Self-supervised contrastive learning of echocardiogram videos enables label-efficient cardiac disease diagnosis

Advances in self-supervised learning (SSL) have shown that self-supervised pretraining on medical imaging data can provide a strong initialization for downstream supervised classification and segmentation. Given the difficulty of obtaining expert labels for medical image recognition tasks, such an "in-domain" SSL initialization is often desirable due to its improved label efficiency over standard transfer learning. However, most efforts toward SSL of medical imaging data are not adapted to video-based medical imaging modalities. With this progress in mind, we developed a self-supervised contrastive learning approach, EchoCLR, catered to echocardiogram videos with the goal of learning strong representations for efficient fine-tuning on downstream cardiac disease diagnosis. EchoCLR leverages (i) distinct videos of the same patient as positive pairs for contrastive learning and (ii) a frame re-ordering pretext task to enforce temporal coherence. When fine-tuned on small portions of labeled data (as few as 51 exams), EchoCLR pretraining significantly improved classification performance for left ventricular hypertrophy (LVH) and aortic stenosis (AS) over other transfer learning and SSL approaches across internal and external test sets. For example, when fine-tuning on 10% of available training data (519 studies), an EchoCLR-pretrained model achieved 0.72 AUROC (95% CI: [0.69, 0.75]) on LVH classification, compared to 0.61 AUROC (95% CI: [0.57, 0.64]) with a standard transfer learning approach. Similarly, using 1% of available training data (53 studies), EchoCLR pretraining achieved 0.82 AUROC (95% CI: [0.79, 0.84]) on severe AS classification, compared to 0.61 AUROC (95% CI: [0.58, 0.65]) with transfer learning. EchoCLR is unique in its ability to learn representations of medical videos and demonstrates that SSL can enable label-efficient disease classification from small, labeled datasets

Improving Fairness of Automated Chest X-ray Diagnosis by Contrastive Learning

Purpose: Limited studies exploring concrete methods or approaches to tackle and enhance model fairness in the radiology domain. Our proposed AI model utilizes supervised contrastive learning to minimize bias in CXR diagnosis. Materials and Methods: In this retrospective study, we evaluated our proposed method on two datasets: the Medical Imaging and Data Resource Center (MIDRC) dataset with 77,887 CXR images from 27,796 patients collected as of April 20, 2023 for COVID-19 diagnosis, and the NIH Chest X-ray (NIH-CXR) dataset with 112,120 CXR images from 30,805 patients collected between 1992 and 2015. In the NIH-CXR dataset, thoracic abnormalities include atelectasis, cardiomegaly, effusion, infiltration, mass, nodule, pneumonia, pneumothorax, consolidation, edema, emphysema, fibrosis, pleural thickening, or hernia. Our proposed method utilizes supervised contrastive learning with carefully selected positive and negative samples to generate fair image embeddings, which are fine-tuned for subsequent tasks to reduce bias in chest X-ray (CXR) diagnosis. We evaluated the methods using the marginal AUC difference ($\delta$ mAUC). Results: The proposed model showed a significant decrease in bias across all subgroups when compared to the baseline models, as evidenced by a paired T-test (p<0.0001). The $\delta$ mAUC obtained by our method were 0.0116 (95\% CI, 0.0110-0.0123), 0.2102 (95% CI, 0.2087-0.2118), and 0.1000 (95\% CI, 0.0988-0.1011) for sex, race, and age on MIDRC, and 0.0090 (95\% CI, 0.0082-0.0097) for sex and 0.0512 (95% CI, 0.0512-0.0532) for age on NIH-CXR, respectively. Conclusion: Employing supervised contrastive learning can mitigate bias in CXR diagnosis, addressing concerns of fairness and reliability in deep learning-based diagnostic methods.Comment: 23 pages, 5 figure

Long-Tailed Classification of Thorax Diseases on Chest X-Ray: A New Benchmark Study

