The heart is a complex organ and much is still unknown about its mechanical function. In order to use simulations to study heart mechanics, fluid and solid components and their interaction should be incorporated into any numerical model. Many previous studies have focused on myocardium motion or blood flow separately, while neglecting their interaction. Previous fluid-structure interaction (FSI) simulations of heart mechanics have made simplifying assumptions about their solid models, which prevented them from accurately predicting the stress-stain behaviour of the myocardium. In this work, a numerical model of the canine left ventricle (LV) is presented, which serves to address the limitations of previous studies. A canine LV myocardium material model was developed for use in conjunction with a commercial finite element code. The material model was modified from its original form to make it suitable for use in simulations. Further, numerical constraints were imposed when calculating the material parameter values, to ensure that the model would be strictly convex. An initial geometry and non-zero stress state are required to start cardiac cycle simulations. These were generated by the static inflation of a passive LV model to an end-diastolic pressure. Comparisons with previous measurements verified that the calculated geometry was representative of end diastole. Stresses calculated at the specified end diastolic pressure showed complex spatial variations, illustrating the superiority of the present approach over a specification of an arbitrary stress distribution to an end-diastolic geometry. In the third part of this study, FSI simulations of the mechanics of the LV were performed over the cardiac cycle. Calculated LV cavity pressures agreed well with previous measurements during most of the cardiac cycle, but deviated from them during rapid filling, which resulted in non-physiological backflow. This study is the first one to present a detailed analysis of the temporal and spatial variations of the properties of both the solid and the fluid components of the canine LV. The observed development of non-uniform pressure distributions in the LV cavity confirms the advantage of performing FSI simulations rather than imposing a uniform fluid pressure on the inner surface of the myocardium during solid-only simulations.

This study examined the effects of short-term high-intensity interval training (HIT) and continuous moderate-intensity training (CMT) on left ventricular (LV) function in young, healthy men. Sixteen untrained men were randomly assigned to HIT (8-12 X 60:75 seconds cycling at 95-100%:10% V˙O2peak) and CMT (90-120 minutes cycling at 65% V˙O2peak) and assessed before and after six sessions of training. LV function was determined at rest and during submaximal exercise using two-dimensional and Doppler echocardiography. HIT and CMT improved V˙O2peak and induced plasma volume expansion to a similar magnitude. Although resting LV function did not change, increased exercise stroke volume and cardiac output was observed, secondary to increases in end-diastolic volume. Numerous ECHO-derived indices of diastolic performance were similarly enhanced during exercise in both groups. Short-term HIT and CMT elicit rapid increases in V˙O2peak and LV filling without global changes in systolic performance or cardiac morphology at rest.

This study examined the effects of short-term high-intensity interval training (HIT) and continuous moderate-intensity training (CMT) on left ventricular (LV) function in young, healthy men. Sixteen untrained men were randomly assigned to HIT (8-12 X 60:75 seconds cycling at 95-100%:10% V˙O2peak) and CMT (90-120 minutes cycling at 65% V˙O2peak) and assessed before and after six sessions of training. LV function was determined at rest and during submaximal exercise using two-dimensional and Doppler echocardiography. HIT and CMT improved V˙O2peak and induced plasma volume expansion to a similar magnitude. Although resting LV function did not change, increased exercise stroke volume and cardiac output was observed, secondary to increases in end-diastolic volume. Numerous ECHO-derived indices of diastolic performance were similarly enhanced during exercise in both groups. Short-term HIT and CMT elicit rapid increases in V˙O2peak and LV filling without global changes in systolic performance or cardiac morphology at rest.

