The universality of deep neural networks across different modalities and their generalization capabilities to unseen domains play an essential role in medical image segmentation. The recent Segment Anything Model (SAM) has demonstrated its potential in both settings. However, the huge computational costs, demand for manual annotations as prompts and conflict-prone decoding process of SAM degrade its generalizability and applicability in clinical scenarios. To address these issues, we propose an efficient self-prompting SAM for universal domain-generalized medical image segmentation, named ESP-MedSAM. Specifically, we first devise the Multi-Modal Decoupled Knowledge Distillation (MMDKD) strategy to construct a lightweight semi-parameter sharing image encoder that produces discriminative visual features for diverse modalities. Further, we introduce the Self-Patch Prompt Generator (SPPG) to automatically generate high-quality dense prompt embeddings for guiding segmentation decoding. Finally, we design the Query-Decoupled Modality Decoder (QDMD) that leverages a one-to-one strategy to provide an independent decoding channel for every modality. Extensive experiments indicate that ESP-MedSAM outperforms state-of-the-arts in diverse medical imaging segmentation tasks, displaying superior modality universality and generalization capabilities. Especially, ESP-MedSAM uses only 4.5\% parameters compared to SAM-H. The source code is available at https://github.com/xq141839/ESP-MedSAM.
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