Quantitative CMR population imaging on 20,000 subjects of the UK Biobank imaging study: LV/RV quantification pipeline and its evaluation.

Population imaging studies generate data for developing and implementing personalised health strategies to prevent, or more effectively treat disease. Large prospective epidemiological studies acquire imaging for pre-symptomatic populations. These studies enable the early discovery of alterations due to impending disease, and enable early identification of individuals at risk. Such studies pose new challenges requiring automatic image analysis. To date, few large-scale population-level cardiac imaging studies have been conducted. One such study stands out for its sheer size, careful implementation, and availability of top quality expert annotation; the UK Biobank (UKB). The resulting massive imaging datasets (targeting ca. 100,000 subjects) has put published approaches for cardiac image quantification to the test. In this paper, we present and evaluate a cardiac magnetic resonance (CMR) image analysis pipeline that properly scales up and can provide a fully automatic analysis of the UKB CMR study. Without manual user interactions, our pipeline performs end-to-end image analytics from multi-view cine CMR images all the way to anatomical and functional bi-ventricular quantification. All this, while maintaining relevant quality controls of the CMR input images, and resulting image segmentations. To the best of our knowledge, this is the first published attempt to fully automate the extraction of global and regional reference ranges of all key functional cardiovascular indexes, from both left and right cardiac ventricles, for a population of 20,000 subjects imaged at 50 time frames per subject, for a total of one million CMR volumes. In addition, our pipeline provides 3D anatomical bi-ventricular models of the heart. These models enable the extraction of detailed information of the morphodynamics of the two ventricles for subsequent association to genetic, omics, lifestyle habits, exposure information, and other information provided in population imaging studies. We validated our proposed CMR analytics pipeline against manual expert readings on a reference cohort of 4620 subjects with contour delineations and corresponding clinical indexes. Our results show broad significant agreement between the manually obtained reference indexes, and those automatically computed via our framework. 80.67% of subjects were processed with mean contour distance of less than 1 pixel, and 17.50% with mean contour distance between 1 and 2 pixels. Finally, we compare our pipeline with a recently published approach reporting on UKB data, and based on deep learning. Our comparison shows similar performance in terms of segmentation accuracy with respect to human experts.

Statistical shape modeling of the left ventricle: myocardial infarct classification challenge.

Statistical shape modeling is a powerful tool for visualizing and quantifying geometric and functional patterns of the heart. After myocardial infarction (MI), the left ventricle typically remodels in response to physiological challenges. Several methods have been proposed in the literature to describe statistical shape changes. Which method best characterizes left ventricular remodeling after MI is an open research question. A better descriptor of remodeling is expected to provide a more accurate evaluation of disease status in MI patients. We therefore designed a challenge to test shape characterization in MI given a set of three-dimensional left ventricular surface points. The training set comprised 100 MI patients, and 100 asymptomatic volunteers (AV). The challenge was initiated in 2015 at the Statistical Atlases and Computational Models of the Heart workshop, in conjunction with the MICCAI conference. The training set with labels was provided to participants, who were asked to submit the likelihood of MI from a different (validation) set of 200 cases (100 AV and 100 MI). Sensitivity, specificity, accuracy and area under the receiver operating characteristic curve were used as the outcome measures. The goals of this challenge were to (1) establish a common dataset for evaluating statistical shape modeling algorithms in MI, and (2) test whether statistical shape modeling provides additional information characterizing MI patients over standard clinical measures. Eleven groups with a wide variety of classification and feature extraction approaches participated in this challenge. All methods achieved excellent classification results with accuracy ranges from 0.83 to 0.98. The areas under the receiver operating characteristic curves were all above 0.90. Four methods showed significantly higher performance than standard clinical measures. The dataset and software for evaluation are available from the Cardiac Atlas Project website1.

Automatic initialization and quality control of large-scale cardiac MRI segmentations.

