Myocardial Radiomics and Mechanics in the Pathology and Prognosis of Cardiovascular Disease

项目总结 尽管在识别和治疗危险因素方面取得了知识进步，但心血管疾病 疾病(CVD)仍然是美国的主要死亡原因，过去15年来一直是全球范围内的死因。 心血管疾病的三个主要致病来源：缺血性冠状动脉疾病、心力衰竭、 和房颤，似乎植根于左心室(LV)的心肌病理生理学，提示 对LV进行更深入的表型分析可能有助于深入了解这些疾病。LV最早形态的检测 功能障碍一直具有挑战性：传统的左心室结构和功能指标与贫乏相关 结果，如质量和射血分数，反映了疾病的晚期。然而，最近的进展 在使用心血管磁共振(CMR)图像对左室心肌进行定量成像时 弥合这一差距。心肌纹理分析是放射组学的一种，即心肌像素的计算 强度和模式，这已显示出区分左室肥厚的病理模式的能力。 此外，包括应变和扭转在内的心肌力学分析已显示出对 对心肌病的评估。因此，越来越多的证据表明，这些技术进步在 影像分析评价亚临床心血管疾病病理性左心室重构 人口。我们假设，这些与生物学相关的新型成像分析的应用， 亚临床疾病表型和结果将使对亚临床LV结构的更细粒度的洞察成为可能 早于显性CVD及其表现形式的功能改变。弗雷明翰和杰克逊心脏研究， 以社区为基础的白人和非裔美国人队列，经过纵向跟踪，提供了机会 通过将先进的二次成像分析与详细的 以及广泛的表型和基因分型，以及临床终点。因此，我们建议的目标是 三个方面：1)首先确定与流行的心血管疾病相关的心肌质地分析和力学模式 和风险因素，2)定义这些表型的生物学和遗传基础，以及3) 了解它们在结构和功能之间的相互联系，以及它们与长期的共同关系 预后。我们目标的执行将阐明潜在的早期疾病的新模式、决定因素和预后 在一个大的种族混杂的队列中，心血管疾病患者的进行性心肌重构和功能障碍。最终，我们的目标是 是为了了解从这项研究中获得的知识，以促进左心室重构组的表型，方法 心血管风险分层，以及病人护理治疗方法的发展。

PROJECT SUMMARY Though knowledge advances have been made in identification and treatment of risk factors, cardiovascular disease (CVD) remains the leading cause of death in the U.S., and has been worldwide for the past 15 years. The mechanisms of three leading sources of CVD morbidity, ischemic coronary artery disease, heart failure, and atrial fibrillation, appear rooted in myocardial pathophysiology of the left ventricle (LV), suggesting that deeper phenotyping of the LV may provide insight into the diseases. The detection of earliest forms of LV dysfunction has been challenging: traditional measures of LV structure and function associated with poor outcomes, such as mass and ejection fraction, reflect advanced stages of disease. However, recent advances in quantitative imaging of the LV myocardium using cardiovascular magnetic resonance (CMR) images may bridge this gap. Myocardial texture analysis is a type of ‘radiomics’, the computation of myocardial pixel intensity and patterns, which has shown the ability to differentiate pathological patterns in LV hypertrophy. Additionally, analysis of myocardial mechanics including strain and torsion have shown prognostic value in evaluation of cardiomyopathies. Thus, increasing evidence indicates roles for these technological advances in imaging analysis to evaluate pathological LV remodeling in subclinical cardiovascular disease in the general population. We hypothesize that application of these novel imaging analytics, correlated with biology, subclinical disease phenotyping, and outcomes, will enable more granular insight into subclinical LV structural and functional changes predating overt CVD and its forms. The Framingham and Jackson Heart Studies, community-based cohorts of whites and African Americans with longitudinal follow up, offer the opportunity to gain insight in CVD development through integration of advanced secondary imaging analysis with detailed and broad phenotyping and genotyping, and clinical end-points. Thus, the objectives of our proposal are threefold: 1) to first identify myocardial texture analysis and mechanics patterns associated with prevalent CVD and risk factors, 2) to define the biological and genetic underpinnings of these phenotypes, and 3) to understand their inter-association between structure and function, and their joint relations with long-term prognosis. Execution of our Aims will elucidate novel patterns, determinants, and prognosis of underlying early and progressive myocardial remodeling and dysfunction in CVD in a large bi-racial cohort. Ultimately, our goal is for knowledge gained from this study to advance phenotyping of LV remodeling groups, methods of cardiovascular risk stratification, and development of therapies for patient care.