Commercial Optical Coherence Tomography System Research Articles

Algorithm and software for field distortion correction in a commercial SD-OCT for corneal curvature assessment.

Accurate assessment of corneal curvatures using frequency domain optical coherence tomography (OCT) with galvanometer scanners remains challenging due to the well-known scan field distortion. This paper presents an algorithm and software for correcting the distortion using only two simple measurements in which a readily available standard sphere is positioned in different depths in front of the OCT scanner. This offers a highly accessible and easily reproducible method for the field distortion correction (FDC). The correction was validated by measuring different spherical phantoms and conducting corneal curvature measurements of ex vivo porcine corneas using a commercial spectral-domain OCT system and a clinically approved swept-source OCT as a reference instrument. Thus, the error in radius measurements of spherical phantoms was reduced by >90% and astigmatism by >80% using FDC. In explanted porcine eyes, the error in astigmatism measurements with the Telesto was reduced by 75% for power and 70% for angle. The best fitting sphere radius was determined up to a deviation of 0.4% from the Anterion. This paper describes a correction algorithm for OCT immanent distortion that is applicable to any scanning OCT setup and enables precise corneal curvature measurements. The MATLAB software for the FDC is publicly available on GitHub.

Sector-Based Regression Strategies to Reduce Refractive Error-Associated Glaucoma Diagnostic Bias When Using OCT and OCT Angiography.

This cross-sectional study aimed to investigate the sectoral variance of optical coherence tomography (OCT) and OCT angiography (OCTA) glaucoma diagnostic parameters across eyes with varying degrees of refractive error. Healthy participants, including individuals with axial ametropia, enrolled in the Hong Kong FAMILY cohort were imaged using the Avanti/AngioVue OCT/OCTA system. The OCT and OCTA parameters obtained include peripapillary nerve fiber layer thickness (NFLT), peripapillary nerve fiber layer plexus capillary density (NFLP-CD), and macular ganglion cell complex thickness (GCCT). Sectoral measurements of NFLT, NFLP-CD, and GCCT were based on sectors and hemispheres. A total of 1339 eyes from 791 participants were stratified based on spherical equivalent refraction: high myopia (<-6 D), low myopia (-6 D to -1 D), emmetropia (-1 D to 1 D), and hyperopia (>1 D). Multivariable broken stick regression models, accounting for age, sex, and signal strength, showed that all NFLT sectors except temporally, the inferior GCCT hemisphere, and half of the NFLP-CD sectors were more affected by ametropia-related covariates than the corresponding global parameters. As expected, the false-positive rates in those sectors were elevated. Finally, sector-specific axial length (AL) and spherical equivalent (SE) adjustments helped reduce the elevated false-positive rates. The effect of optical magnification is even more prominent among sectors than the global parameters. AL- and SE-based adjustments should be individualized to each sector to mitigate this magnification bias effectively. Identifying sectoral differences among diagnostic parameters and adopting these sector-based adjustments into commercial OCT systems will hopefully reduce false-positive rates related to refractive error.

Spectroscopic optical coherence tomography at 1200nm for lipid detection.

Spectroscopic analysis of optical coherence tomography (OCT) data can yield added information about the sample's chemical composition, along with high-resolution images. Typical commercial OCT systems operate at wavelengths that may not be optimal for identifying lipid-containing samples based on absorption features. The main aim of this study was to develop a 1200nm spectroscopic OCT (SOCT) for the classification of lipid-based and water-based samples by extracting the lipid absorption peak at 1210nm from the OCT data. We developed a 1200nm OCT system and implemented a signal processing algorithm that simultaneously retrieves spectroscopic and structural information from the sample. In this study, we validated the performance of our OCT system by imaging weakly scattering phantoms with and without lipid absorption features. An orthogonal projections to latent structures-discriminant analysis (OPLS-DA) model was developed and applied to classify weakly scattering samples based on their absorption features. The OCT system achieved an axial resolution of and a sensitivity of 95dB. The calibrated OPLS-DA model on weakly scattering samples with lipid and water-based absorption features correctly classified 19/20 validation samples. The 1200nm SOCT system can discriminate the lipid-containing weakly scattering samples from water-based weakly scattering samples with good predictive ability.

