OPTO-ELECTRIC MAPPING OF ACTION POTENTIALS

描述（由申请人提供）：心律失常每年夺去美国300-40万人的生命。现有的治疗方法主要基于药物、手术、消融和植入式装置方法。诊断的主要障碍之一是无法无创记录人类患者的动作电位（AP）。唯一可用的技术是有创心内MAP导管，它提供了来自单个部位的高保真记录，迄今尚未被用于高分辨率制图。另外，光学定位技术允许记录成千上万的心外膜或心内膜ap，但它仅用于体外研究，尚未转化为临床电生理（EP）实验室。目前的临床EP研究依赖于电图，电图是由许多细胞产生的动作电位的空间集成电特征。因此，它们在复杂的传导和复极化情况下不容易解释。基于逆问题解的心电图成像（ECGi）的出现，提供了一个令人兴奋的机会，可以从体表电图测绘和使用CT或MRI的全胸成像开始无创地绘制心外膜电图。然而，这种方法只能提供电图，而不能提供动作电位。此外，体表电位测绘模式目前还不能重建心内膜电图，需要侵入性经静脉球囊或篮导管测绘。我们开发了一种新的基于体表电图测量和逆问题求解的非侵入性动作电位重建的AP ECGi方法。然而，关键问题是如何验证这些方法，因为没有高分辨率的绘图技术可用于直接绘制体内动作电位。在这个项目中，我们将开发一个离体验证平台，所有现有的ECG方法和我们的新AP ECGi可以直接比较，同时使用电图和光动作电位的映射。我们将创建一个离体3D模型，围绕langendorff灌注的人类或兔子心脏的人类胸腔。该系统将模拟人类胸腔中的活体心脏，并允许同时获取(i) 240个胸腔表面电图和（ii）使用电压敏感染料从心外膜获得光学动作电位的全景图。我们的新方法将通过AP ECGi的验证，使现有的无创临床心脏电生理仪器取得重大进展。此外，我们将把这些数据集提供给其他对验证他们自己的竞争性ECGi方法感兴趣的研究小组和公司。

DESCRIPTION (provided by applicant): Heart rhythm disorders claim 300-400,000 lives of Americans annually. Existing therapies are primarily based on pharmacological, surgical, ablative, and implantable device approaches. One of the major impediments in diagnostics is the inability to record action potentials (AP) in human patients noninvasively. The only available technique is an invasive intracardiac MAP catheter, which provides high fidelity recording from a single site and thus far has not been adopted for high resolution mapping. Alternatively, optical mapping technology permits recordings of tens of thousands of APs from the epicardium or endocardium, yet it has been used solely for in vitro studies and has not yet been translated to the clinical electrophysiology (EP) laboratory. Current clinical EP studies rely on electrograms, which are the spatially integrated electrical signatures of action potentials produced by numerous cells. Hence, they are not easily interpretable in complex conduction and repolarization cases. The advent of electrocardiographic imaging (ECGi) based on inverse problem solution, has provided an exciting opportunity to map epicardial electrograms noninvasively starting from the body surface electrogram mapping and whole thorax imaging using CT or MRI. However, this method provides only electrograms and not the action potentials. Moreover, body surface potential mapping modalities thus far cannot recreate endocardial electrograms, which requires invasive transvenous balloon or basket catheter mapping. We have developed a novel AP ECGi methodology which aims to noninvasively reconstruct action potentials based on body surface electrogram measurement and inverse problem solution. However, the critical issue is how to validate these methodologies, because there is no high resolution mapping technique available for direct mapping of action potentials in vivo. In this project we will develop an ex vivo validation platform against which all existing ECG methodologies and our new AP ECGi can be directly compared, using simultaneous mapping of electrograms and optical action potentials. We will create an ex vivo 3D model of the human thorax surrounding Langendorff-perfused human or rabbit hearts. The system will simulate a living heart in a human thorax and allow the simultaneous acquisition of (i) 240 thorax surface electrograms and (ii) panoramic mapping of optical action potentials from the epicardium using voltage-sensitive dyes. Our novel method will allow significant advancement of the existing noninvasive clinical cardiac electrophysiology armamentarium by validation of AP ECGi. Moreover, we will make these data sets available to other research groups and companies that are interested in validation of their own competing ECGi methods.