New Design of a Sensor for Ultrahigh Performance SPECT Imaging

描述（由申请人提供）：在各种功能成像技术中，SPECT在小动物疾病模型研究以及患者护理中发挥着重要且日益重要的作用。许多SPECT标记的成像探针具有高度特异性的分布，背景非常少，被用于测量小动物中广泛的重要生物学参数，包括底物代谢，血流，缺氧，蛋白质合成和受体特性。近年来，通过体内转基因表达成像方法的发展，这种重要方式的实用性得到了显着增强。此外，SPECT能够双同位素成像，用于将两个生物过程与单个成像研究相关联。最近对小动物SPECT的需求也受到制药行业的推动，其中生物过程的体内定量以测量药剂的作用机制及其在作用部位的浓度是必要的。 这些应用中的每一个都需要出色的空间分辨率，这不仅是因为要成像的细节尺度很小，而且还因为需要检测和估计任务。同时，高灵敏度也是必不可少的，因为它对于减少图像采集时间、提高时间分辨率、增加患者/动物研究的吞吐量以及减少患者剂量至关重要。虽然基于CCD/准直器的SPECT检测器的新发展已经通过展示亚100微米的固有空间精度来解决分辨率问题，但是还没有实现能够同时提供高分辨率和高灵敏度的检测器。这主要是由于众所周知的效率-分辨率权衡在当前闪烁器和视差误差所产生的倾斜3射线入射在任何闪烁器。因此，能够克服传统的效率-分辨率折衷的新型闪烁体的开发和最小化视差误差的方法的实现对于实现真正的高分辨率、高灵敏度SPECT检测器是至关重要的。 为了解决这些问题，我们建议开发一种新的传感器的基础上的闪烁体的一个独特的设计，耦合到一个非常高的空间分辨率读出。具体而言，闪烁体将为SPECT成像中通常使用的3种能量提供非常高的空间分辨率和高灵敏度，并将允许对每个事件进行相互作用深度（DOI）估计。读出传感器固有的高空间分辨率沿着DOI信息将使检测器能够以具有成本效益的方式实现极其精细和均匀的空间分辨率和高灵敏度。 公共卫生相关性：提出的研究的目标是开发一个非常高的性能，成本效益的小动物单光子发射计算机断层扫描（SPECT）成像传感器。在其他益处中，SPECT研究非常适合于成像放射性标记的抗体和其他物质，其可用于定位和表征小动物中的肿瘤，并且非常适合于开发用于诊断和跟踪人类疾病治疗的新放射性标记剂。这种传感器的开发将显著提高可以进行测量的分辨率和灵敏度，并且这反过来将允许开发用于诊断和分期的上级方法、药物和技术，以及用于减少甚至治愈某些癌症、心脏疾病和循环系统紊乱的进展的治疗。

DESCRIPTION (provided by applicant): Among the various functional imaging techniques, SPECT maintains an important and growing role in the study of disease models in small animals as well as in patient care. Many SPECT-labeled imaging probes that have highly specific distributions with very little background are being used to measure a wide range of biological parameters of importance in small animals including substrate metabolism, blood flow, hypoxia, protein synthesis and receptor characteristics. The utility of this important modality has been significantly enhanced in recent years by the development of methods to image transgene expression in vivo. Furthermore, SPECT is capable of dual-isotope imaging for correlating two biological processes with a single imaging study. Recent demand for small animal SPECT has also been driven by the pharmaceutical industry, where in vivo quantification of biological processes to measure an agent's mechanism of action and its concentration at the site of action is necessary. Each of these applications requires excellent spatial resolution not only because of the small scale of the details to be imaged but also for demanding detection and estimation tasks. Simultaneously, high sensitivity is also essential, as it is critically important for reducing image acquisition time, improving temporal resolution, increasing throughput for patient/animal studies, and reducing patient dose. While new developments in CCD/scintillator-based SPECT detectors have addressed the resolution issue by demonstrating sub- 100 micron intrinsic spatial accuracies, a detector that can simultaneously provide high-resolution and high- sensitivity has not yet been realized. This is primarily due to the well-known efficiency-resolution tradeoff in current scintillators and the parallax errors arising from oblique 3-ray incidences in any scintillator. Thus, the development of a novel scintillator that can overcome the traditional efficiency-resolution tradeoff and implementation of methodologies to minimize parallax errors is crucial for realizing a truly high-resolution, high- sensitivity SPECT detector. To address these issues, we propose to develop a novel sensor based on a scintillator of a unique design, coupled to a very high spatial resolution readout. Specifically, the scintillator will provide very high spatial resolution and high-sensitivity for 3 energies typically used in SPECT imaging and will permit depth-of- interaction (DOI) estimation for every event. The high spatial resolution intrinsic to the readout sensor, along with the DOI information, will enable the detector to achieve extremely fine and uniform spatial resolution and high sensitivity, in a cost-effective manner. PUBLIC HEALTH RELEVANCE: The goal of the proposed research is to develop a very high performance, cost-effective sensor for small animal single photon emission computed tomography (SPECT) imaging. Among other benefits, SPECT studies are well suited to imaging radiolabeled antibodies and other substances that can be used to localize and characterize tumors in small animals and are well suited to the development of new radiolabeled agents for diagnosing and tracking the treatment of diseases in humans. The development of such a sensor will significantly improve the resolution and sensitivity with which measurements can be made, and this, in turn, will allow the development of superior methods, drugs and technologies to diagnose and stage, and treatments to curtail the progression of and even cure, certain cancers, diseases of the heart and disorders of the circulatory system.