Preclinical Translation of New Scintillation Light Detection Concepts for PET

PET 闪烁光检测新概念的临床前转化

• 批准号: 8104972
• 负责人: CRAIG S LEVIN
• 金额: $ 40.89万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2015-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8104972
• 关键词: 3-Dimensional; Algorithms; Animals; Beryllium; Boxing; Cardiovascular system; Cell Therapy; Cells; Clinical; Collection; Coupled; Detection; Development; Devices; Disease; Electronics; Elements; Engineering; Event; Future; Goals; Grant; Height; Image; Imagery; Individual; Life; Light; Lutetium; Measures; Methods; Modification; Molecular; Molecular Profiling; Molecular Target; Nature; Noise; Performance; Phase; Photons; Physiologic pulse; Polymers; Population; Positioning Attribute; Positron-Emission Tomography; Process; Property; Reading; Research; Resolution; Shapes; Signal Transduction; Surface; System; Technology; Testing; Thick; Time; Tissues; Tracer; Translating; Translations; Variant; Width; Work; Yttrium; analog; anticancer research; base; computerized data processing; data acquisition; density; design; detector; digital; improved; innovation; interest; malignant neurologic neoplasms; nanosecond; next generation; novel; pre-clinical; prototype; solid state; ultra high resolution; uptake; voltage; yttria

DESCRIPTION (provided by applicant): We propose to greatly advance the signal detection limits of positron emission tomography (PET) by developing a next-generation pre-clinical PET system capable of substantial improvements in visualization and quantification of cellular and molecular signatures of disease. We will build upon advances made in previous work that explored and developed an innovative concept for a 3-D position sensitive photon scintillation detector technology for small animal PET. The proposed project will first greatly improve upon this promising detector technology, substantially (not incrementally) advancing its performance, while also making it even more practical to implement. We will then translate that advanced technology into a small prototype of a "box- shaped", small animal PET system with adjustable FOV that we will build from a novel multi-layer detector module. In those detector layers, we will incorporate scintillation crystal arrays with 0.5 mm pixels in order to substantially advance the spatial resolution of small animal PET. This goal is facilitated by the new scintillation detection concept, where the scintillation light collection aspect ratio in each crystal element is very high, even for 0.5 mm width elements. The 0.5 mm resolution goal in reconstructed images is also facilitated by the significantly improved 511 keV photon sensitivity enabled by the box-shaped system design, for reasons that we will clarify in this application. The scintillation crystal arrays are coupled to novel, extremely thin, high gain position sensitive photodetectors arranged in an innovative "edge-on" configuration that enables directly measured 511 keV photon interaction depth (DOI) within any crystal, and promotes >90% scintillation light collection efficiency, independent of DOI. The resulting robust, non-varying light signal facilitates superior photon energy and temporal resolutions, which, together with 0.5 mm intrinsic spatial resolution, help to enhance PET signal detection and quantification in the presence of background activity. In this detector module's edge-on, layered arrangement, incoming photons traverse a minimum of ~2 cm thick crystal with a crystal packing fraction of 70% in order to promote high 511 keV photon detection efficiency, while the 0.5 mm DOI resolution helps to preserve spatial resolution uniformity throughout the sensitive volume of the resulting PET system. In addition this detector configuration is able to localize individual 511 keV photon interactions occurring in distinct crystal array layers. This is an unusual capability for a PET detector, which we refer to as "3-D positioning." This capability is important for achieving the desired 0.5 mm reconstructed resolution since incoming photons will often interact in multiple crystal elements of the ultra-high resolution detectors. If successful, the proposed 0.5 mm resolution, high sensitivity, 3-D positioning detectors, in conjunction with new event processing algorithms our group is investigating, enable substantial improvements in resolution, contrast, and reconstructed image signal-to-noise ratio. Impact: If successful, this research will advance the ability of PET to detect, visualize and quantify low concentrations of PET tracer accumulating in cells of interest, thus increasing signal detection capabilities for applications in translational cardiovascular, neurological, and cancer research. PUBLIC HEALTH RELEVANCE: We propose to advance the molecular signal detection limits of positron emission tomography (PET) by improving upon a detector technology we have developed under a previous grant and translating the concept into a next-generation high performance pre-clinical PET system. If successful, this work will yield a log order improvement for non-invasively visualizing and quantifying low abundance molecular targets within tissues of live animal subjects. Although there are many applications where this ultra-low signal sensitivity is needed, this advance is especially important in tracking and quantifying the distribution and proliferation of a small population of cells, a capability that is very much needed to guide the development of new cell-based therapies on the horizon.

