The general purpose of this thesis is to establish capability and accuracy of speckle tracking echocardiography (STE) in assessing left atrial (LA), left ventricular (LV) and right ventricular (RV) function and their correlation with myocardial fibrosis, filling pressure and clinical outcomes in advanced heart failure (HF) patients before and after heart transplantation (HT). I demonstrated that HT recipients had impaired LV twist dynamics in the form of reduced rotation twist angle and untwist rate but time to peak twist was not different from the age matched controls and other cardiac surgical patients. With a longitudinal study conducted on patients with refractory HF, the best prognostic power has been shown by RV strain analysis. Among the indexes of LV function, the LV ejection fraction (LVEF) demonstrated the lowest diagnostic accuracy; instead LV global circumferential strain (GCS) showed a better sensitivity and specificity than LV global longitudinal strain (GLS). When analyzing the relationship between different severity of myocardial fibrosis and LV cavity function, the strongest function parameter that correlated with severity of myocardial fibrosis was GLS. In contrast, none of diastolic LV function or even measures of exercise capacity correlated with myocardial fibrosis. In patients with end-stage HF, global peak atrial longitudinal strain (PALS), an index of atrial reservoir function was dependent by pulmonary capillary wedge pressure (PCWP) and LV fibrosis, but not influenced by LV systolic function. Results from this study confirm previous evidence of correlation between impaired global PALS and increased PCWP.

Cardiovascular diseases are the leading causes of death worldwide and improved diagnostic methods are needed for early intervention and to select the most suitable treatment for patients. Currently, carotid artery plaque vulnerability is typically determined by visually assessing ultrasound B-mode images, which is influenced by user-subjectivity. Since plaque vulnerability is correlated to the mechanical properties of the plaque, quantitative techniques are needed to estimate plaque stiffness as a surrogate for plaque vulnerability, which would reduce subjectivity during plaque assessment. The work in this thesis focused on three noninvasive ultrasound-based techniques to quantitatively assess plaque vulnerability and measure arterial stiffness. In Study I, a speckle tracking algorithm was validated in vitro to assess strain in common carotid artery (CCA) phantom plaques and thereafter applied in vivo to carotid atherosclerotic plaques where the strain results were compared to visual assessments by experienced physicians. In Study II, hard and soft CCA phantom plaques were characterized with shear wave elastography (SWE) by using phase and group velocity analysis while being hydrostatically pressurized followed by validating the results with mechanical tensile testing. In Study III, feasibility of assessing the stiffness of simulated plaques and the arterial wall with SWE was demonstrated in an ex vivo setup in small porcine aortas used as a human CCA model. In Study IV, SWE and pulse wave imaging (PWI) were compared when characterizing homogeneous CCA soft phantom plaques. The techniques developed in this thesis have demonstrated potential to characterize carotid artery plaques. The results show that the techniques have the ability to noninvasively evaluate the mechanical properties of carotid artery plaques, provide additional data when visually assessing B-mode images, and potentially provide improved diagnoses for patients suffering from cerebrovascular diseases. / <p>Doctoral thesis in medical technology and medical sciences</p><p>QC 20160921</p>

Thesis deals with ultrasonographic contrast examinations, that are performed to assess tissue perfusion and non-invasive ultrasound method speckle tracking, overcoming the weaknesses of Doppler techniques used to scanning the movement of the tissue.

