Machine Intelligence for Advanced Medical Data Analysis: Manifold Learning Approach

In the current work, linear and non-linear manifold learning techniques, specifically Principle Component Analysis (PCA) and Laplacian Eigenmaps, are studied in detail. Their applications in medical image and shape analysis are investigated. In the first contribution, a manifold learning-based multi-modal image registration technique is developed, which results in a unified intensity system through intensity transformation between the reference and sensed images. The transformation eliminates intensity variations in multi-modal medical scans and hence facilitates employing well-studied mono-modal registration techniques. The method can be used for registering multi-modal images with full and partial data. Next, a manifold learning-based scale invariant global shape descriptor is introduced. The proposed descriptor benefits from the capability of Laplacian Eigenmap in dealing with high dimensional data by introducing an exponential weighting scheme. It eliminates the limitations tied to the well-known cotangent weighting scheme, namely dependency on triangular mesh representation and high intra-class quality of 3D models. In the end, a novel descriptive model for diagnostic classification of pulmonary nodules is presented. The descriptive model benefits from structural differences between benign and malignant nodules for automatic and accurate prediction of a candidate nodule. It extracts concise and discriminative features automatically from the 3D surface structure of a nodule using spectral features studied in the previous work combined with a point cloud-based deep learning network. Extensive experiments have been conducted and have shown that the proposed algorithms based on manifold learning outperform several state-of-the-art methods. Advanced computational techniques with a combination of manifold learning and deep networks can play a vital role in effective healthcare delivery by providing a framework for several fundamental tasks in image and shape processing, namely, registration, classification, and detection of features of interest

A Markov Random Field Groupwise Registration Framework for Face Recognition

In this paper, we propose a new framework for tackling face recognition problem. The face recognition problem is formulated as groupwise deformable image registration and feature matching problem. The main contributions of the proposed method lie in the following aspects: (1) Each pixel in a facial image is represented by an anatomical signature obtained from its corresponding most salient scale local region determined by the survival exponential entropy (SEE) information theoretic measure. (2) Based on the anatomical signature calculated from each pixel, a novel Markov random field based groupwise registration framework is proposed to formulate the face recognition problem as a feature guided deformable image registration problem. The similarity between different facial images are measured on the nonlinear Riemannian manifold based on the deformable transformations. (3) The proposed method does not suffer from the generalizability problem which exists commonly in learning based algorithms. The proposed method has been extensively evaluated on four publicly available databases: FERET, CAS-PEAL-R1, FRGC ver 2.0, and the LFW. It is also compared with several state-of-the-art face recognition approaches, and experimental results demonstrate that the proposed method consistently achieves the highest recognition rates among all the methods under comparison

Deep learning-based diagnostic system for malignant liver detection

Cancer is the second most common cause of death of human beings, whereas liver cancer is the fifth most common cause of mortality. The prevention of deadly diseases in living beings requires timely, independent, accurate, and robust detection of ailment by a computer-aided diagnostic (CAD) system. Executing such intelligent CAD requires some preliminary steps, including preprocessing, attribute analysis, and identification. In recent studies, conventional techniques have been used to develop computer-aided diagnosis algorithms. However, such traditional methods could immensely affect the structural properties of processed images with inconsistent performance due to variable shape and size of region-of-interest. Moreover, the unavailability of sufficient datasets makes the performance of the proposed methods doubtful for commercial use. To address these limitations, I propose novel methodologies in this dissertation. First, I modified a generative adversarial network to perform deblurring and contrast adjustment on computed tomography (CT) scans. Second, I designed a deep neural network with a novel loss function for fully automatic precise segmentation of liver and lesions from CT scans. Third, I developed a multi-modal deep neural network to integrate pathological data with imaging data to perform computer-aided diagnosis for malignant liver detection. The dissertation starts with background information that discusses the proposed study objectives and the workflow. Afterward, Chapter 2 reviews a general schematic for developing a computer-aided algorithm, including image acquisition techniques, preprocessing steps, feature extraction approaches, and machine learning-based prediction methods. The first study proposed in Chapter 3 discusses blurred images and their possible effects on classification. A novel multi-scale GAN network with residual image learning is proposed to deblur images. The second method in Chapter 4 addresses the issue of low-contrast CT scan images. A multi-level GAN is utilized to enhance images with well-contrast regions. Thus, the enhanced images improve the cancer diagnosis performance. Chapter 5 proposes a deep neural network for the segmentation of liver and lesions from abdominal CT scan images. A modified Unet with a novel loss function can precisely segment minute lesions. Similarly, Chapter 6 introduces a multi-modal approach for liver cancer variants diagnosis. The pathological data are integrated with CT scan images to diagnose liver cancer variants. In summary, this dissertation presents novel algorithms for preprocessing and disease detection. Furthermore, the comparative analysis validates the effectiveness of proposed methods in computer-aided diagnosis

