Development of a Preclinical High-Sensitivity DOI-PET/MRI

 描述(由申请人提供)：将正电子发射计算机断层扫描和核磁共振成像结合成一种混合设备，在临床和临床前环境中都具有作为研究工具的巨大潜力。与PET/CT相比，同步PET/MRI是独一无二的，因为它允许同时从两种模式采集图像，这在监控时变过程中尤其有价值，例如成像过程中的干预效果，或者当需要在PET和MRI之间进行最高程度的空间配准时。我们最近在急性脑缺氧-缺血模型中进行了活体成像研究，在这种模型中，生理的快速变化发生在几分钟的量级上，这为同步PET/MRI的应用提供了一个有趣的例子。虽然PET/MR系统最近已经可以用于人体研究，但临床前领域仍然缺乏真正集成的最先进的系统来实现这些类型的研究 在小动物身上完成，以支持基础和临床前研究。此外，现有的用于同时成像的小动物PET/MRI原型没有充分开发检测灵敏度的潜力，因为它们没有使用相互作用深度(DOI)编码检测器，因此在检测器厚度和效率方面做出了妥协，以维持空间分辨率低计数率的情况。由于稳定性有限或缺乏可靠的衰减校正技术，它们的绝对量化精度也往往受到限制。这项建议的目的是为小鼠和大鼠开发最先进的DOI-PET/MRI全身联合成像，它将使用厚实的闪烁晶体提供~12-16%的灵敏度和1.0 mm量级的空间分辨率。这将是迄今为止开发的最高灵敏度的临床前PET/MRI系统，专为定量动态PET研究与先进的MRI序列相结合而设计，用于神经学、肿瘤学和心脏病学领域的研究。该系统将采用基于MR兼容硅光电倍增管(SiPM)的像素化LSO块探测器，采用基于双端读出的连续DOI编码，并采用新颖而高效的读出方法。此外，我们还将开发一种程序来准确估计PET/MRI FOV内的对象线圈和对象床的对象衰减和衰减，以提供对衰减和散射的完全校正，从而提高小动物系统的量化精度。最后，我们将基于仔细测量PET和MRI系统之间的任何相互干扰的体模实验，并通过在脑缺血-缺氧模型中执行概念验证性小动物研究来验证同时获得的体内PET和MRI测量的定量准确性，来研究该PET/MRI系统的定量性能。

 DESCRIPTION (provided by applicant): The combination of PET and MRI into a hybrid device offers great potential as a research tool in both the clinical and preclinical setting. In contrastto PET/CT, simultaneous PET/MRI is unique as it allows for concurrent acquisition of images from both modalities which is especially valuable in monitoring time-varying processes, for example the effect of an intervention during imaging, or when the highest degree of spatial registration between PET and MRI is required. We have recently conducted in vivo imaging studies in models of acute cerebral hypoxia-ischemia, in which rapid changes in physiology occur on the order of minutes, providing an interesting example of an application for simultaneous PET/MRI. While PET/MR systems have recently become available for human studies, the preclinical field is still lacking truly integrated state-of-the-art systems that would enable these kinds of studies to be done in small animals in support of basic and preclinical research. Furthermore, existing small animal PET/MRI prototypes for simultaneous imaging do not exploit the full potential of detection sensitivity, as they do not use depth-of-interaction (DOI)-encoding detectors and therefore compromise on detector thickness and efficiency to maintain spatial resolution low count rate scenarios. They also are often limited in their absolute quantification accuracy owing to limited stability or the absence of reliable attenuation correction techniques. The purpose of this proposal is to develop a state-of-the-art whole body combined DOI-PET/MRI for mice and rats which will use thick scintillation crystals to provide a sensitivity of ~12-16% and a spatial resolution on the order of 1.0 mm. This will be the highest sensitivity preclinical PET/MRI system developed to date and is designed for quantitative dynamic PET studies in combination with advanced MRI sequences for research in the areas of neurology, oncology and cardiology. This system will employ MR-compatible silicon photomultiplier (SiPM)-based pixelated LSO block detectors with continuous DOI encoding based on dual- ended readout with a novel and highly efficient readout approach. We will furthermore develop a procedure to accurately estimate subject attenuation and attenuation of MR coils and subject bed inside the PET/MRI FOV to provide full correction of attenuation and scatter thus enhancing quantification accuracy in small-animal systems. Finally we will investigate the quantitative performance of this PET/MRI system based on phantom experiments that carefully measure any mutual interference between the PET and MRI systems and also by performing a proof-of-concept small-animal study in a cerebral ischemia-hypoxia model to demonstrate quantitative accuracy of in vivo PET and MRI measurements acquired simultaneously versus separately.