Chromatic Swept-Source Laser Scanning – Konzept für eine zellauflösende konfokale Laserspaltlampe?

Zusammenfassung

Hintergrund Die In-vivo-Charakterisierung der Morphologie des Epithelgewebes der Kornea ist von erheblicher Bedeutung für die Diagnostik, die Krankheitsprognose und die Entwicklung einer Behandlungsstrategie bei Oberflächenerkrankungen des Auges. Im Gegensatz zu vielen alternativen Methoden bietet die In-vivo-Konfokalmikroskopie der Kornea (CCM) nicht nur eine makroskopische Beschreibung des kornealen Gewebes, sondern ermöglicht dessen Darstellung mit zellulärer Auflösung. Die Translation der CCM von der Forschung in die klinische Praxis ist jedoch durch die komplexe und bisher weitgehend manuelle Bedienung der verfügbaren CCM-Systeme erheblich eingeschränkt. Für Tiefenschnittbilder, analog zur konventionellen Spaltlampenmikroskopie, müssen außerdem aufgrund der frontalen Orientierung des Bildfeldes bei der CCM in aufwendigen Tiefenscans Volumenaufnahmen erzeugt werden, aus denen sich anschließend Tiefenschnitte berechnen lassen. Bereits die reine Aufnahmedauer liegt hierbei im Bereich von Sekunden, zusätzlich müssen Bewegungsartefakte aufwendig korrigiert werden.

Material und Methoden Dieser Beitrag stellt das Konzept und die Optiksimulation eines neuen Bildgebungsverfahrens auf Basis eines Swept-Source-Lasers in Verbindung mit einer speziellen chromatischen Optik vor. Hierbei verändert der Laser periodisch seine Wellenlänge und wird aufgrund der wellenlängenabhängigen Aberration der chromatischen Optik in unterschiedlichen Tiefen fokussiert.

Ergebnisse Die Ergebnisse der Optiksimulation versprechen eine gute optische Auflösung bei einer Abbildungstiefe von insgesamt 145 µm.

Schlussfolgerung Das langfristige Ziel ist die konfokalmikroskopische zellauflösende In-vivo-Bildgebung der Kornea in Echtzeit mit verschieden orientierten Schnittrichtungen.

Abstract

Background The in vivo characterisation of corneal epithelial tissue morphology is of considerable importance for diagnosis, disease prognosis, and the development of a treatment strategy for ocular surface diseases. In contrast to many alternative methods, in vivo corneal confocal microscopy (CCM) not only provides a macroscopic description of the corneal tissue but also allows its visualisation with cellular resolution. However, the translation of CCM from research to clinical practice is significantly limited by the complex and still largely manual operation of available CCM systems. In addition, for cross-sectional images, and analogously to conventional slit lamp microscopy, volume data must be acquired in time-consuming depth scans due to the frontal orientation of the image field in CCM, from which depth slices can subsequently be calculated. The pure acquisition time is already in the range of seconds, and additionally, motion artefacts have to be corrected in a sophisticated way.

Materials and Methods This paper presents the concept and optics simulation of a new imaging technique based on a swept-source laser in combination with special chromatic optics. Here, the laser periodically changes its wavelength and is focused at different depths due to the wavelength-dependent aberration of the chromatic optics.

Results The optics simulation results promise good optical resolution at a total imaging depth of 145 µm.

Conclusion The long-term goal is cell-resolving in vivo corneal confocal microscopy in real time with differently oriented sectioning directions.

Schlüsselwörter

Kornea - Konfokalmikroskopie - bildgebende Diagnostik - chromatische Aberration - Swept-Source-Laser - Spaltlampe

Key words

cornea - confocal microscopy - diagnostic imaging - chromatic aberration - swept-source laser - slit lamp

