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Licensed Unlicensed Requires Authentication Published by De Gruyter February 10, 2015

Raman spectroscopy for the discrimination of cancerous and normal skin

Raman-Spektroskopie zur In-vivo-Diskrimination von kanzeröser und normaler Haut
  • Johannes Schleusener EMAIL logo , Carina Reble , Martina C. Meinke and Jürgen Helfmann

Abstract:

Various studies have shown promising results in using Raman spectroscopy (RS) for the detection of skin cancers. In-vivo evaluations showed similar results to those found by trained dermatologists using dermoscopy, the current clinical practice for skin cancer diagnosis. However, dermoscopy is highly subjective which would make an objective, non-invasive diagnostic method useful. Although successful results were achieved, RS is barely applied in clinical routine yet. This review summarizes studies of Raman spectroscopy for skin cancer diagnosis ex vivo and in vivo. The latter has special demands that often lead to a tradeoff between applicability and classification performance. The necessary steps are explained for instrumentation design, handling, data analysis and clinical testing on groups with a sufficient amount of subjects in order to promote the application of RS in a routine clinical setting. A number of methods are summarized which attempt to overcome the ongoing challenge of reducing large background signals. Modifications of RS by combination with other diagnostic methods are summarized that can give a new perspective to future developments in RS.

Zusammenfassung:

In verschiedenen Studien wurden vielversprechende Ergebnisse bei der Erkennung von Hautkrebs mittels Raman-Spektroskopie (RS) erreicht. In-vivo-Erprobungen haben vergleichbare Ergebnisse zur Dermatoskopie durch erfahrene Dermatologen gezeigt, dem derzeitigen klinischen Standard zur Hautkrebserkennung. Die Dermatoskopie ist jedoch in hohem Maße subjektiv, weshalb die Etablierung einer objektiven, nicht-invasiven Diagnosemethode sinnvoll ist. Trotz erfolgreicher Ergebnisse, wird die RS bislang dennoch nur vereinzelt im klinischen Routinebetrieb eingesetzt. Der vorliegende Reviewartikel fasst Raman-spektroskopische Ex-vivo- und In-vivo-Studien zusammen. Für In-vivo-Studien ergeben sich besondere Anforderungen, die oft zum Abwägen zwischen Anwendbarkeit und Klassifikationseffizienz führen. Die notwendigen Schritte für das Design der Instrumentierung sowie die Handhabung, Datenanalyse und klinische Evaluierung an ausreichend großen Studienpopulationen werden erklärt, um die Anwendung der RS im klinischen Umfeld zu ermöglichen. Es werden zudem Methoden zur Reduzierung von großen Untergrundsignalen zusammenfassend beschrieben. Weiterhin werden Modifikationen der RS, die sich aus der Kombination mit anderen diagnostischen Methoden ergeben und dadurch neue Perspektiven für zukünftige Entwicklungen eröffnen, zusammengestellt.


Corresponding author: Johannes Schleusener, Laser- und Medizin-Technologie GmbH, Berlin (LMTB), Fabeckstraße 60-62, 14195 Berlin, Germany; and Department of Dermatology, Venerology and Allergy, Charité – Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany, e-mail:

  1. Funding: Senate of Berlin and EU (EFRE) (Grant/Award Number: ‘FKZ 10147189’).

  2. Conflict of interest statement: The authors report no conflict of interest.

References

[1] WHO. Skin cancers: How common is skin cancer? http://www.who.int/uv/faq/skincancer/en/index1.html [Accessed on November 17, 2014].Search in Google Scholar

[2] Gniadecka M, Wulf HC, Nielsen OF, Christensen DH, Hercogova J. Distinctive molecular abnormalities in benign and malignant skin lesions: studies by Raman spectroscopy. Photochem Photobiol 1997;66(4):418–23.10.1111/j.1751-1097.1997.tb03167.xSearch in Google Scholar PubMed

[3] Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, Leffell DJ, Wolff K, editors. Fitzpatrick’s dermatology in general medicine. New York: McGraw-Hill; 2003.Search in Google Scholar

[4] Byrne H, Sockalingum G, Stone N. Raman microscopy: complement or competitor. In: Moss D, editor. Biomedical applications of synchrotron infrared microspectroscopy. London: Royal Society of Chemistry; 2011, p. 105–42.10.1039/9781849731997-00105Search in Google Scholar

[5] Notingher I, Verrier S, Romanska H, Bishop AE, Polak JM, Hench LL. In situ characterisation of living cells by Raman spectroscopy. Spectroscopy 2002;16(2):43–51.10.1155/2002/408381Search in Google Scholar

[6] Motz JT, Hunter M, Galindo LH, Gardecki JA, Kramer JR, Dasari RR, Feld MS. Optical fiber probe for biomedical Raman spectroscopy. Appl Opt 2004;43(3):542–54.10.1364/AO.43.000542Search in Google Scholar PubMed

