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Label-free multimodal optical biopsy reveals biomolecular and morphological features of diabetic kidney tissue in 2D and 3D

Author

Listed:
  • Anthony A. Fung

    (University of California San Diego)

  • Zhi Li

    (University of California San Diego)

  • Craig Boote

    (Cardiff University)

  • Petar Markov

    (EMBL c/o DESY)

  • Joseph P. Gaut

    (Washington University School of Medicine, Department of Pathology and Immunology)

  • Sanjay Jain

    (Washington University in St. Louis)

  • Lingyan Shi

    (University of California San Diego)

Abstract

Kidney disease, the ninth leading cause of death in the United States, suffers from poor diagnostic efficiency (10%). Traditional biopsies use molecular reagents to enhance diagnostic power but are limited by overlapping spatial and chromatic signals, product quality variability, and additional processing. To address these challenges without disrupting routine diagnostics, we implement label-free imaging modalities—stimulated Raman scattering (SRS), second harmonic generation (SHG), and two-photon fluorescence (TPF)—within a single setup. We identify morphological, lipidomic, and metabolic biomarkers in control and diabetic kidney samples at subcellular resolution. Label-free Stimulated Raman Histology (SRH) reveals distinct collagen morphology, mesangial-glomerular volumes, lipid saturation, redox status, and lipid-protein concentrations previously unrecognized in kidney diseases. Using the same tissue section enhances diagnostic value without compromising limited tissue. These multimodal biomarkers broadly deepen the understanding of kidney disease progression by integrating lipidomic, fibrotic, and metabolic data.

Suggested Citation

  • Anthony A. Fung & Zhi Li & Craig Boote & Petar Markov & Joseph P. Gaut & Sanjay Jain & Lingyan Shi, 2025. "Label-free multimodal optical biopsy reveals biomolecular and morphological features of diabetic kidney tissue in 2D and 3D," Nature Communications, Nature, vol. 16(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59163-w
    DOI: 10.1038/s41467-025-59163-w
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    References listed on IDEAS

    as
    1. Wenxu Zhang & Yajuan Li & Anthony A. Fung & Zhi Li & Hongje Jang & Honghao Zha & Xiaoping Chen & Fangyuan Gao & Jane Y. Wu & Huaxin Sheng & Junjie Yao & Dorota Skowronska-Krawczyk & Sanjay Jain & Ling, 2024. "Multi-molecular hyperspectral PRM-SRS microscopy," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    2. Yuzhu Li & Nir Pillar & Jingxi Li & Tairan Liu & Di Wu & Songyu Sun & Guangdong Ma & Kevin Haan & Luzhe Huang & Yijie Zhang & Sepehr Hamidi & Anatoly Urisman & Tal Keidar Haran & William Dean Wallace , 2024. "Virtual histological staining of unlabeled autopsy tissue," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    3. Stéphane Bancelin & Carole Aimé & Ivan Gusachenko & Laura Kowalczuk & Gaël Latour & Thibaud Coradin & Marie-Claire Schanne-Klein, 2014. "Determination of collagen fibril size via absolute measurements of second-harmonic generation signals," Nature Communications, Nature, vol. 5(1), pages 1-8, December.
    4. Lingyan Shi & Chaogu Zheng & Yihui Shen & Zhixing Chen & Edilson S. Silveira & Luyuan Zhang & Mian Wei & Chang Liu & Carmen Sena-Tomas & Kimara Targoff & Wei Min, 2018. "Optical imaging of metabolic dynamics in animals," Nature Communications, Nature, vol. 9(1), pages 1-17, December.
    5. Christoph Kuppe & Mahmoud M. Ibrahim & Jennifer Kranz & Xiaoting Zhang & Susanne Ziegler & Javier Perales-Patón & Jitske Jansen & Katharina C. Reimer & James R. Smith & Ross Dobie & John R. Wilson-Kan, 2021. "Decoding myofibroblast origins in human kidney fibrosis," Nature, Nature, vol. 589(7841), pages 281-286, January.
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