Tumour grading and discrimination based on class assignment and quantitative texture analysis techniques

Medical imaging represents the utilisation of technology in biology for the purpose of noninvasively revealing the internal structure of the organs of the human body. It is a way to improve the quality of the patient's life through a more precise and rapid diagnosis, and with limited side-effects, leading to an effective overall treatment procedure. The main objective of this thesis is to propose novel tumour discrimination techniques that cover both micro and macro-scale textures encountered in computed tomography (CI') and digital microscopy (DM) modalities, respectively. Image texture can provide significant information on the (ab)normality of tissue, and this thesis expands this idea to tumour texture grading and classification. The fractal dimension (FO) as a texture measure was applied to contrast enhanced CT lung tumour images in an aim to improve tumour grading accuracy from conventional CI' modality, and quantitative performance analysis showed an accuracy of 83.30% in distinguishing between advanced (aggressive) and early stage (non-aggressive) malignant tumours. A different approach was adopted for subtype discrimination of brain tumour OM images via a set of statistical and model-based texture analysis algorithms. The combined Gaussian Markov random field and run-length matrix texture measures outperformed all other combinations, achieving an overall class assignment classification accuracy of 92.50%. Also two new histopathological multi resolution approaches based on applying the FO as the best bases selection for discrete wavelet packet transform, and when fused with the Gabor filters' energy output improved the accuracy to 91.25% and 95.00%, respectively. While noise is quite common in all medical imaging modalities, the impact of noise on the applied texture measures was assessed as well. The developed lung and brain texture analysis techniques can improve the physician's ability to detect and analyse pathologies leading for a more reliable diagnosis and treatment of disease

PREDICTION AND CONTROL OF IMAGE PROPERTIES IN ADVANCED COMPUTED TOMOGRAPHY

Computed Tomography (CT) is an important technique that is in widespread use for disease diagnosis, monitoring, and interventional procedures. There are many varieties of CT including cone-beam CT (CBCT) that has exceptional high spatial resolution and spectral CT that incorporates energy-dependent measurements for advanced material discrimination. The goal of this research is to quantify image properties using a prospective prediction framework for advanced reconstruction in CBCT and spectral CT systems. These predictors analyze the dependencies of image properties on system configuration, acquisition strategy, and reconstruction regularization design. The prospective estimation of image properties facilitates novel system and acquisition design, adaptive and task-driven imaging, and tuning of regularization for robust and reliable performance. The proposed research quantifies the image properties of model-based iterative reconstruction (MBIR) in CBCT and model-based material decomposition (MBMD) in spectral CT, including spatial resolution, the generalized response to local perturbations, and noise correlation. Predictions are derived with a realistic system model including physical blur, noise correlation, and a poly-energetic model that applies to a variety of spectral CT protocols. Reconstruction methods combining data statistical fidelity and various advanced regularization designs are explored. Prediction accuracy is validated with measured image properties in both simulation and physical experiments. The theoretical understanding is applied to applications with prospective reconstruction regularization design

Automated Strategies in Multimodal and Multidimensional Ultrasound Image-based Diagnosis