Publication History

Received: 23 June 2023

Accepted: 24 September 2023

Article published online:
13 December 2023

• Literatur

• 1 Anonymous Methodologies to diagnose and monitor dry eye disease: Report of the Diagnostic Methodology Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf 2007; 5: 108-152
• 2 Wolffsohn JS, Arita R, Chalmers R. et al. TFOS DEWS II Diagnostic Methodology report. Ocul Surf 2017; 15: 539-574
• 3 McDonald JE. Surface phenomena of tear films. Trans Am Ophthalmol Soc 1968; 66: 905-939
• 4 Moussa S, Eppig T, Pattmöller J. et al. Diurnal and zonal analysis of corneal surface temperature in young healthy adults. Eur J Ophthalmol 2013; 23: 641-645
• 5 Denoyer A, Rabut G, Baudouin C. Tear film aberration dynamics and vision-related quality of life in patients with dry eye disease. Ophthalmology 2012; 119: 1811-1818
• 6 Bille JF. ed. High Resolution Imaging in Microscopy and Ophthalmology: New Frontiers in Biomedical Optics [Internet]. Cham (CH): Springer; 2019.
• 7 Han L, Tan B, Hosseinaee Z. et al. Line-scanning SD-OCT for in-vivo, non-contact, volumetric, cellular resolution imaging of the human cornea and limbus. Biomed Opt Express 2022; 13: 4007-4020
• 8 Chen YT, Tsai CY, Chiu YK. et al. En face and cross-sectional corneal tomograms using sub-micron spatial resolution optical coherence tomography. Sci Rep 2018; 8: 14349
• 9 Villani E, Baudouin C, Efron N. et al. In vivo confocal microscopy of the ocular surface: From bench to bedside. Curr Eye Res 2014; 39: 213-231
• 10 Yamaguchi T, Hamrah P, Shimazaki J. Bilateral alterations in corneal nerves, dendritic cells, and tear cytokine levels in ocular surface disease. Cornea 2016; 35 (Suppl. 01) S65-S70
• 11 Cruzat A, Qazi Y, Hamrah P. In vivo confocal microscopy of corneal nerves in health and disease. Ocul Surf 2017; 15: 15-47
• 12 Chan TCY, Wan KH, Shih KC. et al. Advances in dry eye imaging: the present and beyond. Br J Ophthalmol 2018; 102: 295-301
• 13 Wang EF, Misra SL, Patel DV. In vivo confocal microscopy of the human cornea in the assessment of peripheral neuropathy and systemic diseases. Biomed Res Int 2015; 2015: 951081
• 14 Petroll WM, Weaver M, Vaidya S. et al. Quantitative 3-dimensional corneal imaging in vivo using a modified HRT-RCM confocal microscope. Cornea 2013; 32: e36-e43
• 15 Stachs O, Guthoff RF, Aumann S. In vivo confocal scanning laser microscopy. In: Bille JF, ed. High Resolution Imaging in Microscopy and Ophthalmology: New Frontiers in Biomedical Optics Cham (CH): Springer; 2019: 263-284
• 16 Vagenas D, Pritchard N, Edwards K. et al. Optimal image sample size for corneal nerve morphometry. Optom Vis Sci 2012; 89: 812-817
• 17 Parissi M, Karanis G, Randjelovic S. et al. Standardized baseline human corneal subbasal nerve density for clinical investigations with laser-scanning in vivo confocal microscopy. Invest Ophthalmol Vis Sci 2013; 54: 7091-7102
• 18 Kheirkhah A, Muller R, Mikolajczak J. et al. Comparison of standard versus wide-field composite images of the corneal subbasal layer by in vivo confocal microscopy. Invest Ophthalmol Vis Sci 2015; 56: 5801-5807
• 19 Lovblom LE, Halpern EM, Wu T. et al. In vivo corneal confocal microscopy and prediction of future-incident neuropathy in type 1 diabetes: a preliminary longitudinal analysis. Can J Diabetes 2015; 39: 390-397
• 20 Dehghani C, Pritchard N, Edwards K. et al. Risk factors associated with corneal nerve alteration in type 1 diabetes in the absence of neuropathy: a longitudinal in vivo corneal confocal microscopy study. Cornea 2016; 35: 847-852
• 21 Markoulli M, You J, Kim J. et al. Corneal nerve morphology and tear film substance P in diabetes. Optom Vis Sci 2017; 94: 726-731
• 22 Zhivov A, Blum M, Guthoff R. et al. Real-time mapping of the subepithelial nerve plexus by in vivo confocal laser scanning microscopy. Br J Ophthalmol 2010; 94: 1133-1135
