Abstract
This paper reports on the latest advances in line-field confocal optical coherence tomography (LC-OCT), a recently invented imaging technology that now allows the generation of either horizontal (x × y) section images at an adjustable depth or vertical (x × z) section images at an adjustable lateral position, as well as three-dimensional images. For both two-dimensional imaging modes, images are acquired in real-time, with real-time control of the depth and lateral positions. Three-dimensional (x × y × z) images are acquired from a stack of horizontal section images. The device is in the form of a portable probe. The handle of the probe has a button and a scroll wheel allowing the user to control the imaging modes. Using a supercontinuum laser as a broadband light source and a high numerical microscope objective, an isotropic spatial resolution of ∼1 µm is achieved. The field of view of the three-dimensional images is 1.2 mm × 0.5 mm × 0.5 mm (x × y × z). Images of skin tissues are presented to demonstrate the potential of the technology in dermatology.
Keywords: optical coherence tomography (OCT), microscopy, three-dimensional imaging, dermatology
Acknowledgements
The authors thank the whole team of engineers at DAMAE Medical, especially Olivier Levecq, Hicham Azimani, Emmanuel Cohen and Romain Allemand, for their work on the technology and design of the LC-OCT prototype presented in this paper. They also thank Amyn Kassara for providing the segmentation of the three-dimensional images. They are also grateful to Anaïs Barut and David Siret as directors and managers of DAMAE Medical.
Footnotes
Jonas Ogien received his M.S. degree in Optics in 2014 from University of Rochester (USA) and his Ph.D. degree in Physics in 2017 from Paris-Saclay University (France). He also holds an engineering degree from Institut d’Optique Graduate School (France) and currently works as a research engineer at DAMAE Medical, a startup company working on OCT for skin imaging. He is particularly interested in innovative optical methods for high-resolution imaging. His current research focuses on the development of new modalities and optical improvements in OCT.
Anthony Daures received his engineering degree in Physics from Institut National des Sciences Appliquées in Toulouse (France) in 2014. He also holds an M.S. degree in Medical Imaging from University of Paul Sabatier (Toulouse, France). As an image processing engineer with more than seven years of experience, he has worked for different medical imaging companies and has always focused on the development of innovative algorithms. He is currently working as an image quality engineer at DAMAE Medical to improve diagnosis in real-time.
Maxime Cazalas, M.Sc., is a computer science and image processing engineer with over 14 years of experience in medical imaging. Passionate about innovation in the field of medical imaging, he has been involved in the development of new and innovative imaging solutions to assist physicians in delivering the best possible care to their patient. Maxime is currently focused on dermato-oncology, using in vivo optical imaging technics to better understand the pathogenesis of skin tumors, enabling earlier diagnosis and optimal patient-tailored therapy.
Jean-Luc Perrot, Ph.D. & M.D., has a 30-year career as a dermatologist and medical oncologist at Saint-Etienne University Hospital (France). He was the former president of the non-invasive skin imaging group of the French Society of Dermatology. Multimodal skin imaging has developed considerably in his dermatology department where different optical techniques are combined, including confocal microscopy, OCT, LC-OCT, dermatoscopy and Raman spectroscopy. Perrot has been involved in the validation and/or design of several innovative imaging devices. Although he has published numerous books on skin imaging, his primary objective remains the management of patients in the context of daily practice.
Arnaud Dubois received his Ph.D. degree in Physics in 1997 from Paris-Saclay University (France). Since 2006, he is a professor of optics at Université Paris-Saclay, Institut d’Optique Graduate School (France). Pioneer in full-field OCT in the early 2000, Dubois has since been a major contributor to the development of this technology. He has published 120 research articles in scientific journals and conference proceedings and 12 book chapters. He was the scientific editor in 2016 of the first and only handbook entirely devoted to full-field OCT. In 2014, Dubois co-founded DAMAE Medical, a startup company working on an innovative OCT technique for skin imaging.