Multimodal Data Fusion and Quantitative Analysis for Medical Applications

Medical big data is not only enormous in its size, but also heterogeneous and complex in its data structure, which makes conventional systems or algorithms difficult to process. These heterogeneous medical data include imaging data (e.g., Positron Emission Tomography (PET), Computerized Tomography (CT), Magnetic Resonance Imaging (MRI)), and non-imaging data (e.g., laboratory biomarkers, electronic medical records, and hand-written doctor notes). Multimodal data fusion is an emerging vital field to address this urgent challenge, aiming to process and analyze the complex, diverse and heterogeneous multimodal data. The fusion algorithms bring great potential in medical data analysis, by 1) taking advantage of complementary information from different sources (such as functional-structural complementarity of PET/CT images) and 2) exploiting consensus information that reflects the intrinsic essence (such as the genetic essence underlying medical imaging and clinical symptoms). Thus, multimodal data fusion benefits a wide range of quantitative medical applications, including personalized patient care, more optimal medical operation plan, and preventive public health. Though there has been extensive research on computational approaches for multimodal fusion, there are three major challenges of multimodal data fusion in quantitative medical applications, which are summarized as feature-level fusion, information-level fusion and knowledge-level fusion: • Feature-level fusion. The first challenge is to mine multimodal biomarkers from high-dimensional small-sample multimodal medical datasets, which hinders the effective discovery of informative multimodal biomarkers. Specifically, efficient dimension reduction algorithms are required to alleviate "curse of dimensionality" problem and address the criteria for discovering interpretable, relevant, non-redundant and generalizable multimodal biomarkers. • Information-level fusion. The second challenge is to exploit and interpret inter-modal and intra-modal information for precise clinical decisions. Although radiomics and multi-branch deep learning have been used for implicit information fusion guided with supervision of the labels, there is a lack of methods to explicitly explore inter-modal relationships in medical applications. Unsupervised multimodal learning is able to mine inter-modal relationship as well as reduce the usage of labor-intensive data and explore potential undiscovered biomarkers; however, mining discriminative information without label supervision is an upcoming challenge. Furthermore, the interpretation of complex non-linear cross-modal associations, especially in deep multimodal learning, is another critical challenge in information-level fusion, which hinders the exploration of multimodal interaction in disease mechanism. • Knowledge-level fusion. The third challenge is quantitative knowledge distillation from multi-focus regions on medical imaging. Although characterizing imaging features from single lesions using either feature engineering or deep learning methods have been investigated in recent years, both methods neglect the importance of inter-region spatial relationships. Thus, a topological profiling tool for multi-focus regions is in high demand, which is yet missing in current feature engineering and deep learning methods. Furthermore, incorporating domain knowledge with distilled knowledge from multi-focus regions is another challenge in knowledge-level fusion. To address the three challenges in multimodal data fusion, this thesis provides a multi-level fusion framework for multimodal biomarker mining, multimodal deep learning, and knowledge distillation from multi-focus regions. Specifically, our major contributions in this thesis include: • To address the challenges in feature-level fusion, we propose an Integrative Multimodal Biomarker Mining framework to select interpretable, relevant, non-redundant and generalizable multimodal biomarkers from high-dimensional small-sample imaging and non-imaging data for diagnostic and prognostic applications. The feature selection criteria including representativeness, robustness, discriminability, and non-redundancy are exploited by consensus clustering, Wilcoxon filter, sequential forward selection, and correlation analysis, respectively. SHapley Additive exPlanations (SHAP) method and nomogram are employed to further enhance feature interpretability in machine learning models. • To address the challenges in information-level fusion, we propose an Interpretable Deep Correlational Fusion framework, based on canonical correlation analysis (CCA) for 1) cohesive multimodal fusion of medical imaging and non-imaging data, and 2) interpretation of complex non-linear cross-modal associations. Specifically, two novel loss functions are proposed to optimize the discovery of informative multimodal representations in both supervised and unsupervised deep learning, by jointly learning inter-modal consensus and intra-modal discriminative information. An interpretation module is proposed to decipher the complex non-linear cross-modal association by leveraging interpretation methods in both deep learning and multimodal consensus learning. • To address the challenges in knowledge-level fusion, we proposed a Dynamic Topological Analysis framework, based on persistent homology, for knowledge distillation from inter-connected multi-focus regions in medical imaging and incorporation of domain knowledge. Different from conventional feature engineering and deep learning, our DTA framework is able to explicitly quantify inter-region topological relationships, including global-level geometric structure and community-level clusters. K-simplex Community Graph is proposed to construct the dynamic community graph for representing community-level multi-scale graph structure. The constructed dynamic graph is subsequently tracked with a novel Decomposed Persistence algorithm. Domain knowledge is incorporated into the Adaptive Community Profile, summarizing the tracked multi-scale community topology with additional customizable clinically important factors

