Optical Coherence Tomography Intensity Research Articles

OCT Intensity of the Region between Outer Retina Band 2 and Band 3 as a Biomarker for Retinal Degeneration and Therapy.

Optical coherence tomography (OCT) is widely used to probe retinal structure and function. This study investigated the outer retina band (ORB) pattern and reflective intensity for the region between bands 2 and 3 (Dip) in three mouse models of inherited retinal degeneration (Rs1KO, TTLL5KO, RPE65KO) and in human AMD patients from the A2A database. OCT images were manually graded, and reflectivity signals were used to calculate the Dip ratio. Qualitative analyses demonstrated the progressive merging band 2 and band 3 in all three mouse models, leading to a reduction in the Dip ratio compared to wildtype (WT) controls. Gene replacement therapy in Rs1KO mice reverted the ORB pattern to one resembling WT and increased the Dip ratio. The degree of anatomical rescue in these mice was highly correlated with level of transgenic RS1 expression and with the restoration of ERG b-wave amplitudes. While the inner retinal cavity was significantly enlarged in dark-adapted Rs1KO mice, the Dip ratio was not altered. A reduction of the Dip ratio was also detected in AMD patients compared with healthy controls and was also positively correlated with AMD severity on the AMD score. We propose that the ORB and Dip ratio can be used as non-invasive early biomarkers for retina health, which can be used to probe therapeutic gene expression and to evaluate the effectiveness of therapy.

Delineation of three-dimensional tumor margins based on normalized absolute difference mapping via volumetric optical coherence tomography

The extent of surgical resection is an important prognostic factor in the treatment of patients with glioblastoma. Optical coherence tomography (OCT) imaging is one of the adjunctive methods available to achieve the maximal surgical resection. In this study, the tumor margins were visualized with the OCT image obtained from a murine glioma model. A commercialized human glioblastoma cell line (U-87) was employed to develop the orthotopic murine glioma model. A swept-source OCT (SS-OCT) system of 1300 nm was used for three-dimensional imaging. Based on the OCT intensity signal, which was obtained via accumulation of each A-scan data, an en-face optical attenuation coefficient (OAC) map was drawn. Due to the limited working distance of the focused beam, OAC values decrease with depth, and using the OAC difference in the superficial area was chosen to outline the tumor boundary, presenting a challenge in analyzing the tumor margin along the depth direction. To overcome this and enable three-dimensional tumor margin detection, we converted the en-face OAC map into an en-face difference map with x- and y-directions and computed the normalized absolute difference (NAD) at each depth to construct a volumetric NAD map, which was compared with the corresponding H&E-stained image. The proposed method successfully revealed the tumor margin along the peripheral boundaries as well as the margin depth. We believe this method can serve as a useful adjunct in glioma surgery, with further studies necessary for real-world practical applications.

High-sensitivity synchronous angio-lymphography based on a speckle spectrum contrast OCT.

To achieve accurate selection and synchronous imaging of blood vessels and lymph, a speckle spectrum contrast method (SSC) based on spectral-domain optical coherence tomography (SD-OCT) is proposed in this Letter. In this method, the time-lapse optical coherence tomography (OCT) intensity signal is transformed to the Fourier frequency domain. By analyzing the frequency spectrum of the time-lapse OCT intensity signal, a parameter called SSC signal, which represents the ratio of different intervals of the high frequency to the low frequency, is utilized to extract and contrast different types of the vessels in the biological tissues. In the SSC spectrum, the SSC signals of the static tissue, lymphatic vessels, and vascular vessels can be separated in three different frequency intervals, enabling differentiation and synchronous imaging of the lymphatic-vascular vessels. A mouse ear was used to demonstrate the feasibility and efficiency of this method. By using the SSC signal as the imaging parameter, the lymphatic and blood vessels of the mouse ear are differentiated and visualized simultaneously. This study shows the feasibility of the three-dimensional (3D) synchronous angio-lymphography based on the SSC method, which provides a tool to improve the understanding for disease research and treatment.

Depth-dependent attenuation and backscattering characterization of optical coherence tomography by stationary iterative method.

