Frequency multiplexed long range swept source optical coherence tomography

We present a novel swept source optical coherence tomography configuration, equipped with acousto-optic deflectors that can be used to simultaneously acquire multiple B-scans originating from different depths. The sensitivity range of the configuration is evaluated while acquiring five simultaneous B-scans. Then the configuration is employed to demonstrate long range B-scan imaging by combining two simultaneous B-scans from a mouse head sample.OCIS codes: (120.3180) Interferometry, (110.4500) Optical coherence tomography, (170.1065) Acousto-optics, (170.0110) Imaging systems, (110.6880) Three-dimensional image acquisition, (140.3600) Lasers, tunable     

Repeatability of in vivo 3D lamina cribrosa microarchitecture using adaptive optics spectral domain optical coherence tomography

We demonstrate the repeatability of lamina cribrosa (LC) microarchitecture for in vivo 3D optical coherence tomography (OCT) scans of healthy, glaucoma suspects, and glaucomatous eyes. Eyes underwent two scans using a prototype adaptive optics spectral domain OCT (AO-SDOCT) device from which LC microarchitecture was semi-automatically segmented. LC segmentations were used to quantify pore and beam structure through several global microarchitecture parameters. Repeatability of LC microarchitecture was assessed qualitatively and quantitatively by calculating parameter imprecision. For all but one parameters (pore volume) measurement imprecision was <4.7% of the mean value, indicating good measurement reproducibility. Imprecision ranged between 27.3% and 54.5% of the population standard deviation for each parameter, while there was not a significant effect on imprecision due to disease status, indicating utility in testing for LC structural trends.OCIS codes: (100.2000) Digital image processing, (170.4470) Ophthalmology, (110.4500) Optical coherence tomography, (170.1610) Clinical applications, (330.4460) Ophthalmic optics and devices     

Monitoring airway mucus flow and ciliary activity with optical coherence tomography

Muco-ciliary transport in the human airway is a crucial defense mechanism for removing inhaled pathogens. Optical coherence tomography (OCT) is well-suited to monitor functional dynamics of cilia and mucus on the airway epithelium. Here we demonstrate several OCT-based methods upon an actively transporting in vitro bronchial epithelial model and ex vivo mouse trachea. We show quantitative flow imaging of optically turbid mucus, semi-quantitative analysis of the ciliary beat frequency, and functional imaging of the periciliary layer. These may translate to clinical methods for endoscopic monitoring of muco-ciliary transport in diseases such as cystic fibrosis and chronic obstructive pulmonary disease (COPD).OCIS codes: (170.4500) Optical coherence tomography, (110.4153) Motion estimation and optical flow, (170.2655) Functional monitoring and imaging, (170.3880) Medical and biological imaging, (110.6150) Speckle imaging, (110.0113) Imaging through turbid media     

Automatic detection of retinopathy with optical coherence tomography images via a semi-supervised deep learning method

Automatic detection of retinopathy via computer vision techniques is of great importance for clinical applications. However, traditional deep learning based methods in computer vision require a large amount of labeled data, which are expensive and may not be available in clinical applications. To mitigate this issue, in this paper, we propose a semi-supervised deep learning method built upon pre-trained VGG-16 and virtual adversarial training (VAT) for the detection of retinopathy with optical coherence tomography (OCT) images. It only requires very few labeled and a number of unlabeled OCT images for model training. In experiments, we have evaluated the proposed method on two popular datasets. With only 80 labeled OCT images, the proposed method can achieve classification accuracies of 0.942 and 0.936, sensitivities of 0.942 and 0.936, specificities of 0.971 and 0.979, and AUCs (Area under the ROC Curves) of 0.997 and 0.993 on the two datasets, respectively. When comparing with human experts, it achieves expert level with 80 labeled OCT images and outperforms four out of six experts with 200 labeled OCT images. Furthermore, we also adopt the Gradient Class Activation Map (Grad-CAM) method to visualize the key regions that the proposed method focuses on when making predictions. It shows that the proposed method can accurately recognize the key patterns of the input OCT images when predicting retinopathy.     

