Three Dimensional Electrocardiographic Imaging

描述（由申请人提供）：该拟议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，该方法可以在三维（3-D）心脏内无创地标测心脏电活动。仅在美国，每年就有超过40万人死于室性心动过速（VT）和室颤。有效的成像技术的发展是至关重要的介入（和潜在的药理学）的方法来预防和治疗这些恶性心律失常的演变。因此，非侵入性的激动序列和心律失常起源部位的定位映射将对许多患者具有巨大的价值。拟议的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，该方法已率先由PI，它能够从非侵入性体表电位图的3-D心肌成像的激活序列。虽然在3-D中解决心脏逆问题转化为逆问题中的严重欠定性质，但是建议使用心脏兴奋模型，其中并入心脏电生理学知识，将重新定义这种关系。同样新颖的是，所提出的研究是严格验证所提出的3- DEIT在一个封闭的胸部动物模型评估的3-D心内映射。我们在动物模型中的初步结果证明，从无创体表电位测量和计算机断层扫描图像（经3-D心内标测测试）重建整个3-D心肌的激活序列，证明了拟议研究的可行性。该项目的具体目标是：目的1）开发3-D心电图成像方法并在计算机模拟中对其进行评估;目的2）在家兔心脏中使用3-D心内标测在心室起搏期间验证体内3-D心电图成像;目的3）在实验诱导心力衰竭的家兔室性心动过速期间验证3-D心电图成像。拟议研究的成功完成将使我们能够建立一种新的非侵入性心脏功能成像方法，可以定义病理性心律失常（目前不可能）的起始位点，激活序列（和潜在的致心律失常机制）。这项工作的结果也将提供一个关键的基础，建立拟议的3-DEIT作为一种新的断层成像模式，以指导导管消融心律失常，并制定和评估新的治疗方法的效果，针对特定的心律失常机制，治疗室性心动过速患者的心力衰竭（和其他心脏疾病）。

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).