Dispersion compensation for FD-OCT using spectrum reconstruction.

BACKGROUND: In OCT system, the chromatic dispersion of sample decreases the resolution and increases the depth misplacement. The developed numerical dispersion compensation techniques usually do not consider the higher order dispersion and time-consuming. OBJECTIVE: We proposed a numerical compensation technique for correcting depth error and resolution deterioration in Fourier domain optical coherence tomography (FD-OCT). METHODS: Firstly, the rough depth of each scatter in multilayer sample is estimated through magnification curve. Then the depth of a scatter is iterated to minimum the residual of this scatter in the time domain. At last, the spectrum of the scatter is reconstructed and dispersion can be compensated with the tracked depth. RESULTS: The results show that the depth error is corrected to less than resolution level and the resolution is corrected to nearly ideal. CONCLUSIONS: The technique proposed can provide precise sample tomography, thus enhancing the understanding of sample character.

A time delay correction technique for SS-OCT.

BACKGROUND: K-trigger signals from light source or external Mach-Zehnder interferometer are commonly used in swept source optical coherence tomography (SS-OCT) to achieve interference signal sampling and resolution enhancement. But extra signal transmission time is required due to the increased complexity of interference system using k-trigger signals, resulting in a misalignment (a.k.a., time delay) between the k-trigger and the interference signals. OBJECTIVE: The objective of this paper is to propose a numerical technique to correct the time delay between these two signals. METHODS: The time delay is iterated in this technique and each iterated correction result is evaluated through calculating the full width at half maximum (FWHM) of peaks in time-domain. The precise alignment between the k-trigger and interference signals coincides with the minimum value of FWHM. RESULTS: The experimental results show that the FWHM can be improved by up to 50% using this time delay correction technique. CONCLUSIONS: The proposed technique assists to provide precise sample tomography, thus enhancing the way of understanding sample characteristic.

Intelligent epidural needle placement using fiber-probe optical coherence tomography in a piglet model.

Incorrect needle placement during an epidural block causes medical complications such as dural puncture or spinal cord injury. We propose a system combining an optical coherence tomography imaging probe with an automatic identification algorithm to objectively identify the epidural needle-tip position and thus reduce complications during epidural needle insertion. Eight quantitative features were extracted from each two-dimensional optical coherence tomography image during insertion of the needle tip from the skin surface to the epidural space. 847 in vivo optical coherence tomography images were obtained from three anesthetized piglets. The area under the receiver operating characteristic curve was used to quantify the discriminative ability of each feature. We found a combination of six image features-mean value of intensity, mean value with depth, entropy, mean absolute deviation, root mean square, and standard deviation-showed the highest differentiating performance with the shortest processing time. Finally, differentiation of the needle tip inside or outside the epidural space was automatically evaluated using five classifiers: k-nearest neighbor, linear discriminant analysis, quadratic discriminant analysis, linear support vector machines, and quadratic support vector machine. We adopted an 8-fold cross-validation strategy with five classifications. Quadratic support vector machine classification showed the highest sensitivity (97.5%), specificity (95%), and accuracy (96.2%) among the five classifiers. This study provides an intelligent method for objective identification of the epidural space that can increase the success rate of epidural needle insertion.

High-speed, ultrahigh-resolution distal scanning OCT endoscopy at 800 nm for in vivo imaging of colon tumorigenesis on murine models.

We present the first, most compact, ultrahigh-resolution, high-speed, distal scanning optical coherence tomography (OCT) endoscope operating at 800 nm. Achieving high speed imaging while maintaining an ultrahigh axial resolution is one of the most significant challenges with endoscopic OCT at 800 nm. Maintaining an ultrahigh axial resolution requires preservation of the broad spectral bandwidth of the light source throughout the OCT system. To overcome this critical limitation we implemented a distal scanning endoscope with diffractive optics to minimize loss in spectral throughput. In this paper, we employed a customized miniature 900 µm diameter DC micromotor fitted with a micro reflector to scan the imaging beam. We integrated a customized diffractive microlens into the imaging optics to reduce chromatic focal shift over the broad spectral bandwidth of the Ti:Sapphire laser of an approximately 150 nm 3dB bandwidth, affording a measured axial resolution of 2.4 µm (in air). The imaging capability of this high-speed, ultrahigh-resolution distal scanning endoscope was validated by performing 3D volumetric imaging of mouse colon in vivo at 50 frames-per-second (limited only by the A-scan rate of linear CCD array in the spectral-domain OCT system and sampling requirements). The results demonstrated that fine microstructures of colon could be clearly visualized, including the boundary between the absorptive cell layer and colonic mucosa as well the crypt patterns. Furthermore, this endoscope was employed to visualize morphological changes in an enterotoxigenic Bacteriodes fragilis (ETBF) induced colon tumor model. We present the results of our feasibility studies and suggest the potential of this system for visualizing time dependent morphological changes associated with tumorigenesis on murine models in vivo.