Imaging exams, such as chest radiography, will yield a small set of common findings and a much larger set of uncommon findings. While a trained radiologist can learn the visual presentation of rare conditions by studying a few representative examples, teaching a machine to learn from such a "long-tailed" distribution is much more difficult, as standard methods would be easily biased toward the most frequent classes. In this paper, we present a comprehensive benchmark study of the long-tailed learning problem in the specific domain of thorax diseases on chest X-rays. We focus on learning from naturally distributed chest X-ray data, optimizing classification accuracy over not only the common "head" classes, but also the rare yet critical "tail" classes. To accomplish this, we introduce a challenging new long-tailed chest X-ray benchmark to facilitate research on developing long-tailed learning methods for medical image classification. The benchmark consists of two chest X-ray datasets for 19- and 20-way thorax disease classification, containing classes with as many as 53,000 and as few as 7 labeled training images. We evaluate both standard and state-of-the-art long-tailed learning methods on this new benchmark, analyzing which aspects of these methods are most beneficial for long-tailed medical image classification and summarizing insights for future algorithm design. The datasets, trained models, and code are available at https://github.com/VITA-Group/LongTailCXR.Comment: DALI 2022 (MICCAI workshop

Harnessing the power of longitudinal medical imaging for eye disease prognosis using Transformer-based sequence modeling

Deep learning has enabled breakthroughs in automated diagnosis from medical imaging, with many successful applications in ophthalmology. However, standard medical image classification approaches only assess disease presence at the time of acquisition, neglecting the common clinical setting of longitudinal imaging. For slow, progressive eye diseases like age-related macular degeneration (AMD) and primary open-angle glaucoma (POAG), patients undergo repeated imaging over time to track disease progression and forecasting the future risk of developing a disease is critical to properly plan treatment. Our proposed Longitudinal Transformer for Survival Analysis (LTSA) enables dynamic disease prognosis from longitudinal medical imaging, modeling the time to disease from sequences of fundus photography images captured over long, irregular time periods. Using longitudinal imaging data from the Age-Related Eye Disease Study (AREDS) and Ocular Hypertension Treatment Study (OHTS), LTSA significantly outperformed a single-image baseline in 19/20 head-to-head comparisons on late AMD prognosis and 18/20 comparisons on POAG prognosis. A temporal attention analysis also suggested that, while the most recent image is typically the most influential, prior imaging still provides additional prognostic value

How Does Pruning Impact Long-Tailed Multi-Label Medical Image Classifiers?

Pruning has emerged as a powerful technique for compressing deep neural networks, reducing memory usage and inference time without significantly affecting overall performance. However, the nuanced ways in which pruning impacts model behavior are not well understood, particularly for long-tailed, multi-label datasets commonly found in clinical settings. This knowledge gap could have dangerous implications when deploying a pruned model for diagnosis, where unexpected model behavior could impact patient well-being. To fill this gap, we perform the first analysis of pruning's effect on neural networks trained to diagnose thorax diseases from chest X-rays (CXRs). On two large CXR datasets, we examine which diseases are most affected by pruning and characterize class "forgettability" based on disease frequency and co-occurrence behavior. Further, we identify individual CXRs where uncompressed and heavily pruned models disagree, known as pruning-identified exemplars (PIEs), and conduct a human reader study to evaluate their unifying qualities. We find that radiologists perceive PIEs as having more label noise, lower image quality, and higher diagnosis difficulty. This work represents a first step toward understanding the impact of pruning on model behavior in deep long-tailed, multi-label medical image classification. All code, model weights, and data access instructions can be found at https://github.com/VITA-Group/PruneCXR.Comment: Early accepted to MICCAI 202

Towards long-tailed, multi-label disease classification from chest X-ray: Overview of the CXR-LT challenge

