Inverse Projection Representation and Category Contribution Rate for Robust Tumor Recognition

Sparse representation based classification (SRC) methods have achieved remarkable results. SRC, however, still suffer from requiring enough training samples, insufficient use of test samples and instability of representation. In this paper, a stable inverse projection representation based classification (IPRC) is presented to tackle these problems by effectively using test samples. An IPR is firstly proposed and its feasibility and stability are analyzed. A classification criterion named category contribution rate is constructed to match the IPR and complete classification. Moreover, a statistical measure is introduced to quantify the stability of representation-based classification methods. Based on the IPRC technique, a robust tumor recognition framework is presented by interpreting microarray gene expression data, where a two-stage hybrid gene selection method is introduced to select informative genes. Finally, the functional analysis of candidate's pathogenicity-related genes is given. Extensive experiments on six public tumor microarray gene expression datasets demonstrate the proposed technique is competitive with state-of-the-art methods.Comment: 14 pages, 19 figures, 10 table

Dynamic Thermal Imaging for Intraoperative Monitoring of Neuronal Activity and Cortical Perfusion

Neurosurgery is a demanding medical discipline that requires a complex interplay of several neuroimaging techniques. This allows structural as well as functional information to be recovered and then visualized to the surgeon. In the case of tumor resections this approach allows more fine-grained differentiation of healthy and pathological tissue which positively influences the postoperative outcome as well as the patient's quality of life. In this work, we will discuss several approaches to establish thermal imaging as a novel neuroimaging technique to primarily visualize neural activity and perfusion state in case of ischaemic stroke. Both applications require novel methods for data-preprocessing, visualization, pattern recognition as well as regression analysis of intraoperative thermal imaging. Online multimodal integration of preoperative and intraoperative data is accomplished by a 2D-3D image registration and image fusion framework with an average accuracy of 2.46 mm. In navigated surgeries, the proposed framework generally provides all necessary tools to project intraoperative 2D imaging data onto preoperative 3D volumetric datasets like 3D MR or CT imaging. Additionally, a fast machine learning framework for the recognition of cortical NaCl rinsings will be discussed throughout this thesis. Hereby, the standardized quantification of tissue perfusion by means of an approximated heating model can be achieved. Classifying the parameters of these models yields a map of connected areas, for which we have shown that these areas correlate with the demarcation caused by an ischaemic stroke segmented in postoperative CT datasets. Finally, a semiparametric regression model has been developed for intraoperative neural activity monitoring of the somatosensory cortex by somatosensory evoked potentials. These results were correlated with neural activity of optical imaging. We found that thermal imaging yields comparable results, yet doesn't share the limitations of optical imaging. In this thesis we would like to emphasize that thermal imaging depicts a novel and valid tool for both intraoperative functional and structural neuroimaging

High Dimensional Data Set Analysis Using a Large-Scale Manifold Learning Approach

Because of technological advances, a trend occurs for data sets increasing in size and dimensionality. Processing these large scale data sets is challenging for conventional computers due to computational limitations. A framework for nonlinear dimensionality reduction on large databases is presented that alleviates the issue of large data sets through sampling, graph construction, manifold learning, and embedding. Neighborhood selection is a key step in this framework and a potential area of improvement. The standard approach to neighborhood selection is setting a fixed neighborhood. This could be a fixed number of neighbors or a fixed neighborhood size. Each of these has its limitations due to variations in data density. A novel adaptive neighbor-selection algorithm is presented to enhance performance by incorporating sparse ℓ 1-norm based optimization. These enhancements are applied to the graph construction and embedding modules of the original framework. As validation of the proposed ℓ1-based enhancement, experiments are conducted on these modules using publicly available benchmark data sets. The two approaches are then applied to a large scale magnetic resonance imaging (MRI) data set for brain tumor progression prediction. Results showed that the proposed approach outperformed linear methods and other traditional manifold learning algorithms

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

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.