Recent advances in medical imaging have greatly improved the success of cardiovascular and intracardiac interventions. This research aims to improve capacitive micromachined ultrasonic transducers (CMUT) based imaging catheters for intravascular ultrasound (IVUS) and intra-cardiac echocardiography (ICE) for 3-D volumetric imaging through integration of high-k thin film material into the CMUT fabrication and array design. CMUT-on-CMOS integration has been recently achieved and initial imaging of ex-vivo samples with adequate dynamic range for IVUS at 20MHz has been demonstrated; however, for imaging in the heart, higher sensitivities are needed for imaging up to 4-5 cm depth at 20MHz and deeper at 10MHz. Consequently, one research goal is to design 10-20MHz CMUT arrays using integrated circuit (IC) compatible micro fabrication techniques and optimizing transducer performance through high-k dielectrics such as hafnium oxide (HfO2). This thin film material is electrically characterized for its dielectric properties and thermal mechanical stress is measured. Experiments on test CMUTs show a +6dB improvement in receive (Rx) sensitivity, and +6dB improvement in transmit sensitivity in (Pa/V) as compared to a CMUT using silicon nitride isolation (SixNy) layer. CMUT-on-CMOS with HfO2 insulation is successfully integrated and images of a pig-artery was successfully obtained with a 40dB dynamic range for 1x1cm2 planes. Experimental demonstration of side looking capability of single chip CMUT on CMOS system based FL dual ring arrays supported by large signal and FEA simulations was presented. The experimental results which are in agreement with simulations show promising results for the viability of using FL-IVUS CMUT-on-CMOS device with dual mode side-forward looking imaging. Three dimensional images were obtained by the CMUT-on-CMOS array for both a front facing wire and 4 wires that are placed perpendicular to the array surface and ~4 mm away laterally. For a novel array design, a dual gap, dual frequency 2D array was designed, fabricated and verified against the large signal model for CMUTs. Three different CMUT element geometries (2 receive, 1 transmit) were designed to achieve ~20MHz and ~40MHz bands respectively in pulse-echo mode. A system level framework for designing CMUT arrays was described that include effects from imaging design requirements, acoustical cross-talk, bandwidths, signal-to-noise (SNR) optimization and considerations from IC limitations for pulse voltage. Electrical impedance measurements and hydrophone measurements comparisons between design and experiment show differences due to inaccuracies in using SixNy homogenous material in simulation compared to fabricated thin-film stacks (HfO2-AlSi-SixNy). It is concluded that for “thin” membranes the effect of stiffness and mass of HfO2 and AlSi (top electrode) cannot be ignored in the simulation. Also, it is understood that aspect ratio (width to height) <10 will have up to 15% error for center frequency predicted in air when the thin-plate approximation is used for modelling the bending stiffness of the CMUT membrane.

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

No description available.

INTRODUCCIONLa implantación de stent tradicionalmente se realiza con la predilatación de la lesión con balón. Los objetivos del presente estudio fueron los siguientes: 1) conocer la viabilidad, eficacia y seguridad de la implantación de stent sin predilatación en nuestro medio; 2) determinar la tasa de reestenosis clínica y angiográfica, 3) identificar los factores predictivos de reestenosis con dicha técnica, y 4) analizar el patrón de hiperplasia intimal.PACIENTES Y MÉTODOSSe realizaron tres protocolos de estudio: Protocolo A: De 500 angioplastias coronarias consecutivas realizadas en un periodo de 13 meses, se seleccionaron 107 pacientes susceptibles de implantar un stent directo Se analizaron los resultados inmediatos y se compararon los grupos con y sin predilatación.Protocolo B: Se estudiaron 100 pacientes con implantación exitosa de stent con un seguimiento de 12 meses. Se determinaron las tasas de reestenosis clínica y angiográfica y se evaluaron las variables predictoras de reestenosis angiográfica. Esta última se definió como variable continua -pérdida tardía o diámetro luminal mínimo (DLM) en el seguimiento- y variable binaria -estenosis mayor del 50% en el segmento tratado -. Protocolo C: Se incluyeron 45 pacientes a los que se implantó un stent directo con éxito y 23 pacientes de similares características a los que el stent se implantó con predilatación a los que se realizó una ecografía intravascular. Para el estudio de la hiperplasia intimal se establecieron 5 cortes transversales a lo largo del stent en los que se realizaron las siguientes medidas: área transversal del vaso, del stent y de la luz; y se calcularon el porcentaje de placa excluida por el stent y de hiperplasia intimal.RESULTADOSProtocolo A: La implantación resultó exitosa en el 93,5% de los casos. No se logró implantar el stent directo en 7 pacientes. El fracaso se relacionó con la presencia de calcio y la edad. El tiempo de fluoroscopia y la cantidad de contraste empleado fueron inferiores en el grupo de stent directo comparado con el grupo con predilataciónProtocolo B: La reestenosis clínica fue del 