A New Approach for Measurement of Electrical Conductivities of Cardiac Tissues

项目概要/摘要 申请人的长期目标是支持计算技术的进一步发展和临床转化 心脏组织模型。组织电生理学计算模型的关键参数是内部 和细胞外电导率。目前，我们对这些电导率的了解源自 40 年前对动物心脏的心室组织进行的一小部分研究。人体的电导率， 衰老和患病的组织尚未确定。在这项研究中，我们将检验以下假设：一部小说 计算方法和先进的 3D 微电极阵列提供了一种精确测量 用于心脏组织电生理学建模的电导率。我们的方法将有助于测量 电导率张量综合描述了细胞外和细胞的各向异性电特性 生物组织的细胞内结构域。在具体目标 1 中，我们将使用计算方法来评估 3D 微电极阵列的设计和当前的应用协议。我们将改变录音的间距 电极在微电极阵列制造的自由度内。我们也会调查 当前应用的协议和电极位置。最佳阵列和当前应用协议将 在组织替代物的研究中进一步评估。在这些研究中，我们假设基于模型的 该方法能够准确测量各向同性和各向异性介质的电导率。我们会 确定电导率测量的准确性。在具体目标 2 中，我们将探讨 用于测量活体心脏组织电导率的基于建模的方法。使用从中切除的组织 大鼠的左心室，我们将测试计算方法提供可靠测量的假设 活组织的电导率。我们将通过与之前的研究进行比较来评估我们的测量结果。 随后，我们将研究该方法测量左侧电导率的可行性 离体大鼠心脏的心室游离壁。我们将应用已建立的离体大鼠心脏模型 通过主动脉逆行灌注。我们将用与正常相关的解决方案灌注心脏， 细胞外体积增加和减少。我们假设细胞外电导率增加并且 与相比，分别增加和减少细胞外体积的溶液减少 控制。总之，拟议的研究构成了建立拟议创新的关键一步 测量细胞内和细胞外电导率的方法。拟议框架的应用 包括建立人类和老年人心脏不同部位心脏组织的电导率。另外， 该框架的应用将有助于创建各种电导率测量库 心脏病，例如肥厚型心肌病和心室纤维化。我们建议这样一个 图书馆将对计算心血管研究和医学产生持续、强大的影响。

PROJECT SUMMARY/ABSTRACT The applicants’ long-term aim is to support the further advancement and clinical translation of computational models of cardiac tissues. Crucial parameters for computational models of tissue electrophysiology are the intra- and extracellular electrical conductivities. Currently, our knowledge about these conductivities originates from a small set of studies performed 40 years ago on ventricular tissue from animal hearts. Conductivities of human, aged and diseased tissues have still not been established. In this study, we will test the hypothesis that a novel computational approach and advanced 3D microelectrode arrays provide a means for accurate measurement of conductivities for modeling of cardiac tissue electrophysiology. Our approach will facilitate the measurement of conductivity tensors that comprehensively describe the anisotropic electrical properties of the extracellular and intracellular domains of biological tissue. In Specific Aim 1, we will use the computational approach to assess designs of 3D microelectrode arrays and current application protocols. We will vary the spacing of recording electrodes within the degrees of freedom for manufacturing of the microelectrode arrays. We will also investigate protocols and electrode locations for current application. The optimal array and current application protocol will be further assessed in studies on tissue surrogates. In these studies, we hypothesize that the modeling-based approach is capable of accurately measuring the conductivity of both isotropic and anisotropic media. We will determine the accuracy of the conductivity measurements. In Specific Aim 2, we will explore the utility of the modeling-based approach for measurement of conductivity in living cardiac tissues. Using tissues excised from the left ventricle of rat, we will test the hypothesis that the computational approach provides reliable measures of conductivity of living tissues. We will assess our measurements by comparison with prior studies. Subsequently, we will investigate the feasibility of the approach for conductivity measurements of the left ventricular free wall of the isolated rat heart. We will apply an established model of the isolated rat heart based on retrograde perfusion through the aorta. We will perfuse the hearts with solutions associated with normal, increased and decreased extracellular volume. We hypothesize that extracellular conductivities increase and decrease for the solutions that increase and decrease the extracellular volume, respectively, when compared to control. Together, the proposed studies constitute a crucial step towards establishing the proposed innovative approach for measurement of intra- and extracellular conductivities. Applications of the proposed framework include establishing conductivities of cardiac tissues at different sites of the human and aged heart. Also, application of the framework will facilitate the creation of a library of conductivity measurements for various cardiac diseases, for instance, hypertrophic cardiomyopathy and ventricular fibrosis. We suggest that such a library will have a sustained, powerful impact on computational cardiovascular research and medicine.