This PDF file contains the front matter associated with SPIE Proceedings Volume 8213, including the Title Page, Copyright information, Table of Contents, and the Conference Committee listing.

A differential phase contrast (DPC) method is validated for in vivo human retinal and choroidal vasculature visualization using high-speed swept-source optical coherence tomography (SS-OCT) at 1060 nm. The vasculature was identified as regions of motion by creating differential phase variance (DPV) tomograms: multiple B-scans were collected of individual slices through the retina and the variance of the phase differences was calculated. DPV captured the small vessels and the meshwork of capillaries associated with the inner retina in en face images over 4 mm² in a normal subject. En face DPV images were capable of capturing the microvasculature and regions of motion through the inner retina and choroid.

We propose two independent OCT data processing methods allowing visualization and analysis of the blood flow. These methods utilize variations in the OCT intensity images caused by flowing blood. The first method calculates standard deviation of intensity to generate retinal OCT angiograms. We present algorithm of this method and results of application for visualization of the microvasculature in the macular area of the human eye in vivo. The second method calculates cross power spectra of the volumetric intensity images to assess blood flow velocity in three dimensions. Validation of this method for OCT imaging was performed in a flow phantom.

We evaluate methods to visualize human retinal micro-circulation in vivo by standard intensity-based optical coherence tomography (OCT), speckle-variance optical coherence tomography (svOCT), and phase-variance optical coherence tomography (pvOCT). En face projection views created from the same volumetric data set of the human retina using all three data processing methods are created and compared. Additionally we used support vector machine (SVM) based semi-automatic segmentation to generate en face projection views of individual retinal layers. The layers include: first, the whole inner retina (from the nerve fiber layer to the outer nuclear layer), and second, from the ganglion cell layer to the outer nuclear layer. Finally, we compare the retinal vasculature images processed from the three OCT techniques and fluorescein angiography (FA).

Congenital abnormalities of the limbs are common birth defects. These include missing or extra fingers or toes, abnormal limb length, and abnormalities in patterning of bones, cartilage or muscles. Optical Coherence Tomography (OCT) is a 3-D imaging modality, which can produce high-resolution (~8 μm) images of developing embryos with an imaging depth of a few millimeters. Here we demonstrate the capability of OCT to perform 3D imaging of limb development in normal embryos and a mouse model with congenital abnormalities. Our results suggest that OCT is a promising tool to analyze embryonic limb development in mammalian models of congenital defects.

Optical scattering coefficient from ex-vivo unfixed normal and malignant ovarian tissue was quantitatively extracted by fitting optical coherence tomography (OCT) A-line signals to a single scattering model. 1097 average A-line measurements at a wavelength of 1310nm were performed at 108 sites obtained from 18 ovaries. The average scattering coefficient obtained from normal group consisted of 833 measurements from 88 sites was 2.41 mm^-1 (±0.59), while the average coefficient obtained from malignant group consisted of 264 measurements from 20 sites was 1.55 mm^-1 (±0.46). Using a threshold of 2 mm^-1 for each ovary, a sensitivity of 100% and a specificity of 100% were achieved. The amount of collagen within OCT imaging depth was analyzed from the tissue histological section stained with Sirius Red. The average collagen area fraction (CAF) obtained from normal group was 48.4% (±12.3%), while the average CAF obtained from malignant group was 11.4% (±4.7%). Statistical significance of the collagen content was found between the two groups (p < 0.001). The preliminary data demonstrated that quantitative extraction of optical scattering coefficient from OCT images could be a potential powerful method for ovarian cancer detection and diagnosis.

In this pilot study we demonstrate results of structural Fourier domain OCT imaging of the nervous system of Periplaneta americana L. (American cockroach). The purpose of this research is to develop an OCT apparatus enabling structural imaging of insect neural system. Secondary purpose of the presented research is to develop methods of the sample preparation and handling during the OCT imaging experiments. We have performed imaging in the abdominal nerve cord excised from the American cockroach. For this purpose we have developed a Fourier domain / spectral OCT system operating at 820 nm wavelength range.