4%. No se observaron muertes de origen cardiaco. El seguimiento angiográfico se realizó en el 82% de los pacientes. La tasa de reestenosis binaria fue del 11% .La diabetes mellitus se observó en el 55,6 % de los pacientes con reestenosis angiográfica comparado con el 12,3% sin reestenosis (p<0,05). En el análisis multivariado se identificó como variable predictiva de reestenosis binaria y continua a la diabetes mellitus con una odds ratio de 7,1. Asimismo, se identificó al DLM post-stent como factor predictivo de pérdida tardía y el diámetro de referencia como factor predictivo del DLM en el seguimiento.Protocolo C: La presión de inflado fue superior en el grupo de stent directo comparado con el grupo con predilatación (13 ±3 atm versus 10±2 atm, p<0,05). Asimismo las áreas del stent fueron superiores en el grupo sin predilatación comparadas con la implantación convencional. La proliferación intimal fue similar en los 5 cortes analizados a lo largo del stent en ambos grupos. La placa excluida por el stent se correlacionó con la proliferación intimal en el grupo con predilatación (r=0,37; p=0,005) y sin predilatación (r=0,33; p=0,005).CONCLUSIONES: La implantación de stent directo es un procedimiento seguro y eficaz en pacientes seleccionados, con una tasa de reestenosis clínica y angiográfica baja. El factor predictivo más importante de reestenosis angiográfica fue la diabetes mellitus. En el stent directo el patrón de hiperplasia intimal es difuso y homogéneo a lo largo del stent, similar al stent con predilatación. Esta hiperplasia intimal se correlaciona con la placa excluida por el stent. / INTRODUCTIONStent implantation is traditionally performed of the lesion predilatation using a balloon. The aims of the present study were the following: 1) to know the viability, efficacy and safety of the stent implantation without predilatation; 2) to determine the clinic and angiographic restenosis rate, 3) to identify the predictive variables of restenosis, and 4) to analyse the intimal hyperplasia pattern using this technique.PATIENTS AND METHODSThree different protocols were performed:Protocol A: From 500 consecutive angioplasties performed in a 13 months period, 107 patients were selected because of their susceptibility for direct stent implantation. The immediate results were analyzed and the groups with and without predilatation were compared.Protocol B: One hundred patients with successful direct stent implantation were studied for 12 months. The clinic and angiographic restenosis rate were determined and the predictive variables of angiographic reestenosis were evaluated. Angiographic restenosis was defined as continuous variable - late loss or minimum luminal diameter (MLD) during at the follow-up - and as binary variable - stenosis >50% in the treated segment-Protocol C: Forty-five patients with successfully direct stent implantation and 23 patients with similar characteristics in whom predilatation was made, were included. An intravascular echography was performed in all them. For the intimal hiperplasia analysis, five transversal cuts were established through the stent with the following transversal measurements:l area of the vessel, stent and lumen. In addition, the excluded plaque by the stent and the intimal hyperplasia expressed as percentage were calculated.RESULTSProtocol A: The implantation was successful in 93.5% of the patients. Failure to implant a direct stent was observed in 7 patients. This was related with the calcium presence and advanced age The fluoroscopy duration and contrast quantity were lower in the direct stent group than the predilatation group.Protocol B: The clinic restenosis rate was 4%. There were no deaths off cardiac origin. Angiographic follow-up was made in 82% of the patients. The binary reestenosis rate was 11%.Diabetes mellitus was observed in 55.6% of the patients with an angiographic restenosis compared with 12.3% of the patients without reestenosis (p<0.05). Multivariate analysis identified the diabetes mellitus as a predictive variable of binary reestenosis with an odds ratio of 7.1 The minimum luminal diameter immediately post- stent was identified as a predictive variable of late loss and the reference diameter as a predictive variable of the minimum luminal diameter at the follow-up.t.Protocol C: the inflation pressure was higher in the direct stent group compared with predilatation's group (13 ±3 atm versus 10±2 atm, p<0.05). Moreover, the stent areas were bigger in the group with no predilatation compared with the standard implantation. The intimal proliferation was similar in the five cuts analysed through the stent in both groups. The excluded plaque by the stent was correlated with the intimal proliferation in the with (r=0.37; p=0.005) and without (r=0.33; p=0.005) predilatation.CONCLUSIONSThe implantation of the direct stent is a safe and efficient procedure in selected patients with a low clinic and angiographic restenosis rate. The most important predictive factor of the angiographic reestenosis is the presence of diabetes mellitus. The intimal hyperplasia pattern following direct stenting is diffuse and homogeneous through the stent, being similar to the pattern observed with the standard implanation technique. Intimal hyperplasia correlates with the excluded plaque by the stent.