Debiased ambient vibrations optical coherence elastography to profile cell, organoid and tissue mechanical properties

The role of the mechanical environment in defining tissue function, development and growth has been shown to be fundamental. Assessment of the changes in stiffness of tissue matrices at multiple scales has relied mostly on invasive and often specialist equipment such as AFM or mechanical testing devices poorly suited to the cell culture workflow.In this paper, we have developed a unbiased passive optical coherence elastography method, exploiting ambient vibrations in the sample that enables real-time noninvasive quantitative profiling of cells and tissues. We demonstrate a robust method that decouples optical scattering and mechanical properties by actively compensating for scattering associated noise bias and reducing variance. The efficiency for the method to retrieve ground truth is validated in silico and in vitro, and exemplified for key applications such as time course mechanical profiling of bone and cartilage spheroids, tissue engineering cancer models, tissue repair models and single cell. Our method is readily implementable with any commercial optical coherence tomography system without any hardware modifications, and thus offers a breakthrough in on-line tissue mechanical assessment of spatial mechanical properties for organoids, soft tissues and tissue engineering.

Open-source, highly efficient, post-acquisition synchronization for 4D dual-contrast imaging of the mouse embryonic heart over development with optical coherence tomography.

Dynamic imaging of the beating embryonic heart in 3D is critical for understanding cardiac development and defects. Optical coherence tomography (OCT) plays an important role in embryonic heart imaging with its unique imaging scale and label-free contrasts. In particular, 4D (3D + time) OCT imaging enabled biomechanical analysis of the developing heart in various animal models. While ultrafast OCT systems allow for direct volumetric imaging of the beating heart, the imaging speed remains limited, leading to an image quality inferior to that produced by post-acquisition synchronization. As OCT systems become increasingly available to a wide range of biomedical researchers, a more accessible 4D reconstruction method is required to enable the broader application of OCT in the dynamic, volumetric assessment of embryonic heartbeat. Here, we report an open-source, highly efficient, post-acquisition synchronization method for 4D cardiodynamic and hemodynamic imaging of the mouse embryonic heart. Relying on the difference between images to characterize heart wall movements, the method provides good sensitivity to the cardiac activity when aligning heartbeat phases, even at early stages when the heart wall occupies only a small number of pixels. The method works with a densely sampled single 3D data acquisition, which, unlike the B-M scans required by other methods, is readily available in most commercial OCT systems. Compared with an existing approach for the mouse embryonic heart, this method shows superior reconstruction quality. We present the robustness of the method through results from different embryos with distinct heart rates, ranging from 1.24 Hz to 2.13 Hz. Since the alignment process operates on a 1D signal, the method has a high efficiency, featuring sub-second alignment time while utilizing ∼100% of the original image files. This allows us to achieve repeated, dual-contrast imaging of mouse embryonic heart development. This new, open-source method could facilitate research using OCT to study early cardiogenesis.

Regression-Based Strategies to Reduce Refractive Error-Associated Glaucoma Diagnostic Bias When Using OCT and OCT Angiography.

PurposeThe purpose of this study was to correct refractive error-associated bias in optical coherence tomography (OCT) and OCT angiography (OCTA) glaucoma diagnostic parameters.MethodsOCT and OCTA imaging were obtained from participants in the Hong Kong FAMILY cohort. The Avanti/AngioVue OCT/OCTA system was used to measure the peripapillary nerve fiber layer thickness (NFLT), peripapillary nerve fiber layer plexus capillary density (NFLP-CD), macular ganglion cell complex thickness (GCCT), and macular superficial vascular complex vascular density (SVC-VD). Healthy eyes, including ones with axial ametropia, were enrolled for analysis.ResultsA total of 1346 eyes from 792 participants were divided into 4 subgroups: high myopia (<−6D), low myopia (−6D to −1D), emmetropia (−1D to 1D), and hyperopia (>1D). After accounting for age, sex, and signal strength, multivariable regression showed strong dependence in most models for NFLT, GCCT, and NFLP-CD on axial eye length (AL), spherical equivalent (SE) refraction, and apparent optic disc diameter (DD). Optical analysis indicated that AL-related transverse optical magnification variations predominated over anatomic variations and were responsible for these trends. Compared to the emmetropic group, the false positive rates were significantly (Chi-square test P < 0.003) elevated in both myopia groups for NFLT, NFLP-CD, and GCCT. Regression-based adjustment of these diagnostic parameters with AL or SE significantly (McNemar test P < 0.03) reduced the elevated false positive rates.ConclusionsMyopic eyes are biased to have lower NFLT, GCCT, and NFLP-CD measurements. AL- and SE-based adjustments were effective in mitigating this bias.Translational RelevanceAdoption of these adjustments into commercial OCT systems may reduce false positive rates related to refractive error.

