Minimal Elastographic Modeling of Breast Cancer for Model Based Tumour Detection in a Digital Image Elasto Tomography (DIET) System

Digital Image Elasto Tomography (DIET) is a non-invasive breast cancer screening technology that images the surface motion of a breast under harmonic mechanical actuation. A new approach capturing the dynamics and characteristics of tumor behavior is presented. A simple mechanical model of the breast is used to identify a transfer function relating the input harmonic actuation to the output surface displacements using imaging data of a silicone phantom. Areas of higher stiffness cause significant changes of damping and resonant frequencies as seen in the resulting Bode plots. A case study on a healthy and tumor silicone breast phantom shows the potential for this model-based method to clearly distinguish cancerous and healthy tissue as well as correctly predicting the tumor position

Evaluation of Elastographic techniques generated by means of external vibration

Breast cancer is one of the greatest problems of national and international public health, whose incidence among women population shows an increasing trend. Nowadays there are several elastographic techniques, which seek to characterize the tissue, that is, to analyze the response produced by the application of a perturbation in the medium, to describe its mechanical properties. Among the modalities used are ultrasound, nuclear magnetic resonance and optical coherence tomography. On the other hand, among the types of disturbance used are low frequency mechanical waves, a uniform compression force or acoustic radiation force. In this thesis work, ultrasound was used due to its low economical cost in comparison to the other modalities. In addition, the type of perturbation selected was the external mechanical vibration, as it ensures the achievement of quantitative results, there is no risk of temperature rise in the analyzed area and allows the repeatability of the results obtained. Hence, two elastographic techniques were the axes of the present work: vibro-elastography and normal vibration holography. For the first, a calibrated phantom and a gelatin-based phantom were used, in order to characterize and validate the technique over a wide range of excitation frequencies. Posteriorly, 18 patients were analyzed prior biopsy exam, obtaining elastograms and contrasting them with the respective biopsy results. The results suggest that the technique is able to identify the presence of benign or malignant cancer, and the elasticity estimated agree with values reported in the literature. The second technique is proposed in the elastography field for the first time. Based on holography, its experimental scheme is established, and the mathematical expression for shear speed estimation is presented. Results from simulation and experiments performed on homogeneous and heterogeneous phantoms are presented, and the estimates are compared with previously obtained reference values. The results suggest that the estimates are close to the reference values for all media tested, and the technique must be studied in depth to revert artifacts formation.Tesi

Développement d’un prototype d’imagerie médicale utilisant l’élastographie par corrélation d’images numériques

Le Cancer du sein est une maladie répandue chez les femmes; une femme sur 8 en développera une forme. Or, c’est un cancer ayant un taux de survie important, en particulier s’il est détecté dans les premiers stades. Cette constatation a amené les gouvernements à créer des programmes de dépistages généralisésqui utilisent la mammographie X. Cette méthode présente cependant des limitations notamment l’utilisation de rayons ionisants. Le cancer modifie les propriétés des tissus, en particulier les propriétés mécaniques dont la rigidité. Le lien entre maladie et modification de la rigidité a été établi dès l’antiquité. Des travaux menés dans les années 1990 ont permis le développement de l’élastographie, méthode qui permet de mesurer les propriétés mécaniques des tissus. Plusieurs méthodes existent pour cela : mesure de la vitesse de propagation des ondes, des déformations ... À cela s’ajoute le fait que le contraste entre tissus sains et tissus cancéreux en termes de module élastique est bien plus important que le contraste du coefficient d’atténuation aux rayons X. C’est donc une des pistes de remplacement de la mammographie X parmi les plus prometteuses. Dans cette thèse, on présente la mise en œuvre de l’élastographie par corrélation d’images numériques. Cette nouvelle méthode diffère des autres méthodes d’élastographie en cela qu’elle se base uniquement sur la mesure des déplacements de la surface rendant la reconstruction des paramètres mécaniques mal posée. Avec une couverture suffisante de la surface, il devient possible de reconstruire les propriétés mécaniques internes des tissus. Des tests in vitro ont été effectués, permettant la reconstruction des propriétés mécaniques de fantôme avec ou sans inclusion.Abstract: Breast cancer is a widespread disease among women; one over eight will develop one of its form. However, it’s a cancer with a high survival rate, especially if detected early on. This finding has brought governments to develop screening programs using X-ray mammography. But mammography has several downsides, including the use of ionizing radiation. Cancer modifies tissue properties notably stiffness. The link between illness and change in stiffness has been identified since antiquity. Studies in the 1990s have allowed the dévelopment of elastography, a method that aims at measuring the mechanical properties of tissues. Several methods exist: measure of the propagation speed of deformation wave, measure of the deformations … Moreover, stiffness contrast between healthy and cancerous tissue is higher than for the X-ray attenuation coefficient contrast. This makes elastography a promising replacement for X-ray mammography. This thesis presents an implementation of elastography using digital image correlation. This new method differs strongly from other implementations as only surface displacements are measured, making the reconstruction an ill-posed problem. However, with sufficient coverage of the surface, it has become possible to reconstruct the tissue internal mechanical properties throughout. In vitro tests have been carried out to reconstruct the mechanical properties of tissue mimicking silicon phantoms with and without stiff inclusions

