Improving Cross-Domain Generalization in Brain MRIs via Feature Space Stability Regularization

Deep learning models for brain tumor classification from magnetic resonance imaging (MRI) often achieve high in-dataset accuracy but exhibit substantial performance degradation when evaluated on unseen clinical data due to domain shift arising from variations in imaging protocols and intensity distributions. Existing approaches largely rely on architectural scaling or parameter-level regularization, which do not explicitly constrain the stability of learned feature representations. This manuscript proposes Feature Space Stability Regularization (FSSR), a lightweight and model-agnostic training framework that enforces consistency in latent feature representations under realistic, MRI-safe-intensity perturbations. FSSR introduces an auxiliary feature space loss that minimizes the ℓ2 distance between normalized embeddings extracted from the input MRI images and their intensity-perturbed counterparts, alongside standard cross-entropy supervision. This manuscript evaluated FSSR across three convolutional backbones, ResNet-18, ResNet-34, and DenseNet-121, trained exclusively on the Kaggle Brain MRI dataset. Feature space analysis demonstrates that FSSR consistently reduces mean feature deviation and variance across architectures, indicating more stable internal representations. Generalization is assessed via zero-shot evaluation on the fully unseen BRISC-2025 dataset without retraining or fine-tuning. On the source domain, the best-performing configuration achieves 97.71% accuracy and 97.55% macro-F1. Under domain shift, FSSR improves external accuracy by up to 8.20 percentage points and the macro-F1 by up to 12.50 percentage points, with DenseNet-121 achieving a 96.70% accuracy and 96.87% macro-F1 at a domain gap of only 0.94%. Confusion matrix analysis further reveals the reduced class confusion and more stable recall across challenging tumor categories, demonstrating that feature-level stability is a key factor for robust brain MRI classification under domain shift.