Dissertationen zum Thema „Breast tissue imaging“

Thesis (Ph. D.)--Civil and Environmental Engineering, Georgia Institute of Technology, 2008.
Committee Chair: Germanovich, Leonid; Committee Co-Chair: Skrinjar, Oskar; Committee Member: Mayne, Paul; Committee Member: Puzrin, Alexander; Committee Member: Rix, Glenn.

KISS, MIKLOS ZOLTAN. Application of diffraction enhanced imaging for obtaining improved contrast of calcifications in breast tissue. (Under the direction of Dale E. Sayers.) Diffraction enhanced imaging (DEI) has been used to study the improvements in image contrast of calcifications in breast tissue. This new imaging modality has the potential to greatly improve early detection of breast cancer, primarily due to its ability to utilize contrast mechanisms in the breast, which are not possible with existing radiographic methods. Of particular interest is the comparison of the image contrast of calcifications in breast tissue obtained using DEI to those obtained using conventional radiography. The presence of calcifications in breast tissue has been connected to breast cancer, but this relationship is not well understood. The purpose of this dissertation is to study the improvements in image contrast of calcifications in healthy as well as cancerous breast tissue when using synchrotron-based DEI compared to conventional synchrotron-based methods. Image contrast is in part determined by the capabilities of the detector in the imaging system, and this relation was used to determine the effect of the limits of spatial resolution on near-pixel-sized objects, both by experiment and by computer modeling. Consistent definitions for image contrast were presented and applied to test objects, followed by application to breast tissue specimens containing calcifications. In every case, images obtained using DEI exhibited higher image contrast than the corresponding images obtained using normal radiography. The ratio of these contrast values, called the DEI gain, was consistently larger than unity, indicating that DEI does indeed utilize additional contrast mechanisms, such as refraction and scatter rejection, in addition to absorption and provides support for the development of a clinical prototype.

Breast cancer is the most common cancer in women worldwide. In 2009, a novel imaging modality called Shear Wave Elastography (SWE), an ultrasound technique visualising the elasticity of tissue, was introduced to the field of clinical breast imaging. Because malignant tissues are generally stiffer than benign tissues, SWE supports the differentiation of benign / malignant solid breast lesions. However, no standard has yet been defined for the application and the evaluation of results. Furthermore, image evaluation has to be carried out directly from the ultrasound system, complicating long-term and multi-centre studies. This PhD thesis investigated the influences from the imaging process and image evaluation on SWE measurements. Various parameters were appraised with regard to their diagnostic performance, in order to define the best clinical standard. To define more complex image analysis, taking the parameters investigated into account, algorithms were devised to enable automatic assessment of B-mode and SWE images. In this work, influences from the imaging process and image evaluation on the SWE measurements were demonstrated. The influences investigated included: the impact from the region of interest and the imaging plane used; the individual variation in breast composition; the number of images considered and the pressure applied during imaging. The algorithms described within this work achieved a diagnostic accuracy similar to that of manual assessment by a radiology expert. This thesis demonstrated influences from the imaging process and image evaluation on the SWE measurements obtained. Taking these influences into consideration would complicate the clinical application of SWE imaging. However, automatic image evaluation as presented here would overcome this issue. Using the guidelines defined in this PhD thesis also allows for comparison of results taken from different imaging sites.

Breast cancer is the most common form of cancer among women, this type of cancer is diagnosed in around 9000 women every year in Sweden. The most common studies to find breast cancer is through mammography where the breast tissue is compressed and exposed by radiation. Not only does the technique expose the breast tissue for radiation, but it can also be very uncomfortable. There is research on a new kind of scanning where use of microwaves reduces the uncomfortable situation. The MDH research team that are working with this technology needs help to position a transmitter of microwaves to test their equipment. The purpose of this paper is to discover a way to mechanically position a transmitter so that it can be moved along a breast model. The investigation will be made through a product development process in order to review the research question: RQ: “How can a product be designed to position and adjust a microwave transmitter to various locations in order to help testing of cancer research equipment?” By using an agile working methodology in combination with a Design thinking process this thesis includes several sprints that involved continues improvement and feedback from the research team. The first sprint was mostly to discover and experiment on new design ideas as well as control if any of them could work. It resulted in need of measurement changes and redesigning. The second sprint involved measurement corrections. The model itself had the reasonable measurements and the functions worked as expected. However, some of the functions needed to be improved as well as a problem with clearing of the wires to the transmitter itself. The third sprint included changes where more freedom was given and more clearance was made for the wires, but this design turned out to be unpredictable. The fourth sprint included a completely new design to stabilizing the prototype as a result from the researchers’ feedback. To answer the research question, the final design resulted in a 3D printed stand designed to move the transmitter along x-axis as well as rotate around y-axis to adjust to different breast diameters and forms. The stand also includes a rack and pinion design that makes it possible to adjust to different breast lengths. Lastly, the stand makes it possible to gradually move the transmitter around the breast model. However, the final design does not only answer the research question it also fulfils stability and functionality requirements set by the research team. This clarifies why the first iterations needed redesigning. Therefore, the stand is ready for preliminary tests of the researcher’s equipment. To conclude, there are many different design solutions that can answer the research question. However, the design requires stability which reduce the number of design solutions.

Ultrasound is a commonly used imaging modality in diagnosis and pre-operative assessment of breast masses. However, radiologists often find it very difficult to correctly size masses using conventional ultrasound images. Consequently, there exists a strong need for more accurate sizing tools to avoid either the removal of an over-estimated amount of tissue or a second surgical procedure to remove margins involved by tumour not removed in the primary operation. In this thesis, we propose a new method of processing the backscattered ultrasound signals from breast tissue (based on the Fourier spectral analysis) to better estimate the degree of echogenicity and generate parametric images where the visibility of breast mass boundaries is improved (SPV parametric image). Moreover, an algorithm is proposed to recover some anatomical structures (particularly, Cooper’s ligaments) which are shadowed during the image acquisition process (LWSPV parametric image). The information from both algorithms is combined to generate a final SPV+LWSPV parametric image. A 20-case pilot study was conducted on clinical data, which showed that the SPV+LWSPV parametric image added useful information to the B-mode image for clinical assessment in 85% of the cases (increase in diagnostic confidence in at least one boundary). Moreover, in 35% of the cases, the SPV+LWSPV parametric image provided a better definition of the entire boundary. Note that the radiologist knew the final diagnosis from histopathology. In addition, the SPV+LWSPV method has the advantage that it uses the I/Q data from a standard ultrasound equipment without the need for additional hardware. On the basis of these facts, we believe there to be a case for further investigation of the SPV+LWSPV imaging as a useful clinical tool in the pre-operative assessment of breast mass boundaries.