Extracting optical properties of tissue [e.g., the attenuation coefficient () and the backscattering fraction] from the optical coherence tomography (OCT) images is a valuable tool for parametric imaging and related diagnostic applications. Previous attenuation estimation models depend on the assumption of the uniformity of the backscattering fraction () within layers or whole samples, which does not accurately represent real-world conditions. Our aim is to develop a robust and accurate model that calculates depth-wise values of attenuation and backscattering fractions simultaneously from OCT signals. Furthermore, we aim to develop an attenuation compensation model for OCT images that utilizes the optical properties we obtained to improve the visual representation of tissues. Using the stationary iteration method under suitable constraint conditions, we derived the approximated solutions of and on a single scattering model. During the iteration, the estimated value of can be rectified by introducing the large variations of , whereas the small ones were automatically ignored. Based on the calculation of the structure information, the OCT intensity with attenuation compensation was deduced and compared with the original OCT profiles. The preliminary validation was performed in the OCT A-line simulation and Monte Carlo modeling, and the subsequent experiment was conducted on multi-layer silicone-dye- phantoms and ex vivo cow eyes. Our method achieved robust and precise estimation of and for both simulated and experimental data. Moreover, corresponding OCT images with attenuation compensation provided an improved resolution over the entire imaging range. Our proposed method was able to correct the estimation bias induced by the variations of and provided accurate depth-resolved measurements of both and simultaneously. The method does not require prior knowledge of the morphological information of tissue and represents more real-life tissues. Thus, it has the potential to help OCT imaging based disease diagnosis of complex and multi-layer biological tissue.

Mapping optical scattering properties to physical particle information in singly and multiply scattering samples.

Optical coherence tomography (OCT) leverages light scattering by biological tissues as endogenous contrast to form structural images. Light scattering behavior is dictated by the optical properties of the tissue, which depend on microstructural details at the cellular or sub-cellular level. Methods to measure these properties from OCT intensity data have been explored in the context of a number of biomedical applications seeking to access this sub-resolution tissue microstructure and thereby increase the diagnostic impact of OCT. Most commonly, the optical attenuation coefficient, an analogue of the scattering coefficient, has been used as a surrogate metric linking OCT intensity to subcellular particle characteristics. To record attenuation coefficient data that is accurately representative of the underlying physical properties of a given sample, it is necessary to account for the impact of the OCT imaging system itself on the distribution of light intensity in the sample, including the numerical aperture (NA) of the system and the location of the focal plane with respect to the sample surface, as well as the potential contribution of multiple scattering to the reconstructed intensity signal. Although these considerations complicate attenuation coefficient measurement and interpretation, a suitably calibrated system may potentiate a powerful strategy for gaining additional information about the scattering behavior and microstructure of samples. In this work, we experimentally show that altering the OCT system geometry minimally impacts measured attenuation coefficients in samples presumed to be singly scattering, but changes these measurements in more highly scattering samples. Using both depth-resolved attenuation coefficient data and layer-resolved backscattering coefficients, we demonstrate the retrieval of scattering particle diameter and concentration in tissue-mimicking phantoms, and the impact of presumed multiple scattering on these calculations. We further extend our approach to characterize a murine brain tissue sample and highlight a tumor-bearing region based on increased scattering particle density. Through these methods, we not only enhance conventional OCT attenuation coefficient analysis by decoupling the independent effects of particle size and concentration, but also discriminate areas of strong multiple scattering through minor changes to system topology to provide a framework for assessing the accuracy of these measurements.

COMPARATIVE ANALYSIS OF OCT AND OCT ANGIOGRAPHY CHARACTERISTICS IN EARLY DIABETIC RETINOPATHY.

