Computational Methods for Segmentation of Multi-Modal Multi-Dimensional Cardiac Images

Segmentation of the heart structures helps compute the cardiac contractile function quantified via the systolic and diastolic volumes, ejection fraction, and myocardial mass, representing a reliable diagnostic value. Similarly, quantification of the myocardial mechanics throughout the cardiac cycle, analysis of the activation patterns in the heart via electrocardiography (ECG) signals, serve as good cardiac diagnosis indicators. Furthermore, high quality anatomical models of the heart can be used in planning and guidance of minimally invasive interventions under the assistance of image guidance. The most crucial step for the above mentioned applications is to segment the ventricles and myocardium from the acquired cardiac image data. Although the manual delineation of the heart structures is deemed as the gold-standard approach, it requires significant time and effort, and is highly susceptible to inter- and intra-observer variability. These limitations suggest a need for fast, robust, and accurate semi- or fully-automatic segmentation algorithms. However, the complex motion and anatomy of the heart, indistinct borders due to blood flow, the presence of trabeculations, intensity inhomogeneity, and various other imaging artifacts, makes the segmentation task challenging. In this work, we present and evaluate segmentation algorithms for multi-modal, multi-dimensional cardiac image datasets. Firstly, we segment the left ventricle (LV) blood-pool from a tri-plane 2D+time trans-esophageal (TEE) ultrasound acquisition using local phase based filtering and graph-cut technique, propagate the segmentation throughout the cardiac cycle using non-rigid registration-based motion extraction, and reconstruct the 3D LV geometry. Secondly, we segment the LV blood-pool and myocardium from an open-source 4D cardiac cine Magnetic Resonance Imaging (MRI) dataset by incorporating average atlas based shape constraint into the graph-cut framework and iterative segmentation refinement. The developed fast and robust framework is further extended to perform right ventricle (RV) blood-pool segmentation from a different open-source 4D cardiac cine MRI dataset. Next, we employ convolutional neural network based multi-task learning framework to segment the myocardium and regress its area, simultaneously, and show that segmentation based computation of the myocardial area is significantly better than that regressed directly from the network, while also being more interpretable. Finally, we impose a weak shape constraint via multi-task learning framework in a fully convolutional network and show improved segmentation performance for LV, RV and myocardium across healthy and pathological cases, as well as, in the challenging apical and basal slices in two open-source 4D cardiac cine MRI datasets. We demonstrate the accuracy and robustness of the proposed segmentation methods by comparing the obtained results against the provided gold-standard manual segmentations, as well as with other competing segmentation methods

Automatic Assessment of Cardiac Left Ventricular Function Via Magnetic Resonance Images

Automating global and segmental (regional) assessments of cardiac Left Ventricle (LV) function in Magnetic Resonance Images (MRI) has recently sparked an impressive research effort, which has resulted a number of techniques delivering promising performances. However, despite such an effort, the problem is still acknowledged to be challenging, with substantial room for improvements in regard to accuracy. Furthermore, most of the existing techniques are labour intensive, requiring delineations of the endo- and/or epi-cardial boundaries in all frames of a cardiac sequence. On the one hand, global assessments of LV function focus on estimation of the Ejection Fraction (EF), which quantifies how much blood the heart is pumping within each beat. On the other hand, regional assessments focus on comprehensive analysis of the wall motions within each of the standardized segments of the myocardium, the muscle which contracts and sends the blood out of the LV. In clinical practice, the EF is often estimated via manual segmentations of several images in a cardiac sequence. This is prohibitively time consuming, or via automatic segmentations, which is a challenging and computationally expensive task that may result in high estimation errors. Additionally, the diagnosis of the segmental dysfunction is based on visual LV assessments, which are subject to high inter-observer variability. In this thesis, we propose accurate methods to estimate both global and regional LV function with minimal user inputs in real-time from statistics estimated in MRI. From a simple user input, we build image statistics for all the images in a subject dataset. We demonstrate that these statistics are correlated with regional as well as global LV function. Different machine learning techniques have been employed to find these correlations. The regional dysfunction is investigated in terms of a binary/multi-classification problem. A comprehensive evaluation over 20 subjects demonstrated that the estimated EFs correlated very well with those obtained from independent manual segmentations. Furthermore, comparisons with estimating EF with recent segmentation algorithms show that the proposed method yielded a very competitive performance. For regional binary classification, we report a comprehensive experimental evaluation of the proposed algorithm over 928 cardiac segments obtained from 58 subjects. Compared against ground-truth evaluations by experienced radiologists, the proposed algorithm performed competitively, with an overall classification accuracy of 86.09% and a kappa measure of 0.73. We also report a comprehensive experimental evaluation of the proposed multi-classification algorithm over the same dataset. Compared against ground-truth labels assessed by experienced radiologists, the proposed algorithm yielded an overall 4-class accuracy of 74.14%

