Hyperspectral Image Restoration and Super-resolution with Physics-Aware Deep Learning for Biomedical Applications

-cross Abstract: Hyperspectral imaging is a powerful bioimaging tool which can uncover novel insights, thanks to its sensitivity to the intrinsic properties of materials. However, this enhanced contrast comes at the cost of system complexity, constrained by an inherent trade-off between spatial, spectral, and temporal resolution. To overcome this limitation, we present a self-supervised deep learning-based approach that restores and enhances pixel resolution post-acquisition without requiring external training data beyond the images to be restored. Fine-tuned using metrics aligned with the imaging model, our physics-aware method achieves a 16$\times$ pixel super-resolution enhancement and a 12$\times$ imaging speedup without the need of additional training data for transfer learning. Applied to both synthetic and experimental data from five different sample types, including healthy and diseased tissues, we demonstrate that the model preserves biological integrity, as we did not detect systematic loss of biological features or biologically consequential hallucinations in tested datasets. We also concretely demonstrate the model's ability to reveal disease-associated metabolic changes that would otherwise remain undetectable. Furthermore, we provide physical insights into the model's inner workings, paving the way for future refinements that could potentially reveal novel high resolution features in an explainable manner. All methods are available as open-source software on GitHub.