To assess the quantitative characteristics of optical coherence tomography (OCT) and OCT angiography (OCTA) for the objective detection of early diabetic retinopathy (DR). This was a retrospective and cross-sectional study, which was carried out at a tertiary academic practice with a subspecialty. Twenty control participants, 15 people with diabetics without retinopathy (NoDR), and 22 people with mild nonproliferative diabetic retinopathy (NPDR) were included in this study. Quantitative OCT characteristics were derived from the photoreceptor hyperreflective bands, i.e., inner segment ellipsoid (ISe) and retinal pigment epithelium (RPE). OCTA characteristics, including vessel diameter index (VDI), vessel perimeter index (VPI), and vessel skeleton density (VSD), were evaluated. Quantitative OCT analysis indicated that the ISe intensity was significantly trending downward with DR advancement. Comparative OCTA revealed VDI, VPI, and VSD as the most sensitive characteristics of DR. Correlation analysis of OCT and OCTA characteristics revealed weak variable correlation between the two imaging modalities. Quantitative OCT and OCTA analyses revealed photoreceptor and vascular distortions in early DR. Comparative analysis revealed that the OCT intensity ratio, ISe/RPE, has the best sensitivity for early DR detection. Weak variable correlation of the OCT and OCTA characteristics suggests that OCT and OCTA are providing supplementary information for DR detection and classification.

Automated analysis framework for in vivo cardiac ablation therapy monitoring with optical coherence tomography.

Radiofrequency ablation (RFA) is a minimally invasive procedure that is commonly used for the treatment of atrial fibrillation. However, it is associated with a significant risk of arrhythmia recurrence and complications owing to the lack of direct visualization of cardiac substrates and real-time feedback on ablation lesion transmurality. Within this manuscript, we present an automated deep learning framework for in vivo intracardiac optical coherence tomography (OCT) analysis of swine left atria. Our model can accurately identify cardiac substrates, monitor catheter-tissue contact stability, and assess lesion transmurality on both OCT intensity and polarization-sensitive OCT data. To the best of our knowledge, we have developed the first automatic framework for in vivo cardiac OCT analysis, which holds promise for real-time monitoring and guidance of cardiac RFA therapy..

Functional Optical Coherence Tomography for Intrinsic Signal Optoretinography: Recent Developments and Deployment Challenges.

Intrinsic optical signal (IOS) imaging of the retina, also termed as optoretinogram or optoretinography (ORG), promises a non-invasive method for the objective assessment of retinal function. By providing the unparalleled capability to differentiate individual retinal layers, 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.

Deep Learning and Simulation for the Estimation of Red Blood Cell Flux With Optical Coherence Tomography

We present a deep learning and simulation-based method to measure cortical capillary red blood cell (RBC) flux using Optical Coherence Tomography (OCT). This method is more accurate than the traditional peak-counting method and avoids any user parametrization, such as a threshold choice. We used data that was simultaneously acquired using OCT and two-photon microscopy to uncover the distribution of parameters governing the height, width, and inter-peak time of peaks in OCT intensity associated with the passage of RBCs. This allowed us to simulate thousands of time-series examples for different flux values and signal-to-noise ratios, which we then used to train a 1D convolutional neural network (CNN). The trained CNN enabled robust measurement of RBC flux across the entire network of hundreds of capillaries.

P–361 Endometrium optical coherence tomography (OCT) and histomorphometry in implantation window and their relationships with reproductive failure and implantation outcome