The ultimate goal of the study is to provide an imaging tool to detect the earliest signs of glaucoma before clinically visible damage occurs to the retinal nerve fiber layer (RNFL). Studies have shown that the optical reflectance of the damaged RNFL at short wavelength (<560nm) is reduced much more than that at long wavelength, which provides spectral contrasts for imaging the earliest damage to the RNFL. To image the spectral contrasts we built a dual-band spectral-domain optical coherence tomography (SD-OCT) with centered wavelength of 415nm (VIS) and 808nm (NIR), respectively. The light at the two bands was provided by the fundamental and frequency-doubled outputs of a broadband Ti: Sapphire laser. The depth resolutions of the VIS and NIR OCT systems are 12.2μm and 4.7μm in the air. The system was applied to imaging the rat retina in vivo. Significantly different appearances between the OCT cross sectional images at the two bands are observed. The experimental results showed that the dual-band OCT system is feasible for imaging the spectral contrasts of the RNFL.

We present a custom fourier domain optical coherence tomography imaging system for high resolution imaging of mouse retina. In order to overcome aberrations in the mouse eye, we incorporated an adaptive optics system into the sample arm of the OCT system. We used a refraction cancelling lens to minimize aberrations from the cornea, as well as reduce the specular back-reflection. Results of FDOCT images of mouse retina acquired in vivo with and without AO are presented.

This paper demonstrates new wavelength swept light source technology, MEMS tunable VCSELs, for OCT imaging. The VCSEL achieves a combination of ultrahigh sweep speeds, wide spectral tuning range, flexibility in sweep trajectory, and extremely long coherence length, which cannot be simultaneously achieved with other technologies. A second generation prototype VCSEL is optically pumped at 980nm and a low mass electrostatically tunable mirror enables high speed wavelength tuning centered at ~1310nm with ~110nm of tunable bandwidth. Record coherence length >100mm enables extremely long imaging range. By changing the drive waveform, a single 1310nm VCSEL was driven to sweep at speeds from 100kHz to 1.2MHz axial scan rate with unidirectional and bidirectional high duty cycle sweeps. We demonstrate long range and high resolution 1310nm OCT imaging of the human anterior eye at 100kHz axial scan rate and imaging of biological samples at speeds of 60kHz - 1MHz. A first generation 1050nm device is shown to sweep over 100nm. The results of this study suggest that MEMS based VCSEL swept light source technology has unique performance characteristics and will be a critical technology for future ultrahigh speed and long depth range OCT imaging.

Fourier domain mode locked (FDML) lasers provide high sweep rates, broad tuning ranges, and high output powers for optical coherence tomography (OCT) systems. However, presently-known FDML lasers at 1300 nm have relatively short coherence lengths, limiting the size of samples that can be imaged. Furthermore, FDML lasers produce only one useable sweep direction. We report FDML coherence length extension by incorporating advanced dispersion compensation modules (DCMs). DCMs eliminate group velocity dispersion in the cavity, doubling coherence lengths and ensuring uniform axial resolution over the imaging range. Additionally, forward and backward sweeps are nearly identical, removing the need for external buffering stages.

A polarization maintaining buffered Fourier domain mode-locked (FDML) swept source at center wavelength of 1310 nm for multiplying the scanning rate of FDML swept source was demonstrated. The scanning rate of the buffered FDML swept source was doubled without sacrificing the output power of the swept source by combining two orthogonally polarized outputs with a polarization beam combiner (PBC). The stability of the swept source was improved significantly because the polarization state of the laser beam inside the cavity is maintained without any polarization controllers. With the linear polarization states of the output laser beam, the buffered FDML swept source is also ready to be used in a PSOCT system. The swept source is capable of a tuning range of more than 150 nm at a 102 kHz sweeping rate. An FDOCT system was developed with the built swept source.