Many real-world image recognition problems, such as diagnostic medical imaging exams, are "long-tailed" \unicode{x2013} there are a few common findings followed by many more relatively rare conditions. In chest radiography, diagnosis is both a long-tailed and multi-label problem, as patients often present with multiple findings simultaneously. While researchers have begun to study the problem of long-tailed learning in medical image recognition, few have studied the interaction of label imbalance and label co-occurrence posed by long-tailed, multi-label disease classification. To engage with the research community on this emerging topic, we conducted an open challenge, CXR-LT, on long-tailed, multi-label thorax disease classification from chest X-rays (CXRs). We publicly release a large-scale benchmark dataset of over 350,000 CXRs, each labeled with at least one of 26 clinical findings following a long-tailed distribution. We synthesize common themes of top-performing solutions, providing practical recommendations for long-tailed, multi-label medical image classification. Finally, we use these insights to propose a path forward involving vision-language foundation models for few- and zero-shot disease classification

The Germ Cell Nuclear Proteins hnRNP G-T and RBMY Activate a Testis-Specific Exon

The human testis has almost as high a frequency of alternative splicing events as brain. While not as extensively studied as brain, a few candidate testis-specific splicing regulator proteins have been identified, including the nuclear RNA binding proteins RBMY and hnRNP G-T, which are germ cell-specific versions of the somatically expressed hnRNP G protein and are highly conserved in mammals. The splicing activator protein Tra2β is also highly expressed in the testis and physically interacts with these hnRNP G family proteins. In this study, we identified a novel testis-specific cassette exon TLE4-T within intron 6 of the human transducing-like enhancer of split 4 (TLE4) gene which makes a more transcriptionally repressive TLE4 protein isoform. TLE4-T splicing is normally repressed in somatic cells because of a weak 5′ splice site and surrounding splicing-repressive intronic regions. TLE4-T RNA pulls down Tra2β and hnRNP G proteins which activate its inclusion. The germ cell-specific RBMY and hnRNP G-T proteins were more efficient in stimulating TLE4-T incorporation than somatically expressed hnRNP G protein. Tra2b bound moderately to TLE4-T RNA, but more strongly to upstream sites to potently activate an alternative 3′ splice site normally weakly selected in the testis. Co-expression of Tra2β with either hnRNP G-T or RBMY re-established the normal testis physiological splicing pattern of this exon. Although they can directly bind pre-mRNA sequences around the TLE4-T exon, RBMY and hnRNP G-T function as efficient germ cell-specific splicing co-activators of TLE4-T. Our study indicates a delicate balance between the activity of positive and negative splicing regulators combinatorially controls physiological splicing inclusion of exon TLE4-T and leads to modulation of signalling pathways in the testis. In addition, we identified a high-affinity binding site for hnRNP G-T protein, showing it is also a sequence-specific RNA binding protein

Hierarchical structure of cascade of primary and secondary periodicities in Fourier power spectrum of alphoid higher order repeats

<p>Abstract</p> <p>Background</p> <p>Identification of approximate tandem repeats is an important task of broad significance and still remains a challenging problem of computational genomics. Often there is no single best approach to periodicity detection and a combination of different methods may improve the prediction accuracy. Discrete Fourier transform (DFT) has been extensively used to study primary periodicities in DNA sequences. Here we investigate the application of DFT method to identify and study alphoid higher order repeats.</p> <p>Results</p> <p>We used method based on DFT with mapping of symbolic into numerical sequence to identify and study alphoid higher order repeats (HOR). For HORs the power spectrum shows equidistant frequency pattern, with characteristic two-level hierarchical organization as signature of HOR. Our case study was the 16 mer HOR tandem in AC017075.8 from human chromosome 7. Very long array of equidistant peaks at multiple frequencies (more than a thousand higher harmonics) is based on fundamental frequency of 16 mer HOR. Pronounced subset of equidistant peaks is based on multiples of the fundamental HOR frequency (multiplication factor <it>n </it>for <it>n</it>mer) and higher harmonics. In general, <it>n</it>mer HOR-pattern contains equidistant secondary periodicity peaks, having a pronounced subset of equidistant primary periodicity peaks. This hierarchical pattern as signature for HOR detection is robust with respect to monomer insertions and deletions, random sequence insertions etc. For a monomeric alphoid sequence only primary periodicity peaks are present. The 1/<it>f</it>^{<it>β </it>}– noise and periodicity three pattern are missing from power spectra in alphoid regions, in accordance with expectations.</p> <p>Conclusion</p> <p>DFT provides a robust detection method for higher order periodicity. Easily recognizable HOR power spectrum is characterized by hierarchical two-level equidistant pattern: higher harmonics of the fundamental HOR-frequency (secondary periodicity) and a subset of pronounced peaks corresponding to constituent monomers (primary periodicity). The number of lower frequency peaks (secondary periodicity) below the frequency of the first primary periodicity peak reveals the size of <it>n</it>mer HOR, i.e., the number <it>n </it>of monomers contained in consensus HOR.</p

