A predictive model of left ventricle remodeling in the presence of injected polymer

注射聚合物时左心室重塑的预测模型

• 批准号: 10658840
• 负责人: Christian Goodbrake
• 金额: $ 6.95万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-01 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10658840
• 关键词: 3-Dimensional; Affect; Aftercare; American; Anatomy; Animals; Cardiac; Cardiovascular system; Cicatrix; Clinical; Collagen; Combined Modality Therapy; Complex; Computer Models; Congestive Heart Failure; Connective Tissue; Consumption; Data; Deposition; Development; Diffusion Magnetic Resonance Imaging; Evolution; Fiber; Fibroblasts; Future; Geometry; Goals; Growth; Guidelines; Health; Heart; Heart Ventricle; Heart failure; Image; Imaging technology; Impairment; Individual; Infarction; Injection of therapeutic agent; Injections; Investigation; Ischemia; Left; Left Ventricular Remodeling; Left ventricular structure; Leukocytes; Link; Measures; Mechanics; Mitral Valve; Mitral Valve Insufficiency; Modality; Modeling; Muscle Cells; Myocardial; Myocardial Infarction; Myocardium; Nature; Necrosis; Nodule; Organ; Patients; Polymers; Process; Research; Resolution; Shapes; Sheep; Site; Specimen; Stress; Structure; Time; Tissues; Translations; Treatment Protocols; Validation; Ventricular Remodeling; chemokine; cost; cytokine; density; heart function; individual patient; individualized medicine; optimal treatments; phenomenological models; preclinical study; predictive modeling; pressure; response; simulation; therapy development

PROJECT SUMMARY/ABSTRACT In the weeks following myocardial infarction, damaged tissue undergoes a structural change, where myocytes are broken down and removed, and collagenous tissue is restructured. This structural change impairs the tissue's ability to resist internal pressures and if left untreated can lead to aneurysmal growth, ischemic mitral regurgi- tation, and ultimately heart failure. Polymer injection therapy has been clinically shown to reduce post-infarct left-ventricle cardiac wall remodeling, but the development of this treatment thus far has been largely experimen- tal. Optimal therapy parameters, both for generic treatment and for individual patients are currently unknown. Our objective for this proposal is to develop an experimentally guided computational model of left ventricle remodeling that incorporates heart-specific imaging data, which will enable us to systematically optimize the polymer injection therapy by examining the impact of treatment parameters such as injection volume, site density, and polymer stiffness. This heart-specific imaging data will allow us to determine the effect of individual infarct geometry and myocardium microstructure, and to tailor treatment to individual cases. We also seek to use this image data to validate the long term predictions of this model, demonstrating that it can predict the remodeling that occurs, and the impact of different polymer injection configurations. Therefore, it will serve to preemptively consider multiple treatment options so clinicians can choose the best course of action for individual patients. The objectives of this proposal are summarized in the three following specific aims: SA1. Model post-infarct tissue remodeling matching established ovine MI model progression SA2. Validate in a heart-specific pipeline at the tissue and organ levels SA3. Utilize the previously generated model to optimize polymer injection treatment protocol

项目概要/摘要 在心肌梗死后的几周内，受损组织发生结构变化，其中肌细胞 被分解和去除，胶原组织被重组。这种结构变化会损害组织 抵抗内部压力的能力，如果不及时治疗，可能会导致动脉瘤生长、缺血性二尖瓣反流 ，最终导致心力衰竭。聚合物注射疗法已被临床证明可以减少梗死后的发生 左心室心壁重塑，但迄今为止这种治疗的发展主要是实验性的 塔尔。目前尚不清楚一般治疗和个体患者的最佳治疗参数。 我们此提案的目标是开发一种实验引导的左心室计算模型 结合心脏特定成像数据的重塑，这将使我们能够系统地优化 通过检查注射量、部位密度等治疗参数的影响来进行聚合物注射治疗 和聚合物刚度。这种心脏特异性成像数据将使我们能够确定个体梗塞的影响 几何形状和心肌微观结构，并根据具体情况制定治疗方案。我们也寻求利用这个 图像数据来验证该模型的长期预测，证明它可以预测重构 发生的情况以及不同聚合物注射配置的影响。因此，它将起到先发制人的作用 考虑多种治疗方案，以便临床医生可以为个体患者选择最佳的治疗方案。 该提案的目标概括为以下三个具体目标： SA1。梗死后组织重塑模型与已建立的绵羊心肌梗死模型进展相匹配 SA2。在组织和器官水平上在心脏特定管道中进行验证 SA3。利用之前生成的模型来优化聚合物注射处理方案