Nonlinear optical endomicroscopy for label-free functional histology <italic style="font-style: italic">in vivo</italic>

Wenxuan Liang; Gunnsteinn Hall; Bernhard Messerschmidt; Ming-Jun Li; Xingde Li

doi:10.1038/lsa.2017.82

Go to Nature Website

Your Location：

Home >

Browse articles >

Nonlinear optical endomicroscopy for label-free functional histology in vivo

Original Articles

- Nonlinear optical endomicroscopy for label-free functional histology in vivo
- Light: Science & Applications Vol. 6, Issue 4, (2017)
- Affiliations：
  
  1.Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21205, USA
  2.GRINTECH GmbH, Jena 07745, Germany
  3.Science and Technology Division, Corning Incorporated, Corning, NY 14831, USA
- Author bio：
  
  X Li, E-mail: xingde@jhu.edu
- Funds：
- DOI：10.1038/lsa.2017.82
  CLC：
- Published：2017-12，
  
  Published Online：10 May 2017，
  
  Received：01 January 2017，
  
  Revised：06 May 2017，
  
  Accepted：07 May 2017
- Accepted：
Scan QR Code
Liang, W. X. et al. Nonlinear optical endomicroscopy for label-free functional histology in vivo. Light: Science & Applications, 6, e17082 (2017).
DOI：

Liang, W. X. et al. Nonlinear optical endomicroscopy for label-free functional histology in vivo. Light: Science & Applications, 6, e17082 (2017). DOI： 10.1038/lsa.2017.82.

摘要

Abstract

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.

关键词

Keywords

functional histology in vivolabel-free imagingnonlinear endomicroscopytwo-photon metabolic imaging

references

Kiesslich R, Goetz M, Vieth M, Galle PR, Neurath MF. Technology insight: confocal laser endoscopy forin vivodiagnosis of colorectal cancer.Nat Clin Pract Oncol2007;4: 480–490..

Mondal SB, Gao SK, Zhu N, Liang RG, Gruev Vet al. Real-time fluorescence image-guided oncologic surgery.Adv Cancer Res2014;124: 171–211..

Huang SH, Heikal AA, Webb WW. Two-photon fluorescence spectroscopy and microscopy of NAD(P)H and flavoprotein.Biophys J2002;82: 2811–2825..

Campagnola PJ, Loew LM. Second-harmonic imaging microscopy for visualizing biomolecular arrays in cells, tissues and organisms.Nat Biotechnol2003;21: 1356–1360..

Quinn KP, Sridharan GV, Hayden RS, Kaplan DL, Lee Ket al. Quantitative metabolic imaging using endogenous fluorescence to detect stem cell differentiation.Sci Rep2013;3: 3432..

Denk W, Strickler JH, Webb WW. Two-photon laser scanning fluorescence microscopy.Science1990;248: 73–76..

Flusberg BA, Cocker ED, Piyawattanametha W, Jung JC, Cheung ELMet al. Fiber-optic fluorescence imaging.Nat Methods2005;2: 941–950..

Helmchen F, Denk W. Deep tissue two-photon microscopy.Nat Methods2005;2: 932–940..

Zipfel WR, Williams RM, Webb WW. Nonlinear magic: multiphoton microscopy in the biosciences.Nat Biotechnol2003;21: 1369–1377..

Xu C, Zipfel W, Shear JB, Williams RM, Webb WW. Multiphoton fluorescence excitation: new spectral windows for biological nonlinear microscopy.Proc Natl Acad Sci USA1996;93: 10763–10768..

Drobizhev M, Makarov NS, Tillo SE, Hughes TE, Rebane A. Two-photon absorption properties of fluorescent proteins.Nat Methods2011;8: 393–399..

Myaing MT, MacDonald DJ, Li XD. Fiber-optic scanning two-photon fluorescence endoscope.Opt Lett2006;31: 1076–1078..

Fu L, Jain A, Xie HK, Cranfield C, Gu M. Nonlinear optical endoscopy based on a double-clad photonic crystal fiber and a MEMS mirror.Opt Express2006;14: 1027–1032..

Fu L, Jain A, Cranfield C, Xie HK, Gu M. Three-dimensional nonlinear optical endoscopy.J Biomed Opt2007;12: 040501..

Fu L, Gu M. Fibre-optic nonlinear optical microscopy and endoscopy.J Microsc2007;226: 195–206..

Le Harzic R, Riemann I, Weinigel M, König K, Messerschmidt B. Rigid and high-numerical-aperture two-photon fluorescence endoscope.Appl Opt2009;48: 3396–3400..

Piyawattanametha W, Cocker ED, Burns LD, Barretto RPJ, Jung JCet al.In vivobrain imaging using a portable 2.9g two-photon microscope based on a microelectromechanical systems scanning mirror.Opt Lett2009;34: 2309–2311..

