This PDF file contains the front matter associated with SPIE Proceedings Volume 8571, including the Title Page, Copyright Information, Table of Contents, and the Conference Committee listing.

We report design and demonstration of a dual wavelength photothermal (DWP) optical coherence tomography (OCT) system for imaging of a phantom microvessel and measurement of hemoglobin oxygen saturation (SO₂) level. The DWP-OCT system contains a swept-source (SS) two-beam phase-sensitive (PhS) OCT system (1060 nm) and two intensity modulated photothermal excitation lasers (770 nm and 800 nm). The PhS-OCT probe beam (1060 nm) and photothermal excitation beams are combined into one single-mode optical fiber. A galvanometer based two-dimensional achromatic scanning system is designed to provide 14 μm lateral resolution for the PhS-OCT probe beam (1060 nm) and 13 μm lateral resolution for photothermal excitation beams. DWP-OCT system’s sensitivity is 102 dB, axial resolution is 13 μm in tissue and uses a real-time digital dispersion compensation algorithm. Noise floor for optical pathlength measurements is 300 pm in the signal frequency range (380-400 Hz) of photothermal modulation frequencies. Blood SO₂ level is calculated from measured optical pathlength (op) signal in a 300 μm diameter microvessel phantom introduced by the two photothermal excitation beams. En-face and B-scan images of a phantom microvessel are recorded, and six blood samples’ SO₂ levels are measured using DWP-OCT and compared with values provided by a commercial blood oximeter. A mathematical model indicates thermal diffusion introduces a systematic artifact that over-estimates SO₂ values and is consistent with measured data.

We demonstrate a full-field swept-source OCT using an off-axis geometry of the reference illumination. By using holographic refocusing techniques, a uniform lateral resolution is achieved over the measurement depth of approximately 80 Rayleigh lengths. Compared to a standard on-axis setup, artifacts and autocorrelation signals are suppressed and the measurement depth is doubled by resolving the complex conjugate ambiguity. Holographic refocusing was done efficiently by Fourier-domain resampling as demonstrated before in inverse scattering and holoscopy. It allowed to reconstruct a complete volume with about 10μm resolution over the complete measurement depth of more than 10mm. Off-axis full-field swept-source OCT enables high measurement depths, spanning many Rayleigh lengths with reduced artifacts.

This study presents a new method of visualizing hybridized images of retinal spectral domain optical coherence tomography (SDOCT) data comprised of varied directional reflectivity. Due to the varying reflectivity of certain retinal structures relative to angle of incident light, SDOCT images obtained with differing entry positions result in nonequivalent images of corresponding cellular and extracellular structures, especially within layers containing photoreceptor components. Harnessing this property, cross-sectional pathologic and non-pathologic macular images were obtained from multiple pupil entry positions using commercially-available OCT systems, and custom segmentation, alignment, and hybridization algorithms were developed to chromatically visualize the composite variance of reflectivity effects. In these images, strong relative reflectivity from any given direction visualizes as relative intensity of its corresponding color channel. Evident in non-pathologic images was marked enhancement of Henle’s fiber layer (HFL) visualization and varying reflectivity patterns of the inner limiting membrane (ILM) and photoreceptor inner/outer segment junctions (IS/OS). Pathologic images displayed similar and additional patterns. Such visualization may allow a more intuitive understanding of structural and physiologic processes in retinal pathologies.

Optical coherence tomography (OCT) is a non-invasive optical imaging technology for micron-scale cross-sectional imaging of biological tissue and materials. We have been investigating ultrahigh resolution optical coherence tomography (UHR-OCT) using fiber based supercontinuum (SC) source. Although UHR-OCT has many advantages in medical equipments, low penetration depth is a serious limitation for wider applications. Recently, we have demonstrated high penetration depth UHR-OCT by use of fiber based Gaussian shaped SC source at 1.7 μm center wavelength. However, the penetration depth has been limited by the low power of SC source. In this paper, to realize deeper penetration imaging, we have developed the high power Gaussian shaped SC source at 1.7 μm wavelength region based on the custom-made Er-doped ultrashort pulse fiber laser with single-wall carbon nanotube and nonlinear phenomena in fibers. This SC source has 43.3 mW output power, 242 nm full-width at half maximum bandwidth, and 109 MHz repetition rate. The repetition rate and average power were almost twice as large as those of previous SC source. Using this light source, 105 dB sensitivity and ultrahigh resolution of 4.3 μm in tissue were achieved simultaneously. We have demonstrated the UHR-OCT imaging of pig thyroid gland and hamster’s cheek pouch with this developed SC source and compared the images with those measured by the previous SC source. We have observed the fine structures such as round or oval follicles, epithelium, connective tissue band, and muscular layer. From the comparison of the UHR-OCT images and signals, we confirmed the improvement of imaging contrast and penetration depth with the developed SC source.

The purpose of this work is to develop a method to generate external k-clock sampling signals, which provides enhanced depth ranges up to 13.8 mm with commercial reflective Fabry-Perot tunable laser type SS light sources. The strategy to enhance the depth range is to purify the k-sampling clock using electrical filters. We found two depth ranges and one optical delay length, where enhanced depth ranges can be attained. We observed PSFs and OCT images at three selected depth ranges of 6.7, 11.5 and 13.8 mm using newly developed external k-sampling-clock generator. OCT imaging of entire anterior segment of a human eye are demonstrated with depth ranges 11.5 and 13.8 mm.

We developed a micro-motor based miniature catheter with an outer diameter of 3mm for ultrahigh speed endoscopic optical coherence tomography (OCT) using vertical cavity surface-emitting laser (VCSEL) at a 1MHz axial scan rate. The micro-motor can rotate a micro-prism at 1,200-72,000rpm (corresponding to 20- 1,200fps) with less than 5V driving voltage to provide fast and stable scanning, which is not sensitive to the bending of the catheter. The side-viewing probe can be pulled back for a long distance to acquire three-dimensional (3D) dataset covering a large area on the specimen. VCSEL provides high a-line rate to support dense sampling under high frame rate operation. With the use of a C++ based high speed data acquisition (DAQ) system, in vivo three-dimensional OCT imaging in rabbit GI tract with 1.6mm depth range, 11μm axial resolution, 8μm lateral resolution, and frame rate of 400fps is demonstrated.

