Biomicromechanics of Heart Muscle Tissue Function

心脏肌肉组织功能的生物微观力学ellen M. Arruda博士，PIKarl Grosh博士，合作pip摘要在美国，每年有6万名65岁以下的患者死于心肌病导致的终末期心力衰竭。心脏功能由于收缩和舒张损伤而改变；通常舒张功能障碍先于收缩功能障碍。迫切需要对这种疾病进行早期诊断，以便提供适当的治疗。我们在这一领域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，用于心肌病的早期无创检测。这将包括超声心动图，应变成像模块和心脏肌肉组织的本构律。目前的压力负荷可以通过超声心动图的多普勒超声测量提供的实时血流信息来估计。应变成像模块仅在少数专用机器上可用，但目前尚未用于诊断。在生物传感器的发展中，第三个关键要素是心肌组织的预测本构模型，这在本提案中得到了解决。该项目的目的是为心肌组织开发一个本构律，描述其在体内对电和机械刺激的反应方面的整体运动。这将使不同疾病阶段的组织特性变化和超声心动图识别的心肌病心功能变化之间的相关性，以及在收缩功能障碍阶段之前建立心肌病早期诊断的非侵入性标准。本项目还将发展超声心动图应变斑成像技术，以无创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、更早地治疗这些患者。密歇根大学目前研究的犬，处于健康和心脏病的不同阶段，将被安乐死，并切除它们的心室，以研究心肌病时心脏组织反应的变化。将对脑室和乳头状肌组织进行力学试验和组织学检查以确定其特征。病变心肌的物质特性和物理特性的变化将通过使用扩张和肥大的犬群并将其与健康人群进行比较来记录。我们的软组织正交各向异性本构模型将被扩展，包括额外的变形机制在心肌反应中的作用，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群进行评估。心肌病的机制将根据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犬体内弹性成像工具进行测试。这项技术的准确性将通过对同一动物切除的心脏组织进行体外力学测试来检验。心肌病的机制将通过比较排斥前后不同阶段心肌的反应，并将其与超声心动图确定的同一患者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.