A doença aterosclerótica coronariana tem um grande impacto na morbidade e mortalidade em todo mundo. A terapia cardíaca com ondas de choque consiste em uma nova opção potencial para o tratamento de pacientes com doença coronariana crônica e angina refratária. No presente estudo, avaliamos os efeitos das ondas de choque na mecânica do ventrículo esquerdo, avaliados pela ecocardiografia com speckle tracking, assim como nos sintomas clínicos e isquemia miocárdica em pacientes com angina refratária. Estudamos, prospectivamente, 19 pacientes com angina refratária submetidos à terapia com ondas de choque com 3 sessões de tratamento por semana, realizados na primeira, quinta e nona semanas, totalizando 9 semanas de tratamento. A mecânica do ventrículo esquerdo foi avaliada por meio da determinação do strain longitudinal global e segmentar. A perfusão miocárdica foi analisada por cintilografia de perfusão miocárdica com Tecnécio-99m Sestamibi, para determinação do summed stress score (SSS). Parâmetros clínicos foram mensurados pelo escore de angina da Canadian Cardiovascular Society (CCS), escore de insuficiência cardíaca da New York Heart Association (NYHA) e qualidade de vida pelo Seattle Angina Questionnaire (SAQ). Todos os dados foram mensurados antes do início do tratamento e 6 meses após a terapia com ondas de choque. Os nossos resultados demonstraram que as ondas de choque não ocasionaram efeitos colaterais importantes e os pacientes apresentaram melhora significativa dos sintomas. Antes do tratamento, 18 (94,7%) pacientes se apresentavam com angina CCS classe III ou IV, e 6 meses após houve redução para 3 (15,8%) pacientes (p = 0,0001), associada à melhora no SAQ (38,5%; p < 0,001). Treze (68,4%) pacientes estavam em classe funcional III ou IV da NYHA antes do tratamento, com redução significativa para 7 (36,8%); p = 0,014. Nenhuma alteração foi observada no SSS global basal no acompanhamento de 6 meses (15,33 ± 8,60 versus 16,60 ± 8,06, p = 0,155) determinado pela cintilografia miocárdica. No entanto, houve redução significativa no SSS médio dos segmentos isquêmicos tratados (2,1 ± 0,87 pré versus 1,6 ± 1,19 pós-terapia, p = 0,024). O strain longitudinal global do ventrículo esquerdo permaneceu inalterado (-13,03 ± 8,96 pré versus -15,88 ± 3,43 pós-tratamento; p = 0,256). Também não foi observada alteração significativa no strain longitudinal segmentar do ventrículo esquerdo pela ecocardiografia com speckle tracking. Concluímos que a terapia com ondas de choque é um procedimento seguro para tratamento de pacientes com angina refratária, que resulta em melhor qualidade de vida, melhora na perfusão miocárdica dos segmentos tratados e preservação da mecânica ventricular esquerda / Coronary atherosclerotic disease represents a major impact on morbidity and mortality worldwide. Cardiac shock wave therapy is a new potential option for the treatment of patients with chronic coronary disease and refractory angina. In the present study, we sought to determine the effects of shock wave therapy on the left ventricular mechanics, evaluated by speckle tracking echocardiography, as well as on myocardial perfusion and symptoms of patients with refractory angina. We prospectively studied 19 patients undergoing shock wave therapy with 3 sessions per week, on the 1st, 5th and 9th weeks, for a total of 9 weeks of treatment. The left ventricular mechanics was evaluated by global longitudinal strain using the speckle tracking echocardiography. Myocardial perfusion was assessed by myocardial scintigraphy with Technetium-99m Sestamibi, for determination of summed stress score (SSS). Clinical parameters were evaluated by the Canadian Cardiovascular Society (CCS) angina score, New York Heart Association (NYHA ) heart failure score and quality of life by the Seattle Angina Questionnaire (SAQ). All data were measured prior to the treatment and 6 months after shock wave therapy. Our results demonstrated that shock wave therapy did not cause significant side effects and improved symptoms. Before treatment, 18 patients (94.7%) had CCS class III or IV