Learning Shape Priors for Robust Cardiac MR Segmentation from Multi-view Images

© 2019, Springer Nature Switzerland AG. Cardiac MR image segmentation is essential for the morphological and functional analysis of the heart. Inspired by how experienced clinicians assess the cardiac morphology and function across multiple standard views (i.e. long- and short-axis views), we propose a novel approach which learns anatomical shape priors across different 2D standard views and leverages these priors to segment the left ventricular (LV) myocardium from short-axis MR image stacks. The proposed segmentation method has the advantage of being a 2D network but at the same time incorporates spatial context from multiple, complementary views that span a 3D space. Our method achieves accurate and robust segmentation of the myocardium across different short-axis slices (from apex to base), outperforming baseline models (e.g. 2D U-Net, 3D U-Net) while achieving higher data efficiency. Compared to the 2D U-Net, the proposed method reduces the mean Hausdorff distance (mm) from 3.24 to 2.49 on the apical slices, from 2.34 to 2.09 on the middle slices and from 3.62 to 2.76 on the basal slices on the test set, when only 10% of the training data was used

Antipsychotics and Torsadogenic Risk: Signals Emerging from the US FDA Adverse Event Reporting System Database

Background: Drug-induced torsades de pointes (TdP) and related clinical entities represent a current regulatory and clinical burden. Objective: As part of the FP7 ARITMO (Arrhythmogenic Potential of Drugs) project, we explored the publicly available US FDA Adverse Event Reporting System (FAERS) database to detect signals of torsadogenicity for antipsychotics (APs). Methods: Four groups of events in decreasing order of drug-attributable risk were identified: (1) TdP, (2) QT-interval abnormalities, (3) ventricular fibrillation/tachycardia, and (4) sudden cardiac death. The reporting odds ratio (ROR) with 95 % confidence interval (CI) was calculated through a cumulative analysis from group 1 to 4. For groups 1+2, ROR was adjusted for age, gender, and concomitant drugs (e.g., antiarrhythmics) and stratified for AZCERT drugs, lists I and II (http://www.azcert.org, as of June 2011). A potential signal of torsadogenicity was defined if a drug met all the following criteria: (a) four or more cases in group 1+2; (b) significant ROR in group 1+2 that persists through the cumulative approach; (c) significant adjusted ROR for group 1+2 in the stratum without AZCERT drugs; (d) not included in AZCERT lists (as of June 2011). Results: Over the 7-year period, 37 APs were reported in 4,794 cases of arrhythmia: 140 (group 1), 883 (group 2), 1,651 (group 3), and 2,120 (group 4). Based on our criteria, the following potential signals of torsadogenicity were found: amisulpride (25 cases; adjusted ROR in the stratum without AZCERT drugs = 43.94, 95 % CI 22.82-84.60), cyamemazine (11; 15.48, 6.87-34.91), and olanzapine (189; 7.74, 6.45-9.30). Conclusions: This pharmacovigilance analysis on the FAERS found 3 potential signals of torsadogenicity for drugs previously unknown for this risk

DMSO and Betaine Greatly Improve Amplification of GC-Rich Constructs in De Novo Synthesis

In Synthetic Biology, de novo synthesis of GC-rich constructs poses a major challenge because of secondary structure formation and mispriming. While there are many web-based tools for codon optimizing difficult regions, no method currently exists that allows for potentially phenotypically important sequence conservation. Therefore, to overcome these limitations in researching GC-rich genes and their non-coding elements, we explored the use of DMSO and betaine in two conventional methods of assembly and amplification. For this study, we compared the polymerase (PCA) and ligase-based (LCR) methods for construction of two GC-rich gene fragments implicated in tumorigenesis, IGF2R and BRAF. Though we found no benefit in employing either DMSO or betaine during the assembly steps, both additives greatly improved target product specificity and yield during PCR amplification. Of the methods tested, LCR assembly proved far superior to PCA, generating a much more stable template to amplify from. We further report that DMSO and betaine are highly compatible with all other reaction components of gene synthesis and do not require any additional protocol modifications. Furthermore, we believe either additive will allow for the production of a wide variety of GC-rich gene constructs without the need for expensive and time-consuming sample extraction and purification prior to downstream application

Genetic Architecture of Hybrid Male Sterility in Drosophila: Analysis of Intraspecies Variation for Interspecies Isolation