Abstract Study question How do endometrium OCT image characteristics during peri-implantation window correlate with histomorphometry and associate with implantation outcomes in women with reproductive failure? Summary answer Endometrium OCT intensity correlated with stromal cell density and gland size. Endometrium with recurrent implantation failure had low OCT intensity but reversed in successful implantation. What is known already OCT is a non-invasive imaging technique using low energy near-infrared light to capture micrometer-scale resolution images from optical scattering media. An image produced by OCT resembles tissue architecture observed in histology, so OCT imaging has been regarded as “optical biopsy”. Our previous findings demonstrated OCT is better than ultrasound to identify endometrial pathology. We also showed association of OCT signal with microvessel density in peri-implantation endometrium. However, other histomorphometry were not evaluated. It is still unclear whether endometrium OCT image characteristics are different in reproductive failure and can predict implantation outcomes. Study design, size, duration This was a prospective study conducted at teaching hospital of The Chinese University of Hong Kong from Jan 2018 to Dec 2019. 46 infertile women with or without recurrent miscarriage (RM) and implantation failure (RIF) were recruited in this study. Endometrium OCT imaging and subsequent biopsy were performed on the seventh day after luteal hormone surge (LH + 7) in natural cycle prior to the consecutive natural conception or embryo transfer (ET) cycle. Participants/materials, setting, methods At least 5 systematic random endometrium OCT images from uterine fundus, body and lower segment of each subject were included for intensity analysis by two independent observers. OCT intensity of each image was classified as low, moderate, high based on optical range and then average OCT intensity in each uterine region was calculated for group comparison. Endometrium glandular epithelial, stromal, endothelial, uNK cells were defined by standard H&E and specific immunostaining for histomorphometry and correlation. Main results and the role of chance OCT intensity significantly correlated with endometrial cell and gland parameters regardless classifications of reproductive failure and implantation outcome. Higher OCT intensity indicated higher stromal cell density, gland to stromal (G/S) ratio and average gland area, but fewer microvessel and uNK cells. None of the endometrium histomorphometry were significantly different among different reproductive failure types and implantation outcomes, suggesting it may not be sensitive enough to detect the abnormal histological features. However, OCT intensity was significantly lower in the uterine fundus and body of RIF group than in that of infertile and RM groups. There was no significant difference of OCT intensity in the lower part of the endometrium among three groups. It indicates that OCT intensity is a sensitive marker to differentiate endometrium with RIF from the endometrium with other conditions and also endometrium with RIF is characterized with less stromal cells and smaller glands. Compared with infertile group with unsuccessful implantation, OCT intensity was higher in all three parts of the uterus from the infertile group with successful implantation, but the results were not statistically different. The results further implied that endometrial cells and gland size may potentially contribute to the endometrium receptivity for implantation. Limitations, reasons for caution Current endometrium OCT imaging depth is within 3mm, change beyond this thickness is inaccessible but still the most important layer for implantation. This is a pilot and small study with lack of normal fertile control. Endometrium OCT imaging in the same natural conception or ET cycle will be more accurate. Wider implications of the findings: OCT imaging could be used as a potential noninvasive modality to evaluate peri-implantation window endometrium. It enables real-time and in-situ visualization of endometrium structure and pathology with no additional biopsy risk and examination delay. Larger clinical trials are needed to confirm its clinical applications and utilities. Trial registration number CREC 2016.160

Imaging localized fast optical signals of neural activation with optical coherence tomography in awake mice.

We report optical coherence tomography (OCT) imaging of localized fast optical signals (FOSs) arising from whisker stimulation in awake mice. The activated voxels were identified by fitting the OCT intensity signal time course with a response function over a time scale of a few hundred milliseconds after the whisker stimulation. The significantly activated voxels were shown to be localized to the expected brain region for whisker stimulation. The ability to detect functional stimulus-evoked, depth-resolved FOS with intrinsic contrast from the cortex provides a new tool for neural activity studies.

Dynamic light scattering optical coherence tomography to probe motion of subcellular scatterers.

.Optical coherence tomography (OCT) is used to provide anatomical information of biological systems but can also provide functional information by characterizing the motion of intracellular structures. Dynamic light scattering OCT was performed on intact, control MCF-7 breast cancer cells and cells either treated with paclitaxel to induce apoptosis or deprived of nutrients to induce oncosis. Autocorrelations (ACs) of the temporal fluctuations of OCT intensity signals demonstrate a significant decrease in decorrelation time after 24 h in both the paclitaxel-treated and nutrient-deprived cell groups but no significant differences between the two groups. The acquired ACs were then used as input for the CONTIN deconvolution algorithm, and all produced CONTIN outputs with three distinct peaks for all experimental conditions. After 24 h of either paclitaxel treatment or nutrient deprivation, the area-under-the-curve (AUC) of the first peak increased significantly while the AUC of the third peak decreased significantly. These results lend strong support to the hypothesis that ACs acquired from cells are composed of multiple components that correspond to light scattered by different subcellular structures and organelles.

Characterizing the optical properties of human brain tissue with high numerical aperture optical coherence tomography.

