Inferring Geodesic Cerebrovascular Graphs: Image Processing, Topological Alignment and Biomarkers Extraction

A vectorial representation of the vascular network that embodies quantitative features - location, direction, scale, and bifurcations - has many potential neuro-vascular applications. Patient-specific models support computer-assisted surgical procedures in neurovascular interventions, while analyses on multiple subjects are essential for group-level studies on which clinical prediction and therapeutic inference ultimately depend. This first motivated the development of a variety of methods to segment the cerebrovascular system. Nonetheless, a number of limitations, ranging from data-driven inhomogeneities, the anatomical intra- and inter-subject variability, the lack of exhaustive ground-truth, the need for operator-dependent processing pipelines, and the highly non-linear vascular domain, still make the automatic inference of the cerebrovascular topology an open problem. In this thesis, brain vessels’ topology is inferred by focusing on their connectedness. With a novel framework, the brain vasculature is recovered from 3D angiographies by solving a connectivity-optimised anisotropic level-set over a voxel-wise tensor field representing the orientation of the underlying vasculature. Assuming vessels joining by minimal paths, a connectivity paradigm is formulated to automatically determine the vascular topology as an over-connected geodesic graph. Ultimately, deep-brain vascular structures are extracted with geodesic minimum spanning trees. The inferred topologies are then aligned with similar ones for labelling and propagating information over a non-linear vectorial domain, where the branching pattern of a set of vessels transcends a subject-specific quantized grid. Using a multi-source embedding of a vascular graph, the pairwise registration of topologies is performed with the state-of-the-art graph matching techniques employed in computer vision. Functional biomarkers are determined over the neurovascular graphs with two complementary approaches. Efficient approximations of blood flow and pressure drop account for autoregulation and compensation mechanisms in the whole network in presence of perturbations, using lumped-parameters analog-equivalents from clinical angiographies. Also, a localised NURBS-based parametrisation of bifurcations is introduced to model fluid-solid interactions by means of hemodynamic simulations using an isogeometric analysis framework, where both geometry and solution profile at the interface share the same homogeneous domain. Experimental results on synthetic and clinical angiographies validated the proposed formulations. Perspectives and future works are discussed for the group-wise alignment of cerebrovascular topologies over a population, towards defining cerebrovascular atlases, and for further topological optimisation strategies and risk prediction models for therapeutic inference. Most of the algorithms presented in this work are available as part of the open-source package VTrails

A Learning Health System for Radiation Oncology

The proposed research aims to address the challenges faced by clinical data science researchers in radiation oncology accessing, integrating, and analyzing heterogeneous data from various sources. The research presents a scalable intelligent infrastructure, called the Health Information Gateway and Exchange (HINGE), which captures and structures data from multiple sources into a knowledge base with semantically interlinked entities. This infrastructure enables researchers to mine novel associations and gather relevant knowledge for personalized clinical outcomes. The dissertation discusses the design framework and implementation of HINGE, which abstracts structured data from treatment planning systems, treatment management systems, and electronic health records. It utilizes disease-specific smart templates for capturing clinical information in a discrete manner. HINGE performs data extraction, aggregation, and quality and outcome assessment functions automatically, connecting seamlessly with local IT/medical infrastructure. Furthermore, the research presents a knowledge graph-based approach to map radiotherapy data to an ontology-based data repository using FAIR (Findable, Accessible, Interoperable, Reusable) concepts. This approach ensures that the data is easily discoverable and accessible for clinical decision support systems. The dissertation explores the ETL (Extract, Transform, Load) process, data model frameworks, ontologies, and provides a real-world clinical use case for this data mapping. To improve the efficiency of retrieving information from large clinical datasets, a search engine based on ontology-based keyword searching and synonym-based term matching tool was developed. The hierarchical nature of ontologies is leveraged to retrieve patient records based on parent and children classes. Additionally, patient similarity analysis is conducted using vector embedding models (Word2Vec, Doc2Vec, GloVe, and FastText) to identify similar patients based on text corpus creation methods. Results from the analysis using these models are presented. The implementation of a learning health system for predicting radiation pneumonitis following stereotactic body radiotherapy is also discussed. 3D convolutional neural networks (CNNs) are utilized with radiographic and dosimetric datasets to predict the likelihood of radiation pneumonitis. DenseNet-121 and ResNet-50 models are employed for this study, along with integrated gradient techniques to identify salient regions within the input 3D image dataset. The predictive performance of the 3D CNN models is evaluated based on clinical outcomes. Overall, the proposed Learning Health System provides a comprehensive solution for capturing, integrating, and analyzing heterogeneous data in a knowledge base. It offers researchers the ability to extract valuable insights and associations from diverse sources, ultimately leading to improved clinical outcomes. This work can serve as a model for implementing LHS in other medical specialties, advancing personalized and data-driven medicine

Integrating topological features to enhance cardiac disease diagnosis from 3D CMR images

Treballs Finals de Grau de Matemàtiques, Facultat de Matemàtiques, Universitat de Barcelona, Any: 2023, Director: Carles Casacuberta i Polyxeni Gkontra[en] Persistent homology is a technique from the field of algebraic topology for the analysis and characterization of the shape and structure of datasets in multiple dimensions. Its use is based on the identification and quantification of topological patterns in the dataset across various scales. In this thesis, persistent homology is applied with the objective of extracting topological descriptors from three-dimensional cardiovascular magnetic resonance (CMR) imaging. Thereafter, topological descriptors are used for the detection of cardiovascular diseases by means of Machine Learning (ML) techniques. Radiomics has been one of the recently proposed approaches for disease diagnosis. This method involves the extraction and subsequent analysis of a significant number of quantitative descriptors from medical images. These descriptors offer a characterization of the spatial distribution, texture, and intensity of the structures present in the images. This study demonstrates that radiomics and topological descriptors achieve comparable results, providing complementary insights into the underlying structures and characteristics of anatomical tissues. Moreover, the combination of these two methods leads to a further improvement of the performance of ML models, thereby enhancing medical diagnosis

