Volumetric imaging and computation to characterize cardiac electromechanical coupling

体积成像和计算来表征心脏机电耦合

基本信息

批准号：
10629905
负责人：
Yichen Ding
金额：
$ 38.39万
依托单位：
UNIVERSITY OF TEXAS DALLAS
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-04-15 至 2028-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10629905
关键词：
3-Dimensional Affect Amiodarone Anti-Arrhythmia Agents Antibiotics Antidepressive Agents Antiemetics Antifungal Agents Antineoplastic Agents Apical Arrhythmia Biological Models Bradycardia Calcium Calcium Signaling Cardiac Cardiac Myocytes Cell Nucleus Cells Clinical Collaborations Complication Computer Models Computing Methodologies Coupling Custom Developmental Biology Embryo Engineering Erythromycin Fertilization Fishes Fluoxetine Four-dimensional Functional disorder Genetic Genetic Models Goals Heart Heart Atrium Hour Human Image Individual Investigation Life Light Lighting Machine Learning Measures Mechanics Methodology Microscope Morphologic artifacts Motion Myocardial Myocardial Contraction Noise Patients Pattern Penetration Pentamidine Pharmaceutical Preparations Physicians Productivity Psychotropic Drugs Research Resolution Risk Factors Screening procedure Signal Transduction Sinus Structure TG gene Techniques Testing Time Transgenic Organisms Troponin T United States Variant Ventricular Work Zebrafish antimicrobial automated segmentation image processing imaging modality in vivo interest machine learning framework mutant prospective prototype response small molecule spatiotemporal success zebrafish development

3-Dimensional Affect Amiodarone Anti-Arrhythmia Agents Antibiotics Antidepressive Agents Antiemetics Antifungal Agents Antineoplastic Agents Apical Arrhythmia Biological Models Bradycardia Calcium Calcium Signaling Cardiac Cardiac Myocytes Cell Nucleus Cells Clinical Collaborations Complication Computer Models Computing Methodologies Coupling Custom Developmental Biology Embryo Engineering Erythromycin Fertilization Fishes Fluoxetine Four-dimensional Functional disorder Genetic Genetic Models Goals Heart Heart Atrium Hour Human Image Individual Investigation Life Light Lighting Machine Learning Measures Mechanics Methodology Microscope Morphologic artifacts Motion Myocardial Myocardial Contraction Noise Patients Pattern Penetration Pentamidine Pharmaceutical Preparations Physicians Productivity Psychotropic Drugs Research Resolution Risk Factors Screening procedure Signal Transduction Sinus Structure TG gene Techniques Testing Time Transgenic Organisms Troponin T United States Variant Ventricular Work Zebrafish antimicrobial automated segmentation image processing imaging modality in vivo interest machine learning framework mutant prospective prototype response small molecule spatiotemporal success zebrafish development

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项目摘要

PROJECT SUMMARY / ABSTRACT Volumetric imaging and computation to characterize cardiac electromechanical coupling Approximately 450,000 individuals in the United States die suddenly from cardiac arrhythmias every year. Many widely used medications such as antiarrhythmic agents, antimicrobials, anticancer drugs, and psychotropic drugs can cause or exacerbate a variety of arrhythmias. However, the fundamental mechanisms of most clinical arrhythmias remain poorly understood. The ability to prospectively identify potentially arrhythmogenic compounds would be clinically valuable. Recent advances demonstrate that zebrafish are a productive model system to screen small molecules that function as arrhythmic compounds in humans. However, much remains unknown about the involved excitation-contraction coupling abnormalities and mechanisms of arrhythmias associated with specific drugs. Despite the new zebrafish lines gained in past decades, technical difficulties including motion artifact, frame rate, penetration depth, and signal-to-noise ratio limits the in-depth investigation of aberrant calcium activities and contractile dysfunction. For this reason, we seek to integrate our 4-dimensional (4D, 3D spatial + 1D temporal) volumetric imaging with computational model to investigate whether a common mechanism of action underlies drug-induced excitation-contraction coupling abnormalities. In collaboration with Dr. Kelli Carroll (developmental biology), Dr. Catherine Makarewich (calcium signaling), and Dr. Jay Kuo (machine learning), we will test the hypothesis that small molecule-induced bradycardia activates distinct EC coupling abnormalities responsible for various arrhythmias. In Aim 1, we will reveal the 4D calcium activities across the intact heart with high spatiotemporal resolution via our custom-built structured-illumination light-field microscope. In Aim 2, we will elucidate the electromechanical interaction among neighboring cardiomyocytes during 5~10 cardiac cycles. In Aim 3, we will assess the excitation-contraction coupling abnormalities induced by small molecule compounds. In this context, success of this research will establish a new holistic strategy to in vivo investigate sophisticated electromechanical interaction, providing an entry point to further study the underlying mechanism of arrhythmias and prospectively identify arrhythmogenic compounds.

项目摘要 /摘要体积成像和计算以表征心脏机电耦合每年，美国大约有450,000名患者突然死于心脏心律不齐。许多广泛使用的药物，例如抗心律失常剂，抗菌药物，抗癌药和精神药物会导致或加剧各种心律不齐。但是，大多数临床的基本机制心律不齐仍然不足。前瞻性识别潜在心律不齐的能力化合物在临床上是有价值的。最近的进步表明斑马鱼是一种富有成效的模型筛选小分子的系统，这些分子起着人类心律不齐化合物的作用。但是，剩下很多关于心律不齐的涉及激发反应偶联异常和机制的未知与特定药物有关。尽管过去几十年来获得了新的斑马鱼线，但技术困难包括运动伪影，帧速率，穿透深度和信噪比限制了深入研究异常的钙活动和收缩功能障碍。因此，我们试图整合我们的4维（4D，3D空间 + 1D颞）使用计算模型进行体积成像，以研究是否常见作用机理是药物诱导的激发反应偶联异常的基础。与 Kelli Carroll博士（发展生物学），Catherine Makarewich博士（钙信号）和Jay Kuo博士（机器学习），我们将检验以下假设：小分子诱导的心动过缓会激活不同的EC 导致各种心律不齐的耦合异常。在AIM 1中，我们将揭示4D钙活动通过我们定制的结构化灯场，穿越完整的心脏，具有高时空分辨率显微镜。在AIM 2中，我们将阐明相邻心肌细胞之间的机电相互作用在5〜10心脏周期中。在AIM 3中，我们将评估引起的激发反应偶联异常通过小分子化合物。在这种情况下，这项研究的成功将建立一个新的整体策略体内研究复杂的机电相互作用，提供了进一步研究的切入点心律不齐的基本机制，并前瞻性地识别心律不齐化合物。