In ultra-high resolution (UHR-) optical coherence tomography (OCT) group velocity dispersion (GVD) must be corrected for in order to approach the theoretical resolution limit. One approach promises not only compensation, but complete annihilation of even order dispersion effects, and that at all sample depths. This approach has hitherto been demonstrated with an experimentally demanding 'balanced detection' configuration based on using two detectors. We demonstrate intensity correlation (IC) OCT using a conventional spectral domain (SD) UHR-OCT system with a single detector. IC-SD-OCT configurations exhibit cross term ghost images and a reduced axial range, half of that of conventional SD-OCT. We demonstrate that both shortcomings can be removed by applying a novel generic artefact reduction algorithm and using analytic interferograms. We show the superiority of IC-SD-OCT compared to conventional SD-OCT by showing how IC-SD-OCT is able to image spatial structures behind a strongly dispersive silicon wafer. Finally, we question the resolution enhancement of square root 2 that IC-SD-OCT is often believed to have compared to SD-OCT. We show that this is simply the effect of squaring the reflectivity profile as a natural result of processing the product of two intensity spectra instead of a single spectrum.
Optical diffraction tomography (ODT) is a three-dimensional (3D) label-free imaging technique. The 3D refractive index distribution of a sample can be reconstructed from multiple two-dimensional optical field images via ODT. Herein, we introduce a temporally low-coherence ODT technique using a ferroelectric liquid crystal spatial light modulator (FLC SLM). The fast binary-phase modulation provided by the FLC SLM ensures a high spatiotemporal resolution with considerably reduced coherent noise. We demonstrate the performance of the proposed system using various samples, including colloidal micr…
We demonstrate that simultaneous application of optical clearing agents (OCAs) and complex wavefront shaping in optical coherence tomography (OCT) can provide significant enhancement of the penetration depth and imaging quality. OCA reduces optical inhomogeneity of a highly scattering sample, and the wavefront shaping of illumination light controls multiple scattering, resulting in an enhancement of the penetration depth and signal-to-noise ratio. A tissue phantom study shows that concurrent applications of OCA and wavefront shaping successfully operate in OCT imaging. The penetration depth en…
We report experimental evidence and correction of defocus in full-field OCT of biological samples due to mismatch of the refractive index of biological tissues and water. Via a metric based on the image quality, we demonstrate that we are able to compensate this index-induced defocus and to recover a sharp image in depth.
We report on a theoretical model for image formation in full-field optical coherence tomography (FFOCT). Because the spatial incoherence of the illumination acts as a virtual confocal pinhole in FFOCT, its imaging performance is equivalent to a scanning time-gated coherent confocal microscope. In agreement with optical experiments enabling a precise control of aberrations, FFOCT is shown to have nearly twice the resolution of standard imaging at moderate aberration level. Beyond a rigorous study on the sensitivity of FFOCT with respect to aberrations, this theoretical model paves the way towar…
Optical coherence tomography (OCT) is a label-free, non-invasive 3D imaging tool widely used in both biological research and clinical diagnosis. Current OCT modalities can only visualize specimen tomography without chemical information. Here, we report a bondselective full-field OCT (BS-FF-OCT), in which a pulsed mid-infrared laser is used to modulate the OCT signal through the photothermal effect, achieving label-free bond-selective 3D sectioned imaging of highly scattering samples. We first demonstrate BS-FF-OCT imaging of 1 μm PMMA beads embedded in agarose gel. Next, we then show 3D hypers…
We demonstrate experimentally quantum-inspired, spectral-domain intensity optical coherence tomography. We show that the technique allows for both axial resolution improvement and dispersion cancellation compared to conventional optical coherence tomography. The method does not involve scanning and it works with classical light sources and standard photodetectors. The measurements are in excellent agreement with the theoretical predictions. We also propose an approach that enables the elimination of potential artifacts arising from multiple interfaces.
