arXiv:2507.18177v1 Announce Type: cross Abstract: In data-scarce scenarios, deep learning models often overfit to noise and irrelevant patterns, which limits their ability to generalize to unseen samples. To address these challenges in medical image segmentation, we introduce Diff-UMamba, a novel architecture that combines the UNet framework with the mamba mechanism for modeling long-range dependencies. At the heart of Diff-UMamba is a Noise Reduction Module (NRM), which employs a signal differencing strategy to suppress noisy or irrelevant activations within the encoder. This encourages the model to filter out spurious features and enhance task-relevant representations, thereby improving its focus on clinically meaningful regions. As a result, the architecture achieves improved segmentation accuracy and robustness, particularly in low-data settings. Diff-UMamba is evaluated on multiple public datasets, including MSD (lung and pancreas) and AIIB23, demonstrating consistent performance gains of 1-3% over baseline methods across diverse segmentation tasks. To further assess performance under limited-data conditions, additional experiments are conducted on the BraTS-21 dataset by varying the proportion of available training samples. The approach is also validated on a small internal non-small cell lung cancer (NSCLC) dataset for gross tumor volume (GTV) segmentation in cone beam CT (CBCT), where it achieves a 4-5% improvement over the baseline.