We present a miniature motorized endoscopic probe for Optical Frequency Domain Imaging with an outer diameter of 1.65 mm and a rotation speed of 3,000 – 12,500 rpm. This is the smallest motorized high speed OCT probe to our knowledge. The probe has a motorized distal end which provides a significant advantage over proximally driven probes since it does not require a drive shaft to transfer the rotational torque to the distal end of the probe and functions without a fiber rotary junction. The probe has a focal Full Width at Half Maximum of 9.6 μm and a working distance of 0.47 mm. We analyzed the non-uniform rotation distortion and found a location fluctuation of only 1.87° in repeated measurements of the same object. The probe was integrated in a high-speed Optical Frequency Domain Imaging setup at 1310 nm We demonstrated its performance with imaging ex vivo pig bronchial and in vivo goat lung.

We describe a novel spectrometer design for spectral-domain optical coherence tomography (OCT) that enables singleshot inter-pixel shifting (IPS) for extended ranging depth. Compared to other methods of IPS, oblique incidence spectroscopy exploits the high pixel density of 2D cameras to permit sub-pixel-sized sampling of the OCT interferogram during acquisition of a single camera frame. Limited ultimately by fall-off and the pixel size, we demonstrate recovery of signal from samples positioned as deep as four times the base ranging depth of an equivalent traditional spectrometer. We also show for the first time, to the best of our knowledge, the ability to generate arbitrary ranging depths with SDOCT, including non-integer multiples of the base ranging depth.

A new method for lateral resolution improvement of Optical Coherence Tomography (OCT) images is presented. The improvement is independent of the delivery optics and the depth of focus. It is based on the lateral oversampling of the image. In OCT, laterally oversampled signals are backscattered signals from shifted and overlapped resolution volumes. In that way, signals from successive volumes are correlated due to the region shared by adjacent resolution volumes. Resolution can be improved by utilizing the cross correlation of signals from such overlapped volumes. The resolution can be improved by various degrees depending on which pairs of signals are used. In this method signals from all overlapped volumes are combined optimally to improve the resolution using all the available cross correlations. Preliminary results of such an approach on laterally oversampled OCT images have shown that it is possible to achieve a 3.7-fold lateral resolution improvement.

We present a novel time-domain polarization sensitive optical coherence tomography configuration operating at 830 nm, equipped with multichannel acousto-optic deflectors (AOD)s. The system can be used to simultaneously acquire interference information from multiple polarization-sensitive channels and to enable measurement and imaging of backscattered intensity, birefringence, and fast optic axis orientation. The system is employed here to demonstrate polarization sensitive imaging of a thermally damaged muscle tissue.

In this report the application of graphics processing unit (GPU) programming for real-time 3D Fourier domain Optical Coherence Tomography (FdOCT) imaging with implementation of Doppler algorithms for visualization of the flows in capillary vessels is presented. Generally, the time of the data processing of the FdOCT data on the main processor of the computer (CPU) constitute a main limitation for real-time imaging. Employing additional algorithms, such as Doppler OCT analysis, makes this processing even more time consuming. Lately developed GPUs, which offers a very high computational power, give a solution to this problem. Taking advantages of them for massively parallel data processing, allow for real-time imaging in FdOCT. The presented software for structural and Doppler OCT allow for the whole processing with visualization of 2D data consisting of 2000 A-scans generated from 2048 pixels spectra with frame rate about 120 fps. The 3D imaging in the same mode of the volume data build of 220 × 100 A-scans is performed at a rate of about 8 frames per second. In this paper a software architecture, organization of the threads and optimization applied is shown. For illustration the screen shots recorded during real time imaging of the phantom (homogeneous water solution of Intralipid in glass capillary) and the human eye in-vivo is presented.

In this report, we describe how to highly optimize a CUDA based platform to perform real time optical coherence tomography data processing and 3D volumetric rendering using commercially-available cost-effective graphic processing units (GPUs). The maximum complete attainable axial scan processing rate (including memory transfer and rendering frame) was 2.2 megahertz for 16 bits pixel depth and 2048 pixels/A-scan, the maximum 3D volumetric rendering speed is 23 volumes/second (size:1024×256×200). To the best of our knowledge, this is the fastest processing rate reported to date with single-chip GPU and the first implementation of real time video rate volumetric OCT processing and rendering that is capable of matching the ultrahigh-speed OCT acquisition rates.

Traditional Doppler OCT is highly sensitive to motion artifacts due to the dependence on the Doppler angle. This limits its reproducibility in clinical practice. To overcome this limitation, we use a bidirectional technique with a novel rotating scanning scheme. The volume is probed simultaneously from two distinct illumination directions with variable controlled orientations, allowing reconstruction of the true flow velocity, independently of the vessel orientation. A Dove prism in the sample arm permits a rotation of the illumination directions that can be synchronized with the standard beam steering device. The principle is implemented with Swept Source OCT at 1060nm with 100,000 A-Scans/s. We apply the system to human retinal absolute blood velocity measurement by performing segment and circumpapillary time series scans around the optic nerve head. We also demonstrate microvasculature imaging by calculation of squared intensity differences between successive tomograms.

Scattering and fluorescence images provide complementary information about the health condition of the human eye, so getting them in a single measurement, using a single device may significantly improve a quality of diagnosis as it has been already demonstrated in Spectralis (Heidelberg Eng.) OCT instrument. There is still challenge to improve quality of fundus autofluorescence (FAF) images. The biggest obstacle in obtaining in vivo images of sufficient quality is very low fluorescence signal. For eye safety reasons, and because of patient comfort, using highpower fluorescence excitation is not an adequate solution to the low signal problem. In this contribution we show a new detection method in the retinal autofluorescence imaging, which may improve the sensitivity. We used a fast modulated (up to 500 MHz) diode laser of wavelength 473 nm and detected fluorescence in the spectral range 500-680 nm by photomultiplier and lock-in amplifier. Average power of the collimated blue beam on the cornea used for FAF measurements was set to 50 μW, 10 μW, and even 4.5 μW.

