Monitoring of cerebral oxygenation, cerebrovascular reactivity and circulatory function in preterm infants Brain injury in the preterm infant is associated with death and lifelong disability. Cerebral hypoxia and fluctuations in cerebral blood flow in the first two days of life have been implicated in the pathophysiology of haemorrhagic and ischaemic brain injury. Monitoring of haemodynamic changes during the early transitional circulation from in-utero to ex-utero life are currently based on standard measurements of systemic oxygenation and mean arterial blood pressure, with no reliable assessment of end-organ perfusion. In this thesis, measurements using near-infrared spectroscopy (NIRS) and functional echocardiography were made to assess cerebral perfusion and systemic blood flow in a cohort of preterm infants undergoing intensive care. This thesis is divided into four sections: i) The feasibility of continuous monitoring of cerebral oxygenation and cerebrovascular reactivity is demonstrated in a series of case reviews, and the association between cerebral oxygenation and cerebrovascular reactivity with outcome of brain injury and mortality is described. ii) Combining measurements of systemic blood flow with end organ perfusion was applied to define MABPOPT in preterm infants based on an index of cerebrovascular reactivity. Deviations below MABPOPT were associated with intraventricular haemorrhage and mortality. iii) The complexity of brain and systemic signals was studied by using multi-scale entropy analysis. Most studies using cerebral NIRS or systemic measurements of blood flow use linear analysis; however, a complex biological system, such as the human brain, includes many regulatory mechanisms that interact in a complex manner, resulting in effects that cannot be understood wholly through the analysis of its individual constituents. Lower complexity of brain signals was observed in infants who developed intraventricular hemorrhage or died. iv) Changes in systemic and cerebral oxygenation in a cohort of preterm infants in the first 48 hours of life was assessed using functional echocardiography. The patterns of changes in cardiac output and cerebral oxygenation in infants who did and did not have intraventricular haemorrhage are discussed. Furthermore, the relationship between the presence of a haemodynamically significant ductus arteriosus and brain injury is assessed.

A doença renal policística autossômica dominante (DRPAD) felina é caracterizada pela presença de múltiplos cistos localizados em parênquima renal e, ocasionalmente, hepáticoe pancreático, sendo uma importante causa de doença renal crônica terminal. Ela é considerada a enfermidade congênita hereditária mais prevalente dos gatos domésticos, porém, os dados epidemiológicos eclínicos existentes no Brasil são escassos, o que torna o seu controle mais difícil no país. Da mesma forma, a DRPAD em humanos constitui-se na doença renal monogênica mais comum, acometendo 1 em cada 400 a 1.000 indivíduos, com curso clínico muito semelhante a doença em gatos.No presente estudo, 252 felinos da raça Persa e mestiços de Persa do Estado de São Paulo foram avaliados através de teste genético para DRPAD. Os resultados indicaram uma prevalência de apenas 6,35% de gatos portadores da mutação para DRPAD em heterozigose, valor abaixo dos índices registrados em outros países. Do total de animais, uma coorte de 82 felinos da região metropolitana de São Paulo foi selecionada para realização de exames físico, laboratoriais, imagenológicos e genéticos. Estes animais foram separados em dois grupos de acordo com a presença (n=12) ou ausência (n=70) de alterações ultrassonográficas sugestivas de doença renal policística.A sensibilidade e a especificidade entre o teste molecular e o exame ultrassonográfico para DRPAD nos animais estudados foram ambas de 100%. Os animais com alterações genéticas e ultrassonográficas indicativas de doença renal policística autossômica dominante apresentaram aumento significativo no valor de cálcio total sérico, fração de excreção urinária de cálcio e de sódio(p=0,0219; p=0,0275; p=0,0032, respectivamente). Os demais parâmetros clínicos e laboratoriais não diferiram entre os dois grupos de animais. O exame ecocardiográfico revelou que casos de hipertrofia miocárdica foram mais frequente entre os animais positivos para DRPAD (p=0,0001). Dessa forma, é possível concluir que exames de triagem ultrassonográfica e/ou molecular devem ser utilizados para o diagnóstico de animais com DRPAD, visto que, alterações clínicas e laboratoriais sã o