We demonstrate experimentally ghost optical coherence tomography using a broadband incoherent supercontinuum light source with shot-to-shot random spectral fluctuations. The technique is based on ghost imaging in the spectral domain where the object is the spectral interference pattern generated from an optical coherence tomography interferometer in which a physical sample is placed. The image of the sample is obtained from the Fourier transform of the correlation between the spectrally-resolved intensity fluctuations of the supercontinuum and the integrated signal measured at the output of th…
Optical coherence tomography angiography (Angio-OCT), mainly based on the temporal dynamics of OCT scattering signals, has found a range of potential applications in clinical and scientific research. Based on the model of random phasor sums, temporal statistics of the complex-valued OCT signals are mathematically described. Statistical distributions of the amplitude differential and complex differential Angio-OCT signals are derived. The theories are validated through the flow phantom and live animal experiments. Using the model developed, the origin of the motion contrast in Angio-OCT is math…
Second harmonic optical coherence tomography, which uses coherence gating of second-order nonlinear optical response of biological tissues for imaging, is described and demonstrated. Femtosecond laser pulses were used to excite second harmonic waves from collagen harvested from rat tail tendon and a reference nonlinear crystal. Second harmonic interference fringe signals were detected and used for image construction. Because of the strong dependence of second harmonic generation on molecular and tissue structures, this technique offers contrast and resolution enhancement to conventional optica…
We present a novel extended-focus optical coherence microscope (OCM) attaining 0.7 μm axial and 0.4 μm lateral resolution maintained over a depth of 40 μm, while preserving the advantages of Fourier domain OCM. Our method uses an ultra-broad spectrum from a super- continuum laser source. As the spectrum spans from near-infrared to visible wavelengths (240 nm in bandwidth), we call the method visOCM. The combination of such a broad spectrum with a high-NA objective creates an almost isotropic 3D submicron resolution. We analyze the imaging performance of visOCM on microbead samples and demonstr…
A device based on Polarization sensitive optical coherence tomography is developed to monitor blood glucose levels in human subjects. The device was initially tested with tissue phantom. The measurements with human subjects for various glucose concentration levels are found to be linearly dependent on the degree of circular polarization obtainable from the PS-OCT.
A polarization-sensitive optical coherence tomography system based on heterodyning and filtering techniques is built to perform Stokesmetric imaging of different layers of depths in a porcine tendon sample. The complete 4\times4 backscattering Muellermetric images of one layer are acquired using such a system. The images reveal information indiscernible from a conventional OCT system.
We developed a new endogenous approach to reveal subcellular metabolic contrast in fresh ex vivo tissues taking advantage of the time dependence of the full field optical coherence tomography interferometric signals. This method reveals signals linked with local activity of the endogenous scattering elements which can reveal cells where other imaging techniques fail or need exogenous contrast agents. We benefit from the micrometric transverse resolution of full field OCT to image intracellular features. We used this time dependence to identify different dynamics at the millisecond scale on a w…
We analyze an experimental setup in which a quasi-monochromatic spatially coherent beam of light is used to probe a paraxial optical scatterer. We discuss the effect of the spatial coherence of the probe beam on the Mueller matrix representing the scatterer. We show that according to the degree of spatial coherence of the beam, the \emph{same} scattering system can be represented by \emph{different} Mueller matrices. This result should serve as a warning for experimentalists.
We present differential phase-contrast optical coherence tomography (DPC-OCT) with two transversally separated probing beams to sense phase gradients in various directions by employing a rotatable Wollaston prism. In combination with a two-dimensional mathe- matical reconstruction algorithm based on a regularized shape from shading (SfS) method accurate quantitative phase maps can be determined from a set of two orthogonal en-face DPC-OCT images, as exemplified on various technical samples.
We develop a model of full-field optical coherence tomography (FF-OCT) that includes a description of partial temporal and spatial coherence, together with a mean-field scattering theory going beyond the Born approximation. Based on explicit expressions of the FF-OCT signal, we discuss essential features of FF-OCT imaging, such as the influence of partial coherence on the optical transfer function, and on the decay of the signal with depth that is captured by the model. We derive the conditions under which the spatially averaged signal exhibits a pure exponential decay with depth, providing a …
Acousto-optical coherence tomography (AOCT) consists in using random phase jumps on ultrasound and light to achieve a millimeter resolution when imaging thick scattering media. We combined this technique with heterodyne off-axis digital holography. Two-dimensional images of absorbing objects embedded in scattering phantoms are obtained with a good signal-to-noise ratio. We study the impact of the phase modulation characteristics on the amplitude of the acousto-optic signal and on the contrast and apparent size of the absorbing inclusion.