Medical ultrasonography is an effective technique in traditional anatomical and functional diagnosis. However, it requires the visual examination by experienced clinicians, which is a laborious, time consuming and highly subjective procedure. Computer-aided diagnosis (CADx) have been extensively used in clinical practice to support the interpretation of images; nevertheless, current ultrasound CADx still entails a substantial user-dependency and are unable to extract image data for prediction modelling. The aim of this thesis is to propose a set of fully automated strategies to overcome the limitations of ultrasound CADx. These strategies are addressed to multiple modalities (B-Mode, Contrast-Enhanced Ultrasound-CEUS, Power Doppler-PDUS and Acoustic Angiography-AA) and dimensions (2-D and 3-D imaging). The enabling techniques presented in this work are designed, developed and quantitively validated to efficiently improve the overall patients’ diagnosis. This work is subdivided in 2 macro-sections: in the first part, two fully automated algorithms for the reliable quantification of 2-D B-Mode ultrasound skeletal muscle architecture and morphology are proposed. In the second part, two fully automated algorithms for the objective assessment and characterization of tumors’ vasculature in 3-D CEUS and PDUS thyroid tumors and preclinical AA cancer growth are presented. In the first part, the MUSA (Muscle UltraSound Analysis) algorithm is designed to measure the muscle thickness, the fascicles length and the pennation angle; the TRAMA (TRAnsversal Muscle Analysis) algorithm is proposed to extract and analyze the Visible Cross-Sectional Area (VCSA). MUSA and TRAMA algorithms have been validated on two datasets of 200 images; automatic measurements have been compared with expert operators’ manual measurements. A preliminary statistical analysis was performed to prove the ability of texture analysis on automatic VCSA in the distinction between healthy and pathological muscles. In the second part, quantitative assessment on tumor vasculature is proposed in two automated algorithms for the objective characterization of 3-D CEUS/Power Doppler thyroid nodules and the evolution study of fibrosarcoma invasion in preclinical 3-D AA imaging. Vasculature analysis relies on the quantification of architecture and vessels tortuosity. Vascular features obtained from CEUS and PDUS images of 20 thyroid nodules (10 benign, 10 malignant) have been used in a multivariate statistical analysis supported by histopathological results. Vasculature parametric maps of implanted fibrosarcoma are extracted from 8 rats investigated with 3-D AA along four time points (TPs), in control and tumors areas; results have been compared with manual previous findings in a longitudinal tumor growth study. Performance of MUSA and TRAMA algorithms results in 100% segmentation success rate. Absolute difference between manual and automatic measurements is below 2% for the muscle thickness and 4% for the VCSA (values between 5-10% are acceptable in clinical practice), suggesting that automatic and manual measurements can be used interchangeably. The texture features extraction on the automatic VCSAs reveals that texture descriptors can distinguish healthy from pathological muscles with a 100% success rate for all the four muscles. Vascular features extracted of 20 thyroid nodules in 3-D CEUS and PDUS volumes can be used to distinguish benign from malignant tumors with 100% success rate for both ultrasound techniques. Malignant tumors present higher values of architecture and tortuosity descriptors; 3-D CEUS and PDUS imaging present the same accuracy in the differentiation between benign and malignant nodules. Vascular parametric maps extracted from the 8 rats along the 4 TPs in 3-D AA imaging show that parameters extracted from the control area are statistically different compared to the ones within the tumor volume. Tumor angiogenetic vessels present a smaller diameter and higher tortuosity. Tumor evolution is characterized by the significant vascular trees growth and a constant value of vessel diameter along the four TPs, confirming the previous findings. In conclusion, the proposed automated strategies are highly performant in segmentation, features extraction, muscle disease detection and tumor vascular characterization. These techniques can be extended in the investigation of other organs, diseases and embedded in ultrasound CADx, providing a user-independent reliable diagnosis

Image processing in medicine advances for phenotype characterization, computer-assisted diagnosis and surgical planning