References
- 1.Fercher A F. Optical coherence tomography. Journal of Biomedical Optics. 1996;1(2):157–173. doi: 10.1117/12.231361. [DOI] [PubMed] [Google Scholar]
- 2.Podoleanu A G. Optical coherence tomography. Journal of Microscopy. 2012;247(3):209–219. doi: 10.1111/j.1365-2818.2012.03619.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Zysk A M, Nguyen F T, Oldenburg A L, Marks D L, Boppart S A. Optical coherence tomography: a review of clinical development from bench to bedside. Journal of Biomedical Optics. 2007;12(5):051403. doi: 10.1117/1.2793736. [DOI] [PubMed] [Google Scholar]
- 4.Schuman J S, Puliafito C A, Fujimoto J G, Duker J S. Optical Coherence Tomography of Ocular Diseases. 3rd ed. New Jersey: Slack Inc.; 2013. [Google Scholar]
- 5.Bezerra H G, Costa M A, Guagliumi G, Rollins A M, Simon D I. Intracoronary optical coherence tomography: a comprehensive review clinical and research applications. JACC: Cardiovascular Interventions. 2009;2(11):1035–1046. doi: 10.1016/j.jcin.2009.06.019. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Adler D C, Chen Y, Huber R, Schmitt J, Connolly J, Fujimoto J G. Three-dimensional endomicroscopy using optical coherence tomography. Nature Photonics. 2007;1(12):709–716. doi: 10.1038/nphoton.2007.228. [DOI] [Google Scholar]
- 7.Yu X, Ding Q, Hu C, Mu G, Deng Y, Luo Y, Yuan Z, Yu H, Liu L. Evaluating micro-optical coherence tomography as a feasible imaging tool for pancreatic disease diagnosis. IEEE Journal of Selected Topics in Quantum Electronics. 2019;25(1):1–8. doi: 10.1109/JSTQE.2018.2827662. [DOI] [Google Scholar]
- 8.Men J, Huang Y, Solanki J, Zeng X, Alex A, Jerwick J, Zhang Z, Tanzi R E, Li A, Zhou C. Optical coherence tomography for brain imaging and developmental biology. IEEE Journal of Selected Topics in Quantum Electronics. 2016;22(4):120–132. doi: 10.1109/JSTQE.2015.2513667. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Fan Y, Xia Y, Zhang X, Sun Y, Tang J, Zhang L, Liao H. Optical coherence tomography for precision brain imaging, neurosurgical guidance and minimally invasive theranostics. Bioscience Trends. 2018;12(1):12–23. doi: 10.5582/bst.2017.01258. [DOI] [PubMed] [Google Scholar]
- 10.Levine A, Wang K, Markowitz O. Optical coherence tomography in the diagnosis of skin cancer. Dermatologic Clinics. 2017;35(4):465–488. doi: 10.1016/j.det.2017.06.008. [DOI] [PubMed] [Google Scholar]
- 11.Drexler W, Morgner U, Kärtner F X, Pitris C, Boppart S A, Li X D, Ippen E P, Fujimoto J G. In vivo ultrahigh-resolution optical coherence tomography. Optics Letters. 1999;24(17):1221–1223. doi: 10.1364/OL.24.001221. [DOI] [PubMed] [Google Scholar]
- 12.Povazay B, Bizheva K, Unterhuber A, Hermann B, Sattmann H, Fercher A F, Drexler W, Apolonski A, Wadsworth W J, Knight J C, Russell P S J, Vetterlein M, Scherzer E. Submicrometer axial resolution optical coherence tomography. Optics Letters. 2002;27(20):1800–1802. doi: 10.1364/OL.27.001800. [DOI] [PubMed] [Google Scholar]
- 13.Wang Y, Zhao Y, Nelson J S, Chen Z, Windeler R S. Ultrahigh-resolution optical coherence tomography by broadband continuum generation from a photonic crystal fiber. Optics Letters. 2003;28(3):182–184. doi: 10.1364/OL.28.000182. [DOI] [PubMed] [Google Scholar]
