Signed Laplacian Deep Learning with Adversarial Augmentation for Improved Mammography Diagnosis

Computer-aided breast cancer diagnosis in mammography is limited by inadequate data and the similarity between benign and cancerous masses. To address this, we propose a signed graph regularized deep neural network with adversarial augmentation, named \textsc{DiagNet}. Firstly, we use adversarial learning to generate positive and negative mass-contained mammograms for each mass class. After that, a signed similarity graph is built upon the expanded data to further highlight the discrimination. Finally, a deep convolutional neural network is trained by jointly optimizing the signed graph regularization and classification loss. Experiments show that the \textsc{DiagNet} framework outperforms the state-of-the-art in breast mass diagnosis in mammography.Comment: To appear in MICCAI October 201

COIN:Contrastive Identifier Network for Breast Mass Diagnosis in Mammography

Computer-aided breast cancer diagnosis in mammography is a challenging problem, stemming from mammographical data scarcity and data entanglement. In particular, data scarcity is attributed to the privacy and expensive annotation. And data entanglement is due to the high similarity between benign and malignant masses, of which manifolds reside in lower dimensional space with very small margin. To address these two challenges, we propose a deep learning framework, named Contrastive Identifier Network (\textsc{COIN}), which integrates adversarial augmentation and manifold-based contrastive learning. Firstly, we employ adversarial learning to create both on- and off-distribution mass contained ROIs. After that, we propose a novel contrastive loss with a built Signed graph. Finally, the neural network is optimized in a contrastive learning manner, with the purpose of improving the deep model's discriminativity on the extended dataset. In particular, by employing COIN, data samples from the same category are pulled close whereas those with different labels are pushed further in the deep latent space. Moreover, COIN outperforms the state-of-the-art related algorithms for solving breast cancer diagnosis problem by a considerable margin, achieving 93.4\% accuracy and 95.0\% AUC score. The code will release on ***

Innovations in Medical Image Analysis and Explainable AI for Transparent Clinical Decision Support Systems

This thesis explores innovative methods designed to assist clinicians in their everyday practice, with a particular emphasis on Medical Image Analysis and Explainability issues. The main challenge lies in interpreting the knowledge gained from machine learning algorithms, also called black-boxes, to provide transparent clinical decision support systems for real integration into clinical practice. For this reason, all work aims to exploit Explainable AI techniques to study and interpret the trained models. Given the countless open problems for the development of clinical decision support systems, the project includes the analysis of various data and pathologies. The main works are focused on the most threatening disease afflicting the female population: Breast Cancer. The works aim to diagnose and classify breast cancer through medical images by taking advantage of a first-level examination such as Mammography screening, Ultrasound images, and a more advanced examination such as MRI. Papers on Breast Cancer and Microcalcification Classification demonstrated the potential of shallow learning algorithms in terms of explainability and accuracy when intelligible radiomic features are used. Conversely, the union of deep learning and Explainable AI methods showed impressive results for Breast Cancer Detection. The local explanations provided via saliency maps were critical for model introspection, as well as increasing performance. To increase trust in these systems and aspire to their real use, a multi-level explanation was proposed. Three main stakeholders who need transparent models have been identified: developers, physicians, and patients. For this reason, guided by the enormous impact of COVID-19 in the world population, a fully Explainable machine learning model was proposed for COVID-19 Prognosis prediction exploiting the proposed multi-level explanation. It is assumed that such a system primarily requires two components: 1) inherently explainable inputs such as clinical, laboratory, and radiomic features; 2) Explainable methods capable of explaining globally and locally the trained model. The union of these two requirements allows the developer to detect any model bias, the doctor to verify the model findings with clinical evidence, and justify decisions to patients. These results were also confirmed for the study of coronary artery disease. In particular machine learning algorithms are trained using intelligible clinical and radiomic features extracted from pericoronaric adipose tissue to assess the condition of coronary arteries. Eventually, some important national and international collaborations led to the analysis of data for the development of predictive models for some neurological disorders. In particular, the predictivity of handwriting features for the prediction of depressed patients was explored. Using the training of neural networks constrained by first-order logic, it was possible to provide high-performance and explainable models, going beyond the trade-off between explainability and accuracy

Computer-aided Detection of Breast Cancer in Digital Tomosynthesis Imaging Using Deep and Multiple Instance Learning

Breast cancer is the most common cancer among women in the world. Nevertheless, early detection of breast cancer improves the chance of successful treatment. Digital breast tomosynthesis (DBT) as a new tomographic technique was developed to minimize the limitations of conventional digital mammography screening. A DBT is a quasi-three-dimensional image that is reconstructed from a small number of two-dimensional (2D) low-dose X-ray images. The 2D X-ray images are acquired over a limited angular around the breast. Our research aims to introduce computer-aided detection (CAD) frameworks to detect early signs of breast cancer in DBTs. In this thesis, we propose three CAD frameworks for detection of breast cancer in DBTs. The first CAD framework is based on hand-crafted feature extraction. Concerning early signs of breast cancer: mass, micro-calcifications, and bilateral asymmetry between left and right breast, the system includes three separate channels to detect each sign. Next two CAD frameworks automatically learn complex patterns of 2D slices using the deep convolutional neural network and the deep cardinality-restricted Boltzmann machines. Finally, the CAD frameworks employ a multiple-instance learning approach with randomized trees algorithm to classify DBT images based on extracted information from 2D slices. The frameworks operate on 2D slices which are generated from DBT volumes. These frameworks are developed and evaluated using 5,040 2D image slices obtained from 87 DBT volumes. We demonstrate the validation and usefulness of the proposed CAD frameworks within empirical experiments for detecting breast cancer in DBTs

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

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

Generative models improve fairness of medical classifiers under distribution shifts

A ubiquitous challenge in machine learning is the problem of domain generalisation. This can exacerbate bias against groups or labels that are underrepresented in the datasets used for model development. Model bias can lead to unintended harms, especially in safety-critical applications like healthcare. Furthermore, the challenge is compounded by the difficulty of obtaining labelled data due to high cost or lack of readily available domain expertise. In our work, we show that learning realistic augmentations automatically from data is possible in a label-efficient manner using generative models. In particular, we leverage the higher abundance of unlabelled data to capture the underlying data distribution of different conditions and subgroups for an imaging modality. By conditioning generative models on appropriate labels, we can steer the distribution of synthetic examples according to specific requirements. We demonstrate that these learned augmentations can surpass heuristic ones by making models more robust and statistically fair in- and out-of-distribution. To evaluate the generality of our approach, we study 3 distinct medical imaging contexts of varying difficulty: (i) histopathology images from a publicly available generalisation benchmark, (ii) chest X-rays from publicly available clinical datasets, and (iii) dermatology images characterised by complex shifts and imaging conditions. Complementing real training samples with synthetic ones improves the robustness of models in all three medical tasks and increases fairness by improving the accuracy of diagnosis within underrepresented groups. This approach leads to stark improvements OOD across modalities: 7.7% prediction accuracy improvement in histopathology, 5.2% in chest radiology with 44.6% lower fairness gap and a striking 63.5% improvement in high-risk sensitivity for dermatology with a 7.5x reduction in fairness gap