A High Resolution and High Sensitivity Dedicated Mouse Brain PET Scanner

描述（由申请人提供）：现有的小动物PET扫描仪的性能仍然是探测器而不是物理限制。小型动物PET扫描仪的灵敏度和空间分辨率的显著提高，不仅可以改善我们目前能够可视化的信号的量化（通过减少部分体积效应和增加信噪比），而且还可以开辟当代动物PET系统无法达到的重要新应用。原始应用的目标是开发深度编码PET探测器，通过使用位置敏感雪崩光电二极管（psapd）的高效率和精细像素闪烁体阵列的双端读出，同时表现出高空间分辨率和高效率。在当前资助的第四年，我们成功地开发了矩形和锥形氧化硅酸镥（LSO）阵列，晶体尺寸小至0.5毫米，效率非常高（20毫米厚的探测器），相互作用深度（DOI）分辨率为~ 2毫米。实验结果表明，与商用小动物PET系统中使用的探测器相比，该探测器的探测效率、空间分辨率和空间分辨率均匀性都得到了很大的提高。本次更新的目的是应用该探测器技术，开发用于小鼠脑分子成像研究的高空间分辨率（~0.5 mm）和高灵敏度（~20%）的临床前PET扫描仪。拟议的研究计划还将涉及开发新的数据校正和图像重建算法，以充分利用这些探测器的高空间和DOI能力，并将扫描仪应用于选定的概念验证小鼠脑成像研究。本提案的目标是1)为拟议的扫描仪开发电子和数据采集；2)开发晶体尺寸更小的深度编码探测器；3)测量正电子距离和光子共线对PET扫描仪空间分辨率的贡献；4)模拟龙门旋转和连续床台运动是否会提高所提出的扫描仪的图像质量；5)构建拟建的PET扫描仪；6)开发扫描仪的重建和校正算法；7)评估扫描仪的性能；8)进行选定的小鼠体内脑成像研究。这项提议的总体影响是，它将导致基于新型深度编码固态探测器和锥形闪烁体阵列的临床前PET扫描仪，为小鼠大脑的分子成像提供前所未有的空间分辨率和灵敏度组合。这将为发育和衰老的定量分子成像研究、小鼠疾病模型（阿尔茨海默病、帕金森病、中风和神经发育障碍等）的研究以及基于小分子、多肽、纳米颗粒、基因疗法或细胞疗法的新治疗策略的监测开辟新的机会。

DESCRIPTION (provided by applicant): The performance of available small animal PET scanners continues to be detector rather than physics limited. Significant improvements in the sensitivity and spatial resolution of a small animal PET scanner would not only improve the quantification of signals that we are currently able to visualize (by reducing partial volume effects and increasing signal-to-noise) but would also open up important new applications that are beyond the reach of contemporary animal PET systems. The goal of the original application was to develop depth-encoding PET detectors that simultaneously exhibit high spatial resolution and high efficiency by using dual-ended readout of high-efficiency and finely pixelated scintillator arrays with position sensitive avalanche photodiodes (PSAPDs). During the fourth year of the current grant, we have successfully developed both rectangular and tapered lutetium oxyorthosilicate (LSO) arrays with crystal sizes down to 0.5 mm, very high efficiency (20 mm thick detectors) and a depth of interaction (DOI) resolution of ~ 2 mm. A prototype PET scanner was developed using these depth encoding detectors and it was shown that detector efficiency, spatial resolution and spatial resolution uniformity can be greatly improved by using our new detectors compared with the detectors used in commercial small-animal PET systems. The aims of this renewal are to apply this detector technology and develop a high spatial resolution (~0.5 mm) and high sensitivity (~20%) preclinical PET scanner designed for molecular imaging studies in the mouse brain. The proposed research plan will also involve developing novel data correction and image reconstruction algorithms to fully utilize the high spatial and DOI capabilities of these detectors and to apply the scanner for selected proof-of-concept mouse brain imaging studies. The goals of this proposal are 1) to develop electronics and data acquisition for the proposed scanner; 2) to develop depth encoding detectors with even smaller crystal size; 3) to measure the contributions of positron range and photon acolinearity to the spatial resolution of a PET scanner; 4) to simulate whether gantry rotation and continuous bed motion will improve the image quality of the proposed scanner; 5) to construct the proposed PET scanner; 6) to develop reconstruction and correction algorithms for the scanner; 7) to evaluate the performance of the scanner; 8) to perform selected in-vivo mouse brain imaging studies. The overall impact of this proposal is that it will lead to a preclinical PET scanner based on novel depth- encoding solid state detectors and tapered scintillator arrays that provides an unprecedented combination of spatial resolution and sensitivity for molecular imaging of the mouse brain. This will open up new opportunities for quantitative molecular imaging studies of development and aging, studies of murine disease models (Alzheimer's disease, Parkinson's disease, stroke, and neurodevelopmental disorders to name but a few), and monitoring of novel therapeutic strategies based on small molecules, peptides, nanoparticles, gene therapies or cellular therapies. PUBLIC HEALTH RELEVANCE: This proposal seeks to develop a positron emission tomography (PET) scanner that has an unprecedented combination of spatial resolution and sensitivity for imaging the mouse brain. The innovation in this scanner is the use of thick depth-encoding detectors arranged in a small ring diameter to increase the sensitivity and the use of tapered scintillator arrays to further increase the sensitivity. High spatial resolution is achieved by using arrays with very small crystal size and high depth-of-interaction resolution. This scanner will drastically improve the capability of PET to aid in the understanding and treatment of major neurological disorders and diseases such as Alzheimer's disease, Parkinson's disease, stroke and epilepsy.