Computational methods for the analysis of functional 4D-CT chest images.

Medical imaging is an important emerging technology that has been intensively used in the last few decades for disease diagnosis and monitoring as well as for the assessment of treatment effectiveness. Medical images provide a very large amount of valuable information that is too huge to be exploited by radiologists and physicians. Therefore, the design of computer-aided diagnostic (CAD) system, which can be used as an assistive tool for the medical community, is of a great importance. This dissertation deals with the development of a complete CAD system for lung cancer patients, which remains the leading cause of cancer-related death in the USA. In 2014, there were approximately 224,210 new cases of lung cancer and 159,260 related deaths. The process begins with the detection of lung cancer which is detected through the diagnosis of lung nodules (a manifestation of lung cancer). These nodules are approximately spherical regions of primarily high density tissue that are visible in computed tomography (CT) images of the lung. The treatment of these lung cancer nodules is complex, nearly 70% of lung cancer patients require radiation therapy as part of their treatment. Radiation-induced lung injury is a limiting toxicity that may decrease cure rates and increase morbidity and mortality treatment. By finding ways to accurately detect, at early stage, and hence prevent lung injury, it will have significant positive consequences for lung cancer patients. The ultimate goal of this dissertation is to develop a clinically usable CAD system that can improve the sensitivity and specificity of early detection of radiation-induced lung injury based on the hypotheses that radiated lung tissues may get affected and suffer decrease of their functionality as a side effect of radiation therapy treatment. These hypotheses have been validated by demonstrating that automatic segmentation of the lung regions and registration of consecutive respiratory phases to estimate their elasticity, ventilation, and texture features to provide discriminatory descriptors that can be used for early detection of radiation-induced lung injury. The proposed methodologies will lead to novel indexes for distinguishing normal/healthy and injured lung tissues in clinical decision-making. To achieve this goal, a CAD system for accurate detection of radiation-induced lung injury that requires three basic components has been developed. These components are the lung fields segmentation, lung registration, and features extraction and tissue classification. This dissertation starts with an exploration of the available medical imaging modalities to present the importance of medical imaging in today’s clinical applications. Secondly, the methodologies, challenges, and limitations of recent CAD systems for lung cancer detection are covered. This is followed by introducing an accurate segmentation methodology of the lung parenchyma with the focus of pathological lungs to extract the volume of interest (VOI) to be analyzed for potential existence of lung injuries stemmed from the radiation therapy. After the segmentation of the VOI, a lung registration framework is introduced to perform a crucial and important step that ensures the co-alignment of the intra-patient scans. This step eliminates the effects of orientation differences, motion, breathing, heart beats, and differences in scanning parameters to be able to accurately extract the functionality features for the lung fields. The developed registration framework also helps in the evaluation and gated control of the radiotherapy through the motion estimation analysis before and after the therapy dose. Finally, the radiation-induced lung injury is introduced, which combines the previous two medical image processing and analysis steps with the features estimation and classification step. This framework estimates and combines both texture and functional features. The texture features are modeled using the novel 7th-order Markov Gibbs random field (MGRF) model that has the ability to accurately models the texture of healthy and injured lung tissues through simultaneously accounting for both vertical and horizontal relative dependencies between voxel-wise signals. While the functionality features calculations are based on the calculated deformation fields, obtained from the 4D-CT lung registration, that maps lung voxels between successive CT scans in the respiratory cycle. These functionality features describe the ventilation, the air flow rate, of the lung tissues using the Jacobian of the deformation field and the tissues’ elasticity using the strain components calculated from the gradient of the deformation field. Finally, these features are combined in the classification model to detect the injured parts of the lung at an early stage and enables an earlier intervention