Volume-based, layer-independent, disease-agnostic detection of abnormal retinal reflectivity, nonperfusion, and neovascularization using structural and angiographic OCT.

Optical coherence tomography (OCT) is widely used in ophthalmic practice because it can visualize retinal structure and vasculature in vivo and 3-dimensionally (3D). Even though OCT procedures yield data volumes, clinicians typically interpret the 3D images using two-dimensional (2D) data subsets, such as cross-sectional scans or en face projections. Since a single OCT volume can contain hundreds of cross-sections (each of which must be processed with retinal layer segmentation to produce en face images), a thorough manual analysis of the complete OCT volume can be prohibitively time-consuming. Furthermore, 2D reductions of the full OCT volume may obscure relationships between disease progression and the (volumetric) location of pathology within the retina and can be prone to mis-segmentation artifacts. In this work, we propose a novel framework that can detect several retinal pathologies in three dimensions using structural and angiographic OCT. Our framework operates by detecting deviations in reflectance, angiography, and simulated perfusion from a percent depth normalized standard retina created by merging and averaging scans from healthy subjects. We show that these deviations from the standard retina can highlight multiple key features, while the depth normalization obviates the need to segment several retinal layers. We also construct a composite pathology index that measures average deviation from the standard retina in several categories (hypo- and hyper-reflectance, nonperfusion, presence of choroidal neovascularization, and thickness change) and show that this index correlates with DR severity. Requiring minimal retinal layer segmentation and being fully automated, this 3D framework has a strong potential to be integrated into commercial OCT systems and to benefit ophthalmology research and clinical care.

Correlation Between Laser Speckle Flowgraphy and OCT-Derived Retinal and Choroidal Metrics in Healthy Human Eye.

PurposeTo investigate the correlation between laser speckle flowgraphy (LSFG) signals and the quantitative metrics derived from optical coherence tomography (OCT) in normal eyes.MethodsLSFG, OCT, and OCT angiography (OCTA) imaging were performed on normal participants using a custom-designed LSFG system and a commercial swept-source OCT system. Mean (PWM) and amplitude (PWA) of the LSFG pulse waveform were selected to quantify the LSFG signals. Retinal and choroidal maps were obtained using the standard 6 × 6 mm OCT and OCTA scans. Structural and vascular metrics maps, including thickness, vessel area density, vessel skeleton density, and vessel diameter index of the retina, and choroidal thickness (CT), choroidal vessel volume (CVV) and choroidal vessel index (CVI), were employed to quantify the retinal and choroidal properties. Correlation analysis was then performed between the LSFG, retinal, and choroidal metrics maps.ResultsTwelve healthy participants aged 23 to 36 years were enrolled in this study. The spatial distribution of the PWM and PWA values was highly correlated with that of the CT and CVV metrics. On average, Spearman correlation coefficients (ρ) were 0.80 and 0.78 (all P < 0.001) for the correlations between PWM and CT and CVV, respectively, and were 0.61 and 0.63 (all P < 0.05) for the correlations between PWA and CT and CVV, respectively. In comparison, both PWM and PWA were generally weak or not correlated with all the retinal metrics and CVI.ConclusionsLSFG signals were positively correlated with the choroidal thickness and vessel volume, suggesting choroidal blood flows dominate the LSFG signals at the area absent of large retinal vessels.Translational RelevanceThis study illustrates the dominant source of the LSFG signals in the eye.

