Photon interaction depth encoded time-of-flight PET

描述(由申请人提供)：我们建议改进飞行时间(ToF)正电子发射断层扫描(PET)探测器仪器，如果成功，将进一步增强临床上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在PET系统中任何两个探测器元件之间的响应线上的位置。精确的TOF事件定位需要亚纳秒级的符合时间分辨率，以减少沿响应线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，其符合时间分辨率可达到~600-900 ps的半高全宽(FWHM)符合时间分辨率[使用光电倍增管(PMT)]，e2厘米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位置的不确定性。对于所提出的d300ps符合时间分辨率，e2厘米长的晶体中由于光子DOI引起的ToF不确定度是不可忽略的。因此，我们在这项提案中的目标是创建一种具有d300ps半高宽符合时间分辨率的PET探测器，同时还可以测量闪烁晶体中的光子DOI。除了增强光子到达时间信息外，光子DOI分辨率的能力还提高了视场(FOV)的空间分辨率一致性。此外，所提出的设计具有测量多相互作用光子事件的每个个体相互作用的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，该设计基于长度为e2 cm的闪烁晶体的单端读出，一对一地耦合到快速、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来数字化，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TOF事件定位更准确，这可能会影响重建图像的性能，但在本工作中，我们重点研究光子到达时间和符合时间分辨率与光子DOI的关系。如果提出的设计不满足时间和DOI分辨率规范，作为后备计划，将研究基于短闪烁探测器层的替代探测器体系结构。影响：如果成功，使用建议的探测器建立的PET系统将使直径为40厘米的患者的图像信噪比(SNR)提高三倍，并提供空间分辨率和对比度分辨率的增强，这些共同将显著增强可视化和量化位于弥漫背景活动中的疾病的分子特征的能力。或者，可以利用显著的SNR提升来减少注射剂量或扫描时间。 与公共健康相关：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皮秒符合(双光子)时间分辨率和5毫米光子相互作用深度分辨率。如果成功，这一进展将使图像质量和定量准确性大大提高，超过目前的PET系统技术，这将转化为以下好处：(1)改善位于弥漫背景中的细微分子和基于细胞的疾病特征的可视化和量化，或(2)显著减少注射辐射剂量和/或扫描持续时间。这些特点将有助于促进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.