376 research outputs found

    A Deep Learning Approach to Evaluating Disease Risk in Coronary Bifurcations

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    Cardiovascular disease represents a large burden on modern healthcare systems, requiring significant resources for patient monitoring and clinical interventions. It has been shown that the blood flow through coronary arteries, shaped by the artery geometry unique to each patient, plays a critical role in the development and progression of heart disease. However, the popular and well tested risk models such as Framingham and QRISK3 current cardiovascular disease risk models are not able to take these differences when predicting disease risk. Over the last decade, medical imaging and image processing have advanced to the point that non-invasive high-resolution 3D imaging is routinely performed for any patient suspected of coronary artery disease. This allows for the construction of virtual 3D models of the coronary anatomy, and in-silico analysis of blood flow within the coronaries. However, several challenges still exist which preclude large scale patient-specific simulations, necessary for incorporating haemodynamic risk metrics as part of disease risk prediction. In particular, despite a large amount of available coronary medical imaging, extraction of the structures of interest from medical images remains a manual and laborious task. There is significant variation in how geometric features of the coronary arteries are measured, which makes comparisons between different studies difficult. Modelling blood flow conditions in the coronary arteries likewise requires manual preparation of the simulations and significant computational cost. This thesis aims to solve these challenges. The "Automated Segmentation of Coronary Arteries (ASOCA)" establishes a benchmark dataset of coronary arteries and their associated 3D reconstructions, which is currently the largest openly available dataset of coronary artery models and offers a wide range of applications such as computational modelling, 3D printed for experiments, developing, and testing medical devices such as stents, and Virtual Reality applications for education and training. An automated computational modelling workflow is developed to set up, run and postprocess simulations on the Left Main Bifurcation and calculate relevant shape metrics. A convolutional neural network model is developed to replace the computational fluid dynamics process, which can predict haemodynamic metrics such as wall shear stress in minutes, compared to several hours using traditional computational modelling reducing the computation and labour cost involved in performing such simulations

    Deep Representation Learning with Limited Data for Biomedical Image Synthesis, Segmentation, and Detection

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    Biomedical imaging requires accurate expert annotation and interpretation that can aid medical staff and clinicians in automating differential diagnosis and solving underlying health conditions. With the advent of Deep learning, it has become a standard for reaching expert-level performance in non-invasive biomedical imaging tasks by training with large image datasets. However, with the need for large publicly available datasets, training a deep learning model to learn intrinsic representations becomes harder. Representation learning with limited data has introduced new learning techniques, such as Generative Adversarial Networks, Semi-supervised Learning, and Self-supervised Learning, that can be applied to various biomedical applications. For example, ophthalmologists use color funduscopy (CF) and fluorescein angiography (FA) to diagnose retinal degenerative diseases. However, fluorescein angiography requires injecting a dye, which can create adverse reactions in the patients. So, to alleviate this, a non-invasive technique needs to be developed that can translate fluorescein angiography from fundus images. Similarly, color funduscopy and optical coherence tomography (OCT) are also utilized to semantically segment the vasculature and fluid build-up in spatial and volumetric retinal imaging, which can help with the future prognosis of diseases. Although many automated techniques have been proposed for medical image segmentation, the main drawback is the model's precision in pixel-wise predictions. Another critical challenge in the biomedical imaging field is accurately segmenting and quantifying dynamic behaviors of calcium signals in cells. Calcium imaging is a widely utilized approach to studying subcellular calcium activity and cell function; however, large datasets have yielded a profound need for fast, accurate, and standardized analyses of calcium signals. For example, image sequences from calcium signals in colonic pacemaker cells ICC (Interstitial cells of Cajal) suffer from motion artifacts and high periodic and sensor noise, making it difficult to accurately segment and quantify calcium signal events. Moreover, it is time-consuming and tedious to annotate such a large volume of calcium image stacks or videos and extract their associated spatiotemporal maps. To address these problems, we propose various deep representation learning architectures that utilize limited labels and annotations to address the critical challenges in these biomedical applications. To this end, we detail our proposed semi-supervised, generative adversarial networks and transformer-based architectures for individual learning tasks such as retinal image-to-image translation, vessel and fluid segmentation from fundus and OCT images, breast micro-mass segmentation, and sub-cellular calcium events tracking from videos and spatiotemporal map quantification. We also illustrate two multi-modal multi-task learning frameworks with applications that can be extended to other domains of biomedical applications. The main idea is to incorporate each of these as individual modules to our proposed multi-modal frameworks to solve the existing challenges with 1) Fluorescein angiography synthesis, 2) Retinal vessel and fluid segmentation, 3) Breast micro-mass segmentation, and 4) Dynamic quantification of calcium imaging datasets

    Impact of GAN-based Lesion-Focused Medical Image Super-Resolution on Radiomic Feature Robustness

