Histological Brain Imaging Super-resolution with Frequency-guided Diffusion Models

High-resolution histological imaging provides essential detail for quantitative brain modeling, yet acquiring whole-brain data at micrometer scale remains technically and economically challenging. This work introduces Brain-SR, a diffusion-based super-resolution framework designed to reconstruct high-resolution cortical sections from low-resolution BigBrain data. Building upon the InvSR paradigm, our method performs resolution enhancement in the latent space of a pretrained variational autoencoder, guided by a task-specific noise-predictor network. A key contribution is a frequency-domain supervision term that compares the magnitude spectra of predicted and target patches, enforcing spectral consistency while remaining robust to local misalignments. Quantitative evaluations demonstrate that Brain-SR achieves substantial improvements in LPIPS (-27%) and FID (-58%) compared to baseline diffusion Super-Resolution, while spectral analysis confirms accurate recovery of the frequency distribution. The resulting reconstructions preserve neuronal structures consistent with high-resolution references, offering a practical step toward large-scale, morphologically faithful brain histology reconstruction. The code is publicly available to support reproducibility: https://github.com/AImageLab-zip/Brain-SR.