Despite the possible common histopathological features at diagnosis, cancer cells present within breast carcinomas are highly heterogeneous in their molecular signatures. This heterogeneity is responsible for disparate clinical behaviors, treatment responses and long-term outcomes in breast cancer patients. Although the few histopathological markers can partially describe the diversity of cells found in tumor tissue sections, the full molecular characterization of individual cancer cells is currently impossible in routine clinical practice. In this respect, Fourier transform infrared (FTIR) microspectroscopic imaging of histological sections allows obtaining, for each pixel of tissue images, hundreds of independent potential markers, which makes this technique a particularly powerful tool to distinguish cell types and subtypes. As a complement to the conventional clinicopathological evaluation, this spectroscopic approach has the potential to directly reveal molecular descriptors that should allow identifying different clonal lineages found within a single tumor and therefore provide knowledge relevant to diagnosis, prognosis and treatment personalization. Yet, interpretation of infrared (IR) spectra acquired on tissue sections requires a well-established calibration, which is currently missing. Conventionally, mammary epithelial cells are studied in vitro as adherent two-dimensional (2D) monolayers, which lead to the alteration of cell-microenvironmental interplay and consequently to the loss of tissue structure and function. A number of key in vivo-like interactions may be re-established with the use of three-dimensional (3D) laminin-rich extracellular matrix (lrECM)-based culture systems. The aim of this thesis is to investigate by FTIR imaging the influence of the in vitro growth environment (2D culture versus 3D lrECM culture and 3D monoculture versus 3D co-culture with fibroblasts) on a series of thirteen well-characterized human breast cancer cell lines and to determine culture conditions generating spectral phenotypes that are closer to the ones observed in malignant breast tissues. The reference cell lines cultured in a physiologically relevant basement membrane model and having undergone formalin fixation, paraffin embedding (FFPE), a routine treatment used to preserve clinical tissue specimens, could contribute to the construction of a spectral database. The latter could be ultimately employed as a valuable tool to interpret IR spectra of cells present in tumor tissue sections, particularly through the recognition of unique spectral markers.To achieve the goal, we developed and optimized, in a first step, the preparation of samples derived from traditional 2D and 3D lrECM cell cultures in order to preserve their morphological and molecular relevance for FTIR microspectroscopic analysis. We then highlighted the importance of the influence of the growth environment on the cellular phenotype by comparing spectra of 2D- and 3D-cultured breast cancer cell lines between them. A particular focus was placed to establish a correlation between FTIR spectral data and publicly available microarray-based gene expression patterns of the whole series of breast cancer cell lines grown in 2D and 3D lrECM cultures. Our results revealed that, although based on completely different principles, gene expression profiling and FTIR spectroscopy are similarly sensitive to both the cell line identity and the phenotypes induced by cell culture conditions. We also identified by FTIR imaging changes in the chemical content occurring in the microenvironment surrounding cell spheroids grown in 3D lrECM culture model. Finally, we illustrated the impact of the in vivo-like microenvironment on the IR spectra of breast cancer cell lines grown in 3D lrECM co-culture with fibroblasts and compared them with spectra of cell lines grown in 3D lrECM monoculture. Unsupervised statistical data analyses reported that cells grown in 3D co-cultures produce spectral phenotypes similar to the ones observed in FFPE tumor tissue sections from breast carcinoma patients. Altogether, our results suggest that FFPE samples prepared from 3D lrECM cultures of breast cancer cell lines and studied by FTIR microspectroscopic imaging provide reliable information that could be integrated in the setting up of a recognition model aiming to identify and interpret specific spectral signatures of cells present in breast tumor tissue sections.
Le cancer du sein est une maladie très hétérogène, tant au niveau clinique que biologique. Cette hétérogénéité rend impossible la caractérisation moléculaire complète des cellules cancéreuses individuelles dans la pratique clinique courante. Dans ce contexte, l’imagerie infrarouge à transformée de Fourier (FTIR) des coupes tissulaires permet d'obtenir pour chaque pixel d'une image de tissu des centaines de marqueurs potentiels indépendants, ce qui pourrait faire de cette technique un outil particulièrement puissant pour identifier des différents types et sous-types cellulaires. L'interprétation des spectres infrarouges (IR) enregistrés à partir des coupes histologiques nécessite cependant une calibration qui fait actuellement défaut. Cette calibration pourrait être obtenue à partir de lignées cellulaires tumorales bien caractérisées. Traditionnellement, les cellules épithéliales mammaires sont étudiées in vitro sous forme de monocouches adhérentes bidimensionnelles (2D), ce qui conduit à l'altération de la communication entre les cellules et leur environnement et, par conséquent, à la perte de l’architecture et de la fonction du tissu épithélial. Un certain nombre d'interactions physiologiques clés peuvent être rétablies en utilisant des systèmes de culture tridimensionnelle (3D) dans une matrice extracellulaire riche en laminine (lrECM). L'objectif de cette thèse consiste à étudier par imagerie FTIR l'influence du microenvironnement (via une comparaison entre les cultures 2D et 3D lrECM ou les cultures 3D lrECM en présence ou en l’absence de fibroblastes) sur une série de treize lignées de cellules tumorales mammaires humaines bien caractérisées et à déterminer les conditions de culture générant des phénotypes spectraux qui se rapprochent le plus de ceux observés dans les tissus tumoraux. Au cours de ce travail, nous avons mis au point la culture des lignées cellulaires dans un modèle 3D lrECM ainsi qu’une méthodologie de préparation des échantillons offrant la possibilité de les comparer de manière pertinente avec les cellules cancéreuses présentes dans les coupes histologiques. De même, nous avons étudié par imagerie FTIR les effets du microenvironnement sur les lignées de cellules tumorales et inversement. Pour les lignées investiguées, le passage d’une culture 2D à une culture 3D lrECM s’accompagne, en effet, de modifications du spectre IR étroitement corrélées aux modifications du transcriptome. Les marqueurs spectraux indiquent également que l’environnement 3D génère un phénotype cellulaire proche de celui trouvé dans les coupes histologiques. De manière intéressante, cette proximité est d’autant plus renforcée en présence de fibroblastes dans le milieu de culture.
Doctorat en Sciences agronomiques et ingénierie biologique
info:eu-repo/semantics/nonPublished