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Coronary artery disease is a leading cause of death in the Western world. Symptoms present only late in the progression of the disease, limiting treatment options; moreover, the inability to biopsy arterial tissue in a living patient makes it difficult to study the pathology effectively. 89 patients were imaged twice at a one year interval using x-ray angiography (the traditional modality for assessment of arterial stenosis) and intravascular ultrasound (IVUS), which yields a detailed image of the structure of the vessel wall. 32 of these 89 patients were made available for analysis in this study. The Volcano Corp.~IVUS acquisition systems include software that provides a \textit{virtual histology} (VH) characterization of plaque composition that provides information otherwise only available by biopsy. Using a geometric reconstruction method described in previous work, a full working model of wall shear stresses (WSS) produced by blood flow and vessel wall composition is created. Using these, the morphologic structural information gleaned from the 3-D reconstruction, and some additional composite indices, combined with demographic information collected at enrollment and serum biomarkers collected from each patient during imaging, a detailed portrait of each patient's disease state is created, with the objective of predicting disease evolution over a 1 year timescale. We have, in the course of this study, accomplished the following 5 aims towards the goal of predicting localized changes in disease state on a 1 year timescale: Aim 1: Develop and validate a method of compensating for rotational motion of the catheter within the vessel and its effect upon the 3-D orientation of the reconstruction. Aim 2: Develop and validate a method of registering the reconstructed vessels that permits identification of a point-to-point correspondence on all quantitative indices. Aim 3: Successfully reconstruct, register, and analyze image sets for each of as many patients as possible for analysis. Aim 4: Identify statistically significant indices in the data suitable for use as features in a classifier. Aim 5: Construct and assess performance of a classification system that can draw useful conclusions about the 1-year progression of the arterial pathology in a patient not used in the training set. Aim 2 was a complete success. Branches were reliably present in the IVUS data in sufficient quantities to facilitate reliable identification of the overlap and the requisite spatial transformation required to map points from one pullback onto another. Aim 1 was much more problematic. While a method was developed which showed promise, the image acquisition protocol did not provide for orientation of the angiograms with an eye towards bifurcation identification. With neither an analytic model, nor reasonable fiducials, the method developed could only be tested on a small subset of the data, limiting both our confidence in its validation, as well as its usability in this study. It is hoped that the method can be refined and used in any subsequent study, given proper planning during the acquisition of the images, and that in turn the spatial reliability of the reconstructions can be improved beyond what is possible today. Regarding aim 3, 32 patients were ultimately processed completely. Aims 4 and 5 were completed successfully. Meaningful correlations were identified in the data, and the results illustrate that while we were by no means able to obtain perfect classification, we were able to handily beat a both a random, and a maximum likelihood classifier.

Inverse spectral techniques are developed in this dissertation for recovering the shear modulus and residual stress of soft tissues. Shear modulus is one of several quantities for measuring the stiffness of a material, and hence estimating it accurately is an important factor in tissue characterization. Residual stress is a stress that can exist in a body in the absence of externally applied loads, and beneficial for biological growth and remodeling. It is a challenge to recover the two quantities in soft tissues both theoretically and experimentally. The current inverse spectral techniques recover the two unknowns invasively, and are theoretically based on a novel use of the intravascular ultrasound technology (IVUS) by obtaining several natural frequencies of the vessel wall material. As the IVUS is interrogating inside the artery, it produces small amplitude, high frequency time harmonic vibrations superimposed on the quasistatic deformation of the blood pressure pre-stressed and residually stressed artery. The arterial wall is idealized as a nonlinear isotropic cylindrical hyperelastic body for computational convenience. A boundary value problem is formulated for the response of the arterial wall within a specific class of quasistatic deformations reflexive of the response due to imposed blood pressures. Subsequently, a boundary value problem is developed from intravascular ultrasound interrogation generating small amplitude, high frequency time harmonic vibrations superimposed on the quasistatic finite deformations via an asymptotic construction of the solutions. This leads to a system of second order ordinary Sturm-Liouville problems (SLP) with the natural eigenfrequencies from IVUS implementation as eigenvalues of the SLP. They are then employed to reconstruct the shear modulus and residual stress in a nonlinear approach by inverse spectral techniques. The shear modulus is recovered by a multidimensional secant method (MSM). The MSM avoids computing the Jacobian matrix of the equations and is shown to be convenient for manipulation. Residual stress is recovered via an optimization approach (OA) instead of the traditional equation-solving method. The OA increases the robustness of the algorithms by overdetermination of the problem, and comprehensive tests are performed to guarantee the accuracy of the solution. Numerical examples are displayed to show the viability of these techniques.