Quantification of tissue optical properties with optical coherence tomography (OCT) has proven to be useful in evaluating structural characteristics and pathological changes. Previous studies primarily used an exponential model to analyze low numerical aperture (NA) OCT measurements and obtain the total attenuation coefficient for biological tissue. In this study, we develop a systematic method that includes the confocal parameter for modeling the depth profiles of high NA OCT, when the confocal parameter cannot be ignored. This approach enables us to quantify tissue optical properties with higher lateral resolution. The model parameter predictions for the scattering coefficients were tested with calibrated microsphere phantoms. The application of the model to human brain tissue demonstrates that the scattering and back-scattering coefficients each provide unique information, allowing us to differentially identify laminar structures in primary visual cortex and distinguish various nuclei in the midbrain. The combination of the two optical properties greatly enhances the power of OCT to distinguish intricate structures in the human brain beyond what is achievable with measured OCT intensity information alone, and therefore has the potential to enable objective evaluation of normal brain structure as well as pathological conditions in brain diseases. These results represent a promising step for enabling the quantification of tissue optical properties from high NA OCT.

Analyzing external and internal membrane fouling by oil emulsions via 3D optical coherence tomography

Membrane-based filtration is an emerging technique for processing oily wastewater. Improving the efficiency of oil-water separation via membranes entails novel techniques for studying the complex interactions between the oil droplets and membrane underlying fouling. This paper presents the first study that applies optical coherence tomography (OCT) to the characterization of membrane fouling by oil emulsions. A series of dead-end filtration experiments was performed to characterize the rejection of oil droplets (~ 10µm; hexadecane) by the membrane structure (0.45µm PVDF) via three-dimensional (3D) OCT scanning in real time. The experimental results were compared with the control experiments with ~ 10µm glass beads to identify the optical artifacts. Both the external and internal fouling by the oil droplets were successfully revealed by analyzing the variation in OCT intensity at various layers that were mathematically defined in terms of the coordinate surfaces parallel to, and above and below, the feed-membrane interface. The evolution of membrane fouling was quantified by evaluating the fraction of fouling voxels as a function of time at varied depths. This study demonstrates that the OCT-based characterization has the potential to shed light on the complex interactions occurring in oil-water separations via membrane filtration, particularly by providing real-time non-invasive monitoring of internal fouling, the understanding of which is valuable for both fundamental research and practical applications.

K-distribution three-dimensional mapping of biological tissues in optical coherence tomography.

Probability density function (PDF) analysis with K-distribution model of optical coherence tomography (OCT) intensity signals has previously yielded a good representation of the average number of scatterers in a coherence volume for microspheres-in-water systems, and has shown initial promise for biological tissue characterization. In this work, we extend these previous findings, based on single point M-mode or two-dimenstional slice analysis, to full three-dimensional (3D) imaging maps of the shape parameter α of the K-distribution PDF. After selecting a suitably sized 3D evaluation window, and verifying methodology in phantoms, the resultant parametric α images obtained in different animal tissues (rat liver and brain) show new contrasting ability not seen in conventional OCT intensity images.

Phase and amplitude correction in polygon tunable laser-based optical coherence tomography

Phase instability is a serious problem in swept-source optical coherence tomography (OCT) with polygon tunable lasers; however, these devices have additional issues. We found that polygon tunable lasers also have fluctuations in output power and sweep range: the former creates artifacts that may impair the recognition of sample information, and the latter reduces the interference signal utilization during phase correction. We demonstrate a method that uses the calibration signal to quantify these problems and improve system stability and image quality. The proposed amplitude correction and phase correction methods are used to eliminate vertical artifacts and improve the resolution of OCT flow and intensity images while reducing the phase error.

Measuring the depth of crosslinking demarcation line in vivo: Comparison of methods and devices