Digital Image Elasto-Tomography: Mechanical Property Reconstruction from Surface Measured Displacement Data

Interest in elastographic techniques for soft tissue imaging has grown as relevant research continues to indicate a correlation between tissue histology and mechanical stiffness. Digital Image Elasto-Tomography (DIET) presents a novel method for identifying cancerous lesions via a three-dimensional image of elastic properties. Stiffness reconstruction with DIET takes steady-state motion captured with a digital camera array as the input to an elastic property reconstruction algorithm, where finite element methods allow simulation of phantom motion at a range of internal stiffness distributions. The low cost and high image contrast achievable with a DIET system may be particularly suited to breast cancer screening, where traditional modalities such as mammography have issues with limited sensitivity and patient discomfort. Proof of concept studies performed on simulated data sets confirmed the potential of the DIET technique, leading to the development of an experimental apparatus for surface motion capture from a range of soft tissue approximating phantoms. Error studies performed on experimental data from these phantoms using a limited number of shape and modulus parameters indicated that accurate measurements of surface motion provide sufficient information to identify a stiffness distribution in both homogeneous and heterogeneous cases. The elastic reconstruction performed on simulated and experimental data considered both deterministic and stochastic algorithms, with a combination of the two approaches found to give the most accurate results, for a realistic increase in computational cost. The reconstruction algorithm developed has the ability to successfully resolve a hard spherical inclusion within a soft phantom, and in addition demonstrated promise in reconstructing the correct stiffness distribution when no inclusion is present

Viewing life without labels under optical microscopes

Optical microscopes today have pushed the limits of speed, quality, and observable space in biological specimens revolutionizing how we view life today. Further, specific labeling of samples for imaging has provided insight into how life functions. This enabled label-based microscopy to percolate and integrate into mainstream life science research. However, the use of labelfree microscopy has been mostly limited, resulting in testing for bio-application but not bio-integration. To enable bio-integration, such microscopes need to be evaluated for their timeliness to answer biological questions uniquely and establish a long-term growth prospect. The article presents key label-free optical microscopes and discusses their integrative potential in life science research for the unperturbed analysis of biological samples

Viscoelasticity Imaging of Biological Tissues and Single Cells Using Shear Wave Propagation

