Semi-Automatic Graphical Tool for Measuring Coronary Artery Spatially Weighted Calcium Score from Gated Cardiac Computed Tomography Images.

The current standard for measuring coronary artery calcification to determine the extent of atherosclerosis is by calculating the Agatston score from computed tomography (CT). However, the Agatston score disregards pixel values less than 130 Hounsfield Units (HU) and calcium regions less than 1 mm2. Due to this thresholding, the score is not sensitive to small, weakly attenuating regions of calcium deposition and may not detect nascent micro-calcification. A recently proposed metric called the spatially weighted calcium score (SWCS) also utilizes CT but does not include a threshold for HU and does not require elevated signals in contiguous pixels. Thus, the SWCS is sensitive to weakly attenuating, smaller calcium deposits and may improve the measurement of coronary heart disease risk. Currently, the SWCS is underutilized owing to the added computational complexity. To promote translation of the SWCS into clinical research and reliable, repeatable computation of the score, the aim of this study was to develop a semi-automatic graphical tool that calculates both the SWCS and the Agatston score. The program requires gated cardiac CT scans with a calcium hydroxyapatite phantom in the field of view. The phantom allows for deriving a weighting function, from which each pixel's weight is adjusted, allowing for the mitigation of signal variations and variability between scans. With all three anatomical views visible simultaneously, the user traces the course of the four main coronary arteries by placing points or regions of interest. Features such as scroll-to-zoom, double-click to delete, and brightness/contrast adjustment, along with written guidance at every step, make the program user-friendly and easy to use. Once tracing the arteries is complete, the program generates reports, which include the scores and snapshots of any visible calcium. The SWCS may reveal the presence of subclinical disease, which may be used for early intervention and lifestyle changes.

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.

Automatic Assessment of Full Left Ventricular Coverage in Cardiac Cine Magnetic Resonance Imaging with Fisher Discriminative 3D CNN.

Cardiac magnetic resonance (CMR) images play a growing role in the diagnostic imaging of cardiovascular diseases. Full coverage of the left ventricle (LV), from base to apex, is a basic criterion for CMR image quality and necessary for accurate measurement of cardiac volume and functional assessment. Incomplete coverage of the LV is identified through visual inspection, which is time-consuming and usually done retrospectively in the assessment of large imaging cohorts. This paper proposes a novel automatic method for determining LV coverage from CMR images by using Fisher-discriminative three-dimensional (FD3D) convolutional neural networks (CNNs). In contrast to our previous method employing 2D CNNs, this approach utilizes spatial contextual information in CMR volumes, extracts more representative high-level features and enhances the discriminative capacity of the baseline 2D CNN learning framework, thus achieving superior detection accuracy. A two-stage framework is proposed to identify missing basal and apical slices in measurements of CMR volume. First, the FD3D CNN extracts high-level features from the CMR stacks. These image representations are then used to detect the missing basal and apical slices. Compared to the traditional 3D CNN strategy, the proposed FD3D CNN minimizes within-class scatter and maximizes between-class scatter. We performed extensive experiments to validate the proposed method on more than 5,000 independent volumetric CMR scans from the UK Biobank study, achieving low error rates for missing basal/apical slice detection (4.9%/4.6%). The proposed method can also be adopted for assessing LV coverage for other types of CMR image data.

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.

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.

Statistical Interspace Models (SIMs): Application to Robust 3D Spine Segmentation.

Statistical shape models (SSM) are used to introduce shape priors in the segmentation of medical images. However, such models require large training datasets in the case of multi-object structures, since it is required to obtain not only the individual shape variations but also the relative position and orientation among objects. A solution to overcome this limitation is to model each individual shape independently. However, this approach does not take into account the relative position, orientations and shapes among the parts of an articulated object, which may result in unrealistic geometries, such as with object overlaps. In this article, we propose a new Statistical Model, the Statistical Interspace Model (SIM), which provides information about the interaction of all the individual structures by modeling the interspace between them. The SIM is described using relative position vectors between pair of points that belong to different objects that are facing each other. These vectors are divided into their magnitude and direction, each of these groups modeled as independent manifolds. The SIM was included in a segmentation framework that contains an SSM per individual object. This framework was tested using three distinct types of datasets of CT images of the spine. Results show that the SIM completely eliminated the inter-process overlap while improving the segmentation accuracy.