Holographic line field en-face OCT with digital adaptive optics in the retina in vivo.

We demonstrate a high-resolution line field en-face time domain optical coherence tomography (OCT) system using an off-axis holography configuration. Line field en-face OCT produces high speed en-face images at rates of up to 100 Hz. The high frame rate favors good phase stability across the lateral field-of-view which is indispensable for digital adaptive optics (DAO). Human retinal structures are acquired in-vivo with a broadband light source at 840 nm, and line rates of 10 kHz to 100 kHz. Structures of different retinal layers, such as photoreceptors, capillaries, and nerve fibers are visualized with high resolution of 2.8 µm and 5.5 µm in lateral directions. Subaperture based DAO is successfully applied to increase the visibility of cone-photoreceptors and nerve fibers. Furthermore, en-face Doppler OCT maps are generated based on calculating the differential phase shifts between recorded lines.

Enhancement of morphological and vascular features in OCT images using a modified Bayesian residual transform.

A novel image processing algorithm based on a modified Bayesian residual transform (MBRT) was developed for the enhancement of morphological and vascular features in optical coherence tomography (OCT) and OCT angiography (OCTA) images. The MBRT algorithm decomposes the original OCT image into multiple residual images, where each image presents information at a unique scale. Scale selective residual adaptation is used subsequently to enhance morphological features of interest, such as blood vessels and tissue layers, and to suppress irrelevant image features such as noise and motion artefacts. The performance of the proposed MBRT algorithm was tested on a series of cross-sectional and enface OCT and OCTA images of retina and brain tissue that were acquired in-vivo. Results show that the MBRT reduces speckle noise and motion-related imaging artefacts locally, thus improving significantly the contrast and visibility of morphological features in the OCT and OCTA images.

Modified wavelength scanning interferometry for simultaneous tomography and topography of the cornea with Fourier domain optical coherence tomography.

Visual acuity is dependent on corneal shape and size. A minor variation in surface geometry can cause a deformation of corneal geometry, which affects its optical performance. In this work we demonstrate an algorithm for the simultaneous measurement of corneal tomography and topography with a traditional point-scanning Fourier domain optical coherence tomography (FD-OCT) system. A modified wavelength scanning interferometry (mWSI) algorithm enabled topographical evaluation of the surface with nanometer-scale resolution, which is superior to the micrometer-scale resolution of traditional OCT structural imaging. We validated the technique with an optically flat mirror, standard roughness gauges, and atomic force microscopy (AFM). The mirror results show nanometer-scale sensitivity (~3.5 nm), and the mWSI measurements were in good agreement (error ~5%) with the specifications of the roughness comparator and AFM, demonstrating the accuracy of the technique. Following validation, the measurements were made on pig corneas in situ at various artificially controlled intraocular pressures (IOP) and before and after cross-linking (CXL). The results show that the mean surface roughness increased by ~65% after removal of the epithelium in preparation for CXL but did not change as a function of IOP. The demonstrated method could be used for simultaneous measurement of tissue tomography with micrometer-precision and topography with nanometer-precision.

Real-time speckle reduction in optical coherence tomography using the dual window method.

Speckle is an intrinsic noise of interferometric signals which reduces contrast and degrades the quality of optical coherence tomography (OCT) images. Here, we present a frequency compounding speckle reduction technique using the dual window (DW) method. Using the DW method, speckle noise is reduced without the need to acquire multiple frames. A ~25% improvement in the contrast-to-noise ratio (CNR) was achieved using the DW speckle reduction method with only minimal loss (~17%) in axial resolution. We also demonstrate that real-time speckle reduction can be achieved at a B-scan rate of ~21 frames per second using a graphic processing unit (GPU). The DW speckle reduction technique can work on any existing OCT instrument without further system modification or extra components. This makes it applicable both in real-time imaging systems and during post-processing.

