Domain and Geometry Agnostic CNNs for Left Atrium Segmentation in 3D Ultrasound

Segmentation of the left atrium and deriving its size can help to predict and detect various cardiovascular conditions. Automation of this process in 3D Ultrasound image data is desirable, since manual delineations are time-consuming, challenging and observer-dependent. Convolutional neural networks have made improvements in computer vision and in medical image analysis. They have successfully been applied to segmentation tasks and were extended to work on volumetric data. In this paper we introduce a combined deep-learning based approach on volumetric segmentation in Ultrasound acquisitions with incorporation of prior knowledge about left atrial shape and imaging device. The results show, that including a shape prior helps the domain adaptation and the accuracy of segmentation is further increased with adversarial learning

Deep learning for unsupervised domain adaptation in medical imaging: Recent advancements and future perspectives

Deep learning has demonstrated remarkable performance across various tasks in medical imaging. However, these approaches primarily focus on supervised learning, assuming that the training and testing data are drawn from the same distribution. Unfortunately, this assumption may not always hold true in practice. To address these issues, unsupervised domain adaptation (UDA) techniques have been developed to transfer knowledge from a labeled domain to a related but unlabeled domain. In recent years, significant advancements have been made in UDA, resulting in a wide range of methodologies, including feature alignment, image translation, self-supervision, and disentangled representation methods, among others. In this paper, we provide a comprehensive literature review of recent deep UDA approaches in medical imaging from a technical perspective. Specifically, we categorize current UDA research in medical imaging into six groups and further divide them into finer subcategories based on the different tasks they perform. We also discuss the respective datasets used in the studies to assess the divergence between the different domains. Finally, we discuss emerging areas and provide insights and discussions on future research directions to conclude this survey.Comment: Under Revie

Multi-modality cardiac image computing: a survey

Multi-modality cardiac imaging plays a key role in the management of patients with cardiovascular diseases. It allows a combination of complementary anatomical, morphological and functional information, increases diagnosis accuracy, and improves the efficacy of cardiovascular interventions and clinical outcomes. Fully-automated processing and quantitative analysis of multi-modality cardiac images could have a direct impact on clinical research and evidence-based patient management. However, these require overcoming significant challenges including inter-modality misalignment and finding optimal methods to integrate information from different modalities. This paper aims to provide a comprehensive review of multi-modality imaging in cardiology, the computing methods, the validation strategies, the related clinical workflows and future perspectives. For the computing methodologies, we have a favored focus on the three tasks, i.e., registration, fusion and segmentation, which generally involve multi-modality imaging data, either combining information from different modalities or transferring information across modalities. The review highlights that multi-modality cardiac imaging data has the potential of wide applicability in the clinic, such as trans-aortic valve implantation guidance, myocardial viability assessment, and catheter ablation therapy and its patient selection. Nevertheless, many challenges remain unsolved, such as missing modality, modality selection, combination of imaging and non-imaging data, and uniform analysis and representation of different modalities. There is also work to do in defining how the well-developed techniques fit in clinical workflows and how much additional and relevant information they introduce. These problems are likely to continue to be an active field of research and the questions to be answered in the future

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

Explainable cardiac pathology classification on cine MRI with motion characterization by semi-supervised learning of apparent flow

We propose a method to classify cardiac pathology based on a novel approach to extract image derived features to characterize the shape and motion of the heart. An original semi-supervised learning procedure, which makes efficient use of a large amount of non-segmented images and a small amount of images segmented manually by experts, is developed to generate pixel-wise apparent flow between two time points of a 2D+t cine MRI image sequence. Combining the apparent flow maps and cardiac segmentation masks, we obtain a local apparent flow corresponding to the 2D motion of myocardium and ventricular cavities. This leads to the generation of time series of the radius and thickness of myocardial segments to represent cardiac motion. These time series of motion features are reliable and explainable characteristics of pathological cardiac motion. Furthermore, they are combined with shape-related features to classify cardiac pathologies. Using only nine feature values as input, we propose an explainable, simple and flexible model for pathology classification. On ACDC training set and testing set, the model achieves 95% and 94% respectively as classification accuracy. Its performance is hence comparable to that of the state-of-the-art. Comparison with various other models is performed to outline some advantages of our model

