Atlas construction and image analysis using statistical cardiac models

International audienceThis paper presents a brief overview of current trends in the construction of population and multi-modal heart atlases in our group and their application to atlas-based cardiac image analysis. The technical challenges around the construction of these atlases are organized around two main axes: groupwise image registration of anatomical, motion and fiber images and construction of statistical shape models. Application-wise, this paper focuses on the extraction of atlas-based biomarkers for the detection of local shape or motion abnormalities, addressing several cardiac applications where the extracted information is used to study and grade different pathologies. The paper is concluded with a discussion about the role of statistical atlases in the integration of multiple information sources and the potential this can bring to in-silico simulations

Automated Segmentation of Left and Right Ventricles in MRI and Classification of the Myocarfium Abnormalities

A fundamental step in diagnosis of cardiovascular diseases, automated left and right ventricle (LV and RV) segmentation in cardiac magnetic resonance images (MRI) is still acknowledged to be a difficult problem. Although algorithms for LV segmentation do exist, they require either extensive training or intensive user inputs. RV segmentation in MRI has yet to be solved and is still acknowledged a completely unsolved problem because its shape is not symmetric and circular, its deformations are complex and varies extensively over the cardiac phases, and it includes papillary muscles. In this thesis, I investigate fast detection of the LV endo- and epi-cardium surfaces (3D) and contours (2D) in cardiac MRI via convex relaxation and distribution matching. A rapid 3D segmentation of the RV in cardiac MRI via distribution matching constraints on segment shape and appearance is also investigated. These algorithms only require a single subject for training and a very simple user input, which amounts to one click. The solution is sought following the optimization of functionals containing probability product kernel constraints on the distributions of intensity and geometric features. The formulations lead to challenging optimization problems, which are not directly amenable to convex-optimization techniques. For each functional, the problem is split into a sequence of sub-problems, each of which can be solved exactly and globally via a convex relaxation and the augmented Lagrangian method. Finally, an information-theoretic based artificial neural network (ANN) is proposed for normal/abnormal LV myocardium motion classification. Using the LV segmentation results, the LV cavity points is estimated via a Kalman filter and a recursive dynamic Bayesian filter. However, due to the similarities between the statistical information of normal and abnormal points, differentiating between distributions of abnormal and normal points is a challenging problem. The problem was investigated with a global measure based on the Shannon\u27s differential entropy (SDE) and further examined with two other information-theoretic criteria, one based on Renyi entropy and the other on Fisher information. Unlike the existing information-theoretic studies, the approach addresses explicitly the overlap between the distributions of normal and abnormal cases, thereby yielding a competitive performance. I further propose an algorithm based on a supervised 3-layer ANN to differentiate between the distributions farther. The ANN is trained and tested by five different information measures of radial distance and velocity for points on endocardial boundary

Flow pattern analysis for magnetic resonance velocity imaging

Blood flow in the heart is highly complex. Although blood flow patterns have been investigated by both computational modelling and invasive/non-invasive imaging techniques, their evolution and intrinsic connection with cardiovascular disease has yet to be explored. Magnetic resonance (MR) velocity imaging provides a comprehensive distribution of multi-directional in vivo flow distribution so that detailed quantitative analysis of flow patterns is now possible. However, direct visualisation or quantification of vector fields is of little clinical use, especially for inter-subject or serial comparison of changes in flow patterns due to the progression of the disease or in response to therapeutic measures. In order to achieve a comprehensive and integrated description of flow in health and disease, it is necessary to characterise and model both normal and abnormal flows and their effects. To accommodate the diversity of flow patterns in relation to morphological and functional changes, we have described in this thesis an approach of detecting salient topological features prior to analytical assessment of dynamical indices of the flow patterns. To improve the accuracy of quantitative analysis of the evolution of topological flow features, it is essential to restore the original flow fields so that critical points associated with salient flow features can be more reliably detected. We propose a novel framework for the restoration, abstraction, extraction and tracking of flow features such that their dynamic indices can be accurately tracked and quantified. The restoration method is formulated as a constrained optimisation problem to remove the effects of noise and to improve the consistency of the MR velocity data. A computational scheme is derived from the First Order Lagrangian Method for solving the optimisation problem. After restoration, flow abstraction is applied to partition the entire flow field into clusters, each of which is represented by a local linear expansion of its velocity components. This process not only greatly reduces the amount of data required to encode the velocity distribution but also permits an analytical representation of the flow field from which critical points associated with salient flow features can be accurately extracted. After the critical points are extracted, phase portrait theory can be applied to separate them into attracting/repelling focuses, attracting/repelling nodes, planar vortex, or saddle. In this thesis, we have focused on vortical flow features formed in diastole. To track the movement of the vortices within a cardiac cycle, a tracking algorithm based on relaxation labelling is employed. The constraints and parameters used in the tracking algorithm are designed using the characteristics of the vortices. The proposed framework is validated with both simulated and in vivo data acquired from patients with sequential MR examination following myocardial infarction. The main contribution of the thesis is in the new vector field restoration and flow feature abstraction method proposed. They allow the accurate tracking and quantification of dynamic indices associated with salient features so that inter- and intra-subject comparisons can be more easily made. This provides further insight into the evolution of blood flow patterns and permits the establishment of links between blood flow patterns and localised genesis and progression of cardiovascular disease.Open acces