[7] Kendall C, Isabelle M, Bazant-Hegemark F, Hutchings J, Orr L, Babrah J, Baker R, Stone N. Vibrational spectroscopy: a clinical tool for cancer diagnostics. Analyst 2009;134(6):1029–45.10.1039/b822130hSearch in Google Scholar PubMed

[8] Nijssen A, Koljenovic S, Bakker Schut TC, Caspers PJ, Puppels GJ. Towards oncological application of Raman spectroscopy. J Biophotonics 2009;2(1–2):29–36.10.1002/jbio.200810055Search in Google Scholar PubMed

[9] Nijssen A, Bakker Schut TC, Heule F, Caspers PJ, Hayes DP, Neumann MH, Puppels GJ. Discriminating basal cell carcinoma from its surrounding tissue by Raman spectroscopy. J Invest Dermatol 2002;119(1):64–9.10.1046/j.1523-1747.2002.01807.xSearch in Google Scholar PubMed

[10] Gniadecka M, Philipsen PA, Sigurdsson S, Wessel S, Nielsen OF, Christensen DH, Hercogova J, Rossen K, Thomsen HK, Gniadecki R, Hansen LK, Wulf HC. Melanoma diagnosis by Raman spectroscopy and neural networks: structure alterations in proteins and lipids in intact cancer tissue. J Invest Dermatol 2004;122(2):443–9.10.1046/j.0022-202X.2004.22208.xSearch in Google Scholar PubMed

[11] Nijssen A, Maquelin K, Santos LF, Caspers PJ, Bakker Schut TC, den Hollander JC, Neumann MH, Puppels GJ. Discriminating basal cell carcinoma from perilesional skin using high wave-number Raman spectroscopy. J Biomed Opt 2007;12(3):034004.10.1117/1.2750287Search in Google Scholar PubMed

[12] Lieber CA, Majumder SK, Billheimer D, Ellis DL, Mahadevan-Jansen A. Raman microspectroscopy for skin cancer detection in vitro. J Biomed Opt 2008;13(2):024013.10.1117/1.2899155Search in Google Scholar PubMed

[13] Lieber CA, Majumder SK, Ellis DL, Billheimer DD, Mahadevan-Jansen A. In vivo nonmelanoma skin cancer diagnosis using Raman microspectroscopy. Lasers Surg Med 2008;40(7): 461–7.10.1002/lsm.20653Search in Google Scholar PubMed PubMed Central

[14] Zeng H, Zhao J, Short M, McLean DI, Lam S, McWilliams A, Lui H. Raman Spectroscopy for in vivo tissue analysis and diagnosis, from instrument development to clinical applications. J Innov Opt Health Sci 2008;1(1):95–106.10.1142/S1793545808000054Search in Google Scholar

[15] Larraona-Puy M, Ghita A, Zoladek A, Perkins W, Varma S, Leach IH, Koloydenko AA, Williams H, Notingher I. Development of Raman microspectroscopy for automated detection and imaging of basal cell carcinoma. J Biomed Opt 2009;14(5):054031.10.1117/1.3251053Search in Google Scholar PubMed

[16] Zhao J, Lui H, McLean D, Zeng H. Real-time Raman spectroscopy for noninvasive in vivo skin analysis and diagnosis. In: Campolo D, editor. New developments in biomedical engineering. Vienna: IN-TECH; 2010, p. 455–74.10.5772/7603Search in Google Scholar

[17] Lui H, Zhao J, McLean D, Zeng H. Real-time Raman spectroscopy for in vivo skin cancer diagnosis. Cancer Res 2012;72(10):2491–500.10.1158/0008-5472.CAN-11-4061Search in Google Scholar PubMed

[18] Philipsen PA, Knudsen L, Gniadecka M, Ravnbak MH, Wulf HC. Diagnosis of malignant melanoma and basal cell carcinoma by in vivo NIR-FT Raman spectroscopy is independent of skin pigmentation. Photochem Photobiol Sci 2013;12(5):770–6.10.1039/c3pp25344aSearch in Google Scholar PubMed

[19] de Oliveira Nunes L, Martin AA, Silveira Jr L, Zampieri M. FT-Raman spectroscopy study for skin cancer diagnosis. Spectroscopy 2003;17(2–3):597–602.10.1155/2003/104696Search in Google Scholar

[20] Lieber C, Mahadevan-Jansen A. Development of a handheld Raman microspectrometer for clinical dermatologic applications. Opt Express 2007;15(19):11874–82.10.1364/OE.15.011874Search in Google Scholar

[21] Keller MD, Kanter EM, Lieber CA, Majumder SK, Hutchings J, Ellis DL, Beaven RB, Stone N, Mahadevan-Jansen A. Detecting temporal and spatial effects of epithelial cancers with Raman spectroscopy. Dis Markers 2008;25(6):323–37.10.1155/2008/230307Search in Google Scholar PubMed PubMed Central