Doenças coronárias causam a morte de milhões de pessoas anualmente. Uma dessas disfunções é a aterosclerose coronariana, acúmulo de placas lipídicas, fibrosas, e calcificadas na parede das coronárias. Esse acúmulo pode causar tromboses, infarto do miocárdio, ou morte cardíaca súbita. Porém, essas lesões apresentam graus distintos de periculosidade e elasticidade. As predominantemente lipídicas são de alto risco e elasticidade, enquanto as calcificadas e as fibrosas são mais estáveis e menos elásticas. O Ultrassom Intravascular (IVUS) é uma das modalidades de referência em diagnósticos e acompanhamento de doenças coronárias. Contudo, a imagem de IVUS pura fornece apenas informações subjetivas sobre vasos e placas; assim, é importante a criação de métodos e técnicas que possam tornar objetiva a análise dessa informação. Devido a isso, e levando em conta a riqueza de informações espaciais e temporais presentes nas imagens de IVUS, esse trabalho apresenta métodos de segmentação, e extração de características de lesões, que possibilitam a quantização de informações espaciais, e a discriminação de placas de baixo e elevado-risco. Consequentemente, fornecendo subsídios para diagnósticos, e procedimentos terapêuticos mais adequados. O método de segmentação combina Wavelet, Otsu, e Morfologia Matemática, para delineamento da parede do vaso. A avaliação do método foi feita usando 1300 imagens de IVUS, resultando em 92, 72% e 91, 9% de verdadeiros positivos, e 10, 7% e 9, 1% de falsos positivos, para o lúmen e borda da média adventícia, respectivamente. Adicionalmente, foi criado um método simples, para caracterização de placas a partir de suas propriedades mecânicas. Esse procedimento se baseia em computar um índice, chamado taxa de variação da área da placa, em imagens adquiridas pré e pós deformação do vaso e placas. Phantoms foram usados para avaliação, os resultados conseguidos com o índice proposto e um amplamente usado foram comparados. Uma correlação chegando à 99%, uma forte concordância usando Análise de Bland Altman, e Histogramas muito similares entre os dois índices, mostraram que o método proposto equivale ao já estabelecido. / Coronary diseases are the cause of death of millions of people annually. One of these dysfunctions is the coronary atherosclerosis, which is the accumulation of lipidic, fibrous and calcified plaques in the coronary wall. This accumulation may cause thrombosis, myocardial infarction and sudden cardiac death. Nonetheless, the kind of plaques offers different levels of dangerousness and elasticity. The highly lipidic plaques are very elastic, offers high risk, while the calcified and fibrous are more stable and less elastic. The Intravascular Ultrasound (IVUS) is the reference medical imaging modality for diagnostic and treatment of coronary diseases. However, the conventional IVUS images provides only anatomical vessel and plaque information; therefore, it is very important the creation of methods and techniques that could make objective the analysis of this information. Due to that, and taking into account the spatial and time information of IVUS images, this work presents methods of segmentation, and feature extraction of lesions, which make possible the quantization of spatial information, and the discrimination of high, and low risk plaques. Consequently, subsidies for diagnoses and more appropriate therapeutic procedures are provided. The segmentation method combines Wavelet, Otsu, and Mathematical Morphology, for the vessel wall delineation. The method evaluation was performed using 1300 IVUS images, resulting in 92, 72% and 91, 9% of true positives, and 10, 7% and 9, 1% of false positives, for the lumen and media adventitia border, respectively. Additionally, a simple method, for plaque characterization using the regarding mechanical properties was created. The procedure relies on computing an index, ratio of plaque area variation, in acquired images pre and post deformation procedure of vessel wall and plaques. Phantoms were used for evaluation. The results obtained by the proposed index, and a widely used one was compared. A correlation up to 99%, a strong agreement with Bland Altman, and similar Histograms between the two indexes demonstrated the equivalence between them; however, the proposed index is much simpler.