Combining multiple dynamic models and deep learning architectures for tracking the left ventricle endocardium in ultrasound data

We present a new statistical pattern recognition approach for the problem of left ventricle endocardium tracking in ultrasound data. The problem is formulated as a sequential importance resampling algorithm such that the expected segmentation of the current time step is estimated based on the appearance, shape, and motion models that take into account all previous and current images and previous segmentation contours produced by the method. The new appearance and shape models decouple the affine and nonrigid segmentations of the left ventricle to reduce the running time complexity. The proposed motion model combines the systole and diastole motion patterns and an observation distribution built by a deep neural network. The functionality of our approach is evaluated using a dataset of diseased cases containing 16 sequences and another dataset of normal cases comprised of four sequences, where both sets present long axis views of the left ventricle. Using a training set comprised of diseased and healthy cases, we show that our approach produces more accurate results than current state-of-the-art endocardium tracking methods in two test sequences from healthy subjects. Using three test sequences containing different types of cardiopathies, we show that our method correlates well with interuser statistics produced by four cardiologists.Gustavo Carneiro and Jacinto C. Nasciment

Deep learning tools for outcome prediction in a trial fibrilation from cardiac MRI

Tese de mestrado integrado em Engenharia Biomédica e Biofísica (Engenharia Clínica e Instrumentação Médica), Universidade de Lisboa, Faculdade de Ciências, 2021Atrial fibrillation (AF), is the most frequent sustained cardiac arrhythmia, described by an irregular and rapid contraction of the two upper chambers of the heart (the atria). AF development is promoted and predisposed by atrial dilation, which is a consequence of atria adaptation to AF. However, it is not clear whether atrial dilation appears similarly over the cardiac cycle and how it affects ventricular volumes. Catheter ablation is arguably the AF gold standard treatment. In their current form, ablations are capable of directly terminating AF in selected patients but are only first-time effective in approximately 50% of the cases. In the first part of this work, volumetric functional markers of the left atrium (LA) and left ventricle (LV) of AF patients were studied. More precisely, a customised convolutional neural network (CNN) was proposed to segment, across the cardiac cycle, the LA from short axis CINE MRI images acquired with full cardiac coverage in AF patients. Using the proposed automatic LA segmentation, volumetric time curves were plotted and ejection fractions (EF) were automatically calculated for both chambers. The second part of the project was dedicated to developing classification models based on cardiac MR images. The EMIDEC STACOM 2020 challenge was used as an initial project and basis to create binary classifiers based on fully automatic classification neural networks (NNs), since it presented a relatively simple binary classification task (presence/absence of disease) and a large dataset. For the challenge, a deep learning NN was proposed to automatically classify myocardial disease from delayed enhancement cardiac MR (DE-CMR) and patient clinical information. The highest classification accuracy (100%) was achieved with Clinic-NET+, a NN that used information from images, segmentations and clinical annotations. For the final goal of this project, the previously referred NNs were re-trained to predict AF recurrence after catheter ablation (CA) in AF patients using pre-ablation LA short axis in CINE MRI images. In this task, the best overall performance was achieved by Clinic-NET+ with a test accuracy of 88%. This work shown the potential of NNs to interpret and extract clinical information from cardiac MRI. If more data is available, in the future, these methods can potentially be used to help and guide clinical AF prognosis and diagnosis

Developing advanced mathematical models for detecting abnormalities in 2D/3D medical structures.