We succeeded in utilizing our low-coherent quantitative phase microscopy (LC-QPM) to achieve label-free and three-dimensional imaging of string-like structures bridging the free-space between live cells. In past studies, three dimensional morphology of the string-like structures between cells had been investigated by electron microscopies and fluorescence microscopies and these structures were called ”membrane nanotubes” or “tunneling nanotubes.” However, use of electron microscopy inevitably kills these cells and fluorescence microscopy is itself a potentially invasive method. To achieve noninvasive imaging of live cells, we applied our LC-QPM which is a reflection-type, phase resolved and full-field interference microscope employing a low-coherent light source. LC-QPM is able to visualize the three-dimensional morphology of live cells without labeling by means of low-coherence interferometry. The lateral (diffraction limit) and longitudinal (coherence-length) spatial resolution of LC-QPM were respectively 0.49 and 0.93 micrometers and the repeatability of the phase measurement was 0.02 radians (1.0 nm). We successfully obtained three-dimensional morphology of live cultured epithelial cells (cell type: HeLa, derived from cervix cancer) and were able to clearly observe the individual string-like structures interconnecting the cells. When we performed volumetric imaging, a 80 micrometer by 60 micrometer by 6.5 micrometer volume was scanned every 5.67 seconds and 70 frames of a three-dimensional movie were recorded for a duration of 397 seconds. Moreover, the optical phase images gave us detailed information about the three-dimensional morphology of the string-like structure at sub-wavelength resolution. We believe that our LC-QPM will be a useful tool for the study of three-dimensional morphology of live cells.

A motion-compensated hand-held common-path Fourier-domain optical coherence tomography imaging probe has been developed for image guided intervention during microsurgery. A hand-held prototype instrument was designed and fabricated by integrating an imaging fiber probe inside a stainless steel needle which is attached to the ceramic shaft of a piezoelectric motor housed in an aluminum handle. The fiber probe obtains A-scan images. The distance information was extracted from the A-scans to track the sample surface distance and a fixed distance was maintained by a feedback motor control which effectively compensated hand tremor and target movements in the axial direction. Graphical user interface, real-time data processing, and visualization based on a CPU-GPU hybrid programming architecture were developed and used in the implantation of this system. To validate the system, free-hand optical coherence tomography images using various samples were obtained. The system can be easily integrated into microsurgical tools and robotics for a wide range of clinical applications. Such tools could offer physicians the freedom to easily image sites of interest with reduced risk and higher image quality.

Holoscopy is a new imaging approach combining digital holography and full-field Fourier-domain optical coherence tomography. The interference pattern between light scattered by a sample and a defined reference wave is recorded and processed numerically. During reconstruction numerical refocusing is applied, overcoming the limitation of the focal depth and thus a uniform, diffraction limited lateral resolution over the whole measurement depth can be obtained. The advantage of numerical refocusing becomes especially significant for imaging at high numerical apertures (NAs). We use a high-resolution setup based on a Mach-Zehnder interferometer with an high-resolution microscope objective (NA = 0.75). For reliable reconstruction of a sample volume the Rayleigh length of the microscope objective and the axial resolution, given by the spectral range of the light source, need to be matched. For a 0.75 NA objective a tunable light source with a sweeping range of ! 300nm is required. Here we present as a first step a tunable Ti:sapphire laser with a tuning range of 187 nm. By characterizing the spectral properties of the Ti:sapphire laser and determining the axial point spread function we demonstrate the feasibility of this light source for high-resolution holoscopy.

Freehand optical coherence tomography (OCT) systems without mechanical scanners can offer greater freedom to access and image sites of interest. However, the scanning velocity during freehand scan is irregular; therefore pseudo B-scan images obtained by stacking sequentially acquired A-scans have a non-uniform spatial sampling rate in the lateral dimension. In this study, we developed a speckle decorrelation method to estimate lateral displacement between sequentially acquired A-scans and used the information extracted from speckle analysis to correct the time-varying lateral scanning speed. We applied this method to a handheld OCT probe and performed calibration experiments to validate our model. Furthermore we demonstrated distortion-free, freehand OCT imaging of various samples including human tissue, in vivo.

Angle-resolved optical scattering properties of ovarian tissue on different optical coherence tomography (OCT) imaging planes were quantitatively measured by fitting the compounded OCT A-lines into a single scattering model. Higher cross correlation value of angle-resolved scattering coefficients between different OCT imaging planes was found in normal ovaries than was present in malignant ovaries. The mean cross correlation coefficient (MCC) was introduced in this pilot study to characterize and differentiate normal and malignant ovaries. A specificity of 100% and a sensitivity of 100% were achieved by setting MCC threshold at 0.6 in the limited sample population. The collagen properties such as content, structure and directivity were found to be different within OCT imaging penetration depth between normal and malignant ovarian tissue. The homogeneous three-dimensional collagen fiber network observed in the normal ovary effectively explains the stronger cross correlation of angle-resolved scattering properties on different imaging planes while the heterogeneity observed in the malignant ovary suggests a weaker correlation.

Small animal models of human retinal diseases are a critical component of vision research. In this report, we present an ultrahigh-resolution ultrahigh-speed adaptive optics optical coherence tomography (AO-OCT) system for small animal retinal imaging (mouse, fish, etc.). We adapted our imaging system to different types of small animals in accordance with the optical properties of their eyes. Results of AO-OCT images of small animal retinas acquired with AO correction are presented. Cellular structures including nerve fiber bundles, capillary networks and detailed double-cone photoreceptors are visualized.