Différentes techniques d'imagerie par contraste de phase des rayons X ont été récemment développées. Contrairement aux méthodes conventionnelles, qui mesurent les propriétés d'absorption des tissus, ces techniques donnent aussi le contraste du déphasage introduit par l'échantillon. Puisque le changement dans la phase peut être important même quand les différences en atténuation sont faibles ou absentes, le contraste d'image obtenable peut être considérablement augmenté, notamment pour les tissus mous biologiques. Ces méthodes sont donc très prometteuses pour une application dans le domaine médical. Cette Thèse a le but de contribuer à une compréhension plus profonde de ces techniques, en particulier la propagation-based imaging (PBI), la analyzer-based imaging (ABI) et la grating interferometry (GIFM), et d'étudier leur potentiel et la meilleure implémentation pratique pour les applications médicales. Une partie importante de cette Thèse est dédiée à l'utilisation d'algorithmes mathématiques pour l'extraction, à partir des images acquises, d'informations quantitatives (absorption, réfraction et diffusion) concernant l'échantillon. En particulier, cinq parmi les algorithmes les plus connus pour la technique ABI sont analysés théoriquement et comparés expérimentalement, dans les modalités planaire et tomographique, en utilisant des fantômes et des échantillons de tissu mammaire et d'os-cartilage. Une méthode semi-quantitative pour l'acquisition et la reconstruction d'images tomographiques dans les techniques ABI et GIFM est aussi proposée. Les conditions de validité sont analysées en détail et la méthode, permettant une simplification considérable de l'implémentation pratique, est vérifiée expérimentalement sur des fantômes et des échantillons humains. Enfin, une comparaison théorique et expérimentale des techniques PBI, ABI et GIFM est présentée. Les avantages et les désavantages de chacune des techniques sont mis en évidence. Les résultats obtenus par cette analyse peuvent être très utiles pour déterminer quelle technique est la plus adaptée à une application donnée.

Breast cancer is the most common cancer among women worldwide. Several studies have shown that the combination of the different medical image modalities, such as the x-ray mammography and the magnetic resonance imaging (MRI), leads to a more accurate diagnosis. The aim of this thesis is double, on the one hand, to evaluate the similarity between the information obtained from x-ray mammography and from MRI images and, on the other hand, to propose new registration algorithms to perform the correlation between the two image modalities. The problem includes from the biomechanical model construction, obtained from the MRI volume, the mechanical deformation, which is performed during the mammographic acquisition, the x-ray beam simulation traversing the breast in order to obtain the image (pseudo-mammogram) and the registration process to improve the similarity between the real and the synthetic images
El càncer de mama és el tipus de càncer més comú entre les dones de tot el món. Diversos estudis han demostrat que la combinació de diferents modalitats d'imatge mèdica, com ara la mamografia i la ressonància magnètica (MRI), comporta un diagnòstic més precís. L'objectiu d'aquesta tesi és doble, per una banda avaluar la similitud de la informació entre la mamografia de raigs X i la MRI i, d’altra banda, proposar nous algoritmes de registre que serveixin per a correlacionar la posició espacial en les dues modalitats d'imatge. El problema abarca la construcció del model biomecànic de la mama a partir de la ressonància magnètica, la simulació de la deformació que pateix la mama durant l’adquisició mamogràfica, la simulació dels rajos X atravessant la mama fins a obtenir la imatge (pseudo-mamografia) i els mètodes de registre posteriors per tal de millorar la similitud entre la imatge real i la simulada

Photoacoustic computed tomography (PAT) has great potential for application in the biomedical field. It best combines the high contrast of electromagnetic absorption and the high resolution of ultrasonic waves in biological tissues. In Chapter II, we present time-domain reconstruction algorithms for PAT. First, a formal reconstruction formula for arbitrary measurement geometry is presented. Then, we derive a universal and exact back-projection formula for three commonly used measurement geometries, including spherical, planar and cylindrical surfaces. We also find this back-projection formula can be extended to arbitrary measurement surfaces under certain conditions. A method to implement the back-projection algorithm is also given. Finally, numerical simulations are performed to demonstrate the performance of the back-projection formula. In Chapter III, we present a theoretical analysis of the spatial resolution of PAT for the first time. The three common geometries as well as other general cases are investigated. The point-spread functions (PSF's) related to the bandwidth and the sensing aperture of the detector are derived. Both the full-width-at-half-maximum of the PSF and the Rayleigh criterion are used to define the spatial resolution. In Chapter IV, we first present a theoretical analysis of spatial sampling in the PA measurement for three common geometries. Then, based on the sampling theorem, we propose an optimal sampling strategy for the PA measurement. Optimal spatial sampling periods for different geometries are derived. The aliasing effects on the PAT images are also discussed. Finally, we conduct numerical simulations to test the proposed optimal sampling strategy and also to demonstrate how the aliasing related to spatially discrete sampling affects the PAT image. In Chapter V, we first describe a prototype of the RF-induced PAT imaging system that we have built. Then, we present experiments of phantom samples as well as a preliminary study of breast imaging for cancer detection.

