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: 8248197
• 负责人: CRAIG S LEVIN
• 金额: $ 40.25万
• 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/8248197
• 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. 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系统来大幅提高正电子发射断层扫描(PET)的信号检测极限，该系统能够显著改善疾病细胞和分子特征的可视化和量化。我们将在以前工作中取得的进展的基础上，探索和开发用于小动物PET的三维位置敏感光子闪烁探测器技术的创新概念。拟议的项目首先将大大改进这一前景光明的探测器技术，大幅(而不是增量地)提高其性能，同时也使其实施起来更加实用。然后，我们将把这项先进的技术转化为具有可调视野的“盒形”小动物PET系统的小型原型，我们将利用一个新的多层探测器模块来构建该系统。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，其中每个晶体元素中的闪烁光收集纵横比非常高，即使对于0.5 mm宽度的元素也是如此。重建图像的0.5 mm分辨率目标也得益于盒形系统设计实现的显著改进的511keV光子灵敏度，原因我们将在本申请中阐明。闪烁晶体阵列与新颖的超薄、高增益位置灵敏光电探测器相耦合，采用创新的“边缘”配置，可在任何晶体内直接测量511keV光子相互作用深度(DOI)，并提高90%的闪烁光收集效率，而不受DOI的影响。由此产生的强健、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 mm的固有空间分辨率，有助于在存在背景活动的情况下增强PET信号的检测和量化。在该探测器模块的边沿分层布置中，入射光子穿过最小厚度为~2厘米、晶体堆积分数为70%的晶体，以提高高511keV光子的探测效率，而0.5 mm的DOI分辨率有助于在整个PET系统的敏感体积中保持空间分辨率的一致性。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511keV光子相互作用。对于PET探测器来说，这是一种不同寻常的能力，我们称之为“3-D定位”。这种能力对于获得所需的0.5 mm重建分辨率很重要，因为进入的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，建议的0.5 mm分辨率、高灵敏度、3-D定位检测器与我们团队正在研究的新事件处理算法相结合，可以显著提高分辨率、对比度和重建图像的信噪比。影响：如果成功，这项研究将提高PET检测、可视化和量化在感兴趣细胞中积累的低浓度PET示踪剂的能力，从而提高在转译心血管、神经和癌症研究中应用的信号检测能力。 与公共健康相关：我们建议通过改进我们在之前的资助下开发的探测器技术，并将这一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，这项工作将为非侵入性可视化和量化活体动物组织中的低丰度分子靶标带来对数顺序的改进。尽管有许多需要这种超低信号灵敏度的应用，但这一进展在跟踪和量化少数细胞的分布和增殖方面尤其重要，这一能力是非常需要的，以指导即将到来的基于细胞的新疗法的发展。