Computational multimodal imaging with fluorescence diffraction tomography (FDT)

Fluorescence and quantitative phase imaging provide complementary information—fluorescence offers molecular specificity, while phase imaging reveals label-free biophysical properties like refractive index heterogeneity. However, integrating these modalities for thick samples remains challenging. We present fluorescence diffraction tomography (FDT), a method for quantitative 3D refractive index reconstruction from fluorescence images. Using one-photon and two-photon microscopy with advanced algorithms, including physics-informed deep learning, FDT enables multimodal, multiplexed imaging of thick tissues. This approach opens new possibilities for studying the interaction of labeled and label-free structures in complex biological systems.