Continuous advances in imaging technologies enable ever more comprehensive phenotyping of human anatomy and physiology. Concomitant reduction of imaging costs has resulted in widespread use of imaging in large clinical trials and population imaging studies. Magnetic Resonance Imaging (MRI), in particular, offers one-stop-shop multidimensional biomarkers of cardiovascular physiology and pathology. A wide range of analysis methods offer sophisticated cardiac image assessment and quantification for clinical and research studies. However, most methods have only been evaluated on relatively small databases often not accessible for open and fair benchmarking. Consequently, published performance indices are not directly comparable across studies and their translation and scalability to large clinical trials or population imaging cohorts is uncertain. Most existing techniques still rely on considerable manual intervention for the initialization and quality control of the segmentation process, becoming prohibitive when dealing with thousands of images. The contributions of this paper are three-fold. First, we propose a fully automatic method for initializing cardiac MRI segmentation, by using image features and random forests regression to predict an initial position of the heart and key anatomical landmarks in an MRI volume. In processing a full imaging database, the technique predicts the optimal corrective displacements and positions in relation to the initial rough intersections of the long and short axis images. Second, we introduce for the first time a quality control measure capable of identifying incorrect cardiac segmentations with no visual assessment. The method uses statistical, pattern and fractal descriptors in a random forest classifier to detect failures to be corrected or removed from subsequent statistical analysis. Finally, we validate these new techniques within a full pipeline for cardiac segmentation applicable to large-scale cardiac MRI databases. The results obtained based on over 1200 cases from the Cardiac Atlas Project show the promise of fully automatic initialization and quality control for population studies.

Evaluation of state-of-the-art segmentation algorithms for left ventricle infarct from late Gadolinium enhancement MR images.

Studies have demonstrated the feasibility of late Gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) imaging for guiding the management of patients with sequelae to myocardial infarction, such as ventricular tachycardia and heart failure. Clinical implementation of these developments necessitates a reproducible and reliable segmentation of the infarcted regions. It is challenging to compare new algorithms for infarct segmentation in the left ventricle (LV) with existing algorithms. Benchmarking datasets with evaluation strategies are much needed to facilitate comparison. This manuscript presents a benchmarking evaluation framework for future algorithms that segment infarct from LGE CMR of the LV. The image database consists of 30 LGE CMR images of both humans and pigs that were acquired from two separate imaging centres. A consensus ground truth was obtained for all data using maximum likelihood estimation. Six widely-used fixed-thresholding methods and five recently developed algorithms are tested on the benchmarking framework. Results demonstrate that the algorithms have better overlap with the consensus ground truth than most of the n-SD fixed-thresholding methods, with the exception of the Full-Width-at-Half-Maximum (FWHM) fixed-thresholding method. Some of the pitfalls of fixed thresholding methods are demonstrated in this work. The benchmarking evaluation framework, which is a contribution of this work, can be used to test and benchmark future algorithms that detect and quantify infarct in LGE CMR images of the LV. The datasets, ground truth and evaluation code have been made publicly available through the website: https://www.cardiacatlas.org/web/guest/challenges.

An Algorithm for the Segmentation of Highly Abnormal Hearts Using a Generic Statistical Shape Model.

Statistical shape models (SSMs) have been widely employed in cardiac image segmentation. However, in conditions that induce severe shape abnormality and remodeling, such as in the case of pulmonary hypertension (PH) or hypertrophic cardiomyopathy (HCM), a single SSM is rarely capable of capturing the anatomical variability in the extremes of the distribution. This work presents a new algorithm for the segmentation of severely abnormal hearts. The algorithm is highly flexible, as it does not require a priori knowledge of the involved pathology or any specific parameter tuning to be applied to the cardiac image under analysis. The fundamental idea is to approximate the gross effect of the abnormality with a virtual remodeling transformation between the patient-specific geometry and the average shape of the reference model (e.g., average normal morphology). To define this mapping, a set of landmark points are automatically identified during boundary point search, by estimating the reliability of the candidate points. With the obtained transformation, the feature points extracted from the patient image volume are then projected onto the space of the reference SSM, where the model is used to effectively constrain and guide the segmentation process. The extracted shape in the reference space is finally propagated back to the original image of the abnormal heart to obtain the final segmentation. Detailed validation with patients diagnosed with PH and HCM shows the robustness and flexibility of the technique for the segmentation of highly abnormal hearts of different pathologies.

Joint Clustering and Component Analysis of Correspondenceless Point Sets: Application to Cardiac Statistical Modeling.

