MLDA-Net: Multi-Level Deep Aggregation Network for 3D Nuclei Instance Segmentation

Segmentation of cell nuclei from three-dimensional (3D) volumetric fluorescence microscopy images is crucial for biological and clinical analyses. In recent years, convolutional neural networks have become the reliable 3D medical image segmentation standard. However, convolutional layers are limited by their finite receptive fields and weight-sharing mechanisms. Consequently, they struggle to effectively model long-range dependencies and spatial correlations, which may lead to inadequate nuclei segmentation. Moreover, the diversity in nuclear appearance and density poses additional challenges. This work proposes a lightweight multi-layer deep aggregation network, MLDA-Net, incorporating Wide Receptive Field Attention (WRFA). This module effectively simulates the large receptive field generated by self-attention in the Swin Transformer while requiring fewer model parameters. This design implements an extended global sensory field that enhances the ability to capture a wide range of spatial information. In addition, the multiple cross-attention (MCA) module in MLDA-Net enhances the output features of different resolutions from the encoder while maintaining global effectiveness. The Multi-Path Aggregation Feature Pyramid Network (MAFPN) receives multi-scale outputs from the MCA module, generating a robust hierarchical feature pyramid for the final prediction. MLDA-Net outperforms state-of-the-art networks, including 3DU-Net, nnFormer, UNETR, SwinUNETR, and 3DUXNET, on the 3D volumetric datasets NucMM and MitoEM. It achieves average performance improvements of 4% to 7% in F1 score, MIoU, and PQ metrics, thereby establishing new benchmark results.