Les travaux de cette thèse consistent à développer des outils de spectroscopie et d'imagerie térahertz pour des applications médicales. L'objectif est de déterminer le potentiel et l'efficacité de la spectroscopie térahertz et de l'imagerie dans la détection des régions cancéreuses et la distinction entre les tissus malades et sains pour le cancer du sein chez les femmes. La spectroscopie térahertz est une technique sans contact, non ionisante pour obtenir des résultats rapides, comparée à l'analyse clinique standard. Les études expérimentales sont divisées en deux sections principales :Section I :Cette partie se concentre sur la spectroscopie en utilisant un rayonnement THz. La maîtrise de cette technique permet de travailler en mode réflexion ou transmission avec des fréquences dans la bande passante térahertz. Plusieurs types de matériaux ont été utilisés comme fantômes pour la calibration de l'expérience : des solides (silice, téflon, saphir et verre), des liquides (méthanol, eau et alcool) et des tissus biologiques (cancer, fibres et gras), ainsi qu'un mélange (eau-méthanol). Les indices de réfraction, les coefficients d'absorption et les fonctions diélectriques complexes ont d'abord été mesurés et extraits puis fittés avec un modèle de Debye. Les tissus biologiques sont apparus hétérogènes en épaisseur et avec des surfaces qui peuvent être irrégulières, ce qui rend difficile l'extraction d'informations précises, en raison d’artefacts induits. Les signaux ont été traités en suivant un protocole rigoureux : Les mesures sont effectuées sur un support parfaitement caractérisé en transmission pour réduire les incertitudes sur la phase lors des mesures en réflexion. Les signaux THz réfléchis aux interfaces entre l'air / échantillon, air / fenêtre, eau / fenêtre et fenêtre / fenêtre sont utilisés comme signal de base pour estimer et améliorer le rapport signal-bruit dans les mesures de spectroscopie. L'avantage de cette méthode est sa précision, sa simplicité et sa facilité d'application pour un système de réflexion avec un angle d'incidence. La mesure des indices de réfraction et des coefficients d'absorption des échantillons avec des tissus tumoraux et sains a révélé que les régions tumorales présentent des différences significatives par rapport au tissu normal lors de l’interaction tissu-rayonnement térahertz.Section II :La deuxième partie de cette étude porte sur l'imagerie THz pour la détection du cancer du sein, à la fois dans les modes de transmission et de réflexion. Plusieurs types d'échantillons ont été étudiés. Les coupes utilisées comprenaient des tissus inclus en paraffine, des tissus frais sortis du bloc opératoire, fixés au formol et des blocs. Pour cela le spectromètre a été déplacé à l'hôpital. Plus de 50 échantillons ont été ainsi inspectés. TroisIVméthodes de traitement d'image ont été utilisées : le découpage, l'automatisation et le tri d'images manuel. De plus, les images obtenues dans le domaine temporel et dans le domaine fréquentiel ont été analysées pour décrire et identifier les différentes régions du tissu mammaire étudiées et déterminer le contraste entre le tissu sain et le tissu malade. La quantité d'eau différentielle présente dans les tissus malades peut être l'une des origines de contraste. En effet, le tissu cancéreux possède une teneur en eau plus élevée que celle des fibres ou des tissus adipeux normaux, ce qui permet de discriminer les régions cancéreuses, fibreuses et graisseuses sur les images THz
The work of this thesis consists in developing terahertz spectroscopy and imaging tools for medical applications. The goal is to determine the potential and effectiveness of terahertz spectroscopy and imaging in the detection of cancer regions and the distinction between diseased and healthy tissue for breast cancer in women. Terahertz spectroimaging is a non-contact, non-ionizing technique for rapid results compared to standard clinical analysis. Experimental studies are divided into two main sections:Section IThis part focuses on THz spectroscopy using THz radiation. The mastery of this technique makes it possible to work in reflection or transmission mode with frequencies in the terahertz bandwidth. Several types of materials have been used as ghosts for the calibration of the experiment: solids (silica, teflon, sapphire and glass), liquids (methanol, water and alcohol) and biological tissues (cancer, fiber and fat), as well as a mixture (water-methanol). The refractive indices, the absorption coefficients and the complex dielectric functions were first measured and extracted and then fitted with a Debye model. Biological tissues have appeared heterogeneous in thickness and with surfaces that may be irregular, making it difficult to extract accurate information because of induced artifacts. The signals have been processed according to a rigorous protocol: The measurements are carried out on a perfectly characterised substratet in transmission to reduce the uncertainties on the phase during the measurements in reflection. The THz signals reflected at the interfaces between the air / sample, air / window, water / window and window / window are used as a basic signal to estimate and improve the signal-to-noise ratio in the spectroscopy measurements. The advantage of this method is its accuracy, simplicity and ease of application for a reflection system with an angle of incidence. Measurement of refractive indices and absorption coefficients of samples with tumor and healthy tissue revealed that the tumor regions showed significant differences from normal tissue during terahertz tissue-radiation interaction.Section II:The second part of this study focuses on THz imaging for breast cancer detection in both transmission and reflection modes. Several types of samples have been studied. Sections used included paraffin-embedded tissue, fresh tissues removed from the OR, formalin-fixed, and blocks. For this the spectrometer has been moved to the hospital. More than 50 samples were inspected. Three image processing methods were used: cutting, automation and manual image sorting. In addition, time domain and frequency domain images were analyzed to describe and identify the different regions of mammary tissue studied and to determine the contrast between healthy tissue and diseased tissue. The amount of differential water present in diseased tissue can be one of the sources of contrast. In fact, the cancerous tissue has a higher water content than that of normal fibers or adipose tissue, which makes it possible to discriminate the cancerous, fibrous and fatty regions on the THz images

L'élastographie-IRM du sein (MRE) est une technique d'imagerie fonctionnelle non invasive utilisant les propriétés visco-élastiques des tissus et qui permet comme en élastographie-échographie d'évaluer la rigidité d'une lésion. Il est également possible, à la différence de l'élastographie-échographie, d'évaluer le degré de viscosité d'une lésion, et ainsi grâce à la combinaison élasticité/viscosité, comparée à l'analyse des paramètres IRM classiques comme la morphologie ou la cinétique de rehaussement, d'améliorer la caractérisation lésionnelle. Très peu d'études en élastographie-IRM du sein ont été menées à ce jour, essentiellement du fait d'une problématique instrumentale et de mise à disposition d'une antenne dédiée sein équipé d'un dispositif de génération des ondes de cisaillement dans le sein. Dans un premier temps, nous avons pu établir et optimiser une séquence élasto-IRM du sein sur une série de 10 volontaires saines. Cette séquence basée sur un principe de séquence Spin Echo EPI-MRE 3D, a permis l'acquisition de 50 coupes en 10 minutes sur un sein, compatible avec la pratique clinique en IRM du sein. Une approche multifréquence à 37,5 Hz, 75 Hz et 112,5 Hz a été ensuite testée sur les trois dernières volontaires puis transférées à notre population de patientes. Cette séquence multifréquence permettait la continuité de diffusion des ondes dans le sein. 50 patientes présentant des lésions indéterminées ou suspectes du sein (37 cancers, 13 bénins) ont ensuite été incluses dans ce protocole et examinées par IRM du sein classique avec séquence supplémentaire élasto-IRM. Certaines patientes étaient aussi examinées en élasto-échographie. Les données IRM morphologiques, dynamiques et de visco-élasticité IRM ont été corrélées à l'histologie. Nous avons pu montrer que les paramètres visco-élastiques IRM étaient fortement corrélés avec le score de malignité d'une lésion (Bi-RADS ACR) et avec le caractère différentiel bénin/malin. C'est notamment le paramètre Gd qui représente l'élasticité, qui était plus faible en cas de lésion suspecte BI-RADS 5. Le paramètre Gl était plus élevé dans les lésions malignes par rapport aux lésions bénignes, avec un niveau de viscosité statistiquement supérieur dans les lésions malignes. Le meilleur paramètre semble être le rapport y (Gl/Gd) qui était aussi significativement élevé dans les lésions malignes par comparaison avec les lésions bénignes du sein, et qui a été analysé comme un facteur indépendant. En pratique, l'ajout de la séquence MRE à un examen IRM du sein classique a permis dans notre étude d'améliorer significativement la sensibilité de l'IRM (de 78 à 91 %) sans perte de spécificité, celle-ci étant initialement très bonne dans cette étude. Nous n'avons pas en revanche établi de lien entre la fibrose, la quantification vasculaire ou la nécrose pour expliquer ces phénomènes de visco-élasticité des tumeurs. En conclusion, l'élasto-IRM peut s'avérer utile pour améliorer le diagnostic de lésions du sein en IRM. Une poursuite des travaux avec optimisation de la séquence pour qu'elle puisse permettre l'analyse des deux seins sera nécessaire pour sa diffusion en pratique clinique. Ce travail pourrait idéalement se poursuivre sur une plus grande série de patientes.