4D shear stress maps of the developing heart using Doppler optical coherence tomography

Accurate imaging and measurement of hemodynamic forces is vital for investigating how physical forces acting on the embryonic heart are transduced and influence developmental pathways. Of particular importance is blood flow-induced shear stress, which influences gene expression by endothelial cells and potentially leads to congenital heart defects through abnormal heart looping, septation, and valvulogenesis. However no imaging tool has been available to measure shear stress on the endocardium volumetrically and dynamically. Using 4D structural and Doppler OCT imaging, we are able to accurately measure the blood flow in the heart tube in vivo and to map endocardial shear stress throughout the heart cycle under physiological conditions for the first time. These measurements of the shear stress patterns will enable precise titration of experimental perturbations and accurate correlation of shear with the expression of molecules critical to heart development.OCIS codes: (110.4500) Optical coherence tomography, (170.3880) Medical and biological imaging     

Corneal imaging with blue-light optical coherence microscopy

Corneal imaging is important for the diagnostic and therapeutic evaluation of many eye diseases. Optical coherence tomography (OCT) is extensively used in ocular imaging due to its non-invasive and high-resolution volumetric imaging characteristics. Optical coherence microscopy (OCM) is a technical variation of OCT that can image the cornea with cellular resolution. Here, we demonstrate a blue-light OCM as a low-cost and easily reproducible system to visualize corneal cellular structures such as epithelial cells, endothelial cells, keratocytes, and collagen bundles within stromal lamellae. Our blue-light OCM system achieved an axial resolution of 12 µm in tissue over a 1.2 mm imaging depth, and a lateral resolution of 1.6 µm over a field of view of 750 µm × 750 µm.     

High-resolution 1050 nm spectral domain retinal optical coherence tomography at 120 kHz A-scan rate with 6.1 mm imaging depth

We report a newly developed high speed 1050nm spectral domain optical coherence tomography (SD-OCT) system for imaging posterior segment of human eye. The system is capable of an axial resolution at ~10 µm in air, an imaging depth of 6.1 mm in air, a system sensitivity fall-off at ~6 dB/3mm and an imaging speed of 120,000 A-scans per second. We experimentally demonstrate the system’s capability to perform phase-resolved imaging of dynamic blood flow within retina, indicating high phase stability of the SDOCT system. Finally, we show an example that uses this newly developed system to image posterior segment of human eye with a large view of view (10 × 9 mm²), providing detailed visualization of microstructural features from anterior retina to posterior choroid. The demonstrated system parameters and imaging performances are comparable to those that a typical 1 µm swept source OCT would deliver for retinal imaging.OCIS codes: (170.4460) Ophthalmic optics and devices, (170.3880) Medical and biological imaging, (170.4500) Optical coherence tomography     

Comparison of peripapillary choroidal thickness measurements via spectral domain optical coherence tomography with and without enhanced depth imaging

Objectives: To compare peripapillary choroidal thickness (PP-CT) measurements using a spectral domain optical coherence tomography (SD-OCT) device with and without enhanced depth imaging (EDI).

Methods: Sixty healthy subjects aged from 18 to 40 years were included in this study. PP-CTs were measured in the right eyes by manual segmentation via SD-OCT both with and without EDI. The intraclass correlation coefficient (ICC) for each technique and comparison of PP-CT measurements between two techniques were evaluated. The correlation between retinal nerve fiber layer (RNFL) thickness and PP-CT was also explored on images of SD-OCT without EDI.

Results: The PP-CT measurements of 55 subjects were evaluated. The ICC was 0.999 (95% CI: 0.998–1.0, p < 0.001) for SD-OCT with EDI and 0.996 (95% CI: 0.995–0.997, p < 0.001) for SD-OCT without EDI. The mean PP-CT measurements in all regions and the overall mean PP-CT measurements between the two techniques were not different (p > 0.05). Additionally, there was no correlation between RNFL thickness and PP-CT (r = ?0.109; p = 0.335).

Conclusions: The PP-CT measurements via SD-OCT without EDI were consistent with the measurements via SD-OCT with EDI. Ophthalmologists who do not have access to EDI technology can use images of SD-OCT without EDI to measure the peripapillary choroid for research purposes. However, thicker peripapillary choroids cannot be measured using this technique and require further modifications or newer technologies, such as SD-OCT with EDI     

Sparsity based denoising of spectral domain optical coherence tomography images

In this paper, we make contact with the field of compressive sensing and present a development and generalization of tools and results for reconstructing irregularly sampled tomographic data. In particular, we focus on denoising Spectral-Domain Optical Coherence Tomography (SDOCT) volumetric data. We take advantage of customized scanning patterns, in which, a selected number of B-scans are imaged at higher signal-to-noise ratio (SNR). We learn a sparse representation dictionary for each of these high-SNR images, and utilize such dictionaries to denoise the low-SNR B-scans. We name this method multiscale sparsity based tomographic denoising (MSBTD). We show the qualitative and quantitative superiority of the MSBTD algorithm compared to popular denoising algorithms on images from normal and age-related macular degeneration eyes of a multi-center clinical trial. We have made the corresponding data set and software freely available online.     

