Three Dimensional Electrocardiographic Imaging

描述（由申请人提供）：本拟研究项目的长期目标是建立一种高分辨率无创三维心电图成像（3- deit）方法，该方法可以无创地绘制三维（3- d）心脏内的心电活动。仅在美国，每年就有超过40万人死于室性心动过速（VT）和心室颤动。有效成像技术的发展对于预防和治疗这些恶性心律失常的介入（和潜在的药理学）方法的发展至关重要。因此，无创性地绘制激活序列和定位心律失常的起源部位对许多患者具有巨大的价值。拟议研究项目的最终目标是建立和验证一种新的3-D心脏电成像方法，该方法由PI首创，能够通过无创体表电位图对3-D心肌的激活序列进行成像。虽然在3-D中解决心脏逆问题会转化为严重的逆问题不确定性质，但建议使用心脏兴奋模型，其中包含心脏电生理知识，将重新定义这种关系。该研究的另一个新颖之处在于，通过3- d心内测绘评估，在闭胸动物模型中严格验证了所提出的3- DEIT。我们在动物模型中的初步结果表明，通过无创体表电位测量和计算机断层扫描图像（如3-D心内测绘测试）重建了整个3-D心肌的激活序列，证明了所提出研究的可行性。该项目的具体目标是：目标1)开发三维心电图成像方法并在计算机模拟中对其进行评估；目的2)利用兔心脏三维心内成像验证心室起搏期间的活体三维心电图成像；目的3)验证实验性心力衰竭兔室性心动过速的三维心电图成像。该研究的成功完成将使我们能够建立一种新的无创心功能成像方法，该方法可以定义病理性心律失常的起始位点、激活序列（以及潜在的致心律失常机制）（目前尚不可能）。这项工作的结果也将为建立提议的3-DEIT作为一种新的断层成像方式来指导心律失常的导管消融，以及开发和评估针对特定心律失常机制的新治疗方法的效果，以治疗心力衰竭（和其他心脏疾病）患者的VT。

DESCRIPTION (provided by applicant): The long-term goal of this proposed research project is to establish a high-resolution noninvasive 3- dimensional electrocardiographic imaging (3-DEIT) methodology that can noninvasively map cardiac electrical activity within the 3-dimensional (3-D) heart. Sudden death from ventricular tachycardia (VT) and ventricular fibrillation claims over 400,000 lives each year in the United States alone. Development of effective imaging technologies is critical in the evolution of interventional (and potentially pharmacologic) approaches to prevent and treat these malignant arrhythmias. Noninvasive mapping of activation sequence and localization of sites of origin of arrhythmia would thus be of enormous value for numerous patients. The ultimate goal of the proposed research project is to establish and validate a novel 3-D cardiac electrical imaging approach that has been pioneered by the PI which is able to image the activation sequence over the 3-D myocardium from noninvasive body surface potential maps. Although solving the cardiac inverse problem in 3-D translates into severe underdetermined nature in the inverse problem, the proposed use of a heart excitation model, in which cardiac electrophysiological knowledge is incorporated, will redefine this relationship. Also novel to the proposed research is rigorously validating the proposed 3- DEIT in a closed-chest animal model as assessed by 3-D intracardiac mapping. Our preliminary results in an animal model, that demonstrate reconstruction of activation sequence throughout the 3-D myocardium from noninvasive body surface potential measurements and computer tomography images (as tested with 3-D intracardiac mapping), attest to the feasibility of the proposed studies. The specific aims of the proposed project are: Aim 1) To develop 3-D electrocardiographic imaging methods and evaluate it in computer simulations; Aim 2) To validate 3-D electrocardiographic imaging in vivo during ventricular pacing using 3-D intracardiac mapping in the rabbit heart; and Aim 3) To validate 3-D electrocardiographic imaging during ventricular tachycardia in rabbits with experimentally-induced heart failure. The successful completion of the proposed research would enable us to establish a novel noninvasive cardiac functional imaging methodology that could define initiation sites, activation sequences (and potentially arrhythmogenic mechanisms) for pathologic arrhythmias (which is currently not possible). The results of this work would also provide the critical foundation for establishing the proposed 3-DEIT as a novel tomographic imaging modality to guide catheter ablation of arrhythmias, and to develop and to assess the effects of new therapeutic approaches targeted to specific arrhythmia mechanisms for the treatment of VT in patients with heart failure (and other cardiac diseases).