Simple Characterization Scheme for Optical Coherence Tomography Systems With Application to a Commercial and a Near-Isometric Resolution Fibre-Based System

Optical Coherence Tomography (OCT) is a rapidly growing imaging modality in biomedical optics. OCT can perform high-resolution, cross-sectional imaging of the microstructure of biological tissues by measuring the coherent spectrum from the backscattered light. OCT systems with broad spectral bandwidths are often constructed using free-space optics to avoid dispersion by fibre optic components. This paper presents a fibre-based OCT system at a centre wavelength of 1300 nm with an axial resolution of 3.8 µm in air, surpassing any previously reported values to the best of our knowledge. Despite the challenges in transporting a broadband spectrum using fibre-optics, the system investigation was motivated by the ever-increasing demand for commercialization of high-resolution OCT systems and simplification of construction. We also evaluate and demonstrate the direct measurement method for axial resolution using an air wedge. Imaging of biomedical and other samples is demonstrated using a high numerical aperture sample lens and compared with images from a commercial OCT system. We discuss the effect of the improved structural visibility by achieving image voxels closer to an isometric shape with a high NA sample lens.

Differentiation between normal and tumor mammary glands with depth-resolved attenuation coefficient from optical coherence tomography

Optical coherence tomography (OCT) is a well-established imaging technology for high-resolution, cross-sectional imaging of biological tissues. Imaging processing and light attenuation coefficient estimation allows to further improve the OCT diagnostic capability. In this paper we use a commercial OCT system, Telesto II-1325LR from Thorlabs, and demonstrate its ability to differentiate normal and tumor mammary mouse glands with the OCT attenuation coefficient. Using several OCT images of normal and tumor mammary mouse glands (n = 26), a statistical analysis was performed. The attenuation coefficient was calculated in depth, considering a slope of 0.5 mm. The normal glands present a median attenuation coefficient of 0.403 mm−1, comparatively to 0.561 mm−1 obtained for tumor mammary glands. This translates in an attenuation coefficient approximately 39% higher for tumor mammary glands when compared to normal mammary glands. The OCT attenuation coefficient estimation eliminates the subjective analysis provided by direct visualization of the OCT images.

Multi-task learning approach for volumetric segmentation and reconstruction in 3D OCT images.

The choroid is the vascular layer of the eye that supplies photoreceptors with oxygen. Changes in the choroid are associated with many pathologies including myopia where the choroid progressively thins due to axial elongation. To quantize these changes, there is a need to automatically and accurately segment the choroidal layer from optical coherence tomography (OCT) images. In this paper, we propose a multi-task learning approach to segment the choroid from three-dimensional OCT images. Our proposed architecture aggregates the spatial context from adjacent cross-sectional slices to reconstruct the central slice. Spatial context learned by this reconstruction mechanism is then fused with a U-Net based architecture for segmentation. The proposed approach was evaluated on volumetric OCT scans of 166 myopic eyes acquired with a commercial OCT system, and achieved a cross-validation Intersection over Union (IoU) score of 94.69% which significantly outperformed (p<0.001) the other state-of-the-art methods on the same data set. Choroidal thickness maps generated by our approach also achieved a better structural similarity index (SSIM) of 72.11% with respect to the groundtruth. In particular, our approach performs well for highly challenging eyes with thinner choroids. Compared to other methods, our proposed approach also requires lesser processing time and has lower computational requirements. The results suggest that our proposed approach could potentially be used as a fast and reliable method for automated choroidal segmentation.

Delineating papillary dermis around basal cell carcinomas by high and ultrahigh resolution optical coherence tomography-A pilot study.

Bedside diagnosis of skin cancer remains a challenging task. The real-time noninvasive technology of optical coherence tomography (OCT) masters a high diagnostic accuracy in basal cell carcinoma (BCC) but a lower specificity in recognizing imitators and other carcinomas. We investigate the delicate signal of papillary dermis using an in-house developed ultrahigh resolution OCT (UHR-OCT) system with shadow compensation and a commercial multi-focus high resolution OCT (HR-OCT) system for clinical BCC imaging. We find that the HR-OCT system struggled to resolve the dark band signal of papillary dermis where the UHR-OCT located this in all cases and detected changes in signal width. UHR-OCT is able to monitor extension and position of papillary dermis suggesting a novel feature for delineating superficial BCCs in pursuit of a fast accurate diagnosis. Comprehensive studies involving more patients are imperative in order to corroborate results.

