This article presents a novel positive and negative set selection strategy for contrastive learning of medical images based on labels that can be extracted from clinical data. In the medical field, there exists a variety of labels for data that serve different purposes at different stages of a diagnostic and treatment process. Clinical labels and biomarker labels are two examples. In general, clinical labels are easier to obtain in larger quantities because they are regularly collected during routine clinical care, while biomarker labels require expert analysis and interpretation to obtain. Within the field of ophthalmology, previous work has shown that clinical values exhibit correlations with biomarker structures that manifest within optical coherence tomography (OCT) scans. We exploit this relationship by using the clinical data as pseudo-labels for our data without biomarker labels in order to choose positive and negative instances for training a backbone network with a supervised contrastive loss. In this way, a backbone network learns a representation space that aligns with the clinical data distribution available. Afterwards, we fine-tune the network trained in this manner with the smaller amount of biomarker labeled data with a cross-entropy loss in order to classify these key indicators of disease directly from OCT scans. We also expand on this concept by proposing a method that uses a linear combination of clinical contrastive losses. We benchmark our methods against state of the art self-supervised methods in a novel setting with biomarkers of varying granularity. We show performance improvements by as much as 5% in total biomarker detection AUROC.

In this paper, we propose a novel selection strategy for contrastive learning for medical images. On natural images, contrastive learning uses augmentations to select positive and negative pairs for the contrastive loss. However, in the medical domain, arbitrary augmentations have the potential to distort small localized regions that contain the biomarkers we are interested in detecting. A more intuitive approach is to select samples with similar disease severity characteristics, since these samples are more likely to have similar structures related to the progression of a disease. To enable this, we introduce a method that generates disease severity labels for unlabeled OCT scans on the basis of gradient responses from an anomaly detection algorithm. These labels are used to train a supervised contrastive learning setup to improve biomarker classification accuracy by as much as 6% above self-supervised baselines for key indicators of Diabetic Retinopathy.

Clinical diagnosis of the eye is performed over multifarious data modalities including scalar clinical labels, vectorized biomarkers, two-dimensional fundus images, and three-dimensional Optical Coherence Tomography (OCT) scans. Clinical practitioners use all available data modalities for diagnosing and treating eye diseases like Diabetic Retinopathy (DR) or Diabetic Macular Edema (DME). Enabling usage of machine learning algorithms within the ophthalmic medical domain requires research into the relationships and interactions between all relevant data over a treatment period. Existing datasets are limited in that they neither provide data nor consider the explicit relationship modeling between the data modalities. In this paper, we introduce the Ophthalmic Labels for Investigating Visual Eye Semantics (OLIVES) dataset that addresses the above limitation. This is the first OCT and near-IR fundus dataset that includes clinical labels, biomarker labels, disease labels, and time-series patient treatment information from associated clinical trials. The dataset consists of 1268 near-IR fundus images each with at least 49 OCT scans, and 16 biomarkers, along with 4 clinical labels and a disease diagnosis of DR or DME. In total, there are 96 eyes' data averaged over a period of at least two years with each eye treated for an average of 66 weeks and 7 injections. We benchmark the utility of OLIVES dataset for ophthalmic data as well as provide benchmarks and concrete research directions for core and emerging machine learning paradigms within medical image analysis.

We propose a deep-learning based annotation-efficient framework for vessel detection in ultra-widefield (UWF) fundus photography (FP) that does not require de novo labeled UWF FP vessel maps. Our approach utilizes concurrently captured UWF fluorescein angiography (FA) images, for which effective deep learning approaches have recently become available, and iterates between a multi-modal registration step and a weakly-supervised learning step. In the registration step, the UWF FA vessel maps detected with a pre-trained deep neural network (DNN) are registered with the UWF FP via parametric chamfer alignment. The warped vessel maps can be used as the tentative training data but inevitably contain incorrect (noisy) labels due to the differences between FA and FP modalities and the errors in the registration. In the learning step, a robust learning method is proposed to train DNNs with noisy labels. The detected FP vessel maps are used for the registration in the following iteration. The registration and the vessel detection benefit from each other and are progressively improved. Once trained, the UWF FP vessel detection DNN from the proposed approach allows FP vessel detection without requiring concurrently captured UWF FA images. We validate the proposed framework on a new UWF FP dataset, PRIME-FP20, and on existing narrow-field FP datasets. Experimental evaluation, using both pixel-wise metrics and the CAL metrics designed to provide better agreement with human assessment, shows that the proposed approach provides accurate vessel detection, without requiring manually labeled UWF FP training data.

While recent advances in deep learning have significantly advanced the state of the art for vessel detection in color fundus (CF) images, the success for detecting vessels in fluorescein angiography (FA) has been stymied due to the lack of labeled ground truth datasets. We propose a novel pipeline to detect retinal vessels in FA images using deep neural networks (DNNs) that reduces the effort required for generating labeled ground truth data by combining two key components: cross-modality transfer and human-in-the-loop learning. The cross-modality transfer exploits concurrently captured CF and fundus FA images. Binary vessels maps are first detected from CF images with a pre-trained neural network and then are geometrically registered with and transferred to FA images via robust parametric chamfer alignment to a preliminary FA vessel detection obtained with an unsupervised technique. Using the transferred vessels as initial ground truth labels for deep learning, the human-in-the-loop approach progressively improves the quality of the ground truth labeling by iterating between deep-learning and labeling. The approach significantly reduces manual labeling effort while increasing engagement. We highlight several important considerations for the proposed methodology and validate the performance on three datasets. Experimental results demonstrate that the proposed pipeline significantly reduces the annotation effort and the resulting deep learning methods outperform prior existing FA vessel detection methods by a significant margin. A new public dataset, RECOVERY-FA19, is introduced that includes high-resolution ultra-widefield images and accurately labeled ground truth binary vessel maps.