| The modeling of virtual heart, which is an extremely complex system, includes several different research topics, i.e. anatomy, electrophysiology, mechanics, biochemistry, mathematics and computer science. It can reproduce cardiac bioelectrical, myocardial mechanical and cardiovascular load properties by simulation of shape, motion and function of heart under physiological and pathological conditions. A detailed model of the heart will provide a useful complimentary tool to investigate the dynamical behavior quantitatively and intuitively that cannot be achieved in clinic or animal experiments at present. All electromechanical parameters, which may contribute to the diagnosis and treatment of heart diseases, can be traced and analyzed. A further advantage of the mathematical model is that no ethical restrictions with repect to patient and animal experiments exist.With the volume data from magnetic resonance imaging (MRI) scan and myofiber tensor eigenvector data from diffusion tensor MRI (DT-MRI) scan at 7.1 Tesla field strength at Duke University Medical Center, a three-dimentional mathematical biventricular model of canine with fine anatomical structure was successfully constructed firstly according to the knowledge of heart anatomy. The electrical activation conduction sequences of ventricles were then simulated based on the implementiaon of the parallel algorithms for ionic-channel model and monodomain model equations of myocardial excitation propagation. Finally, using the finite element methods with an eight-node isoparametric element, a biventricular electromechanical coupled model of canine was constucted by applying the active forces to the geometric model of ventricles. The material properties of myocardium were assumed to be transversely isotropic with respect to fiber directions. The quantification of characteristics of ventricualr mechanics were then obtained by simulation of motion and deformation of ventricles. After that, the models of heart failure (HF) caused by myocardial infarction (MI) and bundle branch block (BBB) were investigated. A mathematical model of left ventricular pacing site and timing delay optimization during cardiac resynchronization therapy (CRT) was also presented.The main innovations and contributions in the dissertation as bellow:(1) Validate the feasibility of constructing a three-dimentional electromechanical coupled model of biventricle with real geometry and myofiber orientations scanned from MRI and DT-MRI. It was well known that cardiac wall mechanics appeared very sensitive to the geometry and fiber orientations. However, previous cardiac models were often constructed with simple axial symmetrical geometry or linear varied fiber orientations from endocardium to epicardium, which didn't accord with the true characteristics of heart mechanics.(2) Quantitatively analyze the influence of location and size of MI to the extent of infarct expansion (IE) after acute myocardial infarction (AMI). The ventricular motion and distributions of principal strain and stress during systole were used to contrast the extent of IE at different locations and with different size. The results showed that IE occured more in anterior wall (AW) near apex than in posterior wall (PW), and larger transmural MI may contribute a lot to the development of IE, which was in agreement with clinical results. Such quantitative research of IE with virtual heart modeling was seldom found in others'models.(3) Successfully investigate the quantification of mechanical intra-and interventricular asynchrony of BBB and also the asynchronous electrical excitation propagation in BBB. The simulation results showed that there existed inter-and intraventricular systolic dyssynchrony during BBB while RBBB might have more mechanical synchrony and better systolic function of the left ventricle (LV) than LBBB. The ventricles always moved toward the early-activated ventricle and the septum experienced higher stress than left and right ventricular free walls in BBB. Most mathematical heart models have mainly focused on the electrophysiological properties of BBB, and RBBB models are seldom found.(4) Presents methods and strategy to carry out automatic, non-invasive LV electrode position and interventricular delay (VVD) optimization of biventricular pacing in a mathematical LBBB model of canine preoperatively, with the circumferential uniformity ratio estimate (CURE). The results showed that, prior to electrical evaluation index of optimization (i.e. the minimum error between physiological excitation and pathology/therapy) in previous computer models, the mechanical evaluation index (i.e. CURE) could evaluate ventricular synchrony of contraction and hemodynamics better during CRT. It also pointed out the importance of individually adjusting the pacing lead positions as well as the timing delays to the patient's anatomy and pathology, which was in accordance with current clinical studies.In brief, this study suggests that such an electromechanical heart model, incorporating real anatomical geometry and fiber orientations, has the potential to assess the mechanical function of ventricles under physio-pathlogical conditions, which provides probabilities in future's patient-specific computer model of various forms of cardiac pathology for human being. An important purpose of the mordern medicine is to get accurate diagnosis and treatment of diseases from patient-specific physiological informations obtained non-invasively under normal and abnormal condition, and it may be achieved by mathematical models. On one hand, heart modeling may increase our understanding of mechanism of heart diseases; on the other hand, models are always simplified descriptiosn of the real process and thus the results need to be validated by a lot of experimental work. The final goal of heart modeling and simulation is to get fusion of the information from experiments, clinical examination and virtual heart modeling so that doctors can make right decisions of diagnosis and treatment of heart diseases. Combination of forward and backward modeling of heart is of the greastest importance.
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