Biomedical repositories such as the UK Biobank provide increasing access to prospectively collected cardiac imaging, however these data are unlabeled, which creates barriers to their use in supervised machine learning. We develop a weakly supervised deep learning model for classification of aortic valve malformations using up to 4,000 unlabeled cardiac MRI sequences. Instead of requiring highly curated training data, weak supervision relies on noisy heuristics defined by domain experts to programmatically generate large-scale, imperfect training labels. For aortic valve classification, models trained with imperfect labels substantially outperform a supervised model trained on hand-labeled MRIs. In an orthogonal validation experiment using health outcomes data, our model identifies individuals with a 1.8-fold increase in risk of a major adverse cardiac event. This work formalizes a deep learning baseline for aortic valve classification and outlines a general strategy for using weak supervision to train machine learning models using unlabeled medical images at scale.
Background - The aortic valve is an important determinant of cardiovascular physiology and anatomic location of common human diseases. Methods - From a sample of 34,287 white British-ancestry participants, we estimated functional aortic valve area by planimetry from prospectively obtained cardiac MRI sequences of the aortic valve. Aortic valve area measurements were submitted to genome-wide association testing, followed by polygenic risk scoring and phenome-wide screening to identify genetic comorbidities. Results - A genome-wide association study of aortic valve area in these UK Biobank participants showed three significant associations, indexed by rs71190365 (chr13:50764607, DLEU1 , p=1.8×10 -9 ), rs35991305 (chr12:94191968, CRADD , p=3.4×10 -8 ) and chr17:45013271:C:T ( GOSR2 , p=5.6×10 -8 ). Replication on an independent set of 8,145 unrelated European-ancestry participants showed consistent effect sizes in all three loci, although rs35991305 did not meet nominal significance. We constructed a polygenic risk score for aortic valve area, which in a separate cohort of 311,728 individuals without imaging demonstrated that smaller aortic valve area is predictive of increased risk for aortic valve disease (Odds Ratio 1.14, p =2.3×10 -6 ). After excluding subjects with a medical diagnosis of aortic valve stenosis (remaining n=308,683 individuals), phenome-wide association of >10,000 traits showed multiple links between the polygenic score for aortic valve disease and key health-related comorbidities involving the cardiovascular system and autoimmune disease. Genetic correlation analysis supports a shared genetic etiology with between aortic valve area and birthweight along with other cardiovascular conditions. Conclusions - These results illustrate the use of automated phenotyping of cardiac imaging data from the general population to investigate the genetic etiology of aortic valve disease, perform clinical prediction, and uncover new clinical and genetic correlates of cardiac anatomy.
Biomedical repositories such as the UK Biobank provide increasing access to prospectively collected cardiac imaging, however these data are unlabeled which creates barriers to their use in supervised machine learning. We develop a weakly supervised deep learning model for classification of aortic valve malformations using up to 4,000 unlabeled cardiac MRI sequences. Instead of requiring highly curated training data, weak supervision relies on noisy heuristics defined by domain experts to programmatically generate large-scale, imperfect training labels.For aortic valve classification, models trained with imperfect labels substantially outperform a supervised model trained on hand-labeled MRIs. In an orthogonal validation experiment using health outcomes data, our model identifies individuals with a 1.8-fold increase in risk of a major adverse cardiac event. This work formalizes a learning baseline for aortic valve classification and outlines a general strategy for using weak supervision to train machine learning models using unlabeled medical images at scale.May 2, 2019 2/26 apply the CNN-LSTM to a cohort of 9,230 new patients with long-term outcome and MRI data from the UK May 2, 2019 3/26Biobank. In patients identified by our classifier as having BAV, we find a 1.8-fold increase in risk of a major adverse cardiac event. These findings demonstrate how weakly supervised methods help mitigate the lack of expert-labeled training data in cardiac imaging settings, and how real-world health outcomes can be learned directly from large-scale, unlabeled medical imaging data.May 2, 2019 4/26
The aortic valve is an important determinant of cardiovascular physiology and anatomic location of common human diseases. From a sample of 26,142 European-ancestry participants, we estimated functional aortic valve area by planimetry from prospectively obtained cardiac MRI sequences of the aortic valve. A genome-wide association study of aortic valve area in these UK Biobank participants showed two significant associations indexed by rs71190365 (chr13:50764607, DLEU1, p=1.8e-9) and rs35991305 (chr12:94191968, CRADD, p=3.4e-8). From the GWAS findings we constructed a polygenic risk score for aortic valve area, which in a separate cohort of 311,728 individuals without imaging demonstrated that smaller aortic valve area is predictive of increased risk for aortic valve disease (Odds Ratio 0.88, p=2.3e-6). After excluding subjects with a medical diagnosis of aortic valve stenosis (remaining n=310,546 individuals), phenome-wide association of >10,000 traits showed multiple links between the polygenic score for aortic valve disease and key health-related comorbidities involving the cardiovascular system and autoimmune disease. Genetic correlation analysis supports a shared genetic etiology with between aortic valve size and birthweight along with other cardiovascular conditions. These results illustrate the use of automated phenotyping of cardiac imaging data from the general population to investigate the genetic etiology of aortic valve disease, perform clinical prediction, and uncover new clinical and genetic correlates of cardiac anatomy.
Visual knowledge bases such as Visual Genome power numerous applications in computer vision, including visual question answering and captioning, but suffer from sparse, incomplete relationships. All scene graph models to date are limited to training on a small set of visual relationships that have thousands of training labels each. Hiring human annotators is expensive, and using textual knowledge base completion methods are incompatible with visual data. In this paper, we introduce a semi-supervised method that assigns probabilistic relationship labels to a large number of unlabeled images using few' labeled examples. We analyze visual relationships to suggest two types of image-agnostic features that are used to generate noisy heuristics, whose outputs are aggregated using a factor graph-based generative model. With as few as 10 labeled examples per relationship, the generative model creates enough training data to train any existing state-of-the-art scene graph model. We demonstrate that our method outperforms all baseline approaches on scene graph prediction by 5.16 recall@ 100 for PREDCLS. In our limited label setting, we define a complexity metric for relationships that serves as an indicator (R 2 = 0.778) for conditions under which our method succeeds over transfer learning, the de-facto approach for training with limited labels.Hiring more human workers is an ineffective solution to labeling relationships because image annotation is so tedious that seemingly obvious labels are left unannotated. To complement human annotators, traditional text-based knowledge completion tasks have leveraged numerous semi-supervised or distant supervision approaches [6,7,17,34], These
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