Abstract: Systems and methods can perform self-supervised machine learning for improved medical image analysis. As one example, self-supervised learning on ImageNet, followed by additional self-supervised learning on unlabeled medical images from the target domain of interest, followed by fine-tuning on labeled medical images from the target domain significantly improves the accuracy of medical image classifiers such as, for example diagnostic models. Another example aspect of the present disclosure is directed to a novel Multi-Instance Contrastive Learning (MICLe) method that uses multiple different medical images that share one or more attributes (e.g., multiple images that depict the same underlying pathology and/or the same patient) to construct more informative positive pairs for self-supervised learning.