Changes in biomechanical properties of biological soft tissues are often associated with physiological dysfunctions. Since biological soft tissues are hydrated, viscoelasticity is likely suitable to represent its solid-like behavior using elasticity and fluid-like behavior using viscosity. Shear wave elastography is a non-invasive imaging technology invented for clinical applications that has shown promise to characterize various tissue viscoelasticity. It is based on measuring and analyzing velocities and attenuations of propagated shear waves. In this review, principles and technical developments of shear wave elastography for viscoelasticity characterization from organ to cellular levels are presented, and different imaging modalities used to track shear wave propagation are described. At a macroscopic scale, techniques for inducing shear waves using an external mechanical vibration, an acoustic radiation pressure or a Lorentz force are reviewed along with imaging approaches proposed to track shear wave propagation, namely ultrasound, magnetic resonance, optical, and photoacoustic means. Then, approaches for theoretical modeling and tracking of shear waves are detailed. Following it, some examples of applications to characterize the viscoelasticity of various organs are given. At a microscopic scale, a novel cellular shear wave elastography method using an external vibration and optical microscopy is illustrated. Finally, current limitations and future directions in shear wave elastography are presented

Modulography: elasticity imaging of atherosclerotic plaques

Modulography is an experimental elasticity imaging method. It has potential to become an all-in-one in vivo tool (a) for detecting vulnerable atherosclerotic coronary plaques, (b) for assessing information related to their rupture-proneness and (c) for imaging their elastic material composition. Modulography determines a cross-sectional image of the elasticity distribution (=Young's modulus) from deformation (=strain) that is processed from intravascular ultrasound (IVUS) measurements. By looking at this image, cardiologists and other researchers can directly identify and characterize soft and stiff plaque-components of thin-cap fibroatheromas and of heterogeneous plaques. As a diagnostic and pharm

