Fast and Robust Automatic Segmentation Methods for MR Images of Injured and Cancerous Tissues

Magnetic Resonance Imaging: MRI) is a key medical imaging technology. Through in vivo soft tissue imaging, MRI allows clinicians and researchers to make diagnoses and evaluations that were previously possible only through biopsy or autopsy. However, analysis of MR images by domain experts can be time-consuming, complex, and subject to bias. The development of automatic segmentation techniques that make use of robust statistical methods allows for fast and unbiased analysis of MR images. In this dissertation, I propose segmentation methods that fall into two classes---(a) segmentation via optimization of a parametric boundary, and: b) segmentation via multistep, spatially constrained intensity classification. These two approaches are applicable in different segmentation scenarios. Parametric boundary segmentation is useful and necessary for segmentation of noisy images where the tissue of interest has predictable shape but poor boundary delineation, as in the case of lung with heavy or diffuse tumor. Spatially constrained intensity classification is appropriate for segmentation of noisy images with moderate contrast between tissue regions, where the areas of interest have unpredictable shapes, as is the case in spinal injury and brain tumor. The proposed automated segmentation techniques address the need for MR image analysis in three specific applications:: 1) preclinical rodent studies of primary and metastatic lung cancer: approach: a)),: 2) preclinical rodent studies of spinal cord lesion: approach: b)), and: 3) postclinical analysis of human brain cancer: approach: b)). In preclinical rodent studies of primary and metastatic lung cancer, respiratory-gated MRI is used to quantitatively measure lung-tumor burden and monitor the time-course progression of individual tumors. I validate a method for measuring tumor burden based upon average lung-image intensity. The method requires accurate lung segmentation; toward this end, I propose an automated lung segmentation method that works for varying tumor burden levels. The method includes development of a novel, two-dimensional parametric model of the mouse lungs and a multifaceted cost function to optimally fit the model parameters to each image. Results demonstrate a strong correlation: 0.93), comparable with that of fully manual expert segmentation, between the automated method\u27s tumor-burden metric and the tumor burden measured by lung weight. In preclinical rodent studies of spinal cord lesion, MRI is used to quantify tissues in control and injured mouse spinal cords. For this application, I propose a novel, multistep, multidimensional approach, utilizing the Classification Expectation Maximization: CEM) algorithm, for automatic segmentation of spinal cord tissues. In contrast to previous methods, my proposed method incorporates prior knowledge of cord geometry and the distinct information contained in the different MR images gathered. Unlike previous approaches, the algorithm is shown to remain accurate for whole spinal cord, white matter, and hemorrhage segmentation, even in the presence of significant injury. The results of the method are shown to be on par with expert manual segmentation. In postclinical analysis of human brain cancer, access to large collections of MRI data enables scientifically rigorous study of cancers like glioblastoma multiforme, the most common form of malignant primary brain tumor. For this application, I propose an efficient and effective automated segmentation method, the Enhanced Classification Expectation Maximization: ECEM) algorithm. The ECEM algorithm is novel in that it introduces spatial information directly into the classical CEM algorithm, which is otherwise spatially unaware, with low additional computational complexity. I compare the ECEM\u27s performance on simulated data to the standard finite Gaussian mixture EM algorithm, which is not spatially aware, and to the hidden-Markov random field EM algorithm, a commonly-used spatially aware automated segmentation method for MR brain images. I also show sample results demonstrating the ECEM algorithm\u27s ability to segment MR images of glioblastoma

