET受到了相当大的关注。所有这些商用TOF PET相机都实现了~555 ps fwhm定时分辨率，但由于图像中的噪声方差与定时分辨率成比例（即，将定时分辨率减小两倍意味着成像时间或剂量减小两倍），期望获得可能的最佳定时分辨率。此外，这种噪音降低转化为临床益处的方式还没有得到很好的理解。本提案的目的是构建一个原型PET相机，其定时分辨率为~150 ps fwhm（几乎是商业TOF PET相机的四倍），设计方法来量化由飞行时间提供的降噪如何转化为临床效益，然后测量（使用原型相机）图像改善如何取决于定时分辨率。通过设计获得更好的定时分辨率的方法，并通过量化TOF优势作为定时分辨率的函数，我们将指导未来的商业和学术TOF PET相机设计师，让他们做出明智的选择，因为我们的技术开发已经并将继续是“开源的”。“我们计划三个主要发展。在上一个资金周期中，我们构建了一个单环“演示”TOF PET相机与LSO闪烁体晶体，实现326 ps的符合定时分辨率。虽然简单的估计预测，与商业TOF PET相机相比，它将全身成像中的噪声方差降低约2倍，但首要任务是进行全面分析，以更好地表征其临床实用性。具体来说，我们将量化噪声的改善作为时间分辨率的函数，使用模拟，体模和人体受试者研究的组合，包括肿瘤检测和分期的临床相关任务。我们的第二个任务是 重建相机与新开发的闪烁体（LaBr 3：Ce），具有卓越的PET性能（高灵敏度，3%的能量分辨率，和150 ps的定时分辨率），这将提供另一个因素的两倍改进的定时分辨率超过我们的LSO相机。这种定时分辨率比商用TOF PET相机高出近四倍，我们预测与传统（非TOF）PET相机相比，它将大大降低噪声方差（当对35 cm直径的患者进行成像时，降低16倍）！最后一项任务是使用与第一项任务相同的方法分析该相机的性能。

DESCRIPTION (provided by applicant): Simple theory predicts that adding time-of-flight (TOF) information reduces the noise in PET images. This noise reduction can improve image quality, decrease imaging time, decrease injected dose, or achieve a combination of these benefits. The potential impact on translational medicine is large, especially for oncology studies in large patients, where improvement is sorely needed. Thus, time-of-flight PET has received considerable interest, with commercialization of TOF PET cameras in the last five years. All of these commercial TOF PET cameras achieve ~555 ps fwhm timing resolution, but as the noise variance in the image is proportional to the timing resolution (i.e., reducing the timing resolutio by a factor of two implies a factor of two reduction in either the imaging time or dose), there is desire to obtain the best timing resolution possible. In addition, the way in which this noise reduction translates into clinical benefit is not well understood. The purpose of this proposal is o build a prototype PET camera whose timing resolution is ~150 ps fwhm (almost four times better than what commercial TOF PET cameras achieve), devise methods to quantify how the noise reduction afforded by time-of-flight translates into clinical benefit, and then measure (usin the prototype camera) how image improvement depends on the timing resolution. By devising methods for obtaining better timing resolution and by quantifying the TOF benefits as a function of timing resolution, we will guide future commercial and academic TOF PET camera designers by allowing them to make informed choices, as our technical developments have been and will continue to be "open source." We plan three main developments. In the previous funding cycle, we constructed a single-ring "demonstration" TOF PET camera with LSO scintillator crystals that achieves 326 ps coincidence timing resolution. While simple estimates predict that it will reduce the noise variance by a factor of roughly two in whole-body imaging compared to commercial TOF PET cameras, the first task is to perform a thorough analysis to better characterize its clinical utility. Specifically, we will quantify the improvement in noise as a function of timing resolution using a combination of simulation, phantom, and human subject studies, including the clinically relevant tasks of tumor detection and staging. Our second task is to rebuild the camera with a newly developed scintillator (LaBr3:Ce) that has exceptional PET performance (high sensitivity, 3% energy resolution, and 150 ps timing resolution), which will provide another factor of two improvement in timing resolution over our LSO camera. This timing resolution is nearly four times better than commercial TOF PET cameras, and we predict it will give an enormous noise variance reduction (16-fold, when imaging a 35 cm diameter patient) compared to conventional (non-TOF) PET cameras! The final task is to analyze the performance of this camera by using the same methods as in the first task.