Computational methods for the analysis of functional 4D-CT chest images.

Medical imaging is an important emerging technology that has been intensively used in the last few decades for disease diagnosis and monitoring as well as for the assessment of treatment effectiveness. Medical images provide a very large amount of valuable information that is too huge to be exploited by radiologists and physicians. Therefore, the design of computer-aided diagnostic (CAD) system, which can be used as an assistive tool for the medical community, is of a great importance. This dissertation deals with the development of a complete CAD system for lung cancer patients, which remains the leading cause of cancer-related death in the USA. In 2014, there were approximately 224,210 new cases of lung cancer and 159,260 related deaths. The process begins with the detection of lung cancer which is detected through the diagnosis of lung nodules (a manifestation of lung cancer). These nodules are approximately spherical regions of primarily high density tissue that are visible in computed tomography (CT) images of the lung. The treatment of these lung cancer nodules is complex, nearly 70% of lung cancer patients require radiation therapy as part of their treatment. Radiation-induced lung injury is a limiting toxicity that may decrease cure rates and increase morbidity and mortality treatment. By finding ways to accurately detect, at early stage, and hence prevent lung injury, it will have significant positive consequences for lung cancer patients. The ultimate goal of this dissertation is to develop a clinically usable CAD system that can improve the sensitivity and specificity of early detection of radiation-induced lung injury based on the hypotheses that radiated lung tissues may get affected and suffer decrease of their functionality as a side effect of radiation therapy treatment. These hypotheses have been validated by demonstrating that automatic segmentation of the lung regions and registration of consecutive respiratory phases to estimate their elasticity, ventilation, and texture features to provide discriminatory descriptors that can be used for early detection of radiation-induced lung injury. The proposed methodologies will lead to novel indexes for distinguishing normal/healthy and injured lung tissues in clinical decision-making. To achieve this goal, a CAD system for accurate detection of radiation-induced lung injury that requires three basic components has been developed. These components are the lung fields segmentation, lung registration, and features extraction and tissue classification. This dissertation starts with an exploration of the available medical imaging modalities to present the importance of medical imaging in today’s clinical applications. Secondly, the methodologies, challenges, and limitations of recent CAD systems for lung cancer detection are covered. This is followed by introducing an accurate segmentation methodology of the lung parenchyma with the focus of pathological lungs to extract the volume of interest (VOI) to be analyzed for potential existence of lung injuries stemmed from the radiation therapy. After the segmentation of the VOI, a lung registration framework is introduced to perform a crucial and important step that ensures the co-alignment of the intra-patient scans. This step eliminates the effects of orientation differences, motion, breathing, heart beats, and differences in scanning parameters to be able to accurately extract the functionality features for the lung fields. The developed registration framework also helps in the evaluation and gated control of the radiotherapy through the motion estimation analysis before and after the therapy dose. Finally, the radiation-induced lung injury is introduced, which combines the previous two medical image processing and analysis steps with the features estimation and classification step. This framework estimates and combines both texture and functional features. The texture features are modeled using the novel 7th-order Markov Gibbs random field (MGRF) model that has the ability to accurately models the texture of healthy and injured lung tissues through simultaneously accounting for both vertical and horizontal relative dependencies between voxel-wise signals. While the functionality features calculations are based on the calculated deformation fields, obtained from the 4D-CT lung registration, that maps lung voxels between successive CT scans in the respiratory cycle. These functionality features describe the ventilation, the air flow rate, of the lung tissues using the Jacobian of the deformation field and the tissues’ elasticity using the strain components calculated from the gradient of the deformation field. Finally, these features are combined in the classification model to detect the injured parts of the lung at an early stage and enables an earlier intervention