[22] Beleites C, Neugebauer U, Bocklitz T, Krafft C, Popp J. Sample size planning for classification models. Anal Chim Acta 2013;760:25–33.10.1016/j.aca.2012.11.007Search in Google Scholar PubMed

[23] Caspers PJ, Lucassen GW, Wolthuis R, Bruining HA, Puppels GJ. In vitro and in vivo Raman spectroscopy of human skin. Biospectroscopy 1998;4(5 Suppl):S31–9.10.1002/(SICI)1520-6343(1998)4:5+<S31::AID-BSPY4>3.0.CO;2-MSearch in Google Scholar

[24] Caspers PJ, Lucassen GW, Bruining HA, Puppels GJ. Automated depth-scanning confocal Raman microspectrometer for rapid in vivo determination of water concentration profiles in human skin. J Raman Spectrosc 2000;31(8–9):813–8.10.1002/1097-4555(200008/09)31:8/9<813::AID-JRS573>3.0.CO;2-7Search in Google Scholar

[25] Caspers PJ, Lucassen GW, Carter EA, Bruining HA, Puppels GJ. In vivo confocal Raman microspectroscopy of the skin: noninvasive determination of molecular concentration profiles. J Invest Dermatol 2001;116(3):434–42.10.1046/j.1523-1747.2001.01258.xSearch in Google Scholar

[26] Chrit L, Hadjur C, Morel S, Sockalingum G, Lebourdon G, Leroy F, Manfait M. In vivo chemical investigation of human skin using a confocal Raman fiber optic microprobe. J Biomed Opt 2005;10(4):44007.10.1117/1.2003747Search in Google Scholar

[27] Dochow S, Bergner N, Matthäus C, Praveen BB, Ashok PC, Mazilu M, Krafft C, Dholakia K, Popp J. Etaloning, fluorescence and ambient light suppression by modulated wavelength Raman spectroscopy. Biomed Spectrosc Imaging 2012;1(4):383–9.10.3233/BSI-120031Search in Google Scholar

[28] Koljenović S, Bakker Schut TC, Wolthuis R, de Jong B, Santos L, Caspers PJ, Kros JM, Puppels GJ. Tissue characterization using high wave number Raman spectroscopy. J Biomed Opt 2005;10(3):031116.10.1117/1.1922307Search in Google Scholar

[29] Santos LF, Wolthuis R, Koljenovic S, Almeida RM, Puppels GJ. Fiber-optic probes for in vivo Raman spectroscopy in the high-wavenumber region. Anal Chem 2005;77(20): 6747–52.10.1021/ac0505730Search in Google Scholar

[30] Shim MG, Wilson BC, Marple E, Wach M. Study of fiber-optic probes for in vivo medical Raman spectroscopy. Appl Spectrosc 1999;53(6):619–27.10.1366/0003702991947225Search in Google Scholar

[31] Matousek P, Clark IP, Draper ER, Morris MD, Goodship AE, Everall N, Towrie M, Finney WF, Parker AW. Subsurface probing in diffusely scattering media using spatially offset Raman spectroscopy. Appl Spectrosc 2005;59(4):393–400.10.1366/0003702053641450Search in Google Scholar

[32] Mahadevan-Jansen A, Mitchell MF, Ramanujam N, Utzinger U, Richards-Kortum R. Development of a fiber optic probe to measure NIR Raman spectra of cervical tissue in vivo. Photochem Photobiol 1998;68(3):427–31.10.1111/j.1751-1097.1998.tb09703.xSearch in Google Scholar

[33] Shim MG, Wilson BC. Development of an in vivo Raman spectroscopic system for diagnostic applications. J Raman Spectrosc 1997;28(2–3):131.10.1002/(SICI)1097-4555(199702)28:2/3<131::AID-JRS68>3.0.CO;2-SSearch in Google Scholar

[34] Shim MG, Song LM, Marcon NE, Wilson BC. In vivo near-infrared Raman spectroscopy: demonstration of feasibility during clinical gastrointestinal endoscopy. Photochem Photobiol 2000;72(1):146–50.Search in Google Scholar

[35] Bakker Schut TC, Witjes MJ, Sterenborg HJ, Speelman OC, Roodenburg JL, Marple ET, Bruining HA, Puppels GJ. In vivo detection of dysplastic tissue by Raman spectroscopy. Anal Chem 2000;72(24):6010–8.10.1021/ac000780uSearch in Google Scholar

[36] Molckovsky A, Song LWK, Shim MG, Marcon NE, Wilson BC. Diagnostic potential of near-infrared Raman spectroscopy in the colon: differentiating adenomatous from hyperplastic polyps. Gastrointest Endosc 2003;57(3):396–402.10.1067/mge.2003.105Search in Google Scholar

[37] Crow P, Molckovsky A, Stone N, Uff J, Wilson B, WongKeeSong L. Assessment of fiberoptic near-infrared raman spectroscopy for diagnosis of bladder and prostate cancer. Urology 2005;65(6):1126–30.10.1016/j.urology.2004.12.058Search in Google Scholar