Optical coherence tomography (OCT) in the 1060nm range is interesting for in vivo imaging of the human posterior eye segment (retina, choroid, sclera) due to low absorption in water and deep penetration into the tissue. Rapidly tunable light sources, such as Fourier domain mode-locked (FDML) lasers, enable acquisition of densely sampled three-dimensional datasets covering a wide field of view. However, semiconductor optical amplifiers (SOAs)-the typical laser gain media for swept sources-for the 1060nm band could until recently only provide relatively low output power and bandwidth. We have implemented an FDML laser using a new SOA featuring broad gain bandwidth and high output power. The output spectrum coincides with the wavelength range of minimal water absorption, making the light source ideal for OCT imaging of the posterior eye segment. With a moderate SOA current (270 mA) we achieve up to 100nm total sweep range and 12 μm depth resolution in air. By modulating the current, we can optimize the output spectrum and thereby improve the resolution to 9 μm in air (~6.5 μm in tissue). The average output power is higher than 20mW. Both sweep directions show similar performance; hence, both can be used for OCT imaging. This enables an A-scan rate of 350 kHz without buffering the light source output.

We demonstrate a new swept-wavelength laser for optical coherence tomography using a monolithic semiconductor device with no moving parts. The laser is based on a Vernier-Tuned Distributed Bragg Reflector (VTDBR) structure. We show highly-linear sweeps at 200 kHz sweep repetition rates, with peak output power of 20 mW. Using a test interferometer, we demonstrate point-spread functions with 45-55 dB dynamic range. The source provides long coherence length (> 40mm) at up to 200 kHz sweep rates. The laser system has sufficient linearity in optical frequency and stability over time to provide an electronic sample trigger clock (an Electronic K-Clock) that denotes equal optical frequency intervals during the sweep. The laser tuning mechanism is all-electronic, easily adjustable and programmable. We demonstrate both flat and Gaussian power vs. wavelength profiles, programmable sweep rates with the same device, and an adjustable duty cycle of up to 85% at full speed. Because the laser is a monolithic semiconductor structure based on reliable, wafer-scale processes, the manufacturing cost of the laser will decrease rapidly in volume production.

BACKGROUND Complete catheter-tissue contact and permanent tissue destruction are essential for efficient radio-frequency ablation (RFA) during cardiac arrhythmia treatment. Current methods of monitoring lesion formation are indirect and unreliable. We aim to develop optical coherence tomography (OCT) as an imaging guidance for RFA. OBJECTIVES The purpose of this study is to evaluate the feasibility of using OCT catheter to image endocardia wall in active beating hearts through percutaneous access. This is a critical step toward image guided RFA in a clinic setting. METHODS A cone-scanning forward-viewing OCT catheter was advanced into active beating hearts through percutaneous access in four swine. The OCT catheter was steered by an introducer to touch the endocardia wall. The images were then acquired at 10 frames per second at an axial resolution and lateral resolution of 15 μm. RESULTS We report the first in vivo intracardiac OCT imaging through percutaneous access with a thin and flexible OCT catheter. We are able to acquire high quality OCT images in active beating hearts, observe the polarization-related artifacts induced by the birefringence of myocardium and readily evaluate catheter-tissue contact. CONCLUSIONS It is feasible to acquire OCT images in beating hearts through percutaneous access. The observations indicate that OCT could be a promising technique for in vivo guidance of RFA.

Intracoronary optical coherence tomography (OCT) and intravascular ultrasound (IVUS) are two popular techniques for the detection and determination of atherosclerosis. IVUS allows visualization of plaques while also providing a large penetration depth to determine plaque volume. Intracoronary OCT provides the ability to capture microscopic features associated with high risk plaque. Traditionally to utilize the benefits of both modalities, separate probes and systems had to be used one at a time to image a vessel. We present work required to create a combined OCT IVUS system capable of simultaneous imaging to detect atherosclerotic plaques. A novel integrated probe of size 0.69 mm OD featuring sequential placement of components was created to acquire co-registered images within small coronary vessels. By utilizing commercial graphics processing units (GPUs) real time visualization of acquired data is possible up to a maximum 48 frames per second per channel. In vitro studies on human coronary artery samples as well as in vivo studies in rabbits and pigs show various plaque buildups in both OCT and IVUS images which match histology results, demonstrating the capabilities of the system.

