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01.07.2014 | Original Article

Second Harmonic Generation Imaging Distinguishes Both High-Grade Dysplasia and Cancer from Normal Colonic Mucosa

verfasst von: John W. Birk, Micheal Tadros, Koorosh Moezardalan, Oleg Nadyarnykh, Faripour Forouhar, Joseph Anderson, Paul Campagnola

Erschienen in: Digestive Diseases and Sciences | Ausgabe 7/2014

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Abstract

Background and Aim

Second harmonic generation (SHG) is a novel imaging technology that could provide optical biopsy during endoscopy with advantages over current technology. SHG has the unique ability to evaluate the amount of extracellular matrix collagen protein and its alignment.

Methods

Hematoxylin- and eosin-stained slides from colon biopsies (normal, low-grade dysplasia (LGD), high-grade dysplasia (HGD), and cancer) were examined with SHG imaging. Both signal intensity and collagen fiber alignment were measured. Average intensity per pixel (AIPP) was obtained, and an analyzing polarizer was used to calculate β, an alignment parameter.

Results

The mean AIPP for normal mucosa was 48, LGD was 38, HGD was 42, and malignancy was 123 (p < 0.01). The AIPP ROC curve between malignant versus non-malignant tissue was 0.96 (0.93–0.99). An AIPP value of 60 can differentiate malignancy with 87 % sensitivity and 90 % specificity. The mean β for normal tissue was 0.490, LGD was 0.379, HGD was 0.345, and cancer was 0.453 (p = 0.013), with a normal tissue mean rank of 6.5 compared to 2.5 for HGD (p = 0.029).

Conclusions

SHG signal intensity can differentiate malignant from non-malignant colonic polyp tissue with high sensitivity and specificity. Anisotropic polarization can discern HGD from normal colonic polyp tissue. SHG can thus distinguish both HGD and malignant lesions in an objective numeric fashion, without contrast agents or interpretation skills. SHG could be incorporated into endoscopy equipment to enhance white light endoscopy.

Brkic T, Kalauz M, Ostojic R. Novel endoscopic optical techniques for the detection of early gastrointestinal neoplasia. Lijec Vjesn. 2009;131:69–73.PubMed

Monkemuller K, Neumann H, Fry LC. Enteroscopy: advances in diagnostic imaging. Best Pract Res Clin Gastroenterol. 2012;26:221–233.PubMedCrossRef

Aisenberg J. Gastrointestinal endoscopy nears “the molecular era”. Gastrointest Endosc. 2008;68:528–530.PubMedCrossRef

ASGE Technology Committee, Kantsevoy SV, Adler DG, et al. Confocal laser endomicroscopy. Gastrointest Endosc. 2009;70:197–200.PubMedCrossRef

Saftoiu A, Vilman P. Endoscopic ultrasound elastography—a new imaging technique for the visualization of tissue elasticity distribution. J Gastrointestin Liver Dis. 2006;15:161–165.PubMed

Campagnola PJ, Millard AC, Terasaki M, Hoppe PE, Malone CJ, Mohler WA. Three-dimensional high-resolution second-harmonic generation imaging of endogenous structural proteins in biological tissues. Biophys J. 2002;82:493–508.PubMedCentralPubMedCrossRef

Wang M, Reiser KM, Knoesen A. Spectral moment invariant analysis of disorder in polarization-modulated second-harmonic-generation images obtained from collagen assemblies. J Opt Soc Am A Opt Image Sci Vis. 2007;24:3573–3586.PubMedCrossRef

Cox G, Kable E, Jones A, Fraser I, Manconi F, Gorrell MD. 3-dimensional imaging of collagen using second harmonic generation. J Struct Biol. 2003;141:53–62.PubMedCrossRef

Han M, Giese G, Bille JF. Second harmonic generation imaging of collagen fibrils in cornea and sciera. Opt Express. 2005;13:5791–5797.PubMedCrossRef

10.

Nadiarnykh O, LaComb RB, Brewer MA, Campagnola PJ. Alterations of the extracellular matrix in ovarian cancer studied by second harmonic generation imaging microscopy. BMC Cancer. 2010;10:94.

11.