angina, and 6 months later there was a reduction to 3 (15.8%), p = 0.0001, associated with improvement in SAQ ( 38.5%, p < 0.001). Thirteen (68.4%) were in NYHA class III or IV before treatment, with a significant reduction to 7 (36.8%); p = 0.014. No change was observed in the global SSS at 6-months follow-up (from 15.33 ± 8.60 baseline to 16.60 ± 8.06 post-treatment, p = 0.155). However, there was a significant reduction in the mean SSS of the treated ischemic segments (2.1 ± 0.87 pre versus 1.6 ± 1.19 post therapy, p = 0.024). The global longitudinal strain remained unchanged (-13.03 ± 8.96 pre versus -15.88 ± 3.43 6 months post-treatment, p = 0.256). In the same way, no significant difference was observed in the longitudinal strain of the left ventricular segments. We concluded that shock wave therapy is a safe procedure for the treatment of patients with refractory angina, resulting in better quality of life, improved myocardial perfusion of the treated segments, and preservation of left ventricular mechanics

Le projet HORACE consiste en la réalisation d'une horloge atomique compacte de hautes performances exploitant le refroidissement laser d'atomes de 133Cs en "lumière isotrope", en visant principalement le marché des horloges embarquées. Afin d'obtenir un dispositif de faible encombrement, nous réalisons en un lieu unique l'ensemble des phases de la séquence d'horloge (refroidissement, préparation, interrogation et détection). Ceci est rendu possible grâce à l'utilisation d'une cavité d'interrogation à la fois résonnante à la fréquence de la transition d'horloge, et faisant office de sphère intégrante pour la lumière de refroidissement. L'essentiel du travail de thèse présenté ici est consacré à l'étude expérimentale du refroidissement dans le champ de speckle 3D généré à l’intérieur de cette cavité. En limitant le refroidissement à une simple phase de capture, environ 3x108 atomes sont refroidis à des températures cinétiques inférieures à 60 K. Nous montrons par ailleurs qu'une répartition inhomogène de l'énergie optique dans la cavité conduit à scinder la phase de refroidissement sub-Doppler en deux étapes. Malgré le caractère aléatoire de la polarisation entre « grains » de speckle adjacents, la dynamique du refroidissement en régime sub-Doppler que nous observons est identique à celle suivie par des atomes refroidis au sein d’un réseau optique conventionnel. La dernière partie de ce mémoire est consacrée à l’aspect métrologique du projet où la séquence complète de l’horloge est démontrée pour la 1ère fois dans une zone d’interaction unique. Une stabilité relative de fréquence de 2x10-13-1/2 est attendue pour un fonctionnement terrestre de l’horloge. / The HORACE project consists in the development of a high-performance compact atomic clock based on isotropic laser cooling of 133Cs atoms, targeting the needs for on-board clocks. In order to minimize the clock size, the entire clock sequence is performed inside one interaction zone only, including atomic cooling, preparation, interrogation and detection. This is made possible with a microwave interrogation cavity that is both resonant at the clock transition frequency, and used as an integrating sphere for the cooling light as well. This thesis work is mainly dedicated to the experimental study of the atomic cooling in the 3D speckle field generated inside the cavity. By limiting the cooling sequence to a capture phase, about 3x108 atoms can be cooled to kinetic temperatures lower than 60 microkelvins. Besides, we show that an inhomogeneous optical energy repartition in the cavity leads us to perform the sub-Doppler cooling phase in 2 steps. Despite random polarization change from one speckle grain to another, the atomic cooling dynamics observed in the sub-Doppler regime is similar to the one observed in conventional optical lattices. The last part of this thesis is devoted to the metrological aspect where the entire clock sequence is demonstrated for the first time at the same place. The fractional frequency stability of 2x10-13-1/2 should be reached on Earth.

