title: Pseudo-HE images derived from CARS/TPEF/SHG multimodal imaging in combination with Raman-spectroscopy as a pathological screening tool.
abstract: Due to the steadily increasing number of cancer patients worldwide the early diagnosis and treatment of cancer is a major field of research. The diagnosis of cancer is mostly performed by an experienced pathologist via the visual inspection of histo-pathological stained tissue sections. To save valuable time, low quality cryosections are frequently analyzed with diagnostic accuracies that are below those of high quality embedded tissue sections. Thus, alternative means have to be found that enable for fast and accurate diagnosis as the basis of following clinical decision making.
  
  
  
  In this contribution we will show that the combination of the three label-free non-linear imaging modalities CARS (coherent anti-Stokes Raman-scattering), TPEF (two-photon excited autofluorescence) and SHG (second harmonic generation) yields information that can be translated into computational hematoxylin and eosin (HE) images by multivariate statistics. Thereby, a computational HE stain is generated resulting in pseudo-HE overview images that allow for identification of suspicious regions. The latter are analyzed further by Raman-spectroscopy retrieving the tissue's molecular fingerprint.
  
  
  
  The results suggest that the combination of non-linear multimodal imaging and Raman-spectroscopy possesses the potential as a precise and fast tool in routine histopathology.
  
  
  
  As the key advantage, both optical methods are non-invasive enabling for further pathological investigations of the same tissue section, e.g. a direct comparison with the current pathological gold-standard.
authors.affiliation: Institute of Physical Chemistry and Abbe Center of Photonics, Friedrich-Schiller University Jena, Helmholtzweg 4, Jena, Germany. thomas.bocklitz@uni-jena.de.|Leibniz-Institute of Photonic Technology, Albert-Einstein-Str. 9, Jena, 07745, Germany. thomas.bocklitz@uni-jena.de.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Bocklitz
authors.affiliation: Iraqi Centre for Cancer and Medical Genetics Research, Al-Mustansiriya University, Baghdad, Iraq.|Institute of Pathology, University Hospital - Friedrich Schiller University Jena, Ziegelmühlenweg 1, Jena, D-07743, Germany.
authors.forename: Firas Subhi
authors.initials: FS
authors.lastname: Salah
authors.affiliation: Leibniz-Institute of Photonic Technology, Albert-Einstein-Str. 9, Jena, 07745, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Vogler
authors.affiliation: Institute of Physical Chemistry and Abbe Center of Photonics, Friedrich-Schiller University Jena, Helmholtzweg 4, Jena, Germany.|Leibniz-Institute of Photonic Technology, Albert-Einstein-Str. 9, Jena, 07745, Germany.
authors.forename: Sandro
authors.initials: S
authors.lastname: Heuke
authors.affiliation: Institute of Physical Chemistry and Abbe Center of Photonics, Friedrich-Schiller University Jena, Helmholtzweg 4, Jena, Germany.|Leibniz-Institute of Photonic Technology, Albert-Einstein-Str. 9, Jena, 07745, Germany.
authors.forename: Olga
authors.initials: O
authors.lastname: Chernavskaia
authors.affiliation: Clinic for Internal Medicine IV, Jena University Hospital, Jena, 07747, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Schmidt
authors.affiliation: Department of Medicine 1, Friedrich-Alexander-University, Erlangen, 91054, Germany.|Erlangen Graduate School in Advanced Optical Technologies (SAOT), Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Maximilian J
authors.initials: MJ
authors.lastname: Waldner
authors.affiliation: Institute for Tumor Biology and Experimental Therapy, Georg-Speyer-Haus, Paul-Ehrlich-Straße 42-44, Frankfurt, 60596, Germany.
authors.forename: Florian R
authors.initials: FR
authors.lastname: Greten
authors.affiliation: Institute of Pathology, University Hospital - Friedrich Schiller University Jena, Ziegelmühlenweg 1, Jena, D-07743, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Bräuer
authors.affiliation: Institute of Physical Chemistry and Abbe Center of Photonics, Friedrich-Schiller University Jena, Helmholtzweg 4, Jena, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Schmitt
authors.affiliation: Clinic for Internal Medicine IV, Jena University Hospital, Jena, 07747, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Stallmach
authors.affiliation: Institute of Pathology, University Hospital - Friedrich Schiller University Jena, Ziegelmühlenweg 1, Jena, D-07743, Germany.
authors.forename: Iver
authors.initials: I
authors.lastname: Petersen
authors.affiliation: Institute of Physical Chemistry and Abbe Center of Photonics, Friedrich-Schiller University Jena, Helmholtzweg 4, Jena, Germany. juergen.popp@uni-jena.de.|Leibniz-Institute of Photonic Technology, Albert-Einstein-Str. 9, Jena, 07745, Germany. juergen.popp@uni-jena.de.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Popp
mesh_terms: D000236:Adenoma / Q000000981:diagnostic imaging* / Q000473:pathology; D000818:Animals; D001706:Biopsy; D002277:Carcinoma / Q000000981:diagnostic imaging* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology; D055088:Early Detection of Cancer / Q000379:methods*; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D051379:Mice; D008853:Microscopy / Q000379:methods; D064847:Multimodal Imaging / Q000379:methods*; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging / Q000473:pathology; D061848:Optical Imaging / Q000379:methods; D017785:Photons; D013059:Spectrum Analysis, Raman; D013194:Staining and Labeling
keywords: Cancer detection; Multimodal imaging; Pseudo HE-images; Raman spectroscopy