Computational Tools to Describe Cardiac Post-MI Structure and Function Remodeling

描述心脏 MI 后结构和功能重塑的计算工具

• 批准号: 8311647
• 负责人: Siamak Ardekani
• 金额: $ 20.5万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-05 至 2014-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8311647
• 关键词: Algorithms; Anatomy; Animal Model; Animals; Arrhythmia; Attenuated; Cardiac; Cicatrix; Clinical; Clinical Research; Collagen; Computational algorithm; Computing Methodologies; Controlled Study; Coronary; Coronary Arteriosclerosis; Data; Deterioration; Development; Diagnostic; Diffusion Magnetic Resonance Imaging; Dilated Cardiomyopathy; Discipline; Disease; Enzymes; Event; Evolution; Fiber; Future; Gene Proteins; Genetic; Goals; Grant; Heart; Heart Diseases; Heart Ventricle; Image; Infarction; Knowledge; Left; Left Ventricular Dysfunction; Left Ventricular Remodeling; Left ventricular structure; Link; Location; Magnetic Resonance Imaging; Matrix Metalloproteinase Inhibitor; Matrix Metalloproteinases; Measures; Mechanics; Mediating; Methods; Modeling; Monitor; Morbidity - disease rate; Motion; Mus; Muscle Fibers; Myocardial; Myocardial Infarction; Myocardium; Nature; Patients; Physiological; Play; Population; Predisposition; Preparation; Prevention; Process; Pump; Reperfusion Therapy; Resolution; Risk; Role; Shapes; Staging; Structure; System; Testing; Therapeutic; Therapeutic Intervention; Time; Tissues; Tomography, Computed, Scanners; Type 2 Angiotensin II Receptor; Variant; Ventricular; Ventricular Remodeling; Work; analytical method; base; computerized tools; design; detector; disorder risk; extracellular; heart motion; improved; in vivo; mortality; prognostic; response; sham surgery; tool; treatment strategy

DESCRIPTION (provided by applicant): In response to disease, the myocardium undergoes time-dependent remodeling that manifests as alterations of heart shape and motion during the cardiac cycle. For example, in patients with coronary artery disease and left ventricular dysfunction, ventricular remodeling results in a gradual increase of ventricular end-diastolic and end- systolic volumes, wall thinning, changes of chamber geometry, and alterations of heart motion. At the micro-structure scale, the normal 3D organization of muscle fibers in the myocardium that spirals around the left ventricle with a angle that is determined by their transmural location is perturbed. While there have been attempts to identify genes and proteins that are indicative of disease risk, there have been few efforts to quantify and assess regional cardiac shape, fiber orientation, and motion changes to predict disease and to monitor response in various therapies. Our work will focus on developing new algorithms, from the emerging discipline of computational functional anatomy (CFA), for analyzing changes of heart shape (geometry and fiber structure) and motion and exploring the extent to which such image-derived parameters can be used to describe disease state and progression. We will pursue this by employing a reperfused murine model of infarction to measure differences in ventricular geometry, fiber orientation, and motion of the cardiac ventricles using in-vivo 3D time evolving structural and tagged MRI imaging and ex-vivo diffusion tensor imaging in normal vs. infarcted mouse. Prevention of adverse remodeling after myocardial infarction (MI) is a therapeutic challenge as ventricles in many patients continue to enlarge after MI and mortality and morbidity remain significant in spite of therapy. Several studies indicated that extracellular collagen matrix (ECCM) plays an important role in post-MI remodeling and it may appear that treatments that targeting ECCM remodeling might be beneficial. However, the whole matter is further complicated by the fact that infarct and non-infarct zones demonstrate differential pathophysiological responses. Therefore a detailed understanding of temporal/spatial evolution of ECCM remodeling is a necessary step in developing treatment strategies that target both infarcted and non-infarcted zones. CFA methods that are developed in this proposal will be utilized in future studies to acquire valuable information about the effect of substances such as matrix metalloproteinases that degrade ECCM on the ventricular structural remodeling and cardiac mechanics.

描述（由申请人提供）：为了应对疾病，心肌会经历时间依赖性重塑，表现为心动周期期间心脏形状和运动的改变。例如，在患有冠状动脉疾病和左心室功能障碍的患者中，心室重塑导致心室舒张末期和收缩末期容积逐渐增加、室壁变薄、心室几何形状的变化以及心脏运动的改变。在微观结构尺度上，心肌中肌纤维的正常 3D 组织（以由其透壁位置决定的角度围绕左心室螺旋）受到干扰。尽管已经尝试识别指示疾病风险的基因和蛋白质，但很少有人努力量化和评估区域心脏形状、纤维方向和运动变化以预测疾病并监测各种疗法的反应。我们的工作将侧重于开发来自计算功能解剖学 (CFA) 新兴学科的新算法，用于分析心脏形状（几何和纤维结构）和运动的变化，并探索此类图像衍生参数可在多大程度上用于描述疾病状态和进展。我们将通过采用再灌注小鼠梗死模型来测量心室几何形状、纤维取向和心室运动的差异，使用体内 3D 时间演化结构和标记 MRI 成像以及正常与体外扩散张量成像来实现这一目标。 . 梗塞小鼠。预防心肌梗死 (MI) 后的不良重塑是一项治疗挑战，因为许多患者的心室在 MI 后继续扩大，尽管进行了治疗，死亡率和发病率仍然很高。多项研究表明，细胞外胶原基质 (ECCM) 在 MI 后重塑中发挥着重要作用，并且针对 ECCM 重塑的治疗似乎可能是有益的。然而，由于梗塞区和非梗塞区表现出不同的病理生理反应，整个问题变得更加复杂。因此，详细了解 ECCM 重塑的时间/空间演变是制定针对梗塞区和非梗塞区的治疗策略的必要步骤。本提案中开发的 CFA 方法将在未来的研究中使用，以获取有关降解 ECCM 的基质金属蛋白酶等物质对心室结构重塑和心脏力学影响的有价值的信息。