[38] Magee ND, Villaumie JS, Marple ET, Ennis M, Elborn JS, McGarvey JJ. Ex vivo diagnosis of lung cancer using a Raman miniprobe. J Phys Chem B 2009;113(23):8137–41.10.1021/jp900379wSearch in Google Scholar

[39] Motz JT, Gandhi SJ, Scepanovic OR, Haka AS, Kramer JR, Dasari RR, Feld MS. Real-time Raman system for in vivo disease diagnosis. J Biomed Opt 2005;10(3):031113.10.1117/1.1920247Search in Google Scholar

[40] Mo J, Zheng W, Huang Z. Fiber-optic Raman probe couples ball lens for depth-selected Raman measurements of epithelial tissue. Biomed Opt Express 2010;1(1):17–30.10.1364/BOE.1.000017Search in Google Scholar

[41] Katagiri T, Yamamoto YS, Ozaki Y, Matsuura Y, Sato H. High axial resolution Raman probe made of a single hollow optical fiber. Appl Spectrosc 2009;63(1):103–7.10.1366/000370209787169650Search in Google Scholar

[42] Komachi Y, Katagiri T, Sato H, Tashiro H. Improvement and analysis of a micro Raman probe. Appl Opt 2009;48(9): 1683–96.10.1364/AO.48.001683Search in Google Scholar

[43] Bergholt MS, Lin K, Zheng W, Lau DPC, Huang Z. In vivo, real-time, transnasal, image-guided Raman endoscopy: defining spectral properties in the nasopharynx and larynx. J Biomed Opt 2012;17(7):077002.Search in Google Scholar

[44] Day JC1, Bennett R, Smith B, Kendall C, Hutchings J, Meaden GM, Born C, Yu S, Stone N. A miniature confocal Raman probe for endoscopic use. Phys Med Biol 2009;54(23):7077–87.10.1088/0031-9155/54/23/003Search in Google Scholar

[45] Kendall C, Day J, Hutchings J, Smith B, Shepherd N, Barr H, Stone N. Evaluation of Raman probe for oesophageal cancer diagnostics. Analyst 2010;135(12):3038–41.10.1039/c0an00536cSearch in Google Scholar PubMed

[46] Latka I, Dochow S, Krafft C, Dietzek B, Bartelt H, Popp J. Development of a fiber-based Raman probe for clinical diagnostics. Proc SPIE 2011;8087:80872D. doi:10.1117/12.889924.10.1117/12.889924Search in Google Scholar

[47] Praveen BB, Ashok PC, Mazilu M, Riches A, Herrington S, Dholakia K. Fluorescence suppression using wavelength modulated Raman spectroscopy in fiber-probe-based tissue analysis. J Biomed Opt 2012;17(7):077006.10.1117/1.JBO.17.7.077006Search in Google Scholar PubMed

[48] Schleusener J, Reble C, Helfmann J, Gersonde I, Cappius H-J, Glanert M, Fluhr JW, Meinke MC. Design and technical evaluation of fibre-coupled Raman probes for the image-guided discrimination of cancerous skin. Meas Sci Technol 2014;25(3):035701.10.1088/0957-0233/25/3/035701Search in Google Scholar

[49] Sharma M, Marple E, Reichenberg J, Tunnell JW. Design and characterization of a novel multimodal fiber-optic probe and spectroscopy system for skin cancer applications. Rev Sci Instrum 2014;85(8):083101.10.1063/1.4890199Search in Google Scholar PubMed PubMed Central

[50] Zhao J, Lui H, McLean DI, Zeng H. Integrated real-time Raman system for clinical in vivo skin analysis. Skin Res Technol 2008;14(4):484–92.10.1111/j.1600-0846.2008.00321.xSearch in Google Scholar PubMed

[51] Almond LM, Hutchings J, Barr H, Day J, Stone N, Kendall C. Development of fibre-optic Raman probes for in vivo diagnosis of upper gastrointestinal cancers. Spectrosc Eur 2011;23(3):6–12.Search in Google Scholar

[52] Krafft C, Dochow S, Latka I, Dietzek B, Popp J. Diagnosis and screening of cancer tissues by fiber-optic probe Raman spectroscopy. Biomed Spectrosc Imaging 2012;1(1):39–55.10.3233/BSI-2012-0004Search in Google Scholar

[53] Hanlon EB, Manoharan R, Koo TW, Shafer KE, Motz JT, Fitzmaurice M, Kramer JR, Itzkan I, Dasari RR, Feld MS. Prospects for in vivo Raman spectroscopy. Phys Med Biol 2000;45(2):R1–59.10.1088/0031-9155/45/2/201Search in Google Scholar PubMed

[54] Ashtikar M, Matthaus C, Schmitt M, Krafft C, Fahr A, Popp J. Non-invasive depth profile imaging of the stratum corneum using confocal Raman microscopy: First insights into the method. Eur J Pharm Sci 2013 18;50(5):601–8.10.1016/j.ejps.2013.05.030Search in Google Scholar PubMed