The heart is a complex organ and much is still unknown about its mechanical function. In order to use simulations to study heart mechanics, fluid and solid components and their interaction should be incorporated into any numerical model. Many previous studies have focused on myocardium motion or blood flow separately, while neglecting their interaction. Previous fluid-structure interaction (FSI) simulations of heart mechanics have made simplifying assumptions about their solid models, which prevented them from accurately predicting the stress-stain behaviour of the myocardium. In this work, a numerical model of the canine left ventricle (LV) is presented, which serves to address the limitations of previous studies. A canine LV myocardium material model was developed for use in conjunction with a commercial finite element code. The material model was modified from its original form to make it suitable for use in simulations. Further, numerical constraints were imposed when calculating the material parameter values, to ensure that the model would be strictly convex. An initial geometry and non-zero stress state are required to start cardiac cycle simulations. These were generated by the static inflation of a passive LV model to an end-diastolic pressure. Comparisons with previous measurements verified that the calculated geometry was representative of end diastole. Stresses calculated at the specified end diastolic pressure showed complex spatial variations, illustrating the superiority of the present approach over a specification of an arbitrary stress distribution to an end-diastolic geometry. In the third part of this study, FSI simulations of the mechanics of the LV were performed over the cardiac cycle. Calculated LV cavity pressures agreed well with previous measurements during most of the cardiac cycle, but deviated from them during rapid filling, which resulted in non-physiological backflow. This study is the first one to present a detailed analysis of the temporal and spatial variations of the properties of both the solid and the fluid components of the canine LV. The observed development of non-uniform pressure distributions in the LV cavity confirms the advantage of performing FSI simulations rather than imposing a uniform fluid pressure on the inner surface of the myocardium during solid-only simulations.

Heart failure is the clinical syndrome accompanying the inability of the heart to maintain a cardiac output required to meet the metabolic requirements and accommodate venous return, and is one of the leading causes of mortality in United States. Accurate imaging of the heart and its failure is important for successful patient management and treatment. Multiple cardiac imaging modalities provide complementary information about the heart – LV function and wall motion, anatomy, myocardial viability and ischemia. In many instances, it is necessary for a patient to undergo multiple imaging sessions to obtain diagnostic clinical information with confidence. It would be beneficial to the individual and the health care system if a single imaging modality could yield reliable clinical information about the heart, leading to a reduced cost, anxiety and an increased diagnostic confidence. This thesis proposes methods that would make cardiac MRI perform an improved assessment of LV function, wall motion, and viability, such that cardiac MRI is taken one step closer to being a single stop solution for imaging of heart. Conventional cardiac MR imaging is performed at a temporal resolution of around 40 ms per cardiac phase. While the global left ventricular (LV) function can be reliably established at this temporal resolution, functional metrics characterizing transient function like peak filling and ejection rates are not accurately assessed. A high temporal resolution is necessary to characterize such transient LV function and wall motion mechanics. This thesis proposes methods to acquire cine-images of the heart at a higher temporal resolution (~ 6 ms) and algorithms to acquire the LV volume across all cardiac phases that would yield functional metrics characterizing LV function and wall motion mechanics. The validation of these algorithms was performed on human subjects. Cardiac MR imaging is the current gold standard of myocardial viability imaging, in which scarred regions of the heart following myocardial infarction are visualized. However viability imaging faces image quality challenges in patients with severe arrhythmias and in cases where a higher spatial resolution, and hence a longer acquisition time, is desired. This thesis also proposes an arrhythmia insensitive inversion recovery (AIIR) algorithm that would significantly reduce artifacts that degrade image quality, thereby extending viability imaging to higher spatial resolution and in patients with severe arrhythmia. Simulations, experimental validation on phantoms and clinical verification on patients are performed. Results from high temporal resolution imaging reveal that obtaining cine cardiac MR images at a temporal resolution of 6 ms per cardiac phase is feasible. Appropriate validated algorithms yield LV time-volume curve from which LV functional metrics are reliably extracted. A dependence on temporal resolution is revealed, and a temporal resolution cut-off of 12 ms is proposed to reliably capture the temporal dynamics of the LV. Also, results from cardiac viability imaging show that the AIIR algorithm performs significantly better than conventional imaging methods in both phantoms and human subjects, as shown by the blinded expert scores, leading to a better image quality. In conclusion, this thesis proposes and implements methods that help cardiac MRI yield 1) a better function and wall motion assessment of the heart through high temporal resolution imaging and 2) a better assessment of myocardial viability through the AIIR algorithm.

published_or_final_version / Paediatrics and Adolescent Medicine / Master / Master of Medical Sciences

