Dependence of ultrahigh resolution optical coherence tomography using supercontinuum

Optical coherence tomography (OCT) is a noninvasive cross-sectional imaging technique with micrometer resolution. The theoretical axial resolution is determined by the center wavelength and bandwidth of the light source, and the wider the bandwidth, the higher the axial resolution. The characteristics of OCT imaging depend on the optical wavelength used. In this paper, we investigated the wavelength dependence of ultrahigh-resolution (UHR) OCT using a supercontinuum for biomedical imaging. Wideband, high-power, low-noise supercontinua (SC) were generated at λ = 0.8, 1.1, 1.3, and 1.7 μ m based on ultrashort pulses and nonlinear fibers. The wavelength dependence of OCT imaging was examined quantitatively using biological phantoms. Ultrahigh-resolution imaging of a rat lung was demonstrated with λ = 0.8–1.0 μ m UHR-OCT. The variation of alveolar volume was estimated using three-dimensional image analysis. Finally, UHR-spectral domain-OCT and optical coherence microscopy at 1.7 μ m were developed, and high-resolution and high-penetration imaging of turbid tissue, especially mouse brain, was demonstrated.

Optical coherence tomography (OCT) is a non-invasive cross-sectional imaging technique with micrometer resolution. We have been investigating ultrahigh-resolution (UHR)-OCT using supercontinuum. The characteristics of OCT imaging depend on the optical wavelength used. In order to investigate the wavelength dependence of UHR-OCT, the wideband, high-power, low-noise supercontinua were generated at wavelengths of 0.8, 1.1, 1.3, and 1.7 um based on ultrashort pulses and nonlinear fibers. The wavelength dependence of OCT imaging was examined quantitatively using biological phantoms and rat lung tissue. Then we developed UHR-OCT and optical coherence microscopy (OCM) at 1.7 um, which is called as “Optical Window III”. The high-resolution and high-penetration imaging of mouse brain was demonstrated.

In recent years, optical coherence tomography (OCT) became gained importance in medical disciplines like ophthalmology, due to its noninvasive optical imaging technique with micrometer resolution and short measurement time. It enables e. g. the measurement and visualization of the depth structure of the retina. In other medical disciplines like dermatology, histopathological analysis is still the gold standard for skin cancer diagnosis. The EU-funded project VIAMOS (Vertically Integrated Array-type Mirau-based OCT System) proposes a new type of OCT system combined with micro-technologies to provide a hand-held, low-cost and miniaturized OCT system. The concept is a combination of full-field and full-range swept-source OCT (SS-OCT) detection in a multi-channel sensor based on a micro-optical Mirau-interferometer array, which is fabricated by means of wafer fabrication. This paper presents the study of an experimental proof-of-concept OCT system as a one-channel sensor with bulk optics. This sensor is a Linnik-interferometer type with similar optical parameters as the Mirau-interferometer array. A commercial wavelength tunable light source with a center wavelength at 845nm and 50nm spectral bandwidth is used with a camera for parallel OCT A-Scan detection. In addition, the reference microscope objective lens of the Linnik-interferometer is mounted on a piezo-actuated phase-shifter. Phase-shifting interferometry (PSI) techniques are applied for resolving the conjugate complex artifact and consequently contribute to an increase of image quality and depth range. A suppression ratio of the complex conjugate term of 36 dB is shown and a system sensitivity greater than 96 dB could be measured.

Optical coherence microscopy (OCM) is a high-resolution imaging technique based on optical coherence tomography and confocal microscopy. The recent studies on OCM operating at 800-1300 nm spectral region have shown that OCM enables to visualize micrometer- or sub-micrometer-scale structures of animal tissues. Although OCMs offers such high-resolution label-free imaging capability of animal tissues, the imaging depth was restricted by multiple light scattering and light absorption of water in samples. Here, for high-resolution deep-tissue imaging, we developed an OCM in the 1700-nm spectral band by using a supercontinuum (SC) source with a Gaussian-like spectral shape in the wavelength region. Recently, it has been reported that the 1700-nm spectral band is a promising choice for enhancing the imaging depth in the observation of turbid scattering tissues because of the low attenuation coefficient of light. In this study, to clarify that the 1700-nm OCM has a potential to realize the enhanced imaging depth, we compared the attenuation of the signal-to-noise ratio between the 1700-nm and 1300-nm OCM imaging of a mouse brain under the same signal detection sensitivity condition. The result shows that the 1700-nm OCM enables us to achieve the enhanced imaging depth. In this 1700-nm OCM, we also confirmed that the lateral resolution of 1.3 µm and axial resolution of 2.8 µm in tissue were achieved.