- 14.Aguirre A, Nishizawa N, Fujimoto J, Seitz W, Lederer M, Kopf D. Continuum generation in a novel photonic crystal fiber for ultrahigh resolution optical coherence tomography at 800 nm and 1300 nm. Optics Express. 2006;14(3):1145–1160. doi: 10.1364/OE.14.001145. [DOI] [PubMed] [Google Scholar]
- 15.Leitgeb R A. En face optical coherence tomography: a technology review. Biomedical Optics Express. 2019;10(5):2177–2201. doi: 10.1364/BOE.10.002177. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Choma M, Sarunic M, Yang C, Izatt J. Sensitivity advantage of swept source and Fourier domain optical coherence tomography. Optics Express. 2003;11(18):2183–2189. doi: 10.1364/OE.11.002183. [DOI] [PubMed] [Google Scholar]
- 17.Lee K S, Rolland J P. Bessel beam spectral-domain high-resolution optical coherence tomography with micro-optic axicon providing extended focusing range. Optics Letters. 2008;33(15):1696–1698. doi: 10.1364/OL.33.001696. [DOI] [PubMed] [Google Scholar]
- 18.Leitgeb R A, Villiger M, Bachmann A H, Steinmann L, Lasser T. Extended focus depth for Fourier domain optical coherence microscopy. Optics Letters. 2006;31(16):2450–2452. doi: 10.1364/OL.31.002450. [DOI] [PubMed] [Google Scholar]
- 19.Tamborski S, Lyu H C, Dolezyczek H, Malinowska M, Wilczynski G, Szlag D, Lasser T, Wojtkowski M, Szkulmowski M. Extended-focus optical coherence microscopy for high-resolution imaging of the murine brain. Biomedical Optics Express. 2016;7(11):4400–4414. doi: 10.1364/BOE.7.004400. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Liu L, Chu K K, Houser G H, Diephuis B J, Li Y, Wilsterman E J, Shastry S, Dierksen G, Birket S E, Mazur M, Byan-Parker S, Grizzle W E, Sorscher E J, Rowe S M, Tearney G J. Method for quantitative study of airway functional microanatomy using micro-optical coherence tomography. PLoS One. 2013;8(1):e54473. doi: 10.1371/journal.pone.0054473. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Liu L, Liu C, Howe W C, Sheppard C J R, Chen N. Binary-phase spatial filter for real-time swept-source optical coherence microscopy. Optics Letters. 2007;32(16):2375–2377. doi: 10.1364/OL.32.002375. [DOI] [PubMed] [Google Scholar]
- 22.Yin B, Chu K K, Liang C P, Singh K, Reddy R, Tearney G J. µOCT imaging using depth of focus extension by self-imaging wavefront division in a common-path fiber optic probe. Optics Express. 2016;24(5):5555–5564. doi: 10.1364/OE.24.005555. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Ralston T S, Marks D L, Carney P S, Boppart S A. Interferometric synthetic aperture microscopy. Nature Physics. 2007;3(2):129–134. doi: 10.1038/nphys514. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Coquoz S, Bouwens A, Marchand P J, Extermann J, Lasser T. Interferometric synthetic aperture microscopy for extended focus optical coherence microscopy. Optics Express. 2017;25(24):30807–30819. doi: 10.1364/OE.25.030807. [DOI] [PubMed] [Google Scholar]
- 25.Yu L, Rao B, Zhang J, Su J, Wang Q, Guo S, Chen Z. Improved lateral resolution in optical coherence tomography by digital focusing using two-dimensional numerical diffraction method. Optics Express. 2007;15(12):7634–7641. doi: 10.1364/OE.15.007634. [DOI] [PubMed] [Google Scholar]
- 26.Fechtig D J, Kumar A, Drexler W, Leitgeb R A. Full range line-field parallel swept source imaging utilizing digital refocusing. Journal of Modern Optics. 2015;62(21):1801–1807. doi: 10.1080/09500340.2014.990938. [DOI] [Google Scholar]
