Biomedical Image Processing and Classification

Biomedical image processing is an interdisciplinary field involving a variety of disciplines, e.g., electronics, computer science, physics, mathematics, physiology, and medicine. Several imaging techniques have been developed, providing many approaches to the study of the human body. Biomedical image processing is finding an increasing number of important applications in, for example, the study of the internal structure or function of an organ and the diagnosis or treatment of a disease. If associated with classification methods, it can support the development of computer-aided diagnosis (CAD) systems, which could help medical doctors in refining their clinical picture

Advances in the Role of Quantitative NMR in Medicine: Deep Learning applied to MR Fingerprinting and Trabecular Bone Volume Fraction Estimation through Single-Sided NMR

Nuclear Magnetic Resonance (NMR) has been a powerful and widespread tool since its birth thanks to its flexibility in assessing properties of physical systems without being invasive and without using ionizing radiations. Although applications of NMR for medical purposes have rapidly developed since the introduction of MR imaging (MRI), most of the clinical protocols retrieve qualitative information about biological tissues. Being able to retrieve also quantitative information with NMR may be beneficial to identify biomarkers for understanding and describing the pathophysiology of complex diseases in many tissues. However, established quantitative MRI (qMRI) methods require long scan times that not only can represent more exposure to image artifacts and more discomfort for the patient, but they also increase the costs of MRI protocols. To improve the clinical feasibility of quantitative NMR, one can focus on optimizing qMRI protocols to increase data acquisition efficiency, i.e. minimizing the acquisition times and maximising the number of retrieved information. Alternatively, one can focus on the application of low-cost, portable and low maintenance NMR devices in the medical field, such as single-sided devices. This Ph.D thesis presents studies that aim to advance the role of quantitative NMR in medicine using the two directions stated above. The first part of the thesis proposes a deep learning approach based on deep Fully Connected Networks (NN), for pixel-wise MR parameter prediction task in Magnetic Resonance Fingerprinting (MRF) as a solution to overcome the curse of dimensionality affecting the gold standard dictionary approach. The second part proposes a methodology to assess the trabecular bone-volume-to-total-volume (BV/TV) ratio using single-side NMR by means of NMR relaxometry measurements. Nowadays there are not well-established methodologies to assess trabecular BV/TV that are suitable for wide screening campaigns of the population at risk of bone fractures related to diseases such as osteoporosis

Doctor of Philosophy

dissertationImage-based biomechanics, particularly numerical modeling using subject-specific data obtained via imaging, has proven useful for elucidating several biomechanical processes, such as prediction of deformation due to external loads, applicable to both normal function and pathophysiology of various organs. As the field evolves towards applications that stretch the limits of imaging hardware and acquisition time, the information traditionally expected as input for numerical routines often becomes incomplete or ambiguous, and requires specific acquisition and processing strategies to ensure physical accuracy and compatibility with predictive mathematical modeling. These strategies, often derivatives or specializations of traditional mechanics, effectively extend the nominal capability of medical imaging hardware providing subject-specific information coupled with the option of using the results for predictive numerical simulations. This research deals with the development of tools for extracting mechanical measurements from a finite set of imaging data and finite element analysis in the context of constructing structural atlases of the heart, understanding the biomechanics of the venous vasculature, and right ventricular failure. The tools include: (1) application of Hyperelastic Warping image registration to displacement-encoded MRI for reconstructing absolute displacement fields, (2) combination of imaging and a material parameter identification approach to measure morphology, deformation, and mechanical properties of vascular tissue, and (3) extrapolation of diffusion tensor MRI acquired at a single time point for the prediction the structural changes across the cardiac cycle with mechanical simulations. Selected tools were then applied to evaluate structural changes in a reversible animal model for right ventricular failure due to pressure overload

Machine learning approaches to model cardiac shape in large-scale imaging studies