The heart is a complex organ and much is still unknown about its mechanical function. In order to use simulations to study heart mechanics, fluid and solid components and their interaction should be incorporated into any numerical model. Many previous studies have focused on myocardium motion or blood flow separately, while neglecting their interaction. Previous fluid-structure interaction (FSI) simulations of heart mechanics have made simplifying assumptions about their solid models, which prevented them from accurately predicting the stress-stain behaviour of the myocardium. In this work, a numerical model of the canine left ventricle (LV) is presented, which serves to address the limitations of previous studies. A canine LV myocardium material model was developed for use in conjunction with a commercial finite element code. The material model was modified from its original form to make it suitable for use in simulations. Further, numerical constraints were imposed when calculating the material parameter values, to ensure that the model would be strictly convex. An initial geometry and non-zero stress state are required to start cardiac cycle simulations. These were generated by the static inflation of a passive LV model to an end-diastolic pressure. Comparisons with previous measurements verified that the calculated geometry was representative of end diastole. Stresses calculated at the specified end diastolic pressure showed complex spatial variations, illustrating the superiority of the present approach over a specification of an arbitrary stress distribution to an end-diastolic geometry. In the third part of this study, FSI simulations of the mechanics of the LV were performed over the cardiac cycle. Calculated LV cavity pressures agreed well with previous measurements during most of the cardiac cycle, but deviated from them during rapid filling, which resulted in non-physiological backflow. This study is the first one to present a detailed analysis of the temporal and spatial variations of the properties of both the solid and the fluid components of the canine LV. The observed development of non-uniform pressure distributions in the LV cavity confirms the advantage of performing FSI simulations rather than imposing a uniform fluid pressure on the inner surface of the myocardium during solid-only simulations.

Thesis (Ph.D.)--Biomedical Engineering, Georgia Institute of Technology, 2008. / Committee Chair: Oshinski, John N.; Committee Member: Fyfe, Derek A.; Committee Member: León, Angel R.; Committee Member: Skrinjar, Oskar; Committee Member: Taylor, W. Robert.

Os estudos relacionados ao coração têm sido realizados ao longo dos anos de forma bastante comum, tendo em vista a grande importância que este órgão tem na medicina. Problemas relacionados ao mesmo são uma das principais causas de mortes e internações no Brasil e no mundo, por causa disso, avanços no que diz respeito a inovações tecnológicas e novas metodologias de estudo tem sido propostas cada vez com mais freqüência, e, o suíno tem se mostrado um modelo bastante útil, pois apresenta diversas similaridades em relação ao ser humano.O uso da estereologia se encaixa nesta nova busca, pois através de suas ferramentas nos proporciona excelentes resultados a níveis de mensuração, e quantificação de estruturas microscópicas. O objetivo desse estudo foi obter valores referentes à quantificação de cardiomiócitos do ventrículo esquerdo em suínos normais. Utilizaram-se 3 suínos fêmeas pesando em torno de 25kg, os quais após serem eutanasiados tiveram o coração retirado e suas câmaras separadas. Em seguida lâminas referentes a esse material foram preparadas e fotografadas, para serem analizadas utilizando-se o disector e o nucleator como ferramentas estereologicas. Os resultados nos mostram que a média de peso do ventrículo esquerdo dos animais foi de 660 mg, o volume médio dos cardiomiócitos foi de 16.32 µm³, a média do numero de cardiomiócitos foi de 3,91x108, enquanto que a média do volume de cardiomiócitos que ocupam o ventrículo esquerdo foi de 3,32x106. / Investigations involving the heart have been largely carried out all over the years due to its importance in medicine. Heart diseases are the one of the major causes of deaths and hospitalizations in Brazil and worldwide. In this context, technological innovations and progresses in methodological investigation have been frequently proposed; Swine has been shown as a useful model due to similarities to human. The application of stereological tools for investigations in the morphology of the heart has been intensely applied based on the reliability on the results for measuring and quantification. This study aimed to evaluate morphological and quantitative aspects of cardiomyocytes in the left ventricle in healthy swine. Three female swine, averaging 25 kg were euthanasiated and have the hearth chambers separated. Left ventricles were fixed and slides obtained. Images were acquired and analyzed by dissector and nucleator. The results showed us that the average weight of the left ventricle of the animals was 660 mg, the mean volume of cardiomyocytes was 16:32 µm3, the average number of cardiomyocytes was 3.91 x108, while the average volume of cardiomyocytes that occupy the left ventricle was 3.32 x106.