Optical coherence tomography (OCT) is a non-invasive imaging technique with many applications and widespread use in ophthalmology [1]. The axial resolution in OCT is inversely proportional to the bandwidth of the optical source used, but the improved axial resolution comes at the price of more significant effects of dispersion stemming from the imaging system and the imaged medium. In recent years, spectral intensity (SI) OCT has been shown, as a classical realisation of quantum OCT, to remove even orders of dispersion intrinsically [2, 3]. One major drawback of SI OCT is however halving of the imaging range which is crucial in spectrometer based OCT which is limited by the spectral resolution, and hence number of pixels of the spectrometer. In this work we demonstrate SI OCT with the full imaging range.

Clinical Imaging with Optical Coherence Tomography

Optical coherence tomography (OCT) is a non-invasive optical imaging technique with a micrometer resolution that may potentially offer real-time bedside imaging of sufficient detail to allow for morphological discrimination between different types of bullae. To explore the potential of OCT in bullous skin disorders by looking at a set of patients with skin blisters of known origin and study the OCT images for possible hallmarks of the blistering level. OCT provides cross-sectional, tomographic images of the skin. A consecutive series of patients were recruited and their lesions imaged by OCT: 3 patients with bullous pemphigoid (BP), 1 patient with extensive bullae following burns, 1 patient with pemphigus, 1 patient with subcorneal pustular dermatosis, and a patient with Dariers disease. The latter two were included due to similarity to pemphigus with respect to the level of defect cell adhesion. In OCT images, BP bullae are easily depicted as dark, ovoid to round well-demarquated areas, and BP bulla morphology is clearly different from the burn blisters and the pemphigus-like disease with respect to the blistering level. Differentiation of epidermal and subepidermal blisters is demonstrated using OCT. The variation within pemphigoid lesions and pemphigus-like diseases is however too subtle to allow for differential diagnosis; this may be ascribed to limited resolution. Enhanced resolution of OCT may overcome this obstacle.

Melanoma accounts for 75% of all skin cancer deaths. Pulsed photothermal radiometry (PPTR), optical coherence tomography (OCT) and ultrasound (US) are non-invasive imaging techniques that may be used to measure melanoma thickness, thus, determining surgical margins. We constructed a series of PDMS tissue phantoms simulating melanomas of different thicknesses. PPTR, OCT and US measurements were recorded from PDMS tissue phantoms and results were compared in terms of axial imaging range, axial resolution and imaging time. A Monte Carlo simulation and three-dimensional heat transfer model was constructed to simulate PPTR measurement. Experimental results show that PPTR and US can provide a wide axial imaging range (75 μm-1.7 mm and 120-910 μm respectively) but poor axial resolution (75 and 120 μm respectively) in PDMS tissue phantoms, while OCT has the most superficial axial imaging range (14-450 μm) but highest axial resolution (14 μm). The Monte Carlo simulation and three-dimensional heat transfer model give good agreement with PPTR measurement. PPTR and US are suited to measure thicker melanoma lesions (>400 μm), while OCT is better to measure thin melanoma lesions (<400 μm).

OCT-A is becoming more popular in recent years and there is a high demand to improve the quality of angiograms as well as to extract quantitative information. We applied various processing methods for microvasculature enhancement like Hessian-Frangi to a data set obtained with Bessel and Gaussian OCT systems. We used angiogenesis, fractal and multifractal analysis to extract more quantitative information. We applied the processing methods for healthy, stroke, tumor progression and the results of enhanced processing and quantitative analysis for those are presented in this letter. Full Text: PDF ReferencesJ. G. Fujimoto, C. Pitris, S. A. Boppart, and M. E. Brezinski, "Optical coherence microscopy as a novel, non-invasive method for the 4D live imaging of early mammalian embryos", Neoplasia (New York, NY), 2000, 2(1-2):9-25 CrossRef O. Liba, E. D. SoRelle, D. Sen, and A. de la Zerda, "Contrast-enhanced optical coherence tomography with picomolar sensitivity for functional in vivo imaging", Sci Rep. 2016, 6(1):23337. CrossRef O Liba, M. D. Lew, E. D. SoRelle, et al., "Speckle-modulating optical coherence tomography in living mice and humans", Nat Commun. 2017, 8:15845. CrossRef K. Karnowski, A. Ajduk, B. Wieloch, et al., "Optical coherence microscopy as a novel, non-invasive method for the 4D live imaging of early mammalian embryos", Sci Rep. 2017, 7(1):4165. CrossRef V. J. Srinivasan, S. Sakadžić, I. Gorczynska, et al., "Quantitative cerebral blood flow with Optical Coherence Tomography", Opt Express. 2010, 18(3):2477. CrossRef S. Tamborski, H. C. Lyu, H. Dolezyczek, et al. Extended-focus optical coherence microscopy for high-resolution imaging of the murine brain. Biomed Opt Express. 2016, 7(11):4400-4414. CrossRef A. F. Frangi, W. J. Niessen, K. L. Vincken, and M. A. Viergever, "Multiscale vessel enhancement filtering", Lect Notes Comput Sc. 1998;1496:130–137 CrossRef A. A. Ucuzian, A. A. Gassman, A. T. East, and H. P. Greisler , Journal of burn care &amp; research: official publication of the American Burn Association 2010 , 31(1):158. CrossRef R. Lopes, and Betrouni, N. (2009). "Fractal and multifractal analysis: A review", Med. Image Anal. 13, 634–649. CrossRef J. W. Baish and R. K. Jain., "Correspondence re: J. W. Baish and R. K. Jain, Fractals and Cancer. Cancer Res., 60: 3683-3688, 2000.", Cancer Res. 2000, Jul 15, 60(14):3683-8. DirectLink