描述（由申请人提供）：我们建议通过开发下一代临床前 PET 系统来大大提高正电子发射断层扫描 (PET) 的信号检测极限，该系统能够显着改进疾病细胞和分子特征的可视化和量化。我们将在之前工作中取得的进展的基础上，探索和开发用于小动物 PET 的 3D 位置敏感光子闪烁探测器技术的创新概念。拟议的项目将首先极大地改进这种有前途的探测器技术，大幅（而不是逐步）提高其性能，同时也使其更加实用。然后，我们将把这项先进技术转化为“盒形”小动物 PET 系统的小型原型，该系统具有可调节的 FOV，我们将利用新型多层探测器模块构建该系统。在这些探测器层中，我们将采用 0.5 毫米像素的闪烁晶体阵列，以大幅提高小动物 PET 的空间分辨率。新的闪烁检测概念促进了这一目标，其中每个晶体元件中的闪烁光收集纵横比非常高，即使对于 0.5 毫米宽度的元件也是如此。盒形系统设计显着提高了 511 keV 光子灵敏度，也促进了重建图像中 0.5 毫米分辨率的目标，原因我们将在本应用中阐明。闪烁晶体阵列与新颖、极薄、高增益位置敏感的光电探测器耦合，这些光电探测器以创新的“边缘式”配置排列，可以直接测量任何晶体内的 511 keV 光子相互作用深度 (DOI)，并提高 >90% 的闪烁光收集效率，与 DOI 无关。由此产生的稳健、不变的光信号有助于实现卓越的光子能量和时间分辨率，再加上 0.5 毫米的固有空间分辨率，有助于增强存在背景活动时的 PET 信号检测和量化。在该探测器模块的边缘分层排列中，入射光子穿过至少约 2 cm 厚的晶体，晶体堆积率为 70%，以提高 511 keV 光子探测效率，而 0.5 mm DOI 分辨率有助于保持最终 PET 系统整个敏感体积的空间分辨率均匀性。此外，该探测器配置能够定位不同晶体阵列层中发生的单个 511 keV 光子相互作用。对于 PET 探测器来说，这是一种不寻常的功能，我们将其称为“3D 定位”。此功能对于实现所需的 0.5 毫米重建分辨率非常重要，因为入射光子通常会在超高分辨率探测器的多个晶体元件中相互作用。如果成功，所提出的 0.5 毫米分辨率、高灵敏度、3D 定位探测器与我们小组正在研究的新事件处理算法相结合，可以显着提高分辨率、对比度和重建图像信噪比。影响：如果成功，这项研究将提高 PET 检测、可视化和量化感兴趣细胞中积累的低浓度 PET 示踪剂的能力，从而提高转化心血管、神经学和癌症研究应用的信号检测能力。 公共健康相关性：我们建议通过改进我们在先前资助下开发的检测器技术并将该概念转化为下一代高性能临床前 PET 系统，来提高正电子发射断层扫描 (PET) 的分子信号检测极限。如果成功，这项工作将为活体动物受试者组织内低丰度分子靶标的非侵入性可视化和量化带来对数顺序的改进。尽管有许多应用需要这种超低信号灵敏度，但这一进步对于跟踪和量化一小群细胞的分布和增殖尤其重要，而这种能力对于指导即将到来的新的基于细胞的疗法的开发非常需要。