Raman spectroscopy for the discrimination of cancerous and normal skin

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.

[1]  Martina C Meinke,et al.  Perturbation Factors in the Clinical Handling of a Fiber-Coupled Raman Probe for Cutaneous in Vivo Diagnostic Raman Spectroscopy , 2015, Applied spectroscopy.

[2]  Matthew D. Keller,et al.  Combined Raman spectroscopy and optical coherence tomography device for tissue characterization. , 2008, Optics letters.

[3]  Stefan Andree,et al.  Spectral in vivo signature of carotenoids in visible light diffuse reflectance from skin in comparison to ex vivo absorption spectra , 2013 .

[4]  S Webb,et al.  Adapting IMRT delivery fraction-by-fraction to cater for variable intrafraction motion , 2008, Physics in medicine and biology.

[5]  Nicholas Stone,et al.  Investigation of support vector machines and Raman spectroscopy for lymph node diagnostics. , 2010, The Analyst.

[6]  T C Bakker Schut,et al.  Tissue characterization using high wave number Raman spectroscopy. , 2005, Journal of biomedical optics.

[7]  A. Kuzuhara Analysis of structural changes in bleached keratin fibers (black and white human hair) using Raman spectroscopy , 2006, Biopolymers.

[8]  N Stone,et al.  Assessment of fiberoptic near-infrared raman spectroscopy for diagnosis of bladder and prostate cancer. , 2005, Urology.

[9]  Pavel Matousek,et al.  Fluorescence suppression in resonance Raman spectroscopy using a high-performance picosecond Kerr gate , 2001 .

[10]  H. Barr,et al.  Advances in the clinical application of Raman spectroscopy for cancer diagnostics. , 2013, Photodiagnosis and photodynamic therapy.

[11]  James W Tunnell,et al.  Design and characterization of a novel multimodal fiber-optic probe and spectroscopy system for skin cancer applications. , 2014, The Review of scientific instruments.

[12]  Christian Matthäus,et al.  Non-invasive depth profile imaging of the stratum corneum using confocal Raman microscopy: first insights into the method. , 2013, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[13]  Kishan Dholakia,et al.  Fluorescence suppression using wavelength modulated Raman spectroscopy in fiber-probe-based tissue analysis. , 2012, Journal of biomedical optics.

[14]  Gregory W. Auner,et al.  A robust method for automated background subtraction of tissue fluorescence , 2007 .

[15]  Christian Matthäus,et al.  Etaloning, fluorescence and ambient light suppression by modulated wavelength Raman spectroscopy , 2012 .

[16]  Yuji Matsuura,et al.  Subsurface sensing of biomedical tissues using a miniaturized Raman probe: study of thin-layered model samples. , 2008, Analytica chimica acta.

[17]  Masahiro Ando,et al.  Disentangling dynamic changes of multiple cellular components during the yeast cell cycle by in vivo multivariate Raman imaging. , 2012, Analytical chemistry.

[18]  Jürgen Popp,et al.  Classification of Raman spectra of single cells with autofluorescence suppression by wavelength modulated excitation , 2013 .

[19]  Gerwin J Puppels,et al.  Fiber-optic probes for in vivo Raman spectroscopy in the high-wavenumber region. , 2005, Analytical chemistry.

[20]  D. Moss Biomedical Applications of Synchrotron Infrared Microspectroscopy , 2010 .

[21]  Hervé Rigneault,et al.  Kagome hollow-core photonic crystal fiber probe for Raman spectroscopy. , 2012, Optics letters.

[22]  Anita Mahadevan-Jansen,et al.  Development of a handheld Raman microspectrometer for clinical dermatologic applications. , 2007, Optics express.

[23]  G. Puppels,et al.  Combined in vivo confocal Raman spectroscopy and confocal microscopy of human skin. , 2003, Biophysical journal.