Combination of structural and vascular optical coherence tomography for differentiating oral lesions of mice in different carcinogenesis stages.

Differentiating between early malignancy and benign lesions in oral cavities is difficult using current optical tools. As has been shown in previous studies, microvascular changes in squamous epithelium can be regarded as a key marker for diagnosis. We propose the combination of structural and vascular optical coherence tomography (OCT) imaging for the investigation of disease related changes. Progressive thickness changes of epithelium and the destruction of underlying lamina propria was observed during cancer development in a 4- nitroquinoline-1-oxide (4NQO) mouse model. At the same time, microvascular changes in hyperplasia, dysplasia, carcinoma in situ and advanced cancer were observed. Findings from OCT imaging were compared with histology.

Wide-field quantitative micro-elastography of human breast tissue.

Currently, 20-30% of patients undergoing breast-conserving surgery require a second surgery due to insufficient surgical margins in the initial procedure. We have developed a wide-field quantitative micro-elastography system for the assessment of tumor margins. In this technique, we map tissue elasticity over a field-of-view of ~46 × 46 mm. We performed wide-field quantitative micro-elastography on thirteen specimens of freshly excised tissue acquired from patients undergoing a mastectomy. We present wide-field optical coherence tomography (OCT) images, qualitative (strain) micro-elastograms and quantitative (elasticity) micro-elastograms, acquired in 10 minutes. We demonstrate that wide-field quantitative micro-elastography can extend the range of tumors visible using OCT-based elastography by providing contrast not present in either OCT or qualitative micro-elastography and, in addition, can reduce imaging artifacts caused by a lack of contact between tissue and the imaging window. Also, we describe how the combined evaluation of OCT, qualitative micro-elastograms and quantitative micro-elastograms can improve the visualization of tumor.

Effect of patch size and network architecture on a convolutional neural network approach for automatic segmentation of OCT retinal layers.

Deep learning strategies, particularly convolutional neural networks (CNNs), are especially suited to finding patterns in images and using those patterns for image classification. The method is normally applied to an image patch and assigns a class weight to the patch; this method has recently been used to detect the probability of retinal boundary locations in OCT images, which is subsequently used to segment the OCT image using a graph-search approach. This paper examines the effects of a number of modifications to the CNN architecture with the aim of optimizing retinal layer segmentation, specifically the effect of patch size as well as the network architecture design on CNN performance and subsequent layer segmentation. The results demonstrate that increasing patch size can improve the performance of the classification and provides a more reliable segmentation in the analysis of retinal layer characteristics in OCT imaging. Similarly, this work shows that changing aspects of the CNN network design can also significantly improve the segmentation results. This work also demonstrates that the performance of the method can change depending on the number of classes (i.e. boundaries) used to train the CNN, with fewer classes showing an inferior performance due to the presence of similar image features between classes that can trigger false positives. Changes in the network (patch size and or architecture) can be applied to provide a superior segmentation performance, which is robust to the class effect. The findings from this work may inform future CNN development in OCT retinal image analysis.

Real-time corneal segmentation and 3D needle tracking in intrasurgical OCT.

Ophthalmic procedures demand precise surgical instrument control in depth, yet standard operating microscopes supply limited depth perception. Current commercial microscope-integrated optical coherence tomography partially meets this need with manually-positioned cross-sectional images that offer qualitative estimates of depth. In this work, we present methods for automatic quantitative depth measurement using real-time, two-surface corneal segmentation and needle tracking in OCT volumes. We then demonstrate these methods for guidance of ex vivo deep anterior lamellar keratoplasty (DALK) needle insertions. Surgeons using the output of these methods improved their ability to reach a target depth, and decreased their incidence of corneal perforations, both with statistical significance. We believe these methods could increase the success rate of DALK and thereby improve patient outcomes.

Circumferential-scanning endoscopic optical coherence tomography probe based on a circular array of six 2-axis MEMS mirrors.