Computer aided assessment of CT scans of traumatic brain injury patients

A thesis submitted in partial fulfilment for the degree of Doctor of PhilosophyOne of the serious public health problems is the Traumatic Brain Injury, also known as silent epidemic, affecting millions every year. Management of these patients essentially involves neuroimaging and noncontrast CT scans are the first choice amongst doctors. Significant anatomical changes identified on the neuroimages and volumetric assessment of haemorrhages and haematomas are of critical importance for assessing the patients’ condition for targeted therapeutic and/or surgical interventions. Manual demarcation and annotation by experts is still considered gold standard, however, the interpretation of neuroimages is fraught with inter-observer variability and is considered ’Achilles heel’ amongst radiologists. Errors and variability can be attributed to factors such as poor perception, inaccurate deduction, incomplete knowledge or the quality of the image and only a third of doctors confidently report the findings. The applicability of computer aided dianosis in segmenting the apposite regions and giving ’second opinion’ has been positively appraised to assist the radiologists, however, results of the approaches vary due to parameters of algorithms and manual intervention required from doctors and this presents a gap for automated segmentation and estimation of measurements of noncontrast brain CT scans. The Pattern Driven, Content Aware Active Contours (PDCAAC) Framework developed in this thesis provides robust and efficient segmentation of significant anatomical landmarks, estimations of their sizes and correlation to CT rating to assist the radiologists in establishing the diagnosis and prognosis more confidently. The integration of clinical profile of the patient into image segmentation algorithms has significantly improved their performance by highlighting characteristics of the region of interest. The modified active contour method in the PDCAAC framework achieves Jaccard Similarity Index (JI) of 0.87, which is a significant improvement over the existing methods of active contours achieving JI of 0.807 with Simple Linear Iterative Clustering and Distance Regularized Level Set Evolution. The Intraclass Correlation Coefficient of intracranial measurements is >0.97 compared with radiologists. Automatic seeding of the initial seed curve within the region of interest is incorporated into the method which is a novel approach and alleviates limitation of existing methods. The proposed PDCAAC framework can be construed as a contribution towards research to formulate correlations between image features and clinical variables encompassing normal development, ageing, pathological and traumatic cases propitious to improve management of such patients. Establishing prognosis usually entails survival but the focus can also be extended to functional outcomes, residual disability and quality of life issues

Applications of Medical Physics

Applications of Medical Physics” is a Special Issue of Applied Sciences that has collected original research manuscripts describing cutting-edge physics developments in medicine and their translational applications. Reviews providing updates on the latest progresses in this field are also included. The collection includes a total of 20 contributions by authors from 9 different countries, which cover several areas of medical physics, spanning from radiation therapy, nuclear medicine, radiology, dosimetry, radiation protection, and radiobiology

Towards Interpretable Machine Learning in Medical Image Analysis

Over the past few years, ML has demonstrated human expert level performance in many medical image analysis tasks. However, due to the black-box nature of classic deep ML models, translating these models from the bench to the bedside to support the corresponding stakeholders in the desired tasks brings substantial challenges. One solution is interpretable ML, which attempts to reveal the working mechanisms of complex models. From a human-centered design perspective, interpretability is not a property of the ML model but an affordance, i.e., a relationship between algorithm and user. Thus, prototyping and user evaluations are critical to attaining solutions that afford interpretability. Following human-centered design principles in highly specialized and high stakes domains, such as medical image analysis, is challenging due to the limited access to end users. This dilemma is further exacerbated by the high knowledge imbalance between ML designers and end users. To overcome the predicament, we first define 4 levels of clinical evidence that can be used to justify the interpretability to design ML models. We state that designing ML models with 2 levels of clinical evidence: 1) commonly used clinical evidence, such as clinical guidelines, and 2) iteratively developed clinical evidence with end users are more likely to design models that are indeed interpretable to end users. In this dissertation, we first address how to design interpretable ML in medical image analysis that affords interpretability with these two different levels of clinical evidence. We further highly recommend formative user research as the first step of the interpretable model design to understand user needs and domain requirements. We also indicate the importance of empirical user evaluation to support transparent ML design choices to facilitate the adoption of human-centered design principles. All these aspects in this dissertation increase the likelihood that the algorithms afford interpretability and enable stakeholders to capitalize on the benefits of interpretable ML. In detail, we first propose neural symbolic reasoning to implement public clinical evidence into the designed models for various routinely performed clinical tasks. We utilize the routinely applied clinical taxonomy for abnormality classification in chest x-rays. We also establish a spleen injury grading system by strictly following the clinical guidelines for symbolic reasoning with the detected and segmented salient clinical features. Then, we propose the entire interpretable pipeline for UM prognostication with cytopathology images. We first perform formative user research and found that pathologists believe cell composition is informative for UM prognostication. Thus, we build a model to analyze cell composition directly. Finally, we conduct a comprehensive user study to assess the human factors of human-machine teaming with the designed model, e.g., whether the proposed model indeed affords interpretability to pathologists. The human-centered design process is proven to be truly interpretable to pathologists for UM prognostication. All in all, this dissertation introduces a comprehensive human-centered design for interpretable ML solutions in medical image analysis that affords interpretability to end users

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.

Deep Learning in Medical Image Analysis

The accelerating power of deep learning in diagnosing diseases will empower physicians and speed up decision making in clinical environments. Applications of modern medical instruments and digitalization of medical care have generated enormous amounts of medical images in recent years. In this big data arena, new deep learning methods and computational models for efficient data processing, analysis, and modeling of the generated data are crucially important for clinical applications and understanding the underlying biological process. This book presents and highlights novel algorithms, architectures, techniques, and applications of deep learning for medical image analysis