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: 10389507
• 负责人: Christian Goodbrake
• 金额: $ 6.72万
• 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/10389507
• 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; Lead; 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

项目摘要/摘要 在心肌梗塞后的几周内，损坏的组织经历了结构性变化，其中心肌细胞发生 分解并去除，并恢复胶原组织。这种结构性变化会损害组织 抵抗内部压力的能力，如果未治疗，可以导致动脉瘤的生长，缺血性二尖瓣流体 态度，最终是心力衰竭。聚合物注射疗法已在临床上显示可减少感染后 左内心脏壁重塑，但是到目前为止，这种治疗的发展在很大程度上是实验性的 塔尔。目前尚不清楚用于通用治疗的最佳治疗参数和针对个别患者的最佳治疗参数。 我们对该建议的目标是开发左心室的实验指导的计算模型 重塑包含心脏特异性成像数据，这将使我们能够系统地优化 聚合物注射疗法通过检查治疗参数的影响，例如注射量，位点密度， 和聚合物刚度。这种特定心脏的成像数据将使我们能够确定个体梗塞的效果 几何学和心肌微观结构，并针对单个病例量身定制治疗。我们也寻求使用这个 图像数据以验证该模型的长期预测，表明它可以预测重塑 发生这种情况，以及不同聚合物注射配置的影响。因此，它将有助于抢先 考虑多种治疗选择，以便临床医生可以为个别患者选择最佳的行动方案。 该提案的目标总结在以下三个特定目的中： SA1。模型侵入后组织重塑匹配已建立的卵子MI模型进展 SA2。在组织和器官水平的心脏特异性管道中验证 SA3。利用先前生成的模型来优化聚合物注射治疗方案