title: Multiphoton microscopy as a diagnostic imaging modality for lung cancer.
abstract: Lung cancer is the leading killer among all cancers for both men and women in the US, and is associated with one of the lowest 5-year survival rates. Current diagnostic techniques, such as histopathological assessment of tissue obtained by computed tomography guided biopsies, have limited accuracy, especially for small lesions. Early diagnosis of lung cancer can be improved by introducing a real-time, optical guidance method based on the in vivo application of multiphoton microscopy (MPM). In particular, we hypothesize that MPM imaging of living lung tissue based on two-photon excited intrinsic fluorescence and second harmonic generation can provide sufficient morphologic and spectroscopic information to distinguish between normal and diseased lung tissue. Here, we used an experimental approach based on MPM with multichannel fluorescence detection for initial discovery that MPM spectral imaging could differentiate between normal and neoplastic lung in ex vivo samples from a murine model of lung cancer. Current results indicate that MPM imaging can directly distinguish normal and neoplastic lung tissues based on their distinct morphologies and fluorescence emission properties in non-processed lung tissue. Moreover, we found initial indication that MPM imaging differentiates between normal alveolar tissue, inflammatory foci, and lung neoplasms. Our long-term goal is to apply results from ex vivo lung specimens to aid in the development of multiphoton endoscopy for in vivo imaging of lung abnormalities in various animal models, and ultimately for the diagnosis of human lung cancer.
authors.affiliation: School of Applied and Engineering Physics, Cornell University, Ithaca, NY.
authors.forename: Ina
authors.initials: I
authors.lastname: Pavlova
authors.forename: Kelly R
authors.initials: KR
authors.lastname: Hume
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Yazinski
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Peters
authors.forename: Robert S
authors.initials: RS
authors.lastname: Weiss
authors.forename: Watt W
authors.initials: WW
authors.lastname: Webb
references.citation: Chest. 2003 Jan;123(1 Suppl):115S-128S
references.pmid: 12527571
references.citation: J Biol Chem. 2005 Jul 1;280(26):25119-26
references.pmid: 15863500
references.citation: Eur Radiol. 2004 Jul;14(7):1234-40
references.pmid: 14963689
references.citation: J Biomed Opt. 2009 Jul-Aug;14(4):044034
references.pmid: 19725745
references.citation: Proc Natl Acad Sci U S A. 2003 Jun 10;100(12):7075-80
references.pmid: 12756303
references.citation: J Neurophysiol. 2004 Apr;91(4):1908-12
references.pmid: 14668300
references.citation: AJR Am J Roentgenol. 1985 Feb;144(2):281-8
references.pmid: 3871271
references.citation: Nat Biotechnol. 2003 Nov;21(11):1369-77
references.pmid: 14595365
references.citation: Opt Express. 2009 Mar 2;17(5):3679-89
references.pmid: 19259208
references.citation: AJR Am J Roentgenol. 2007 Apr;188(4):891-3
references.pmid: 17377018
references.citation: Clin Gastroenterol Hepatol. 2008 Jan;6(1):95-101
references.pmid: 18065276
references.citation: Cancer Res. 2004 Apr 1;64(7):2307-16
references.pmid: 15059877
references.citation: Nat Methods. 2009 Jul;6(7):511-2
references.pmid: 19525959
references.citation: Science. 1990 Apr 6;248(4951):73-6
references.pmid: 2321027
references.citation: Proc SPIE Int Soc Opt Eng. 2009;7161:
references.pmid: 19360140
references.citation: Microsc Res Tech. 2007 Feb;70(2):162-70
references.pmid: 17177275
references.citation: Cancer Res. 2008 Apr 15;68(8):2652-60
references.pmid: 18413732
references.citation: Opt Lett. 2006 Apr 15;31(8):1076-8
references.pmid: 16625908
references.citation: CA Cancer J Clin. 2008 Mar-Apr;58(2):71-96
references.pmid: 18287387
references.citation: Science. 2004 Jul 2;305(5680):99-103
references.pmid: 15232110
references.citation: Genes Dev. 2001 Dec 15;15(24):3243-8
references.pmid: 11751630
references.citation: Gastrointest Endosc Clin N Am. 2008 Jul;18(3):451-66, viii
references.pmid: 18674696