Deep Learning in Cardiac Magnetic Resonance Image Analysis and Cardiovascular Disease Diagnosis

Cardiovascular diseases (CVDs) are the leading cause of death in the world, accounting for 17.9 million deaths each year, 31\% of all global deaths. According to the World Health Organisation (WHO), this number is expected to rise to 23 million by 2030. As a noninvasive technique, medical imaging with corresponding computer vision techniques is becoming more and more popular for detecting, understanding, and analysing CVDs. With the advent of deep learning, there are significant improvements in medical image analysis tasks (e.g. image registration, image segmentation, mesh reconstruction from image), achieving much faster and more accurate registration, segmentation, reconstruction, and disease diagnosis. This thesis focuses on cardiac magnetic resonance images, systematically studying critical tasks in CVD analysis, including image registration, image segmentation, cardiac mesh reconstruction, and CVD prediction/diagnosis. We first present a thorough review of deep learning-based image registration approaches, and subsequently, propose a novel solution to the problem of discontinuity-preserving intra-subject cardiac image registration, which is generally ignored in previous deep learning-based registration methods. On the basis of this, a joint segmentation and registration framework is further proposed to learn the joint relationship between these two tasks, leading to better registration and segmentation performance. In order to characterise the shape and motion of the heart in 3D, we present a deep learning-based 3D mesh reconstruction network that is able to recover accurate 3D cardiac shapes from 2D slice-wise segmentation masks/contours in a fast and robust manner. Finally, for CVD prediction/diagnosis, we design a multichannel variational autoencoder to learn the joint latent representation of the original cardiac image and mesh, resulting in a shape-aware image representation (SAIR) that serves as an explainable biomarker. SAIR has been shown to outperform traditional biomarkers in the prediction of acute myocardial infarction and the diagnosis of several other CVDs, and can supplement existing biomarkers to improve overall predictive performance

From Fully-Supervised Single-Task to Semi-Supervised Multi-Task Deep Learning Architectures for Segmentation in Medical Imaging Applications