We present a novel circumferential-scan endoscopic optical coherence tomography (OCT) probe by using a circular array of six electrothermal microelectromechanical (MEMS) mirrors and six C-lenses. The MEMS mirrors have a 0.5 mm × 0.5 mm mirror plate and a chip size of 1.5 mm × 1.3 mm. Each MEMS mirror can scan up to 45° at a voltage of less than 12 V. Six of those mirrors have been successfully packaged to a probe head; full circumferential scans have been demonstrated. Furthermore, each scan unit is composed of a MEMS mirror and a C-lens and the six scan units can be designed with different focal lengths to adapt for lesions with uneven surfaces. Configured with a swept source OCT system, this MEMS array-based circumferential scanning probe has been applied to image a swine's small intestine wrapped on a 20 mm-diameter glass tube. The OCT imaging result shows that this new MEMS endoscopic OCT has promising applications in large tubular organs.

Volumetric macro- and micro-scale assessment of crystalline lens opacities in cataract patients using long-depth-range swept source optical coherence tomography.

We demonstrate an optimized optical platform for the three-dimensional (3-D) visualization of crystalline lens opacities in vivo in the eyes of patients with different types and grades of cataracts. We developed a prototype long-depth-range swept source optical coherence tomography (SS-OCT) instrument operating at the speed of 50 kA-scans/second and at the central wavelength of 1 µm to perform high-resolution imaging of the whole anterior segment of the eye. Volumetric data sets of cataractous eyes were acquired and processed to obtain contrast-enhanced high-resolution images of lenticular structures and opacifications. The results showed lens micro- and macro-scale features related to possible cataract development such as cortical spokes, water clefts and enhanced scattering in the lens nucleus. The results demonstrate also the ability of this SS-OCT imaging to locate and characterize opacities quantitatively. The instrument might be a useful tool in the high-resolution preoperative evaluation of crystalline lens opacities in cataract patients.

Integrated RFA/PSOCT catheter for real-time guidance of cardiac radio-frequency ablation.

Radiofrequency ablation (RFA) is an important standard therapy for cardiac arrhythmias, but direct monitoring of tissue treatment is currently lacking. We demonstrate an RFA catheter integrated with polarization sensitive optical coherence tomography (PSOCT) for directly monitoring the RFA process in real time. The integrated RFA/OCT catheter was modified from a standard clinical RFA catheter and includes a miniature forward-viewing cone-scanning OCT probe. The PSOCT system was validated with a quarter-wave plate while the RFA function of the integrated catheter was validated by comparing lesion sizes with those made with an unmodified RFA catheter. Additionally, the integrated catheter guided catheter-tissue apposition and monitored RFA lesion formation in cardiac tissue in real time. The results show that catheter-tissue contact can be characterized by observing the features of the blood and tissue in the acquired OCT images and that RFA lesion formation can be confirmed by monitoring the change in phase retardance in the acquired PSOCT images. This system demonstrates the feasibility of an integrated RFA/OCT catheter to deliver RF energy and image the cardiac wall simultaneously and justifies further research into use of this technology to aid RFA therapy for cardiac arrhythmias.

Active contour method for ILM segmentation in ONH volume scans in retinal OCT.

The optic nerve head (ONH) is affected by many neurodegenerative and autoimmune inflammatory conditions. Optical coherence tomography can acquire high-resolution 3D ONH scans. However, the ONH's complex anatomy and pathology make image segmentation challenging. This paper proposes a robust approach to segment the inner limiting membrane (ILM) in ONH volume scans based on an active contour method of Chan-Vese type, which can work in challenging topological structures. A local intensity fitting energy is added in order to handle very inhomogeneous image intensities. A suitable boundary potential is introduced to avoid structures belonging to outer retinal layers being detected as part of the segmentation. The average intensities in the inner and outer region are then rescaled locally to account for different brightness values occurring among the ONH center. The appropriate values for the parameters used in the complex computational model are found using an optimization based on the differential evolution algorithm. The evaluation of results showed that the proposed framework significantly improved segmentation results compared to the commercial solution.

Full ocular biometry through dual-depth whole-eye optical coherence tomography.

