Optical microscopy has evolved from quantitative phase imaging to three-dimensional tomography, yet existing label-free techniques face critical limitations in computational complexity and contrast enhancement. Here, we present high-frequency scattering tomography (HFST), a robust label-free platform integrating angled LED illumination with z-scanning to decode three-dimensional structural information through scattered field filtering analysis. HFST alleviates complex reconstruction processes while achieving contrast enhancement. HFST is demonstrated through three-dimensional imaging of 200-nm fluorescent polystyrene microspheres and sub-organelles inside COS7 cells, especially low-density regions inside the nucleolus. The results reveal that HFST establishes a new paradigm for non-invasive and robust volumetric analysis in biomedical research.
Ma et al. (2026) studied this question.