Medical imaging is routinely performed in clinics worldwide for the diagnosis and treatment of numerous medical conditions in children and adults. With the advent of these medical imaging modalities, radiologists can visualize both the structure of the body as well as the tissues within the body. However, analyzing these high-dimensional (2D/3D/4D) images demands a significant amount of time and effort from radiologists. Hence, there is an ever-growing need for medical image computing tools to extract relevant information from the image data to help radiologists perform efficiently. Image analysis based on machine learning has pivotal potential to improve the entire medical imaging pipeline, providing support for clinical decision-making and computer-aided diagnosis. To be effective in addressing challenging image analysis tasks such as classification, detection, registration, and segmentation, specifically for medical imaging applications, deep learning approaches have shown significant improvement in performance. While deep learning has shown its potential in a variety of medical image analysis problems including segmentation, motion estimation, etc., generalizability is still an unsolved problem and many of these successes are achieved at the cost of a large pool of datasets. For most practical applications, getting access to a copious dataset can be very difficult, often impossible. Annotation is tedious and time-consuming. This cost is further amplified when annotation must be done by a clinical expert in medical imaging applications. Additionally, the applications of deep learning in the real-world clinical setting are still limited due to the lack of reliability caused by the limited prediction capabilities of some deep learning models. Moreover, while using a CNN in an automated image analysis pipeline, it’s critical to understand which segmentation results are problematic and require further manual examination. To this extent, the estimation of uncertainty calibration in a semi-supervised setting for medical image segmentation is still rarely reported. This thesis focuses on developing and evaluating optimized machine learning models for a variety of medical imaging applications, ranging from fully-supervised, single-task learning to semi-supervised, multi-task learning that makes efficient use of annotated training data. The contributions of this dissertation are as follows: (1) developing a fully-supervised, single-task transfer learning for the surgical instrument segmentation from laparoscopic images; and (2) utilizing supervised, single-task, transfer learning for segmenting and digitally removing the surgical instruments from endoscopic/laparoscopic videos to allow the visualization of the anatomy being obscured by the tool. The tool removal algorithms use a tool segmentation mask and either instrument-free reference frames or previous instrument-containing frames to fill in (inpaint) the instrument segmentation mask; (3) developing fully-supervised, single-task learning via efficient weight pruning and learned group convolution for accurate left ventricle (LV), right ventricle (RV) blood pool and myocardium localization and segmentation from 4D cine cardiac MR images; (4) demonstrating the use of our fully-supervised memory-efficient model to generate dynamic patient-specific right ventricle (RV) models from cine cardiac MRI dataset via an unsupervised learning-based deformable registration field; and (5) integrating a Monte Carlo dropout into our fully-supervised memory-efficient model with inherent uncertainty estimation, with the overall goal to estimate the uncertainty associated with the obtained segmentation and error, as a means to flag regions that feature less than optimal segmentation results; (6) developing semi-supervised, single-task learning via self-training (through meta pseudo-labeling) in concert with a Teacher network that instructs the Student network by generating pseudo-labels given unlabeled input data; (7) proposing largely-unsupervised, multi-task learning to demonstrate the power of a simple combination of a disentanglement block, variational autoencoder (VAE), generative adversarial network (GAN), and a conditioning layer-based reconstructor for performing two of the foremost critical tasks in medical imaging — segmentation of cardiac structures and reconstruction of the cine cardiac MR images; (8) demonstrating the use of 3D semi-supervised, multi-task learning for jointly learning multiple tasks in a single backbone module – uncertainty estimation, geometric shape generation, and cardiac anatomical structure segmentation of the left atrial cavity from 3D Gadolinium-enhanced magnetic resonance (GE-MR) images. This dissertation summarizes the impact of the contributions of our work in terms of demonstrating the adaptation and use of deep learning architectures featuring different levels of supervision to build a variety of image segmentation tools and techniques that can be used across a wide spectrum of medical image computing applications centered on facilitating and promoting the wide-spread computer-integrated diagnosis and therapy data science

Incorporating Cardiac Substructures Into Radiation Therapy For Improved Cardiac Sparing

Growing evidence suggests that radiation therapy (RT) doses to the heart and cardiac substructures (CS) are strongly linked to cardiac toxicities, though only the heart is considered clinically. This work aimed to utilize the superior soft-tissue contrast of magnetic resonance (MR) to segment CS, quantify uncertainties in their position, assess their effect on treatment planning and an MR-guided environment. Automatic substructure segmentation of 12 CS was completed using a novel hybrid MR/computed tomography (CT) atlas method and was improved upon using a 3-dimensional neural network (U-Net) from deep learning. Intra-fraction motion due to respiration was then quantified. The inter-fraction setup uncertainties utilizing a novel MR-linear accelerator were also quantified. Treatment planning comparisons were performed with and without substructure inclusions and methods to reduce radiation dose to sensitive CS were evaluated. Lastly, these described technologies (deep learning U-Net) were translated to an MR-linear accelerator and a segmentation pipeline was created. Automatic segmentations from the hybrid MR/CT atlas was able to generate accurate segmentations for the chambers and great vessels (Dice similarity coefficient (DSC) \u3e 0.75) but coronary artery segmentations were unsuccessful (DSC\u3c0.3). After implementing deep learning, DSC for the chambers and great vessels was ≥0.85 along with an improvement in the coronary arteries (DSC\u3e0.5). Similar accuracy was achieved when implementing deep learning for MR-guided RT. On average, automatic segmentations required ~10 minutes to generate per patient and deep learning only required 14 seconds. The inclusion of CS in the treatment planning process did not yield statistically significant changes in plan complexity, PTV, or OAR dose. Automatic segmentation results from deep learning pose major efficiency and accuracy gains for CS segmentation offering high potential for rapid implementation into radiation therapy planning for improved cardiac sparing. Introducing CS into RT planning for MR-guided RT presented an opportunity for more effective sparing with limited increase in plan complexity