Dynamic full-field optical coherence tomography (D-FFOCT) has recently emerged as an invaluable live label-free and non-invasive imaging modality able to image subcellular biological structures and their metabolic activity within complex 3D samples. However, D-FFOCT suffers from fringe artefacts when imaging nearby reflective surfaces and is highly sensitive to vibrations. Here, we present interface Self-Referenced (iSR) D-FFOCT, an alternative configuration to D-FFOCT that takes advantage of the presence of the sample coverslip in between the sample and the objective by using it as a defocuse…
Current spectroscopic optical coherence tomography (OCT) methods rely on a posteriori numerical calculation. We present an alternative for accessing optically the spectroscopic information in OCT, i.e. without any post-processing, by using a grating based correlation and a wavelength demultiplexing system. Conventional A-scan and spectrally resolved A-scan are directly recorded on the image sensor. Furthermore, due to the grating based system, no correlation scan is necessary. In the frame of this paper we present the principle of the system as well as first experimental results.
We propose a numerical method for compensating dispersion effects in optical coherence tomography that does not require a priori knowledge of dispersive properties of the sample. The method is based on the generalized autoconvolution function, and its principle of operation can be intuitively visualized using the Wigner distribution function formalism.
Acousto-Optical Coherence Tomography (AOCT) is a variant of Acousto Optic Imaging (also called Ultrasound modulated Optical Tomography) that makes possible to get resolution along the ultrasound propagation axis $z$. We present here new AOCT experimental results, and we study how the $z$ resolution depends on time step between phase jumps $T_ϕ$, or on the correlation length $Δz$. By working at low resolution, we perform a quantitative comparison of the $z$ measurements with the theoretical Point Spread Function (PSF). We present also images recorded with different $z$ resolution, and we qualit…
The Optical coherence tomography (OCT) is a powerful interferometric imaging technique widely used in medical fields such as ophthalmology, cardiology and dermatology, for which footprint and cost are becoming increasingly important. Here we present a platform for miniaturized sources for OCT based on chip-scale lithographically-defined microresonators. We show that the proposed platform is compatible with standard commercial spectral domain (SD) OCT systems and enable imaging of human tissue with an image quality comparable to the one achieved with tabletop commercial sources. This platform p…
Korea Advanced Institute of Science and Technology (KAIST)（韩国科学技术院）；KAIST Institute for Health Science and Technology, KAIST（韩国科学技术院健康科学与技术研究所）；Graduate School of Medical Science and Engineering, KAIST（韩国科学技术院医学科学与工程研究生院）；Department of Mechanical Engineering, KAIST（韩国科学技术院机械工程系）；Graduate School of Stem Cell and Regenerative Biology, KAIST（韩国科学技术院干细胞与再生生物学研究生院）；Department of Pathology, Gangnam Severance Hospital, Yonsei University College of Medicine（延世大学医学院江南世福兰斯医院病理科）；Center for Genome Engineering, Institute for Basic Science（基础科学研究院基因组工程中心）；BioMedical Research Center (BMRC), KAIST（韩国科学技术院生物医学研究中心）；Tomocube Inc.（Tomocube公司）
Full-field swept-source optical coherence tomography (FF-SS-OCT) and laser Doppler holography (LDH) are two holographic imaging techniques presenting unique capabilities for ophthalmology. We report on interlaced FF-SS-OCT and LDH imaging with a single instrument. Effectively, retinal blood flow and pulsation could be quasi-simultaneously monitored. This instrument holds potential for a wide scope of ophthalmic applications.