To assess the interrelationship of different methods of measuring the demarcation line depth after corneal collagen crosslinking (CXL). University eye clinic, Oslo, Norway. Prospective case series. Eyes having CXL for progressive keratoconus were evaluated 1month after CXL by invitro confocal microscopy (IVCM), optical coherence tomography (OCT), and Scheimpflug imaging. When applying IVCM, the depth of the CXL demarcation line was measured with 2 methods; that is, IVCM keratocyte disappearance and IVCM intensity increase. With OCT, the evaluations were made by measuring the depth of the corneal stromal demarcation line. Scheimpflug imaging was used with 2 depth-measuring methods; that is manual Scheimpflug and objective Scheimpflug intensity change. The demarcation line depths in the central cornea were compared by the intraclass correlation coefficient (ICC) and pairwise comparison of the measured treated depth. If acceptable correlations (ICC>0.7) were found, Bland-Altman analysis was performed. Twenty eyes of 20 patients were evaluated. Acceptable correlations were found between depth measurements using OCT-IVCM keratocyte disappearance (ICC=0.80), OCT-IVCM intensity increase (ICC=0.75), and IVCM intensity increase-IVCM keratocyte disappearance (ICC=0.91). The Bland-Altman plots of these 3 pairs showed sufficient levels of agreement. Using pairwise comparison of these pairs, the measured depths were in the same level by the OCT-IVCM intensity increase only (P=.529). Scheimpflug images were inaccurate for measuring the CXL demarcation line depth. The 2 confocal microscopy methods and OCT images showed good correlation. Of these 3 pairs, only measurements with OCT and IVCM intensity increase depths were in the same level.

Fourier-Domain Optical Coherence Tomography Signal Analysis and Numerical Modeling

In this work the theory of the optical coherence tomography (OCT) signal after sampling, in dispersive media, with noise, and for a turbid medium is presented. The analytical theory is demonstrated with a one-dimensional numerical OCT model for (single) reflectors, dispersive media, and turbid media. For dispersive media the deterioration of the OCT axial resolution is quantified analytically and numerically. The OCT signal to noise ratio (SNR) is analyzed in the Fourier-domain and simulated with the numerical model. For an SNR based on the OCT intensity the conventional shot noise limited SNR is derived whereas for an SNR based on the OCT amplitude a 6.7 dB higher SNR is demonstrated. The OCT phase stability is derived in the Fourier-domain as 2SNR−1 and is validated using the numerical OCT model. The OCT single scattering model is simulated with the one-dimensional numerical model and applied to the simulation of an OCT image of a two-layered sample.

Probability density function formalism for optical coherence tomography signal analysis: a controlled phantom study.

The distribution of backscattered intensities as described by the probability density function (PDF) of tissue-scattered light contains information that may be useful for tissue assessment and diagnosis, including characterization of its pathology. In this Letter, we examine the PDF description of the light scattering statistics in a well characterized tissue-like particulate medium using optical coherence tomography (OCT). It is shown that for low scatterer density, the governing statistics depart considerably from a Gaussian description and follow the K distribution for both OCT amplitude and intensity. The PDF formalism is shown to be independent of the scatterer flow conditions; this is expected from theory, and suggests robustness and motion independence of the OCT amplitude (and OCT intensity) PDF metrics in the context of potential biomedical applications.

High-resolution contrast-enhanced optical coherence tomography in mice retinae.

Optical coherence tomography (OCT) is a noninvasive interferometric imaging modality providing anatomical information at depths of millimeters and a resolution of micrometers. Conventional OCT images limit our knowledge to anatomical structures alone, without any contrast enhancement. Therefore, here we have, for the first time, optimized an OCT-based contrast-enhanced imaging system for imaging single cells and blood vessels in vivo inside the living mouse retina at subnanomolar sensitivity. We used bioconjugated gold nanorods (GNRs) as exogenous OCT contrast agents. Specifically, we used anti-mouse CD45 coated GNRs to label mouse leukocytes and mPEG-coated GNRs to determine sensitivity of GNR detection in vivo inside mice retinae. We corroborated OCT observations with hyperspectral dark-field microscopy of formalin-fixed histological sections. Our results show that mouse leukocytes that otherwise do not produce OCT contrast can be labeled with GNRs leading to significant OCT intensity equivalent to a 0.5 nM GNR solution. Furthermore, GNRs injected intravenously can be detected inside retinal blood vessels at a sensitivity of ∼0.5 nM, and GNR-labeled cells injected intravenously can be detected inside retinal capillaries by enhanced OCT contrast. We envision the unprecedented resolution and sensitivity of functionalized GNRs coupled with OCT to be adopted for longitudinal studies of retinal disorders.