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 recent developments of functional OCT for ORG measurement, OCT intensity- and phase-based IOS processing. Technical challenges and perspectives of quantitative IOS analysis and ORG interpretations are discussed.
Spatially or temporally resolved phase-based optoretinography with actively-tracked point-scanning optical coherence tomography
Medical Laser Center Lübeck GmbH（吕贝克医学激光中心有限公司）；Institute of Biomedical Optics, University of Lübeck（吕贝克大学生物医学光学研究所）；Heidelberg Engineering GmbH（海德堡工程有限公司）；Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL)（北气道研究中心（ARCN），德国肺病研究中心（DZL）成员）
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…
High-resolution optical imaging methods, such as confocal microscopy and full-field optical coherence tomography, capture flat optical sections of the sample. If the sample is curved, the optical field sections through several sample layers and the view of each layer is reduced. Here we present curved-field optical coherence tomography, capable of capturing optical sections of arbitrary curvature. We test the device on a challenging task of imaging the human cornea in vivo and achieve 10x larger viewing area comparing to the clinical state-of-the-art. This enables more precise cell and nerve c…
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…
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.
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…
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.
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.
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 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 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…
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.
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…
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…
We demonstrate in vivo endoscopic optical coherence tomography (OCT) imaging in the forward direction using a flexible fiber bundle. In comparison to current conventional forward looking probe schemes, our approach simplifies the endoscope design by avoiding the integration of any beam steering components in the distal probe end due to 2D scanning of a focused light beam over the proximal fiber bundle surface. We describe the challenges that arise when OCT imaging with a fiber bundle is performed, such as multimoding or cross-coupling. The performance of different fiber bundles with varying pa…
Imaging airway tissue, optical coherence tomography (OCT) provides cross-sectional images of tissue structures, shows cilia movement and mucus secretion, but does not provide sufficient contrast to differentiate individual cells. By using fast sequences of microscopic resolution OCT (mOCT) images, OCT can picture small signal fluctuations (dynamic) OCT and overcomes the lack in contrast caused by speckle noise. In this way, OCT visualizes airway morphology on a cellular level and allows to track the dynamic behavior of immune cells, as well as mucus transport and secretion. Here, we demonstrat…
Multiple light scattering in tissue limits the penetration of optical coherence tomography (OCT) imaging. Here, we present in-vivo OCT imaging of a live mouse using wavefront shaping to enhance the penetration depth. A digital micro-mirror device (DMD) was used in a spectral-domain OCT system for complex wavefront shaping of an incident beam which resulted in the optimal delivery of light energy into deep tissue. Ex-vivo imaging of chicken breasts and mouse ear tissues showed enhancements in the strength of the image signals and the penetration depth, and in-vivo imaging of the tail of a live …
Corneal evaluation in ophthalmology necessitates cellular-resolution and fast imaging techniques allowing accurate diagnoses. Currently, the fastest volumetric imaging technique is Fourier-domain full-field optical coherence tomography (FD-FF-OCT) that uses a fast camera and a rapidly tunable laser source. Here, we demonstrate high-resolution, high-speed, non-contact corneal volumetric imaging in vivo with FD-FF-OCT that can acquire a single 3D volume with a voxel rate of 7.8 GHz. The spatial coherence of the laser source was suppressed to prevent it from focusing to a spot on the retina, and …
Noninvasive, non-contact and \textit{in vivo} monitoring of blood glucose is a long needed pathology tool for saving patients from recurring pain and hassle that can accompany conventional blood glucose testing methods. Optical coherence tomography known for its high axial resolution imaging modality is adopted in this article for monitoring glucose levels in tissue like media non-invasively. Making use of changes in reduced scattering coefficient due to the refractive-index mismatch between the extracellular fluid and the cellular membranes and armed with a theoretical model, we establish a c…
The speckle statistics of optical coherence tomography images of biological tissue have been studied using several historical probability density functions. A recent hypothesis implies that underlying power-law distributions in the medium structure, such as the fractal branching vasculature, will contribute to power-law probability distributions of speckle statistics. Specifically, these are the Burr type XII distribution for speckle amplitude, the Lomax distribution for intensity, and the generalized logistic distribution for log amplitude. In this study, these three distributions are fitted …
We demonstrate a preliminary setup of a combined MHz-OCT and RGB narrowband reflection microscope and investigate the performance of the new RGB branch and different display modes of colored OCT data sets.