FundaÃÃo Cearense de Apoio ao Desenvolvimento Cientifico e TecnolÃgico / O auxÃlio ao diagnÃstico atravÃs da visualizaÃÃo de imagens mÃdicas vÃm sendo utilizado em diversas Ãreas da Medicina tais como pneumologia, cardiologia, traumatologia, neurologia, dentre outras. Na Ãrea da cardiologia, vÃrias aplicaÃÃes clÃnicas tÃm sido propostas para a anÃlise de doenÃas cardÃacas atravÃs da quantificaÃÃo e avaliaÃÃo da dessincronia ventricular esquerda durante a deformaÃÃo do mÃsculo cardÃaco (miocÃrdio). Existem, atualmente, duas tÃcnicas utilizadas na aferiÃÃo da deformaÃÃo miocÃrdica em duas dimensÃes: Doppler Tecidual (DT) e Strain 2D (St2D). A primeira tÃcnica possui desvantagens quanto à dependÃncia do Ãngulo de insonaÃÃo do transdutor durante o exame ecocardiogrÃfico, diminuindo a chance de reprodutibilidade do resultado das mediÃÃes entre especialistas. A segunda tÃcnica, recentemente introduzida e tambÃm chamada de Speckle Tracking, consiste no acompanhamento de marcadores acÃsticos naturais existentes na imagem produzida pelo ultrassom. Neste sentido, vÃ-se a importÃncia do estudo de tÃcnicas para rastrear esses marcadores acÃsticos. A presente dissertaÃÃo realiza uma anÃlise comparativa entre oito algoritmos de estimaÃÃo de deslocamento baseados na tÃcnica de Casamento de Blocos (CB) e trÃs algoritmos baseados na tÃcnica de Fluxo Ãptico (FO), que sÃo as duas atuais tÃcnicas amplamente citadas na literatura. A anÃlise à realizada mediante vÃdeos sintÃticos e vÃdeos mÃdicos de exames ecocardiogrÃficos. A avaliaÃÃo das tÃcnicas em vÃdeos sintÃticos à realizada quanto à trajetÃria e à deformaÃÃo. Jà a avaliaÃÃo em vÃdeos de exames ecocardiogrÃficos à realizada quanto Ãs curvas e taxas de deformaÃÃo. Na anÃlise da trajetÃria sÃo aplicadas duas mÃtricas de avaliaÃÃo das tÃcnicas: correlaÃÃo mÃdia e erro quadrÃtico mÃdio. Para a anÃlise das curvas e das taxas de deformaÃÃo a mÃtrica usada à o valor do erro quadrÃtico mÃdio em relaÃÃo à deformaÃÃo global (global strain) do miocÃrdio. Os resultados indicam que o desempenho idÃntico de alguns estimadores de deslocamento os reduzem de oito para seis algoritmos. A tÃcnica de CB mostra-se viÃvel para o rastreamento de marcas acÃsticas mas à dependente das dimensÃes adotadas nos blocos. Em relaÃÃo Ãs tÃcnicas de FO, o algoritmo de Lucas e Kanade Piramidal à o que obtÃm melhor resultado nos testes realizados, produzindo curvas de deformaÃÃo global com erro mÃdio de 0,47%, enquanto os valores de erro dos outros algoritmos de FO estÃo em torno de 10%. No caso, os erros dos estimadores de CB variam de 1% a 16%. / Aided diagnosis by visualization of medical images has been used in several medical fields such as pulmonology, cardiology, traumatology, neurology, and others. In cardiology, several clinical applications have been proposed for the analysis of heart disease by quantification and evaluation of ventricular dyssynchrony during deformation of the heart muscle (myocardium). There are currently two techniques used in the measurement of myocardial deformation in two dimensions: Tissue Doppler and 2D Strain. The first technique has drawbacks regarding the dependence on the angle of insonation of the transducer during the echocardiographic examination, which reduce the chance of reproducibility of measurements among experts. The second technique, recently introduced and also called Speckle Tracking, consists of tracking the natural acoustic markers in the image produced by ultrasound. In this sense we see the importance of studying techniques to track these acoustic markers. This thesis performs a comparative analysis of eight algorithms from time-delay estimators based on the block matching technique and three algorithms based on the optical flow technique, which are the two current techniques widely presented in the literature. The analysis is performed using synthetic videos and medical videos from echocardiographic examinations. The evaluation of the techniques in synthetic videos is performed on the trajectory and deformation. The assessment in echocardiographic videos is held regarding the strain curves and strain rates. In the analysis of the trajectory are applied two metrics for evaluating techniques: mean correlation and mean square error. For the analysis of strain curves and of strain rate the measure used is the value of the mean square error relative to global strain of myocardium. The results indicate that the identical performance of some estimators reduce the time-delay estimators from eight to six algorithms. The block matching technique appears to be a viable technique for tracking acoustic marks but is dependent on the dimensions adopted in the blocks. Regarding optical flow techniques, the Lucas and Kanade Pyramidal algorithm is the one which gets the best results in the tests performed herein and produce global strain curves average error of 0.47 %, while the error values of the other optical flow algorithms are around 10 %. In case, the block matching time-delay estimators errors vary from 1% to 16%.

