Enhanced computer assisted detection of polyps in CT colonography

This thesis presents a novel technique for automatically detecting colorectal polyps in computed tomography colonography (CTC). The objective of the documented computer assisted diagnosis (CAD) technique is to deal with the issue of false positive detections without adversely affecting polyp detection sensitivity. The thesis begins with an overview of CTC and a review of the associated research areas, with particular attention given to CAD-CTC. This review identifies excessive false positive detections as a common problem associated with current CAD-CTC techniques. Addressing this problem constitutes the major contribution of this thesis. The documented CAD-CTC technique is trained with, and evaluated using, a series of clinical CTC data sets These data sets contain polyps with a range of different sizes and morphologies. The results presented m this thesis indicate the validity of the developed CAD-CTC technique and demonstrate its effectiveness m accurately detecting colorectal polyps while significantly reducing the number of false positive detections

Feature extraction to aid disease detection and assessment of disease progression in CT and MR colonography

Computed tomographic colonography (CTC) is a technique employed to examine the whole colon for cancers and premalignant adenomas (polyps). Oral preparation is taken to fully cleanse the colon, and gas insufflation maximises the attenuation contrast between the enoluminal colon surface and the lumen. The procedure is performed routinely with the patient both prone and supine to redistribute gas and residue. This helps to differentiate fixed colonic pathology from mobile faecal residue and also helps discover pathology occluded by retained fluid or luminal collapse. Matching corresponding endoluminal surface locations with the patient in the prone and supine positions is therefore an essential aspect of interpretation by radiologists; however, interpretation can be difficult and time consuming due to the considerable colonic deformations that occur during repositioning. Hence, a method for automated registration has the potential to improve efficiency and diagnostic accuracy. I propose a novel method to establish correspondence between prone and supine CT colonography acquisitions automatically. The problem is first simplified by detecting haustral folds which are elongated ridgelike endoluminal structures and can be identified by curvature based measurements. These are subsequently matched using appearance based features, and their relative geometric relationships. It is shown that these matches can be used to find correspondence along the full length of the colon, but may also be used in conjunction with other registration methods to achieve a more robust and accurate result, explicitly addressing the problem of colonic collapse. The potential clinical value of this method has been assessed in an external clinical validation, and the application to follow-up CTC surveillance has been investigated. MRI has recently been applied as a tool to quantitatively evaluate the therapeutic response to therapy in patients with Crohn's disease, and is the preferred choice for repeated imaging. A primary biomarker for this evaluation is the measurement of variations of bowel wall thickness on changing from the active phase of the disease to remission; however, a poor level of interobserver agreement of measured thickness is reported and therefore a system for accurate, robust and reproducible measurements is desirable. I propose a novel method which will automatically track sections of colon, by estimating the positions of elliptical cross sections. Subsequently, estimation of the positions of the inner and outer bowel walls are made based on image gradient information and therefore a thickness measurement value can be extracted

Deep Networks Based Energy Models for Object Recognition from Multimodality Images

Object recognition has been extensively investigated in computer vision area, since it is a fundamental and essential technique in many important applications, such as robotics, auto-driving, automated manufacturing, and security surveillance. According to the selection criteria, object recognition mechanisms can be broadly categorized into object proposal and classification, eye fixation prediction and saliency object detection. Object proposal tends to capture all potential objects from natural images, and then classify them into predefined groups for image description and interpretation. For a given natural image, human perception is normally attracted to the most visually important regions/objects. Therefore, eye fixation prediction attempts to localize some interesting points or small regions according to human visual system (HVS). Based on these interesting points and small regions, saliency object detection algorithms propagate the important extracted information to achieve a refined segmentation of the whole salient objects. In addition to natural images, object recognition also plays a critical role in clinical practice. The informative insights of anatomy and function of human body obtained from multimodality biomedical images such as magnetic resonance imaging (MRI), transrectal ultrasound (TRUS), computed tomography (CT) and positron emission tomography (PET) facilitate the precision medicine. Automated object recognition from biomedical images empowers the non-invasive diagnosis and treatments via automated tissue segmentation, tumor detection and cancer staging. The conventional recognition methods normally utilize handcrafted features (such as oriented gradients, curvature, Haar features, Haralick texture features, Laws energy features, etc.) depending on the image modalities and object characteristics. It is challenging to have a general model for object recognition. Superior to handcrafted features, deep neural networks (DNN) can extract self-adaptive features corresponding with specific task, hence can be employed for general object recognition models. These DNN-features are adjusted semantically and cognitively by over tens of millions parameters corresponding to the mechanism of human brain, therefore leads to more accurate and robust results. Motivated by it, in this thesis, we proposed DNN-based energy models to recognize object on multimodality images. For the aim of object recognition, the major contributions of this thesis can be summarized below: 1. We firstly proposed a new comprehensive autoencoder model to recognize the position and shape of prostate from magnetic resonance images. Different from the most autoencoder-based methods, we focused on positive samples to train the model in which the extracted features all come from prostate. After that, an image energy minimization scheme was applied to further improve the recognition accuracy. The proposed model was compared with three classic classifiers (i.e. support vector machine with radial basis function kernel, random forest, and naive Bayes), and demonstrated significant superiority for prostate recognition on magnetic resonance images. We further extended the proposed autoencoder model for saliency object detection on natural images, and the experimental validation proved the accurate and robust saliency object detection results of our model. 2. A general multi-contexts combined deep neural networks (MCDN) model was then proposed for object recognition from natural images and biomedical images. Under one uniform framework, our model was performed in multi-scale manner. Our model was applied for saliency object detection from natural images as well as prostate recognition from magnetic resonance images. Our experimental validation demonstrated that the proposed model was competitive to current state-of-the-art methods. 3. We designed a novel saliency image energy to finely segment salient objects on basis of our MCDN model. The region priors were taken into account in the energy function to avoid trivial errors. Our method outperformed state-of-the-art algorithms on five benchmarking datasets. In the experiments, we also demonstrated that our proposed saliency image energy can boost the results of other conventional saliency detection methods