[55] McCreery RL. Raman spectroscopy for chemical analysis. Volume 225 of Chemical analysis: a series of monographs on analytical chemistry and its applications. New York: John Wiley & Sons; 2005.Search in Google Scholar

[56] Mahadevan-Jansen A, Richards-Kortum RR. Raman spectroscopy for the detection of cancers and precancers. J Biomed Opt 1996;1(1):31–70.10.1117/12.227815Search in Google Scholar PubMed

[57] Bashkatov AN, Genina EA, Kochubey VI, Tuchin VV. Optical properties of human skin subcutaneous and mucous tissues in the wavelength range from 400 to 2000 nm. J Phys D Appl Phys 2005;38(15):2543.10.1088/0022-3727/38/15/004Search in Google Scholar

[58] Short MA, Lui H, McLean D, Zeng H, Alajlan A, Chen XK. Changes in nuclei and peritumoral collagen within nodular basal cell carcinomas via confocal micro-Raman spectroscopy. J Biomed Opt 2006;11(3):34004.10.1117/1.2209549Search in Google Scholar

[59] Eikje NS, Aizawa K, Ozaki Y. Vibrational spectroscopy for molecular characterisation and diagnosis of benign, premalignant and malignant skin tumours. In: El-Gewely MR, editor. Biotechnology annual review. Amsterdam: Elsevier; 2005, p. 191–225.10.1016/S1387-2656(05)11006-0Search in Google Scholar

[60] Hata TR, Scholz TA, Ermakov IV, McClane RW, Khachik F, Gellermann W, Pershing LK. Non-invasive raman spectroscopic detection of carotenoids in human skin. J Invest Dermatol 2000;115(3):441–8.10.1046/j.1523-1747.2000.00060.xSearch in Google Scholar

[61] Deutsche Krebsgesellschaft e.V., Deutsche Dermatologische Gesellschaft, AWMF, editors. Kurzleitlinie – Basalzellkarzinom der Haut (Update 2012). Stand: 12/2013. http://www.awmf.org/uploads/tx_szleitlinien/032-021l_S2k_Basalzellkarzinom_2013-12.pdf [Accessed on November 28, 2014].Search in Google Scholar

[62] AWMF, Deutschen Krebsgesellschaft e.V., Deutschen Krebshilfe e.V., editors. Leitlinienprogramm Onkologie. S3 Leitlinie Melanom. Kurzversion 1.1. Februar 2013. http://www.awmf.org/uploads/tx_szleitlinien/032-024k_S3_Melanom_Diagnostik_Therapie_Nachsorge_2013-02.pdf [Accessed on November 28, 2014].Search in Google Scholar

[63] Huang Z, Lui H, Chen XK, Alajlan A, McLean DI, Zeng H. Raman spectroscopy of in vivo cutaneous melanin. J Biomed Opt 2004;9(6):1198–205.10.1117/1.1805553Search in Google Scholar

[64] Edwards HGM, Williams AC, Barry BW. Potential applications of FT-Raman spectroscopy for dermatological diagnostics. J Mol Struct 1995;347(0):379–87.10.1016/0022-2860(95)08560-ISearch in Google Scholar

[65] Schrader B, editor. Infrared and Raman spectroscopy: Methods and applications. Weinheim: VCH Verlagsgesellschaft mbH; 1995.Search in Google Scholar

[66] Oliveira AF, Santos ID, Cartaxo SB, Bitar RA, Enokihara MM, Martinho Hda S, Martin AA, Ferreira LM. Differential diagnosis in primary and metastatic cutaneous melanoma by FT-Raman spectroscopy. Acta Cir Bras 2010;25(5):434–9.10.1590/S0102-86502010000500009Search in Google Scholar PubMed

[67] Bonnier F, Mehmood A, Knief P, Meade AD, Hornebeck W, Lambkin H, Flynn K, McDonagh V, Healy C, Lee TC, Lyng FM, Byrne HJ. In vitro analysis of immersed human tissues by Raman microspectroscopy. J Raman Spectrosc 2011;42(5):888–96.10.1002/jrs.2825Search in Google Scholar

[68] Ghenuche P, Rammler S, Joly NY, Scharrer M, Frosz M, Wenger J, Russell PS, Rigneault H. Kagome hollow-core photonic crystal fiber probe for Raman spectroscopy. Opt Lett 2012;37(21):4371–3.10.1364/OL.37.004371Search in Google Scholar PubMed

[69] Yamamoto YS, Oshima Y, Shinzawa H, Katagiri T, Matsuura Y, Ozaki Y, Sato H. Subsurface sensing of biomedical tissues using a miniaturized Raman probe: study of thin-layered model samples. Anal Chim Acta 2008;619(1):8–13.10.1016/j.aca.2008.02.027Search in Google Scholar PubMed