We report on the simultaneous and localized measurements of the diffusion coefficient and flow velocity based on the normalized autocorrelation function using optical coherence tomography (OCT). Our results on a flowing solution of polystyrene spheres show that the flow velocity and the diffusion coefficient can be reliably estimated in a regime determined by the sample diffusivity, the local flow velocity, and the Gaussian beam waist. We experimentally show that a smaller beam waist results in an improvement of the velocity sensitivity at cost of the precision and accuracy of the estimation o…
Due to its noninvasive character, optical coherence tomography (OCT) has become a popular diagnostic method in clinical settings. However, the low-coherence interferometric imaging procedure is inevitably contaminated by heavy speckle noise, which impairs both visual quality and diagnosis of various ocular diseases. Although deep learning has been applied for image denoising and achieved promising results, the lack of well-registered clean and noisy image pairs makes it impractical for supervised learning-based approaches to achieve satisfactory OCT image denoising results. In this paper, we p…
Clinical tracking systems are popular but typically require specific tracking markers. During the last years, scanning speed of optical coherence tomography (OCT) has increased to A-scan rates above 1 MHz allowing to acquire volume scans of moving objects. Thorefore, we propose a markerless tracking system based on OCT to obtain small volumetric images including information of sub-surface structures at high spatio-temporal resolution. In contrast to conventional vision based approaches, this allows identifying natural landmarks even for smooth and homogeneous surfaces. We describe the optomech…
Forward-viewing endoscopic optical coherence tomography (OCT) provides 3D imaging in vivo, and can be combined with widefield fluorescence imaging by use of a double-clad fiber. However, it is technically challenging to build a high-performance miniaturized 2D scanning system with a large field-of-view. In this paper we demonstrate how a 1D scanning probe, which produces cross-sectional OCT images (B-scans) and 1D fluorescence T-scans, can be transformed into a 2D scanning probe by manual scanning along the second axis. OCT volumes are assembled from the B-scans using speckle decorrelation mea…
Optical coherence tomography (OCT) is a powerful biomedical imaging technology that relies on the coherent detection of backscattered light to image tissue morphology in vivo. As a consequence, OCT is susceptible to coherent noise (speckle noise), which imposes significant limitations on its diagnostic capabilities. Here we show a method based purely on light manipulation that is able to entirely remove the speckle noise originating from turbid samples without any compromise in resolution. We refer to this method as Speckle-Free OCT (SFOCT). Using SFOCT, we succeeded in revealing small structu…
Dynamic full-field optical coherence tomography (D-FFOCT) has recently emerged as a label-free imaging tool, capable of resolving cell types and organelles within 3D live samples, whilst monitoring their activity at tens of milliseconds resolution. Here, a D-FFOCT module design is presented which can be coupled to a commercial microscope with a stage top incubator, allowing non-invasive label-free longitudinal imaging over periods of minutes to weeks on the same sample. Long term volumetric imaging on human induced pluripotent stem cell-derived retinal organoids is demonstrated, highlighting t…
Objective: To explore the ability of polarisation-sensitive optical coherence tomography (PS-OCT) to rapidly identify subtle signs of tissue degeneration in the equine joint. Design: Polarisation-sensitive optical coherence tomography (PS-OCT) images were systematically acquired in four locations along the medial and lateral condyles of the third metacarpal bone in 5 equine specimens. Intensity and retardation PS-OCT images, and anomalies observed therein, were then compared and validated with high resolution images of the tissue sections obtained using Differential Interference contrast (DIC)…
A prospective study was performed on neurosurgical samples from 18 patients to evaluate the use of Full-Field Optical Coherence Tomography (FF-OCT) in brain tumor diagnosis. FF-OCT captures en face slices of tissue samples at 1\mum resolution in 3D with a typical 200\mum imaging depth. A 1cm2 specimen is scanned at a single depth and processed in about 5 minutes. This rapid imaging process is non-invasive and 30 requires neither contrast agent injection nor tissue preparation, which makes it particularly well suited to medical imaging applications. Temporal chronic epileptic parenchyma and bra…
We present a finite difference time domain (FDTD) model for computation of A line scans in time domain optical coherence tomography (OCT). By simulating only the end of the two arms of the interferometer and computing the interference signal in post processing, it is possible to reduce the computational time required by the simulations and, thus, to simulate much bigger environments. Moreover, it is possible to simulate successive A lines and thus obtaining a cross section of the sample considered. In this paper we present the model applied to two different samples: a glass rod filled with wat…
Optical Coherence Tomography (OCT) is a non-invasive depth resolved optical imaging modality, that enables high resolution, cross-sectional imaging in biological tissues and materials at clinically relevant depths. Though OCT offers high resolution imaging, the best ultra-high-resolution OCT systems are limited to imaging structural changes with a resolution of one micron on a single B-scan within very limited depth. Nanosensitive OCT (nsOCT) is a recently developed technique that is capable of providing enhanced sensitivity of OCT to structural changes. Improving the sensitivity of OCT to det…
