OPTO-ELECTRIC MAPPING OF ACTION POTENTIALS

描述(申请人提供)：每年有300-40万美国人死于心律失常。现有的治疗方法主要基于药理学、外科、消融术和植入性装置的方法。诊断的主要障碍之一是无法无创地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，它提供从单个部位的高保真记录，到目前为止还没有被用于高分辨率标测。或者，光学标测技术允许从心外膜或心内膜记录数万个AP，但它仅用于体外研究，尚未被翻译到临床电生理(EP)实验室。目前的临床EP研究依赖于电信号，它是由大量细胞产生的动作电位的空间集成电信号。因此，它们在复杂的传导和复极化情况下不容易解释。基于逆问题求解的心电成像(ECGi)的出现，为利用CT或MRI从体表心电标测和全胸成像开始无创标测心外膜电信号提供了一个令人振奋的机会。然而，这种方法只提供了心电信号，而不是动作电位。此外，到目前为止，体表电位标测方法不能重建心内膜电信号，这需要有创性的经静脉球囊或篮形导管标测。我们开发了一种新的AP ECGi方法，旨在基于体表电信号测量和逆问题求解来非侵入性地重建动作电位。然而，关键的问题是如何验证这些方法，因为目前还没有高分辨率的标测技术可用于在活体内直接标测动作电位。在这个项目中，我们将开发一个体外验证平台，通过同步映射心电图和光学动作电位，可以直接与所有现有的心电方法和我们的新AP ECGi进行比较。我们将创建一个人体胸部的体外3D模型，环绕着兰登多夫灌流的人或兔的心脏。该系统将在人的胸腔内模拟一颗活的心脏，并允许同时采集(I)240个胸部表面电信号和(Ii)使用电压敏感染料从心外膜全景绘制光学动作电位图。通过对AP ECGi的验证，我们的新方法将使现有的非侵入性临床心脏电生理学设备得到显着发展。此外，我们将把这些数据集提供给其他对验证自己的竞争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.