Economic Evaluation of Potential Applications of Gene Expression Profiling in Clinical Oncology

Histopathological analysis of tumor is currently the main tool used to guide cancer management. Gene expression profiling may provide additional valuable information for both classification and prognostication of individual tumors. A number of gene expression profiling assays have been developed recently to inform therapy decisions in women with early stage breast cancer and help identify the primary tumor site in patients with metastatic cancer of unknown primary. The impact of these assays on health and economic outcomes, if introduced into general practice, has not been determined. I aimed to conduct an economic evaluation of regulatory-approved gene expression profiling assays for breast cancer and cancer of unknown primary for the purpose of determining whether these technologies represent value for money from the perspective of the Canadian health care system. I developed decision-analytic models to project the lifetime clinical and economic consequences of early stage breast cancer and metastatic cancer of unknown primary. I used Manitoba Cancer Registry and Manitoba administrative health databases to model current “real-world” Canadian clinical practices. I applied available data about gene expression profiling assays from secondary sources on these models to predict the impact of these assays on current clinical and economic outcomes. In the base case, gene expression profiling assays in early stage breast cancer and cancer of unknown primary resulted in incremental cost effectiveness ratios of less than $100,000 per quality-adjusted life-year gained. These results were most sensitive to the uncertainty associated with the accuracy of the assay, patient-physician response to gene expression profiling information and patient survival. The potential application of these gene expression profiling assays in clinical oncology appears to be cost-effective in the Canadian healthcare system. Field evaluation of these assays to establish their impact on cancer management and patient survival may have a large societal impact and should be initiated in Canada to ensure their clinical utility and cost-effectiveness. The use of Canadian provincial administrative population data in decision modeling is useful to quantify uncertainty about gene expression profiling assays and guide the use of novel funding models such as conditional funding alongside a field evaluation

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

Radiomics and Machine Learning in the Prediction of Cardiovascular Disease

Carotid atherosclerosis is a major risk factor for ischaemic stroke which is a leading cause of death worldwide. For stroke survivors, 1 in 4 will have another stroke within five years. Carotid CT angiography (CTA) is commonly performed following an ischaemic stroke or transient ischemic attack to help guide patient management in the secondary prevention of stroke. For example, carotid endarterectomy surgery plus medical therapy or medical therapy alone. The degree of carotid stenosis is the mainstay in making this decision and uses only one aspect of anatomical information that can be obtained from a carotid CTA scan. Radiomics, sometimes called ‘texture analysis’, is the extraction of quantitative data from medical images that may not be apparent to the naked eye and has already demonstrated clinical utility in oncology for applications ranging from lesion characterisation to tumour grading and prognostication. Machine learning refers to the process of learning from experience (in this case data), rather than following pre-programmed rules. This thesis presents the findings of a proof-of-principle study to assess the value of radiomics in identifying the ‘vulnerable plaque’ and the ‘vulnerable patient’ within the context of cerebrovascular events. To evaluate the potential of radiomic features as imaging biomarkers, their reproducibility and robustness to morphological perturbations were assessed, as well as their biological associations with both PET and immunohistochemistry data. The ability of radiomic features to classify different carotid artery types, namely, culprit, non-culprit and asymptomatic carotid arteries was assessed using several machine learning classifiers. This was subsequently compared with a deep learning approach, which has greater capacity for data mining than feature-based machine learning approaches. Overall, radiomics could extract further useful information from carotid CTA scans. Culprit versus non-culprit carotid arteries in symptomatic patients and asymptomatic carotid arteries from asymptomatic patients had different radiomic profiles that could be leveraged using machine learning for better classification performance than carotid calcification or carotid PET imaging alone. Reliable and robust CT-based carotid radiomic features were identified that were associated with the degree of inflammation underlying the carotid artery. If validated with future prospective studies, this has the potential to improve personalised patient care in stroke management and advance clinical decision-making.Cambridge School of Clinical Medicine, the Medical Research Council's Doctoral Training Partnership and the Frank Edward Elmore Fun

