EVALUATION OF CARDIAC AUTONOMIC INNERVATION BY PET

通过 PET 评估心脏自主神经支配

• 批准号: 2223746
• 负责人: DONALD M WIELAND
• 金额: $ 31.09万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-02-01 至 1997-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2223746
• 关键词: autoradiography; diabetic neuropathy; electrophysiology; heart innervation; heart transplantation; histopathology; human subject; longitudinal human study; myocardium disorder; neurons; noninvasive diagnosis; positron emission tomography; radiotracer; ventricular fibrillation

Evaluation of the myocardial autonomic nervous system has previously been limited to animal models because of the unavailability of noninvasive methods, which could be used in humans. With the advent of radiopharmaceuticals which specifically delineate presynaptic and parasympathetic nerve terminals, integrity of the autonomic nervous system can be quantitatively assessed using positron emission tomography (PET). Animal studies have validated these new imaging approaches and initial clinical studies have provided excellent image quality necessary for the regional definition of tracer kinetics. This proposal will focus on the clinical application of neuronal imaging using PET in cardiac disease states which are known to affect the autonomic innervation of the heart. These studies will provide the base for the possible clinical application of these tracer approaches in the therapeutic management of patients. Initial studies with the catecholamine analogue C-11 hydroxyephedrine as well as parasympathetic tracer F-18 benzovesamicol will focus on the definition of tracer kinetics in the normal and denervated human heart. Incidence and time course in reinnervation of the human transplanted heart will be investigated since preliminary data suggest regional catecholamine uptake sites in patients with remote cardiac transplant. Longitudinal studies in patients with diabetic neuropathy using tracers for the sympathetic as well as the parasympathetic nervous system may elucidate the time course and natural history of autonomic dysfunction in this patient population. The major effort of this proposal will focus on the definition of the sympathetic and parasympathetic nervous system in patients with dilated cardiomyopathy. Regional myocardial kinetics of C-11 hydroxyephedrine will be used to quantitate the catecholamine storage capacity of the presynaptic neuron. Scintigraphic measurements will be correlated with regional electrophysiologic parameters such as effective refractory period and fibrillation threshold using electrophysiologic mapping techniques during open heart surgery. These functional measurements will be supplemented by tissue analysis for catecholamine content and histopathological integrity of the neuronal structures in corresponding sites. In addition, patients undergoing cardiac transplantation will undergo PET imaging prior to this procedure and the scintigraphic results will be compared with regional tissue analysis of the ex-planted cardiomyopathic heart using biochemical and autoradiographic techniques. This integrated approach using imaging technologies, electrophysiologic testing, and in-vitro tissue characterization including autoradiography will represent an unique definition of the autonomic nervous system in patients with various degree of dilated cardiomyopathy.

此前曾对心肌自主神经系统进行过评估 由于缺乏非侵入性手段，仅限于动物模型 方法，可用于人类。 随着 专门描绘突触前和突触前的放射性药物 副交感神经末梢，自主神经系统的完整性 可以使用正电子发射断层扫描（PET）进行定量评估。 动物研究验证了这些新的成像方法和初步结果 临床研究提供了必要的卓越图像质量 示踪动力学的区域定义。 该提案将重点关注 PET神经元成像在心脏病中的临床应用 已知影响心脏自主神经支配的状态。 这些研究将为可能的临床应用提供基础 这些示踪剂方法在患者治疗管理中的应用。 儿茶酚胺类似物 C-11 羟基麻黄碱的初步研究 以及副交感神经示踪剂 F-18 苯并维沙米考将重点关注 正常和去神经支配的人类心脏中示踪动力学的定义。 人类移植心脏神经支配的发生率和时间进程 将进行调查，因为初步数据表明区域儿茶酚胺 远程心脏移植患者的摄取位点。 纵向 使用示踪剂对糖尿病神经病变患者进行的研究 交感神经系统和副交感神经系统可以阐明 该患者自主神经功能障碍的时间过程和自然史 人口。 该提案的主要工作将集中在定义上 患者交感神经和副交感神经系统的变化 扩张型心肌病。 C-11 的局部心肌动力学 羟基麻黄碱将用于定量儿茶酚胺储存量 突触前神经元的能力。 闪烁照相测量将 与区域电生理参数相关，例如有效 使用电生理学测量不应期和颤动阈值 心脏直视手术期间的绘图技术。 这些功能性的 儿茶酚胺组织分析将补充测量结果 神经元结构的内容和组织病理学完整性 相应站点。 此外，接受心脏病治疗的患者 移植之前将进行 PET 成像，并且 闪烁扫描结果将与区域组织分析进行比较 使用生化和放射自显影技术体外移植心肌病心脏 技术。 这种综合方法使用成像技术、电生理学 测试和体外组织表征，包括放射自显影 将代表自主神经系统的独特定义 患有不同程度扩张型心肌病的患者。