- 27.Mo J, de Groot M, de Boer J F. Focus-extension by depth-encoded synthetic aperture in optical coherence tomography. Optics Express. 2013;21(8):10048–10061. doi: 10.1364/OE.21.010048. [DOI] [PubMed] [Google Scholar]
- 28.Holmes J. Proceedings of the 1st Canterbury Workshop on Optical Coherence Tomography and Adaptive Optics. Canterbury: SPIE; 2008. Theory and applications of multi-beam OCT. [Google Scholar]
- 29.Holmes J, Hattersley S, Stone N, Bazant-Hegemark F, Barr H. Proceedings of Coherence Domain Optical Methods and Optical Coherence Tomography in Biomedicine XII. San Jose: SPIE; 2008. Multi-channel fourier domain OCT system with superior lateral resolution for biomedical applications. [Google Scholar]
- 30.Yi L, Sun L, Ding W. Multifocal spectral-domain optical coherence tomography based on Bessel beam for extended imaging depth. Journal of Biomedical Optics. 2017;22(10):1–8. doi: 10.1117/1.JBO.22.10.106016. [DOI] [PubMed] [Google Scholar]
- 31.Li J, Luo Y, Wang X, Wang N, Bo E, Chen S, Chen S, Chen S, Tsai M T, Liu L. Extending the depth of focus of fiber-optic optical coherence tomography using a chromatic dual-focus design. Applied Optics. 2018;57(21):6040–6046. doi: 10.1364/AO.57.006040. [DOI] [PubMed] [Google Scholar]
- 32.Nam A S, Ren J, Bouma B E, Vakoc B J. Demonstration of triband multi-focal imaging with optical coherence tomography. Applied Sciences (Basel, Switzerland) 2018;8(12):2395. doi: 10.3390/app8122395. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 33.Huber R, Wojtkowski M, Fujimoto J G, Jiang J Y, Cable A E. Three-dimensional and C-mode OCT imaging with a compact, frequency swept laser source at 1300 nm. Optics Express. 2005;13(26):10523–10538. doi: 10.1364/OPEX.13.010523. [DOI] [PubMed] [Google Scholar]
- 34.Rolland J P, Meemon P, Murali S, Thompson K P, Lee K S. Gabor-based fusion technique for optical coherence microscopy. Optics Express. 2010;18(4):3632–3642. doi: 10.1364/OE.18.003632. [DOI] [PubMed] [Google Scholar]
- 35.Lee K S, Thompson K P, Meemon P, Rolland J P. Cellular resolution optical coherence microscopy with high acquisition speed for in-vivo human skin volumetric imaging. Optics Letters. 2011;36(12):2221–2223. doi: 10.1364/OL.36.002221. [DOI] [PubMed] [Google Scholar]
- 36.Liu S, Mulligan J A, Adie S G. Volumetric optical coherence microscopy with a high space-bandwidth-time product enabled by hybrid adaptive optics. Biomedical Optics Express. 2018;9(7):3137–3152. doi: 10.1364/BOE.9.003137. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 37.Schmitt J M, Lee S L, Yung K M. An optical coherence microscope with enhanced resolving power in thick tissue. Optics Communications. 1997;142(4–6):203–207. doi: 10.1016/S0030-4018(97)00280-0. [DOI] [Google Scholar]
- 38.Lexer F, Hitzenberger C K, Drexler W, Molebny S, Sattmann H, Sticker M, Fercher A F. Dynamic coherent focus OCT with depth-independent transversal resolution. Journal of Modern Optics. 1999;46(3):541–553. doi: 10.1080/09500349908231282. [DOI] [Google Scholar]
- 39.Qi P A, Himmer P A, Gordon M L, Yang VXD, Dickensheets D L, Vitkin I A. Dynamic focus control in high-speed optical coherence tomography based on a microelectromechanical mirror. Optics Communications. 2004;232(1–6):123–128. doi: 10.1016/j.optcom.2004.01.015. [DOI] [Google Scholar]
