Quantitative Molecular Imaging of Heart Failure by 123I-MIBG SPECT

描述（由申请人提供）：生物靶向标记物成像因其提供早期疾病检测、改善个体化风险分层和监测药物治疗的潜力而受到越来越多的关注。分子示踪剂123 I-MIBG（123 I-MIBG）是去甲肾上腺素的类似物，为心脏交感神经支配成像提供了一种非侵入性方法。本项目的总体目标是开发用于心力衰竭123 I-MIBG分子成像定量的临床软件工具，以促进这一重要成像技术在常规临床实践中的临床转化。该项目的具体目标是：1）开发用于改进心力衰竭患者的临床123 I-MIBG SPECT成像的量化的软件方法，2）开发用于从Aim 1的重建的123 I-MIBG SPECT图像投影的平面视图精确自动量化HMR和WR的新的软件方法，以及3）使用来自心脏123 I-MIBG成像的III期临床试验的图像数据和临床结果的回顾性分析，对在目标1和2中开发的软件工具进行临床验证。最近完成的III期临床试验的结果表明，123 I-MIBG心脏成像可以识别2年内发生致命性心脏事件风险较低的心力衰竭患者亚群，并有可能定义心力衰竭进展、室性心律失常或心源性死亡可能性增加的患者。这些有希望的结果是基于简单的全球定量测量心脏123 I-MIBG的摄取，如心脏纵隔比（HMR）和洗脱率（WR），使用平面放射性核素成像。然而，最近的数据表明，缺乏标准化的采集和处理协议的平面成像限制了123 I-MIBG的广泛使用的适用性。此外，单光子发射计算机断层扫描（SPECT）成像具有更准确的定量123 I-MIBG摄取和保留的潜力。不幸的是，SPECT定量已被成像123 I标记的示踪剂的物理性质，和特征性的快速交感神经元洗脱和低心脏滞留的123 I-MIBG在心力衰竭患者的阻碍。拟议的项目将通过开发一种全面的方法来改善123 I-MIBG SPECT的量化，包括应用SPECT迭代重建的最新进展，校正光子衰减，散射和间隔穿透和探测器响应建模以及发射图像中左心室（LV）自动分割的新方法来解决这些限制。我们预计，成功的结果，拟议的项目将提供自动化的定量方法，软件工具和验证数据，这将是非常有用的，在未来的努力，以确定准则和标准的收购和处理的123 I-MIBG分子成像的心力衰竭。 公共卫生相关性：使用分子成像技术管理心力衰竭患者是一项最新进展，可实现更个性化的患者护理，改善不良事件风险评估，并可能降低与心力衰竭相关的医疗保健成本。该提案将开发必要的成像软件，以推进分子成像技术的临床实践，并促进更广泛的临床采用这一有前途的进展，在照顾心力衰竭患者。

DESCRIPTION (provided by applicant): Imaging of biologically targeted markers is gaining increased attention for its potential to provide early disease detection, improved individualized risk stratification and monitoring of medical therapies. The molecular tracer 123I-metaiodobenzylguanidine (123I-MIBG) is an analog of norepinephrine which provides a noninvasive approach for imaging the sympathetic innervations of the heart. The overall goal of this project is to develop clinical software tools for quantification of 123I-MIBG molecular imaging of heart failure to facilitate clinical translation of this important imaging technology to routine clinical practice. The specific aims of this project are to: 1) develop software methods for improved quantification of clinical 123I-MIBG SPECT imaging of heart failure patients, 2) develop a novel software method for accurate automated quantification of HMR and WR from planar views projected from the reconstructed 123I-MIBG SPECT images of Aim 1, and 3) clinical validation of the software tools developed in Aims 1 and 2 using retrospective analysis of image data and clinical outcomes from Phase III clinical trials of cardiac 123I-MIBG imaging. The results of recently completed Phase III trials have demonstrated that 123I-MIBG cardiac imaging can identify a subpopulation of heart failure patients with low 2-year risk of fatal cardiac events and the potential to define patients with increased likelihood of heart failure progression, ventricular arrhythmias, or cardiac death. These promising results are based on simple global quantitative measures of cardiac 123I-MIBG uptake, such as the heart-to-mediastinum ratio (HMR) and washout rate (WR), using planar radionuclide imaging. However, recent data has shown that the lack of standardized acquisition and processing protocols for planar imaging has limited the applicability of 123I-MIBG for widespread use. Moreover, single photon emission computed tomography (SPECT) imaging has the potential for more accurate quantification of 123I-MIBG uptake and retention. Unfortunately SPECT quantification has been hampered by the physical properties of imaging 123I labeled tracers, and the characteristically rapid sympathetic neuronal washout and low cardiac retention of 123I-MIBG in heart failure patients. The proposed project will address these limitations by developing a comprehensive approach for improved quantification of 123I-MIBG SPECT, including the application of recent advances in SPECT iterative reconstruction with corrections for photon attenuation, scatter and septal penetration and detector response modeling and novel methods for automated segmentation of the left ventricle (LV) in emission images. We anticipate that the successful outcome of the proposed project will provide automated quantification methods, software tools and validation data that will be extremely useful in future efforts to define guidelines and standards for the acquisition and processing of 123I-MIBG molecular imaging of heart failure. PUBLIC HEALTH RELEVANCE: The use of molecular imaging for management of heart failure patients is a recent advance that enables more individualized patient care, improved assessment of risk for adverse events, and can potentially reduce the healthcare costs associated with heart failure. This proposal will develop imaging software necessary for advancing molecular imaging technology to the clinic practice and facilitate wider clinical adoption of this promising advance in the care of heart failure patients.