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Cancer is one of the biggest health problems worldwide, and the breast cancer is the one that causes more deaths among women. Also it is the second most frequent type in the world. The chances of survival for a patient with breast cancer increases the sooner this disease is discovered. Several Computer Aided Detection/Diagnosis Systems has been used to assist health professionals. This work presents a methodology to discriminate and classify mammographic tissues regions in mass and non-mass. For this purpose the Shannon-Wiener‟s Diversity Index, which is applied to measure the biodiversity in ecosystem, is used to describe pattern of breast image region with four approaches: global, in circles, in rings and directional. After, a Support Vector Machine is used to classify the regions in mass and non-mass. The methodology presents promising results for classification of mammographic tissues regions in mass and non-mass, achieving 99.85% maximum accuracy.
O câncer é um dos maiores problemas de saúde mundial, sendo o câncer de mama o que mais causa óbito entre as mulheres e o segundo tipo mais freqüente no mundo. As chances de uma paciente sobreviver ao câncer de mama aumentam à medida que a doença é descoberta mais cedo. Diversos Sistemas de Detecção e Diagnóstico auxiliados por computador (Computer Aided Detection/Diagnosis) têm sido utilizados para auxiliar profissionais de saúde. Este trabalho apresenta uma metodologia de discriminação e classificação de regiões de tecidos de mamografias em massa e não massa. Para este propósito utiliza-se o Índice de Diversidade de Shannon-Wiener, comumente aplicado para medir a biodiversidade em um ecossistema, para descrever padrões de regiões de imagens de mama com quatro abordagens: global, em círculos, em anéis e direcional. Em seguida, utiliza-se o classificador Support Vector Machine para classificar estas regiões em massa e não massa. A metodologia apresenta resultados promissores para a classificação de regiões de tecidos de mamografia em massa e não massa, obtendo uma acurácia máxima de 99,85%.

Breast cancer is fast becoming the leading cause of mortality in women worldwide. As of this year, there are more than 3.1 million women with a history of breast cancer in the U.S., and about 41,760 women are expected to die from this disease. Neoadjuvant chemotherapy (NAC) has become a well-established therapy in the treatment of patients with locally advanced or primarily inoperable breast cancer. It consists of 3-9 months of drug treatment to shrink the tumor size before surgical removal of any remaining mass. A pathological complete response (pCR) is defined as complete disappearance of the tumor before surgery and correlates with 5-year overall survival of the treated patient. However, only 15-40% of subjects who undergo NAC will achieve a pCR, while the remaining patients do not benefit from a therapy that has considerable side effects. In this Ph.D. thesis, I explore the potential of diffuse optical tomography (DOT) for breast cancer imaging and NAC monitoring. The overall objective is two-fold. First, I seek to identify breast cancer patients who will not respond to NAC shortly after the initiation of a 5-9 months therapy regimen. Identifying these patients early will allow a switch to a more promising therapy and avoiding months of ineffective therapy with a drug regimen that has considerable side effects. Second, I use the optical data simultaneously obtained from the contralateral, non-tumor bearing breast to better understand the factors that modulate breast density and the source of its contrast in DOT. This work analyzed DOT data from 105 patients with stage II-III breast cancer under NAC regimen. Data processing and image analysis protocols were developed to more effectively evaluate static tissue contrast and dynamic functional imaging of the breast. Notably, we observed that there are differences in the time evolution of DOT features between pCR and non-pCR tumors under NAC, and DOT features can contribute to the successful prediction of pCR status from pretreatment imaging. Lastly, our analysis demonstrated a positive correlation between DOT feature and mammographic density classification, which could lead to research on the potential use of DOT as a predictor of breast cancer as well as an assessment tool to longitudinally evaluate the efficacy of chemoprevention strategies. These findings represent important steps towards the translation of DOT into current clinical workflow to contribute to better-personalized breast cancer therapies and breast cancer risk management.

Breast conserving surgery (BCS) is a common treatment option for breast cancer patients. The goal of BCS is to remove the entire tumor from the breast while preserving as much normal tissue as possible for a better cosmetic outcome after surgery. Specifically, the excised specimen must have at least 2 mm of normal tissue surrounding the diseased mass. Unfortunately, a staggering 20-70% of patients undergoing BCS require repeated surgeries due to the incomplete removal of the tumor diagnosed post-operatively. Due to these high re-excision rates as well as limited post-operative histopathological sampling of the tumor specimen, there is an unmet clinical need for margin assessment. Quantitative diffuse reflectance spectral imaging has previously been explored as a promising, method for providing real-time visual maps of tissue composition to help surgeons determine breast tumor margins to ensure the complete removal of the disease during breast conserving surgery. We have leveraged the underlying sources of contrast in breast tissue, specifically total hemoglobin content, beta-carotene content, and tissue scattering, and developed various fiber optics based spectral imaging systems for this clinical application. Combined with a fast inverse Monte Carlo model of reflectance, previous studies have shown that this technology may be able to decrease re-excision rates for BCS. However, these systems, which all consist of a broadband source, fiber optics probes, an imaging spectrograph and a CCD, have severe limitations in system footprint, tumor area coverage, and speed for acquisition and analysis. The fiber based spectral imaging systems are not scalable to smaller designs that cover a large surveillance area at a very fast speed, which ultimately makes them impractical for use in the clinical environment. The objective of this dissertation was to design, develop, test, and show clinical feasibility of a novel wide field spectral imaging system that utilizes the same scientific principles of previously developed fiber optics based imaging systems, but improves upon the technical issues, such as size, complexity, and speed,to meet the demands of the intra-operative setting.

First, our simple re-design of the system completely eliminated the need for an imaging spectrograph and CCD by replacing them with an array of custom annular photodiodes. The geometry of the photodiodes were designed with the goal of minimizing optical crosstalk, maximizing SNR, and achieving the appropriate tissue sensing depth of up to 2 mm for tumor margin assessment. Without the imaging spectrograph and CCD, the system requires discrete wavelengths of light to launch into the tissue sample. A wavelength selection method that combines an inverse Monte Carlo model and a genetic algorithm was developed in order to optimize the wavelength choices specifically for the underlying breast tissue optical contrast. The final system design consisted of a broadband source with an 8-slot filter wheel containing the optimized set of wavelength choices, an optical light guide and quartz light delivery tube to send the 8 wavelengths of light in free space through the back apertures of each annular photodiode in the imaging array, an 8-channel integrating transimpedance amplifier circuit with a switch box and data acquisition card to collect the reflectance signal, and a laptop computer that controls all the components and analyzes the data.