• 23 Turuwhenua JT, Patel DV, McGhee CNJ. Fully automated montaging of laser scanning in vivo confocal microscopy images of the human corneal subbasal nerve plexus. Invest Ophthalmol Vis Sci 2012; 53: 2235-2242
• 24 Edwards K, Pritchard N, Gosschalk K. et al. Wide-field assessment of the human corneal subbasal nerve plexus in diabetic neuropathy using a novel mapping technique. Cornea 2012; 31: 1078-1082
• 25 Allgeier S, Maier S, Mikut R. et al. Mosaicking the subbasal nerve plexus by guided eye movements. Invest Ophthalmol Vis Sci 2014; 55: 6082-6089
• 26 Allgeier S, Bartschat A, Bohn S. et al. 3D confocal laser-scanning microscopy for large-area imaging of the corneal subbasal nerve plexus. Sci Rep 2018; 8: 7468
• 27 Patel SV, McLaren JW, Hodge DO. et al. Normal human keratocyte density and corneal thickness measurement by using confocal microscopy in vivo. Invest Ophthalmol Vis Sci 2001; 42: 333-339
• 28 Prakasam RK, Winter K, Schwiede M. et al. Characteristic quantities of corneal epithelial structures in confocal laser scanning microscopic volume data sets. Cornea 2013; 32: 636-643
• 29 Sterenczak KA, Winter K, Sperlich K. et al. Morphological characterization of the human corneal epithelium by in vivo confocal laser scanning microscopy. Quant Imaging Med Surg 2021; 11: 1737-1750
• 30 Li J, Jester JV, Cavanagh HD. et al. On-line 3-dimensional confocal imaging in vivo. Invest Ophthalmol Vis Sci 2000; 41: 2945-2953
• 31 Scarpa F, Fiorin D, Ruggeri A. In vivo three-dimensional reconstruction of the cornea from confocal microscopy images. Annu Int Conf IEEE Eng Med Biol Soc 2007; 2007: 747-750
• 32 Zhivov A, Stachs O, Stave J. et al. In vivo three-dimensional confocal laser scanning microscopy of corneal surface and epithelium. Br J Ophthalmol 2009; 93: 667-672
• 33 Petroll WM, Robertson DM. In vivo confocal microscopy of the cornea: new developments in image acquisition, reconstruction, and analysis using the HRT-Rostock Corneal Module. Ocul Surf 2015; 13: 187-203
• 34 Bohn S, Sperlich K, Allgeier S. et al. Cellular in vivo 3D imaging of the cornea by confocal laser scanning microscopy. Biomed Opt Express 2018; 9: 2511-2525
• 35 Allgeier S, Zhivov A, Eberle F. et al. Image reconstruction of the subbasal nerve plexus with in vivo confocal microscopy. Invest Ophthalmol Vis Sci 2011; 52: 5022-5028
• 36 Auksorius E, Borycki D, Stremplewski P. et al. In vivo imaging of the human cornea with high-speed and high-resolution Fourier-domain full-field optical coherence tomography. Biomed Opt Express 2020; 11: 2849-2865
• 37 Rayer M, Mansfield D. Chromatic confocal microscopy using staircase diffractive surface. Appl Opt 2014; 53: 5123-5130
• 38 Dobson SL, Sun PC, Fainman Y. Diffractive lenses for chromatic confocal imaging. Appl Opt 1997; 36: 4744-4748
• 39 Novak J, Miks A. Hyperchromats with linear dependence of longitudinal chromatic aberration on wavelength. Optik 2005; 116: 165-168
• 40 Tearney GJ, Shishkov M, Bouma BE. Spectrally encoded miniature endoscopy. Opt Lett 2002; 27: 412-414
• 41 Boudoux C, Yun S, Oh W. et al. Rapid wavelength-swept spectrally encoded confocal microscopy. Opt Express 2005; 13: 8214-8221
• 42 Kim S, Hwang J, Heo J. et al. Spectrally encoded slit confocal microscopy using a wavelength-swept laser. J Biomed Opt 2015; 20: 036016
• 43 Kang DK, Suter MJ, Boudoux C. et al. Co-registered spectrally encoded confocal microscopy and optical frequency domain imaging system. J Microsc 2010; 239: 87-91
• 44 Lyda W, Gronle M, Fleischle D. et al. Advantages of chromatic-confocal spectral interferometry in comparison to chromatic confocal microscopy. Meas Sci Technol 2012; 23: 054009
• 45 Olsovsky C, Shelton R, Carrasco-Zevallos O. et al. Chromatic confocal microscopy for multi-depth imaging of epithelial tissue. Biomed Opt Express 2013; 4: 732-740