Nonlinear optical endomicroscopy for label-free functional histology in vivo

Wenxuan Liang, Gunnsteinn Hall, Bernhard Messerschmidt, Ming Jun Li, Xingde Li

Research output: Contribution to journalArticlepeer-review

55 Scopus citations


This manuscript reports on the first two-photon, label-free, metabolic imaging of biological tissues in vivo at histological resolution on an extremely compact, fiber-optic endomicroscopy platform. This system provides new opportunities for performing non-invasive and functional histological imaging of internal organs in vivo, in situ and in real time. As a routine clinical procedure, traditional histology has made significant impacts on medicine. However, the procedure is invasive and time consuming, suffers random sampling errors, and cannot provide in vivo functional information. The technology reported here features an extremely compact and flexible fiber-optic probe ∼2 mm in diameter, enabling direct access to internal organs. Unprecedented two-photon imaging quality comparable to a large bench-top laser scanning microscope was achieved through technological innovations in double-clad fiber optics and miniature objective lenses (among many others). In addition to real-time label-free visualization of biological tissues in situ with subcellular histological detail, we demonstrated for the first time in vivo two-photon endomicroscopic metabolic imaging on a functioning mouse kidney model. Such breakthroughs in nonlinear endoscopic imaging capability present numerous promising opportunities for paradigm-shifting applications in both clinical diagnosis and basic research.

Original languageEnglish (US)
Article numbere17082
JournalLight: Science and Applications
Issue number11
StatePublished - Nov 3 2017


  • functional histology in vivo
  • label-free imaging
  • nonlinear endomicroscopy
  • two-photon metabolic imaging

ASJC Scopus subject areas

  • Electronic, Optical and Magnetic Materials
  • Atomic and Molecular Physics, and Optics


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