Purpose. It is suspected that the abnormalities of aqueous outflow pump composed of trabecular meshwork (TM) and Schlemm’s canal (SC) results in the increased outflow resistance and then elevated intraocular pressure (IOP) in initial glaucoma. In order to explore the casual mechanism and the early diagnosis of glaucoma, the dynamic characterizations of aqueous outflow pump were explored.
Methods. As a functional extension of optical coherence tomography (OCT), tissue Doppler OCT (tissue-DOCT) method capable of measuring the slow tissue movement was developed. The tissue-DOCT imaging was conducted on the corneo-scleral limbus of 4 monkey eyes. The eye was mounted in an anterior segment holder, together with a perfusion system to control the mean IOP and to induce the cyclic IOP transients with amplitude 3 mm Hg at frequency 1 pulse/second. IOP was monitored on-line by a pressure transducer. Tissue-DOCT data and pressure data were recorded simultaneously. The IOP-transient induced Doppler velocity, displacement and strain rate of TM and the normalized area of SC were quantified at 7 different mean IOPs (5, 8, 10, 20, 30, 40, 50 mm Hg).
Results. The outflow system, including TM, SC and CCs, was visualized in the micro-structural imaging. The IOP-transient induced pulsatile TM movement and SC deformation were detected and quantified by tissue-DOCT. The TM movement was depth-dependent and the largest movement was located in the area closest to SC endothelium (SCE). Both the pulsations of TM and SC were found to be synchronous with the IOP pulse wave. At 8 mm Hg IOP, the global TM movement was around 0.65μm during one IOP transient. As IOP elevated, a gradual attenuation of TM movement and SC deformation was observed.
Conclusions. The observed pulsation of TM and SC induced by the pulsatile IOP transients was in good agreement with the predicated role of TM and SC acting as a biomechanical pump (pumping aqueous from anterior chamber into SC and from SC into CCs) in the aqueous outflow system. As the IOP elevated, the attenuated pulsation amplitude of the aqueous outflow pump indicated the failure of the mechanical pump and the increase of aqueous outflow resistance. The promising results revealed the potential of using the proposed tissue-DOCT for diagnosis and associated therapeutic guidance of the initial and progressive glaucoma process by monitoring the pulsation of the outflow pump.

Here we demonstrate our use of phase stabilized swept-source optical coherence elastography (PhS-SSOCE) to assess elastic wave propagation in gelatin phantoms. From these measurements, Young’s moduli of the samples were determined. Low-amplitude (<10μm) mechanical waves were introduced using a focused air pulse on gelatin of different concentrations. Elastic wave amplitude and velocity were measured at multiple points on the phantom surface using a phase-resolved method. The results demonstrate that this method is capable of resolving very small changes in wave amplitude (~ 10 nm) as well as differences in wave velocity due to material stiffness. We further demonstrate use of this method for measurements with a contact lens, a silicone eye model and with the eye of an 18-month-old mouse in vivo. This non-destructive, non-invasive measurement system produces minimal tissue excitation and has high measurement sensitivity. These traits make this make this method useful for in vivo study of the biomechanical properties of ocular and other tissues.

We show results of a project which focuses on detection of activity in neural tissue with Optical Coherence Tomography (OCT) methods. Experiments were performed in neural cords dissected from the American cockroach (Periplaneta americana L.). Functional OCT imaging was performed with ultrahigh resolution spectral / Fourier domain OCT system (axial resolution 2.5 μm). Electrical stimulation (voltage pulses) was applied to the sensory cercal nerve of the neural cord. Optical detection of functional activation of the sample was performed in the connective between the terminal abdominal ganglion and the fifth abdominal ganglion. Functional OCT data were collected over time with the OCT beam illuminating selected single point in the connectives (i.e. OCT M-scans were acquired). Phase changes of the OCT signal were analyzed to visualize occurrence of activation in the neural cord. Electrophysiology recordings (microelectrode method) were also performed as a reference method to demonstrate electrical response of the sample to stimulation.

Peripheral arterial disease (PAD) leads to an increased risk of myocardial infarction and stroke, increased mortality, and reduced quality of life. The mouse hind limb ischemia (HLI) model is the most commonly used system for studying the mechanisms of collateral vessel formation and for testing new PAD therapies, but there is a lack of techniques for acquiring physiologically-relevant, quantitative data intravitally in this model. In this work, non-invasive, quantitative optical imaging techniques were applied to the mouse HLI model over a time course. Optical coherence tomography (OCT) imaged changes in blood flow (Doppler OCT) and microvessel morphology (speckle variance OCT) through the skin of haired mice with high resolution. Hyperspectral imaging was also used to quantify blood oxygenation. In ischemic limbs, blood oxygenation in the footpad was substantially reduced after induction of ischemia followed by complete recovery by three weeks, consistent with standard measures. Three dimensional images of the vasculature distal to vessel occlusion acquired with speckle variance OCT revealed changes in OCT flow signal and vessel morphology. Taken together, OCT and hyperspectral imaging enable intravital acquisition of both functional and morphological data which fill critical gaps in understanding structure-function relationships that contribute to recovery in the mouse HLI model. Therefore, these optical imaging methods hold promise as tools for studying the mechanisms of vascular recovery and evaluating novel therapeutic treatments in preclinical studies.

We describe a novel dual-functional optical coherence tomography (OCT) system with both a fiber probe using a sapphire ball lens for cross-sectional imaging and sensing, and a 3-D bulk scanner for 3-D OCT imaging. A theoretical sensitivity model for Common Path (CP)-OCT was proposed to assess its optimal performance based on an unbalanced photodetector configuration. A probe design with working distances (WD) 415μm and lateral resolution 11 μm was implemented with sensitivity up to 88dB. To achieve high-speed data processing and real-time three-dimensional visualization, we use graphics processing unit (GPU) based real-time signal processing and visualization to boost the computing performance of swept source optical coherence tomography. Both the basal turn and facial nerve bundles inside the cadaveric human cochlea temporal bone can be clearly identified and 3D images can be rendered with the OCT system, which was integrated with a flexible robotic arm for robotically assisted microsurgery.