We propose a new method of determining the optical axis (OA), pupillary axis (PA), and visual axis (VA) of the human eye by using dual-depth whole-eye optical coherence tomography (OCT). These axes, as well as the angles "α" between the OA and VA and "κ" between PA and VA, are important in many ophthalmologic applications, especially in refractive surgery. Whole-eye images are reconstructed based on simultaneously acquired images of the anterior segment and retina. The light from a light source is split into two orthogonal polarization components for imaging the anterior segment and retina, respectively. The OA and PA are identified based on their geometric definitions by using the anterior segment image only, while the VA is detected through accurate correlation between the two images. The feasibility of our approach was tested using a model eye and human subjects.

Assessment of temporary cerebral effects induced by focused ultrasound with optical coherence tomography angiography.

Focused ultrasound (FUS) in combination with microbubbles temporally and locally increases the permeability of the blood-brain barrier (BBB) for facilitating drug delivery. However, the temporary effects of FUS on the brain microstructure and microcirculation need to be addressed. We used label-free optical coherence tomography (OCT) and OCT angiography (OCTA) to investigate the morphological and microcirculation changes in mouse brains due to FUS exposure at different power levels. Additionally, the recovery progress of the induced effects was studied. The results show that FUS exposure causes cerebral vessel dilation and can be identified and quantitatively analyzed via OCT/OCTA. Micro-hemorrhages can be detected when an excessive FUS exposure power is applied, causing the degradation of OCTA signal owing to strong scattering by leaked red blood cells (RBCs) and weaker backscattered intensity from RBCs in vessels. The vessel dilation effect due to FUS exposure was found to abate in several hours. This study demonstrates that the FUS-induced cerebral transiently dilated effects can be in-vivo differentiated and monitored with OCTA, and shows the feasibility of using OCT/OCTA as a novel tool for long-time monitoring of cerebral vascular dynamics during FUS-BBB opening process.

Compact akinetic swept source optical coherence tomography angiography at 1060 nm supporting a wide field of view and adaptive optics imaging modes of the posterior eye.

Imaging of the human retina with high resolution is an essential step towards improved diagnosis and treatment control. In this paper, we introduce a compact, clinically user-friendly instrument based on swept source optical coherence tomography (SS-OCT). A key feature of the system is the realization of two different operation modes. The first operation mode is similar to conventional OCT imaging and provides large field of view (FoV) images (up to 45° × 30°) of the human retina and choroid with standard resolution. The second operation mode enables it to optically zoom into regions of interest with high transverse resolution using adaptive optics (AO). The FoV of this second operation mode (AO-OCT mode) is 3.0° × 2.8° and enables the visualization of individual retinal cells such as cone photoreceptors or choriocapillaris. The OCT engine is based on an akinetic swept source at 1060 nm and provides an A-scan rate of 200 kHz. Structural as well as angiographic information can be retrieved from the retina and choroid in both operational modes. The capabilities of the prototype are demonstrated in healthy and diseased eyes.

Investigation of artifacts in retinal and choroidal OCT angiography with a contrast agent.

Optical coherence tomography angiography (OCTA) has recently emerged for imaging vasculature in clinical ophthalmology. Yet, OCTA images contain artifacts that remain challenging to interpret. To help explain these artifacts, we perform contrast-enhanced OCTA with a custom-designed wide-field ophthalmoscope in rats in vivo. We choose an intravascular contrast agent (Intralipid) with particles that are more isotropically scattering and more symmetrically shaped than red blood cells (RBCs). Then, by examining how OCTA artifacts change after contrast agent injection, we attribute OCTA artifacts to RBC-specific properties. In this work, we investigate retinal and choroidal OCTA in rats with or without melanosomes, both before and after contrast agent injection, at a wavelength at which scattering dominates the image contrast (1300 nm). First, baseline images suggest that high backscattering of choroidal melanosomes accounts for the relatively dark appearance of choroidal vessel lumens in OCTA. Second, Intralipid injection tends to eliminate the hourglass pattern artifact in OCTA images of vessel lumens and highlights vertical capillaries that were previously faint in OCTA, showing that RBC orientation is important in determining OCTA signal. Third, Intralipid injection increases lumen signal without significantly affecting the tails, suggesting that projection artifacts, or tails, are due to RBC multiple scattering. Fourth, Intralipid injection increases the side-to-top signal ratio less in choroidal vessel lumens of pigmented rats, suggesting that melanosome multiple scattering makes the hourglass artifact less prominent. This study provides the first direct experimental in vivo evidence to explain light scattering-related artifacts in OCTA.