Diversos estudos indicam que a deficiência de estrógeno aumenta a incidência de doenças cardiovasculares em mulheres na pós-menopausa. Os efeitos decorrentes da deprivação de estrógeno no miocárdio ainda não estão totalmente esclarecidos. Estudos têm evidenciado efeitos benéficos da atividade física no sistema cardiovascular, em qualquer condição, em especial na menopausa. Utilizando ratos Wistar, como modelo experimental, os objetivos deste trabalho são: a) verificar se a ooforectomia e a atividade física produzem alterações no miocárdio do ventrículo esquerdo, b) verificar se a realização do exercício físico aeróbico tem efeito sobre essas alterações. Para a realização deste estudo foram utilizadas 15 ratas com 6 meses de idade, da linhagem Wistar, distribuídas em 3 grupos de 5 ratas cada: GC- Ratas com 6 meses de idade sem ooforectomia e sem atividade física; GS- Ratas com 6 meses de idade com ooforectomia bilateral sem atividade física; GA- Ratas com 6 meses de idade com ooforectomia bilateral que realizaram atividade física (corrida em esteira) durante 3 meses. Os animais dos 3 grupos foram eutanasiados com 9 meses de idade. A avaliação foi realizada através de microscopia de luz e estereologia. Os cortes histológicos foram corados por: Hematoxilina-Eosina e Picrosírius. Na parede do ventrículo esquerdo foram estimadas as densidades de volume dos cardiomiócitos, do tecido conjuntivo e a densidade de comprimento e densidade de volume dos vasos intramiocárdicos. Foi estimado o número total de núcleos de cardiomiócitos e sua densidade numérica foi estimada através do método disector. Os dados quantitativos dos três grupos foram estatisticamente comparados através do ANOVA e teste de Tukey. Os resultados mostraram que houve um aumento de peso nos animais do GS e GA em relação ao GC. Quanto ao treinamento, os animais do GA tiveram melhor rendimento nos TEMs. Quanto ao volume do VE, observamos uma diminuição, embora não significante, nos animais do GS e GA em relação ao GC. A densidade de volume dos vasos intramiocárdicos foi maior no GC que no GA. As diferenças não foram estatisticamente significantes em relação à ooforectomia e ao exercício físico para os parâmetros: densidade de volume dos cardiomiócitos e do tecido conjuntivo, densidade de comprimento dos vasos intramiocárdicos, densidade numérica dos núcleos dos cardiomiócitos, número total de núcleos de cardiomiócitos e densidade numérica do colágeno. Esses dados nos levam a concluir que a ooforectomia acarreta alterações no volume do ventrículo esquerdo e a atividade física diminui a densidade de volume dos vasos intramiocárdicos. Quanto aos outros itens, nem a ooforectomia, nem a atividade física, isoladamente ou associada, parecem influenciar de maneira significativa nestes dados. / Severals studies indicate that the estrogen deficiency increase the incidence of the cardiovascular diseases in women in the post-menopausal period. The effects of the estrogen deprivation in the myocardium still remain unclear. Studies have proved beneficial effects of the physical activity in the cardiovascular system, especially in the menopause. Using Wistar rats, as an experimental model, the aims of this work are: a-) to check if the ooforectomy and the physical activity produce alterations in the left ventricle of the myocardium; b-) to check if the aerobic exercise realization affects these alterations. To achieve these goals it was used 15 Wistar rats of 6 months of age, distributed in 3 groups of five rats each: Control group- Rats with six months of age without ooforectomy and physical activity; GS- Rats with six months of age with ofoorectomy bilateral and without physical activity and, GA- Rats with six months of age with ooforectomy bilateral and physical activity during 3 months. Al rats were euthanasied with 9 months of age. The results were obtained by using light microscopy were and stereology. The histological section was stained with Hematoxylin and Eosin, and Picrosirius stain. On the wall of the left ventricle were estimated the density of volume of the cardiomiocyt, of the connective tissue and the density of length and the density of volume of the intramyocardial vessels. It was estimated the total number of nuclei of cardiomiocyt and its numerical density was estimated a cross the disector method. The data of the three groups were statistically compared for the ANOVA and Tukey´s test. The results showed that there was an increase in the weight in the animals of GS and of GA. In relation to training, the animals of GA obtained the best income in the TEMs. In relation to the volume of the left ventricle, it was observed a decrease, although not significant, in the animals of GS and GA. The density of volume of the intramyocardial vessels was higher in the GC than GA. In relation to the ooforectomy and the physical exercise for the items: density of volume of the cardiomiocyt and of the connective tissue, density of length of the intramyocardial vessels, numerical density of nuclei of cardiomiocyt, total number of nuclei of cardiomiocyt and numerical density of collagen, the differences werent significant. We can conclude that the ooforectomy result in changes in the volume of the left ventricle and that the physical activity decrease the density of volume of the intramyocardial. In relation to the other items, neither the ooforectomy, neither the physical activity, alone or together, seem doesn\'t affect these data.