Reference-Free Multi-Modality Volume Registration of X-Ray Microscopy and Light-Sheet Fluorescence Microscopy

Recently, X-ray microscopy (XRM) and light-sheet fluorescence microscopy (LSFM) have emerged as two pivotal imaging tools in preclinical research on bone remodeling diseases, offering micrometer-level resolution. Integrating these complementary modalities provides a holistic view of bone microstructures, facilitating function-oriented volume analysis across different disease cycles. However, registering such independently acquired large-scale volumes is extremely challenging under real and reference-free scenarios. This paper presents a fast two-stage pipeline for volume registration of XRM and LSFM. The first stage extracts the surface features and employs two successive point cloud-based methods for coarse alignment. The second stage fine-tunes the initial alignment using a modified cross-correlation method, ensuring precise volumetric registration. Moreover, we propose residual similarity as a novel metric to assess the alignment of two complementary modalities. The results imply robust gradual improvement across the stages. In the end, all correlating microstructures, particularly lacunae in XRM and bone cells in LSFM, are precisely matched, enabling new insights into bone diseases like osteoporosis which are a substantial burden in aging societies.