Traditional phase-resolve Doppler method demonstrates great success for in-vivo imaging of blood flow and blood vessel. However, the phase-resolved methods always require high phase stability of the system. During phase instable situations, the performance of the phase-resolved methods will be degraded. We propose a modified Doppler variance algorithm that is based on the intensity or amplitude value. Performances of the proposed algorithm are compared with traditional phase-resolved Doppler variance and color Doppler methods for two phase instability systems. The proposed algorithm demonstrates good performances without phase instability induced artifacts.

Bladder carcinoma in situ (CIS) remains a clinical challenge. We compare the efficacies and potential limitations of surface imaging modalities, e.g., white light (WL), fluorescence (FC), blue-light imaging (BL) and 3D optical coherence tomography (3D OCT) for early diagnosis of bladder CIS. SV40T transgenic mice, which develop carcinoma in situ in about 8 to 20 weeks then high grade papillary tumor in the bladder, were employed as the rodent carcinogenesis model to closely mimic human bladder CIS. A total of 30 mice (i.e., SV40T mice blinded with its back strain Balb/c mice) were enrolled in the study, including 20 with CIS and 10 with normal or benign lesions of the bladder mucosa. Our results show that the low diagnostic sensitivities and specificities of WL, FC and BL for early CIS were significantly enhanced by quantitative 3D OCT to 95.0% and 90.0%, suggesting the value of image-guided 3D OCT for future clinical diagnosis of CIS in vivo.

We demonstrate the acquisition of densely sampled wide-field 3D OCT datasets of the human retina in 0.3s. This performance is achieved with a multi-MHz Fourier domain mode-locked (FDML) laser source operating at 1050nm. A two-beam setup doubles the 3.35MHz laser sweep rate to 6.7MHz, which is 16x faster than results achieved with any non-FDML source used for retinal OCT. We discuss two main benefits of these high line rates: First, large datasets over an ultra-wide field of view can be acquired with a low probability of distortions. Second, even if eye movements occur, now the scan rate is high enough to directly correct even the fastest saccades without loss of information.

We report on detailed characterization of a newly developed ultra-high speed optical coherence tomography (OCT) system using arrayed wave guide at 1.3 μm. An axial resolution of 27 μm, a depth range of 3.98 mm, and a detection speed of 2.5 or 10 MHz axial scan per second have been achieved. We also discuss the effectiveness of a semiconductor optical amplifier (SOA) in the system. The system sensitivity without SOA was about 78 dB, which is far less than the shot-noise-limited sensitivity because of relative intensity noise and loss of optical intensity in the system. To improve the low sensitivity, we used the SOA in the system and achieved a sensitivity of 94 dB with a probe power of 10 mW, which allowed us good imaging quality in biomedical applications. The OCT system is also capable to display a volumetric tomography continuously in real time by using field programmable gate arrays (FPGA) and general purpose graphical processing unit (GPGPU) for high-speed parallel data processing. We present several tissue images such as human finger skin, finger near nail and extracted trachea of a pig.

We present a novel optical coherence tomography (OCT) system design that employs coherence revival-based heterodyning and polarization encoding to simultaneously image the ocular anterior segment and the retina. Coherence revival heterodyning allows for multiple depths within a sample to be simultaneously imaged and frequency encoded by carefully controlling the optical pathlength of each sample path. A polarization-encoded sample arm was used to direct orthogonal polarizations to the anterior segment and retina. This design is a significant step toward realizing whole-eye OCT, which would enable customized ray-traced modeling of patient eyes to improve refractive surgical interventions, as well as the elimination of optical artifacts in retinal OCT diagnostics. We demonstrated the feasibility of this system by acquiring images of the anterior segments and retinas of healthy human volunteers.

Doppler Fourier domain optical coherence tomography is able to be used for in vivo blood flow measurement. In conventional methods, the highest velocity that can be measured is limited to the range the phase shift between two successively recorded depth profiles at the same probe-beam location, which cannot exceed (-π, π), otherwise phase wrapping will occur. This phase-wrapping limit is determined by the time interval between two consecutive A-scans. We present a novel approach to shorten the time interval between two consecutive A-scans and thus increase the phase-wrapping limit by using an area scan camera to record the interference spectrum in a streak mode. To demonstrate the effectiveness of this method, the blood flows in HH18 and HH19 chick hearts were imaged and phase wrapping free Doppler images were obtained.