Wu YC, Leng YX, Xi JF, Li XD. Scanning all-fiber-optic endomicroscopy system for 3D nonlinear optical imaging of biological tissues.Opt Express2009;17: 7907–7915..

Wu YC, Xi JF, Cobb MJ, Li XD. Scanning fiber-optic nonlinear endomicroscopy with miniature aspherical compound lens and multimode fiber collector.Opt Lett2009;34: 953–955..

Zhao YB, Nakamura H, Gordon RJ. Development of a versatile two-photon endoscope for biological imaging.Biomed Opt Express2010;1: 1159–1172..

Rivera DR, Brown CM, Ouzounov DG, Pavlova I, Kobat Det al. Compact and flexible raster scanning multiphoton endoscope capable of imaging unstained tissue.Proc Natl Acad Sci USA2011;108: 17598–17603..

Brown CM, Rivera DR, Pavlova I, Ouzounov DG, Williams WOet al.In vivoimaging of unstained tissues using a compact and flexible multiphoton microendoscope.J Biomed Opt2012;17: 040505..

Ducourthial G, Leclerc P, Mansuryan T, Fabert M, Brevier Jet al. Development of a real-time flexible multiphoton microendoscope for label-free imaging in a live animal.Sci Rep2015;5: 18303..

Liang WX, Murari K, Zhang YY, Chen YP, Li MJet al. Increased illumination uniformity and reduced photodamage offered by the Lissajous scanning in fiber-optic two-photon endomicroscopy.J Biomed Opt2012;17: 021108..

Dudley DJ, Branch DW, Edwin SS, Mitchell MD. Induction of preterm birth in mice by RU486.Biol Reprod1996;55: 992–995..

Akins ML, Luby-Phelps K, Mahendroo M. Second harmonic generation imaging as a potential tool for staging pregnancy and predicting preterm birth.J Biomed Opt2010;15: 026020..

Zhang Y, Akins ML, Murari K, Xi J, Li M-Jet al. A compact fiber-optic SHG scanning endomicroscope and its application to visualize cervical remodeling during pregnancy.Proc Natl Acad Sci USA2012;109: 12878–12883..

Antonyuk BP, Antonyuk VB. Second-harmonic generation in Ge-doped silica fibres: experiment and theory.J Mod Opt1998;45: 257–268..

Udovich JA, Kirkpatrick ND, Kano A, Tanbakuchi A, Utzinger Uet al. Spectral background and transmission characteristics of fiber optic imaging bundles.Appl Opt2008;47: 4560–4568..

Chang Y-C, Ye JY, Thomas T, Chen Y, Baker JRet al. Two-photon fluorescence correlation spectroscopy through a dual-clad optical fiber.Opt Express2008;16: 12640–12649..

Engelbrecht CJ, Johnston RS, Seibel EJ, Helmchen F. Ultra-compact fiber-optic two-photon microscope for functional fluorescence imagingin vivo.Opt Express2008;16: 5556–5564..

Stone T, George N. Hybrid diffractive-refractive lenses and achromats.Appl Opt1988;27: 2960–2971..

Suematsu M, Oda M, Suzuki H, Kaneko H, Watanabe Net al. Intravital and electron microscopic observation of Ito cells in rat hepatic microcirculation.Microvasc Res1993;46: 28–42..

Orzekowsky-Schroeder R, Klinger A, Martensen B, Blessenohl M, Gebert Aet al.In vivospectral imaging of different cell types in the small intestine by two-photon excited autofluorescence.J Biomed Opt2011;16: 116025..

Skala MC, Riching KM, Gendron-Fitzpatrick A, Eickhoff J, Eliceiri KWet al.In vivomultiphoton microscopy of NADH and FAD redox states, fluorescence lifetimes, and cellular morphology in precancerous epithelia.Proc Natl Acad Sci USA2007;104: 19494–19499..

Hall AM, Rhodes GJ, Sandoval RM, Corridon PR, Molitoris BA.In vivomultiphoton imaging of mitochondrial structure and function during acute kidney injury.Kidney Int2013;83: 72–83..

Hall AM, Unwin RJ, Parker N, Duchen MR. Multiphoton imaging reveals differences in mitochondrial function between nephron segments.J Am Soc Nephrol2009;20: 1293–1302..

Views

Downloads

CSCD

Alert me when the article has been cited

Submit

Tools

Publicity Resources

No data

Related Author

No data

Related Institution

No data

⁰

Nonlinear optical endomicroscopy for label-free functional histology in vivo

DOI：10.1038/lsa.2017.82

摘要

Abstract

关键词

Keywords

references