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    Dissertation presented as the partial requirement for obtaining a Master's degree in Data Science and Advanced Analytics, specialization in Data ScienceRobust machine learning models based on radiomic features might allow for accurate diagnosis, prognosis, and medical decision-making. Unfortunately, the lack of standardized radiomic feature extraction has hampered their clinical use. Since the radiomic features tend to be affected by low voxel statistics in regions of interest, increasing the sample size would improve their robustness in clinical studies. Therefore, we propose a Generative Adversarial Network (GAN)-based lesion-focused framework for Computed Tomography (CT) image Super-Resolution (SR); for the lesion (i.e., cancer) patch-focused training, we incorporate Spatial Pyramid Pooling (SPP) into GANConstrained by the Identical, Residual, and Cycle Learning Ensemble (GAN-CIRCLE). At 2× SR, the proposed model achieved better perceptual quality with less blurring than the other considered state-of-the-art SR methods, while producing comparable results at 4× SR. We also evaluated the robustness of our model’s radiomic feature in terms of quantization on a different lung cancer CT dataset using Principal Component Analysis (PCA). Intriguingly, the most important radiomic features in our PCAbased analysis were the most robust features extracted on the GAN-super-resolved images. These achievements pave the way for the application of GAN-based image Super-Resolution techniques for studies of radiomics for robust biomarker discoveryModelos de machine learning robustos baseados em atributos radiômicos possibilitam diagnósticos e decisões médicas mais precisas. Infelizmente, por causa da falta de padronização na extração de atributos radiômicos, sua utilização em contextos clínicos tem sido restrita. Considerando que atributos radiômics tendem a ser afetados pelas estatítiscas de voxels de baixo volume nas regiões de interesse, o aumento to tamanho da amostra tem o potencial de melhorar a robustez desses atributos em estudos clínicos. Portanto, esse trabalho propões um framework baseado numa rede neural generativa (GAN) focada na região de interesse para a super-resolução de imagens de Tomografia Computadorizada (CT). Para treinar a rede de forma concentrada na lesão (i.e. cancer), incorporamos a tecnica de Spatial Pyramid Pooling no framework da GAN-CIRCLE. Nos experimentos de super-resolução 2×, o modelo proposto alcançou melhor qualidade perceptual com menos embaçamento do que outros métodos estado-da-arte considerados. A robustez dos atributos radiômics das imagens super-resolvidas geradas pelo modelo também foram analizadas em termos de quantização em um banco de imagens diferente, contendo imagens de tomografia computadorizada de câncer de pulmão, usando anaálise de componentes principaiss (PCA). Intrigantemente, os atributos radiômicos mais importantes nessa análise foram também os atributos mais robustos extraídos das imagens super-resolvidas pelo método proposto. Esses resultados abrem caminho para a aplicação de técnicas de super-resolução baseadas em redes neurais generativas aplicadas a estudos de radômica para a descoberta de biomarcadores robustos.This work was partially supported by The Mark Foundation for Cancer Research and Cancer Research UK Cambridge Centre [C9685/A25177], the Wellcome Trust Innovator Award, UK [215733/Z/19/Z] and the CRUK National Cancer Imaging Translational Accelerator (NCITA) [C42780/A27066]. Additional support was also provided by the National Institute of Health Research (NIHR) Cambridge Biomedical Research Centre (BRC-1215-20014). This works was also finantially supported by national funds through the FCT (Fundação para a Ciência e a Tecnologia) by the projects GADgET (DSAIPA/DS/0022/2018) and the Slovenian Research Agency (research core funding no. P5-0410).This work was partially supported by The Mark Foundation for Cancer Research and Cancer Research UK Cambridge Centre [C9685/A25177], the Wellcome Trust Innovator Award, UK [215733/Z/19/Z] and the CRUK National Cancer Imaging Translational Accelerator (NCITA) [C42780/A27066]. Additional support was also provided by the National Institute of Health Research (NIHR) Cambridge Biomedical Research Centre (BRC-1215-20014). This works was also finantially supported by national funds through the FCT (Fundação para a Ciência e a Tecnologia) by the projects GADgET (DSAIPA/DS/0022/2018) and the Slovenian Research Agency (research core funding no. P5-0410)

    Intraoperative Quantification of Bone Perfusion in Lower Extremity Injury Surgery

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    Orthopaedic surgery is one of the most common surgical categories. In particular, lower extremity injuries sustained from trauma can be complex and life-threatening injuries that are addressed through orthopaedic trauma surgery. Timely evaluation and surgical debridement following lower extremity injury is essential, because devitalized bones and tissues will result in high surgical site infection rates. However, the current clinical judgment of what constitutes “devitalized tissue” is subjective and dependent on surgeon experience, so it is necessary to develop imaging techniques for guiding surgical debridement, in order to control infection rates and to improve patient outcome. In this thesis work, computational models of fluorescence-guided debridement in lower extremity injury surgery will be developed, by quantifying bone perfusion intraoperatively using Dynamic contrast-enhanced fluorescence imaging (DCE-FI) system. Perfusion is an important factor of tissue viability, and therefore quantifying perfusion is essential for fluorescence-guided debridement. In Chapters 3-7 of this thesis, we explore the performance of DCE-FI in quantifying perfusion from benchtop to translation: We proposed a modified fluorescent microsphere quantification technique using cryomacrotome in animal model. This technique can measure bone perfusion in periosteal and endosteal separately, and therefore to validate bone perfusion measurements obtained by DCE-FI; We developed pre-clinical rodent contaminated fracture model to correlate DCE-FI with infection risk, and compare with multi-modality scanning; Furthermore in clinical studies, we investigated first-pass kinetic parameters of DCE-FI and arterial input functions for characterization of perfusion changes during lower limb amputation surgery; We conducted the first in-human use of dynamic contrast-enhanced texture analysis for orthopaedic trauma classification, suggesting that spatiotemporal features from DCE-FI can classify bone perfusion intraoperatively with high accuracy and sensitivity; We established clinical machine learning infection risk predictive model on open fracture surgery, where pixel-scaled prediction on infection risk will be accomplished. In conclusion, pharmacokinetic and spatiotemporal patterns of dynamic contrast-enhanced imaging show great potential for quantifying bone perfusion and prognosing bone infection. The thesis work will decrease surgical site infection risk and improve successful rates of lower extremity injury surgery
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