Continuous 3D Spatial Transcriptomics Reconstruction via Histology-Informed Implicit Neural Representations

Three-dimensional spatial transcriptomics (3D ST) enables the analysis of gene-expression patterns across tissue depths. However, 3D ST measurements are acquired from discrete 2D tissue sections, which are often sparsely sampled due to high acquisition costs. To address this limitation, we propose a histology-informed multi-task implicit neural representation (HIM-INR) for continuous 3D gene-expression reconstruction from sparse ST observations. HIM-INR jointly reconstructs gene-expression profiles and histological representations using an INR with a shared backbone, leveraging densely sampled histological images as auxiliary spatial supervision. Once trained, HIM-INR predicts gene expression at arbitrary 3D coordinates without requiring histological images. Experiments on two 3D ST datasets demonstrate improved reconstruction over existing methods, particularly as the number of missing ST sections increases.