Contrastive learning, which aims to capture general representation from unlabeled images to initialize the medical analysis models, has been proven effective in alleviating the high demand for expensive annotations. Current methods mainly focus on instance-wise comparisons to learn the global discriminative features, however, pretermitting the local details to distinguish tiny anatomical structures, lesions, and tissues. To address this challenge, in this paper, we propose a general unsupervised representation learning framework, named local discrimination (LD), to learn local discriminative features for medical images by closely embedding semantically similar pixels and identifying regions of similar structures across different images. Specifically, this model is equipped with an embedding module for pixel-wise embedding and a clustering module for generating segmentation. And these two modules are unified by optimizing our novel region discrimination loss function in a mutually beneficial mechanism, which enables our model to reflect structure information as well as measure pixel-wise and region-wise similarity. Furthermore, based on LD, we propose a center-sensitive one-shot landmark localization algorithm and a shape-guided cross-modality segmentation model to foster the generalizability of our model. When transferred to downstream tasks, the learned representation by our method shows a better generalization, outperforming representation from 18 state-of-the-art (SOTA) methods and winning 9 out of all 12 downstream tasks. Especially for the challenging lesion segmentation tasks, the proposed method achieves significantly better performance.

Automatic rib fracture recognition from chest X-ray images is clinically important yet challenging due to weak saliency of fractures. Weakly Supervised Learning (WSL) models recognize fractures by learning from large-scale image-level labels. In WSL, Class Activation Maps (CAMs) are considered to provide spatial interpretations on classification decisions. However, the high-responding regions, namely Supporting Regions of CAMs may erroneously lock to regions irrelevant to fractures, which thereby raises concerns on the reliability of WSL models for clinical applications. Currently available Mixed Supervised Learning (MSL) models utilize object-level labels to assist fitting WSL-derived CAMs. However, as a prerequisite of MSL, the large quantity of precisely delineated labels is rarely available for rib fracture tasks. To address these problems, this paper proposes a novel MSL framework. Firstly, by embedding the adversarial classification learning into WSL frameworks, the proposed Biased Correlation Decoupling and Instance Separation Enhancing strategies guide CAMs to true fractures indirectly. The CAM guidance is insensitive to shape and size variations of object descriptions, thereby enables robust learning from bounding boxes. Secondly, to further minimize annotation cost in MSL, a CAM-based Active Learning strategy is proposed to recognize and annotate samples whose Supporting Regions cannot be confidently localized. Consequently, the quantity demand of object-level labels can be reduced without compromising the performance. Over a chest X-ray rib-fracture dataset of 10966 images, the experimental results show that our method produces rational Supporting Regions to interpret its classification decisions and outperforms competing methods at an expense of annotating 20% of the positive samples with bounding boxes.