A New Approach for Measurement of Electrical Conductivities of Cardiac Tissues

项目摘要/摘要 申请者的长期目标是支持计算的进一步发展和临床翻译。 心脏组织模型。组织电生理学计算模型的关键参数是 以及细胞外的电导率。目前，我们关于这些导电性的知识来源于 40年前，对动物心脏的心脏组织进行了一系列小范围的研究。人的导电性， 老化和患病的组织仍未建立起来。在这项研究中，我们将检验一个假设，即一部小说 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。我们的方法将有助于测量 电导张量全面描述细胞外和细胞外各向异性电学性质 生物组织的胞内域。在具体目标1中，我们将使用计算方法来评估 三维微电极阵列的设计和当前的应用协议。我们将改变录制的间隔 用于制造微电极阵列的自由度内的电极。我们还将调查 适用于当前应用的协议和电极位置。最佳阵列和当前应用程序协议将 在对组织替代物的研究中将进一步进行评估。在这些研究中，我们假设基于建模的 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 基于模型的活体心脏组织电导率测量方法。用切开的组织 ，我们将检验计算方法提供可靠测量方法的假设 活组织的传导性。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，我们将研究该方法用于左侧电导率测量的可行性。 大鼠离体心的心室游离壁。我们将应用一种已建立的大鼠离体心模型 通过大动脉逆行灌流。我们将用与正常， 增加和减少细胞外体积。我们假设细胞外电导增加并且 分别增加和减少细胞外体积的溶液与 控制力。综上所述，拟议的研究是朝着建立拟议的创新 测量细胞内和细胞外电导率的方法。拟议框架的应用 包括在人和老年人心脏的不同部位建立心脏组织的电导率。另外， 该框架的应用将有助于建立各种不同类型的电导率测量库 心脏疾病，例如肥厚性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.