Degree of polarization uniformity (DOPU) imaging obtained by polarization-sensitive optical coherence tomography (PS-OCT) has the potential to provide biomarkers for retinal diseases. It highlights abnormalities in the retinal pigment epithelium that are not always clear in the OCT intensity images. However, a PS-OCT system is more complicated than conventional OCT. We present a neural-network-based approach to estimate the DOPU from standard OCT images. DOPU images were used to train a neural network to synthesize the DOPU from single-polarization-component OCT intensity images. DOPU images w…
Optical coherence tomography (OCT) uses low-coherence reflectometry to obtain cross-sectional images of inhomogeneous media, such as biological tissue. OCT is particularly useful in the biomedical ea, since the imaging can be performed non-invasively, and in a relatively short time. As such, OCT is not only used in research, but has proven to be effective in clinical practice, with the fields of its application continuing to grow. In OCT, essentially, the reflectance of each cross-section along the depth direction is obtained with high spatial resolution ($\bm {\sim10\,μ}$m), revealing the str…
Approximately 90% of cancers have their origins in epithelial tissues and this leads to epithelial thickening, but the ultrastructural changes and underlying architecture is less well known. Depth resolved label free visualization of nanoscale tissue morphology is required to reveal the extent and distribution of ultrastructural changes in underlying tissue, but is difficult to achieve with existing imaging modalities. We developed a nanosensitive optical coherence tomography (nsOCT) approach to provide such imaging based on dominant axial structure with a few nanometre detection accuracy. nsO…
Optical coherence tomography angiography (OCTA) has been established as a powerful tool for investigating vascular diseases and is expected to become a standard of care technology. However, its widespread clinical usage is hindered by technical gaps such as limited field of view (FOV), lack of quantitative flow information, and suboptimal motion correction. Here we report a new imaging platform, termed spectrally extended line field (SELF) OCTA that provides advanced solutions to the above-mentioned challenges. SELF-OCTA breaks the speed limitations and achieves two-fold gain in FOV without sa…
PURPOSE: Establishing and obtaining consistent quantitative indices of retinal thickness from a variety of clinically used Spectral-Domain Optical Coherence Tomography scanners. DESIGN: Retinal images from five Spectral-Domain Optical Coherence Tomography scanners were used to determine total retinal thickness with scanner-specific correction factors establishing consistency of thickness measurement across devices. PARTICIPANTS: 55 Fovea-centered Spectral-Domain Optical Coherence Tomography volumes from eleven subjects were analyzed, obtained from Cirrus HD-OCT, RS-3000, Heidelberg Spectralis,…
Recent studies have shown potential for using polarisation sensitive optical coherence tomography (PS-OCT) to study cartilage morphology, and to be potentially used as an in-vivo, non-invasive tool for detecting osteoarthritic changes. However, there has been relatively limited ability of this method to quantify the subtle changes that occur in the early stages of cartilage degeneration. An established mechanical indenting technique that has previously been used to examine the microstructural response of articular cartilage was employed to fix the bovine samples in an indented state. The sampl…
A polarization-multiplexed, dual-beam setup is proposed to expand the field of view for a swept source optical coherence tomography angiography (OCTA) system. This method used a Wollaston prism to split sample path light into two orthogonal-polarized beams. This allowed two beams to shine on the cornea at an angle separation of ~ 14 degrees, which led to a separation of ~ 4.2 mm on the retina. A 3-mm glass plate was inserted into one of the beam paths to set a constant path length difference between the two polarized beams so the interferogram from the two beams are coded at different frequenc…
Early diagnosis of ocular diseases improves the understanding of pathophysiology and helps with accurate monitoring and effective treatment. Advanced multimodal ocular imaging platforms play a crucial role in the visualization of the ocular components and provide clinicians with a valuable tool for evaluating different eye diseases. Here, for the first time, we present a non-contact, multimodal photoacoustic remote sensing (PARS) microscopy and swept-source optical coherence tomography (SS-OCT) for in-vivo functional and structural imaging of the eye. The system provides complementary imaging …
Label-free metabolic imaging of non-alcoholic fatty liver disease (NAFLD) mouse liver is demonstrated ex vivo by dynamic optical coherence tomography (OCT). The NAFLD mouse is a methionine choline-deficient (MCD)-diet model, and two mice fed MCD diet for 1 and 2 weeks are involved in addition to a normal-diet mouse. The dynamic OCT is based on repeating raster scan and logarithmic intensity variance (LIV) analysis which enables volumetric metabolic imaging with a standard-speed (50,000 A-lines/s) OCT system. Metabolic domains associated with lipid droplet accumulation and inflammation are clea…
Imaging nuclei of keratinocytes in the stratified squamous epithelium has been a subject of intense research since nucleus associated cellular atypia is the key criteria for the screening and diagnosis of epithelial cancers and their precursors. However, keratinocyte nuclei have been reported to be either low scattering or high scattering, so that these inconsistent reports might have led to misinterpretations of optical images, and more importantly, hindered the establishment of optical diagnostic criteria. We disclose that they are generally low scattering in the core using Micro-optical coh…
University of Vienna（维也纳大学）；Christian Doppler Laboratory for Mathematical Modeling and Simulation of Next Generations of Ultrasound Devices (MaMSi)（下一代超声设备数学建模与模拟克里斯蒂安·多普勒实验室）；Johann Radon Institute for Computational and Applied Mathematics (RICAM)（约翰·拉登计算与应用数学研究所）；Medical University of Vienna（维也纳医科大学）