Optical coherence elastography (OCE) provides images of tissue elasticity and has potential for several clinical applications, including guidance of tumor resection. However, advancement toward clinical implementation of OCE is currently limited by the technique’s small imaging depth in tissue (1-2 mm), as well as a lack of validation of the elastic contrast generated in OCE. We have overcome the depth limitation of current OCE techniques by developing a method for performing OCE via a needle probe. Our technique, needle OCE, uses an OCT needle probe to perform axial measurements of tissue deformation during needle insertion, and has demonstrated potential for subsurface detection of the boundaries of diseased tissue. In this paper, we demonstrate how elastic contrast is generated in needle OCE by performing measurements in tissue phantoms and porcine airway wall. In addition, we have developed a finite element model of tissue deformation in compression OCE as a first step toward better understanding of the generation and interpretation of contrast in OCE images. We show initial results demonstrating excellent agreement between measured and simulated deformation in a tissue phantom.

We characterized ovarian tissue by using polarization-sensitive optical coherence tomography (PS-OCT). Phase retardation changing rate along with optical scattering coefficient and phase retardation were extracted from 33 ex vivo human ovaries from 18 patients. By using phase retardation changing rate as a classifier, we could achieve 71% sensitivity and 100% specificity. Combining those three parameters together, we could achieve 100% sensitivity and 100% specificity. These initial results showed that the quantitative analysis of PS-OCT could be a useful tool to characterize normal and malignant ovarian tissue.

We combine a focused air-puff system with phase-sensitive optical coherence tomography (PhS-OCT) to measure the elasticity of soft tissues. Surface waves (SWs) on soft tissues are induced by a low-pressure, short-duration air stream from an air-puff system and measured using a high-sensitivity PhS-OCT imaging system. Young’s modulus of soft tissues can be quantified based on the group velocity of SWs. To precisely control the excitation pressure, the air-puff system was characterized with a high-resolution analog pressure transducer. We studied the feasibility of this method for the non-contact detection of soft-tissue tumors. Ex vivo human fat and myxoma were used for these pilot experiments. Results demonstrate that this optical non-contact technique can be used to differentiate soft-tissue tumors from normal tissues based on measurements of their elasticity.

Photothermal optical coherence tomography (PT-OCT) has the potential to increase the molecular specificity of OCT for in vivo pre-clinical studies of cancer, in order to better understand drug uptake and treatment response. However, the use of PT-OCT to image contrast agents in vivo has yet to be demonstrated. Here, we characterize PT-OCT imaging of gold nanorod (GNR) contrast agents, and we further apply these techniques for in vivo imaging. The PT-OCT signal was characterized and compared to a numerical model of the bio-heat equation with respect to varying photothermal chop frequency, photothermal laser power, OCT image reflectivity, and concentration of GNRs. PT-OCT images were taken of GNR+ and GNR- solid agarose phantoms in capillary tubes, and 400 pM GNR matrigel injections into a mouse ear. Experimental PT-OCT data varied as predicted with closed form models of the bio-heat equation. Increasing the concentration of GNRs caused a linear increase in the PT-OCT signal, with GNR sensitivity as low as 7.5 pM compared to a scattering control (p<0.01). PT-OCT images in capillary tubes and the live mouse ear demonstrated an appreciable increase in signal in the presence of GNRs compared to controls. The demonstrated in vivo PT-OCT capabilities using GNR contrast agents is sufficient to image molecular expression, based on published molecular imaging studies employing GNR contrast agents in vivo. Therefore, this work demonstrates an important transition of PT-OCT to in vivo imaging, and marks the next step towards its use for in vivo molecular imaging.

An electronic method of k-space linearization for an analogue camera for use in optical coherence tomography is demonstrated. The method applies a chirp to the data transfer clock signal of the camera in order to temporally compensate for diffraction that is non-linear in wavenumber. The optimum parameters are obtained experimentally and theoretically and are shown to be in good accordance. Close to maximum measurable axial range, by applying this method, we report a narrowing of the FWHM of the point spread function by a factor of 5.6 and improve its magnitude by 9.8 dB.

In this study, we demonstrate the use of inter-Ascan speckle decorrelation analysis of optical coherence tomography (OCT) to assess fluid flow. This method allows quantitative measurement of fluid flow in a plane normal to the scanning beam. To validate this method, OCT images were obtained from a micro fluid channel with bovine milk flowing at different speeds. We also imaged a blood vessel from in vivo animal models and performed speckle analysis to asses blood flow.

In optical coherence tomography (OCT), unbiased and low variance Doppler frequency estimators are desirable for blood velocity estimation. Hardware improvements in OCT mean that ever higher acquisition rates are possible. However, it is known that the Kasai autocorrelation estimator, unexpectedly, performs worse as acquisition rates increase. Here we suggest that maximum likelihood estimators (MLEs) that utilize prior knowledge of noise statistics can perform better. We show that the additive white Gaussian noise maximum likelihood estimator (AWGN MLE) has a superior performance to the Kasai autocorrelation estimate under additive shot noise conditions. It can achieve the Cramer-Rao Lower Bound (CRLB) for moderate data lengths and signal-to-noise ratios (SNRs). However, being a parametric estimator, it has the disadvantages of sensitivity to outliers, signal contamination and deviations from noise model assumptions. We show that under multiplicative decorrelation noise conditions, the AWGN MLE performance deteriorates, while the Kasai estimator still gives reasonable estimates. Hence, we further develop a multiplicative noise MLE for use under multiplicative noise dominant conditions. According to simulations, this estimator is superior to both the AWGN MLE and the Kasai estimator under these conditions, but requires knowledge of the decorrelation statistics. It also requires more computation. For actual data, the decorrelation MLE appears to perform adequately without parameter optimization. Hence we conclude that it is preferable to use a maximum likelihood approach in OCT Doppler frequency estimation when noise statistics are known or can be accurately estimated.

