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

Cardiac motion estimation from medical images: a regularisation framework applied on pairwise image registration displacement fields

Accurate cardiac motion estimation from medical images such as ultrasound is important for clinical evaluation. We present a novel regularisation layer for cardiac motion estimation that will be applied after image registration and demonstrate its effectiveness. The regularisation utilises a spatio-temporal model of motion, b-splines of Fourier, to fit to displacement fields from pairwise image registration. In the process, it enforces spatial and temporal smoothness and consistency, cyclic nature of cardiac motion, and better adherence to the stroke volume of the heart. Flexibility is further given for inclusion of any set of registration displacement fields. The approach gave high accuracy. When applied to human adult Ultrasound data from a Cardiac Motion Analysis Challenge (CMAC), the proposed method is found to have 10% lower tracking error over CMAC participants. Satisfactory cardiac motion estimation is also demonstrated on other data sets, including human fetal echocardiography, chick embryonic heart ultrasound images, and zebrafish embryonic microscope images, with the average Dice coefficient between estimation motion and manual segmentation at 0.82–0.87. The approach of performing regularisation as an add-on layer after the completion of image registration is thus a viable option for cardiac motion estimation that can still have good accuracy. Since motion estimation algorithms are complex, dividing up regularisation and registration can simplify the process and provide flexibility. Further, owing to a large variety of existing registration algorithms, such an approach that is usable on any algorithm may be useful

A Generative Shape Compositional Framework: Towards Representative Populations of Virtual Heart Chimaeras

Generating virtual populations of anatomy that capture sufficient variability while remaining plausible is essential for conducting in-silico trials of medical devices. However, not all anatomical shapes of interest are always available for each individual in a population. Hence, missing/partially-overlapping anatomical information is often available across individuals in a population. We introduce a generative shape model for complex anatomical structures, learnable from datasets of unpaired datasets. The proposed generative model can synthesise complete whole complex shape assemblies coined virtual chimaeras, as opposed to natural human chimaeras. We applied this framework to build virtual chimaeras from databases of whole-heart shape assemblies that each contribute samples for heart substructures. Specifically, we propose a generative shape compositional framework which comprises two components - a part-aware generative shape model which captures the variability in shape observed for each structure of interest in the training population; and a spatial composition network which assembles/composes the structures synthesised by the former into multi-part shape assemblies (viz. virtual chimaeras). We also propose a novel self supervised learning scheme that enables the spatial composition network to be trained with partially overlapping data and weak labels. We trained and validated our approach using shapes of cardiac structures derived from cardiac magnetic resonance images available in the UK Biobank. Our approach significantly outperforms a PCA-based shape model (trained with complete data) in terms of generalisability and specificity. This demonstrates the superiority of the proposed approach as the synthesised cardiac virtual populations are more plausible and capture a greater degree of variability in shape than those generated by the PCA-based shape model.Comment: 15 pages, 4 figure

Statistical Medial Model dor Cardiac Segmentation and Morphometry

In biomedical image analysis, shape information can be utilized for many purposes. For example, irregular shape features can help identify diseases; shape features can help match different instances of anatomical structures for statistical comparison; and prior knowledge of the mean and possible variation of an anatomical structure\u27s shape can help segment a new example of this structure in noisy, low-contrast images. A good shape representation helps to improve the performance of the above techniques. The overall goal of the proposed research is to develop and evaluate methods for representing shapes of anatomical structures. The medial model is a shape representation method that models a 3D object by explicitly defining its skeleton (medial axis) and deriving the object\u27s boundary via inverse-skeletonization . This model represents shape compactly, and naturally expresses descriptive global shape features like thickening , bending , and elongation . However, its application in biomedical image analysis has been limited, and it has not yet been applied to the heart, which has a complex shape. In this thesis, I focus on developing efficient methods to construct the medial model, and apply it to solve biomedical image analysis problems. I propose a new 3D medial model which can be efficiently applied to complex shapes. The proposed medial model closely approximates the medial geometry along medial edge curves and medial branching curves by soft-penalty optimization and local correction. I further develop a scheme to perform model-based segmentation using a statistical medial model which incorporates prior shape and appearance information. The proposed medial models are applied to a series of image analysis tasks. The 2D medial model is applied to the corpus callosum which results in an improved alignment of the patterns of commissural connectivity compared to a volumetric registration method. The 3D medial model is used to describe the myocardium of the left and right ventricles, which provides detailed thickness maps characterizing different disease states. The model-based myocardium segmentation scheme is tested in a heterogeneous adult MRI dataset. Our segmentation experiments demonstrate that the statistical medial model can accurately segment the ventricular myocardium and provide useful parameters to characterize heart function