Incorporating Cardiac Substructures Into Radiation Therapy For Improved Cardiac Sparing

Growing evidence suggests that radiation therapy (RT) doses to the heart and cardiac substructures (CS) are strongly linked to cardiac toxicities, though only the heart is considered clinically. This work aimed to utilize the superior soft-tissue contrast of magnetic resonance (MR) to segment CS, quantify uncertainties in their position, assess their effect on treatment planning and an MR-guided environment. Automatic substructure segmentation of 12 CS was completed using a novel hybrid MR/computed tomography (CT) atlas method and was improved upon using a 3-dimensional neural network (U-Net) from deep learning. Intra-fraction motion due to respiration was then quantified. The inter-fraction setup uncertainties utilizing a novel MR-linear accelerator were also quantified. Treatment planning comparisons were performed with and without substructure inclusions and methods to reduce radiation dose to sensitive CS were evaluated. Lastly, these described technologies (deep learning U-Net) were translated to an MR-linear accelerator and a segmentation pipeline was created. Automatic segmentations from the hybrid MR/CT atlas was able to generate accurate segmentations for the chambers and great vessels (Dice similarity coefficient (DSC) \u3e 0.75) but coronary artery segmentations were unsuccessful (DSC\u3c0.3). After implementing deep learning, DSC for the chambers and great vessels was ≥0.85 along with an improvement in the coronary arteries (DSC\u3e0.5). Similar accuracy was achieved when implementing deep learning for MR-guided RT. On average, automatic segmentations required ~10 minutes to generate per patient and deep learning only required 14 seconds. The inclusion of CS in the treatment planning process did not yield statistically significant changes in plan complexity, PTV, or OAR dose. Automatic segmentation results from deep learning pose major efficiency and accuracy gains for CS segmentation offering high potential for rapid implementation into radiation therapy planning for improved cardiac sparing. Introducing CS into RT planning for MR-guided RT presented an opportunity for more effective sparing with limited increase in plan complexity

Leveraging Supervoxels for Medical Image Volume Segmentation With Limited Supervision

The majority of existing methods for machine learning-based medical image segmentation are supervised models that require large amounts of fully annotated images. These types of datasets are typically not available in the medical domain and are difficult and expensive to generate. A wide-spread use of machine learning based models for medical image segmentation therefore requires the development of data-efficient algorithms that only require limited supervision. To address these challenges, this thesis presents new machine learning methodology for unsupervised lung tumor segmentation and few-shot learning based organ segmentation. When working in the limited supervision paradigm, exploiting the available information in the data is key. The methodology developed in this thesis leverages automatically generated supervoxels in various ways to exploit the structural information in the images. The work on unsupervised tumor segmentation explores the opportunity of performing clustering on a population-level in order to provide the algorithm with as much information as possible. To facilitate this population-level across-patient clustering, supervoxel representations are exploited to reduce the number of samples, and thereby the computational cost. In the work on few-shot learning-based organ segmentation, supervoxels are used to generate pseudo-labels for self-supervised training. Further, to obtain a model that is robust to the typically large and inhomogeneous background class, a novel anomaly detection-inspired classifier is proposed to ease the modelling of the background. To encourage the resulting segmentation maps to respect edges defined in the input space, a supervoxel-informed feature refinement module is proposed to refine the embedded feature vectors during inference. Finally, to improve trustworthiness, an architecture-agnostic mechanism to estimate model uncertainty in few-shot segmentation is developed. Results demonstrate that supervoxels are versatile tools for leveraging structural information in medical data when training segmentation models with limited supervision