Phase-sensitive imaging of the outer retina using optical coherence tomography and adaptive optics

The cone photoreceptor's outer segment (OS) experiences changes in optical path length, both in response to visible stimuli and as a matter of its daily course of renewal and shedding. These changes are of interest, to quantify function in healthy cells and assess dysfunction in diseased ones. While optical coherence tomography (OCT), combined with adaptive optics (AO), has permitted unprecedented three-dimensional resolution in the living retina, it has not generally been able to measure these OS dynamics, whose scale is smaller than OCT's axial resolution of a few microns. A possible solution is to take advantage of the phase information encoded in the OCT signal. Phase-sensitive implementations of spectral-domain optical coherence tomography (SD-OCT) have been demonstrated, capable of resolving sample axial displacements much smaller than the imaging wavelength, but these have been limited to ex vivo samples. In this paper we present a novel technique for retrieving phase information from OCT volumes of the outer retina. The key component of our technique is quantification of phase differences within the retina. We provide a quantitative analysis of such phase information and show that-when combined with appropriate methods for filtering and unwrapping-it can improve the sensitivity to OS length change by more than an order of magnitude, down to 45 nm, slightly thicker than a single OS disc. We further show that phase sensitivity drops off with retinal eccentricity, and that the best location for phase imaging is close to the fovea. We apply the technique to the measurement of sub-resolution changes in the OS over matters of hours. Using custom software for registration and tracking, these microscopic changes are monitored in hundreds of cones over time. In two subjects, the OS was found to have average elongation rates of 150 nm/hr, values which agree with our previous findings.     

Integrated adaptive optics optical coherence tomography and adaptive optics scanning laser ophthalmoscope system for simultaneous cellular resolution in vivo retinal imaging

We describe an ultrahigh-resolution (UHR) retinal imaging system that combines adaptive optics Fourier-domain optical coherence tomography (AO-OCT) with an adaptive optics scanning laser ophthalmoscope (AO-SLO) to allow simultaneous data acquisition by the two modalities. The AO-SLO subsystem was integrated into the previously described AO-UHR OCT instrument with minimal changes to the latter. This was done in order to ensure optimal performance and image quality of the AO- UHR OCT. In this design both imaging modalities share most of the optical components including a common AO-subsystem and vertical scanner. One of the benefits of combining Fd-OCT with SLO includes automatic co-registration between two acquisition channels for direct comparison between retinal structures imaged by both modalities (e.g., photoreceptor mosaics or microvasculature maps). Because of differences in the detection scheme of the two systems, this dual imaging modality instrument can provide insight into retinal morphology and potentially function, that could not be accessed easily by a single system. In this paper we describe details of the components and parameters of the combined instrument, including incorporation of a novel membrane magnetic deformable mirror with increased stroke and actuator count used as a single wavefront corrector. We also discuss laser safety calculations for this multimodal system. Finally, retinal images acquired in vivo with this system are presented.     

High-speed spectral domain optical coherence tomography using non-uniform fast Fourier transform

The useful imaging range in spectral domain optical coherence tomography (SD-OCT) is often limited by the depth dependent sensitivity fall-off. Processing SD-OCT data with the non-uniform fast Fourier transform (NFFT) can improve the sensitivity fall-off at maximum depth by greater than 5dB concurrently with a 30 fold decrease in processing time compared to the fast Fourier transform with cubic spline interpolation method. NFFT can also improve local signal to noise ratio (SNR) and reduce image artifacts introduced in post-processing. Combined with parallel processing, NFFT is shown to have the ability to process up to 90k A-lines per second. High-speed SD-OCT imaging is demonstrated at camera-limited 100 frames per second on an ex-vivo squid eye.     

