title: In vivo multiphoton tomography and fluorescence lifetime imaging of human brain tumor tissue.
abstract: High resolution multiphoton tomography and fluorescence lifetime imaging differentiates glioma from adjacent brain in native tissue samples ex vivo. Presently, multiphoton tomography is applied in clinical dermatology and experimentally. We here present the first application of multiphoton and fluorescence lifetime imaging for in vivo imaging on humans during a neurosurgical procedure. We used a MPTflex™ Multiphoton Laser Tomograph (JenLab, Germany). We examined cultured glioma cells in an orthotopic mouse tumor model and native human tissue samples. Finally the multiphoton tomograph was applied to provide optical biopsies during resection of a clinical case of glioblastoma. All tissues imaged by multiphoton tomography were sampled and processed for conventional histopathology. The multiphoton tomograph allowed fluorescence intensity- and fluorescence lifetime imaging with submicron spatial resolution and 200 picosecond temporal resolution. Morphological fluorescence intensity imaging and fluorescence lifetime imaging of tumor-bearing mouse brains and native human tissue samples clearly differentiated tumor and adjacent brain tissue. Intraoperative imaging was found to be technically feasible. Intraoperative image quality was comparable to ex vivo examinations. To our knowledge we here present the first intraoperative application of high resolution multiphoton tomography and fluorescence lifetime imaging of human brain tumors in situ. It allowed in vivo identification and determination of cell density of tumor tissue on a cellular and subcellular level within seconds. The technology shows the potential of rapid intraoperative identification of native glioma tissue without need for tissue processing or staining.
authors.affiliation: University Medical Centre, Johannes Gutenberg-University, Langenbeckstraße 1, 55101, Mainz, Germany. sven.kantelhardt@web.de.
authors.forename: Sven R
authors.initials: SR
authors.lastname: Kantelhardt
authors.affiliation: University Medical Centre, Johannes Gutenberg-University, Langenbeckstraße 1, 55101, Mainz, Germany.
authors.forename: Darius
authors.initials: D
authors.lastname: Kalasauskas
authors.affiliation: Department for Biophotonics and Laser Technology, Saarland University, Campus A5.1, 66123, Saarbrücken, Germany.|JenLab GmbH, Schillerstrasse 1, 07745, Jena, Germany.
authors.forename: Karsten
authors.initials: K
authors.lastname: König
authors.affiliation: University Medical Centre, Johannes Gutenberg-University, Langenbeckstraße 1, 55101, Mainz, Germany.
authors.forename: Ella
authors.initials: E
authors.lastname: Kim
authors.affiliation: JenLab GmbH, Schillerstrasse 1, 07745, Jena, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Weinigel
authors.affiliation: Department for Biophotonics and Laser Technology, Saarland University, Campus A5.1, 66123, Saarbrücken, Germany.
authors.forename: Aisada
authors.initials: A
authors.lastname: Uchugonova
authors.affiliation: University Medical Centre, Johannes Gutenberg-University, Langenbeckstraße 1, 55101, Mainz, Germany.
authors.forename: Alf
authors.initials: A
authors.lastname: Giese
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000601:surgery; D005453:Fluorescence; D005910:Glioma / Q000175:diagnosis* / Q000601:surgery; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D036641:Microscopy, Fluorescence, Multiphoton / Q000379:methods*; D061848:Optical Imaging / Q000379:methods*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
keywords: Fluorescence lifetime imaging; Glioma surgery; Multiphoton tomography; Optical biopsy; Optical tissue analysis; Two-photon microscopy
references.citation: FASEB J. 2006 Oct;20(12):2050-7
references.pmid: 17012257
references.citation: Lasers Surg Med. 2008 Apr;40(4):273-81
references.pmid: 18412229
references.citation: Neurosurgery. 2006 Apr;58(4):759-67; discussion 759-67
references.pmid: 16575340
references.citation: J Biomed Opt. 2010 Sep-Oct;15(5):056022
references.pmid: 21054116
references.citation: Cell Cycle. 2011 Jun 15;10(12):2017-20
references.pmid: 21558804
references.citation: Science. 2005 Jan 28;307(5709):538-44
references.pmid: 15681376
references.citation: Acta Neurochir (Wien). 2009 Mar;151(3):253-62; discussion 262
references.pmid: 19238321
references.citation: Microsc Microanal. 2013 Aug;19(4):791-8
references.pmid: 23702007
references.citation: Neurosurgery. 2008 Mar;62(3):564-76; discussion 564-76
references.pmid: 18425006
references.citation: J Microsc. 2000 Nov;200(Pt 2):83-104
references.pmid: 11106949
references.citation: Acta Neurochir (Wien). 2009 May;151(5):507-17; discussion 517
references.pmid: 19343270
references.citation: J Innov Opt Health Sci. 2014 Jan 3;7(5):1330010
references.pmid: 25075226
references.citation: Oncologist. 2006 Feb;11(2):165-80
references.pmid: 16476837
references.citation: Lasers Surg Med. 2006 Jul;38(6):588-97
references.pmid: 16736504
references.citation: Ann Biomed Eng. 2006 Jan;34(1):3-14
references.pmid: 16450199
references.citation: Neuro Oncol. 2007 Apr;9(2):103-12
references.pmid: 17325340
references.citation: Sci Transl Med. 2015 Jun 17;7(292):292ra100
references.pmid: 26084803
references.citation: J Biomed Opt. 2003 Jul;8(3):432-9
references.pmid: 12880349
references.citation: PLoS One. 2010 Jun 30;5(6):e11323
references.pmid: 20614029
references.citation: IEEE Trans Nanobioscience. 2009 Mar;8(1):65-71
references.pmid: 19304503
references.citation: Scanning. 2012 May-Jun;34(3):181-5
references.pmid: 21898461
references.citation: Cancer Res. 2014 May 15;74(10):2688-97
references.pmid: 24686168
references.citation: PLoS One. 2012;7(9):e43460
references.pmid: 22984428
references.citation: Anal Bioanal Chem. 2012 May;403(3):719-25
references.pmid: 22367289
references.citation: Invest Ophthalmol Vis Sci. 2014 Jun 26;55(7):4438-47
references.pmid: 24970255
references.citation: Biomed Opt Express. 2014 Feb 07;5(3):664-74
references.pmid: 24688804
references.citation: J Clin Oncol. 2003 Apr 15;21(8):1624-36
references.pmid: 12697889
references.citation: Microsc Res Tech. 2008 Dec;71(12):887-96
references.pmid: 18816597
references.citation: Adv Exp Med Biol. 2012;746:12-25
references.pmid: 22639156
references.citation: Proc Natl Acad Sci U S A. 2010 Mar 2;107(9):4317-22
references.pmid: 20160097
references.citation: Anal Bioanal Chem. 2011 Jul;400(9):2801-16
references.pmid: 21537917
references.citation: Neurosurgery. 2013 Jan;72 Suppl 1:19-26
references.pmid: 23254808
references.citation: Surg Endosc. 2014 Jan;28(1):36-41
references.pmid: 24002915