A compact microscope setup for multimodal nonlinear imaging in clinics and its application to disease diagnostics

Tobias Meyer; Martin Baumgartl; Thomas Gottschall; Torbjörn Pascher; Andreas Wuttig; Christian Matthäus; Bernd F. M. Romeike; Bernhard R. Brehm; Jens Limpert; Andreas Tünnermann; Orlando Guntinas-Lichius; Benjamin Dietzek; Michael Schmitt; Jürgen Popp

doi:10.1039/C3AN00354J

A compact microscope setup for multimodal nonlinear imaging in clinics and its application to disease diagnostics†

Tobias Meyer,^a Martin Baumgartl,^b Thomas Gottschall,^b Torbjörn Pascher,^cd Andreas Wuttig,^a Christian Matthäus,^a Bernd F. M. Romeike,^e Bernhard R. Brehm,^f Jens Limpert,^b Andreas Tünnermann,^bg Orlando Guntinas-Lichius,^h Benjamin Dietzek,^ai Michael Schmittⁱ and Jürgen Popp*^ai

Author affiliations

* Corresponding authors

^a Institute of Photonic Technology Jena IPHT, Albert-Einstein-Strasse 9, 07745 Jena, Germany
E-mail: juergen.popp@ipht-jena.de
Fax: +49 3641206399
Tel: +49 3641206300

^b Institute of Applied Physics and Abbe Center of Photonics, Friedrich-Schiller-University Jena, Albert-Einstein-Str. 15, 07745 Jena, Germany
E-mail: jens.limpert@uni-jena.de
Fax: +49 3641947802
Tel: +49 3641947811

^c Pascher Instruments AB, Stora Rabybyaväg 24, 22478 Lund, Sweden

^d Department of Chemical Physics Lund University, Kemicentrum, Getingevägen 60, 22241 Lund, Sweden
E-mail: Torbjorn.Pascher@chemphys.lu.se
Fax: +46 46134155
Tel: +46 46134155

^e Institute of Pathology, Department of Neuropathology, Jena University Hospital – Friedrich-Schiller-University, Erlanger Allee 101, 07740 Jena, Germany
E-mail: Bernd.Romeike@med.uni-jena.de
Fax: +49 36419324752
Tel: +49 36419324755

^f Catholic Clinic – Koblenz, Internal Medicine & Cardiology, Rudolf Virchow Str. 9, 56073 Koblenz, Germany

^g Fraunhofer Institute for Applied Optics and Precision Engineering, Albert-Einstein-Str. 7, 07745 Jena, Germany
E-mail: andreas.tuennermann@iof.fraunhofer.de
Fax: +49 3641807600
Tel: +49 3641807201

^h Department of Otorhinolaryngology, University Hospital, Lessingstr. 2, 07743 Jena, Germany
E-mail: orlando.guntinas@med.uni-jena.de
Fax: +49 3641935129
Tel: +49 3641935127

ⁱ Institute of Physical Chemistry and Abbe Center of Photonics, Friedrich-Schiller-University Jena, Helmholtzweg 4, 07743 Jena, Germany
E-mail: juergen.popp@uni-jena.de
Fax: +49 3641948302
Tel: +49 3641948320

Abstract

The past years have seen increasing interest in nonlinear optical microscopic imaging approaches for the investigation of diseases due to the method's unique capabilities of deep tissue penetration, 3D sectioning and molecular contrast. Its application in clinical routine diagnostics, however, is hampered by large and costly equipment requiring trained staff and regular maintenance, hence it has not yet matured to a reliable tool for application in clinics. In this contribution implementing a novel compact fiber laser system into a tailored designed laser scanning microscope results in a small footprint easy to use multimodal imaging platform enabling simultaneously highly efficient generation and acquisition of second harmonic generation (SHG), two-photon excited fluorescence (TPEF) as well as coherent anti-Stokes Raman scattering (CARS) signals with optimized CARS contrast for lipid imaging for label-free investigation of tissue samples. The instrument combining a laser source and a microscope features a unique combination of the highest NIR transmission and a fourfold enlarged field of view suited for investigating large tissue specimens. Despite its small size and turnkey operation rendering daily alignment dispensable the system provides the highest flexibility, an imaging speed of 1 megapixel per second and diffraction limited spatial resolution. This is illustrated by imaging samples of squamous cell carcinoma of the head and neck (HNSCC) and an animal model of atherosclerosis allowing for a complete characterization of the tissue composition and morphology, i.e. the tissue's morphochemistry. Highly valuable information for clinical diagnostics, e.g. monitoring the disease progression at the cellular level with molecular specificity, can be retrieved. Future combination with microscopic probes for in vivo imaging or even implementation in endoscopes will allow for in vivo grading of HNSCC and characterization of plaque deposits towards the detection of high risk plaques.

This article is part of the themed collection: Optical Diagnosis

Analyst

A compact microscope setup for multimodal nonlinear imaging in clinics and its application to disease diagnostics†

Abstract

Supplementary files

Article information

Download Citation

Permissions

A compact microscope setup for multimodal nonlinear imaging in clinics and its application to disease diagnostics

Social activity

Search articles by author

Spotlight

Advertisements