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Expanding Multimodal Microscopy by High Spectral Resolution Coherent Anti-Stokes Raman Scattering Imaging for Clinical Disease Diagnostics

Meyer, Tobias ; Chemnitz, Mario ; Baumgartl, Martin ; Gottschall, Thomas ; Pascher, Torbjörn LU ; Matthaeus, Christian ; Romeike, Bernd F. M. ; Brehm, Bernhard R. ; Limpert, Jens and Tuennermann, Andreas , et al. (2013) In Analytical Chemistry 85(14). p.6703-6715
Abstract
Over the past years fast label-free nonlinear imaging modalities providing molecular contrast of endogenous disease markers with subcellular spatial resolution have been emerged. However, applications of these imaging modalities in clinical settings are still at the very beginning. This is because single nonlinear imaging modalities such as second-harmonic generation (SHG) and two-photon excited fluorescence (TPEF) have only limited value for diagnosing diseases due to the small number of endogenous markers. Coherent anti-Stokes Raman scattering (CARS) microscopy on the other hand can potentially be added to SHG and TPEF to visualize a much broader range of marker molecules. However, CARS requires a second synchronized laser source and the... (More)
Over the past years fast label-free nonlinear imaging modalities providing molecular contrast of endogenous disease markers with subcellular spatial resolution have been emerged. However, applications of these imaging modalities in clinical settings are still at the very beginning. This is because single nonlinear imaging modalities such as second-harmonic generation (SHG) and two-photon excited fluorescence (TPEF) have only limited value for diagnosing diseases due to the small number of endogenous markers. Coherent anti-Stokes Raman scattering (CARS) microscopy on the other hand can potentially be added to SHG and TPEF to visualize a much broader range of marker molecules. However, CARS requires a second synchronized laser source and the detection of a certain wavenumber range of the vibrational spectrum to differentiate multiple molecules, which results in increased experimental complexity and often inefficient excitation of SHG and TPEF signals. Here we report the application of a novel near-infrared (NIR) fiber laser of 1 MHz repetition rate, 65 ps pulse duration, and 1 cm(-1) spectral resolution to realize an efficient but experimentally simple SGH/TPEF/multiplex CARS multimodal imaging approach for a label-free characterization of composition of complex tissue samples. This is demonstrated for arterial tissue specimens demonstrating differentiation of elastic fibers, triglycerides, collagen, myelin, cellular cytoplasm, and lipid droplets by analyzing the CARS spectra within the C-H stretching region only. A novel image analysis approach for multispectral CARS data based on colocalization allows correlating spectrally distinct pixels to morphologic structures. Transfer of this highly precise but compact and simple to use imaging approach into clinical settings is expected in the near future. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Analytical Chemistry
volume
85
issue
14
pages
6703 - 6715
publisher
The American Chemical Society (ACS)
external identifiers
  • wos:000322059600025
  • scopus:84880525679
  • pmid:23781826
ISSN
1520-6882
DOI
10.1021/ac400570w
language
English
LU publication?
yes
additional info
The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Chemical Physics (S) (011001060)
id
4e37bc0c-27fd-4f66-9f15-6653ede3d90b (old id 4043052)
date added to LUP
2016-04-01 10:05:58
date last changed
2022-03-27 04:51:04
@article{4e37bc0c-27fd-4f66-9f15-6653ede3d90b,
  abstract     = {{Over the past years fast label-free nonlinear imaging modalities providing molecular contrast of endogenous disease markers with subcellular spatial resolution have been emerged. However, applications of these imaging modalities in clinical settings are still at the very beginning. This is because single nonlinear imaging modalities such as second-harmonic generation (SHG) and two-photon excited fluorescence (TPEF) have only limited value for diagnosing diseases due to the small number of endogenous markers. Coherent anti-Stokes Raman scattering (CARS) microscopy on the other hand can potentially be added to SHG and TPEF to visualize a much broader range of marker molecules. However, CARS requires a second synchronized laser source and the detection of a certain wavenumber range of the vibrational spectrum to differentiate multiple molecules, which results in increased experimental complexity and often inefficient excitation of SHG and TPEF signals. Here we report the application of a novel near-infrared (NIR) fiber laser of 1 MHz repetition rate, 65 ps pulse duration, and 1 cm(-1) spectral resolution to realize an efficient but experimentally simple SGH/TPEF/multiplex CARS multimodal imaging approach for a label-free characterization of composition of complex tissue samples. This is demonstrated for arterial tissue specimens demonstrating differentiation of elastic fibers, triglycerides, collagen, myelin, cellular cytoplasm, and lipid droplets by analyzing the CARS spectra within the C-H stretching region only. A novel image analysis approach for multispectral CARS data based on colocalization allows correlating spectrally distinct pixels to morphologic structures. Transfer of this highly precise but compact and simple to use imaging approach into clinical settings is expected in the near future.}},
  author       = {{Meyer, Tobias and Chemnitz, Mario and Baumgartl, Martin and Gottschall, Thomas and Pascher, Torbjörn and Matthaeus, Christian and Romeike, Bernd F. M. and Brehm, Bernhard R. and Limpert, Jens and Tuennermann, Andreas and Schmitt, Michael and Dietzek, Benjamin and Popp, Juergen}},
  issn         = {{1520-6882}},
  language     = {{eng}},
  number       = {{14}},
  pages        = {{6703--6715}},
  publisher    = {{The American Chemical Society (ACS)}},
  series       = {{Analytical Chemistry}},
  title        = {{Expanding Multimodal Microscopy by High Spectral Resolution Coherent Anti-Stokes Raman Scattering Imaging for Clinical Disease Diagnostics}},
  url          = {{http://dx.doi.org/10.1021/ac400570w}},
  doi          = {{10.1021/ac400570w}},
  volume       = {{85}},
  year         = {{2013}},
}