tardias. Exames eletro e ecocardiográficos devem ser rotineiramente realizados nos felinos císticos. Ainda, a caracterização clínica da DRPAD em gatos ressalta não apenas sua grande importância para medicina felina, mas também para a comunidade médica devido à correlação com a doença humana, representando um modelo ortólogo espontâneo, em animal de porte médio, para o estudo dessa enfermidade e validação de novos procedimentos terapêuticos. / Autosomal dominant polycystic kidney disease (ADPKD) in feline is characterized by the presence of multiple cists located in the renal parenchyma and occasionally, in liver and pancreas, and is an important cause of terminal chronic renal disease. It is considered worldwide as the most prevalent congenital illness in domestic cats. However, in Brazil the epidemiological and clinical data are barely existent, which difficultythe control of the disease. In the same way, the human ADPKD is the most common monogenic kidney disease. It affects 1 in every 400 to 1000 individuals, with a clinical course very similar to the disease in feline. In this research, 252 Persians and crossbreed cats from São Paulo state were assessed through the genetic test for ADPKD. The results indicated a prevalence of only 6.35% of cats carring the mutation for ADPKD in heterozygosis. This value is below the indexes reported in other countries. A cohort of 82 cats was selected in the metropolitan region of São Paulo to perform physical, laboratory, imaging and genetic tests. These animals were divided into two groups according to the presence (n = 12) or absence (n = 70) of ultrasound changes suggestive of polycystic kidney disease. The sensitivity and specificity between molecular tests and ultrasonography exam for ADPKD in the sample were both 100%. The animals with ultrasonography and genetic modifications, indicatives of ADPKD, presented a significant increase in the amount of total serum calcium, urinary fractional excretion of calcium and sodium(p=0,0219; p=0,0275; p=0,0032, respectively). Other clinical and laboratory parameters did not differ between the two groups of animals with and without the disease. Echocardiographic examination revealed that cases of myocardial hypertrophy were more frequent among animals positive for ADPKD (p = 0.0001). In conclusion, ultrasound exams and/ or molecular screening should be used to diagnostic animals with ADPKD, since the clinical and laboratory abnormalities are late. Electrocardiography and echocardiography examinations should be routinely performed in cystic cats. Still, the clinical characterization of ADPKD in cats not only highlights its importance to feline medicine, but also for the medical community due to the correlation with human disease, as an ortholog spontaneous model for the study of this disease.

Introdução: O tromboembolismo é uma grave complicação da fibrilação atrial (FA), particularmente em pacientes que vão se submeter à cardioversão, química ou elétrica. Para reduzir esse risco, os pacientes submetem-se à anticoagulação clássica, que vem sendo praticada há várias décadas. Apesar desta abordagem, em pacientes plenamente anticoagulados, não se conhece a prevalência de trombo ou contraste espontâneo no átrio esquerdo (AE). Por essa razão, alguns autores sugerem a realização do ecotransesofágico (ECOTEE) para confirmar o sucesso do tratamento e reduzir o risco de complicações tromboembólicas após a reversão. Os objetivos deste estudo foram: a) avaliar a prevalência de trombos e contraste espontâneo ao ECOTEE em pacientes que vão ser submetidos à cardioversão sob regime de anticoagulação plena; b) avaliar a incidência de tromboembolismo até 30 dias após o procedimento; c) avaliar a influência das variáveis clínicas (doenças associadas) e do ECOTEE (tamanho e volume indexado do AE, fração de ejeção ventricular; velocidade de fluxo no apêndice atrial esquerdo), além do escore CHA2DS2VASc e níveis de pró-BNP plasmático sobre a formação de trombo/contraste espontâneo. Métodos: Foram incluídos 85 pacientes (62 homens; média de idade 61±12 anos) com FA não valvar com indicação para cardioversão. Todos receberam varfarina com controle da taxa de INR. Quando se considerava o paciente plenamente anticoagulado (INR ente 2 e 3 por três semanas consecutivas), era prescrito um fármaco antiarrítmico (propafenona, sotalol ou amiodarona) cuja escolha se baseou em critérios clínicos. Na ausência de normalização do ritmo, eram encaminhados para cardioversão elétrica (CVE). No dia da CVE, os pacientes submetiam-se ao ECOTEE cujo resultado só era conhecido no