Clinical coherent anti-Stokes Raman scattering and multiphoton tomography of human skin with a femtosecond laser and photonic crystal fiber

Breunig, Hans Georg; Weinigel, Martin; Bückle, Rainer; Kellner-Höfer, Marcel; Lademann, Jürgen; Darvin, Maxim E.; Sterry, Wolfram; König, Karsten

doi:10.1088/1612-2011/10/2/025604

Cited by 64 publications

(44 citation statements)

References 31 publications

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“…At present SHG is one of the new high-resolution nonlinear-optical imaging methods for the study of intact tissues and cell structures [276][277][278][279][280][281][282][283][284]. Similar to multiphoton fluorimetry, the SHG method has a few important advantages compared to the methods of linear spectroscopy and imaging, since the exciting near infrared light is weakly scattered by the tissue, while the second harmonic generation occurs already inside the tissue, in the small focal region of the focused laser beam.…”

Section: Nonlinear and Raman Microscopymentioning

confidence: 99%

“…The SHG in skin is provided, mainly, by the dermis due to its major component, the collagen that possesses considerable nonlinear susceptibility [280][281][282][283]. Obviously, the reduction of scattering due to optical clearing for the incident long-wave light and, particularly, for the short-wave second-harmonic detected light can improve the SG images of the collagen structures of the dermis in the forward direction and worsen the signal in the reflection mode.…”

Section: Nonlinear and Raman Microscopymentioning

confidence: 99%

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Optical clearing of biological tissues: prospects of application in medical diagnostics and phototherapy

Genina

Bashkatov

Sinichkin

et al. 2015

JBPE

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Abstract.A review of specific features and methods of optical clearing and related interaction of light with tissues is presented. Physical and molecular mechanisms of immersion, compression, and photodynamic/photothermal optical clearing of some fibrous and cellular tissues are discussed. The possibility of efficient control of the tissue optical properties, particularly, the reduction of light scattering in tissues is demonstrated, which facilitates the increased efficiency of various optical visualisation methods (optical biopsy) used in medical purposes. © 2015 Samara State Aerospace University (SSAU).Keywords: tissue, optical clearing, optical diagnostics, imaging. 1, 404-413 (1997). 5. C. L. Smithpeter, A. K. Dunn, A. J. Welch, and R. Richards-Kortum, "Penetration depth limits of in vivo confocal reflectance imaging," Appl. Opt. 37, 2749Opt. 37, -2754Opt. 37, (1998. 6. V. V. Tuchin, L. V. Wang, and D. A. Zimnyakov, Optical Polarization in Biomedical Applications, SpringerVerlag, New York, NY, USA (2006). 7. R. Drezek, A. Dunn, and R. Richards-Kortum, "Light scattering from cells: finite-difference time-domain simulations and goniometric measurements," Appl. Opt. 38(16), 3651-3661 (1999). 8. K. Sokolov, R. Drezek, K. Gossagee, and R. Richards-Kortum, "Reflectance spectroscopy with polarized light:is it sensitive to cellular and nuclear morphology," Opt. Express 5, 302-317 (1999). 9. D. W. Leonard, and K. M. Meek, "Refractive indices of the collagen fibrils and extrafibrillar material of the corneal stroma," Biophysical J. 72, 1382-1387 (1997). 10. A. G. Borovoi, E. I. Naats, and U. G. Oppel, "Scattering of light by a red blood cell," J. Biomed. Opt. 3, 364-372 (1998). 11. A. N. Yaroslavsky, A. V. Priezzhev, J. Rodriguez, I. V. Yaroslavsky, and H. Battarbee, "Optics of blood,"Chap. 2 in Handbook of Optical Biomedical Diagnostics, V. V. Tuchin, Ed., pp. 169-216, PM107 SPIE Press, Bellingham, WA, USA (2002). 12. G. Mazarevica, T. Freivalds, and A. Jurka, "Properties of erythrocyte light refraction in diabetic patients," J.Biomed. Opt. 7, 244-247 (2002). 13. M. Friebel, and M. Meinke, "Model function to calculate the refractive index of native hemoglobin in the wavelength range of 250-1100 nm dependent on concentration," Appl. Opt. 45(12), 2838-2842 (2006). Appl. Opt. 35(19), 3413-3420 (1996). 34. D. Zhu, J. Wang, Z. Zhi, X. Wen, and Q. Luo, "Imaging dermal blood flow through the intact rat skin with an optical clearing method," J. Biomed. Opt. 15, 026008 (2010 241. K. König, G. Flemming, and R. Hibst, "Laser-induced autofluorescence spectroscopy of dental caries lesion," Cell. Mol. Biol. 44, 1293-1300. 242. E. G. Borisova, T. T. Uzunov, and L. A. Avramov, "Early differentiation between caries and tooth demineralization using laser-induced autofluorescence spectroscopy," Lasers Surg. Med. 34, 249-253 (2004 -20(12), 1512-1516 (1984). 245. K. Konig, H. Schneckenburger, and R. Hibst, "Time-gated in vivo autofluorescence imaging of dental caries,"Cell. Mol. Biol. 45, 233-239 (1999). 246. E. Borisova, P. Tr...