Estimating and understanding motion : from diagnostic to robotic surgery

Estimating and understanding motion from an image sequence is a central topic in computer vision. The high interest in this topic is because we are living in a world where many events that occur in the environment are dynamic. This makes motion estimation and understanding a natural component and a key factor in a widespread of applications including object recognition , 3D shape reconstruction, autonomous navigation and medica! diagnosis. Particularly, we focus on the medical domain in which understanding the human body for clinical purposes requires retrieving the organs' complex motion patterns, which is in general a hard problem when using only image data. In this thesis, we cope with this problem by posing the question - How to achieve a realistic motion estimation to offer a better clinical understanding? We focus this thesis on answering this question by using a variational formulation as a basis to understand one of the most complex motions in the human's body, the heart motion, through three different applications: (i) cardiac motion estimation for diagnostic, (ii) force estimation and (iii) motion prediction, both for robotic surgery. Firstly, we focus on a central topic in cardiac imaging that is the estimation of the cardiac motion. The main aim is to offer objective and understandable measures to physicians for helping them in the diagnostic of cardiovascular diseases. We employ ultrafast ultrasound data and tools for imaging motion drawn from diverse areas such as low-rank analysis and variational deformation to perform a realistic cardiac motion estimation. The significance is that by taking low-rank data with carefully chosen penalization, synergies in this complex variational problem can be created. We demonstrate how our proposed solution deals with complex deformations through careful numerical experiments using realistic and simulated data. We then move from diagnostic to robotic surgeries where surgeons perform delicate procedures remotely through robotic manipulators without directly interacting with the patients. As a result, they lack force feedback, which is an important primary sense for increasing surgeon-patient transparency and avoiding injuries and high mental workload. To solve this problem, we follow the conservation principies of continuum mechanics in which it is clear that the change in shape of an elastic object is directly proportional to the force applied. Thus, we create a variational framework to acquire the deformation that the tissues undergo due to an applied force. Then, this information is used in a learning system to find the nonlinear relationship between the given data and the applied force. We carried out experiments with in-vivo and ex-vivo data and combined statistical, graphical and perceptual analyses to demonstrate the strength of our solution. Finally, we explore robotic cardiac surgery, which allows carrying out complex procedures including Off-Pump Coronary Artery Bypass Grafting (OPCABG). This procedure avoids the associated complications of using Cardiopulmonary Bypass (CPB) since the heart is not arrested while performing the surgery on a beating heart. Thus, surgeons have to deal with a dynamic target that compromisetheir dexterity and the surgery's precision. To compensate the heart motion, we propase a solution composed of three elements: an energy function to estimate the 3D heart motion, a specular highlight detection strategy and a prediction approach for increasing the robustness of the solution. We conduct evaluation of our solution using phantom and realistic datasets. We conclude the thesis by reporting our findings on these three applications and highlight the dependency between motion estimation and motion understanding at any dynamic event, particularly in clinical scenarios.L’estimació i comprensió del moviment dins d’una seqüència d’imatges és un tema central en la visió per ordinador, el que genera un gran interès perquè vivim en un entorn ple d’esdeveniments dinàmics. Per aquest motiu és considerat com un component natural i factor clau dins d’un ampli ventall d’aplicacions, el qual inclou el reconeixement d’objectes, la reconstrucció de formes tridimensionals, la navegació autònoma i el diagnòstic de malalties. En particular, ens situem en l’àmbit mèdic en el qual la comprensió del cos humà, amb finalitats clíniques, requereix l’obtenció de patrons complexos de moviment dels òrgans. Aquesta és, en general, una tasca difícil quan s’utilitzen només dades de tipus visual. En aquesta tesi afrontem el problema plantejant-nos la pregunta - Com es pot aconseguir una estimació realista del moviment amb l’objectiu d’oferir una millor comprensió clínica? La tesi se centra en la resposta mitjançant l’ús d’una formulació variacional com a base per entendre un dels moviments més complexos del cos humà, el del cor, a través de tres aplicacions: (i) estimació del moviment cardíac per al diagnòstic, (ii) estimació de forces i (iii) predicció del moviment, orientant-se les dues últimes en cirurgia robòtica. En primer lloc, ens centrem en un tema principal en la imatge cardíaca, que és l’estimació del moviment cardíac. L’objectiu principal és oferir als metges mesures objectives i comprensibles per ajudar-los en el diagnòstic de les malalties cardiovasculars. Fem servir dades d’ultrasons ultraràpids i eines per al moviment d’imatges procedents de diverses àrees, com ara l’anàlisi de baix rang i la deformació variacional, per fer una estimació realista del moviment cardíac. La importància rau en que, en prendre les dades de baix rang amb una penalització acurada, es poden crear sinergies en aquest problema variacional complex. Mitjançant acurats experiments numèrics, amb dades realístiques i simulades, hem demostrat com les nostres propostes solucionen deformacions complexes. Després passem del diagnòstic a la cirurgia robòtica, on els cirurgians realitzen procediments delicats remotament, a través de manipuladors robòtics, sense interactuar directament amb els pacients. Com a conseqüència, no tenen la percepció de la força com a resposta, que és un sentit primari important per augmentar la transparència entre el cirurgià i el pacient, per evitar lesions i per reduir la càrrega de treball mental. Resolem aquest problema seguint els principis de conservació de la mecànica del medi continu, en els quals està clar que el canvi en la forma d’un objecte elàstic és directament proporcional a la força aplicada. Per això hem creat un marc variacional que adquireix la deformació que pateixen els teixits per l’aplicació d’una força. Aquesta informació s’utilitza en un sistema d’aprenentatge, per trobar la relació no lineal entre les dades donades i la força aplicada. Hem dut a terme experiments amb dades in-vivo i ex-vivo i hem combinat l’anàlisi estadístic, gràfic i de percepció que demostren la robustesa de la nostra solució. Finalment, explorem la cirurgia cardíaca robòtica, la qual cosa permet realitzar procediments complexos, incloent la cirurgia coronària sense bomba (off-pump coronary artery bypass grafting o OPCAB). Aquest procediment evita les complicacions associades a l’ús de circulació extracorpòria (Cardiopulmonary Bypass o CPB), ja que el cor no s’atura mentre es realitza la cirurgia. Això comporta que els cirurgians han de tractar amb un objectiu dinàmic que compromet la seva destresa i la precisió de la cirurgia. Per compensar el moviment del cor, proposem una solució composta de tres elements: un funcional d’energia per estimar el moviment tridimensional del cor, una estratègia de detecció de les reflexions especulars i una aproximació basada en mètodes de predicció, per tal d’augmentar la robustesa de la solució. L’avaluació de la nostra solució s’ha dut a terme mitjançant conjunts de dades sintètiques i realistes. La tesi conclou informant dels nostres resultats en aquestes tres aplicacions i posant de relleu la dependència entre l’estimació i la comprensió del moviment en qualsevol esdeveniment dinàmic, especialment en escenaris clínics.Postprint (published version

