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: 8646914
• 负责人: CRAIG S LEVIN
• 金额: $ 56.19万
• 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 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8646914
• 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; Geometry; 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; data acquisition; density; design; detector; digital; improved; innovation; interest; malignant neurologic neoplasms; nanosecond; next generation; novel; pre-clinical; prototype; public health relevance; signal processing; 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系统来极大地提高正电子发射断层扫描（PET）的信号检测极限，该系统能够在疾病的细胞和分子特征的可视化和量化方面取得实质性进展。我们将在之前的工作中探索和开发用于小动物PET的三维位置敏感光子闪烁探测器技术的创新概念的基础上取得进展。提议的项目将首先极大地改进这种有前途的探测器技术，实质性地（而不是增量地）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一个“盒子形”的小型原型，我们将用一种新型多层探测器模块构建具有可调视场的小动物PET系统。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，以大大提高小动物PET的空间分辨率。新的闪烁探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长宽比非常高，即使是0.5 mm宽度的元件。重建图像中的0.5 mm分辨率目标也得益于盒形系统设计显著提高的511 keV光子灵敏度，其原因我们将在本应用中阐明。闪烁晶体阵列耦合到新颖的、极薄的、高增益的位置敏感光电探测器，以创新的“边对边”配置排列，可以在任何晶体内直接测量511 keV光子相互作用深度（DOI），并提高bbb90 %的闪烁光收集效率，独立于DOI。由此产生的鲁棒、不变的光信号有利于优越的光子能量和时间分辨率，再加上0.5 mm的固有空间分辨率，有助于在背景活动存在下增强PET信号的检测和量化。在该检测器模块的边缘上分层排列中，入射光子穿过至少2 cm厚的晶体，晶体填充率为70%，以提高511 keV的光子检测效率，而0.5 mm DOI分辨率有助于保持整个PET系统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发生在不同晶体阵列层中的单个511 keV光子相互作用。这是PET探测器不寻常的功能，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，提议的0.5 mm分辨率，高灵敏度，3-D定位探测器，结合我们小组正在研究的新的事件处理算法，可以在分辨率，对比度和重建图像信噪比方面取得实质性的改进。影响：如果成功，这项研究将提高PET检测、可视化和量化低浓度PET示踪剂在感兴趣的细胞中积累的能力，从而提高信号检测能力，应用于转化心血管、神经和癌症研究。