dia seguinte após a cardioversão. Os pacientes recebiam alta com anticoagulante e retornavam ao ambulatório após 30 dias quando realizavam outro ECOTEE. Resultados: Todos os pacientes foram cardiovertidos com INR na faixa terapêutica (2,9±0,7). A reversão com fármacos ocorreu em 9/85 pacientes (10,6%); 67/76 pacientes submeteram-se à CVE e, destes, 58/67 (86%) reverteram ao ritmo sinusal. O ECOTEE antes da CVE evidenciou trombo no AE em 8/85 pacientes (9,4%) e contraste espontâneo em 36/85 pacientes (42,3%). Nenhuma variável clínica, escore CHA2DS2VASc, níveis plasmáticos de pró-BNP ou variáveis ecocardiográficas identificou pacientes com maior probabilidade de apresentar trombo/contraste espontâneo no AE. Após 30 dias, houve normalização das variáveis do ECOTEE. Em 5/8 (62,5%) pacientes, os trombos desapareceram e surgiu em outros dois pacientes (2,3%). O contraste espontâneo desapareceu em 24/38 (63%) pacientes. Não houve registro de nenhum caso de tromboembolismo sistêmico em 30 dias. A taxa de recorrência de FA foi de 21%. Conclusões: a) trombo atrial/contraste espontâneo foi detectado em 9,4% da população e nenhuma variável clínica ou ecocardiográfica identificou pacientes de risco; b) houve melhora das variáveis do ECOTEE após a reversão ao ritmo sinusal; d) o sucesso global da cardioversão foi de 88% e a taxa de recorrência de FA de 21% em 30 dias; c) não houve registro de tromboembolismo sistêmico em 30 dias, em ritmo sinusal ou em FA. / Introduction: Thromboembolism is a serious complication of atrial fibrillation (AF), particularly in patients who will undergo chemical or electrical cardioversion. To reduce this risk patients receive classic anticoagulant therapy, which has been practiced for several decades. Despite this approach, it is not known the prevalence of thrombus or spontaneous contrast in the left atrium (LA) in patients fully anticoagulated. For this reason, some authors have recommended the transesophageal echocardiogram (TEECHO) to reduce the risk of thromboembolic complications after cardioversion. The objectives of this study were: a) to evaluate the prevalence of thrombus and spontaneous contrast by TEECHO in patients about to undergo cardioversion under full anticoagulation regime; b) evaluate the incidence of thromboembolism within 30 days after the procedure; c) evaluate the influence of clinical variables (associated diseases) and TEECHO parameters (LA size and LA indexed volume, ventricular ejection fraction, flow velocity in the left atrial appendage), CHA2DS2VASc score and plasma pro-BNP levels on thrombus/spontaneous contrast formation. Methods: We included 85 patients (62 men; mean age 61 ± 12 years) with non-valvular AF referred for cardioversion. All received warfarin with INR control. When considering the patient fully anticoagulated (INR in the range of 2 to 3 for three weeks) it was prescribed an anti-arrhythmic drug (propafenone, sotalol or amiodarone) whose choice was based on clinical criteria. In the absence of normal rhythm, patients were referred for electrical cardioversion (ECV). On the day of ECV, all patients were submitted to the ECOTEE whose result was known only the next day after cardioversion. The patients were discharged with anticoagulant and returned to the clinic after 30 days when another ECOTEE was performed. Results: All patients were cardioverted with INR in the therapeutic range (2.9±0.7). Sinus rhythm was restored with drugs in 9/85 patients (10.6%); 67/76 patients underwent ECV and 58/67 (86%) reverted to sinus rhythm. The TEECHO before cardioversion showed a thrombus in LA in 8/85 patients (9.4%) and spontaneous contrast in 36/85 patients (42.3%). No clinical variable, CHA2DS2VASc score, pro-BNP plasma levels or echocardiography variables identified patients with an increased likelihood of thrombus/spontaneous contrast in LA. After 30 days, there was normalization of TEECHO variables. In 5/8 (62.5%) patients thrombi disappeared and appeared in two patients (2.3%). Spontaneous contrast disappeared in 24/38 (63%) patients. There were no reports of any case of systemic thromboembolism in 30 days. The AF recurrence rate was 21%. Conclusions: a) LA thrombus/ spontaneous contrast were detected in 9.4% of the population and no clinical or echocardiography variable identified patients at risk; b) there was an improvement of TEECHO variables after reversion to sinus rhythm; d) the overall success of cardioversion was 88% and the AF recurrence rate was 21% in 30 days; c) there was no systemic thromboembolism in 30 days, in patients in sinus rhythm or AF.