Recent improvements in non-invasive imaging, together with the introduction of fully-automated segmentation algorithms and big data analytics, has paved the way for large-scale population-based imaging studies. These studies promise to increase our understanding of a large number of medical conditions, including cardiovascular diseases. However, analysis of cardiac shape in such studies is often limited to simple morphometric indices, ignoring large part of the information available in medical images. Discovery of new biomarkers by machine learning has recently gained traction, but often lacks interpretability. The research presented in this thesis aimed at developing novel explainable machine learning and computational methods capable of better summarizing shape variability, to better inform association and predictive clinical models in large-scale imaging studies. A powerful and flexible framework to model the relationship between three-dimensional (3D) cardiac atlases, encoding multiple phenotypic traits, and genetic variables is first presented. The proposed approach enables the detection of regional phenotype-genotype associations that would be otherwise neglected by conventional association analysis. Three learning-based systems based on deep generative models are then proposed. In the first model, I propose a classifier of cardiac shapes which exploits task-specific generative shape features, and it is designed to enable the visualisation of the anatomical effect these features encode in 3D, making the classification task transparent. The second approach models a database of anatomical shapes via a hierarchy of conditional latent variables and it is capable of detecting, quantifying and visualising onto a template shape the most discriminative anatomical features that characterize distinct clinical conditions. Finally, a preliminary analysis of a deep learning system capable of reconstructing 3D high-resolution cardiac segmentations from a sparse set of 2D views segmentations is reported. This thesis demonstrates that machine learning approaches can facilitate high-throughput analysis of normal and pathological anatomy and of its determinants without losing clinical interpretability.Open Acces

Advanced Computational Methods for Oncological Image Analysis

[Cancer is the second most common cause of death worldwide and encompasses highly variable clinical and biological scenarios. Some of the current clinical challenges are (i) early diagnosis of the disease and (ii) precision medicine, which allows for treatments targeted to specific clinical cases. The ultimate goal is to optimize the clinical workflow by combining accurate diagnosis with the most suitable therapies. Toward this, large-scale machine learning research can define associations among clinical, imaging, and multi-omics studies, making it possible to provide reliable diagnostic and prognostic biomarkers for precision oncology. Such reliable computer-assisted methods (i.e., artificial intelligence) together with clinicians’ unique knowledge can be used to properly handle typical issues in evaluation/quantification procedures (i.e., operator dependence and time-consuming tasks). These technical advances can significantly improve result repeatability in disease diagnosis and guide toward appropriate cancer care. Indeed, the need to apply machine learning and computational intelligence techniques has steadily increased to effectively perform image processing operations—such as segmentation, co-registration, classification, and dimensionality reduction—and multi-omics data integration.

On Improving Generalization of CNN-Based Image Classification with Delineation Maps Using the CORF Push-Pull Inhibition Operator

Deployed image classification pipelines are typically dependent on the images captured in real-world environments. This means that images might be affected by different sources of perturbations (e.g. sensor noise in low-light environments). The main challenge arises by the fact that image quality directly impacts the reliability and consistency of classification tasks. This challenge has, hence, attracted wide interest within the computer vision communities. We propose a transformation step that attempts to enhance the generalization ability of CNN models in the presence of unseen noise in the test set. Concretely, the delineation maps of given images are determined using the CORF push-pull inhibition operator. Such an operation transforms an input image into a space that is more robust to noise before being processed by a CNN. We evaluated our approach on the Fashion MNIST data set with an AlexNet model. It turned out that the proposed CORF-augmented pipeline achieved comparable results on noise-free images to those of a conventional AlexNet classification model without CORF delineation maps, but it consistently achieved significantly superior performance on test images perturbed with different levels of Gaussian and uniform noise

Medical Image Analytics (Radiomics) with Machine/Deeping Learning for Outcome Modeling in Radiation Oncology