Wavefront sensorless adaptive optics optical coherence tomography for in vivo retinal imaging in mice

We present wavefront sensorless adaptive optics (WSAO) Fourier domain optical coherence tomography (FD-OCT) for in vivo small animal retinal imaging. WSAO is attractive especially for mouse retinal imaging because it simplifies optical design and eliminates the need for wavefront sensing, which is difficult in the small animal eye. GPU accelerated processing of the OCT data permitted real-time extraction of image quality metrics (intensity) for arbitrarily selected retinal layers to be optimized. Modal control of a commercially available segmented deformable mirror (IrisAO Inc.) provided rapid convergence using a sequential search algorithm. Image quality improvements with WSAO OCT are presented for both pigmented and albino mouse retinal data, acquired in vivo.OCIS codes: (170.4460) Ophthalmic optics and devices, (110.1080) Active or adaptive optics, (110.4500) Optical coherence tomography     

Volumetric (3D) compressive sensing spectral domain optical coherence tomography

In this work, we proposed a novel three-dimensional compressive sensing (CS) approach for spectral domain optical coherence tomography (SD OCT) volumetric image acquisition and reconstruction. Instead of taking a spectral volume whose size is the same as that of the volumetric image, our method uses a sub set of the original spectral volume that is under-sampled in all three dimensions, which reduces the amount of spectral measurements to less than 20% of that required by the Shan-non/Nyquist theory. The 3D image is recovered from the under-sampled spectral data dimension-by-dimension using the proposed three-step CS reconstruction strategy. Experimental results show that our method can significantly reduce the sampling rate required for a volumetric SD OCT image while preserving the image quality.OCIS codes: (170.4500) Optical coherence tomography, (100.3010) Image reconstruction techniques     

Imaging the eye fundus with real-time en-face spectral domain optical coherence tomography

Real-time display of processed en-face spectral domain optical coherence tomography (SD-OCT) images is important for diagnosis. However, due to many steps of data processing requirements, such as Fast Fourier transformation (FFT), data re-sampling, spectral shaping, apodization, zero padding, followed by software cut of the 3D volume acquired to produce an en-face slice, conventional high-speed SD-OCT cannot render an en-face OCT image in real time. Recently we demonstrated a Master/Slave (MS)-OCT method that is highly parallelizable, as it provides reflectivity values of points at depth within an A-scan in parallel. This allows direct production of en-face images. In addition, the MS-OCT method does not require data linearization, which further simplifies the processing. The computation in our previous paper was however time consuming. In this paper we present an optimized algorithm that can be used to provide en-face MS-OCT images much quicker. Using such an algorithm we demonstrate around 10 times faster production of sets of en-face OCT images than previously obtained as well as simultaneous real-time display of up to 4 en-face OCT images of 200 × 200 pixels² from the fovea and the optic nerve of a volunteer. We also demonstrate 3D and B-scan OCT images obtained from sets of MS-OCT C-scans, i.e. with no FFT and no intermediate step of generation of A-scans.OCIS codes: (120.3180) Interferometry, (110.4500) Optical coherence tomography, (170.0110) Imaging systems, (200.4960) Parallel processing     

In vivo imaging of human photoreceptor mosaic with wavefront sensorless adaptive optics optical coherence tomography

Wavefront sensorless adaptive optics optical coherence tomography (WSAO-OCT) is a novel imaging technique for in vivo high-resolution depth-resolved imaging that mitigates some of the challenges encountered with the use of sensor-based adaptive optics designs. This technique replaces the Hartmann Shack wavefront sensor used to measure aberrations with a depth-resolved image-driven optimization algorithm, with the metric based on the OCT volumes acquired in real-time. The custom-built ultrahigh-speed GPU processing platform and fast modal optimization algorithm presented in this paper was essential in enabling real-time, in vivo imaging of human retinas with wavefront sensorless AO correction. WSAO-OCT is especially advantageous for developing a clinical high-resolution retinal imaging system as it enables the use of a compact, low-cost and robust lens-based adaptive optics design. In this report, we describe our WSAO-OCT system for imaging the human photoreceptor mosaic in vivo. We validated our system performance by imaging the retina at several eccentricities, and demonstrated the improvement in photoreceptor visibility with WSAO compensation.OCIS codes: (110.4500) Optical coherence tomography, (010.1080) Active or adaptive optics, (220.1000) Aberration compensation, (170.0110) Imaging systems, (170.4470) Ophthalmology, (120.3890) Medical optics instrumentation     

Automated segmentation of retinal blood vessels in spectral domain optical coherence tomography scans