Evaluation of a Self-Imaging SD-OCT System for Remote Monitoring of Patients with Neovascular Age Related Macular Degeneration.

The treatment of patients with neovascular age-related macular degeneration (nAMD) requires frequent office visits to identify fluid in the retina that requires treatment. Frequent office-based examinations using optical coherence tomography (OCT) are a burden on patients and their care givers. The development of OCT systems that can be self-operated by patients at home offers the potential for precise remote monitoring and improved individualized therapy. An investigational spectral domain OCT system (Notal Vision Home OCT, NVHO) for automatic patient-guided self-imaging intended for commercialization was evaluated in a total of 69 study participants with neovascular age-related macular degeneration with regard to image quality and usability. An artificial intelligence-based algorithm was used to identify, quantify and map intra- and subretinal fluids. Successful imaging with the NHVO was performed in all patients and in 93% of the enrolled eyes. The positive percent agreement and negative percent agreement for detection of fluid, intraretinal fluid, and subretinal fluid in at least one of three consecutive NHVO images was 97/95%, 96/94% and 100/98%, respectively, when compared to commercial in-office OCT systems. In 1.4% of the recorded eyes, fluid was only detected outside of the central 10 × 10° field of view but seen on a commercial OCT system with a larger field of view. The device operation for scanning their own eyes without assistance was rated by 95% of patients as easy. The analysis and depiction of fluid distribution and volume in a longitudinal case study illustrated the acute nature and anti-VEGF therapy response of nAMD. The evaluated OCT system for home use meets the requirements for self-controlled imaging by nAMD patients with regard to image quality, field of view and usability. Image analysis based on artificial intelligence can potentially support clinicians in the assessment and utilization of large amounts of data generated by daily home OCT imaging.

Abstract 2725: Long-term live imaging of ovarian cancer invasion using optical coherence tomography

Abstract Ovarian cancer is a lethal gynecological disease but the histological subtypes of ovarian cancer differ in their biology and clinical behavior. We have previously demonstrated that ovarian carcinoma cell line behavior is related to the primary tumor origin, providing a rationale for in vitro modelling to identify differences between ovarian tumor types. To better understand the in vivo behavior of ovarian tumors we are developing a patient-specific ex vivo model that can be used to investigate individual patient tumor behavior, alongside a microscopy tool that allows live imaging to investigate tumor invasion and eventually response to therapy over time. Optical coherence tomography (OCT) is a non-damaging imaging technique used clinically to investigate ocular disease in vivo. Real time live imaging of ovarian cancer cell lines over 5 days was established on a commercial OCT system using non-serous ovarian cancer cell lines TOV21G and A2780 seeded onto a collagen/fibroblast matrix. We have previously used histology to reveal that TOV21G cells invade into collagen with a spindle-like morphology characteristic of sarcomatous tumor cell invasion whereas A2780 invade in clusters characteristic of epithelial tumor cells. Using live OCT imaging we have visualized how these different invasive patterns develop over time. Live imaging facilitates investigation of different invasive behaviors with greater granularity, resolving differences in phenotypic behavior. We are now developing machine learning algorithms that can quantitatively analyze the speed, depth and frequency of invasion over time. High-grade serous (HGS) carcinomas commonly spread transcoelomically along peritoneal surfaces, seeding secondary tumors on and in the peritoneum and omentum. We have demonstrated that HGS cell lines do not invade into common in vitro extracellular matrix substitutes such as matrigel and collagen, highlighting the need for a biological technique that better recapitulates the in vivo behavior. We have developed ex vivo cultures using patient-derived tumor and matched normal omentum to better mimic in vivo invasive behavior. We have used both tissue slices and mechanically dissociated tumor cells cultured with patient omentum compared with in vitro derived collagen/fibroblast matrices, demonstrating retention of tumor viability over a 10 day period. We are now using the OCT technique to live image and quantitatively analyze patient tumor-omentum interactions over time, comparing those data with histology to determine the interaction with invasion substrate at fixed time points over the 10 day culture period. OCT is a promising and novel tool for the investigation of tumor invasion ex vivo. Applying this to ovarian cancer patient-derived matched tumor and omentum provides the opportunity to assess not only invasive capacity but also patient-specific response to therapy. Citation Format: Amelia Hallas-Potts, Jonathan H. Mason, Jessica H. Lim, Michael Churchman, Pierre Bagnaninchi, Charlie Gourley, C. Simon Herrington. Long-term live imaging of ovarian cancer invasion using optical coherence tomography [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2725.

