Improving Neuropathological Reconstruction Fidelity via AI Slice Imputation

Abstract Neuropathological analyses benefit from spatially precise volumetric reconstructions that enhance anatomical delineation and improve morphometric accuracy. Prior work has shown the feasibility of reconstructing 3D brain volumes from 2D dissection photographs. However, these outputs often exhibit coarse, overly smooth reconstructions of structures, especially under high anisotropy (i.e., reconstructions from thick slabs). Here, we introduce a computationally efficient super-resolution step that imputes slices to generate anatomically consistent isotropic volumes from anisotropic 3D reconstructions of dissection photographs.By training on domain-randomized synthetic data, we ensure that our method generalizes across dissection protocols and remains robust to large slab thicknesses and hallucination effects. The imputed volumes yield improved automated segmentations, achieving higher Dice scores, particularly in cortical and white matter regions. Validation on surface reconstruction and atlas registration tasks demonstrates more accurate cortical surfaces and alignment with the target template. By enhancing the resolution and anatomical fidelity of photograph-based reconstructions, our approach strengthens the bridge between neuropathology and neuroimaging. Our method is publicly available at https://surfer.nmr.mgh.harvard.edu/fswiki/mri_3d_photo_recon.