Molecular Imaging of Cardiac Hypertrophy Using microPET and Pinhole SPECT

描述（由申请人提供）：充血性心力衰竭（CHF）是美国的主要死亡原因，在我们的老龄化人口中是一个日益严重的问题。本研究拟以自发性高血压大鼠（SHR）为高血压相关病理生理学模型，利用临床针孔SPECT/CT扫描仪，研究放射性核素分子成像技术，定量研究心脏的变形、灌注、神经支配和代谢变化。人类和SHR对CHF治疗的反应相似，表明SHR是高血压所致心力衰竭主要类别的适当模型。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，离体磁共振扩散张量成像、同步PET/MRI和组织病理学将提供机械和生物化学结构相关性。使用SHR模型的初步数据表明，这种技术发展是可能的。新技术将改善诊断，监测进展，并评估疾病的治疗。由于我们的技术方法使用针孔临床SPECT/CT和放射性药物，反映血流，代谢，神经支配和结构力学，因此开发的技术可以直接转化为临床仪器，以更好地管理心力衰竭患者。该项目的独特之处在于开发了用于从缓慢旋转的相机成像大鼠快速循环的投影中估计输入函数的技术，应用机械模型来检测肥大心脏中变形的早期变化，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，和准直器响应由蒙特卡罗模拟确定。结合新的动态和传统的临床成像协议与改进的心脏描述（生理，机械和生化）将使我们能够获得更好的心脏特性的规范，并研究由疾病引起的心脏分子变化如何影响这些特性。对科学界有用的基于针孔的动物断层扫描的创新是准直器设计、机架运动校准、锥形束几何形状的重建算法以及衰减和散射的时空建模。这些技术的发展将提供定量灌注，生化动力学和壁动力学的方法。

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.