Nonlocal Graph-PDEs and Riemannian Gradient Flows for Image Labeling

In this thesis, we focus on the image labeling problem which is the task of performing unique pixel-wise label decisions to simplify the image while reducing its redundant information. We build upon a recently introduced geometric approach for data labeling by assignment flows [ APSS17 ] that comprises a smooth dynamical system for data processing on weighted graphs. Hereby we pursue two lines of research that give new application and theoretically-oriented insights on the underlying segmentation task. We demonstrate using the example of Optical Coherence Tomography (OCT), which is the mostly used non-invasive acquisition method of large volumetric scans of human retinal tis- sues, how incorporation of constraints on the geometry of statistical manifold results in a novel purely data driven geometric approach for order-constrained segmentation of volumetric data in any metric space. In particular, making diagnostic analysis for human eye diseases requires decisive information in form of exact measurement of retinal layer thicknesses that has be done for each patient separately resulting in an demanding and time consuming task. To ease the clinical diagnosis we will introduce a fully automated segmentation algorithm that comes up with a high segmentation accuracy and a high level of built-in-parallelism. As opposed to many established retinal layer segmentation methods, we use only local information as input without incorporation of additional global shape priors. Instead, we achieve physiological order of reti- nal cell layers and membranes including a new formulation of ordered pair of distributions in an smoothed energy term. This systematically avoids bias pertaining to global shape and is hence suited for the detection of anatomical changes of retinal tissue structure. To access the perfor- mance of our approach we compare two different choices of features on a data set of manually annotated 3 D OCT volumes of healthy human retina and evaluate our method against state of the art in automatic retinal layer segmentation as well as to manually annotated ground truth data using different metrics. We generalize the recent work [ SS21 ] on a variational perspective on assignment flows and introduce a novel nonlocal partial difference equation (G-PDE) for labeling metric data on graphs. The G-PDE is derived as nonlocal reparametrization of the assignment flow approach that was introduced in J. Math. Imaging & Vision 58(2), 2017. Due to this parameterization, solving the G-PDE numerically is shown to be equivalent to computing the Riemannian gradient flow with re- spect to a nonconvex potential. We devise an entropy-regularized difference-of-convex-functions (DC) decomposition of this potential and show that the basic geometric Euler scheme for inte- grating the assignment flow is equivalent to solving the G-PDE by an established DC program- ming scheme. Moreover, the viewpoint of geometric integration reveals a basic way to exploit higher-order information of the vector field that drives the assignment flow, in order to devise a novel accelerated DC programming scheme. A detailed convergence analysis of both numerical schemes is provided and illustrated by numerical experiments

Automated Morphometric Characterization of the Cerebral Cortex for the Developing and Ageing Brain

Morphometric characterisation of the cerebral cortex can provide information about patterns of brain development and ageing and may be relevant for diagnosis and estimation of the progression of diseases such as Alzheimer's, Huntington's, and schizophrenia. Therefore, understanding and describing the differences between populations in terms of structural volume, shape and thickness is of critical importance. Methodologically, due to data quality, presence of noise, PV effects, limited resolution and pathological variability, the automated, robust and time-consistent estimation of morphometric features is still an unsolved problem. This thesis focuses on the development of tools for robust cross-sectional and longitudinal morphometric characterisation of the human cerebral cortex. It describes techniques for tissue segmentation, structural and morphometric characterisation, cross-sectional and longitudinally cortical thickness estimation from serial MRI images in both adults and neonates. Two new probabilistic brain tissue segmentation techniques are introduced in order to accurately and robustly segment the brain of elderly and neonatal subjects, even in the presence of marked pathology. Two other algorithms based on the concept of multi-atlas segmentation propagation and fusion are also introduced in order to parcelate the brain into its multiple composing structures with the highest possible segmentation accuracy. Finally, we explore the use of the Khalimsky cubic complex framework for the extraction of topologically correct thickness measurements from probabilistic segmentations without explicit parametrisation of the edge. A longitudinal extension of this method is also proposed. The work presented in this thesis has been extensively validated on elderly and neonatal data from several scanners, sequences and protocols. The proposed algorithms have also been successfully applied to breast and heart MRI, neck and colon CT and also to small animal imaging. All the algorithms presented in this thesis are available as part of the open-source package NiftySeg

Analysis of Retinal Image Data to Support Glaucoma Diagnosis

Fundus kamera je široce dostupné zobrazovací zařízení, které umožňuje relativně rychlé a nenákladné vyšetření zadního segmentu oka – sítnice. Z těchto důvodů se mnoho výzkumných pracovišť zaměřuje právě na vývoj automatických metod diagnostiky nemocí sítnice s využitím fundus fotografií. Tato dizertační práce analyzuje současný stav vědeckého poznání v oblasti diagnostiky glaukomu s využitím fundus kamery a navrhuje novou metodiku hodnocení vrstvy nervových vláken (VNV) na sítnici pomocí texturní analýzy. Spolu s touto metodikou je navržena metoda segmentace cévního řečiště sítnice, jakožto další hodnotný příspěvek k současnému stavu řešené problematiky. Segmentace cévního řečiště rovněž slouží jako nezbytný krok předcházející analýzu VNV. Vedle toho práce publikuje novou volně dostupnou databázi snímků sítnice se zlatými standardy pro účely hodnocení automatických metod segmentace cévního řečiště.Fundus camera is widely available imaging device enabling fast and cheap examination of the human retina. Hence, many researchers focus on development of automatic methods towards assessment of various retinal diseases via fundus images. This dissertation summarizes recent state-of-the-art in the field of glaucoma diagnosis using fundus camera and proposes a novel methodology for assessment of the retinal nerve fiber layer (RNFL) via texture analysis. Along with it, a method for the retinal blood vessel segmentation is introduced as an additional valuable contribution to the recent state-of-the-art in the field of retinal image processing. Segmentation of the blood vessels also serves as a necessary step preceding evaluation of the RNFL via the proposed methodology. In addition, a new publicly available high-resolution retinal image database with gold standard data is introduced as a novel opportunity for other researches to evaluate their segmentation algorithms.