Detecting abnormalities in two-dimensional (2D) and three-dimensional (3D) medical structures is among the most interesting and challenging research areas in the medical imaging field. Obtaining the desired accurate automated quantification of abnormalities in medical structures is still very challenging. This is due to a large and constantly growing number of different objects of interest and associated abnormalities, large variations of their appearances and shapes in images, different medical imaging modalities, and associated changes of signal homogeneity and noise for each object. The main objective of this dissertation is to address these problems and to provide proper mathematical models and techniques that are capable of analyzing low and high resolution medical data and providing an accurate, automated analysis of the abnormalities in medical structures in terms of their area/volume, shape, and associated abnormal functionality. This dissertation presents different preliminary mathematical models and techniques that are applied in three case studies: (i) detecting abnormal tissue in the left ventricle (LV) wall of the heart from delayed contrast-enhanced cardiac magnetic resonance images (MRI), (ii) detecting local cardiac diseases based on estimating the functional strain metric from cardiac cine MRI, and (iii) identifying the abnormalities in the corpus callosum (CC) brain structure—the largest fiber bundle that connects the two hemispheres in the brain—for subjects that suffer from developmental brain disorders. For detecting the abnormal tissue in the heart, a graph-cut mathematical optimization model with a cost function that accounts for the object’s visual appearance and shape is used to segment the the inner cavity. The model is further integrated with a geometric model (i.e., a fast marching level set model) to segment the outer border of the myocardial wall (the LV). Then the abnormal tissue in the myocardium wall (also called dead tissue, pathological tissue, or infarct area) is identified based on a joint Markov-Gibbs random field (MGRF) model of the image and its region (segmentation) map that accounts for the pixel intensities and the spatial interactions between the pixels. Experiments with real in-vivo data and comparative results with ground truth (identified by a radiologist) and other approaches showed that the proposed framework can accurately detect the pathological tissue and can provide useful metrics for radiologists and clinicians. To estimate the strain from cardiac cine MRI, a novel method based on tracking the LV wall geometry is proposed. To achieve this goal, a partial differential equation (PDE) method is applied to track the LV wall points by solving the Laplace equation between the LV contours of each two successive image frames over the cardiac cycle. The main advantage of the proposed tracking method over traditional texture-based methods is its ability to track the movement and rotation of the LV wall based on tracking the geometric features of the inner, mid-, and outer walls of the LV. This overcomes noise sources that come from scanner and heart motion. To identify the abnormalities in the CC from brain MRI, the CCs are aligned using a rigid registration model and are segmented using a shape-appearance model. Then, they are mapped to a simple unified space for analysis. This work introduces a novel cylindrical mapping model, which is conformal (i.e., one to one transformation and bijective), that enables accurate 3D shape analysis of the CC in the cylindrical domain. The framework can detect abnormalities in all divisions of the CC (i.e., splenium, rostrum, genu and body). In addition, it offers a whole 3D analysis of the CC abnormalities instead of only area-based analysis as done by previous groups. The initial classification results based on the centerline length and CC thickness suggest that the proposed CC shape analysis is a promising supplement to the current techniques for diagnosing dyslexia. The proposed techniques in this dissertation have been successfully tested on complex synthetic and MR images and can be used to advantage in many of today’s clinical applications of computer-assisted medical diagnostics and intervention

Role of deep learning techniques in non-invasive diagnosis of human diseases.