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

Image-guided Simulation of Heterogeneous Tissue Deformation For Augmented Reality during Hepatic Surgery

International audienceThis paper presents a method for real-time augmentation of vas- cular network and tumors during minimally invasive liver surgery. Internal structures computed from pre-operative CT scans can be overlaid onto the laparoscopic view for surgery guidance. Com- pared to state-of-the-art methods, our method uses a real-time biomechanical model to compute a volumetric displacement field from partial three-dimensional liver surface motion. This permits to properly handle the motion of internal structures even in the case of anisotropic or heterogeneous tissues, as it is the case for the liver and many anatomical structures. Real-time augmentation results are presented on in vivo and ex vivo data and illustrate the benefits of such an approach for minimally invasive surgery

Development, Implementation and Pre-clinical Evaluation of Medical Image Computing Tools in Support of Computer-aided Diagnosis: Respiratory, Orthopedic and Cardiac Applications

Over the last decade, image processing tools have become crucial components of all clinical and research efforts involving medical imaging and associated applications. The imaging data available to the radiologists continue to increase their workload, raising the need for efficient identification and visualization of the required image data necessary for clinical assessment. Computer-aided diagnosis (CAD) in medical imaging has evolved in response to the need for techniques that can assist the radiologists to increase throughput while reducing human error and bias without compromising the outcome of the screening, diagnosis or disease assessment. More intelligent, but simple, consistent and less time-consuming methods will become more widespread, reducing user variability, while also revealing information in a more clear, visual way. Several routine image processing approaches, including localization, segmentation, registration, and fusion, are critical for enhancing and enabling the development of CAD techniques. However, changes in clinical workflow require significant adjustments and re-training and, despite the efforts of the academic research community to develop state-of-the-art algorithms and high-performance techniques, their footprint often hampers their clinical use. Currently, the main challenge seems to not be the lack of tools and techniques for medical image processing, analysis, and computing, but rather the lack of clinically feasible solutions that leverage the already developed and existing tools and techniques, as well as a demonstration of the potential clinical impact of such tools. Recently, more and more efforts have been dedicated to devising new algorithms for localization, segmentation or registration, while their potential and much intended clinical use and their actual utility is dwarfed by the scientific, algorithmic and developmental novelty that only result in incremental improvements over already algorithms. In this thesis, we propose and demonstrate the implementation and evaluation of several different methodological guidelines that ensure the development of image processing tools --- localization, segmentation and registration --- and illustrate their use across several medical imaging modalities --- X-ray, computed tomography, ultrasound and magnetic resonance imaging --- and several clinical applications: Lung CT image registration in support for assessment of pulmonary nodule growth rate and disease progression from thoracic CT images. Automated reconstruction of standing X-ray panoramas from multi-sector X-ray images for assessment of long limb mechanical axis and knee misalignment. Left and right ventricle localization, segmentation, reconstruction, ejection fraction measurement from cine cardiac MRI or multi-plane trans-esophageal ultrasound images for cardiac function assessment. When devising and evaluating our developed tools, we use clinical patient data to illustrate the inherent clinical challenges associated with highly variable imaging data that need to be addressed before potential pre-clinical validation and implementation. In an effort to provide plausible solutions to the selected applications, the proposed methodological guidelines ensure the development of image processing tools that help achieve sufficiently reliable solutions that not only have the potential to address the clinical needs, but are sufficiently streamlined to be potentially translated into eventual clinical tools provided proper implementation. G1: Reducing the number of degrees of freedom (DOF) of the designed tool, with a plausible example being avoiding the use of inefficient non-rigid image registration methods. This guideline addresses the risk of artificial deformation during registration and it clearly aims at reducing complexity and the number of degrees of freedom. G2: The use of shape-based features to most efficiently represent the image content, either by using edges instead of or in addition to intensities and motion, where useful. Edges capture the most useful information in the image and can be used to identify the most important image features. As a result, this guideline ensures a more robust performance when key image information is missing. G3: Efficient method of implementation. This guideline focuses on efficiency in terms of the minimum number of steps required and avoiding the recalculation of terms that only need to be calculated once in an iterative process. An efficient implementation leads to reduced computational effort and improved performance. G4: Commence the workflow by establishing an optimized initialization and gradually converge toward the final acceptable result. This guideline aims to ensure reasonable outcomes in consistent ways and it avoids convergence to local minima, while gradually ensuring convergence to the global minimum solution. These guidelines lead to the development of interactive, semi-automated or fully-automated approaches that still enable the clinicians to perform final refinements, while they reduce the overall inter- and intra-observer variability, reduce ambiguity, increase accuracy and precision, and have the potential to yield mechanisms that will aid with providing an overall more consistent diagnosis in a timely fashion