A novel MRA-based framework for the detection of changes in cerebrovascular blood pressure.

Background: High blood pressure (HBP) affects 75 million adults and is the primary or contributing cause of mortality in 410,000 adults each year in the United States. Chronic HBP leads to cerebrovascular changes and is a significant contributor for strokes, dementia, and cognitive impairment. Non-invasive measurement of changes in cerebral vasculature and blood pressure (BP) may enable physicians to optimally treat HBP patients. This manuscript describes a method to non-invasively quantify changes in cerebral vasculature and BP using Magnetic Resonance Angiography (MRA) imaging. Methods: MRA images and BP measurements were obtained from patients (n=15, M=8, F=7, Age= 49.2 ± 7.3 years) over a span of 700 days. A novel segmentation algorithm was developed to identify brain vasculature from surrounding tissue. The data was processed to calculate the vascular probability distribution function (PDF); a measure of the vascular diameters in the brain. The initial (day 0) PDF and final (day 700) PDF were used to correlate the changes in cerebral vasculature and BP. Correlation was determined by a mixed effects linear model analysis. Results: The segmentation algorithm had a 99.9% specificity and 99.7% sensitivity in identifying and delineating cerebral vasculature. The PDFs had a statistically significant correlation to BP changes below the circle of Willis (p-value = 0.0007), but not significant (p-value = 0.53) above the circle of Willis, due to smaller blood vessels. Conclusion: Changes in cerebral vasculature and pressure can be non-invasively obtained through MRA image analysis, which may be a useful tool for clinicians to optimize medical management of HBP

Computational models for stuctural analysis of retinal images

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University LondonThe evaluation of retina structures has been of great interest because it could be used as a non-intrusive diagnosis in modern ophthalmology to detect many important eye diseases as well as cardiovascular disorders. A variety of retinal image analysis tools have been developed to assist ophthalmologists and eye diseases experts by reducing the time required in eye screening, optimising the costs as well as providing efficient disease treatment and management systems. A key component in these tools is the segmentation and quantification of retina structures. However, the imaging artefacts such as noise, intensity homogeneity and the overlapping tissue of retina structures can cause significant degradations to the performance of these automated image analysis tools. This thesis aims to provide robust and reliable automated retinal image analysis technique to allow for early detection of various retinal and other diseases. In particular, four innovative segmentation methods have been proposed, including two for retinal vessel network segmentation, two for optic disc segmentation and one for retina nerve fibre layers detection. First, three pre-processing operations are combined in the segmentation method to remove noise and enhance the appearance of the blood vessel in the image, and a Mixture of Gaussians is used to extract the blood vessel tree. Second, a graph cut segmentation approach is introduced, which incorporates the mechanism of vectors flux into the graph formulation to allow for the segmentation of very narrow blood vessels. Third, the optic disc segmentation is performed using two alternative methods: the Markov random field image reconstruction approach detects the optic disc by removing the blood vessels from the optic disc area, and the graph cut with compensation factor method achieves that using prior information of the blood vessels. Fourth, the boundaries of the retinal nerve fibre layer (RNFL) are detected by adapting a graph cut segmentation technique that includes a kernel-induced space and a continuous multiplier based max-flow algorithm. The strong experimental results of our retinal blood vessel segmentation methods including Mixture of Gaussian, Graph Cut achieved an average accuracy of 94:33%, 94:27% respectively. Our optic disc segmentation methods including Markov Random Field and Compensation Factor also achieved an average sensitivity of 92:85% and 85:70% respectively. These results obtained on several public datasets and compared with existing methods have shown that our proposed methods are robust and efficient in the segmenting retinal structures such the blood vessels and the optic disc.Brunel University Londonhttp://bura.brunel.ac.uk/bitstream/2438/10387/1/FulltextThesis.pd