En esta Tesis presentamos nuestras contribuciones al estado del arte en procesamiento digital de imágenes médicas, articulando nuestra exposición en torno a los tres principales objetivos de la adquisición de imágenes en medicina: la prevención, el diagnóstico y el tratamiento de las enfermedades. La prevención de la enfermedad se puede conseguir a veces mediante una caracterización cuidadosa de los fenotipos propios de la misma. Tal caracterización a menudo se alcanza a partir de imágenes. Presentamos nuestro trabajo en caracterización del enfisema pulmonar a partir de imágenes TAC (Tomografía Axial Computerizada) de tórax en alta resolución, a través del análisis de las texturas locales de la imagen. Nos proponemos llenar el vacío existente entre la práctica clínica actual, y las sofisticadas pero costosas técnicas de caracterización de regiones texturadas, disponibles en la literatura. Lo hacemos utilizando la distribución local de intensidades como un descriptor adecuado para determinar el grado de destrucción de tejido en pulmones enfisematosos. Se presentan interesantes resultados derivados del análisis de varios cientos de imágenes para niveles variables de severidad de la enfermedad, sugiriendo tanto la validez de nuestras hipótesis, como la pertinencia de este tipo de análisis para la comprensión de la enfermedad pulmonar obstructiva crónica. El procesado de imágenes médicas también puede asistir en el diagnóstico y detección de enfermedades. Presentamos nuestras contribuciones a este campo, que consisten en técnicas de segmentación y cuantificación de imágenes dermatoscópicas de lesiones de la piel. La segmentación se obtiene mediante un novedoso algoritmo basado en contornos activos que explota al máximo el contenido cromático de las imágenes, gracias a la maximización de la discrepancia mediante comparaciones cross-bin. La cuantificación de texturas en lesiones melanocíticas se lleva a cabo utilizando un modelado de los patrones de pigmentación basado en campos aleatorios de Markov, en un esfuerzo por adoptar la tendencia emergente en dermatología: la detección de la malignidad mediante el análisis de la irregularidad de la textura. Los resultados para ambas técnicas son validados con un conjunto significativo de imágenes dermatológicas, sugiriendo líneas interesantes para la detección automática del melanoma maligno. Cuando la enfermedad ya está presente, el tratamiento digital de imágenes puede asistir en la planificación quirúrgica y la intervención guiada por imagen. La planificación terapeútica, ejemplicada por la planificación de cirugía plástica usando realidad virtual, se aborda en nuestro trabajo en segmentación de hueso/grasa/músculo en imágenes TAC. Usando un abordaje interactivo e incremental, nuestro sistema permite obtener segmentaciones precisas a partir de unos cuantos clics de ratón para una gran variedad de condiciones de adquisición y frente a anatomícas anormales. Presentamos nuestra metodología, y nuestra validación experimental profusa basada tanto en segmentaciones manuales como en valoraciones subjetivas de los usuarios, e indicamos referencias al lector que detallan los beneficios obtenidos con el uso de la plataforma de planifificación que utiliza nuestro algoritmo. Como conclusión presentamos una disertación final sobre la importancia de nuestros resultados y las líneas probables de trabajo futuro hacía el objetivo último de mejorar el cuidado de la salud mediante técnicas de tratamiento digital de imágenes médicas.In this Thesis we present our contributions to the state-of-the-art in medical image processing, articulating our exposition around the three main roles of medical imaging: disease prevention, diagnosis and treatment. Disease prevention can sometimes be achieved by proper characterization of disease phenotypes. Such characterization is often attained from the standpoint of imaging. We present our work in characterization of emphysema from highresolution computed-tomography images via quanti_cation of local texture. We propose to _ll the gap between current clinical practice and sophisticated texture approaches by the use of local intensity distributions as an adequate descriptor for the degree of tissue destruction in the emphysematous lung. Interesting results are presented from the analysis of several hundred datasets of lung CT for varying disease severity, suggesting both the correctness of our hypotheses and the pertinence of _ne emphysema quanti_cation for understanding of chronic obstructive pulmonary disease. Medical image processing can also assist in the diagnosis and detection of disease. We introduce our contributions to this_eld, consisting of segmentation and quanti_cation techniques in application to dermatoscopy images of skin lesions. Segmentation is achieved via a novel active contour algorithm that fully exploits the color content of the images, via cross-bin histogram dissimilarity maximization. Texture quanti_cation in the context of melanocytic lesions is performed using modelization of the pigmentation patterns via Markov random elds, in an e_ort to embrace the emerging trend in dermatology: malignancy assessment based on texture irregularity analysis. Experimental results for both, the segmentation and quanti_cation proposed techniques, will be validated on a signi_cant set of dermatoscopy images, suggesting interesting pathways towards automatic detection and diagnosis of malignant melanoma. Once disease has occurred, image processing can assist in therapeutical planning and image-guided intervention. Therapeutical planning, exempli_ed by virtual reality surgical planning, is tackled by our work in segmentation of bone/fat/muscle in CT images for plastic surgery planning. Using an interactive, incremental approach, our system is able to provide accurate segmentations based on a couple of mouse-clicks for a wide variety of imaging conditions and abnormal anatomies. We present our methodology, and provide profuse experimental validation based on manual segmentations and subjective assessment, and refer the reader to related work reporting on the clinical bene_ts obtained using the virtual reality platform hosting our algorithm. As a conclusion we present a _nal dissertation on the signi_cance of our results and the probable lines of future work towards fully bene_tting healthcare using medical image processing

Mechanoresponsive drug delivery materials

Stimuli-responsive drug delivery materials release their payloads in response to physiological or external cues and are widely reported for stimuli such as pH, temperature, ionic strength, electrical potential, or applied magnetic field. While a handful of reports exist on materials responsive to mechanical stimuli, this area receives considerably less attention. This dissertation therefore explores three-dimensional networks and polymer-metal composites as mechanoresponsive biomaterials by using mechanical force to either trigger the release of entrapped agents or change the conformation of implants. At the nanoscale, shear is demonstrated as a mechanical stimulus for the release of a monoclonal antibody from nanofibrous, low molecular weight hydrogels formed from bio-inspired small molecule gelators. Using their self-healing, shear-thinning properties, mechanoresponsive neutralization of tumor necrosis factor alpha (TNFα) in a cell culture bioassay is achieved, suggesting utility for treating rheumatoid arthritis. Reaching the microscale, mechanical considerations are incorporated within the design of cisplatin-loaded meshes for sustained local drug delivery, which are fabricated through electrospinning a blend of polycaprolactone and poly(caprolactone-co-glycerol monostearate). These meshes are compliant, amenable to stapling/suturing, and they exhibit bulk superhydrophobicity (i.e., extraordinary resistance to wetting), which sustains release of cisplatin >90 days in vitro and significantly delays tumor recurrence in an in vivo murine lung cancer resection model. This polymer chemistry/processing strategy is then generalized by applying it to the poly(lactide-co-glycolide) family of biomedical polymers. As a macroscopic approach, a tunable, tension-responsive multilayered drug delivery device is developed, which consists of a water-absorbent core flanked by two superhydrophobic microparticle coatings. Applied strain initiates coating fracture to cause core hydration and subsequent drug release, with rates dependent on strain magnitude. Finally, macroscopic, shape-changing polymer-composite materials are developed to improve the current functionality of breast biopsy markers. This shape change provides a means to prevent marker migration from its intended site—a current clinical problem. In summary, mechanoresponsive systems are described, ranging from the nano- to macroscopic scale, for applications in drug delivery and biomedical devices. These studies add to the nascent field of mechanoresponsive biomedical materials and the arsenal of drug delivery techniques required to combat cancer and other medical ailments.2017-10-27T00:00:00