Les maladies cardiovasculaires sont de nos jours un problème de santé majeur. L'amélioration des méthodes liées au diagnostic de ces maladies représente donc un réel enjeu en cardiologie. Le coeur étant un organe en perpétuel mouvement, l'analyse du mouvement cardiaque est un élément clé pour le diagnostic. Par conséquent, les méthodes dédiées à l'estimation du mouvement cardiaque à partir d'images médicales, plus particulièrement en échocardiographie, font l'objet de nombreux travaux de recherches. Cependant, plusieurs difficultés liées à la complexité du mouvement du coeur ainsi qu'à la qualité des images échographiques restent à surmonter afin d'améliorer la qualité et la précision des estimations. Dans le domaine du traitement d'images, les méthodes basées sur l'apprentissage suscitent de plus en plus d'intérêt. Plus particulièrement, les représentations parcimonieuses et l'apprentissage de dictionnaires ont démontré leur efficacité pour la régularisation de divers problèmes inverses. Cette thèse a ainsi pour but d'explorer l'apport de ces méthodes, qui allient parcimonie et apprentissage, pour l'estimation du mouvement cardiaque. Trois principales contributions sont présentées, chacune traitant différents aspects et problématiques rencontrées dans le cadre de l'estimation du mouvement en échocardiographie. Dans un premier temps, une méthode d'estimation du mouvement cardiaque se basant sur une régularisation parcimonieuse est proposée. Le problème d'estimation du mouvement est formulé dans le cadre d'une minimisation d'énergie, dont le terme d'attache aux données est construit avec l'hypothèse d'un bruit de Rayleigh multiplicatif. Une étape d'apprentissage de dictionnaire permet une régularisation exploitant les propriétés parcimonieuses du mouvement cardiaque, combinée à un terme classique de lissage spatial. Dans un second temps, une méthode robuste de flux optique est présentée. L'objectif de cette approche est de robustifier la méthode d'estimation développée au premier chapitre de manière à la rendre moins sensible aux éléments aberrants. Deux régularisations sont mises en oeuvre, imposant d'une part un lissage spatial et de l'autre la parcimonie des champs de mouvements dans un dictionnaire approprié. Afin d'assurer la robustesse de la méthode vis-à-vis des anomalies, une stratégie de minimisation récursivement pondérée est proposée. Plus précisément, les fonctions employées pour cette pondération sont basées sur la théorie des M-estimateurs. Le dernier travail présenté dans cette thèse, explore une méthode d'estimation du mouvement cardiaque exploitant une régularisation parcimonieuse combinée à un lissage à la fois dans les domaines spatial et temporel. Le problème est formulé dans un cadre général d'estimation de flux optique. La régularisation temporelle proposée impose des trajectoires de mouvement lisses entre images consécutives. De plus, une méthode itérative d'estimation permet d'incorporer les trois termes de régularisations, tout en rendant possible le traitement simultané d'un ensemble d'images. Dans cette thèse, les contributions proposées sont validées en employant des images synthétiques et des simulations réalistes d'images ultrasonores. Ces données avec vérité terrain permettent d'évaluer la précision des approches considérées, et de souligner leur compétitivité par rapport à des méthodes de l'état-del'art. Pour démontrer la faisabilité clinique, des images in vivo de patients sains ou atteints de pathologies sont également considérées pour les deux premières méthodes. Pour la dernière contribution de cette thèse, i.e., exploitant un lissage temporel, une étude préliminaire est menée en utilisant des données de simulation. / Cardiovascular diseases have become a major healthcare issue. Improving the diagnosis and analysis of these diseases have thus become a primary concern in cardiology. The heart is a moving organ that undergoes complex deformations. Therefore, the quantification of cardiac motion from medical images, particularly ultrasound, is a key part of the techniques used for diagnosis in clinical practice. Thus, significant research efforts have been directed toward developing new cardiac motion estimation methods. These methods aim at improving the quality and accuracy of the estimated motions. However, they are still facing many challenges due to the complexity of cardiac motion and the quality of ultrasound