[24]  Maxim E. Darvin,et al.  Non-invasive in vivo determination of the carotenoids beta-carotene and lycopene concentrations in the human skin using the Raman spectroscopic method , 2005 .

[25]  William F. Finney,et al.  Subsurface Probing in Diffusely Scattering Media Using Spatially Offset Raman Spectroscopy , 2005, Applied spectroscopy.

[26]  Ingo Gersonde,et al.  Quantitative Raman spectroscopy in turbid media. , 2010, Journal of biomedical optics.

[27]  D. McLean,et al.  Automated Autofluorescence Background Subtraction Algorithm for Biomedical Raman Spectroscopy , 2007, Applied Spectroscopy.

[28]  L. M. Almond,et al.  Preclinical evaluation of a Raman spectroscopic probe for endoscopic classification of oesophageal pathologies , 2012, Other Conferences.

[29]  Wei Zheng,et al.  Fiber-optic Raman probe couples ball lens for depth-selected Raman measurements of epithelial tissue , 2010, Biomedical optics express.

[30]  Hugh J. Byrne,et al.  In Vitro Analysis of Immersed Human Tissues by Raman Microspectroscopy , 2011 .

[31]  Roxana Savastru,et al.  Optical techniques for the noninvasive diagnosis of skin cancer , 2013, Journal of Cancer Research and Clinical Oncology.

[32]  Ines Latka,et al.  Development of a fiber-based Raman probe for clinical diagnostics , 2011, European Conference on Biomedical Optics.

[33]  H. Martens,et al.  Extended multiplicative signal correction and spectral interference subtraction: new preprocessing methods for near infrared spectroscopy. , 1991, Journal of pharmaceutical and biomedical analysis.

[34]  Brian C. Wilson,et al.  In vivo Near-infrared Raman Spectroscopy: Demonstration of Feasibility During Clinical Gastrointestinal Endoscopy¶ , 2000, Photochemistry and photobiology.

[35]  Haishan Zeng,et al.  Integrated real‐time Raman system for clinical in vivo skin analysis , 2008, Skin research and technology : official journal of International Society for Bioengineering and the Skin (ISBS) [and] International Society for Digital Imaging of Skin (ISDIS) [and] International Society for Skin Imaging.

[36]  Gajendra P. Singh,et al.  Near-Infrared Raman Spectroscopy Using Hollow-Core Photonic Bandgap Fibers , 2010 .

[37]  B. Dietzek,et al.  Raman and CARS microspectroscopy of cells and tissues. , 2009, The Analyst.

[38]  A. Mahadevan-Jansen,et al.  Raman microspectroscopy for skin cancer detection in vitro. , 2008, Journal of biomedical optics.

[39]  H. Barr,et al.  Development of fibre-optic Raman probes for in vivo diagnosis of upper gastrointestinal cancers , 2011 .

[40]  S. Lam,et al.  RAMAN SPECTROSCOPY FOR IN VIVO TISSUE ANALYSIS AND DIAGNOSIS, FROM INSTRUMENT DEVELOPMENT TO CLINICAL APPLICATIONS , 2008 .

[41]  Yukihiro Ozaki,et al.  Vibrational spectroscopy for molecular characterisation and diagnosis of benign, premalignant and malignant skin tumours. , 2005, Biotechnology annual review.

[42]  H. Bruining,et al.  In vitro and in vivo Raman spectroscopy of human skin. , 1998, Biospectroscopy.

[43]  C. Hadjur,et al.  In vivo chemical investigation of human skin using a confocal Raman fiber optic microprobe. , 2005, Journal of biomedical optics.

[44]  B. Wilson,et al.  Development of an In Vivo Raman Spectroscopic System for Diagnostic Applications , 1997 .

[45]  Johannes Kiefer,et al.  Light-emitting diode based shifted-excitation Raman difference spectroscopy (LED-SERDS). , 2013, The Analyst.