This newly designed wide field spectral imaging system was tested in tissue-mimicking liquid phantoms and achieved comparable performance to previous clinically-validated fiber optics based systems in its ability to extract optical properties with high accuracy. The system was also tested in various biological samples, including a murine tumor model, porcine tissue, and human breast tissue, for the direct comparison with its fiber optics based counterparts. The photodiode based imaging system achieved comparable or better SNR, comparable extractions of optical properties extractions for all tissue types, and feasible improvements in speed and coverage for future iterations. We show proof of concept in performing fast, wide field spectral imaging with a simple, inexpensive design. With a reduction in size, cost, number of wavelengths used, and overall complexity, the system described by this dissertation allows for a more seamless scaling to higher pixel number and density in future iterations of the technology, which will help make this a clinically translatable tool for breast tumor margin assessment.

Dissertation

In 2011, an estimated 230,480 new cases of invasive breast cancer were diagnosed among women, as well as an estimated 57,650 additional cases of in situ breast cancer [1]. Breast conserving surgery (BCS) is a recommended surgical choice for women with early stage breast cancer (stages 0, I, II) and for those with Stage II-III disease who undergo successful neo-adjuvant treatment to reduce their tumor burden [2, 3]. Cancer within 2mm of a margin following BCS increases the risk of local recurrence and mortality [4-6]. Margin assessment presents an unmet clinical need. Breast tissue is markedly heterogeneous which makes identifying cancer foci within benign tissue challenging. Optical spectroscopy can provide surgeons with intra-operative diagnostic tools. Here, ex-vivo breast tissue is evaluated to determine which sources of optical contrast have the potential to detect malignancy at the margins in women of differing breast composition. Then, H&E images of ex-vivo breast tissue sites are quantified to further deconstruct the relationship between optical scattering and the underlying tissue morphology.

Diffuse reflectance spectra were measured from benign and malignant sites from the margins of lumpectomy specimens. Benign and malignant sites were compared and then stratified by tissue type and depth. The median and median absolute deviance (MAD) was calculated for each category. The frequencies of the benign tissue types were separated by menopausal status and compared to the corresponding optical properties.

H&E images were then taken of the malignant and benign sites and quantified to describe the % adipose, % collagen and % glands. Adipose sites, images at 10x, were predominantly fatty and quantified according to adipocyte morphology. H&E-stained adipose tissue sections were analyzed with an automated image processing algorithm to extract average cell area and cell density. Non-adipose sites were imaged with a 2.5x objective. Grids of 200µm boxes corresponding to the 3mm x 2mm area were overlaid on each non-adipose image. The non-adipose images were classified as the following: adipose and collagen (fibroadipose); collagen and glands (fibroglandular); adipose, collagen and glands (mixed); and malignant sites. Correlations between <&mus′> and % collagen in were determined in benign sites. Age, BMI, and MBD were then correlated to <&mus′> in the adipose and non-adipose sites. Variability in <&mus′> was determined to be related to collagen and not adipose content. In order to further investigate this relationship, the importance of age, BMI and MBD was analyzed after adjusting for the % collagen. Lastly, the relationship between % collagen and % glands was analyzed to determine the relative contributions of % collagen and % glands <&mus′>. Statistics were calculated using Wilcoxon rank-sum tests, Pearson correlation coefficients and linear fits in R.

The diagnostic ability of the optical parameters was linked to the distance of tumor from the margin as well as menopausal status. [THb] showed statistical differences from <&mus′> between malignant (<&mus′>: 8.96cm-1±2.24MAD, [THb]: 42.70&muM±29.31MAD) compared to benign sites (<&mus′>: 7.29cm-1±2.15MAD, [THb]: 32.09&muM±16.73MAD) (p<0.05). Fibroglandular (FG) sites exhibited increased <&mus′> while adipose sites showed increased [&beta-carotene] within benign tissues. Scattering differentiated between ductal carcinoma in situ (DCIS) (9.46cm-1±1.06MAD) and invasive ductal carcinoma (IDC) (8.00cm-1±1.81MAD), versus adipose sites (6.50cm-1±1.95MAD). [&beta-carotene] showed marginal differences between DCIS (19.00&muM±6.93MAD, and FG (15.30&muM±5.64MAD). [THb] exhibited statistical differences between positive sites (92.57&muM±18.46MAD) and FG (34.12&muM±22.77MAD), FA (28.63&muM±14.19MAD), and A (30.36&muM±14.86MAD). Due to decreased fibrous content and increased adipose content, benign sites in post-menopausal patients exhibited lower <&mus′>, but higher [&beta-carotene] than pre-menopausal patients.

Further deconstructing the relationship between optical scattering and tissue morphology resulted in a positive relationship between <&mus′> and % collagen (r=0.28, p=0.00034). Increased variability was observed in sites with a higher percentage of collagen. In adipose tissues MBD was negatively correlated with age (r=-0.19, p=0.006), BMI (r=-0.33, p=2.3e-6) and average cell area (r=-0.15, p=0.032) but positively related to the log of the average cell density (r=0.17, p=0.12). In addition, BMI was positively correlated to average cell area (r=0.31, p=1.2e-5) and negatively related to log of the cell density (r=-0.28, p=7.6e-5). In non-adipose sites, age was negatively correlated to <&mus′> in benign (r=-0.32, p=4.7e-5) and malignant (r=-0.32, p=1.4e-5) sites and this correlation varied significantly by the collagen level (r=-0.40 vs. -0.13). BMI was negatively correlated to <&mus′> in benign (r=-0.32, p=4e-5) and malignant (r=-0.31, p=2.8e-5) sites but this relationship did not vary by collagen level. MBD was positively correlated to <&mus′> in benign (r=0.22, p=0.01) and malignant (r=0.21, p=4.6e-3) sites. Optical scattering was shown to be tied to patient demographics. Lastly, the analysis of collagen vs. glands was narrowed to investigate sites with glands between 0-40% (the dynamic range of the data), the linear model reflected an equivalent relationship to scattering from % glands and the % collagen in benign sites (r=0.18 vs. r=0.17). In addition, the malignant sites showed a stronger positive relationship (r=0.64, p=0.005) to <&mus′> compared to the benign sites (r=0.52, p=0.03).

The data indicate that the ability of an optical parameter to differentiate benign from malignant breast tissues is dictated by patient demographics. Scattering differentiated between malignant and adipose sites and would be most effective in post-menopausal women. [&beta-carotene] or [THb] may be more applicable in pre-menopausal women to differentiate malignant from fibrous sites. Patient demographics are therefore an important component to incorporate into optical characterization of breast specimens. Through the subsequent stepwise analysis of tissue morphology, <&mus′> was positively correlated to collagen and negatively correlated to age and BMI. Increased variability of <&mus′> with collagen level was not dependent on the adipose contribution. A stronger correlation between age and <&mus′> was seen in high collagen sites compared to low collagen sites. Contributions from collagen and glands to <&mus′> were independent and equivalent in benign sites; glands showed a stronger correlation to <&mus′> in malignant sites than collagen. This information will help develop improved scattering models and additional technologies from separating fibroglandular sites from malignant sites and ultimately improve margin assessment.

