HistoNeRF: An Accessible and Intelligent Approach for Comprehensive 2D-to-3D Histological Assessment

Histological analysis is central to biomedical research and diagnostic pathology, yet conventional two-dimensional (2D) sectioning captures only limited aspects of tissue architecture. Critical spatial relationships-such as tumor boundaries, stromal organization, and vascular networks-remain obscured, restricting diagnostic accuracy and biological interpretation. HistoNeRF addresses these limitations by adapting Neural Radiance Fields (NeRF) to reconstruct three-dimensional (3D) tissue volumes from routine histological sections. In this study, 84 toluidine blue (TB)-stained murine ovarian sections were digitized, alignment-corrected, and integrated into volumetric models. Tissue segmentation was performed using a convolutional neural network, while visualization was achieved through an interactive, GPU-accelerated interface. To ensure accessibility and reproducibility, a Python-based graphical application (HistoNeRF GUI) was developed following Human-Computer Interaction (HCI) principles and containerized with Docker, allowing installation-free deployment via Docker Hub. HistoNeRF produced high-fidelity 3D reconstructions (SSIM = 0.92; Dice similarity coefficient = 0.88), enabling expert histologists to better visualize follicular structures, stromal compartments, and vascular elements. The containerized GUI was deployed successfully from Docker Hub, providing immediate access to 3D reconstruction without a complex local setup. By overcoming the inherent constraints of 2D microscopy, HistoNeRF enhances the visualization, interpretability, and reproducibility of histological architecture. The HCI-guided, cross-platform interface supports scalability and rapid adoption in digital pathology workflows. Although validation was limited to murine ovarian tissue and one staining protocol, this framework can be extended across tissue types and clinical datasets. HistoNeRF bridges routine histology and 3D volumetric analysis through accurate, interactive reconstructions that advance diagnostic precision and biomedical research. While demonstrated on 84 serial TB-stained ovarian sections, broader validation across tissues, stains, and pathological conditions remains future work; to support this, we provide a Dockerized, modular pipeline for straightforward extension.