[46]  Nicholas Stone,et al.  Assessment of robustness and transferability of classification models built for cancer diagnostics using Raman spectroscopy , 2011 .

[47]  W. Coleman,et al.  Fitzpatrickʼs Dermatology in General Medicine , 2008 .

[48]  H. Barr,et al.  Raman spectroscopy for identification of epithelial cancers. , 2004, Faraday discussions.

[49]  T. B. Bakker Schut,et al.  Discriminating basal cell carcinoma from its surrounding tissue by Raman spectroscopy. , 2002, The Journal of investigative dermatology.

[50]  O. Lindahl,et al.  A combined tactile and Raman probe for tissue characterization—design considerations , 2012 .

[51]  J. Popp,et al.  Sample size planning for classification models. , 2012, Analytica chimica acta.

[52]  J. Polak,et al.  In situ Characterisation of Living Cells by Raman Spectroscopy , 2002 .

[53]  H. Barr,et al.  Evaluation of Raman probe for oesophageal cancer diagnostics. , 2010, The Analyst.

[54]  Riccardo Cicchi,et al.  Combined fluorescence‐Raman spectroscopic setup for the diagnosis of melanocytic lesions , 2014, Journal of biophotonics.

[55]  Anita Mahadevan-Jansen,et al.  A clinical instrument for combined raman spectroscopy‐optical coherence tomography of skin cancers , 2011, Lasers in surgery and medicine.

[56]  Ingo Gersonde,et al.  Correction of Raman signals for tissue optical properties , 2009, European Conference on Biomedical Optics.

[57]  Mads S. Bergholt,et al.  Fiber‐optic Raman spectroscopy probes gastric carcinogenesis in vivo at endoscopy , 2013, Journal of Biophotonics.

[58]  D. McLean,et al.  Real-time Raman Spectroscopy for in Vivo Skin Cancer Diagnosis Raman Spectroscopy of Skin Cancer , 2022 .

[59]  Anita Mahadevan-Jansen,et al.  In vivo nonmelanoma skin cancer diagnosis using Raman microspectroscopy , 2008, Lasers in surgery and medicine.

[60]  Ines Latka,et al.  Diagnosis and screening of cancer tissues by fiber-optic probe Raman spectroscopy , 2012 .

[61]  Abigail S Haka,et al.  Real-time Raman system for in vivo disease diagnosis. , 2005, Journal of biomedical optics.

[62]  N. Ramanujam,et al.  Development of a Fiber Optic Probe to Measure NIR Raman Spectra of Cervical Tissue In Vivo , 1998, Photochemistry and photobiology.

[63]  L. K. Hansen,et al.  Melanoma diagnosis by Raman spectroscopy and neural networks: structure alterations in proteins and lipids in intact cancer tissue. , 2004, The Journal of investigative dermatology.

[64]  S. Wada,et al.  Biomedical applications of a new portable Raman imaging probe , 2001 .

[65]  Kishan Dholakia,et al.  Online fluorescence suppression in modulated Raman spectroscopy. , 2010, Analytical chemistry.

[66]  H. Byrne,et al.  Raman Microscopy: Complement or Competitor , 2010 .

[67]  Ioan Notingher,et al.  Development of Raman microspectroscopy for automated detection and imaging of basal cell carcinoma. , 2009, Journal of biomedical optics.

[68]  Jürgen Popp,et al.  How to pre-process Raman spectra for reliable and stable models? , 2011, Analytica chimica acta.

[69]  H. Tashiro,et al.  Improvement and analysis of a micro Raman probe. , 2009, Applied optics.

[70]  Wei Zheng,et al.  In vivo, real-time, transnasal, image-guided Raman endoscopy: defining spectral properties in the nasopharynx and larynx. , 2012, Journal of biomedical optics.

[71]  G. Puppels,et al.  Towards oncological application of Raman spectroscopy , 2009, Journal of biophotonics.