Background: The genetic basis of postzygotic isolation is a central puzzle in evolutionary biology. Evolutionary forces causing hybrid sterility or inviability act on the responsible genes while they still are polymorphic, thus we have to study these traits as they arise, before isolation is complete. Methodology/Principal Findings: Isofemale strains of D. mojavensis vary significantly in their production of sterile F 1 sons when females are crossed to D. arizonae males. We took advantage of the intraspecific polymorphism, in a novel design, to perform quantitative trait locus (QTL) mapping analyses directly on F1 hybrid male sterility itself. We found that the genetic architecture of the polymorphism for hybrid male sterility (HMS) in the F1 is complex, involving multiple QTL, epistasis, and cytoplasmic effects. Conclusions/Significance: The role of extensive intraspecific polymorphism, multiple QTL, and epistatic interactions in HMS in this young species pair shows that HMS is arising as a complex trait in this system. Directional selection alone would be unlikely to maintain polymorphism at multiple loci, thus we hypothesize that directional selection is unlikely to be the only evolutionary force influencing postzygotic isolation

Feature tracking cardiac magnetic resonance via deep learning and spline optimization

Feature tracking Cardiac Magnetic Resonance (CMR) has recently emerged as an area of interest for quantification of regional cardiac function from balanced, steady state free precession (SSFP) cine sequences. However, currently available techniques lack full automation, limiting reproducibility. We propose a fully automated technique whereby a CMR image sequence is first segmented with a deep, fully convolutional neural network (CNN) architecture, and quadratic basis splines are fitted simultaneously across all cardiac frames using least squares optimization. Experiments are performed using data from 42 patients with hypertrophic cardiomyopathy (HCM) and 21 healthy control subjects. In terms of segmentation, we compared state-of-the-art CNN frameworks, U-Net and dilated convolution architectures, with and without temporal context, using cross validation with three folds. Performance relative to expert manual segmentation was similar across all networks: pixel accuracy was ∼ 97%, intersection-over-union (IoU) across all classes was ∼ 87%, and IoU across foreground classes only was ∼ 85%. Endocardial left ventricular circumferential strain calculated from the proposed pipeline was significantly different in control and disease subjects (−25.3% vs −29.1%, p = 0.006), in agreement with the current clinical literature

Ω-Net (Omega-Net): Fully automatic, multi-view cardiac MR detection, orientation, and segmentation with deep neural networks

Pixelwise segmentation of the left ventricular (LV) myocardium and the four cardiac chambers in 2-D steady state free precession (SSFP) cine sequences is an essential preprocessing step for a wide range of analyses. Variability in contrast, appearance, orientation, and placement of the heart between patients, clinical views, scanners, and protocols makes fully automatic semantic segmentation a notoriously difficult problem. Here, we present Ω-Net (Omega-Net): A novel convolutional neural network (CNN) architecture for simultaneous localization, transformation into a canonical orientation, and semantic segmentation. First, an initial segmentation is performed on the input image; second, the features learned during this initial segmentation are used to predict the parameters needed to transform the input image into a canonical orientation; and third, a final segmentation is performed on the transformed image. In this work, Ω-Nets of varying depths were trained to detect five foreground classes in any of three clinical views (short axis, SA; four-chamber, 4C; two-chamber, 2C), without prior knowledge of the view being segmented. This constitutes a substantially more challenging problem compared with prior work. The architecture was trained using three-fold cross-validation on a cohort of patients with hypertrophic cardiomyopathy (HCM, ) and healthy control subjects (). Network performance, as measured by weighted foreground intersection-over-union (IoU), was substantially improved for the best-performing Ω-Net compared with U-Net segmentation without localization or orientation (0.858 vs 0.834). In addition, to be comparable with other works, Ω-Net was retrained from scratch using five-fold cross-validation on the publicly available 2017 MICCAI Automated Cardiac Diagnosis Challenge (ACDC) dataset. The Ω-Net outperformed the state-of-the-art method in segmentation of the LV and RV bloodpools, and performed slightly worse in segmentation of the LV myocardium. We conclude that this architecture represents a substantive advancement over prior approaches, with implications for biomedical image segmentation more generally

SiSSR: Simultaneous subdivision surface registration for the quantification of cardiac function from computed tomography in canines