Advances in Design by Metallic Materials: Synthesis, Characterization, Simulation and Applications

Very recently, a great deal of attention has been paid by researchers and technologists to trying to eliminate metal materials in the design of products and processes in favor of plastics and composites. After a few years, it is possible to state that metal materials are even more present in our lives and this is especially thanks to their ability to evolve. This Special Issue is focused on the recent evolution of metals and alloys with the scope of presenting the state of the art of solutions where metallic materials have become established, without a doubt, as a successful design solution thanks to their unique properties

Multifractal techniques for analysis and classification of emphysema images

This thesis proposes, develops and evaluates different multifractal methods for detection, segmentation and classification of medical images. This is achieved by studying the structures of the image and extracting the statistical self-similarity measures characterized by the Holder exponent, and using them to develop texture features for segmentation and classification. The theoretical framework for fulfilling these goals is based on the efficient computation of fractal dimension, which has been explored and extended in this work. This thesis investigates different ways of computing the fractal dimension of digital images and validates the accuracy of each method with fractal images with predefined fractal dimension. The box counting and the Higuchi methods are used for the estimation of fractal dimensions. A prototype system of the Higuchi fractal dimension of the computed tomography (CT) image is used to identify and detect some of the regions of the image with the presence of emphysema. The box counting method is also used for the development of the multifractal spectrum and applied to detect and identify the emphysema patterns. We propose a multifractal based approach for the classification of emphysema patterns by calculating the local singularity coefficients of an image using four multifractal intensity measures. One of the primary statistical measures of self-similarity used in the processing of tissue images is the Holder exponent (α-value) that represents the power law, which the intensity distribution satisfies in the local pixel neighbourhoods. The fractal dimension corresponding to each α-value gives a multifractal spectrum f(α) that was used as a feature descriptor for classification. A feature selection technique is introduced and implemented to extract some of the important features that could increase the discriminating capability of the descriptors and generate the maximum classification accuracy of the emphysema patterns. We propose to further improve the classification accuracy of emphysema CT patterns by combining the features extracted from the alpha-histograms and the multifractal descriptors to generate a new descriptor. The performances of the classifiers are measured by using the error matrix and the area under the receiver operating characteristic curve (AUC). The results at this stage demonstrated the proposed cascaded approach significantly improves the classification accuracy. Another multifractal based approach using a direct determination approach is investigated to demonstrate how multifractal characteristic parameters could be used for the identification of emphysema patterns in HRCT images. This further analysis reveals the multi-scale structures and characteristic properties of the emphysema images through the generalized dimensions. The results obtained confirm that this approach can also be effectively used for detecting and identifying emphysema patterns in CT images. Two new descriptors are proposed for accurate classification of emphysema patterns by hybrid concatenation of the local features extracted from the local binary patterns (LBP) and the global features obtained from the multifractal images. The proposed combined feature descriptors of the LBP and f(α) produced a very good performance with an overall classification accuracy of 98%. These performances outperform other state-of-the-art methods for emphysema pattern classification and demonstrate the discriminating power and robustness of the combined features for accurate classification of emphysema CT images. Overall, experimental results have shown that the multifractal could be effectively used for the classifications and detections of emphysema patterns in HRCT images

Roughening interfaces in spatial population dynamics

The spatial structure and geometry of biological systems can have a strong effect on that system’s evolutionary dynamics. In particular, spatially structured populations may invade one another, giving rise to invasion fronts that may exhibit qualitatively different evolutionary dynamics in different dimensions or geometric configurations. For examples of invasion fronts arising in nature, one might think of a thin layer of bacteria cells growing on a Petri dish, an animal species expanding into new territory, or a cancerous tumor growing into and competing with the surrounding healthy tissue. Perhaps the most well-studied class of invasion fronts in population genetics is the Fisher wave, which was developed to explain how an advantageous gene sweeps throughout a population. In this thesis, I will focus on the study of invasion fronts which develop an enhanced roughness due to internal dynamics of the invading population; namely, I make use of simple lattice and analytic models to explore how the interface between an unstable, mutating population and a healthy bystander population develops an enhanced roughness as the mutating population approaches a population collapse via mutational meltdown. I discuss the differences in this roughening behavior for populations in different dimensions and geometries and show that universal aspects of the roughness may be captured by studying how the characteristic size of the interface changes with time