In this study we design a succession of three increasingly adept diffuse optical devices towards the simultaneous 3D imaging of blood flow and fluorescence contrasts in relatively deep tissues. These metrics together can provide future insights into the relationship between blood flow distributions and fluorescent or fluorescently tagged agents. A noncontact diffuse correlation tomography (ncDCT) device was firstly developed to recover flow by mechanically scanning a lens-based apparatus across the sample. The novel flow reconstruction technique and measuring boundary curvature were advanced in tandem. The establishment of CCD camera detection with a high sampling density and flow recovery by speckle contrast followed with the next instrument, termed speckle contrast diffuse correlation tomography (scDCT). In scDCT, an optical switch sequenced coherent near-infrared light into contact-based source fibers around the sample surface. A fully noncontact reflectance mode device finalized improvements by combining noncontact scDCT (nc_scDCT) and diffuse fluorescence tomography (DFT) techniques. In the combined device, a galvo-mirror directed polarized light to the sample surface. Filters and a cross polarizer in stackable tubes promoted extracting flow indices, absorption coefficients, and fluorescence concentrations (indocyanine green, ICG). The scDCT instrumentation was validated through detection of a cubical solid tissue-like phantom heterogeneity beneath a liquid phantom (background) surface where recovery of its center and dimensions agreed with the known values. The combined nc_scDCT/DFT identified both a cubical solid phantom and a tube of stepwise varying ICG concentration (absorption and fluorescence contrast). The tube imaged by nc_scDCT/DFT exhibited expected trends in absorption and fluorescence. The tube shape, orientation, and localization were recovered in general agreement with actuality. The flow heterogeneity localization was successfully extracted and its average relative flow values in agreement with previous studies. Increasing ICG concentrations induced notable disturbances in the tube region (≥ 0.25 μM/1 μM for 785 nm/830 nm) suggesting the graduating absorption (320% increase at 785 nm) introduced errors. We observe that 830 nm is lower in the ICG absorption spectrum and the correspondingly measured flow encountered less influence than 785 nm. From these results we anticipate the best practice in future studies to be utilization of a laser source with wavelength in a low region of the ICG absorption spectrum (e.g., 830 nm) or to only monitor flow prior to ICG injection or post-clearance. In addition, ncDCT was initially tested in a mouse tumor model to examine tumor size and averaged flow changes over a four-day interval. The next steps in forwarding the combined device development include the straightforward automation of data acquisition and filter rotation and applying it to in vivo tumor studies. These animal/clinical models may seek information such as simultaneous detection of tumor flow, fluorescence, and absorption contrasts or analyzing the relationship between variably sized fluorescently tagged nanoparticles and their tumor deposition relationship to flow distributions.

