Photon interaction depth encoded time-of-flight PET

描述（由申请人提供）：我们建议推进飞行时间（ToF）正电子发射断层扫描（PET）探测器仪器，如果成功，将进一步增强在临床中可视化和量化疾病分子特征的能力。ToF PET使用 探测到的符合光子的到达时间差，以更好地估计正电子湮没沿着PET系统中任意两个探测器元件之间的响应线的位置。精确的ToF事件定位需要亚纳秒符合时间分辨率，以减少沿响应线沿着的湮灭光子发射位置的不确定性。对于最先进的临床ToF PET系统（使用光电倍增管（PMT）实现约600-900 ps半峰全宽（FWHM）符合时间分辨率），e2 cm长探测器晶体内的光子相互作用深度（DoI）不确定性不会显著影响ToF位置不确定性。对于建议的d300 ps符合时间分辨率，由于e2 cm长度晶体内的光子DoI导致的ToF不确定性不可忽略。因此，我们在本提案中的目标是创建具有d300 ps FWHM符合时间分辨率的PET探测器，其还测量闪烁晶体内的光子DoI。除了增强光子到达时间信息外，光子DoI分辨率的能力还促进了整个视场（FoV）的空间分辨率均匀性。此外，所提出的设计具有测量多相互作用光子事件的每个单独相互作用的3D位置和能量的独特能力，这可以被利用来进一步提高空间分辨率和对比度分辨率。为了实现这些设计目标，我们建议探索一种新的探测器设计的基础上，单端读出的e2厘米长的闪烁晶体耦合一对一的快速，高增益硅光电倍增管（SiPM）光电探测器阵列。完整的探测器信号波形将通过新颖的商业上可用的采样架构进行数字化，并且DoI（和3D定位）信息通过与每个事件的数字化探测器脉冲形状的各种参数（例如脉冲高度、上升沿和下降沿频率模式）的相关性来确定。在PET系统中，DoI信息导致沿响应线的更准确的ToF事件定位沿着，这可能会影响重建图像的性能，但在这项工作中，我们专注于研究光子到达时间和符合时间分辨率对光子DoI的依赖性。如果拟议的设计不符合时间和DoI分辨率规格，作为备用计划，将研究基于短闪烁探测器层的替代探测器架构。影响：如果成功的话，对于40 cm直径的患者，与非ToF系统相比，使用所提出的探测器构建的PET系统将使图像信噪比（SNR）增加三倍，并提供空间分辨率和对比度分辨率的增强，这将大大增强对弥漫性背景活动中存在的疾病的分子特征进行可视化和量化的能力。或者，可以利用显著的SNR提升来减少注入剂量或扫描时间。 公共卫生相关性：我们建议开发一种先进而实用的光子探测器技术，适用于新一代临床“飞行时间”正电子发射断层扫描（PET）系统，该系统在整个探测器体积内具有优于300皮秒的符合（双光子）时间分辨率和5 mm光子相互作用深度分辨率。如果成功的话，这种进步将使得能够在当前PET系统技术上实质性地增强图像质量和定量准确性，这将转化为益处，诸如（1）改善对存在于扩散背景中的疾病的基于细微分子和细胞的特征的可视化和量化，或（2）实质性地减少注入的辐射剂量和/或扫描持续时间。这些功能将有助于促进PET的更广泛使用，并扩大其在疾病临床管理中的作用。

DESCRIPTION (provided by applicant): We propose to advance time-of-flight (ToF) positron emission tomography (PET) detector instrumentation that, if successful, will further enhance abilities to visualize and quantify molecular signatures of disease in the clinic. ToF PET uses the arrival time difference of detected coincidence photons to better estimate the position of the positron annihilation along the response line between any two detector elements in the PET system. Accurate ToF event positioning requires sub- nanosecond coincidence time resolution to reduce the uncertainty in annihilation photon emission location along a response line. For state-of-the-art clinical ToF PET systems, which achieve ~600-900 ps full-width-at-half-maximum (FWHM) coincidence time resolution [using photomultiplier tubes (PMTs)], the photon depth of interaction (DoI) uncertainty within the e2 cm length detector crystals does not significantly affect ToF position uncertainty. For the proposed d300 ps coincidence time resolution, the ToF uncertainty due to photon DoI within e2 cm length crystals cannot be ignored. Thus, our goal in this proposal is to create a PET detector with d300 ps FWHM coincidence time resolution that also measures photon DoI within the scintillation crystal. In addition to enhancing photon arrival time information, the capability for photon DoI resolution also promotes spatial resolution uniformity across the field of view (FoV). Furthermore, the proposed design has the unique capability to measure the 3D position and energy of each individual interaction of multi-interaction photon events, which can be exploited to further improve spatial resolution and contrast resolution. To achieve these design goals, we propose to explore a new detector design based on single ended readout of e2 cm length scintillation crystals coupled one-to-one to arrays of fast, high-gain silicon photomultiplier (SiPM) photodetectors. The full detector signal waveforms will be digitized by novel, commercially available sampling architectures, and DoI (and 3D positioning) information is determined by correlation with various parameters of the digitized detector pulse shape for each event, such as pulse height, rise and falling edge frequency patterns. In a PET system, DoI information leads to more accurate ToF event positioning along a response line that can impact reconstructed image performance, but in this work we focus on studying dependence of photon arrival time and coincidence time resolution on photon DoI. If the proposed design does not meet the time and DoI resolution specifications, as a backup plan, an alternative detector architecture based on layers of short scintillation detectors will be studied. Impact: If successful, a PET system built with the proposed detectors will increase image signal-to-noise ratio (SNR) three-fold compared to a non-ToF system for a 40 cm diameter patient, and provide enhancement of spatial resolution and contrast resolution that together will substantially enhance the ability to visualiz and quantify molecular signatures of disease residing in diffuse background activity. Alternatively the substantial SNR boost can be exploited to reduce injected dose or scan time. PUBLIC HEALTH RELEVANCE: We propose to develop an advanced, yet practical photon detector technology appropriate for a new-generation clinical "time-of-flight" positron emission tomography (PET) system that has better than 300 pico-seconds coincidence (two-photon) time resolution and 5 mm photon interaction depth resolution within the entire detector volume. If successful, such an advance would enable substantial enhancements to image quality and quantitative accuracy over current PET system technology that would translate into benefits such as (1) improved visualization and quantification of subtle molecular and cellular-based signatures of disease residing in a diffuse background, or (2) substantially reduced injected radiation dose and/or scan duration. These features would both help to promote more widespread use of PET as well as expand its role in the clinical management of disease.