Image-based quantitative analysis (radiomics) has gained great attention recently. Radiomics possesses promising potentials to be applied in the clinical practice of radiotherapy and to provide personalized healthcare for cancer patients. However, there are several challenges along the way that this thesis will attempt to address. Specifically, this thesis focuses on the investigation of repeatability and reproducibility of radiomics features, the development of new machine/deep learning models, and combining these for robust outcomes modeling and their applications in radiotherapy. Radiomics features suffer from robustness issues when applied to outcome modeling problems, especially in head and neck computed tomography (CT) images. These images tend to contain streak artifacts due to patients’ dental implants. To investigate the influence of artifacts for radiomics modeling performance, we firstly developed an automatic artifact detection algorithm using gradient-based hand-crafted features. Then, comparing the radiomics models trained on ‘clean’ and ‘contaminated’ datasets. The second project focused on using hand-crafted radiomics features and conventional machine learning methods for the prediction of overall response and progression-free survival for Y90 treated liver cancer patients. By identifying robust features and embedding prior knowledge in the engineered radiomics features and using bootstrapped LASSO to select robust features, we trained imaging and dose based models for the desired clinical endpoints, highlighting the complementary nature of this information in Y90 outcomes prediction. Combining hand-crafted and machine learnt features can take advantage of both expert domain knowledge and advanced data-driven approaches (e.g., deep learning). Thus, we proposed a new variational autoencoder network framework that modeled radiomics features, clinical factors, and raw CT images for the prediction of intrahepatic recurrence-free and overall survival for hepatocellular carcinoma (HCC) patients in this third project. The proposed approach was compared with widely used Cox proportional hazard model for survival analysis. Our proposed methods achieved significant improvement in terms of the prediction using the c-index metric highlighting the value of advanced modeling techniques in learning from limited and heterogeneous information in actuarial prediction of outcomes. Advances in stereotactic radiation therapy (SBRT) has led to excellent local tumor control with limited toxicities for HCC patients, but intrahepatic recurrence still remains prevalent. As an extension of the third project, we not only hope to predict the time to intrahepatic recurrence, but also the location where the tumor might recur. This will be clinically beneficial for better intervention and optimizing decision making during the process of radiotherapy treatment planning. To address this challenging task, firstly, we proposed an unsupervised registration neural network to register atlas CT to patient simulation CT and obtain the liver’s Couinaud segments for the entire patient cohort. Secondly, a new attention convolutional neural network has been applied to utilize multimodality images (CT, MR and 3D dose distribution) for the prediction of high-risk segments. The results showed much improved efficiency for obtaining segments compared with conventional registration methods and the prediction performance showed promising accuracy for anticipating the recurrence location as well. Overall, this thesis contributed new methods and techniques to improve the utilization of radiomics for personalized radiotherapy. These contributions included new algorithm for detecting artifacts, a joint model of dose with image heterogeneity, combining hand-crafted features with machine learnt features for actuarial radiomics modeling, and a novel approach for predicting location of treatment failure.PHDApplied PhysicsUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/163092/1/liswei_1.pd

Improved 3D MR Image Acquisition and Processing in Congenital Heart Disease

Congenital heart disease (CHD) is the most common type of birth defect, affecting about 1% of the population. MRI is an essential tool in the assessment of CHD, including diagnosis, intervention planning and follow-up. Three-dimensional MRI can provide particularly rich visualization and information. However, it is often complicated by long scan times, cardiorespiratory motion, injection of contrast agents, and complex and time-consuming postprocessing. This thesis comprises four pieces of work that attempt to respond to some of these challenges. The first piece of work aims to enable fast acquisition of 3D time-resolved cardiac imaging during free breathing. Rapid imaging was achieved using an efficient spiral sequence and a sparse parallel imaging reconstruction. The feasibility of this approach was demonstrated on a population of 10 patients with CHD, and areas of improvement were identified. The second piece of work is an integrated software tool designed to simplify and accelerate the development of machine learning (ML) applications in MRI research. It also exploits the strengths of recently developed ML libraries for efficient MR image reconstruction and processing. The third piece of work aims to reduce contrast dose in contrast-enhanced MR angiography (MRA). This would reduce risks and costs associated with contrast agents. A deep learning-based contrast enhancement technique was developed and shown to improve image quality in real low-dose MRA in a population of 40 children and adults with CHD. The fourth and final piece of work aims to simplify the creation of computational models for hemodynamic assessment of the great arteries. A deep learning technique for 3D segmentation of the aorta and the pulmonary arteries was developed and shown to enable accurate calculation of clinically relevant biomarkers in a population of 10 patients with CHD