Doenças coronárias causam a morte de milhões de pessoas anualmente. Uma dessas disfunções é a aterosclerose coronariana, acúmulo de placas lipídicas, fibrosas, e calcificadas na parede das coronárias. Esse acúmulo pode causar tromboses, infarto do miocárdio, ou morte cardíaca súbita. Porém, essas lesões apresentam graus distintos de periculosidade e elasticidade. As predominantemente lipídicas são de alto risco e elasticidade, enquanto as calcificadas e as fibrosas são mais estáveis e menos elásticas. O Ultrassom Intravascular (IVUS) é uma das modalidades de referência em diagnósticos e acompanhamento de doenças coronárias. Contudo, a imagem de IVUS pura fornece apenas informações subjetivas sobre vasos e placas; assim, é importante a criação de métodos e técnicas que possam tornar objetiva a análise dessa informação. Devido a isso, e levando em conta a riqueza de informações espaciais e temporais presentes nas imagens de IVUS, esse trabalho apresenta métodos de segmentação, e extração de características de lesões, que possibilitam a quantização de informações espaciais, e a discriminação de placas de baixo e elevado-risco. Consequentemente, fornecendo subsídios para diagnósticos, e procedimentos terapêuticos mais adequados. O método de segmentação combina Wavelet, Otsu, e Morfologia Matemática, para delineamento da parede do vaso. A avaliação do método foi feita usando 1300 imagens de IVUS, resultando em 92, 72% e 91, 9% de verdadeiros positivos, e 10, 7% e 9, 1% de falsos positivos, para o lúmen e borda da média adventícia, respectivamente. Adicionalmente, foi criado um método simples, para caracterização de placas a partir de suas propriedades mecânicas. Esse procedimento se baseia em computar um índice, chamado taxa de variação da área da placa, em imagens adquiridas pré e pós deformação do vaso e placas. Phantoms foram usados para avaliação, os resultados conseguidos com o índice proposto e um amplamente usado foram comparados. Uma correlação chegando à 99%, uma forte concordância usando Análise de Bland Altman, e Histogramas muito similares entre os dois índices, mostraram que o método proposto equivale ao já estabelecido. / Coronary diseases are the cause of death of millions of people annually. One of these dysfunctions is the coronary atherosclerosis, which is the accumulation of lipidic, fibrous and calcified plaques in the coronary wall. This accumulation may cause thrombosis, myocardial infarction and sudden cardiac death. Nonetheless, the kind of plaques offers different levels of dangerousness and elasticity. The highly lipidic plaques are very elastic, offers high risk, while the calcified and fibrous are more stable and less elastic. The Intravascular Ultrasound (IVUS) is the reference medical imaging modality for diagnostic and treatment of coronary diseases. However, the conventional IVUS images provides only anatomical vessel and plaque information; therefore, it is very important the creation of methods and techniques that could make objective the analysis of this information. Due to that, and taking into account the spatial and time information of IVUS images, this work presents methods of segmentation, and feature extraction of lesions, which make possible the quantization of spatial information, and the discrimination of high, and low risk plaques. Consequently, subsidies for diagnoses and more appropriate therapeutic procedures are provided. The segmentation method combines Wavelet, Otsu, and Mathematical Morphology, for the vessel wall delineation. The method evaluation was performed using 1300 IVUS images, resulting in 92, 72% and 91, 9% of true positives, and 10, 7% and 9, 1% of false positives, for the lumen and media adventitia border, respectively. Additionally, a simple method, for plaque characterization using the regarding mechanical properties was created. The procedure relies on computing an index, ratio of plaque area variation, in acquired images pre and post deformation procedure of vessel wall and plaques. Phantoms were used for evaluation. The results obtained by the proposed index, and a widely used one was compared. A correlation up to 99%, a strong agreement with Bland Altman, and similar Histograms between the two indexes demonstrated the equivalence between them; however, the proposed index is much simpler.

Close integration of front-end electronics and the transducer array within the catheter is critical for successful implementation of CMUT-based intravascular ultrasound (IVUS) imaging catheters to enable next generation imaging tools. Therefore, this research developed and implemented custom-designed electronic circuits and systems integrated with an IC compatible transducer technology for realization of miniature IVUS imaging catheters operating at 10-50 MHz frequency range. In one path of this research, an IC is custom designed in a 0.35-um CMOS process to monolithically integrate with a CMUT array (CMUT-on-CMOS) to realize a single-chip, highly-flexible, forward-looking (FL) IVUS imaging system. The amplifiers that are custom-designed achieved transducer thermal-mechanical noise dominated receive performance in a CMUT-on-CMOS implementation. In parallel to the FL-IVUS effort, for realization of a side-looking IVUS catheter based on an annular phased array, a dynamic receive beamformer IC is custom designed also in a 0.35-um CMOS process. Overall, the circuits and systems developed as part of this dissertation form a critical step in the translation of the research on CMUT-based IVUS catheters into real clinical applications for better management of coronary arterial diseases.