Biomicromechanics of Heart Muscle Tissue Function

心肌组织功能的生物微观力学Ellen M.Arruda，Ph.，PIKarl Grosh，Ph.，co-PI摘要在美国，每年有6万名65岁以下的患者死于心肌病所致的终末期心力衰竭。心脏功能因收缩和舒张期受损而改变；通常舒张期功能障碍先于收缩部分。迫切需要对这种疾病进行非常早期的诊断，以便提供适当的治疗。我们在这方面工作的长期目标是开发一种基于超声心动图的心肌组织生物传感器，用于心肌病的早期非侵入性检测。这将由超声心动图、应变成像模块和心肌组织的本构定律组成。目前，可以通过超声心动图的多普勒超声测量获得的实时血流信息来估计压力负荷。应变成像模块只在几台专门的机器上可用，但目前还没有用于诊断。在生物传感器的开发中至关重要的第三个要素是心肌组织的预测性本构模型，也是本提案中提到的。该项目的目的是开发心肌组织的本构定律，描述其在活体内对电和机械刺激的反应的整体运动。这将使不同疾病阶段的组织特性变化与超声心动图确定的心脏功能变化与心肌病相关，并建立在收缩功能障碍阶段之前早期诊断心肌病的非侵入性标准。该项目还将开发通过超声心动图的应变散斑成像，以非侵入性地检测心肌病患者的早期疾病。这些研究将有助于更好地了解这一过程的机制，并更好地和更早地治疗这些患者。密歇根大学目前的研究涉及的犬在健康和心脏病的不同阶段将被实施安乐死，并切除其心室，以调查心肌病心脏组织反应的变化。机械测试和组织学将在脑室和乳头肌组织上进行，以确定它们的特征。通过使用扩张和肥大的犬种群并将它们与健康种群进行比较，将记录病变心肌的材料特性和物理特性的变化。我们的软组织正交各向异性本构模型将通过包括额外的变形机制在心肌响应中的作用来扩展，例如肌肉活动和粘弹性。此外，建模方法继续捕捉病变心肌反应的能力将使用不同的犬类进行评估。心肌病的机制将通过模型中物理参数的变化来描述。为该项目捐赠的商业超声应变成像模块将作为使用犬类进行体内弹性成像的工具进行测试。这项技术的准确性将通过对相同动物的心脏组织进行体外机械测试来检验。心肌病的机制将通过比较排斥反应前后不同阶段的心肌反应，并与相同患者的超声心动图确定的心功能变化进行比较来研究。

Biomicromechanics of Heart Muscle Tissue FunctionEllen M. Arruda, Ph. D., PIKarl Grosh, Ph. D., co-PIAbstractSixty thousand patients under the age of 65 die each year from end-stage heart failure in the U.S. as a result of cardiomyopathy. Cardiac function is altered as a result of both systolic and diastolic impairment; usually the diastolic dysfunction precedes the systolic component. There is a critical need for very early diagnosis of this disease in order to provide an appropriate treatment. The long-term objective of our work in this area is the development of an echocardiograph-based biosensor of heart muscle tissue for early non-invasive detection of cardiomyopathy. This will consist of an echocardiograph, a strain imaging module and a constitutive law for heart muscle tissue. Currently pressure loads can be estimated via real-time blood flow information available from the doppler ultrasound measurements of the echocardiograph. A module for strain imaging is available on only a few specialized machines, but it is currently not used for diagnosis. The third element that is critically needed in the development of a biosensor, and addressed in this Proposal, is a predictive constitutive model of the heart muscle tissue. The aim of this Project is to develop a constitutive law for cardiac muscle tissue that describes its overall motion in terms of its response to electrical and mechanical stimuli in vivo. This will enable a correlation between changes in tissue properties with various stages of disease and echocardiograph-identified changes in cardiac function with cardiomyopathy, as well as the establishment of non-invasive criteria for the early diagnosis of cardiomyopathy prior to the stage of systolic dysfunction. Strain speckle imaging via echocardiographs will also be developed in this Project to non-invasively detect early stages of disease in patients with cardiomyopathy. These studies will lead to a better understanding of the mechanism of this process and better and earlier treatment of these patients.Canines involved in current studies at University of Michigan, in various stages of health and cardiac disease, will be euthanized and their ventricles excised for investigation of the changes in cardiac tissue response with cardiomyopathy. Mechanical tests and histology will be conducted on the ventricle and papillary muscle tissue to characterize them. Changes in material properties and physical characteristics with diseased myocardium will be documented by using dilated and hypertrophied canine populations and comparing them to the healthy populations. Our orthotropic constitutive model for soft tissue will be extended by including the role of additional deformation mechanisms in the response of myocardium, such as muscle activity and viscoelasticity. Moreover, the ability of the modeling approach to continue to capture the response of diseased myocardium will be assessed using the various canine populations. Mechanisms of cardiomyopathies will be described in terms of the changes in the physical parameters in the model. A commerical ultrasound strain imaging module donated for this project will be tested as a tool for in vivo elastography using canines. The accuracy of this technique will be examined by in vitro mechanical testing of excised cardiac tissue from the same animals. Mechanisms for cardiomyopathy will be examined by comparing the response of the myocardium at various stages before and after rejection and comparing these with echocardiograph-identified changes in cardiac function in the same patients.