Recent improvements in cardiac computed tomography (CCT) allow for whole-heart functional studies to be acquired at low radiation dose (<2mSv) and high-temporal resolution (<100ms) in a single heart beat. Although the extraction of regional functional information from these images is of great clinical interest, there is a paucity of research into the quantification of regional function from CCT, contrasting with the large body of work in echocardiography and cardiac MR. Here we present the Simultaneous Subdivision Surface Registration (SiSSR) method: a fast, semi-automated image analysis pipeline for quantifying regional function from contrast-enhanced CCT. For each of thirteen adult male canines, we construct an anatomical reference mesh representing the left ventricular (LV) endocardium, obviating the need for a template mesh to be manually sculpted and initialized. We treat this generated mesh as a Loop subdivision surface, and adapt a technique previously described in the context of 3-D echocardiography to register these surfaces to the endocardium efficiently across all cardiac frames simultaneously. Although previous work performs the registration at a single resolution, we observe that subdivision surfaces naturally suggest a multiresolution approach, leading to faster convergence and avoiding local minima. We additionally make two notable changes to the cost function of the optimization, explicitly encouraging plausible biological motion and high mesh quality. Finally, we calculate an accepted functional metric for CCT from the registered surfaces, and compare our results to an alternate state-of-the-art CCT method

Calculation of Anatomical and Functional Metrics Using Deep Learning in Cardiac MRI: Comparison Between Direct and Segmentation-Based Estimation

In this paper we propose a collection of left ventricle (LV) quantification methods using different versions of a common neural network architecture. In particular, we compare the accuracy obtained with direct calculation (regression) of the desired metrics, a segmentation network and a novel combined approach. We also introduce temporal dynamics through the use of a Long Short-Term Memory (LSTM) network. We train and evaluate our methods on MICCAI 2018 Left Ventricle Full Quantification Challenge dataset. We perform 5-fold cross-validation on the training dataset and compare our results with the state-of-the-art methods evaluated on the same dataset. In our experiments, segmentation-based methods outperform all the other variants as well as current state of the art. The introduction of LSTM does produces only minor improvements in accuracy. The novel segmentation/estimation network improves the results on estimation-only but does not reach the accuracy of segmentation-based metric calculation

SMOD - Data Augmentation Based on Statistical Models of Deformation to Enhance Segmentation in 2D Cine Cardiac MRI

Deep learning has revolutionized medical image analysis in recent years. Nevertheless, technical, ethical and financial constraints along with confidentiality issues still limit data availability, and therefore the performance of these approaches. To overcome such limitations, data augmentation has proven crucial. Here we propose SMOD, a novel augmentation methodology based on Statistical Models of Deformations, to segment 2D cine scans in cardiac MRI. In brief, the shape variability of the training set space is modelled so new images with the appearance of the original ones but unseen shapes within the space of plausible realistic shapes are generated. SMOD is compared to standard augmentation providing quantitative improvement, especially when the training data available is very limited or the structures to segment are complex and highly variable. We finally propose a state-of-art, deep learning 2D cardiac MRI segmenter for normal and hypertrophic cardiomyopathy hearts with an epicardium and endocardium mean Dice score of 0.968 in short and long axis

Left ventricular strain is abnormal in preclinical and overt hypertrophic cardiomyopathy: Cardiac MR feature tracking

Purpose To evaluate myocardial strain and circumferential transmural strain difference (cTSD; the difference between epicardial and endocardial circumferential strain) in a genotyped cohort with hypertrophic cardiomyopathy (HCM) and to explore correlations between cTSD and other anatomic and functional markers of disease status. Left ventricular (LV) dysfunction may indicate early disease in preclinical HCM (sarcomere mutation carriers without LV hypertrophy). Cardiac MRI feature tracking may be used to evaluate myocardial strain in carriers of HCM sarcomere mutation. Materials and Methods Participants with HCM and their family members participated in a prospective, multicenter, observational study (HCMNet). Genetic testing was performed in all participants. Study participants underwent cardiac MRI with temporal resolution at 40 msec or less. LV myocardial strain was analyzed by using feature-tracking software. Circumferential strain was measured at the epicardial and endocardial surfaces; their difference yielded the circumferential transmural strain difference (cTSD). Multivariable analysis to predict HCM status was performed by using multinomial logistic regression adjusting for age, sex, and LV parameters. Results Ninety-nine participants were evaluated (23 control participants, 34 participants with preclinical HCM [positive for sarcomere mutation and negative for LV hypertrophy], and 42 participants with overt HCM [positive for sarcomere mutation and negative for LV hypertrophy]). The average age was 25 years ± 11 and 44 participants (44%) were women. Maximal LV wall thickness was 9.5 mm ± 1.4, 9.8 mm ± 2.2, and 16.1 mm ± 5.3 in control participants, participants with preclinical HCM (P = .496 vs control participants), and participants with overt HCM (P Conclusion Cardiac MRI feature tracking identifies myocardial dysfunction not only in participants with overt hypertrophic cardiomyopathy, but also in carriers of sarcomere mutation without left ventricular hypertrophy, suggesting that contractile abnormalities are present even when left ventricular wall thickness is normal.</p