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: 8451846
• 负责人: CRAIG S LEVIN
• 金额: $ 54.92万
• 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/8451846
• 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; public health relevance; 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.

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，大大提高正电子发射断层扫描（PET）的信号检测限，该系统能够显著改善疾病细胞和分子特征的可视化和定量。我们将建立在以前的工作，探索和开发了一个创新的概念，为小动物PET的3-D位置敏感的光子闪烁探测器技术取得的进展。拟议的项目将首先大大改进这种有前途的探测器技术，大幅（而不是渐进地）提高其性能，同时使其更加实用。然后，我们将把先进的技术转化为一个“盒形”的小型原型，小动物PET系统与可调FOV，我们将建立从一个新颖的多层探测器模块。在这些探测器层中，我们将采用0.5 mm像素的闪烁晶体阵列，以大幅提高小动物PET的空间分辨率。新的闪烁探测概念有助于实现这一目标，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0.5mm宽度的元件也是如此。通过盒形系统设计实现的显著提高的511 keV光子灵敏度也有助于实现重建图像中的0.5 mm分辨率目标，其原因我们将在本申请中阐明。闪烁晶体阵列耦合到新型的、极薄的、高增益位置敏感的光电探测器，该光电探测器以创新的“边缘上”配置布置，该配置使得能够在任何晶体内直接测量511 keV光子相互作用深度（DOI），并且促进>90%的闪烁光收集效率，而与DOI无关。所得到的鲁棒的、不变的光信号促进了上级光子能量和时间分辨率，其与0.5 mm的固有空间分辨率一起有助于在存在背景活动的情况下增强PET信号检测和量化。在该探测器模块的边缘上的分层布置中，入射光子穿过最小约2 cm厚的晶体，晶体填充分数为70%，以促进高511 keV光子探测效率，而0.5 mm DOI分辨率有助于保持整个所得PET系统的敏感体积的空间分辨率均匀性。此外，这种探测器配置能够定位在不同的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，这是一种不寻常的能力，我们称之为“3-D定位”。“这种能力对于实现所需的0.5 mm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。如果成功的话，所提出的0.5 mm分辨率，高灵敏度，3-D定位探测器，结合新的事件处理算法，我们的小组正在研究，使分辨率，对比度和重建图像的信噪比显着改善。影响力：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，从而提高在转化心血管，神经和癌症研究中应用的信号检测能力。