Optical coherence microscopy (OCM) has unique advantages of high-resolution volumetric imaging without relying on exogenous labels or dyes. It combines the coherence-gated depth discrimination of optical coherence tomography (OCT) with the high lateral resolution of confocal microscopy, offering an excellent balance between the resolutions and imaging depth. However, as the lateral resolution becomes higher, the imaging depth of OCM decreases and its three-dimensional imaging capability is greatly degraded. To overcome this limitation, we used amplitude apodization to create quasi-Bessel beam illumination in order to extend the depth of focus. The lateral and axial resolutions of our OCM system were measured to be 1.6 μm and 2.9 μm in tissue. The imaging depth was extended by ~3.0X (~100 μm) beyond that of the standard Gaussian beam OCM. Using zebrafish embryos as a test system, we demonstrate extendedfocus OCM for structural imaging studies, which revealed the detailed anatomy deep in embryos.

High-Definition and 3-dimensional Imaging of Macular Pathologies with High-speed Ultrahigh-Resolution Optical Coherence Tomography

Optical coherence microscopy (OCM) is a novel technique complementary to optical coherence tomography (OCT) which combines low-coherence interferometry with confocal microscopy to achieve micron-scale resolution imaging in highly scattering media. OCM may be implemented using a single-mode fiber-optic low-coherence interferometer (See Fig. 1). A high numerical aperture objective is used to focus sample-arm light into the specimen, and the reference arm length of the interferometer is adjusted to match the sample arm focal plane optical depth. The sample arm of the interferometer comprises a scanning confocal microscope, in which either the sample or the probe beam is laterally scanned in a raster pattern, and the optical fiber acts as a single-mode confocal aperture for combined light illumination and collection. The reference arm length of the interferometer establishes the depth position of an interferometric “coherence gate” in the sample, from which backscattered light is preferentially collected. Initial studies of OCM in scattering phantoms have demonstrated that this technique provides increased optical sectioning depth compared to confocal microscopy alone.

Optical coherence microscopy (OCM) is a non-destructive 3-dimentional (3D) imaging technique with micrometer-scale resolution, which is based on optical coherence tomography (OCT) and confocal microscopy [1-3]. Recently, it has been demonstrated that the OCT imaging depth is improved by using 1700 nm spectral band, so called “optical window 3”, due to the lower light absorption and a local minimum of water absorption in the wavelength region [4-8]. In our group, we developed a supercontinuum (SC) laser source at the 1700-nm wavelength region and demonstrated that 1700-nm OCT allows us to visualize the structures of mouse brain at a depth up to 1.7 mm [9-11]. We also successfully demonstrated 3D highresolution visualization of myelinated axons in a mouse brain with 1700-nm OCM, which we developed based on a time-domain low-coherence interferometer [12]. In this presentation, we report high-resolution spectral-domain OCM (SD-OCM) at the 1700-nm spectral band for improving the imaging acquisition speed of 1700-nm OCM.

Optical coherence tomography (OCT) is a method for imaging the internal structure of biological tissue in vivo with micron resolution. OCT has been recognized as an extremely promising tool for the diagnosis of pathological changes in biological tissue (Chauhan et al., 2001; Fercher et al., 2003). The coherence–domain range in OCT is performed by using a Michelson interferometer. By measuring singly back scattered light as a function of depth, OCT has the potential to image the structure of tissue with a high resolution and sensitivity. It is of importance for a diagnostics of structures inside a cornea, a cornea edema, for a quantitative imaging of the optic disc in glaucoma, for an evaluation of retinal thickness, etc. in ophthalmology. The high axial resolution of OCT is realized by the use of a broadband light source whereas the lateral resolution is determined by the numerical aperture (NA) of the focusing lens. Although a high NA of a conventional focusing lens in the sample arm of the imaging optical system enables high lateral resolution imaging, but low axial resolution. A low NA is required to achieve a large depth of focus, but in this case we deal with the low lateral resolution. The improvement of the axial–lateral resolution is a very important problem in imaging OCT-systems. Furthermore, a restriction of an imaging method is closely connected with a problem of tissue light–scattering: it leads to the decreasing in the focal depth of a probing beam and an image involves a “noisy”–speckle field superimposed on imaged structures as a result of scattering by a volume medium.

Towards high resolution imaging of human airways with optical coherence microscopy