IDA-MIL: Classification of Glomerular with Spike-like Projections via Multiple Instance Learning with Instance-level Data Augmentation

Tiny spike-like projections on the basement membrane of glomeruli are the main pathological feature of membranous nephropathy at stage II (MN II), which is the most significant stage for the diagnosis and treatment of renal disease. Pathological technology is the gold standard in the diagnosis of spike-like and other MNs, and automatic classification of spike-like projection is a crucial step in assisting pathologists in their diagnosis. However, owing to hard-to-label spile-like projections and the scarcity of patient data, classification of glomeruli with spike-like projections based on supervised learning methods is a challenging task.To overcome the aforementioned problems, the idea of integrating weakly-supervised learning and data augmentation methods is utilized in designing the classification framework. Specifically, a multiple instance learning with instance-level data augmentation (IDA-MIL) method for the classification of glomeruli with spike-like projections is established in this paper. The proposed classification framework first trains the MIL model on a dataset with image-level labels, and the well-trained MIL model is used to extract instances that include spike-like projections in the whole glomerular image. Then, rather than using an image-level generative adversarial network (ImgGAN), an instance-level generative adversarial network (InsGAN) based on the StyleGAN2-ADA model is trained on the spike-like instances obtained by the MIL model and synthesizes new spike-like projection instances. Finally, the synthesized spike-like instances are extended to the training dataset to further improve the classification performance of MIL.The designed IDA-MIL model is verified and evaluated from two aspects based on the in-house dataset. On the one hand, the performance comparisons between InsGAN and ImgGAN on five metrics, which involve FID, KID, Precision, Recall and IS, show that InsGAN obtains a better score and can synthesize effective spike-like projections. However, the proposed IDA-MIL model achieves the best classification performance with an accuracy of 0.9405. Then, to make nephrologists believe the inference result of the proposed model, we use heatmap technology to visualize the basis of the model inferences and show the top 4 probability spike-like instances per glomerulus. Furthermore, we analyze the correlation between the disease and the proportion of spike-like instances in bags from historical cases.Compared with the ImgGAN, the InsGAN can synthesize natural and varied spike-like projections, which results in the classification performance of the MIL model achieving great improvement by adding synthesized instance samples into the training dataset. The heatmap of spike-like inferences and the proportion of spike-like instances can help nephrologists to make a preliminary reliable diagnosis in clinical practice. This work provides a valuable reference for medical image classification with limited data and small-scale lesions based on deep learning.