Optical coherence tomography (OCT) has seen widespread success as an in vivo clinical diagnostic 3D imaging modality, impacting areas including ophthalmology, cardiology, and gastroenterology. Despite its many advantages, such as high sensitivity, speed, and depth penetration, OCT suffers from several shortcomings that ultimately limit its utility as a 3D microscopy tool, such as its pervasive coherent speckle noise and poor lateral resolution required to maintain millimeter-scale imaging depths. Here, we present 3D optical coherence refraction tomography (OCRT), a computational extension of O…
The potential for improving the penetration depth of optical coherence tomography systems by using increasingly longer wavelength light sources has been known since the inception of the technique in the early 1990s. Nevertheless, the development of mid-infrared optical coherence tomography has long been challenged by the maturity and fidelity of optical components in this spectral region, resulting in slow acquisition, low sensitivity, and poor axial resolution. In this work, a mid-infrared spectral-domain optical coherence tomography system operating at 4 micron central wavelength with an axi…
Quantum information technologies harness the intrinsic nature of quantum theory to beat the limitations of the classical methods for information processing and communication. Recently, the application of quantum features to metrology has attracted much attention. Quantum optical coherence tomography (QOCT), which utilizes two-photon interference between entangled photon pairs, is a promising approach to overcome the problem with optical coherence tomography (OCT): As the resolution of OCT becomes higher, degradation of the resolution due to dispersion within the medium becomes more critical. H…
Multiple scattering of waves in disordered media is a nightmare whether it be for detection or imaging purposes. The best approach so far to get rid of multiple scattering is optical coherence tomography. It basically combines confocal microscopy and coherence time-gating to discriminate ballistic photons from a predominant multiple scattering background. Nevertheless, the imaging depth range remains limited to 1 mm at best in human soft tissues. Here we propose a matrix approach of optical imaging to push back this fundamental limit. By combining a matrix discrimination of ballistic waves and…
Intrinsic optical signal (IOS) imaging of the retina, also termed as optoretinography (ORG), promises a noninvasive method for objective assessment of retinal function. By providing unparalleled capability to differentiate individual layers of the retina, functional optical coherence tomography (OCT) has been actively investigated for intrinsic signal ORG measurements. However, clinical deployment of functional OCT for quantitative ORG is still challenging due to the lack of a standardized imaging protocol and the complication of IOS sources and mechanisms. This article aims to summarize recen…
Inverse spectroscopic optical coherence tomography (IS-OCT) methods apply inverse problem formulations to acquired spectra to estimate depth-resolved sample properties. In the current study, we modelled the time-frequency-distributions using Lambert-Beer law and implemented IS-OCT using backscattering spectra calculated from Mie theory, then demonstrated the algorithm on polystyrene microspheres under idealized conditions. The results are significant because the method generates depth dependent estimates of both the concentration and diameter of scattering particles.
We present a general theory of optical coherence tomography (OCT), which synthesizes the fundamental concepts and implementations of OCT under a common 3D k-space framework. At the heart of this analysis is the Fourier diffraction theorem, which relates the coherent interaction between a sample and plane wave to the Ewald sphere in the 3D k-space representation of the sample. While only the axial dimension of OCT is typically analyzed in k-space, we show that embracing a fully 3D k-space formalism allows explanation of nearly every fundamental physical phenomenon or property of OCT, including …
We demonstrate a different scheme to perform optical sectioning of a sample based on the concept of induced coherence [Zou et al., Phys. Rev. Lett. 67, 318 (1991)]. This can be viewed as a different type of optical coherence tomography scheme where the varying reflectivity of the sample along the direction of propagation of an optical beam translates into changes of the degree of first-order coherence between two beams. As a practical advantage the scheme allows probing the sample with one wavelength and measuring photons with another wavelength. In a bio-imaging scenario, this would result in…
We demonstrate that polarization-sensitive optical coherence tomography (PS-OCT) is suitable to map the stress distribution within materials in a contactless and non-destructive way. In contrast to transmission photoelasticity measurements the samples do not have to be transparent but can be of scattering nature. Denoising and analysis of fringe patterns in single PS-OCT retardation images are demonstrated to deliver the basis for a quantitative whole-field evaluation of the internal stress state of samples under investigation.