[72]  B. Dietzek,et al.  Multicore fiber with integrated fiber Bragg gratings for background-free Raman sensing. , 2012, Optics express.

[73]  H. Bruining,et al.  In vivo confocal Raman microspectroscopy of the skin: noninvasive determination of molecular concentration profiles. , 2001, The Journal of investigative dermatology.

[74]  Haishan Zeng,et al.  Raman spectroscopy of in vivo cutaneous melanin. , 2004, Journal of biomedical optics.

[75]  R. Richards-Kortum,et al.  Raman spectroscopy for the detection of cancers and precancers. , 1996, Journal of biomedical optics.

[76]  Bernhard Schrader,et al.  Infrared and Raman spectroscopy : methods and applications , 1995 .

[77]  A. N. Bashkatov,et al.  Optical properties of human skin, subcutaneous and mucous tissues in the wavelength range from 400 to 2000 nm , 2005 .

[78]  O. Lindahl,et al.  Combining scanning haptic microscopy and fibre optic Raman spectroscopy for tissue characterization , 2012, Journal of medical engineering & technology.

[79]  H. Wulf,et al.  Diagnosis of malignant melanoma and basal cell carcinoma by in vivo NIR-FT Raman spectroscopy is independent of skin pigmentation , 2013, Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology.

[80]  Anita Mahadevan-Jansen,et al.  Integrated system for combined Raman spectroscopy-spectral domain optical coherence tomography. , 2011, Journal of biomedical optics.

[81]  Anita Mahadevan-Jansen,et al.  Detecting Temporal and Spatial Effects of Epithelial Cancers with Raman Spectroscopy , 2009, Disease markers.

[82]  T. B. Bakker Schut,et al.  Discriminating basal cell carcinoma from perilesional skin using high wave-number Raman spectroscopy. , 2007, Journal of biomedical optics.

[83]  D. Kartashov,et al.  Ionization spectrum broadening and frequency blue-shift of high-intensity femtosecond laser pulses in gas-filled capillary tubes , 2002 .

[84]  Airton Abrahão Martin,et al.  FT-Raman spectroscopy study for skin cancer diagnosis , 2003 .

[85]  W. Margulis,et al.  Raman probes based on optically-poled double-clad fiber and coupler. , 2012, Optics express.

[86]  J. McGarvey,et al.  Ex vivo diagnosis of lung cancer using a Raman miniprobe. , 2009, The journal of physical chemistry. B.

[87]  Heinz-Detlef Kronfeldt,et al.  Rapid shifted excitation Raman difference spectroscopy with a distributed feedback diode laser emitting at 785 nm , 2006 .

[88]  C. Kendall,et al.  Vibrational spectroscopy: a clinical tool for cancer diagnostics. , 2009, The Analyst.

[89]  R Marchesini,et al.  Monte Carlo simulation of light fluence in tissue in a cylindrical diffusing fibre geometry. , 1999, Physics in medicine and biology.

[90]  Dmitry Martyshkin,et al.  Effective suppression of fluorescence light in Raman measurements using ultrafast time gated charge coupled device camera , 2004 .

[91]  J. Roodenburg,et al.  In vivo detection of dysplastic tissue by Raman spectroscopy. , 2000, Analytical chemistry.

[92]  Brian C Wilson,et al.  Diagnostic potential of near-infrared Raman spectroscopy in the colon: differentiating adenomatous from hyperplastic polyps. , 2003, Gastrointestinal endoscopy.

[93]  Michael S Feld,et al.  Optical fiber probe for biomedical Raman spectroscopy. , 2004, Applied optics.

[94]  Chen-Yuan Dong,et al.  Multiphoton fluorescence and second harmonic generation microscopy for imaging infectious keratitis. , 2007, Journal of biomedical optics.

[95]  N. Bendsøe,et al.  Multimodal imaging to study the morphochemistry of basal cell carcinoma , 2010, Journal of biophotonics.

