A New Approach for Measurement of Electrical Conductivities of Cardiac Tissues

测量心脏组织电导率的新方法

• 批准号: 10162414
• 负责人: Derek J Dosdall
• 金额: $ 7.75万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-01 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10162414
• 关键词: 3-Dimensional; Accounting; Anisotropy; Aorta; Arrhythmia; Biological; Cardiac; Cardiac Surgery procedures; Cardiology; Cardioplegic Solutions; Cardiovascular system; Clinical; Computer Models; Diagnosis; Disease; Disease model; Electric Conductivity; Electrodes; Electrophysiology (science); Exhibits; Extracellular Domain; Feasibility Studies; Fibrosis; Freedom; Heart; Heart Diseases; Heart failure; Human; Hypertrophic Cardiomyopathy; Knowledge; Left; Left ventricular structure; Libraries; Location; Measurement; Measures; Medicine; Microelectrodes; Microtomy; Modeling; Noise; Patients; Perfusion; Polynomial Models; Property; Protocols documentation; Publishing; Rattus; Reporting; Research; Sampling; Site; Techniques; Technology; Temperature; Testing; Tissue Model; Tissues; Ventricular; Work; aged; animal tissue; base; clinical translation; design; electric field; electrical measurement; electrical property; extracellular; human model; innovation; mathematical methods; novel; novel strategies; relating to nervous system; response

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.

项目摘要/摘要 申请人的长期目标是支持计算的进一步发展和临床翻译 心脏组织的模型。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 一组研究于40年前对动物心脏的心室组织进行的研究。人类的电导率 尚未建立老化和解散的组织。在这项研究中，我们将检验一个新颖的假设 计算方法和高级3D微电极阵列为准确测量 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，可全面描述细胞外和细胞外的各向异性电特性 生物组织的细胞内结构域。在特定目标1中，我们将使用计算方法评估 3D微电极阵列和当前应用程序协议的设计。我们将改变录制的间距 微电极阵列制造自由度之内的电极。我们还将调查 当前应用的协议和电极位置。最佳数组和当前应用程序协议将 在组织替代物的研究中得到进一步评估。在这些研究中，我们假设基于建模的 方法能够准确测量各向同性和各向异性培养基的电导率。我们将 确定电导率测量的准确性。在特定目标2中，我们将探讨 基于建模的方法，用于测量活心脏组织中的电导率。使用优秀的组织 大鼠的左心室，我们将检验以下假设：计算方法提供可靠的测量值 活组织的电导率。我们将通过与先前的研究进行比较来评估我们的测量。 随后，我们将研究该方法的可行性，用于左侧的电导率测量 孤立的大鼠心脏的心室无壁。我们将采用基于孤立的大鼠心脏的既定模型 通过主动脉逆行灌注。我们将使用与正常相关的解决方案来刺激心脏 细胞外体积增加和增加。我们假设细胞外导力增加，并且 与相比 控制。拟议的研究共同构成了建立拟议创新的关键步骤 测量细胞内电导率和细胞外电导率的方法。拟议框架的应用 包括在人和老年心脏的不同部位建立心脏组织的电导率。还， 框架的应用将有助于为各种电导率测量库创建 心脏疾病，例如肥厚性心肌病和心室纤维化。我们建议这样的 图书馆将对计算心血管研究和医学产生持续，强大的影响。

项目成果

Approaches for determining cardiac bidomain conductivity values: progress and challenges.

• DOI: 10.1007/s11517-020-02272-z
• 发表时间: 2020-12
• 期刊: Medical & biological engineering & computing
• 影响因子: 3.2
• 作者: Johnston BM;Johnston PR
• 通讯作者: Johnston PR

A modified approach to determine the six cardiac bidomain conductivities.

• DOI: 10.1016/j.compbiomed.2021.104549
• 发表时间: 2021-08
• 期刊: Computers in biology and medicine
• 影响因子: 7.7

Confocal microscopy-based estimation of intracellular conductivities in myocardium for modeling of the normal and infarcted heart.

• DOI: 10.1016/j.compbiomed.2022.105579
• 发表时间: 2022-07
• 期刊: Computers in biology and medicine
• 影响因子: 7.7

Improving the accuracy of retrieved cardiac electrical conductivities.

• DOI: 10.21914/anziamj.v63.17148
• 发表时间: 2022
• 期刊: The ANZIAM journal