- 40.Divetia A, Hsieh T H, Zhang J, Chen Z, Bachman M, Li G P. Dynamically focused optical coherence tomography for endoscopic applications. Applied Physics Letters. 2005;86(10):103902. doi: 10.1063/1.1879096. [DOI] [Google Scholar]
- 41.Yang V X D, Munce N, Pekar J, Gordon M L, Lo S, Marcon N E, Wilson B C, Vitkin I A. Micromachined array tip for multifocus fiber-based optical coherence tomography. Optics Letters. 2004;29(15):1754–1756. doi: 10.1364/OL.29.001754. [DOI] [PubMed] [Google Scholar]
- 42.Dubois A, Levecq O, Azimani H, Davis A, Ogien J, Siret D, Barut A. Line-field confocal time-domain optical coherence tomography with dynamic focusing. Optics Express. 2018;26(26):33534–33542. doi: 10.1364/OE.26.033534. [DOI] [PubMed] [Google Scholar]
- 43.Dubois A, Levecq O, Azimani H, Siret D, Barut A, Suppa M, Del Marmol V, Malvehy J, Cinotti E, Rubegni P, Perrot J L. Line-field confocal optical coherence tomography for high-resolution non-invasive imaging of skin tumors. Journal of Biomedical Optics. 2018;23(10):1–9. doi: 10.1117/1.JBO.23.10.106007. [DOI] [PubMed] [Google Scholar]
- 44.Ogien J, Siret D, Levecq O, Azimani H, David A, Xue W, Perrot J L, Dubois A. Proceedings of Optical Coherence Tomography and Coherence Domain Optical Methods in Biomedicine XXIII. San Francisco: SPIE; 2019. Line-field confocal optical coherence tomography. [Google Scholar]
- 45.Davis A, Levecq O, Azimani H, Siret D, Dubois A. Simultaneous dual-band line-field confocal optical coherence tomography: application to skin imaging. Biomedical Optics Express. 2019;10(2):694–706. doi: 10.1364/BOE.10.000694. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 46.Dubois A, Xue W, Levecq O, Bulkin P, Coutrot A L, Ogien J. Mirau-based line-field confocal optical coherence tomography. Optics Express. 2020;28(6):7918–7927. doi: 10.1364/OE.389637. [DOI] [PubMed] [Google Scholar]
- 47.Ogien J, Levecq O, Azimani H, Dubois A. Dual-mode line-field confocal optical coherence tomography for ultrahigh-resolution vertical and horizontal section imaging of human skin in vivo. Biomedical Optics Express. 2020;11(3):1327–1335. doi: 10.1364/BOE.385303. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 48.Larkin K G. Efficient nonlinear algorithm for envelope detection in white light interferometry. Journal of the Optical Society of America A, Optics, Image Science, and Vision. 1996;13(4):832–843. doi: 10.1364/JOSAA.13.000832. [DOI] [Google Scholar]
- 49.Cazalas M, Levecq O, Azimani H, Siret D, Barut A, Suppa M, del Marmol V, Malvehy J, Cinotti E, Rubegni P, Perrot J L, Dubois A. Proceedings of Photonics in Dermatology and Plastic Surgery 2019. San Francisco: SPIE; 2019. Skin lesion imaging with line-field confocal optical coherence tomography. [Google Scholar]
- 50.Dejonckheere G, Suppa M, Marmol V, Meyer T, Stockfleth E. The actinic dysplasia syndrome-diagnostic approaches defining a new concept in field carcinogenesis with multiple cSCC. Journal of the European Academy of Dermatology and Venereology. 2019;33(S8):16–20. doi: 10.1111/jdv.15949. [DOI] [PubMed] [Google Scholar]