Control and optimization methods in biomedical systems: from cells to humans

Optimization and control theory are well developed techniques to quantize, model, understand and optimize real world systems and they have been widely used in engineering, economics, and science. In this thesis, we focus on applications in biomedical systems ranging from cells to microbial communities, and to something as complex as the human body. The first problem we consider is that of medication dosage control for drugs delivered intravenously to the patient. We focus specifically on a blood thinner (called bivalirudin) used in the post cardiac surgery Intensive Care Unit (ICU). We develop two approaches (a model-free and a model-based one) that predict the effect of bivalirudin. After obtaining the model and its best fit parameters by solving a non-linear optimization problem, we develop automatic dosage controllers that adaptively regulate its effect to desired levels. Our algorithms are validated using actual data from a large hospital in the Boston area. In the second problem, we introduce a cellular objective function inference mechanism in metabolic networks. We develop an inverse optimization method, called InvFBA (Inverse Flux Balance Analysis), to infer the objective functions of growing cells by using their reaction fluxes. InvFBA can be seen as an inverse version of FBA (Flux Balance Analysis) which predicts the distribution of the cell's reaction fluxes by using a hypothetical objective function. The objective functions can be linear, quadratic and non-parametric. The efficiency of the InvFBA approach matches the structure of the FBA and ensures scalability to large networks and optimality of the solution. After testing our algorithm on simulated E. coli data and time-dependent S. oneidensis fluxes inferred from gene expression data, we apply our inverse approach to flux measurements in long-term evolved E. coli strains, revealing objective functions that provide insight into metabolic adaptation trajectories. In the final problem in this thesis, we formulate a novel resource allocation problem in microbial ecosystems. We consider a given number of microbial species living symbiotically in a community and a list of all metabolic reactions present in the community, expressed in terms of the metabolite proportions involved in each reaction. We are interested in allocating reactions to organisms so that each organism maintains a minimal level of growth and the community optimizes certain objectives, such as maximizing growth and/or the uptake of specific compounds from the common environment. We leverage tools from Flux Balance Analysis (FBA) and formulate the problem as a mixed integer linear programming problem. We test our method in a toy model involving two organisms that can only survive through cross-feeding, demonstrating that the method can recover this interaction. We also test the method in a community of two simplified bacteria described in terms of their core, simplified metabolic network. We demonstrate that the method can obtain syntrophic cross-feeding species that would be very difficult to design manually