Correlation mapping optical coherence tomography (cmOCT) is an alternative robust method for obtaining volumetric images of dynamic perfusion within the microcirculatory tissue beds in vivo. The cmOCT method uses a 2D correlation mapping algorithm on the intensity OCT images to extract depth resolved flow map from static tissue background. The earlier reported cmOCT was based on a commercial swept-source OCT system, which uses a scanning protocol with dense sampling between adjacent B-frame, such that the inter frame separation was within the resolution limit of the OCT system to ensure strong correlation between adjacent frames. However, this scanning protocol requires a relatively long scan time and high density B-frame images to reconstruct the volumetric perfusion map, which degraded the system performance for fast wide-field in vivo imaging applications. In order to overcome this limitation we implemented a custom built high-speed spectral domain OCT and introduced a new scanning protocol for high-speed and high sensitive imaging of cmOCT. The new scan protocol measures repeated B-scans at the same location to generate a high sensitivity correlation map between successive B-frames. This scanning protocol can provide fast wide scanning with relatively short scanning time.

We report on a new calibration technique that permits the accurate extraction of sample Jones matrix and hence fast-axis orientation by using fiber-based polarization-sensitive optical coherence tomography (PS-OCT) that is completely based on non polarization maintaining fiber such as SMF-28. In this technique, two quarter waveplates are used to completely specify the parameters of the system fibers in the sample arm so that the Jones matrix of the sample can be determined directly. The device was validated on measurements of a quarter waveplate and an equine tendon sample by a single-mode fiber-based swept-source PS-OCT system.

This paper highlights the extended Jones matrix calculus based multi-angle study carried out to understand the depth dependent structural orientation of the collagen fibers in articular cartilage using polarization-sensitive optical coherence tomography (PS-OCT). A 3D lamellar model for the collagen fiber orientation, with a quadratic profile for the arching of the collagen fibers in transitional zone which points towards an ordered arrangement of fibers in that zone is the basis of the organization architecture of collagen fibers in articular cartilage. Experimental data for both ex-vivo bovine fetlock and human patellar cartilage samples are compared with theoretical predictions, with a good quantitative agreement for bovine and a reasonable qualitative agreement for human articular cartilage samples being obtained

Protein crystals are required for X-ray crystallography to determine three-dimensional structures of proteins at atomic resolution. The conventional microscopy is currently used for observation and screening of protein crystals. However, the three-dimensional imaging, which is important for automated treatment of protein crystals, is generally difficult by light microscopy. In addition, the protein crystals in the media are frequently difficult to identify by conventional light microscopy owing to the appearance of salt crystals or amorphous materials. In this work, we successfully demonstrated micro-scale, non-invasive, three-dimensional cross-sectional imaging of protein crystals using ultrahigh resolution optical coherence tomography (UHR-OCT). A low noise, Gaussian like, high power supercontinuum at wavelength of 800 nm was used as the light source. The axial resolution of 2 um in sample and the sensitivity of 95 dB were achieved. Since the protein crystal has homogeneous nano-structure, the optical scattering is negligibly small. Therefore, we used gel-inclusion technique to enhance the intensity of scattered signals, and clear, sharp 3D cross-sectional images of protein crystals were successfully observed. As the gel concentration was increased, the OCT signal intensity was increased. Using this method, the protein crystals surrounded by substantial amount of precipitates could be visualized, which is difficult by conventional light microscopy. The discrimination of protein and salt crystals was also demonstrated by the OCT signal intensity. The wavelength dependence of OCT imaging for protein crystal was examined at wavelength of 800-1700 nm regions. It was confirmed that the finest images were observed using 800 nm wavelength system.

We demonstrate the dynamic OCT analysis of mental sweating of a few tens of eccrine sweat glands on a human fingertip. We propose a novel method for evaluation of the amount of excess sweat in response to mental stress, where the en-face OCT images of the spiral lumen of the eccrine sweat gland are constructed by data acquisition of the 128 B-mode OCT images. The dynamic analysis of mental sweating is performed by the time-sequential piled-up en-face OCT images with the frame spacing of 3.3 sec. Strong non-uniformity is observed in mental sweating where the amount of excess sweat in response to sound stress and physical stress is different for each sweat gland.

The temperature sensitivity of the spectral characteristics of ZnCdS nanoparticles both stabilized and coated with polyacrylic acid is compared. It is shown that the luminescence of the nanoparticles has two temperature-dependent parameters, namely, the intensity and the peak position. Variations in these parameters are due to the distortion of the energy states of luminescent surface defects. Aggregation of the nanoparticles does not distort obtained dependencies. Temperature sensitivity is higher for the nanoparticles coated with a layer of polyacrylic acid.

We have measured changes in optical coherence signals during the application of an external electric field to tissue samples. We employed the swept-source OCT engine with a broadband light source of 140-nm spectral bandwidth centered at 1300 nm. Switching the polarity of the electric field induced significant reversible changes in the phase of the OCT signal. Since the phase signal was corrupted by phase noise, it required a formidable signal processing to obtain the images of electrically induced phase changes.

We have demonstrated a wavelength-swept fiber laser based on dispersion tuning method. In this method, the light in a dispersive laser cavity is intensity modulated and actively mode-locked, and the lasing wavelength can be changed by controlling the modulation frequency. As the dispersion-tuned laser does not include any tunable filters, the sweep rate and range are not limited by mechanical moving parts. We have reported the wavelength-swept laser which has the tuning range of over 100nm with the sweep rate of 200kHz, and we have applied the laser to the swept-source optical coherence tomography (SS-OCT) system. Although we have successfully obtained the OCT image of the human finger at 1kHz sweep rate, we could not obtain OCT images at higher sweep rate because of the performance degradation of the laser. As this laser cavity included 100m long dispersion compensating fiber (DCF), the long laser cavity increased the photon lifetime and resulted in the output power decrease and the linewidth broadening at higher sweep rate. In order to solve these problems, we inserted a reflective semiconductor optical amplifier (RSOA) and a chirped fiber Bragg grating (CFBG) into the laser cavity. Use of these devices made it possible to shorten the cavity length drastically and the laser performance at high sweep rate is significantly improved. We could achieve that the sweep range of 60nm and the output power of 8.4mW at 100kHz sweep. We applied the laser to swept-source OCT system and we successfully obtained images of an adhesive tape at up to 250kHz sweep.