Advances in Whole-Eye Optical Coherence Tomography Imaging.

Contemporary anterior segment and retinal optical coherence tomography (OCT) systems only image their particular designated region of the eye and cannot image both areas of the eye at the same time. This separation is due to the differences in optical system design needed to properly image the front or back of the eye and also due to limitations in the imaging depth of current commercial OCT systems. More recently, research and commercial OCT systems capable of "whole-eye" imaging have been described. These whole-eye OCT systems enable applications such as ocular biometry for cataract surgery, ocular shape analysis for myopia, and others. Further, these whole-eye OCT systems allow us to image the eye as an integrated whole rather than as separate, independent divisions.

Two optical coherence tomography systems detect topical gold nanoshells in hair follicles, sweat ducts and measure epidermis.

Optical coherence tomography (OCT) is an established imaging technology for in vivo skin investigation. Topical application of gold nanoshells (GNS) provides contrast enhancement in OCT by generating a strong hyperreflective signal from hair follicles and sweat glands, which are the natural skin openings. This study explores the utility of 150 nm diameter GNS as contrast agent for OCT imaging. GNS was massaged into skin and examined in four skin areas of 11 healthy volunteers. A commercial OCT system and a prototype with 3 μm resolution (UHR-OCT) were employed to detect potential benefits of increased resolution and variability in intensity generated by the GNS. In both OCT-systems GNS enhanced contrast from hair follicles and sweat ducts. Highest average penetration depth of GNS was in armpit 0.64 mm ± SD 0.17, maximum penetration depth was 1.20 mm in hair follicles and 15 to 40 μm in sweat ducts. Pixel intensity generated from GNS in hair follicles was significantly higher in UHR-OCT images (P = .002) and epidermal thickness significantly lower 0.14 vs 0.16 mm (P = .027). This study suggests that GNSs are interesting candidates for increasing sensitivity in OCT diagnosis of hair and sweat gland disorders and demonstrates that choice of OCT systems influences results.

The value of ultrahigh resolution OCT in dermatology - delineating the dermo-epidermal junction, capillaries in the dermal papillae and vellus hairs.

Optical coherence tomography (OCT) imaging of the skin is gaining recognition and is increasingly applied to dermatological research. A key dermatological parameter inferred from an OCT image is the epidermal (Ep) thickness as a thickened Ep can be an indicator of a skin disease. Agreement in the literature on the signal characters of Ep and the subjacent skin layer, the dermis (D), is evident. Ambiguities of the OCT signal interpretation in the literature is however seen for the transition region between the Ep and D, which from histology is known as the dermo-epidermal junction (DEJ); a distinct junction comprised of the lower surface of a single cell layer in epidermis (the stratum basale) connected to an even thinner membrane (the basement membrane). The basement membrane is attached to the underlying dermis. In this work we investigate the impact of an improved axial and lateral resolution on the applicability of OCT for imaging of the skin. To this goal, OCT images are compared produced by a commercial OCT system (Vivosight from Michaelson Diagnostics) and by an in-house built ultrahigh resolution (UHR-) OCT system for dermatology. In 11 healthy volunteers, we investigate the DEJ signal characteristics. We perform a detailed analysis of the dark (low) signal band clearly seen for UHR-OCT in the DEJ region where we, by using a transition function, find the signal transition of axial sub-resolution character, which can be directly attributed to the exact location of DEJ, both in normal (thin/hairy) and glabrous (thick) skin. To our knowledge no detailed delineating of the DEJ in the UHR-OCT image has previously been reported, despite many publications within this field. For selected healthy volunteers, we investigate the dermal papillae and the vellus hairs and identify distinct features that only UHR-OCT can resolve. Differences are seen in tracing hairs of diameter below 20 μm, and in imaging the dermal papillae where, when utilising the UHR-OCT, capillary structures are identified in the hand palm, not previously reported in OCT studies and specifically for glabrous skin not reported in any other in vivo optical imaging studies.