- 51.Pedrazzani M, Breugnot J, Rouaud-Tinguely P, Cazalas M, Davis A, Bordes S, Dubois A, Closs B. Comparison of line-field confocal optical coherence tomography images with histological sections: validation of a new method for in vivo and non-invasive quantification of superficial dermis thickness. Skin Research and Technology. 2020;26(3):398–404. doi: 10.1111/srt.12815. [DOI] [PubMed] [Google Scholar]
- 52.Ogien J, Levecq O, Cazalas M, Suppa M, del Marmol V, Malvehy J, Cinotti E, Rubegni P, Perrot J L, Dubois A. Proceedings of Photonics in Dermatology and Plastic Surgery 2020. San Francisco: SPIE; 2020. Handheld line-field confocal optical coherence tomography for dermatology. [Google Scholar]
- 53.Monnier J, Tognetti L, Miyamoto M, Suppa M, Cinotti E, Fontaine M, Perez J, Orte Cano C, Yélamos O, Puig S, Dubois A, Rubegni P, Marmol V, Malvehy J, Perrot J L. In vivo characterization of healthy human skin with a novel, non-invasive imging technique: line-field confocal optical coherence tomography. Journal of the European Academy of Dermatology and Venereology, 2020, doi:10.1111/jdv.16857 [DOI] [PubMed]
- 54.Ruini C, Sattler E. Line-field confocal optical coherence tomography: the golden goose? Aktuelle Dermatologie. 2020;46:148–151. doi: 10.1055/a-1072-7002. [DOI] [Google Scholar]
- 55.Tognetti L, Rizzo A, Fiorani D, Cinotti E, Perrot J L, Rubegni P. New findings in non-invasive imaging of aquagenic keratoderma: Line-field optical coherence tomography, dermoscopy and reflectance confocal microscopy. Skin Research and Technology, 2020, doi:10.1111/srt.12882 [DOI] [PubMed]
- 56.Ruini C, Schuh S, Sattler E, Welzel J. Line-field confocal optical coherence tomography-practical applications in dermatology and comparison with established imaging methods. Skin Research and Technology, 2020, doi:10.1111/srt.12949 [DOI] [PubMed]
- 57.Tognetti L, Fiorani D, Cinotti E, Rubegni P. Tridimensional skin imaging in aquagenic keratoderma: virtual histology by line-field confocal optical coherence tomography. International Journal of Dermatology, 2020, doi:10.1111/ijd.15169 [DOI] [PubMed]
- 58.Tognetti L, Fiorani D, Suppa M, Cinotti E, Fontaine M, Marmol V D, Rubegni P, Perrot J L. Examination of circumscribed palmar hypokeratosis with line-field confocal optical coherence tomography: dermoscopic, ultrasonographic and histopathologic correlates. Indian Journal of Dermatology, Venereology and Leprology. 2020;86(2):206–208. doi: 10.4103/ijdvl.IJDVL_546_19. [DOI] [PubMed] [Google Scholar]
- 59.Tognetti L, Carraro A, Lamberti A, Cinotti E, Suppa M, Luc Perrot J, Rubegni P. Kaposi sarcoma of the glans: new findings by line field confocal optical coherence tomography examination. Skin Research and Technology, 2020, doi:10.1111/srt.12938 [DOI] [PubMed]
- 60.Ruini C, Schuh S, Pellacani G, French L, Welzel J, Sattler E. In vivo imaging of Sarcoptes scabiei infestation using line-field confocal optical coherence tomography. Journal of the European Academy of Dermatology and Venereology, 2020, doi:10.1111/jdv.16671 [DOI] [PubMed]
- 61.Rennie D. Nailfold dermatoscopy in general practice. Australian Family Physician. 2015;44(11):809–812. [PubMed] [Google Scholar]
- 62.Xue W, Ogien J, Levecq O, Dubois A. Line-field confocal optical coherence tomography based on a Mirau interferometer. In: Proceedings of Unconventional Optical Imaging II. SPIE, 2020