Accurate Segmentation of Vertebral Bodies and Processes Using Statistical Shape Decomposition and Conditional Models.

Detailed segmentation of the vertebrae is an important pre-requisite in various applications of image-based spine assessment, surgery and biomechanical modeling. In particular, accurate segmentation of the processes is required for image-guided interventions, for example for optimal placement of bone grafts between the transverse processes. Furthermore, the geometry of the processes is now required in musculoskeletal models due to their interaction with the muscles and ligaments. In this paper, we present a new method for detailed segmentation of both the vertebral bodies and processes based on statistical shape decomposition and conditional models. The proposed technique is specifically developed with the aim to handle the complex geometry of the processes and the large variability between individuals. The key technical novelty in this work is the introduction of a part-based statistical decomposition of the vertebrae, such that the complexity of the subparts is effectively reduced, and model specificity is increased. Subsequently, in order to maintain the statistical and anatomic coherence of the ensemble, conditional models are used to model the statistical inter-relationships between the different subparts. For shape reconstruction and segmentation, a robust model fitting procedure is used to exclude improbable inter-part relationships in the estimation of the shape parameters. Segmentation results based on a dataset of 30 healthy CT scans and a dataset of 10 pathological scans show a point-to-surface error improvement of 20% and 17% respectively, and the potential of the proposed technique for detailed vertebral modeling.

A framework for the merging of pre-existing and correspondenceless 3D statistical shape models.

The construction of statistical shape models (SSMs) that are rich, i.e., that represent well the natural and complex variability of anatomical structures, is an important research topic in medical imaging. To this end, existing works have addressed the limited availability of training data by decomposing the shape variability hierarchically or by combining statistical and synthetic models built using artificially created modes of variation. In this paper, we present instead a method that merges multiple statistical models of 3D shapes into a single integrated model, thus effectively encoding extra variability that is anatomically meaningful, without the need for the original or new real datasets. The proposed framework has great flexibility due to its ability to merge multiple statistical models with unknown point correspondences. The approach is beneficial in order to re-use and complement pre-existing SSMs when the original raw data cannot be exchanged due to ethical, legal, or practical reasons. To this end, this paper describes two main stages, i.e., (1) statistical model normalization and (2) statistical model integration. The normalization algorithm uses surface-based registration to bring the input models into a common shape parameterization with point correspondence established across eigenspaces. This allows the model fusion algorithm to be applied in a coherent manner across models, with the aim to obtain a single unified statistical model of shape with improved generalization ability. The framework is validated with statistical models of the left and right cardiac ventricles, the L1 vertebra, and the caudate nucleus, constructed at distinct research centers based on different imaging modalities (CT and MRI) and point correspondences. The results demonstrate that the model integration is statistically and anatomically meaningful, with potential value for merging pre-existing multi-modality statistical models of 3D shapes.

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.

Fusing correspondenceless 3D point distribution models.

This paper presents a framework for the fusion of multiple point distribution models (PDMs) with unknown point correspondences. With this work, models built from distinct patient groups and imaging modalities can be merged, with the aim to obtain a PDM that encodes a wider range of anatomical variability. To achieve this, two technical challenges are addressed in this work. Firstly, the model fusion must be carried out directly on the corresponding means and eigenvectors as the original data is not always available and cannot be freely exchanged across centers for various legal and practical reasons. Secondly, the PDMs need to be normalized before fusion as the point correspondence is unknown. The proposed framework is validated by integrating statistical models of the left and right ventricles of the heart constructed from different imaging modalities (MRI and CT) and with different landmark representations of the data. The results show that the integration is statistically and anatomically meaningful and that the quality of the resulting model is significantly improved.