The correct segmentation of blood vessels in optical coherence tomography (OCT) images may be an important requirement for the analysis of intra-retinal layer thickness in human retinal diseases. We developed a shape model based procedure for the automatic segmentation of retinal blood vessels in spectral domain (SD)-OCT scans acquired with the Spectralis OCT system. The segmentation procedure is based on a statistical shape model that has been created through manual segmentation of vessels in a training phase. The actual segmentation procedure is performed after the approximate vessel position has been defined by a shadowgraph that assigns the lateral vessel positions. The active shape model method is subsequently used to segment blood vessel contours in axial direction. The automated segmentation results were validated against the manual segmentation of the same vessels by three expert readers. Manual and automated segmentations of 168 blood vessels from 34 B-scans were analyzed with respect to the deviations in the mean Euclidean distance and surface area. The mean Euclidean distance between the automatically and manually segmented contours (on average 4.0 pixels respectively 20 μm against all three experts) was within the range of the manually marked contours among the three readers (approximately 3.8 pixels respectively 18 μm for all experts). The area deviations between the automated and manual segmentation also lie within the range of the area deviations among the 3 clinical experts. Intra reader variability for the experts was between 0.9 and 0.94. We conclude that the automated segmentation approach is able to segment blood vessels with comparable accuracy as expert readers and will provide a useful tool in vessel analysis of whole C-scans, and in particular in multicenter trials.     

Improved visualization of outer retinal morphology with aberration cancelling reflective optical design for adaptive optics - optical coherence tomography

We present an aberration cancelling optical design for a reflective adaptive optics - optical coherence tomography (AO-OCT) retinal imaging system. The optical performance of this instrument is compared to our previous multimodal AO-OCT/AO-SLO retinal imaging system. The feasibility of new instrumentation for improved visualization of microscopic retinal structures is discussed. Examples of images acquired with this new AO-OCT instrument are presented.OCIS codes: (110.4500) Optical coherence tomography, (010.1080) Active or adaptive optics, (220.1000) Aberration compensation, (170.0110) Imaging systems, (170.4470) Ophthalmology, (120.3890) Medical optics instrumentation     

Imaging flow dynamics in murine coronary arteries with spectral domain optical Doppler tomography

Blood flow in murine epicardial and intra-myocardial coronary arteries was measured in vivo with spectral domain optical Doppler tomography (SD-ODT). Videos at frame rates up to 180 fps were collected and processed to extract phase shifts associated with moving erythrocytes in the coronary arteries. Radial averaging centered on the vessel lumen provided spatial smoothing of phase noise in a single cross-sectional frame for instantaneous peak velocity measurement without distortion of the flow profile. Temporal averaging synchronized to the cardiac cycle (i.e., gating) was also performed to reduce phase noise, although resulting in lower flow profiles. The vessel angle with respect to incident imaging beam was measured with three-dimensional raster scans collected from the same region as the high speed cross-sectional scans. The variability in peak phase measurement was 10-15% from cycle to cycle on a single animal but larger for measurements among animals. The inter-subject variability is attributed to factors related to real physiological and anatomical differences, instrumentation variables, and measurement error. The measured peak instantaneous flow velocity in a ~40-μm diameter vessel was 23.5 mm/s (28 kHz Doppler phase shift). In addition to measurement of the flow velocity, we observed several dynamic features of the vessel and surrounding myocardium in the intensity and phase sequences, including asymmetric vessel deformation and rapid flow reversal immediately following maximum flow, in confirmation of known coronary artery flow dynamics. SD-ODT is an optical imaging tool that can provide in vivo measures of structural and functional information on cardiac function in small animals.     

Interlaced spectrally encoded confocal scanning laser ophthalmoscopy and spectral domain optical coherence tomography

Scanning laser ophthalmoscopy (SLO) and spectral domain optical coherence tomography (SDOCT) have become essential clinical diagnostic tools in ophthalmology by allowing for video-rate noninvasive en face and depth-resolved visualization of retinal structure. Current generation multimodal imaging systems that combine both SLO and OCT as a means of image tracking remain complex in their hardware implementations. Here, we combine a spectrally encoded confocal scanning laser ophthalmoscope (SECSLO) with an ophthalmic SDOCT system. This novel implementation of an interlaced SECSLO-SDOCT system allows for video-rate SLO fundus images to be acquired alternately with high-resolution SDOCT B-scans as a means of image aiming, guidance, and registration as well as motion tracking. The system shares the illumination source, detection system, and scanning optics between both SLO and OCT as a method of providing a simple multimodal ophthalmic imaging system that can readily be implemented as a table-top or hand-held device.