A recent advance in optical coherence tomography (OCT), termed swept-source OCT, is generalized into a new technique, Fourier-domain OCT. It represents a realization of a full-field OCT system in place of the conventional serial image acquisition in transverse directions typically implemented in "flying-spot" mode. To realize the full-field image acquisition, a Fourier holography system illuminated with a swept-source is employed instead of a Michelson interferometer commonly used in OCT. Fourier-domain OCT offers a new leap in signal-to-noise ratio improvement, as compared to flying-spot OCT …
Optical coherence tomography is state-of-the-art in non-invasive imaging of biological structures. Spectral Domain Optical Co-herence Tomography is the popularly used variation of this technique, but its performance is limited by the bandwidth and res-olution of the system. In this work, we theoretically formulate the use of phase modulators and delay lines to act as filters on the tomography system and scan multiple channels. Various channels are then combined in a digital computer using filter bank theory to improve the sampling rate . The combination of multiple channels allows for increasi…
We present a new interferometric technique for measuring Coherent Anti-Stokes Raman Scattering (CARS) and Second Harmonic Generation (SHG) signals. Heterodyne detection is employed to increase the sensitivity in both CARS and SHG signal detection, which can also be extended to different coherent processes. The exploitation of the mentioned optical nonlinearities for molecular contrast enhancement in Optical Coherence Tomography (OCT) is presented. Numerical simulations for both coherent nonlinear processes are performed in order to determine the properties of the signal expected at the exit of…
This short textbook was written for someone who newly start studying, doing research, or development about optical coherence tomography (OCT) or using OCT. The first chapter summarizes the concept and the history of OCT. In the second chapter, the technologies of OCT are summarized, which includes the mathematical principle, hardware implementation, the instructions for designs such as interferometer and wavelength selections, and theories of resolutions and sensitivity. In the third chapter, some examples of ophthalmic applications of OCT are described. In the last chapter, instructions for n…
Acousto-Optical Coherence Tomography (AOCT) is variant of Acousto Optic Imaging (called also ultrasonic modulation imaging) that makes possible to get z resolution with acoustic and optic Continuous Wave (CW) beams. We describe here theoretically the AOCT e ect, and we show that the Acousto Optic tagged photons remains coherent if they are generated within a speci c z region of the sample. We quantify the z selectivity for both the tagged photon eld, and for the M. Lesa re et al. photorefractive signal.
This dissertation relates to the transition of the state of the art of swept source optical coherence tomography (SS-OCT) systems to a new realm in which the image acquisition speed is improved by an order of magnitude. With the aid of a better quality imaging technology, the speed-up factor will considerably shorten the eye-exam clinical visits which in turn improves the patient and doctor interaction experience. These improvements will directly lower associated medical costs for eye-clinics and patients worldwide. There are several other embodiments closely related to Optical Coherence Tomog…
In optical coherence tomography (OCT), axial resolution and signal-to-noise ratio (SNR) are typically viewed as uncoupled parameters. We show that this is only true for mirror-like surfaces, and that in diffuse scattering samples such as tissue there is an inherent coupling between axial resolution and measurement SNR. We explain the origin of this coupling and demonstrate that it can be used to achieve increased imaging penetration depth at the expense of resolution. Finally, we argue that this coupling should be considered during OCT system design processes that seek to balance competing nee…
We report on Mid-infrared (MIR) OCT at 4 $μ$m based on collinear sum-frequency upconversion and promote the A-scan scan rate to 3 kHz. We demonstrate the increased imaging speed for two spectral realizations, one providing an axial resolution of 8.6 $μ$m, and one providing a record axial resolution of 5.8 $μ$m. Image performance is evaluated by sub-surface micro-mapping of a plastic glove and real-time monitoring of CO$_2$ in parallel with OCT imaging.
We demonstrate label-free drug response evaluations of human breast (MCF-7) and colon (HT-29) cancer spheroids via dynamic optical coherence tomography (OCT). The MCF-7 and HT-29 spheroids were treated with paclitaxel (PTX, or Taxol) and the active metabolite of irinotecan (SN-38), respectively. The drugs were applied using 0 (control), 0.1, 1, and 10 uM concentrations with treatment times of 1, 3, and 6 days. The samples were scanned using a repeated raster scan protocol and two dynamic OCT algorithms, logarithmic intensity variance (LIV) and late OCT correlation decay speed (OCDSl) analyses,…
We have developed a multimodal photoacoustic remote sensing (PARS) microscope combined with swept source optical coherence tomography for in vivo, non-contact retinal imaging. Building on the proven strength of multiwavelength PARS imaging, the system is applied for estimating retinal oxygen saturation in the rat retina. The capability of the technology is demonstrated by imaging both microanatomy and the microvasculature of the retina in vivo. To our knowledge this is the first time a non-contact photoacoustic imaging technique is employed for in vivo oxygen saturation measurement in the reti…