Deep Causal Learning for Robotic Intelligence

This invited review discusses causal learning in the context of robotic intelligence. The paper introduced the psychological findings on causal learning in human cognition, then it introduced the traditional statistical solutions on causal discovery and causal inference. The paper reviewed recent deep causal learning algorithms with a focus on their architectures and the benefits of using deep nets and discussed the gap between deep causal learning and the needs of robotic intelligence

Computational Modeling for Abnormal Brain Tissue Segmentation, Brain Tumor Tracking, and Grading

This dissertation proposes novel texture feature-based computational models for quantitative analysis of abnormal tissues in two neurological disorders: brain tumor and stroke. Brain tumors are the cells with uncontrolled growth in the brain tissues and one of the major causes of death due to cancer. On the other hand, brain strokes occur due to the sudden interruption of the blood supply which damages the normal brain tissues and frequently causes death or persistent disability. Clinical management of these brain tumors and stroke lesions critically depends on robust quantitative analysis using different imaging modalities including Magnetic Resonance (MR) and Digital Pathology (DP) images. Due to uncontrolled growth and infiltration into the surrounding tissues, the tumor regions appear with a significant texture variation in the static MRI volume and also in the longitudinal imaging study. Consequently, this study developed computational models using novel texture features to segment abnormal brain tissues (tumor, and stroke lesions), tracking the change of tumor volume in longitudinal images, and tumor grading in MR images. Manual delineation and analysis of these abnormal tissues in large scale is tedious, error-prone, and often suffers from inter-observer variability. Therefore, efficient computational models for robust segmentation of different abnormal tissues is required to support the diagnosis and analysis processes. In this study, brain tissues are characterized with novel computational modeling of multi-fractal texture features for multi-class brain tumor tissue segmentation (BTS) and extend the method for ischemic stroke lesions in MRI. The robustness of the proposed segmentation methods is evaluated using a huge amount of private and public domain clinical data that offers competitive performance when compared with that of the state-of-the-art methods. Further, I analyze the dynamic texture behavior of tumor volume in longitudinal imaging and develop post-processing frame-work using three-dimensional (3D) texture features. These post-processing methods are shown to reduce the false positives in the BTS results and improve the overall segmentation result in longitudinal imaging. Furthermore, using this improved segmentation results the change of tumor volume has been quantified in three types such as stable, progress, and shrinkage as observed by the volumetric changes of different tumor tissues in longitudinal images. This study also investigates a novel non-invasive glioma grading, for the first time in literature, that uses structural MRI only. Such non-invasive glioma grading may be useful before an invasive biopsy is recommended. This study further developed an automatic glioma grading scheme using the invasive cell nuclei morphology in DP images for cross-validation with the same patients. In summary, the texture-based computational models proposed in this study are expected to facilitate the clinical management of patients with the brain tumors and strokes by automating large scale imaging data analysis, reducing human error, inter-observer variability, and producing repeatable brain tumor quantitation and grading

Accurate Segmentation of CT Pelvic Organs via Incremental Cascade Learning and Regression-based Deformable Models

Accurate segmentation of male pelvic organs from computed tomography (CT) images is important in image guided radiotherapy (IGRT) of prostate cancer. The efficacy of radiation treatment highly depends on the segmentation accuracy of planning and treatment CT images. Clinically manual delineation is still generally performed in most hospitals. However, it is time consuming and suffers large inter-operator variability due to the low tissue contrast of CT images. To reduce the manual efforts and improve the consistency of segmentation, it is desirable to develop an automatic method for rapid and accurate segmentation of pelvic organs from planning and treatment CT images. This dissertation marries machine learning and medical image analysis for addressing two fundamental yet challenging segmentation problems in image guided radiotherapy of prostate cancer. Planning-CT Segmentation. Deformable models are popular methods for planning-CT segmentation. However, they are well known to be sensitive to initialization and ineffective in segmenting organs with complex shapes. To address these limitations, this dissertation investigates a novel deformable model named regression-based deformable model (RDM). Instead of locally deforming the shape model, in RDM the deformation at each model point is explicitly estimated from local image appearance and used to guide deformable segmentation. As the estimated deformation can be long-distance and is spatially adaptive to each model point, RDM is insensitive to initialization and more flexible than conventional deformable models. These properties render it very suitable for CT pelvic organ segmentation, where initialization is difficult to get and organs may have complex shapes. Treatment-CT Segmentation. Most existing methods have two limitations when they are applied to treatment-CT segmentation. First, they have a limited accuracy because they overlook the availability of patient-specific data in the IGRT workflow. Second, they are time consuming and may take minutes or even longer for segmentation. To improve both accuracy and efficiency, this dissertation combines incremental learning with anatomical landmark detection for fast localization of the prostate in treatment CT images. Specifically, cascade classifiers are learned from a population to automatically detect several anatomical landmarks in the image. Based on these landmarks, the prostate is quickly localized by aligning and then fusing previous segmented prostate shapes of the same patient. To improve the performance of landmark detection, a novel learning scheme named "incremental learning with selective memory" is proposed to personalize the population-based cascade classifiers to the patient under treatment. Extensive experiments on a large dataset show that the proposed method achieves comparable accuracy to the state of the art methods while substantially reducing runtime from minutes to just 4 seconds.Doctor of Philosoph