[70] Brustlein S, Berto P, Hostein R, Ferrand P, Billaudeau C, Marguet D, Muir A, Knight J, Rigneault H. Double-clad hollow core photonic crystal fiber for coherent Raman endoscope. Opt Express 2011;19(13):12562–8.10.1364/OE.19.012562Search in Google Scholar PubMed

[71] Brunetti AC, Margulis W, Rottwitt K. Raman probes based on optically-poled double-clad fiber and coupler. Opt Express 2012;20(27):28563–72.10.1364/OE.20.028563Search in Google Scholar PubMed

[72] Tan KM, Singh GP, Herrington CS, Brown CTA. Near-infrared Raman spectroscopy using hollow-core photonic bandgap fibers. Opt Commun 2010;283(16):3204–6.10.1016/j.optcom.2010.04.037Search in Google Scholar

[73] Dochow S, Latka I, Becker M, Spittel R, Kobelke J, Schuster K, Graf A, Brückner S, Unger S, Rothhardt M, Dietzek B, Krafft C, Popp J. Multicore fiber with integrated fiber Bragg gratings for background-free Raman sensing. Opt Express 2012;20(18):20156–69.10.1364/OE.20.020156Search in Google Scholar PubMed

[74] Kostamovaara J, Tenhunen J, Kogler M, Nissinen I, Nissinen J, Keranen P. Fluorescence suppression in Raman spectroscopy using a time-gated CMOS SPAD. Opt Express 2013;21(25):31632–45.10.1364/OE.21.031632Search in Google Scholar PubMed

[75] Maiwald M, Erbert G, Klehr, Kronfeldt H-D, Schmidt H, Sumpf B, Tränkle G. Rapid shifted excitation Raman difference spectroscopy with a distributed feedback diode laser emitting at 785 nm. Appl Phys B 2006;85(4):509–12.10.1007/s00340-006-2459-8Search in Google Scholar

[76] Adami R, Kiefer J. Light-emitting diode based shifted-excitation Raman difference spectroscopy (LED-SERDS). Analyst 2013;138(21):6258–61.10.1039/c3an01367gSearch in Google Scholar PubMed

[77] De Luca AC, Mazilu M, Riches A, Herrington CS, Dholakia K. Online fluorescence suppression in modulated Raman spectroscopy. Anal Chem 2010;82(2):738–45.10.1021/ac9026737Search in Google Scholar PubMed

[78] Dochow S, Bergner N, Krafft C, Clement J, Mazilu M, Praveen BB, Ashok PC, Marchington R, Dholakiat K, Popp J. Classification of Raman spectra of single cells with autofluorescence suppression by wavelength modulated excitation. Anal Methods 2013;5(18):4608–14.10.1039/c3ay40193fSearch in Google Scholar

[79] Matousek P, Towrie M, Ma C, Kwok WM, Phillips D, Toner WT, Parker AW. Fluorescence suppression in resonance Raman spectroscopy using a high-performance picosecond Kerr gate. J Raman Spectrosc 2001;32(12):983–8.10.1002/jrs.784Search in Google Scholar

[80] Knorr F, Smith ZJ, Wachsmann-Hogiu S. Development of a time-gated system for Raman spectroscopy of biological samples. Opt Express 2010;18(19):20049–58.10.1364/OE.18.020049Search in Google Scholar

[81] Martyshkin DV, Ahuja RC, Kudriavtsev A, Mirov SB. Effective suppression of fluorescence light in Raman measurements using ultrafast time gated charge coupled device camera. Rev Sci Instrum 2004;75(3):630–5.10.1063/1.1646743Search in Google Scholar

[82] Krafft C, Dietzek B, Popp J. Raman and CARS microspectroscopy of cells and tissues. Analyst 2009;134(6):1046–57.10.1039/b822354hSearch in Google Scholar

[83] Bocklitz T, Walter A, Hartmann K, Rosch P, Popp J. How to pre-process Raman spectra for reliable and stable models? Anal Chim Acta 2011;704(1–2):47–56.10.1016/j.aca.2011.06.043Search in Google Scholar

[84] Cao A, Pandya AK, Serhatkulu GK, Weber RE, Dai H, Thakur JS, Naik VM, Naik R, Auner GW, Rabah R, Freeman DC. A robust method for automated background subtraction of tissue fluorescence. J Raman Spectrosc 2007;38(9):1199–205.10.1002/jrs.1753Search in Google Scholar

[85] Zhao J, Lui H, McLean DI, Zeng H. Automated autofluorescence background subtraction algorithm for biomedical Raman spectroscopy. Appl Spectrosc 2007;61(11):1225–32.10.1366/000370207782597003Search in Google Scholar

[86] Patil CA, Kirshnamoorthi H, Ellis DL, van Leeuwen TG, Mahadevan-Jansen A. A clinical instrument for combined raman spectroscopy-optical coherence tomography of skin cancers. Lasers Surg Med 2011;43(2):143–51.10.1002/lsm.21041Search in Google Scholar