Ajeti V, Nadiarnykh O, Ponik SM, Keely PJ, Eliceiri KW, Campagnola PJ. Structural changes in mixed col I/Col V collagen gels probed by SHG microscopy: implications for probing stromal alterations in human breast cancer. Biomed Opt Express. 2011;2:2307–2316.PubMedCentralPubMedCrossRef

12.

Débarre D, Supatto W, Pena A, et al. Imaging lipid bodies in cells and tissues using third-harmonic generation microscopy. Nat Methods. 2006;3:47–53.PubMedCrossRef

13.

Deniset-Besseau A, Duboisse J, Benkhou E, Hache F, Brevet P, Schanne-Klein M. Measurement of the second-order hyperpolarizability of the collagen triple helix and determination of its physical origin. J Phys Chem B. 2009;113:13437–13445.PubMedCrossRef

14.

Han M, Zickler L, Giese G, Walter M, Loesel FH, Bille JF. Second-harmonic imaging of cornea after intrastromal femtosecond laser ablation. J Biomed Opt. 2004;9:760–766.PubMedCrossRef

15.

Lacomb R, Nadiarnykh O, Campagnola PJ. Quantitative SHG imaging of the diseased state osteogenesis imperfecta: experiment and simulation. Biophys J. 2008;94:4104.

16.

Lin S, Jee S, Kuo C, et al. Discrimination of basal cell carcinoma from normal dermal stroma by quantitative multiphoton imaging. Opt Lett. 2006;31:2756–2758.PubMedCrossRef

17.

Matteini P, Ratto F, Rossi F, et al. Photothermally-induced disordered patterns of corneal collagen revealed by SHG imaging. Opt Express. 2009;17:4868–4878.PubMedCrossRef

18.

Nadiarnykh O, Plotnikov S, Mohler WA, Kalajzic I, Redford-Badwal D, Campagnola PJ. Second harmonic generation imaging microscopy studies of osteogenesis imperfecta. J Biomed Opt. 2007;12:051805.

19.

Plotnikov S, Juneja V, Isaacson AB, Mohler WA, Campagnola PJ. Optical clearing for improved contrast in second harmonic generation imaging of skeletal muscle. Biophys J. 2006;90:328–339.PubMedCentralPubMedCrossRef

20.

Provenzano PP, Eliceiri KW, Campbell JM, Inman DR, White JG, Keely PJ. Collagen reorganization at the tumor-stromal interface facilitates local invasion. BMC Med. 2006;4:38.

21.

Strupler M, Pena A, Hernest M, et al. Second harmonic imaging and scoring of collagen in fibrotic tissues. Opt Express. 2007;15:4054–4065.PubMedCrossRef

22.

Sun W, Chang S, Tai DCS, et al. Nonlinear optical microscopy: use of second harmonic generation and two-photon microscopy for automated quantitative liver fibrosis studies. J Biomed Opt. 2008;13:064010.

23.

Tai S, Tsai T, Lee W, et al. Optical biopsy of fixed human skin with backward-collected optical harmonics signals. Opt Express. 2005;13:8231–8242.PubMedCrossRef

24.

Tan H-, Sun Y, Lo W, et al. Multiphoton fluorescence and second harmonic generation imaging of the structural alterations in keratoconus ex vivo. Invest Ophthalmol Vis Sci. 2006;47:5251–5259.PubMedCrossRef

25.

Theodossiou TA, Thrasivoulou C, Ekwobi C, Becker DL. Second harmonic generation confocal microscopy of collagen type I from rat tendon cryosections. Biophys J. 2006;91:4665–4677.PubMedCentralPubMedCrossRef

26.

Williams RM, Zipfel WR, Webb WW. Interpreting second-harmonic generation images of collagen I fibrils. Biophys J. 2005;88:1377–1386.PubMedCentralPubMedCrossRef

27.

Yeh AT, Choi B, Nelson JS, Tromberg BJ. Reversible dissociation of collagen in tissues. J Invest Dermatol. 2003;121:1332–1335.PubMedCrossRef

28.

Brown E, McKee T, diTomaso E, et al. Dynamic imaging of collagen and its modulation in tumors in vivo using second-harmonic generation. Nat Med. 2003;9:796–800.PubMedCrossRef

29.

Cicchi R, Massi D, Sestini S, et al. Multidimensional non-linear laser imaging of basal cell carcinoma. Opt Express. 2007;15:10135–10148.PubMedCrossRef

30.