Machine learning, a sub-discipline in the domain of artificial intelligence, concentrates on algorithms able to learn and/or adapt their structure (e.g., parameters) based on a set of observed data. The adaptation is performed by optimizing over a cost function. Machine learning obtained a great attention in the biomedical community because it offers a promise for improving sensitivity and/or specificity of detection and diagnosis of diseases. It also can increase objectivity of the decision making, decrease the time and effort on health care professionals during the process of disease detection and diagnosis. The potential impact of machine learning is greater than ever due to the increase in medical data being acquired, the presence of novel modalities being developed and the complexity of medical data. In all of these scenarios, machine learning can come up with new tools for interpreting the complex datasets that confront clinicians. Much of the excitement for the application of machine learning to biomedical research comes from the development of deep learning which is modeled after computation in the brain. Deep learning can help in attaining insights that would be impossible to obtain through manual analysis. Deep learning algorithms and in particular convolutional neural networks are different from traditional machine learning approaches. Deep learning algorithms are known by their ability to learn complex representations to enhance pattern recognition from raw data. On the other hand, traditional machine learning requires human engineering and domain expertise to design feature extractors and structure data. With increasing demands upon current radiologists, there are growing needs for automating the diagnosis. This is a concern that deep learning is able to address. In this dissertation, we present four different successful applications of deep learning for diseases diagnosis. All the work presented in the dissertation utilizes medical images. In the first application, we introduce a deep-learning based computer-aided diagnostic system for the early detection of acute renal transplant rejection. The system is based on the fusion of both imaging markers (apparent diffusion coefficients derived from diffusion-weighted magnetic resonance imaging) and clinical biomarkers (creatinine clearance and serum plasma creatinine). The fused data is then used as an input to train and test a convolutional neural network based classifier. The proposed system is tested on scans collected from 56 subjects from geographically diverse populations and different scanner types/image collection protocols. The overall accuracy of the proposed system is 92.9% with 93.3% sensitivity and 92.3% specificity in distinguishing non-rejected kidney transplants from rejected ones. In the second application, we propose a novel deep learning approach for the automated segmentation and quantification of the LV from cardiac cine MR images. We aimed at achieving lower errors for the estimated heart parameters compared to the previous studies by proposing a novel deep learning segmentation method. Using fully convolutional neural networks, we proposed novel methods for the extraction of a region of interest that contains the left ventricle, and the segmentation of the left ventricle. Following myocardial segmentation, functional and mass parameters of the left ventricle are estimated. Automated Cardiac Diagnosis Challenge dataset was used to validate our framework, which gave better segmentation, accurate estimation of cardiac parameters, and produced less error compared to other methods applied on the same dataset. Furthermore, we showed that our segmentation approach generalizes well across different datasets by testing its performance on a locally acquired dataset. In the third application, we propose a novel deep learning approach for automated quantification of strain from cardiac cine MR images of mice. For strain analysis, we developed a Laplace-based approach to track the LV wall points by solving the Laplace equation between the LV contours of each two successive image frames over the cardiac cycle. Following tracking, the strain estimation is performed using the Lagrangian-based approach. This new automated system for strain analysis was validated by comparing the outcome of these analysis with the tagged MR images from the same mice. There were no significant differences between the strain data obtained from our algorithm using cine compared to tagged MR imaging. In the fourth application, we demonstrate how a deep learning approach can be utilized for the automated classification of kidney histopathological images. Our approach can classify four classes: the fat, the parenchyma, the clear cell renal cell carcinoma, and the unusual cancer which has been discovered recently, called clear cell papillary renal cell carcinoma. Our framework consists of three convolutional neural networks and the whole-slide kidney images were divided into patches with three different sizes to be inputted to the networks. Our approach can provide patch-wise and pixel-wise classification. Our approach classified the four classes accurately and surpassed other state-of-the-art methods such as ResNet (pixel accuracy: 0.89 Resnet18, 0.93 proposed). In conclusion, the results of our proposed systems demonstrate the potential of deep learning for the efficient, reproducible, fast, and affordable disease diagnosis

When Cardiac Biophysics Meets Groupwise Statistics: Complementary Modelling Approaches for Patient-Specific Medicine

This habilitation manuscript contains research on biophysical and statistical modeling of the heart, as well as interactions between these two approaches