[96]  Juha Kostamovaara,et al.  Fluorescence suppression in Raman spectroscopy using a time-gated CMOS SPAD. , 2013, Optics express.

[97]  Haishan Zeng,et al.  Changes in nuclei and peritumoral collagen within nodular basal cell carcinomas via confocal micro-Raman spectroscopy. , 2006, Journal of biomedical optics.

[98]  Richard L. McCreery,et al.  Raman Spectroscopy for Chemical Analysis , 2000 .

[99]  C. Krafft,et al.  Biomedical applications of Raman and infrared spectroscopy to diagnose tissues , 2006 .

[100]  Hein Putter,et al.  The bootstrap: a tutorial , 2000 .

[101]  Joachim W. Fluhr,et al.  Design and technical evaluation of fibre-coupled Raman probes for the image-guided discrimination of cancerous skin , 2014 .

[102]  R. Dasari,et al.  Prospects for in vivo Raman spectroscopy , 2000 .

[103]  H. Wulf,et al.  Distinctive Molecular Abnormalities in Benign and Malignant Skin Lesions: Studies by Raman Spectroscopy , 1997, Photochemistry and photobiology.

[104]  Gerwin J. Puppels,et al.  Automated depth-scanning confocal Raman microspectrometer for rapidin vivo determination of water concentration profiles in human skin , 2000 .

[105]  R. Bitar,et al.  Differential diagnosis in primary and metastatic cutaneous melanoma by FT-Raman spectroscopy. , 2010, Acta cirurgica brasileira.

[106]  Hervé Rigneault,et al.  Double-clad hollow core photonic crystal fiber for coherent Raman endoscope. , 2011, Optics express.

[107]  Sebastian Schlücker,et al.  Raman microspectroscopy: a comparison of point, line, and wide-field imaging methodologies. , 2003, Analytical chemistry.

[108]  Ingo Gersonde,et al.  Evaluation of Raman spectroscopic macro raster scans of native cervical cone biopsies using histopathological mapping , 2014, Journal of biomedical optics.

[109]  F. Khachik,et al.  Non-invasive raman spectroscopic detection of carotenoids in human skin. , 2000, The Journal of investigative dermatology.

[110]  Brian W. Barry,et al.  Potential applications of FT-Raman spectroscopy for dermatological diagnostics , 1995 .

[111]  Brian C. Wilson,et al.  Study of Fiber-Optic Probes for in vivo Medical Raman Spectroscopy , 1999 .

[112]  Anita Mahadevan-Jansen,et al.  Assessing Variability of in Vivo Tissue Raman Spectra , 2013, Applied spectroscopy.

[113]  Yuji Matsuura,et al.  High Axial Resolution Raman Probe Made of a Single Hollow Optical Fiber , 2009, Applied spectroscopy.

[114]  Airton Abrahão Martin,et al.  FT-Raman spectroscopy for the differentiation between cutaneous melanoma and pigmented nevus. , 2010, Acta cirurgica brasileira.

[115]  Andreas Volkmer,et al.  Vibrational imaging and microspectroscopies based on coherent anti-Stokes Raman scattering microscopy , 2005 .

[116]  Sebastian Wachsmann-Hogiu,et al.  Development of a time-gated system for Raman spectroscopy of biological samples. , 2010, Optics express.

[117]  Haishan Zeng,et al.  Real-Time Raman Spectroscopy for Noninvasive in vivo Skin Analysis and Diagnosis , 2010 .

[118]  Siyuan Yu,et al.  A miniature confocal Raman probe for endoscopic use , 2009, Physics in medicine and biology.

[119]  I. Notinghera,et al.  In situ characterisation of living cells by Raman spectroscopy , 2014 .

[120]  Andreas Kelz,et al.  The ERA2 facility: towards application of a fibre-based astronomical spectrograph for imaging spectroscopy in life sciences , 2012, Other Conferences.