Campagnola P. Second harmonic generation imaging microscopy: applications to diseases diagnostics. Anal Chem. 2011;83:3224–3231.PubMedCentralPubMedCrossRef

31.

Shen Y. The Principles of Nonlinear Optics. New York: Wiley-Interscience; 1984.

32.

Campagnola PJ, Loew LM. Second-harmonic imaging microscopy for visualizing biomolecular arrays in cells, tissues and organisms. Nat Biotechnol. 2003;21:1356–1360.PubMedCrossRef

33.

Odin C, Le Grand Y, Renault A, Gailhouste L, Baffet G. Orientation fields of nonlinear biological fibrils by second harmonic generation microscopy. J Microsc. 2008;229:32–38.PubMedCrossRef

34.

Ricciardelli C, Rodgers RJ. Extracellular matrix of ovarian tumors. Semin Reprod Med. 2006;24:270–282.PubMedCrossRef

35.

Pupa SM, Menard S, Forti S, Tagliabue E. New insights into the role of extracellular matrix during tumor onset and progression. J Cell Physiol. 2002;192:259–267.PubMedCrossRef

36.

Theret N, Musso O, Turlin B, et al. Increased extracellular matrix remodeling is associated with tumor progression in human hepatocellular carcinomas. Hepatology. 2001;34:82–88.PubMedCrossRef

37.

Huang S, Van Arsdall M, Tedjarati S, et al. Contributions of stromal metalloproteinase-9 to angiogenesis and growth of human ovarian carcinoma in mice. J Natl Cancer Inst. 2002;94:1134–1142.PubMedCrossRef

38.

Hugo H, Ackland ML, Blick T, et al. Epithelial–mesenchymal and mesenchymal–epithelial transitions in carcinoma progression. J Cell Physiol. 2007;213:374–383.PubMedCrossRef

39.

Provenzano PP, Inman DR, Eliceiri KW, et al. Collagen density promotes mammary tumor initiation and progression. BMC Med. 2008;6:11.

40.

Freund I, Deutsch M, Sprecher A. Connective tissue polarity. Optical second-harmonic microscopy, crossed-beam summation, and small-angle scattering in rat-tail tendon. Biophys J. 1986;50:693–712.PubMedCentralPubMedCrossRef

41.

Cicchi R, Kapsokalyvas D, De Giorgi V, et al. Scoring of collagen organization in healthy and diseased human dermis by multiphoton microscopy. J Biophotonics. 2010;3:34–43.PubMedCrossRef

42.

LaComb R, Nadiarnykh O, Townsend SS, Campagnola PJ. Phase matching considerations in second harmonic generation from tissues: effects on emission directionality, conversion efficiency and observed morphology. Opt Commun. 2008;281:1823–1832.PubMedCentralPubMedCrossRef

43.

Plotnikov SV, Millard AC, Campagnola PJ, Mohler WA. Characterization of the myosin-based source for second-harmonic generation from muscle sarcomeres. Biophys J. 2006;90:693–703.PubMedCentralPubMedCrossRef

44.

Zhuo S, Zhu X, Wu G, Chen J, Xie S. Quantitative biomarkers of colonic dysplasia based on intrinsic second-harmonic generation signal. J Biomed Opt. 2011;16:120501.PubMedCrossRef

45.

Zhuo S, Yan J, Chen G, et al. Label-free imaging of basement membranes differentiates normal, precancerous, and cancerous colonic tissues by second-harmonic generation microscopy. PLoS One. 2012;7:e38655.PubMedCentralPubMedCrossRef

Titel: Second Harmonic Generation Imaging Distinguishes Both High-Grade Dysplasia and Cancer from Normal Colonic Mucosa
verfasst von: John W. Birk
Micheal Tadros
Koorosh Moezardalan
Oleg Nadyarnykh
Faripour Forouhar
Joseph Anderson
Paul Campagnola
Publikationsdatum: 01.07.2014
Verlag: Springer US
Erschienen in: Digestive Diseases and Sciences / Ausgabe 7/2014
Print ISSN: 0163-2116
Elektronische ISSN: 1573-2568
DOI: https://doi.org/10.1007/s10620-014-3121-7

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Background and Aim

Methods

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