Deep Learning-based Solutions to Improve Diagnosis in Wireless Capsule Endoscopy

[eng] Deep Learning (DL) models have gained extensive attention due to their remarkable performance in a wide range of real-world applications, particularly in computer vision. This achievement, combined with the increase in available medical records, has made it possible to open up new opportunities for analyzing and interpreting healthcare data. This symbiotic relationship can enhance the diagnostic process by identifying abnormalities, patterns, and trends, resulting in more precise, personalized, and effective healthcare for patients. Wireless Capsule Endoscopy (WCE) is a non-invasive medical imaging technique used to visualize the entire Gastrointestinal (GI) tract. Up to this moment, physicians meticulously review the captured frames to identify pathologies and diagnose patients. This manual process is time- consuming and prone to errors due to the challenges of interpreting the complex nature of WCE procedures. Thus, it demands a high level of attention, expertise, and experience. To overcome these drawbacks, shorten the screening process, and improve the diagnosis, efficient and accurate DL methods are required. This thesis proposes DL solutions to the following problems encountered in the analysis of WCE studies: pathology detection, anatomical landmark identification, and Out-of-Distribution (OOD) sample handling. These solutions aim to achieve robust systems that minimize the duration of the video analysis and reduce the number of undetected lesions. Throughout their development, several DL drawbacks have appeared, including small and imbalanced datasets. These limitations have also been addressed, ensuring that they do not hinder the generalization of neural networks, leading to suboptimal performance and overfitting. To address the previous WCE problems and overcome the DL challenges, the proposed systems adopt various strategies that utilize the power advantage of Triplet Loss (TL) and Self-Supervised Learning (SSL) techniques. Mainly, TL has been used to improve the generalization of the models, while SSL methods have been employed to leverage the unlabeled data to obtain useful representations. The presented methods achieve State-of-the-art results in the aforementioned medical problems and contribute to the ongoing research to improve the diagnostic of WCE studies.[cat] Els models d’aprenentatge profund (AP) han acaparat molta atenció a causa del seu rendiment en una àmplia gamma d'aplicacions del món real, especialment en visió per ordinador. Aquest fet, combinat amb l'increment de registres mèdics disponibles, ha permès obrir noves oportunitats per analitzar i interpretar les dades sanitàries. Aquesta relació simbiòtica pot millorar el procés de diagnòstic identificant anomalies, patrons i tendències, amb la conseqüent obtenció de diagnòstics sanitaris més precisos, personalitzats i eficients per als pacients. La Capsula endoscòpica (WCE) és una tècnica d'imatge mèdica no invasiva utilitzada per visualitzar tot el tracte gastrointestinal (GI). Fins ara, els metges revisen minuciosament els fotogrames capturats per identificar patologies i diagnosticar pacients. Aquest procés manual requereix temps i és propens a errors. Per tant, exigeix un alt nivell d'atenció, experiència i especialització. Per superar aquests inconvenients, reduir la durada del procés de detecció i millorar el diagnòstic, es requereixen mètodes eficients i precisos d’AP. Aquesta tesi proposa solucions que utilitzen AP per als següents problemes trobats en l'anàlisi dels estudis de WCE: detecció de patologies, identificació de punts de referència anatòmics i gestió de mostres que pertanyen fora del domini. Aquestes solucions tenen com a objectiu aconseguir sistemes robustos que minimitzin la durada de l'anàlisi del vídeo i redueixin el nombre de lesions no detectades. Durant el seu desenvolupament, han sorgit diversos inconvenients relacionats amb l’AP, com ara conjunts de dades petits i desequilibrats. Aquestes limitacions també s'han abordat per assegurar que no obstaculitzin la generalització de les xarxes neuronals, evitant un rendiment subòptim. Per abordar els problemes anteriors de WCE i superar els reptes d’AP, els sistemes proposats adopten diverses estratègies que aprofiten l'avantatge de la Triplet Loss (TL) i les tècniques d’auto-aprenentatge. Principalment, s'ha utilitzat TL per millorar la generalització dels models, mentre que els mètodes d’autoaprenentatge s'han emprat per aprofitar les dades sense etiquetar i obtenir representacions útils. Els mètodes presentats aconsegueixen bons resultats en els problemes mèdics esmentats i contribueixen a la investigació en curs per millorar el diagnòstic dels estudis de WCE