Mechanical and morphometric characterization of cancellous bone

[EN] Bone fracture is a social health problem of increasing magnitude because of its prevalence in aged population due to osteoporosis. Bone quality is often characterized by bone mineral density (BMD) measured at cancellous bone regions using dual-energy X-ray absorptiometry (DXA). However, BMD alone cannot predict several cases because not only density is important, but also microstructure plays an important role in cancellous bone strength. The mechanical properties can be used as indicators of bone integrity as a function of age, disease or treatment. Therefore, cancellous bone fracture characterization and its relationship to microstructure has not been completely solved in the literature and is relevant to improve fracture prediction. In this thesis, we aim at characterizing cancellous bone morphometry and mechanical behavior. Morphometry is estimated through the analysis of micro-computed tomography (micro-CT) images of vertebral cancellous bone specimens. With regards to the mechanical behavior, we calculate elastic, yield and failure properties at the apparent and tissue levels. To determine them, we followed different approaches: compression tests, finite element models and micro-CT phantoms. We have developed finite element models that reproduce the elastic and failure response of cancellous bone under compression conditions. We modeled failure as a combination of continuum damage mechanics and the element deletion technique. The numerical models permitted to estimate elastic and failure properties. Failure properties were consistent with results reported in the literature. Specifically, our results revealed that yield strain is relatively constant (0.7 %) over a range of apparent densities, while failure strain presents a wider range of variation. A single strain parameter (equivalent strain) was found as an accurate descriptor of cancellous bone compression failure. Image-based numerical models usually need for the action of a technician to segment the images. Therefore, we studied the sensitivity to variations of the segmentation threshold on the morphometry and the elastic properties of vertebral cancellous bone specimens of different bone volume fractions. The apparent modulus is highly sensitive to the segmentation threshold. We report variations between 45 and 120 % for a ± 15 % threshold variation. Other parameters, such as BS/BV, BS/TV, Tb.Sp, Tb.N, Conn.D and fractal dimension were influenced significantly. Digital image correlation (DIC) was applied to images taken during compression testing to analyze displacement fields at failure and characterize them. Some variables were explored to describe failure and a study is done about how DIC parameters influence the strain field obtained. Facet and step sizes have a relevant effect on the failure strain estimation, and an increment of both parameters reduces the strain estimation up to 40 %. Besides, several parameters combination led to correct failure pattern detection, so values reported in the literature should be referred to the parameters used. Furthermore, we explored if cancellous bone microstructure acts (non-speckle/texture approach) as a proper pattern to calculate displacements using DIC technique. As regards relationships between microstructure and mechanics, single and multiple parameter analysis were performed to assess the morphometric variables that control the explanation of mechanical properties variation. Bone volume fraction (BV/TV), bone surface to volume ratio (BS/BV), mean trabecular thickness (Tb.Th) and fractal dimension (D) presented the best linear correlations to the elastic properties, while both the yield and failure strains did not show correlation to any morphometric parameter. The regressions obtained permit to estimate those mechanical properties that describe the state of a specimen.[ES] Las fracturas óseas constituyen un problema social de salud con magnitud creciente por su prevalencia en la población de edad avanzada debido a la osteoporosis. La calidad del hueso suele caracterizarse mediante la estimación de la densidad mineral ósea (DMO) en regiones de hueso trabecular, utilizando absorciometría de rayos X de energía dual (DXA). No obstante, la DMO por si sola no es capaz de predecir numerosos casos de fractura porque no solo importa la pérdida de densidad, sino que la microestructura también tiene un papel principal en la resistencia del hueso. Las propiedades mecánicas del hueso pueden usarse como indicadores de su integridad en función de la edad, enfermedad o tratamiento. Por lo tanto, la caracterización de la fractura de hueso trabecular y su relación con la microestructura no se ha resuelto de forma completa en la literatura y es relevante para mejorar las predicciones de fractura. En esta tesis, nuestro principal objetivo es caracterizar la morfometría y el comportamiento mecánico del hueso trabecular. Estimamos la morfometría a través del análisis de imágenes obtenidas por micro tomografía computerizada (micro-CT) de muestras de hueso trabecular vertebral de cerdo. Respecto al comportamiento mecánico, calculamos propiedades elásticas, de plasticidad y fractura a escala aparente y de tejido. Para determinar esas propiedades, hemos seguido diferentes procedimientos: ensayos a compresión, modelos de elementos finitos y fantomas de calibración micro-CT. Los modelos de elementos finitos desarrollados reproducen la respuesta elástica y de fallo bajo condiciones de compresión en hueso trabecular, modelando el fallo como combinación de mecánica del daño contínuo y la técnica de eliminación de elementos. Los modelos numéricos desarrollados han permitido estimar propiedades elásticas y de fallo. En concreto, las deformaciones de inicio de fallo estimadas son relativamente constantes para las muestras analizadas (0.7 %), mientras que las deformaciones últimas de fallo presentan