Molecular Imaging of Cardiac Hypertrophy Using microPET and Pinhole SPECT

描述(申请人提供)：充血性心力衰竭(CHF)在美国是一个主要的死亡原因，在我们老龄化的人口中是一个日益严重的问题。这项拟议的项目旨在开发放射性核素分子成像技术，使用临床针孔SPECT/CT扫描仪，以自发性高血压大鼠(SHR)作为高血压相关病理生理学的模型，量化心脏变形、灌流、神经和代谢的变化。人类和SHR对CHF治疗反应的相似性表明，SHR是一种适合于主要类型的高血压所致心力衰竭的模型。MicroPET和针孔SPECT的联合应用为改进和评估已开发的技术提供了工具。此外，体外磁共振扩散张量成像、同步的PET/MRI和组织病理学将提供机械和生化结构上的关联。使用SHR模型的初步数据表明，这种技术发展是可能的。这些新技术将改进诊断、监测进展并评估治疗方法。由于我们的技术方法使用针孔临床SPECT/CT和反映血流、新陈代谢、神经支配和结构力学的放射性药物，因此开发的技术可以直接转化为临床仪器，以便更好地管理心力衰竭患者。该项目的独特之处在于开发了从大鼠缓慢旋转的摄像机成像快速循环的投影中估计输入函数的技术，应用力学模型来检测肥大心脏变形的早期变化，以及使用图像检测过程的模型来量化示踪剂的动力学，其中衰减、散射和准直器响应的影响是通过蒙特卡罗模拟确定的。将新的动态和传统的临床成像方案与对心脏(生理、机械和生化)的改进描述相结合，将使我们能够更好地指定心脏的属性，并研究疾病导致的心脏分子变化如何影响这些属性。对科学界有用的基于针孔的动物断层扫描的创新包括准直器设计、龙门运动校准、锥形光束几何重建算法以及衰减和散射的时空建模。这些技术的发展将为量化血流灌注、生化动力学和室壁动力学提供方法。

DESCRIPTION (provided by applicant): Congestive heart failure (CHF), a major cause of death in the US, is a growing problem in our aging population. This proposed project is directed at developing radionuclide molecular imaging technologies using a clinical pinhole SPECT/CT scanner to quantify the changes in deformation, perfusion, innervation, and metabolism in the heart using the spontaneous hypertensive rat (SHR) as a model of hypertensive related pathophysiology. The similarity in the response to CHF treatment for humans and for SHR suggests that the SHR is an appropriate model for a major class of heart failures that are due to hypertension. The combined application of both microPET and pinhole SPECT provides tools to improve and evaluate developed technology. In addition, ex vivo magnetic resonance diffusion tensor imaging, simultaneous PET/MRI, and histopathology will provide mechanical and biochemical structural correlates. Preliminary data using the SHR model indicate that such technological developments are possible. The new technologies will improve diagnosis, monitor progression, and evaluate therapy for the disease. Because our technological approach uses pinhole clinical SPECT/CT and radiopharmaceuticals that reflect flow, metabolism, innervation, and structural mechanics, the developed techniques can be directly translated to clinical instruments for better management of patients with heart failure. The uniqueness of this project is the development of techniques for estimating input function from projections of a slow rotating camera imaging fast circulation in a rat, the application of mechanical models to detect early changes in deformation in the hypertrophied heart, and the quantification of the kinetics of tracers using models of the image detection process in which the effects of attenuation, scatter, and collimator response are determined from Monte Carlo simulations. Combining new dynamic and conventional clinical imaging protocols with improved descriptions of the heart (physiological, mechanical, and biochemical) will allow us to obtain better specification of the heart's properties and to study how molecular changes in the heart caused by disease affect these properties. Innovations for pinhole-based tomography of animals that are useful to the scientific community are collimator design, gantry motion calibration, reconstruction algorithms for cone beam geometry, and spatiotemporal modeling of attenuation and scatter. The development of these technologies will provide methods for quantifying perfusion, biochemical kinetics, and wall dynamics.