Construction of Statistical Shape Models (SSMs) from arbitrary point sets is a challenging problem due to significant shape variation and lack of explicit point correspondence across the training data set. In medical imaging, point sets can generally represent different shape classes that span healthy and pathological exemplars. In such cases, the constructed SSM may not generalize well, largely because the probability density function (pdf) of the point sets deviates from the underlying assumption of Gaussian statistics. To this end, we propose a generative model for unsupervised learning of the pdf of point sets as a mixture of distinctive classes. A Variational Bayesian (VB) method is proposed for making joint inferences on the labels of point sets, and the principal modes of variations in each cluster. The method provides a flexible framework to handle point sets with no explicit point-to-point correspondences. We also show that by maximizing the marginalized likelihood of the model, the optimal number of clusters of point sets can be determined. We illustrate this work in the context of understanding the anatomical phenotype of the left and right ventricles in heart. To this end, we use a database containing hearts of healthy subjects, patients with Pulmonary Hypertension (PH), and patients with Hypertrophic Cardiomyopathy (HCM). We demonstrate that our method can outperform traditional PCA in both generalization and specificity measures.

Effect of statistically derived fiber models on the estimation of cardiac electrical activation.

Myocardial fiber orientation plays a critical role in the electrical activation and subsequent contraction of the heart. To increase the clinical potential of electrophysiological (EP) simulation for the study of cardiac phenomena and the planning of interventions, accurate personalization of the fibers is a necessary yet challenging task. Due to the difficulties associated with the in vivo imaging of cardiac fiber structure, researchers have developed alternative techniques to personalize fibers. Thus far, cardiac simulation was performed mainly based on rule-based fiber models. More recently, there has been a significant interest in data-driven and statistically derived fiber models. In particular, our predictive method in [1] allows us to estimate the unknown subject-specific fiber orientation based on the more easily available shape information. The aim of this work is to estimate the effect of using such statistical predictive models for the estimation of cardiac electrical activation times and patterns. To this end, we perform EP simulations based on a database of ten canine ex vivo diffusion tensor imaging (DTI) datasets that include normal and failing cases. To assess the strength of the fiber models under varying conditions, we consider both sinus rhythm and biventricular pacing simulations. The results show that 1) the statistically derived fibers improve the estimation of the local activation times by an average of 53.7% over traditional rule-based models, and that 2) the obtained electrical activations are consistently similar to those of the DTI-based fibers.

Statistical personalization of ventricular fiber orientation using shape predictors.

This paper presents a predictive framework for the statistical personalization of ventricular fibers. To this end, the relationship between subject-specific geometry of the left (LV) and right ventricles (RV) and fiber orientation is learned statistically from a training sample of ex vivo diffusion tensor imaging datasets. More specifically, the axes in the shape space which correlate most with the myocardial fiber orientations are extracted and used for prediction in new subjects. With this approach and unlike existing fiber models, inter-subject variability is taken into account to generate latent shape predictors that are statistically optimal to estimate fiber orientation at each individual myocardial location. The proposed predictive model was applied to the task of personalizing fibers in 10 canine subjects. The results indicate that the ventricular shapes are good predictors of fiber orientation, with an improvement of 11.4% in accuracy over the average fiber model.

Automatic cardiac LV segmentation in MRI using modified graph cuts with smoothness and interslice constraints.

PURPOSE: Magnetic resonance imaging (MRI), specifically late-enhanced MRI, is the standard clinical imaging protocol to assess cardiac viability. Segmentation of myocardial walls is a prerequisite for this assessment. Automatic and robust multisequence segmentation is required to support processing massive quantities of data. METHODS: A generic rule-based framework to automatically segment the left ventricle myocardium is presented here. We use intensity information, and include shape and interslice smoothness constraints, providing robustness to subject- and study-specific changes. Our automatic initialization considers the geometrical and appearance properties of the left ventricle, as well as interslice information. The segmentation algorithm uses a decoupled, modified graph cut approach with control points, providing a good balance between flexibility and robustness. RESULTS: The method was evaluated on late-enhanced MRI images from a 20-patient in-house database, and on cine-MRI images from a 15-patient open access database, both using as reference manually delineated contours. Segmentation agreement, measured using the Dice coefficient, was 0.81±0.05 and 0.92±0.04 for late-enhanced MRI and cine-MRI, respectively. The method was also compared favorably to a three-dimensional Active Shape Model approach. CONCLUSION: The experimental validation with two magnetic resonance sequences demonstrates increased accuracy and versatility.