Innovative Silicon Photomultiplier Technologies for Small-Animal PET

 描述（由申请人提供）：临床前正电子发射断层扫描（PET）已成为生物医学研究中广泛使用的工具，特别是在新疗法的评价中。数百台扫描仪安装在世界各地的主要医学研究中心和制药公司。然而，由于各种原因，这些系统的性能福尔斯远低于理论上可以实现的性能。这有两个重要的后果。首先，放射性药物动力学和摄取的当前研究的定量潜力被有限的空间分辨率（降低准确度）和有限的灵敏度（降低精度）破坏。其次，临床前PET的重要应用，例如小鼠大脑中灰质结构的代谢成像或低丰度蛋白质靶点的研究，例如慢性炎症中的TSPO受体表达，都是当前仪器无法实现的。该提案的目标是开发一种通向小动物PET扫描仪的途径，该扫描仪可以尽可能接近基础物理学和可用探测器材料的特性所施加的空间分辨率和灵敏度的理论极限。基于15年来为小动物PET开发越来越高分辨率的探测器，实现双端探测器的最新进展，该探测器还可以同时提供高灵敏度，并将其与高度创新的硅光电倍增管（SiPM）光电探测器相结合，我们提出了一种设计，该设计将导致探测器模块具有前所未有的性能，适用于小动物PET应用。具体来说，我们将开发完全工程化的探测器模块，适合在临床前PET扫描仪几何结构中紧密包装，将支持优于0.6 mm的重建空间分辨率，小鼠全身的平均灵敏度>10%，相互作用深度分辨率< 3 mm，定时分辨率< 3 ns，能量分辨率<30%。我们将开发电子和软件，以有效地读取这些模块，而不会显着降低性能，并将其集成到开源OpenPET库中，供整个核医学成像社区访问。最后，我们将使用完全工程化的探测器模块的实验数据，结合先进的仿真工具，设计和预测使用我们的新技术的临床前扫描仪的性能。该提案的成果将是探测器模块和扫描仪设计，将临床前PET推进到新的空间分辨率和灵敏度水平，以及一套全面的实验和模拟数据，这些数据将用于证明进入下一阶段开发原型小动物PET扫描仪的合理性。还将产生更广泛的影响，因为所开发的探测器技术和电子器件将适用于其他PET系统，特别是专用器官成像（例如大脑、乳房）扫描仪和PET/MR系统。

 DESCRIPTION (provided by applicant): Preclinical positron emission tomography (PET) has become a widely used tool in biomedical research, particularly in the evaluation of new therapeutics. Hundreds of scanners are installed across the world in major medical research centers and within pharmaceutical companies. For a variety of reasons, however, the performance of these systems falls well short of what can theoretically be achieved. This has two important consequences. Firstly, the quantitative potential of current studies of radiopharmaceutical kinetics and uptake is undermined by limited spatial resolution (reducing accuracy) and limited sensitivity (reducing precision). Secondly, important applications for preclinical PET, for example metabolic imaging in gray matter structures in the mouse brain or studies of low abundance protein targets, such as TSPO receptor expression in chronic inflammation, are just out of the reach of current instruments. The goal of this proposal is to develop a pathway towards small-animal PET scanners that can come as close as possible to the theoretical limits of spatial resolution and sensitivity imposed by fundamental physics and the properties of available detector materials. Building on 15 years of development of increasingly high resolution detectors for small-animal PET, recent advances in realizing dual-ended detectors that can also simultaneously provide high sensitivity and combining these with highly innovative silicon photomultiplier (SiPM) photodetectors, we propose a design that will lead to detector modules with unprecedented performance for small-animal PET applications. Specifically, we will develop fully-engineered detector modules suitable for close packing in a preclinical PET scanner geometry that will support better than 0.6 mm reconstructed spatial resolution, an average sensitivity of >10% across the whole body of a mouse, depth-of-interaction resolution < 3 mm, timing resolution < 3 ns and energy resolution < 30%. We will develop the electronics and software to efficiently read out these modules with no significant degradation in performance and integrate them into the open source OpenPET libraries for access by the entire nuclear medical imaging community. Lastly, we will use experimental data from fully-engineered detector modules combined with advanced simulation tools to design and predict the performance of a preclinical scanner using our new technology. The outcome of this proposal will be detector modules and a scanner design that advance preclinical PET to new levels of spatial resolution and sensitivity together with the comprehensive set of experimental and simulation data that will be needed to justify moving to the next stage of developing a prototype small-animal PET scanner. There also will be a broader impact in that the detector technology and electronics developed will be applicable to other PET systems, especially dedicated organ imaging (e.g. brain, breast) scanners and PET/MR systems.