🤖 AI Summary
This study addresses the challenging problem of reference-free, cross-modal, large-scale 3D volumetric registration between X-ray microscopy (XRM) and light-sheet fluorescence microscopy (LSFM) data, essential for multiscale correlation analysis of bone microstructure and cellular function. Methodologically, we propose a novel two-stage, reference-free registration framework: (1) a coarse stage leveraging surface point-cloud feature extraction and continuous point-cloud registration; and (2) a fine stage employing an improved mutual-correlation-based volumetric registration. Crucially, we introduce a residual-based similarity metric to objectively assess registration quality. Experimental results demonstrate sub-micrometer accuracy—specifically, precise alignment of XRM-resolved bone lacunae with LSFM-labeled osteocytes (localization error < 0.5 μm). This enables significantly enhanced reliability and spatial resolution in structure–function coupling analysis for age-related bone disorders such as osteoporosis.
📝 Abstract
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.