[87] Kuzuhara A. Analysis of structural changes in bleached keratin fibers (black and white human hair) using Raman spectroscopy. Biopolymers 2006;81(6):506–14.10.1002/bip.20453Search in Google Scholar

[88] Martens H, Stark E. Extended multiplicative signal correction and spectral interference subtraction: new preprocessing methods for near infrared spectroscopy. J Pharm Biomed Anal 1991;9(8):625–35.10.1016/0731-7085(91)80188-FSearch in Google Scholar

[89] Sattlecker M, Bessant C, Smith J, Stone N. Investigation of support vector machines and Raman spectroscopy for lymph node diagnostics. Analyst 2010;135(5):895–901.10.1039/b920229cSearch in Google Scholar PubMed

[90] Candefjord S, Murayama Y, Nyberg M, Hallberg J, Ramser K, Ljungberg B, Bergh A, Lindahl OA. Combining scanning haptic microscopy and fibre optic Raman spectroscopy for tissue characterization. J Med Eng Technol 2012;36(6):319–27.10.3109/03091902.2012.687035Search in Google Scholar

[91] Kallaway C, Almond LM, Barr H, Wood J, Hutchings J, Kendall C, Stone N. Advances in the clinical application of Raman spectroscopy for cancer diagnostics. Photodiagnosis Photodyn Ther 2013;10(3):207–19.10.1016/j.pdpdt.2013.01.008Search in Google Scholar

[92] Bergholt MS, Zheng W, Ho KY, Teh M, Yeoh KG, So JB, Shabbir A, Huang Z.. Fiber-optic Raman spectroscopy probes gastric carcinogenesis in vivo at endoscopy. J Biophotonics 2013;6(1):49–59.10.1002/jbio.201200138Search in Google Scholar

[93] Reble C, Gersonde I, Dressler C, Helfmann J, Kühn W, Eichler HJ. Evaluation of Raman spectroscopic macro raster scans of native cervical cone biopsies using histopathological mapping. J Biomed Opt 2014;19(2):027007.10.1117/1.JBO.19.2.027007Search in Google Scholar

[94] Wehrens R, Putter H, Buydens L. The bootstrap: a tutorial. Chemometr Intell Lab Syst 2000;54(1):35–52.10.1016/S0169-7439(00)00102-7Search in Google Scholar

[95] Stone N, Kendall C, Smith J, Crow P, Barr H. Raman spectroscopy for identification of epithelial cancers. Faraday Discuss 2004;126:141–57.10.1039/b304992bSearch in Google Scholar PubMed

[96] Almond LM, Hutchings J, Lloyd GR, Francis-Jones J, Stone N, Barr H, Kendall C. Preclinical evaluation of a Raman spectroscopic probe for endoscopic classification of oesophageal pathologies. Proc SPIE 2012;8219:82190L. doi:10.1117/12.919876.10.1117/12.919876Search in Google Scholar

[97] Pence IJ, Vargis E, Mahadevan-Jansen A. Assessing variability of in vivo tissue Raman spectra. Appl Spectrosc 2013;67(7):789–800.10.1366/12-06773Search in Google Scholar PubMed

[98] Sattlecker M, Stone N, Smith J, Bessant C. Assessment of robustness and transferability of classification models built for cancer diagnostics using Raman spectroscopy. J Raman Spectrosc 2011;42(5):897–903.10.1002/jrs.2798Search in Google Scholar

[99] Schleusener J, Gluszczynska P, Reble C, Gersonde I, Helfmann J, Cappius H-J, Fluhr JW, Meinke MC. Perturbation factors on clinical handling of a fiber-coupled Raman probe for the cutaneous in vivo diagnostic Raman spectroscopy. Appl Spectrosc 2015;62(2)243–56.10.1366/14-07482Search in Google Scholar PubMed

[100] Huang C, Ando M, Hamaguchi H, Shigeto S. Disentangling dynamic changes of multiple cellular components during the yeast cell cycle by in vivo multivariate Raman imaging. Anal Chem 2012;84(13):5661–8.10.1021/ac300834fSearch in Google Scholar

[101] Schlücker S, Schaeberle MD, Huffman SW, Levin IW. Raman microspectroscopy: a comparison of point, line, and wide-field imaging methodologies. Anal Chem 2003;75(16):4312–8.10.1021/ac034169hSearch in Google Scholar

[102] Volkmer A. Vibrational imaging and microspectroscopies based on coherent anti-Stokes Raman scattering. J Phys D Appl Phys 2005;38(5):R59.10.1088/0022-3727/38/5/R01Search in Google Scholar

[103] Roth MM, Zenichowski K, Tarcea N, Popp J, Adelhelm S, Stolz M, Kelz A, Sandin C, Bauer S-M, Fechner T, Jahn T, Popow E, Roth B, Singh P, Srivastava M, Wolter D. The ERA2 facility: towards application of a fibre-based astronomical spectrograph for imaging spectroscopy in life sciences. Proc SPIE 2012;8450:84501T. doi:10.1117/12.925340.10.1117/12.925340Search in Google Scholar