Dissertation

Over the past 25 years of development and innovation, optical coherence tomography (OCT) has successfully fills the gap between the ex vivo high-resolution optical microscopy technologies and in vivo low-resolution medical imaging modalities, including computed tomography (CT), magnetic resonance imaging (MRI), ultrasound (US). Ultrahigh resolution (UHR) OCT categorizes OCT systems with an axial resolution below 3 µm in tissue. With the improved resolution, UHR OCT may impart the knowledge of detailed structures of the tissues that are almost close to what histology may provide. This is how UHR OCT can act as a bridge between radiology and histology. This thesis will present an ultrahigh-resolution (UHR) spectral domain (SD) OCT system that features both high axial resolution and long imaging range, and will demonstrate its applications in human myocardium and breast tissue imaging. The UHR OCT system accommodates a supercontinuum light source, and a home-built spectrometer designed to achieve optimized imaging performance. Specifically, the spectrometer features a customized focusing lenses that are comprised of off-the-shelf optics and a 2k-pixel camera to minimize the cost of the instrument. The system manifests an axial resolution of 2.72 µm and a lateral resolution of 5.52 µm, with a large imaging range of 1.78 mm. The sensitivity of the system is 93 dB with a 6-dB sensitivity fall-off range of 0.89 mm. For human myocardium, currently there is no high-resolution non-destructive real-time imaging modality available for biopsy guidance. As a real-time and non-destructive imaging tool, UHR OCT offers additional benefits compared with standard OCT, which are illustrated by successful delineation of micro-structures such as thin elastic fibers and Purkinje fibers in the endomyocardial side. These structures are otherwise not visible within standard-resolution OCT images. Moreover, by adding the cross-polarization (CP) functionality to the UHR SD system, different types of myocardial tissue can be better delineated through the CP contrast. The functional information provided by CP-OCT may also facilitate automatic tissue classification by using A-line signals. For breast tissue imaging, we show qualitatively and quantitatively that UHR OCT images may enable better visualization of detailed features in different types of breast tissue, including healthy and cancerous ones. UHR OCT images of new breast cancer types such as phyllodes tumor, necrotic tumor and fibrotic focus carcinoma are provided for future references. Features developed from UHR OCT images enable a better yield from relevance vector machine (RVM) based stochastic classification model, compared with that from standard resolution OCT images. UHR OCT shows a great promise for automated classification of different tissue types in human breast tissue based off on UHR OCT images. Lastly, we present our endeavor to miniaturize the UHR OCT system on chip. We explore a chip-based optical frequency comb source that may enable UHR OCT at longer wavelengths to achieve better signal penetration in the future. We characterize the performance of the novel source, including the axial resolution and noise, and show that it holds the promise to be adopted in UHR OCT imaging. In addition, we also demonstrate an on-chip tunable reference arm that allows high-topology high-resolution OCT imaging. The compactness of the devices pave the way to the ultimate miniaturization of OCT system.

This thesis reports the work done towards design and fabrication of a versatile and low cost, frequency domain DOT (Diffuse Optical Tomography) Imager. A design which uses only a single fiber for the source and a single fiber bundle for the detector is reported. From near the source, to diametrically opposite to the source, the detected intensity of scattered light varies by three to four orders in magnitude, depending on the tissue/phantom absorption and scattering properties. The photo multiplier tube’s (PMT’s) gain is controlled to operate it in the linear range, thus increasing the dynamic range of detection. Increasing the dynamic range by multi channel data acquisition is also presented. Arresting the oscillations of a stepper using a negative torque braking method is also adopted in this application for increasing the speed of data acquisition. The finite element method (FEM) for obtaining photon density solution to the transport equation and the model based iterative image reconstruction (MPBIIR) algorithm are developed for verifying the experimental prototype. Simulation studies presented towards the end of this thesis work provide insight into the nature of measurements. The optical absorption reconstructed images from the simulation, verified the validity of implementation of the reconstruction method for further reconstructions from data gathered from the developed imager. A single iteration of MOBIIR to segment the region of interest (ROI) using an homogeneous measurement estimate is presented. Using the single iteration MOBIIR to obtain a relatively more accurate starting value for the optical absorption coefficient, and the reconstruction results for data obtained from tissue mimicking solid epoxy-resin phantom with a single in-homogeneity inclusion is also presented to demonstrate the imager prototype.