We demonstrate a novel ultra-broad tunable bandwidth and narrow instantaneous line-width swept laser source using combined tunable filters working at 1290 nm center wavelength for application in optical coherence tomography. The combined filters consist of a fiber Fabry-Perot tunable filter (FFP-TF) and a polygon mirror with scanning grating based filter. The FFP-TF has the narrow free spectral range (FSR) but ultra-high spectral resolution (narrow instantaneous bandwidth) driven at high frequency far from resonant frequency. The polygon filter in the Littrow configuration is composed of fiber collimator, polygon mirror driven by function generator, and diffractive grating with low groove. Polygon filter coarsely tunes with wide turning range and then FFP-TF finely tunes with narrow band-pass filtering. In contrast to traditional method using single tunable filter, the trade-off between bandwidth and instantaneous line-width is alleviated. The combined filters can realize ultra wide scan range and fairly narrow instantaneous bandwidth simultaneously. Two semiconductor optical amplifiers (SOA) in the parallel manner are used as the gain medium. The wide bandwidth could be obtained by these parallel SOAs to be suitable for sufficient wide range of the polygon filter’s FSR because each SOA generates its own spectrum independently. The proposed swept laser source provides an edge-to-edge scanning range of 180 nm covering 1220 to 1400 nm with instantaneous line-width of about 0.03 nm at sweeping rate of 23.3 kHz. The swept laser source with combined filters offers broadband tunable range with narrow instantaneous line-width, which especially benefits for high resolution and deep imaging depth optical frequency domain imaging.

We show a broad range of swept source performances based on a highly-flexible external cavity laser architecture. Specifically, we demonstrate a 40-kHz 1300-nm swept source with 10 mm coherence length realized in a compact butterfly package. Fast wavelength sweeping is achieved through a 1D 20-kHz MEMS mirror in combination with an advanced diffraction grating. The MEMS mirror is a resonant electrostatic mirror that performs harmonic oscillation only within a narrow frequency range, resulting in low-jitter and long-term phase-stable sinusoidal bidirectional sweep operation with an A-scan rate of 40 kHz. The source achieves a coherence length of 10 mm for both the up- and downsweep and an OCT sensitivity of 105 dB.

We developed an FPGA-based engine for Fourier-domain OCT that performs real-time signal processing based on Non- Uniform Fast Fourier Transform (NUFFT). The basic NUFFT algorithm is discussed and compared with cubic-spline interpolation regarding efficient re-sampling in k-space with different phase nonlinearities of sinusoidal swept sources. The NUFFT algorithm was adapted for an implementation in an FPGA and its accuracy is analyzed and assessed using simulated numerical data. When implemented, the NUFFT algorithm allows a processing performance at a sampling rate of 100 MS/s. The real-time processing capability was tested with sinusoidal bi-directional swept sources with A-scan rates of 50 kHz.

We have developed a Swept-Source Optical Coherence Tomography (Ss-OCT) system with high-speed, real-time signal processing on a commercially available Data-Acquisition (DAQ) board with a Field-Programmable Gate Array (FPGA). The Ss-OCT system simultaneously acquires OCT and k-clock reference signals at 500MS/s. From the k-clock signal of each A-scan we extract a remap vector for the k-space linearization of the OCT signal. The linear but oversampled interpolation is followed by a 2048-point FFT, additional auxiliary computations, and a data transfer to a host computer for real-time, live-streaming of B-scan or volumetric C-scan OCT visualization. We achieve a 100 kHz A-scan rate by parallelization of our hardware algorithms, which run on standard and affordable, commercially available DAQ boards. Our main development tool for signal analysis as well as for hardware synthesis is MATLAB® with add-on toolboxes and 3rd-party tools.

The transition of optical coherence tomography (OCT) technology from the lab environment towards the more challenging clinical and point-of-care settings is continuing at a rapid pace. On one hand this translation opens new opportunities and avenues for growth, while on the other hand it also presents a new set of challenges and constraints under which OCT systems have to operate. OCT systems in the clinical environment are not only required to be user friendly and easy to operate, but should also be portable, have a smaller form factor coupled with low cost and reduced power consumption. Digital signal processors (DSP) are in a unique position to satisfy the computational requirements for OCT at a much lower cost and power consumption compared to the existing platforms such as CPU and graphics processing units (GPUs). In this work, we describe the implementation of optical coherence tomography (OCT) and interferometric synthetic aperture microscopy (ISAM) processing on a floating point multi-core DSP (C6678, Texas Instruments). ISAM is a computationally intensive data processing technique that is based on the re-sampling of the Fourier space of the data to yield spatially invariant transverse resolution in OCT. Preliminary results indicate that 2DISAM processing at 70,000 A-lines/sec and OCT at 180,000 A-lines/sec can be achieved with the current implementation using available DSP hardware.

The purpose of this study was to show how to favorably mix two e_ects to improve the sensitivity with depth in Fourier domain optical coherence tomography (OCT): Talbot bands (TB) and Gabor-based fusion (GF) technique. TB operation is achieved by directing the two beams, from the object arm and from the reference arm in the OCT interferometer, along parallel separate paths towards the spectrometer. By changing the lateral gap between the two beams in their path towards the spectrometer, the position for the maximum sensitivity versus the optical path difference in the interferometer is adjusted. For five values of the focus position, the gap between the two beams is readjusted to reach maximum sensitivity. Then, similar to the procedure employed in the GF technique, a composite image is formed by edging together the parts of the five images that exhibited maximum brightness. The combined procedure, TB/GF is examined for four different values of the beam diameters of the two beams. Also we demonstrate volumetric FD-OCT images with mirror term attenuation and sensitivity profile shifted towards higher OPD values by applying a Talbot bands configuration.