Efficient deep learning-based automated diagnosis from echocardiography with contrastive self-supervised learning

Abstract Background Advances in self-supervised learning (SSL) have enabled state-of-the-art automated medical image diagnosis from small, labeled datasets. This label efficiency is often desirable, given the difficulty of obtaining expert labels for medical image recognition tasks. However, most efforts toward SSL in medical imaging are not adapted to video-based modalities, such as echocardiography. Methods We developed a self-supervised contrastive learning approach, EchoCLR, for echocardiogram videos with the goal of learning strong representations for efficient fine-tuning on downstream cardiac disease diagnosis. EchoCLR pretraining involves (i) contrastive learning, where the model is trained to identify distinct videos of the same patient, and (ii) frame reordering, where the model is trained to predict the correct of video frames after being randomly shuffled. Results When fine-tuned on small portions of labeled data, EchoCLR pretraining significantly improves classification performance for left ventricular hypertrophy (LVH) and aortic stenosis (AS) over other transfer learning and SSL approaches across internal and external test sets. When fine-tuning on 10% of available training data (519 studies), an EchoCLR-pretrained model achieves 0.72 AUROC (95% CI: [0.69, 0.75]) on LVH classification, compared to 0.61 AUROC (95% CI: [0.57, 0.64]) with a standard transfer learning approach. Similarly, using 1% of available training data (53 studies), EchoCLR pretraining achieves 0.82 AUROC (95% CI: [0.79, 0.84]) on severe AS classification, compared to 0.61 AUROC (95% CI: [0.58, 0.65]) with transfer learning. Conclusions EchoCLR is unique in its ability to learn representations of echocardiogram videos and demonstrates that SSL can enable label-efficient disease classification from small amounts of labeled data

Biometric contrastive learning for data-efficient deep learning from electrocardiographic images

Objective: Artificial intelligence (AI) detects heart disease from images of electrocardiograms (ECGs). However, traditional supervised learning is limited by the need for large amounts of labeled data. We report the development of Biometric Contrastive Learning (BCL), a self-supervised pretraining approach for label-efficient deep learning on ECG images. Materials and Methods: Using pairs of ECGs from 78 288 individuals from Yale (2000-2015), we trained a convolutional neural network to identify temporally separated ECG pairs that varied in layouts from the same patient. We fine-tuned BCL-pretrained models to detect atrial fibrillation (AF), gender, and LVEF < 40%, using ECGs from 2015 to 2021. We externally tested the models in cohorts from Germany and the United States. We compared BCL with ImageNet initialization and general-purpose self-supervised contrastive learning for images (simCLR). Results: While with 100% labeled training data, BCL performed similarly to other approaches for detecting AF/Gender/LVEF < 40% with an AUROC of 0.98/0.90/0.90 in the held-out test sets, it consistently outperformed other methods with smaller proportions of labeled data, reaching equivalent performance at 50% of data. With 0.1% data, BCL achieved AUROC of 0.88/0.79/0.75, compared with 0.51/0.52/0.60 (ImageNet) and 0.61/0.53/0.49 (simCLR). In external validation, BCL outperformed other methods even at 100% labeled training data, with an AUROC of 0.88/0.88 for Gender and LVEF < 40% compared with 0.83/0.83 (ImageNet) and 0.84/0.83 (simCLR). Discussion and Conclusion: A pretraining strategy that leverages biometric signatures of different ECGs from the same patient enhances the efficiency of developing AI models for ECG images. This represents a major advance in detecting disorders from ECG images with limited labeled data