Le cancer du sein est le cancer le plus fréquent chez la femme. Il demeure la cause de mortalité la plus importante chez les femmes âgées entre 35 et 55 ans. Au Canada, plus de 20 000 nouveaux cas sont diagnostiqués chaque année. Les études scientifiques démontrent que l'espérance de vie est étroitement liée à la précocité du diagnostic. Les moyens de diagnostic actuels comme la mammographie, l'échographie et la biopsie comportent certaines limitations. Par exemple, la mammographie permet de diagnostiquer la présence d’une masse suspecte dans le sein, mais ne peut en déterminer la nature (bénigne ou maligne). Les techniques d’imagerie complémentaires comme l'échographie ou l'imagerie par résonance magnétique (IRM) sont alors utilisées en complément, mais elles sont limitées quant à la sensibilité et la spécificité de leur diagnostic, principalement chez les jeunes femmes (< 50 ans) ou celles ayant un parenchyme dense. Par conséquent, nombreuses sont celles qui doivent subir une biopsie alors que leur lésions sont bénignes. Quelques voies de recherche sont privilégiées depuis peu pour réduire l`incertitude du diagnostic par imagerie ultrasonore. Dans ce contexte, l’élastographie dynamique est prometteuse. Cette technique est inspirée du geste médical de palpation et est basée sur la détermination de la rigidité des tissus, sachant que les lésions en général sont plus rigides que le tissu sain environnant. Le principe de cette technique est de générer des ondes de cisaillement et d'en étudier la propagation de ces ondes afin de remonter aux propriétés mécaniques du milieu via un problème inverse préétabli. Cette thèse vise le développement d'une nouvelle méthode d'élastographie dynamique pour le dépistage précoce des lésions mammaires. L'un des principaux problèmes des techniques d'élastographie dynamiques en utilisant la force de radiation est la forte atténuation des ondes de cisaillement. Après quelques longueurs d'onde de propagation, les amplitudes de déplacement diminuent considérablement et leur suivi devient difficile voir impossible. Ce problème affecte grandement la caractérisation des tissus biologiques. En outre, ces techniques ne donnent que l'information sur l'élasticité tandis que des études récentes montrent que certaines lésions bénignes ont les mêmes élasticités que des lésions malignes ce qui affecte la spécificité de ces techniques et motive la quantification de d'autres paramètres mécaniques (e.g.la viscosité). Le premier objectif de cette thèse consiste à optimiser la pression de radiation acoustique afin de rehausser l'amplitude des déplacements générés. Pour ce faire, un modèle analytique de prédiction de la fréquence de génération de la force de radiation a été développé. Une fois validé in vitro, ce modèle a servi pour la prédiction des fréquences optimales pour la génération de la force de radiation dans d'autres expérimentations in vitro et ex vivo sur des échantillons de tissu mammaire obtenus après mastectomie totale. Dans la continuité de ces travaux, un prototype de sonde ultrasonore conçu pour la génération d'un type spécifique d'ondes de cisaillement appelé ''onde de torsion'' a été développé. Le but est d'utiliser la force de radiation optimisée afin de générer des ondes de cisaillement adaptatives, et de monter leur utilité dans l'amélioration de l'amplitude des déplacements. Contrairement aux techniques élastographiques classiques, ce prototype permet la génération des ondes de cisaillement selon des parcours adaptatifs (e.g. circulaire, elliptique,…etc.) dépendamment de la forme de la lésion. L’optimisation des dépôts énergétiques induit une meilleure réponse mécanique du tissu et améliore le rapport signal sur bruit pour une meilleure quantification des paramètres viscoélastiques. Il est aussi question de consolider davantage les travaux de recherches antérieurs par un appui expérimental, et de prouver que ce type particulier d'onde de torsion peut mettre en résonance des structures. Ce phénomène de résonance des structures permet de rehausser davantage le contraste de déplacement entre les masses suspectes et le milieu environnant pour une meilleure détection. Enfin, dans le cadre de la quantification des paramètres viscoélastiques des tissus, la dernière étape consiste à développer un modèle inverse basé sur la propagation des ondes de cisaillement adaptatives pour l'estimation des paramètres viscoélastiques. L'estimation des paramètres viscoélastiques se fait via la résolution d'un problème inverse intégré dans un modèle numérique éléments finis. La robustesse de ce modèle a été étudiée afin de déterminer ces limites d'utilisation. Les résultats obtenus par ce modèle sont comparés à d'autres résultats (mêmes échantillons) obtenus par des méthodes de référence (e.g. Rheospectris) afin d'estimer la précision de la méthode développée. La quantification des paramètres mécaniques des lésions permet d'améliorer la sensibilité et la spécificité du diagnostic. La caractérisation tissulaire permet aussi une meilleure identification du type de lésion (malin ou bénin) ainsi que son évolution. Cette technique aide grandement les cliniciens dans le choix et la planification d'une prise en charge adaptée.
Breast cancer is the most frequent cancer in women and the leading cause of death for women between 35 and 55 years old. In Canada, more than 20,000 new cases are diagnosed each year. Most of the previous works have shown that life expectancy is closely related to the precocity of diagnosis. Current diagnostic imaging methods such as mammography, sonography, MRI present limitations such as irradiation (mammography), low specificity and low resolution (sonography) and high cost (MRI). For example, about 95% of abnormalities detected by mammography are proven to be benign lesions after complementary examinations (biopsy). Sonography is useful as a complementary examination but the low resolution of its images, its low specificity (54% for women less than 50 years) and its operator dependent interpretation seriously limit the use of this modality alone. MRI is a non-invasive technique with a relatively high sensitivity (86% for women below 50 years), but its limitations are the high cost and the waiting time for medical examination, which dedicate it as a monitoring technique in high-risk patients. It is therefore necessary to examine new noninvasive and cost effective methods. In this context, dynamic elastography is a promising approach. It is an emerging quantitative medical imaging technique inspired from palpation and based on the determination of elastic properties (stiffness) of tissues. This thesis aims the development of a novel dynamic ultrasound elastography method for early detection of breast lesions. One of the main problems of dynamic elastography techniques using remote palpation (acoustic radiation force) is the strong attenuation of shear waves. After few wavelengths of propagation, displacement amplitudes considerably decrease and their tracking becomes difficult even impossible. This problem greatly affects biological tissue characterization. Moreover, these techniques give only the information about elasticity while recent studies show that some benign lesions have the same elasticity as malignant lesions which affect the specificity of these techniques and motivate investigation of other physical parameters (e.g. viscosity). The first objective of this thesis is to optimize the acoustic radiation force using frequency adaptation to enhance the amplitude of displacements. An analytical model has been developed to predict the optimal frequency for the generation of the radiation force. Once validated on phantoms (in vitro), this model was used for the prediction of the optimal frequencies for the generation of the radiation force in tissue mimicking phantoms and ex vivo human breast cancer samples obtained after total mastectomy. Gains in magnitude were between 20% to158% for in vitro measurements on agar-gelatin phantoms, and 170% to 336% for ex vivo measurements on a human breast sample, depending on focus depths and attenuations of tested samples. The signal-to-noise ratio was also improved by more than four folds with adapted sequences. We conclude that frequency adaptation is a complementary technique that is efficient for the optimization of displacement amplitudes. This technique can be used safely to optimize the deposited local acoustic energy, without increasing the risk of damaging tissues and transducer elements. In the second part of this thesis, a prototype of an ultrasound probe for the generation of a specific type of adaptive shear waves called ''adaptive torsional shear waves'' has been developed. The goal was to use the optimized radiation force (developed in the first part) to generate adaptive torsional shear wave, and prove their utility in improving the amplitude of displacement. During their inward propagation, the amplitude of displacement generated by torsional shear waves was enhanced and the signal to noise ratio improved due to the constructive interferences. Torsional shear waves can also resonate heterogeneities which further enhance the displacement contrast between suspicious masses and its surrounding medium. Finally, in the context of assessment of mechanical proprieties of tissue, the last step of this thesis is to develop an inverse problem based on the propagation of adaptive torsional shear waves to estimate the viscoelastic parameters. A finite element method (FEM) model was developed to solve the inverse wave propagation problem and obtain viscoelastic properties of interrogated media. The inverse problem was formulated and solved in the frequency domain and its robustness was evaluated. The proposed model was validated in vitro with two independent rheology methods on several homogeneous and heterogeneous breast tissue mimicking phantoms over a broad range of frequencies (up to 400Hz). The obtained results were in good agreement with reference rheology methods with discrepancies between 8% and 38% for shear modulus and from 9% to 67% for loss modulus. The robustness study showed that the proposed inverse problem solution yielded a good estimation of the storage (19%) and loss moduli (32%) even with very noisy signals.