This paper proposes a novel rotary endoscopic probe for spectral-domain optical coherence tomography (SD-OCT). The probe with a large N.A. objective lens is driven by an ultra-small hollow rectangular ultrasonic motor for circular scanning. Compared to the conventional driven techniques, the hollow ultrasonic motor enables the fiber to pass through its inside. Therefore the fiber, the objective lens and the motor are all at the same side. This enables 360 degree unobstructed imaging without any shadow resulted from power wire as in the conventional motor-driven endoscopic OCT. Moreover, it shortens the length of the rigid tip and enhances the flexibility of the probe. Meanwhile, the ultrasonic motor is robust, simple, quiet and of high torque, very suitable for OCT endoscopic probe. The side length of the motor is 0.7 mm with 5mm in length. The outer diameter of the probe is 1.5mm. A significant improvement in the lateral resolution is demonstrated due to the novel design of the objective lens. A right-angle lens is utilized instead of the traditional right-angle prism as the last optics close to the sample, leading to a reduction of the working distance and an enlargement of the N.A. of the objective lens. It is demonstrated that the endoscopic SD-OCT system achieves an axial resolution of ~7μm, a lateral resolution of ~6μm and a SNR of ~96dB.

We present a high-speed complex conjugate resolved 1 μm swept source optical coherence tomography [SS-OCT] system using coherence revival of the light source for clinical imaging of the anterior segment of the eye. High-speed of 100,000 A-scans/sec and 1 μm imaging window of OCT permits dense 3D imaging of the anterior segment, minimizing the influence of motion artifacts and deep penetration of images for topographic analysis. The swept laser performance with internal clocking was adapted to achieve extended imaging depth requirements. The feasibility of our instrument for visualization of the anterior segment of patients with the Boston Keratoprosthesis (KPro) was discussed. The relations between of the KPro and the surrounding tissue were also demonstrated.

Refractive surgeons and cataract surgeons need accurate measurements of corneal curvature/power. Increased expectations of patients, the increasing number of patients having undergone prior surgeries and patients with corneal pathologies dictate the need for reliable curvature measurements to enhance the predictability and the quality of surgical outcomes. Eye movements can negatively influence these measurements. We present a model of eye movements based on peak saccade velocities and formulate criteria for obtaining OCT topography within ¼ of a diopter. Using these criteria we illustrate how next generation MHz systems will allow full corneal OCT topography in both healthy and pathological corneas

Most of the optical coherence tomographic (OCT) systems for high resolution imaging of biological specimens are based on refractive type microscope objectives, which are optimized for specific wave length of the optical source. In this study, we present the feasibility of using commercially available reflective type objective for high sensitive and high resolution structural and functional imaging of cochlear microstructures of an excised guinea pig through intact temporal bone. Unlike conventional refractive type microscopic objective, reflective objective are free from chromatic aberrations due to their all-reflecting nature and can support a broadband of spectrum with very high light collection efficiency.

Optical coherence tomography (OCT) is a promising candidate for monitoring the bottom of the drilled channel during cochleostomy to prevent injury to the critical structure under the bone tissue. While the thickness of the overlaying bone tissue is changed during the drilling process, the wave front of the backscattered light is also altered, resulting in changing speckle patterns of the observed structures in the sequential historical scans. By averaging the different patterns in these scans, named history compounding, the speckles can be reduced and the detection of critical structure becomes much easier. Before averaging, the refractive index of bone tissue 𝑛𝑏 has to be compensated so that the speckles of the same structure in different historical scans can be aligned together. An accurate method for measuring the refractive index n_b using OCT is presented. Experiments were conducted to evaluate history compounding and the new technique is proved to be an effective, flexible and intuitive speckle reduction technique for OCT guided cochleostomy as well as hard tissue ablation of other kind.

We describe the design and performance of a long coherence length, swept-source anatomical OCT (aOCT) system for pediatric airway imaging. A fiber-optic catheter is designed to be accommodated by a small-bore bronchoscope, and is scanned distally in a helical scan pattern to provide aOCT during bronchoscopy. We discuss particular challenges associated with the need for large imaging range, low SNR roll-off, and small catheter diameter. We present 3-D visualizations of airway phantoms and discuss optimization of the airway surface geometry obtained by aOCT. Accurate reconstruction of airway geometry will enable predictive modeling of patients suffering from airway obstruction.

The most established technique for the identification at biometric access control systems is the human fingerprint. While every human fingerprint is unique, fingerprints can be faked very easily by using thin layer fakes. Because commercial fingerprint scanners use only a two-dimensional image acquisition of the finger surface, they can only hardly differentiate between real fingerprints and fingerprint fakes applied on thin layer materials. A Swept Source OCT system with an A-line rate of 20 kHz and a lateral and axial resolution of approximately 13 μm, a centre wavelength of 1320 nm and a band width of 120 nm (FWHM) was used to acquire fingerprints and finger tips with overlying fakes. Three-dimensional volume stacks with dimensions of 4.5 mm x 4 mm x 2 mm were acquired. The layering arrangement of the imaged finger tips and faked finger tips was analyzed and subsequently classified into real and faked fingerprints. Additionally, sweat gland ducts were detected and consulted for the classification. The manual classification between real fingerprints and faked fingerprints results in almost 100 % correctness. The outer as well as the internal fingerprint can be recognized in all real human fingers, whereby this was not possible in the image stacks of the faked fingerprints. Furthermore, in all image stacks of real human fingers the sweat gland ducts were detected. The number of sweat gland ducts differs between the test persons. The typical helix shape of the ducts was observed. In contrast, in images of faked fingerprints we observe abnormal layer arrangements and no sweat gland ducts connecting the papillae of the outer fingerprint and the internal fingerprint. We demonstrated that OCT is a very useful tool to enhance the performance of biometric control systems concerning attacks by thin layer fingerprint fakes.