un rango de variación mayor. Por otro lado, encontramos que la deformación equivalente es el descriptor más preciso del fallo a compresión del hueso trabecular. Normalmente, los modelos numéricos basados en imágenes suelen necesitar la acción de un técnico para segmentar las imágenes. En este sentido, estudiamos la sensibilidad de la morfometría y la estimación de propiedades elásticas ante variaciones en el umbral de segmentación en muestras con distinta fracción en volumen. Hemos obtenido que la rigidez aparente es muy sensible a cambios en el umbral de segmentación, con variaciones entre 45 y 120 % para una variación de ± 15 % del umbral de segmentación. Otros parámetros, como BS/BV, BS/TV, Tb.Sp, Tb.N, Conn.D y la dimensión fractal se ven afectados significativamente. Por otro lado, hemos aplicado la técnica correlación digital por imagen (DIC) para caracterizar campos de desplazamientos en el fallo a compresión del hueso trabecular, a partir del análisis de imágenes tomadas durante el ensayo de las muestras. Además, estudiamos la influencia de algunos parámetros de la técnica DIC en el campo de deformaciones obtenido. También, hemos explorado la aplicación DIC sin el uso de moteado, utilizando como patrón de reconocimiento la propia microestructura trabecular. En relación al estudio de la influencia de la microestructura en la respuesta mecánica, hemos calculado correlaciones de uno y varios parámetros para analizar qué variables morfométricas explican la variación de las propiedades mecánicas. La fracción en volumen de hueso (BV/TV), la relación entre el área y el volumen de hueso (BS/BV), el espesor trabecular medio (Tb.Th) y la dimensión fractal (D) presentan las mejores correlaciones lineales respecto a las propiedades elásticas, mientras que las deformaciones de inicio de plasticidad y fractura no mostraron correlación con ningún parámetro morfométrico.[CA] Les fractures òssies constitueixen un problema social de salut amb magnitud creixent per la seua prevalença en la població d'edat avançada a causa de l'osteoporosi. La qualitat de l'os sol caracteritzar-se mitjançant l'estimació de la densitat mineral òssia (DMO) en regions d'os trabecular, utilitzant absorciometria de raigs X d'energia dual (DXA). No obstant això, la DMO per si sola no és capaç de predir nombrosos casos de fractura perquè no sols importa la pèrdua de densitat, sinó que la microestructura també té un paper principal en la resistència de l'os. Les propietats mecàniques de l'os poden usar-se com a indicadors de la seua integritat en funció de l'edat, malaltia o tractament. Per tant, la caracterització de la fractura d'os trabecular i la seua relació amb la microestructura no s'ha resolt de manera completa en la literatura i és rellevant per a millorar les prediccions de fractura. En aquesta tesi, el nostre principal objectiu és caracteritzar la morfometria i el comportament mecànic de l'os trabecular. Estimem la morfometria a través de l'anàlisi d'imatges obtingudes per micro tomografia automatitzada (micro-CT) de mostres d'os trabecular vertebral de porc. Respecte al comportament mecànic, calculem propietats elàstiques, de plasticitat i fractura a escala aparent i de teixit. Per a determinar aqueixes propietats, hem seguit diferents procediments: assajos a compressió, models d'elements finits i fantomas de calibratge micro-CT. Hem desenvolupat models d'elements finits que reprodueixen la resposta elàstica i de fallada sota condicions de compressió en os trabecular, modelant la fallada com a combinació de mecànica del dany continu i la tècnica d'eliminació d'elements. Els models numèrics desenvolupats han permés estimar propietats elàstiques i de fallada. Les nostres estimacions respecte a propietats de fallada són consistents amb valors reportats en la literatura. En concret, les deformacions d'inici de fallada estimades són relativament constants per a les mostres analitzades (0.7 %), mentre que les deformacions últimes de fallada presenten un rang de variació major. D'altra banda, trobem que la deformació equivalent és el descriptor més precís de la fallada a compressió de l'os trabecular. Els models numèrics basats en imatges solen necessitar l'acció d'un tècnic per a segmentar les imatges. En aquest sentit, estudiem la sensibilitat de la morfometria i l'estimació de propietats elàstiques davant variacions en el llindar de segmentació en mostres amb diferent fracció en volum. Hem obtingut que la rigidesa aparent és molt sensible a canvis en el llindar de segmentació, amb variacions entre 45 i 120 % per a una variació de ± 15 % del llindar de segmentació. Altres paràmetres, com BS/BV, BS/TV, Tb.Sp, Tb.N, Conn.D i la dimensió fractal es veuen afectats significativament. D'altra banda, hem aplicat la tècnica correlació digital per imatge (DIC) per a caracteritzar camps de desplaçaments en la fallada a compressió de l'os trabecular, a partir de l'anàlisi d'imatges preses durant l'assaig de les mostres. A més, estudiem la influència d'alguns paràmetres de la tècnica DIC en el camp de deformacions obtingut. També, hem explorat l'aplicació DIC sense l'ús de clapejat, utilitzant com a patró de reconeixement la pròpia microestructura trabecular. En relació a l'estudi de la influència de la microestructura en la resposta mecànica, hem calculat correlacions d'un i diversos paràmetres per a analitzar quines variables morfomètriques expliquen la variació de les propietats mecàniques. La fracció en volum d'os (BV/TV), la relació entre l'àrea i el volum d'os (BS/BV), la espessor trabecular mitjà (Tb.th) i la dimensió fractal (D) presenten les millors correlacions lineals respecte a les propietats elàstiques, mentre que les deformacions d'inici de plasticitat i fractura no van mostrar correlació amb cap paràmetre morfomètric.Belda González, R. (2020). Mechanical and morphometric characterization of cancellous bone [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/149376TESI