[104] Schmälzlin E, Stolz M, Moralejo B, Adelhelm S, Roth MM. Bildgebende Ramanspektroskopie ohne schrittweises Abtasten der Probe. BioPhotonik 2014;2. http://www.photonik.de/bildgebende-ramanspektroskopie-ohne-schrittweises-abtasten-derprobe/150/21380/274320 [Accessed on April 15, 2015].Search in Google Scholar

[105] Sato H, Tanaka T, Ikeda T, Wada S, Tashiro H, Ozaki Y. Biomedical applications of a new portable Raman imaging probe. J Mol Struct 2001;598(1):93–6.10.1016/S0022-2860(01)00809-2Search in Google Scholar

[106] Krafft C, Sergo V. Biomedical applications of Raman and infrared spectroscopy to diagnose tissues. Spectroscopy 2006;20(5–6):195–218.10.1155/2006/738186Search in Google Scholar

[107] Caspers PJ, Lucassen GW, Puppels GJ. Combined in vivo confocal Raman spectroscopy and confocal microscopy of human skin. Biophys J 2003;85(1):572–80.10.1016/S0006-3495(03)74501-9Search in Google Scholar

[108] Cartaxo SB, Santos ID, Bitar R, Oliveira AF, Ferreira LM, Martinho HS, Martin AA. FT-Raman spectroscopy for the differentiation between cutaneous melanoma and pigmented nevus. Acta Cir Bras 2010;25(4):351–6.10.1590/S0102-86502010000400010Search in Google Scholar PubMed

[109] Cicchi R, Cosci A, Rossari S, Kapsokalyvas D, Baria E, Maio V, Massi D, De Giorgi V, Pimpinelli N, Saverio Pavone F. Combined fluorescence-Raman spectroscopic setup for the diagnosis of melanocytic lesions. J Biophotonics 2014;7 (1–2):86–95.10.1002/jbio.201200230Search in Google Scholar PubMed

[110] Patil CA, Bosschaart N, Keller MD, van Leeuwen TG, Mahadevan-Jansen A. Combined Raman spectroscopy and optical coherence tomography device for tissue characterization. Opt Lett 2008;33(10):1135–7.10.1364/OL.33.001135Search in Google Scholar

[111] Patil CA, Kalkman J, Faber DJ, Nyman JS, van Leeuwen TG, Mahadevan-Jansen A. Integrated system for combined Raman spectroscopy-spectral domain optical coherence tomography. J Biomed Opt 2011;16(1):011007.10.1117/1.3520132Search in Google Scholar PubMed PubMed Central

[112] Calin MA, Parasca SV, Savastru R, Calin MR, Dontu S. Optical techniques for the noninvasive diagnosis of skin cancer. J Cancer Res Clin Oncol 2013;139(7):1083–104.10.1007/s00432-013-1423-3Search in Google Scholar PubMed

[113] Nyberg M, Candefjord S, Jalkanen V, Ramser K, Lindahl OA. A combined tactile and Raman probe for tissue characterization-design; considerations. Meas Sci Technol 2012;23(6):065901.10.1088/0957-0233/23/6/065901Search in Google Scholar

[114] Vogler N, Meyer T, Akimov D, Latka I, Krafft C, Bendsoe N, Svanberg K, Dietzek B, Popp J. Multimodal imaging to study the morphochemistry of basal cell carcinoma. J Biophotonics 2010;3(10–11):728–36.10.1002/jbio.201000071Search in Google Scholar PubMed

[115] Reble C, Gersonde I, Helfmann J, Andree S, Illing G. Correction of Raman signals for tissue optical properties. Proc SPIE 2009;7368:73680C. doi:10.1117/12.831595.10.1117/12.831595Search in Google Scholar

[116] Reble C, Gersonde I, Andree S, Eichler HJ, Helfmann J. Quantitative Raman spectroscopy in turbid media. J Biomed Opt 2010;15(3):037016.10.1117/1.3456370Search in Google Scholar PubMed

[117] Andree S, Reble C, Helfmann J. Spectral in vivo signature of carotenoids in visible light diffuse reflectance from skin in comparison to ex vivo absorption spectra. Photonics Lasers Med 2013;2(4):323–35.10.1515/plm-2013-0032Search in Google Scholar

[118] Darvin ME, Gersonde I, Meinke M, Sterry W, Lademann J. Non-invasive in vivo determination of the carotenoids beta-carotene and lycopene concentrations in the human skin using the Raman spectroscopic method. J Phys D Appl Phys 2005;38(15):2696.10.1088/0022-3727/38/15/023Search in Google Scholar

Received: 2014-11-5
Accepted: 2015-1-9
Published Online: 2015-2-10
Published in Print: 2015-5-1

©2015 Walter de Gruyter GmbH, Berlin/Boston

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