Machine learning strategies for diagnostic imaging support on histopathology and optical coherence tomography

Tesis por compendio[ES] Esta tesis presenta soluciones de vanguardia basadas en algoritmos de computer vision (CV) y machine learning (ML) para ayudar a los expertos en el diagnóstico clínico. Se centra en dos áreas relevantes en el campo de la imagen médica: la patología digital y la oftalmología. Este trabajo propone diferentes paradigmas de machine learning y deep learning para abordar diversos escenarios de supervisión en el estudio del cáncer de próstata, el cáncer de vejiga y el glaucoma. En particular, se consideran métodos supervisados convencionales para segmentar y clasificar estructuras específicas de la próstata en imágenes histológicas digitalizadas. Para el reconocimiento de patrones específicos de la vejiga, se llevan a cabo enfoques totalmente no supervisados basados en técnicas de deep-clustering. Con respecto a la detección del glaucoma, se aplican algoritmos de memoria a corto plazo (LSTMs) que permiten llevar a cabo un aprendizaje recurrente a partir de volúmenes de tomografía por coherencia óptica en el dominio espectral (SD-OCT). Finalmente, se propone el uso de redes neuronales prototípicas (PNN) en un marco de few-shot learning para determinar el nivel de gravedad del glaucoma a partir de imágenes OCT circumpapilares. Los métodos de inteligencia artificial (IA) que se detallan en esta tesis proporcionan una valiosa herramienta de ayuda al diagnóstico por imagen, ya sea para el diagnóstico histológico del cáncer de próstata y vejiga o para la evaluación del glaucoma a partir de datos de OCT.[CA] Aquesta tesi presenta solucions d'avantguarda basades en algorismes de *computer *vision (CV) i *machine *learning (ML) per a ajudar als experts en el diagnòstic clínic. Se centra en dues àrees rellevants en el camp de la imatge mèdica: la patologia digital i l'oftalmologia. Aquest treball proposa diferents paradigmes de *machine *learning i *deep *learning per a abordar diversos escenaris de supervisió en l'estudi del càncer de pròstata, el càncer de bufeta i el glaucoma. En particular, es consideren mètodes supervisats convencionals per a segmentar i classificar estructures específiques de la pròstata en imatges histològiques digitalitzades. Per al reconeixement de patrons específics de la bufeta, es duen a terme enfocaments totalment no supervisats basats en tècniques de *deep-*clustering. Respecte a la detecció del glaucoma, s'apliquen algorismes de memòria a curt termini (*LSTMs) que permeten dur a terme un aprenentatge recurrent a partir de volums de tomografia per coherència òptica en el domini espectral (SD-*OCT). Finalment, es proposa l'ús de xarxes neuronals *prototípicas (*PNN) en un marc de *few-*shot *learning per a determinar el nivell de gravetat del glaucoma a partir d'imatges *OCT *circumpapilares. Els mètodes d'intel·ligència artificial (*IA) que es detallen en aquesta tesi proporcionen una valuosa eina d'ajuda al diagnòstic per imatge, ja siga per al diagnòstic histològic del càncer de pròstata i bufeta o per a l'avaluació del glaucoma a partir de dades d'OCT.[EN] This thesis presents cutting-edge solutions based on computer vision (CV) and machine learning (ML) algorithms to assist experts in clinical diagnosis. It focuses on two relevant areas at the forefront of medical imaging: digital pathology and ophthalmology. This work proposes different machine learning and deep learning paradigms to address various supervisory scenarios in the study of prostate cancer, bladder cancer and glaucoma. In particular, conventional supervised methods are considered for segmenting and classifying prostate-specific structures in digitised histological images. For bladder-specific pattern recognition, fully unsupervised approaches based on deep-clustering techniques are carried out. Regarding glaucoma detection, long-short term memory algorithms (LSTMs) are applied to perform recurrent learning from spectral-domain optical coherence tomography (SD-OCT) volumes. Finally, the use of prototypical neural networks (PNNs) in a few-shot learning framework is proposed to determine the severity level of glaucoma from circumpapillary OCT images. The artificial intelligence (AI) methods detailed in this thesis provide a valuable tool to aid diagnostic imaging, whether for the histological diagnosis of prostate and bladder cancer or glaucoma assessment from OCT data.García Pardo, JG. (2022). Machine learning strategies for diagnostic imaging support on histopathology and optical coherence tomography [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/182400Compendi