Measurement of tissue hemodynamics provides vital information for the assessment of tissue viability. This thesis reports three noninvasive near-infrared diffuse optical systems for spectroscopic measurements and tomographic imaging of tissue hemodynamics in vulnerable tissues with the goal of disease diagnosis and treatment monitoring. A hybrid near-infrared spectroscopy/diffuse correlation spectroscopy (NIRS/DCS) instrument with a contact fiber-optic probe was developed and utilized for simultaneous and continuous monitoring of blood flow (BF), blood oxygenation, and oxidative metabolism in exercising gastrocnemius. Results measured by the hybrid NIRS/DCS instrument in 37 subjects (mean age: 67 ± 6) indicated that vitamin D supplement plus aerobic training improved muscle metabolic function in older population. To reduce the interference and potential infection risk on vulnerable tissues caused by the contact measurement, a noncontact diffuse correlation spectroscopy/tomography (ncDCS/ncDCT) system was then developed. The ncDCS/ncDCT system employed optical lenses to project limited numbers of sources and detectors on the tissue surface. A motor-driven noncontact probe scanned over a region of interest to collect boundary data for three dimensional (3D) tomographic imaging of blood flow distribution. The ncDCS was tested for BF measurements in mastectomy skin flaps. Nineteen (19) patients underwent mastectomy and implant-based breast reconstruction were measured before and immediately after mastectomy. The BF index after mastectomy in each patient was normalized to its baseline value before surgery to get relative BF (rBF). Since rBF values in the patients with necrosis (n = 4) were significantly lower than those without necrosis (n = 15), rBF levels can be used to predict mastectomy skin flap necrosis. The ncDCT was tested for 3D imaging of BF distributions in chronic wounds of 5 patients. Spatial variations in BF contrasts over the wounded tissues were observed, indicating the capability of ncDCT in detecting tissue hemodynamic heterogeneities. To improve temporal/spatial resolution and avoid motion artifacts due to a long mechanical scanning of ncDCT, an electron-multiplying charge-coupled device based noncontact speckle contrast diffuse correlation tomography (scDCT) was developed. Validation of scDCT was done by imaging both high and low BF contrasts in tissue-like phantoms and human forearms. In a wound imaging study using scDCT, significant lower BF values were observed in the burned areas/volumes compared to surrounding normal tissues in two patients with burn. One limitation in this study was the potential influence of other unknown tissue optical properties such as tissue absorption coefficient (µa) on BF measurements. A new algorithm was then developed to extract both µa and BF using light intensities and speckle contrasts measured by scDCT at multiple source-detector distances. The new algorithm was validated using tissue-like liquid phantoms with varied values of µa and BF index. In-vivo validation and application of the innovative scDCT technique with the new algorithm is the subject of future work.

No description available.

Le principal but de cette thèse est d'adapter une méthode basée sur le retournement temporel, la méthode DORT (Décomposition de l'opérateur Retournement Temporel), a l'imagerie médicale. La plupart des résultats concernent aussi d'autres domaines de l'imagerie acoustique. En effet, l'échographie médicale a subi un important développement, mais reste limite chez certains patients par le fait que les tissus sont inhomogènes. La focalisation, et donc la qualité de l'image sont fortement dégrades par la traversée de milieu inhomogènes. Pour corriger ce problème et obtenir une bonne focalisation, il est nécessaire d'estimer les fonctions de Green de points du milieu. Nous proposons une approche par retournement temporel. Nous étendons la théorie de la méthode DORT au mode d'acquisition échographique, et introduisons le model de transducteurs virtuels qui permet de traiter le problème facilement. Ensuite, nous étendons la méthode aux signaux aléatoire (speckle) qui sont les signaux majoritaires en imagerie médicale, et en proposons une interprétation statistique basée sur le théorème de Van Cittert Zernike. L'étude des objets étendus est aussi faite. Finalement, échographie médicale utilise des signaux larges bandes, alors que la méthode DORT est principalement une méthode monochromatique. Des méthodes permettant d'obtenir les fonctions de Green temporelles sont développes dans le chapitre 5. En particulier, nous présentons la décomposition de Opérateur Retournement Temporel dans le domaine temporel, ce qui fait intervenir un tenseur d'ordre 4.