A patch distribution-based active learning method for multiple instance Alzheimer's disease diagnosis

•We introduce a block-wise Hash difference measure to replace Euclidean distance, which significantly preserves spatial and structural information within each patch.•We design a Patch-Level Global and Local Attention-based Multi-Instance deep Learning Model that utilizes attention mechanisms to enhance Alzheimer's disease diagnosis performance and interpretability.•We construct a Patch-Level Instance Distribution-based Active Learning Strategy which aim at selecting the least discriminative samples from the candidate data set based on both sample-level and decision-level Gaussian distributions, and incorporating them into the training set to minimize labeling costs.•Experiments demonstrated the effectiveness of our proposed methods. Medical data, particularly the complex brain imaging structures, acquisition presents significant difficulties and high diagnostic expenses, resulting in a scarcity of the trainable samples in the real-world scenarios. To overcome this limitation, we present an active learning-based sampling strategy that selects the most informative samples from the unlabeled candidate sample pool for expert annotation, leading to high classification performance with a reduced number of training samples. This study adopts a patch-level perspective and introduces a multi-instance learning framework for Alzheimer's Disease diagnosis. Initially, a patch pre-selection module is designed to identify pathology-prone regions while excluding background areas and irrelevant information. Subsequently, an inner-patch local attention mechanism block and an outer-patch global attention mechanism block are developed to enhance the extraction of discriminative local and global information by the network model. Finally, an active learning sampling strategy is devised to minimize the costs associated with data acquisition and expert annotation in medical domain. The effectiveness of the proposed network framework and active learning strategy was validated through four sets of control experiments on the ADNI dataset.