Brainlesion: Glioma, Multiple Sclerosis, Stroke and Traumatic Brain Injuries

This two-volume set LNCS 12962 and 12963 constitutes the thoroughly refereed proceedings of the 7th International MICCAI Brainlesion Workshop, BrainLes 2021, as well as the RSNA-ASNR-MICCAI Brain Tumor Segmentation (BraTS) Challenge, the Federated Tumor Segmentation (FeTS) Challenge, the Cross-Modality Domain Adaptation (CrossMoDA) Challenge, and the challenge on Quantification of Uncertainties in Biomedical Image Quantification (QUBIQ). These were held jointly at the 23rd Medical Image Computing for Computer Assisted Intervention Conference, MICCAI 2020, in September 2021. The 91 revised papers presented in these volumes were selected form 151 submissions. Due to COVID-19 pandemic the conference was held virtually. This is an open access book

Improving the domain generalization and robustness of neural networks for medical imaging

Deep neural networks are powerful tools to process medical images, with great potential to accelerate clinical workflows and facilitate large-scale studies. However, in order to achieve satisfactory performance at deployment, these networks generally require massive labeled data collected from various domains (e.g., hospitals, scanners), which is rarely available in practice. The main goal of this work is to improve the domain generalization and robustness of neural networks for medical imaging when labeled data is limited. First, we develop multi-task learning methods to exploit auxiliary data to enhance networks. We first present a multi-task U-net that performs image classification and MR atrial segmentation simultaneously. We then present a shape-aware multi-view autoencoder together with a multi-view U-net, which enables extracting useful shape priors from complementary long-axis views and short-axis views in order to assist the left ventricular myocardium segmentation task on the short-axis MR images. Experimental results show that the proposed networks successfully leverage complementary information from auxiliary tasks to improve model generalization on the main segmentation task. Second, we consider utilizing unlabeled data. We first present an adversarial data augmentation method with bias fields to improve semi-supervised learning for general medical image segmentation tasks. We further explore a more challenging setting where the source and the target images are from different data distributions. We demonstrate that an unsupervised image style transfer method can bridge the domain gap, successfully transferring the knowledge learned from labeled balanced Steady-State Free Precession (bSSFP) images to unlabeled Late Gadolinium Enhancement (LGE) images, achieving state-of-the-art performance on a public multi-sequence cardiac MR segmentation challenge. For scenarios with limited training data from a single domain, we first propose a general training and testing pipeline to improve cardiac image segmentation across various unseen domains. We then present a latent space data augmentation method with a cooperative training framework to further enhance model robustness against unseen domains and imaging artifacts.Open Acces

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

The Multimodal Brain Tumor Image Segmentation Benchmark (BRATS)

In this paper we report the set-up and results of the Multimodal Brain Tumor Image Segmentation Benchmark (BRATS) organized in conjunction with the MICCAI 2012 and 2013 conferences. Twenty state-of-the-art tumor segmentation algorithms were applied to a set of 65 multi-contrast MR scans of low-and high-grade glioma patients-manually annotated by up to four raters-and to 65 comparable scans generated using tumor image simulation software. Quantitative evaluations revealed considerable disagreement between the human raters in segmenting various tumor sub-regions (Dice scores in the range 74%-85%), illustrating the difficulty of this task. We found that different algorithms worked best for different sub-regions (reaching performance comparable to human inter-rater variability), but that no single algorithm ranked in the top for all sub-regions simultaneously. Fusing several good algorithms using a hierarchical majority vote yielded segmentations that consistently ranked above all individual algorithms, indicating remaining opportunities for further methodological improvements. The BRATS image data and manual annotations continue to be publicly available through an online evaluation system as an ongoing benchmarking resource