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Section: Nonlinear and Raman Microscopymentioning

confidence: 99%

Section: Nonlinear and Raman Microscopymentioning

confidence: 99%

Optical clearing of biological tissues: prospects of application in medical diagnostics and phototherapy

Genina

Bashkatov

Sinichkin

et al. 2015

JBPE

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“…Several efforts have been undertaken to bring multimodal nonlinear imaging into more clinical applications. [7][8][9] Nonetheless, the widespread transfer to a clinical environment for routine biomedical imaging is still at an early stage. To facilitate this transition, two key aspects have to be taken into consideration in the microscopy platforms design: the detection scheme and laser technology.…”

Section: Introductionmentioning

confidence: 99%

Epi-detecting label-free multimodal imaging platform using a compact diode-pumped femtosecond solid-state laser

Andreana

Le²,

Hansen

et al. 2017

J. Biomed. Opt

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-detecting label-free multimodal imaging platform using a compact diode-pumped femtosecond solid-state laser," J. Biomed. Opt. 22(9), 091517 (2017), doi: 10.1117/1.JBO.22.9.091517. Abstract. We have developed an epi-detected multimodal nonlinear optical microscopy platform based on a compact and cost-effective laser source featuring simultaneous acquisition of signals arising from hyperspectral coherent anti-Stokes Raman scattering (CARS), two-photon fluorescence, and second harmonic generation. The laser source is based on an approach using a frequency-doubled distributed Bragg reflector-tapered diode laser to pump a femtosecond Ti:sapphire laser. The operational parameters of the laser source are set to the optimum trade-off between the spectral and temporal requirements for these three modalities, achieving sufficient spectral resolution for CARS in the lipid region. The experimental results on a biological tissue reveal that the combination of the epi-detection scheme and the use of a compact diode-pumped femtosecond solid-state laser in the nonlinear optical microscope is promising for biomedical applications in a clinical environment. © The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.

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“…8 CARS can be applied to provide supplementary information on the distribution of lipids in human skin. [9][10][11][12] Lipids are nonfluorescent, but rich in Raman-active CH 2 groups with a stretch vibrational transition at 2845 cm −1 . 13 In human skin, they are, for instance, part of (i) the superficial skin barrier (cholesterol), 14 (ii) the cellular membrane (phospholipids), and (iii) the dermis, stored inside dermal adipocytes as energy reservoirs.…”

Section: Introductionmentioning

confidence: 99%

“…During the last decade, "CE marked" AF/SHG based tomographs have been developed including systems with an additional CARS option. [10][11][12]20 The certified clinical AF/SHG-CARS tomograph MPTflex CARS (JenLab, Germany) as a mobile flexible nonlinear imaging system not only simplifies in vivo AF/SHG imaging of human skin 9,[24][25][26] but is also a multipurpose system which can be used for small animal research, in vivo stem cell tracking 27 and ex vivo biopsy imaging. Free-space-beam delivery inside an articulated optical mirror arm is provided by active beam position control.…”

Section: Introductionmentioning

confidence: 99%

Multipurpose nonlinear optical imaging system forin vivoandex vivomultimodal histology

et al. 2015

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Abstract. We report on a flexible multipurpose nonlinear microscopic imaging system based on a femtosecond excitation source and a photonic crystal fiber with multiple miniaturized time-correlated single-photon counting detectors. The system provides the simultaneous acquisition of e.g., two-photon autofluorescence, secondharmonic generation, and coherent anti-Stokes Raman scattering images. Its flexible scan head permits ex vivo biological imaging with subcellular resolution such as rapid biopsy examination during surgery as well as imaging on small as well as large animals. Above all, such an arrangement perfectly matches the needs for the clinical investigation of human skin in vivo where knowledge about the distribution of endogenous fluorophores, second-harmonic generation-active collagen as well as nonfluorescent lipids is of high interest.

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Clinical coherent anti-Stokes Raman scattering and multiphoton tomography of human skin with a femtosecond laser and photonic crystal fiber

Cited by 64 publications

References 31 publications

Optical clearing of biological tissues: prospects of application in medical diagnostics and phototherapy

Optical clearing of biological tissues: prospects of application in medical diagnostics and phototherapy

Epi-detecting label-free multimodal imaging platform using a compact diode-pumped femtosecond solid-state laser

Multipurpose nonlinear optical imaging system forin vivoandex vivomultimodal histology

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