Nondestructive Optical Toxicity Assays of 3D Liver Spheroids with Optical Coherence Tomography

AbstractDrug‐induced liver injury (DILI) is the leading cause of failure in preclinical drug development and withdrawals. Given the central role of the liver in drug metabolism and detoxification, strong incentives exist to create new physiologically relevant, human‐based, 3D in vitro liver models which will offer better prediction of DILI. However, most cell metabolic assays are designed for 2D culture and are not always suitable to assess 3D cultures; in addition, there is an emerging need to develop novel nondestructive assays to assess cell activity in a time‐lapse fashion. In this study, optical coherence tomography (OCT) is used to measure the viability on 3D liver spheroids after acetaminophen exposure used as a model of DILI. Using HepaRG cells, 3D liver spheroids are grown simultaneously to the conventional 2D DILI model for 9 d and are exposed to 5, 10, 20, and 40 × 10−3 m acetaminophen for 24 h. It is shown that OCT can image noninvasively, and label free, the cell metabolic activity, thus enabling the assessment of viability of the 3D spheroids. This correlates well with cellular metabolic activity measured by biochemical assays. This method is translatable to any 3D tissue model and can be performed using any commercial OCT system.

Statistical Models of Signal and Noise and Fundamental Limits of Segmentation Accuracy in Retinal Optical Coherence Tomography.

Optical coherence tomography (OCT) has revolutionized diagnosis and prognosis of ophthalmic diseases by visualization and measurement of retinal layers. To speed up the quantitative analysis of disease biomarkers, an increasing number of automatic segmentation algorithms have been proposed to estimate the boundary locations of retinal layers. While the performance of these algorithms has significantly improved in recent years, a critical question to ask is how far we are from a theoretical limit to OCT segmentation performance. In this paper, we present the Cramèr-Rao lower bounds (CRLBs) for the problem of OCT layer segmentation. In deriving the CRLBs, we address the important problem of defining statistical models that best represent the intensity distribution in each layer of the retina. Additionally, we calculate the bounds under an optimal affine bias, reflecting the use of prior knowledge in many segmentation algorithms. Experiments using in vivo images of human retina from a commercial spectral domain OCT system are presented, showing potential for improvement of automated segmentation accuracy. Our general mathematical model can be easily adapted for virtually any OCT system. Furthermore, the statistical models of signal and noise developed in this paper can be utilized for the future improvements of OCT image denoising, reconstruction, and many other applications.

Motion of intracochlear structures measured with a commercial optical coherence tomography (OCT) system

Most knowledge of the motion of cochlear structures has been limited to measurements through the round window at the extreme base of the cochlea or through a hole made in the cochlear capsule, which can modify cochlear mechanics. Optical coherence tomography (OCT) provides the ability to measure shape or motion of structures through a thin layer of tissue or bone. The motion of cochlear structures has been measured in the mouse cochlear apex without making an opening into the cochlea, using a custom OCT system. Here we describe intracochlear vibrometry using a commercial OCT system. Specimens were prepared by opening the middle ear while maintaining part of the cartilaginous ear canal. A Thorlabs 905nm Ganymede III-HR OCT system with 100-kHz camera frame rate was used to measure cochlear anatomy in a 2-D radial slice (B-scan) and dynamic displacements along a line (A-line) that intersected several cochlear structures in response to tones presented to the ear canal. Differences in the magnitude and phase of the displacements along the A-line show differences in the motion of cochlear structures. These data will provide information for validating 3D finite element models of the cochlea. [Work supported by NIDCD R01 DC07910.]