images. Recently, learning-based techniques have received a growing interest in the field of image processing. More specifically, sparse representations and dictionary learning strategies have shown their efficiency in regularizing different ill-posed inverse problems. This thesis investigates the benefits that such sparsity and learning-based techniques can bring to cardiac motion estimation. Three main contributions are presented, investigating different aspects and challenges that arise in echocardiography. Firstly, a method for cardiac motion estimation using a sparsity-based regularization is introduced. The motion estimation problem is formulated as an energy minimization, whose data fidelity term is built using the assumption that the images are corrupted by multiplicative Rayleigh noise. In addition to a classical spatial smoothness constraint, the proposed method exploits the sparse properties of the cardiac motion to regularize the solution via an appropriate dictionary learning step. Secondly, a fully robust optical flow method is proposed. The aim of this work is to take into account the limitations of ultrasound imaging and the violations of the regularization constraints. In this work, two regularization terms imposing spatial smoothness and sparsity of the motion field in an appropriate cardiac motion dictionary are also exploited. In order to ensure robustness to outliers, an iteratively re-weighted minimization strategy is proposed using weighting functions based on M-estimators. As a last contribution, we investigate a cardiac motion estimation method using a combination of sparse, spatial and temporal regularizations. The problem is formulated within a general optical flow framework. The proposed temporal regularization enforces smoothness of the motion trajectories between consecutive images. Furthermore, an iterative groupewise motion estimation allows us to incorporate the three regularization terms, while enabling the processing of the image sequence as a whole. Throughout this thesis, the proposed contributions are validated using synthetic and realistic simulated cardiac ultrasound images. These datasets with available groundtruth are used to evaluate the accuracy of the proposed approaches and show their competitiveness with state-of-the-art algorithms. In order to demonstrate clinical feasibility, in vivo sequences of healthy and pathological subjects are considered for the first two methods. A preliminary investigation is conducted for the last contribution, i.e., exploiting temporal smoothness, using simulated data.

Assessment of left ventricular (LV) function is one of the most common requests made to cardiac imaging services. This demand stems from a large body of evidence that shows abnormal LV systolic and, more recently, diastolic function has important prognostic and treatment related implications for patients with a wide range of cardiovascular diseases. The vast majority of information supporting the use of conventional measures of LV function, such as ejection fraction, originates from population studies and large clinical trials. However, the application of these measurements to individual patients is far less defined, especially when used for serial evaluation. Central to these concerns is the relative paucity of data surrounding the test-retest reliability of conventional measures in clinical settings. Newer measures of LV function have been developed over recent years, with several techniques becoming widely used in clinical practice (i.e. tissue Doppler imaging) and others remaining largely research tools (i.e. 3D echocardiography, tissue strain/strain rate). Possible benefits of new technologies include improved identification and early detection of myocardial disease, improved reliability for monitoring progression of disease, and the development of novel methods to assess response to therapy. Despite this potential, the application and clinical utility of these techniques above and beyond more conventional measures remains in many cases to be adequately characterized. This thesis addresses several of these issues: from variability of novel and conventional measures of LV function in clinical practice, to new applications of novel functional measures in clinical settings.

Thesis (Ph. D.)--Ohio State University, 2006. / Title from first page of PDF file. Includes bibliographical references (p. 143-150).

