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

描述(由申请人提供)：生物靶向标记物的成像因其提供早期疾病检测、改进的个体化风险分层和监测医疗治疗的潜力而受到越来越多的关注。分子示踪剂~(123)I-间碘苯基胍(~(123)I-MIBG)是去甲肾上腺素的类似物，为心脏交感神经的成像提供了一种非侵入性的方法。该项目的总体目标是开发用于量化心力衰竭的123I-MIBG分子成像的临床软件工具，以促进这一重要成像技术的临床转化为常规临床实践。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123I-MIBG SPECT成像的量化的软件方法；2)开发一种新的软件方法，用于从重建的AIM 1的123I-MIBG SPECT图像的平面投影投影精确地自动定量HMR和WR；以及3)使用对心脏123I-MIBG成像第三阶段临床试验的图像数据和临床结果的回顾分析，对在AIM 1和2中开发的软件工具进行临床验证。最近完成的第三阶段试验的结果表明，123I-MIBG心脏成像可以确定两年内发生致命心脏事件的风险较低的心力衰竭患者亚群，并有可能确定心力衰竭进展、室性心律失常或心脏死亡的可能性增加的患者。这些有希望的结果是基于简单的心脏摄取123I-MIBG的全球定量测量，例如心脏与纵隔的比率(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，缺乏标准化的平面成像采集和处理协议限制了123I-MIBG的广泛应用。此外，单光子发射计算机断层扫描(SPECT)成像有可能更准确地定量123I-MIBG的摄取和滞留。不幸的是，~(123)I-MIBG显像剂的物理性质以及心力衰竭患者交感神经元的快速清除和低心脏滞留的特点阻碍了SPECT的定量。拟议的项目将通过开发一种全面的方法来改进123I-MIBG SPECT的量化，包括应用SPECT迭代重建的最新进展，修正光子衰减、散射和间隔穿透，以及探测器响应建模，以及用于自动分割发射图像中的左心室(LV)的新方法，从而解决这些限制。我们预计，拟议项目的成功结果将提供自动化的量化方法、软件工具和验证数据，这些将在未来为心力衰竭的123I-MIBG分子成像的获取和处理制定指南和标准的努力中非常有用。 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，它可以实现更个性化的患者护理，改进对不良事件的风险评估，并有可能降低与心力衰竭相关的医疗成本。这项提议将开发必要的成像软件，将分子成像技术推向临床实践，并促进这一在治疗心力衰竭患者方面的有希望的进步在临床上得到更广泛的采用。

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.