CausalDisenSeg: A Causality-Guided Disentanglement Framework with Counterfactual Reasoning for Robust Brain Tumor Segmentation Under Missing Modalities

Existing brain tumor segmentation methods usually utilize multiple Magnetic Resonance Imaging (MRI) modalities in brain tumor images for segmentation, which can achieve better segmentation performance. However, in clinical applications, some modalities are often missing due to resource constraints, resulting in significant performance degradation for methods that rely on complete modality segmentation. In this paper, we propose a Multimodal feature distillation with Mamba-Transformer hybrid network (MMTSeg) for accurate brain tumor segmentation with missing modalities. We first employ a Multimodal Feature Distillation (MFD) module to distill feature-level multimodal knowledge into different unimodalities to extract complete modality information. We further develop an Unimodal Feature Enhancement (UFE) module to model the semantic relationship between global and local information. Finally, we built a Cross-Modal Fusion (CMF) module to explicitly align the global correlations across modalities, even when some modalities are missing. Complementary features within and across modalities are refined by the Mamba-Transformer hybrid architectures in both the UFE and CMF modules, dynamically capturing long-range dependencies and global semantic information for complex spatial contexts. A boundary-wise loss function is employed as the segmentation loss of the proposed MMTSeg to minimize boundary discrepancies for a distance-based metric. Our ablation study demonstrates the importance of the proposed feature enhancement and fusion modules in the proposed network and the Transformer with Mamba block for improving the performance of brain tumor segmentation with missing modalities. Extensive experiments on the BraTS 2018 and BraTS 2020 datasets demonstrate that the proposed MMTSeg framework outperforms state-of-the-art methods when modalities are missing.

Accurate brain tumor segmentation using multi-parametric MRI is critical for effective treatment planning. However, in clinical settings, complete acquisition of all MRI sequences is not always possible. The absence of certain MRI modalities results in substantial performance degradation in existing segmentation methods, which typically rely on naive feature concatenation or direct fusion strategies. To address this limitation, we propose a novel segmentation model D3Seg which is designed to maintain stable performance under missing-modality settings. D3Seg introduces Multi-hop Modality Graph Fusion (MMGF) to model higher-order inter-modality dependencies, a lightweight diffusion-based imputation mechanism to compensate for missing T1ce and FLAIR feature representations in latent space, and probability-space decision refinement to mitigate dominant-class overconfidence and improve delineation of underrepresented tumor subregions. We evaluate the proposed D3Seg model on BraTS 2023 Glioma as the primary benchmark and further test it on a subset of the external BraTS 2023 Meningioma cohort to assess generalization across tumor pathologies. The results are compared with the state-of-the-art models under different missing-modality conditions. The proposed model achieves approximately 1.5-2.0% Dice improvement on enhancing tumor (ET) and around 1.0% on tumor core (TC) across multiple missing-modality configurations compared to the current state-of-the-art model on BraTS Glioma dataset. Cross-cohort evaluation on BraTS Meningioma dataset demonstrates the generalizability of the proposed model, showing consistent improvements in the challenging TC and ET regions, with approximately 1.5-3.0% and 1.5-6.5% gains respectively across several missing-modality configurations.

Multimodal brain tumor segmentation typically leverages multiple MRI modalities, yet incomplete modality acquisition is common in clinical practice due to protocol heterogeneity and scan failures. Although recent methods maintain segmentation accuracy under missing modality conditions, they frequently overlook prediction reliability, leading to miscalibrated confidence estimates that hinder clinical adoption. Existing calibration techniques are largely modality-agnostic or assume that prediction difficulty decreases monotonically as additional modalities become available. However, in brain tumor segmentation, prediction difficulty depends primarily on which modalities are absent rather than how many, leading to combination-specific and spatially heterogeneous calibration errors. To address this, we propose Missing Modality-Aware Local Temperature Scaling (MMA-LTS), a post-hoc voxel-wise confidence calibration method. It estimates a spatially adaptive temperature field conditioned on a modality-availability learnable token and a voxel-wise difficulty score. Experiments on BraTS 2020 and FeTS 2024 show that MMA-LTS improves calibration while preserving the segmentation accuracy of state-of-the-art models across diverse missing-modality scenarios, thereby enhancing trustworthiness toward clinical deployment.