Thesis (Ph. D.)--Ohio State University, 2006. / Available online via OhioLINK's ETD Center; full text release delayed at author's request until 2007 Sep 12

Chronic aortic regurgitation (AR) of varying degree affects 13% of men and 8.5% of women. In persons with severe AR, the expected length of life and its quality are influenced. Some individuals remain asymptomatic for a long period, due to effective compensatory mechanisms, but dysfunction of the left ventricle (LV) usually begins before symptoms appear and can be irreversible by then. This thesis addresses questions of LV function and optimal time for operation of patients suffering from chronic AR. Moreover, detailed echocardiographic studies of the anatomy of the normal aortic valve have been performed to obtain a better understanding of the in vivo anatomic relations within the aortic root. Patients with chronic AR, without concomitant cardiac disease, were studied both retrospectively (n=88) and prospectively (n=29) and the aortic valves of persons (n=32) free from cardiac disease were investigated. For the retrospectively studied patients, survival was 82% at 10 years which is an improvement compared with previously published results. The majority of the patients, however, had LV dysfunction preoperatively. By studying patients prospectively by echocardiography, radionuclide ventriculography (MUGA) and cardiopulmonary exercise testing (CPET) our aim was to evaluate the predictive value of measurements of LV function at rest and during exercise for postoperative outcome. LV diameters were markedly elevated prior to and diminished significantly after surgery. Patients with an abnormal exercise ejection fraction (EF) response by MUGA preoperatively, presented the same reaction postoperatively. This could not be predicted by LV function determination at rest, or by NYHA functional class. In spite of median NYHA class II, these patients had a low work capacity on CPET, which was neither improved 6 months postoperatively nor correlated to echocardiographic LV dimensions. Thus, both MUGA and CPET may be useful complements for timing of surgery in patients with chronic AR. Assuming that patients would benefit from preservation of their native valves the normal aortic valve was studied to gain detailed information about the echocardiographic anatomy and relations within the normal aortic root. This extended examination of the aortic root may facilitate a better planning of aortic valve‐preserving interventions in the future.

The last decades less invasive monitoring and analytical tools have been developed for the evaluation of myocardial mechanics in clinical praxis. In critical care, these are longed-for complements to pulmonary artery catheter monitoring, additionally offering previously inaccessible information. This work is aimed, during fluid-replacement and oxygen therapy, to determine the physiological interface of ventricular and vascular mechanical properties, which result in the transfer of blood from the heart to appropriate circulatory beds. In prospective clinical studies we investigated previously cardiovascular healthy adults during hyperoxemia, and during preoperative acute normovolemic hemodilution or early fluid resuscitation of severe burn victims. Echocardiography was used in all studies, transthoracic for healthy volunteers and transesophageal for patients. For vascular parameters and for control purposes pulmonary artery Swan-Ganz catheter, calibrated external pulse recordings, whole body impedance cardiography, and transpulmonel thermodilution method were applied. We detected no significant change in blood pressure or heart rate, the two most often used parameters for patient monitoring. During preoperative acute normovolemic hemodilution a reduction of hemoglobin to 80 g/l did not compromise systolic or diastolic myocardial function. Cardiac volumes and flow increased with a concomitant fall in systemic vascular resistance while oxygen delivery seemed maintained. Supplemental oxygen therapy resulted in a linear dose-response between arterial oxygen and cardiovascular parameters, suggesting a direct vascular effect. Cardiac flow decreased and vascular resistance increased from hyperoxemia, and a decrease of venous return implied extracardial blood-pooling. Severe burns result in hypovolemic shock if not properly treated. The commonly used Parkland fluid replacement strategy, with urinary output and mean arterial pressure as endpoints, has recently been questioned. Applying this strategy, only transient early central hypovolemia was recorded, while dimensional preload, global left ventricular systolic function and oxygen delivery or consumption remained within normal ranges during the first 36 hours after accident. Signs of restrictive left ventricular diastolic function were detected in all patients and regional unstable systolic dysfunction was recognized in every other patient, and was consistent with myocardial marker leakage. Severe burns thereby cause myocardial stiffness and systolic regional dysfunction, which may not be prevented only by central normovolemia and adequate oxygenation. / On the day of the defence date the status of article II was: In Press.

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.