We present a method to obtain instantaneous quadrature components of the complex interferometric signal for depth-ambiguity free and full range optical frequency domain imaging, based on the Pancharatnam-Berry phase. This wavelength independent method allowed for a complex conjugate suppression of 45 dB, over an optical bandwidth of 80 nm. Furthermore, we investigated the versatility of this setup to perform polarization sensitive measurements. The sample Jones vector was fitted using the Newton-Raphson method, allowing sample birefringence and optical axis calculation.

The influence of the individual spectrometer components on the depth dependent sensitivity fall-off (roll-off) in spectral-domain optical coherence tomography (SD-OCT) is investigated. We present a method for the characterization of the roll-off in SD-OCT systems via modulation transfer function (MTF) analysis. The MTF of different image sensors was measured in a newly developed setup, which uses the interference of two coherent light beams. Different contributions, i.e. diffraction, aberrations and sampling effects, to the MTF of a spectrometer of commercially available SD-OCT systems is calculated and is compared with roll-off measurements. The difference was below -2 dB at 90 % of the maximum measurement depth.

It is demonstrated that modulation of active gain in each arm may be used to control the optical power that interrogates multiple paths at the same time. Using this concept, simultaneous interrogation of ten depths in a sample at 75 microns apart is demonstrated, with less attenuation from one recirculation to the next than we previously reported.

We introduce a swept source FDOCT imaging system that allows measuring simultaneously the reflected light and scattered light (bright field) and the scattered light only (dark field) in two different channels through separate Gaussian and Bessel detection. Specular reflections can then be used to obtain knowledge about the sample time evolution with high SNR for phase analysis. Based on this configuration, we provide a proof-of principle study for resolving ultrasound pulse trains with high temporal resolution on surfaces, which potentially provides a novel phase sensitive all optical detection scheme for the combination of OCT with photoacoustic imaging.

Rehydratable, lyophilized platelets loaded with superparamagnetic iron oxides (SPIOs) has the potential to provide magnetomotive imaging contrast to sites of vascular damage, including thrombosis complicating atherosclerosis and hemorrhage. Magnetomotive optical coherence tomography (MMOCT) contrasts SPIO-platelets based on their nanoscale, magnetically-induced motion. We report improvements in MMOCT imaging contrast and sensitivity by optimizing the magnetic properties and SPIO loading of the platelets. SPIO-platelets have been shown to specifically adhere to sites of vascular damage in porcine arteries ex vivo. This may lead to new methods for detecting internal bleeding and monitoring the formation of blood clots using infused SPIO-platelets.

Hearing in mammals, depend on an amplifying motion which hypothetically uses force from outer hair cells (OHC) motility to enhance sound induced vibration of the organ of Corti of cochlea. In this hypothesis the differential motion among key structures in this organ and the timing of the OHC force generation is essential for cochlear amplification to occur. Using a time domain optical coherence tomography system which allows us to make vibration measurements we were able to measure differential motion of two functionally important surfaces, namely, basilar membrane and reticular lamina. The reticular lamina vibrates at higher amplitude than the basilar membrane and has significant phase lead over basilar membrane vibration. The differential motion, that is, different amplitude and phase of vibration, become less as the energy of the sound stimulus is increased and the amplification processes in the organ of Corti are quenched.

Optical coherence tomography (OCT) is becoming a popular tool for imaging morphology in the middle and inner ear. Vibratory measurements of the structures of the ear facilitate better understanding of the function and limitations of the ear. We have developed an algorithm that enables a standard spectrometer based OCT system to measure the full spectrum (90 kHz) frequency response of the mouse ear by incorporating coherently interleaved sampling, increasing the effective Nyquist rate of the system by a factor of 5+. The algorithm is evaluated by measuring the frequency response of a mouse tympanic membrane to a pure tone stimulus.

Spectral and Time domain OCT (STdOCT) is a data analysis scheme proposed for sensitive Doppler imaging. In this work we show that it has an additional feature: when compared to those created using complex or amplitude averaging, tomograms prepared using STdOCT have the highest contrast to noise ratio and preserve high signal to noise ratio and image dynamic range. Images of uniformly scattering phantom as well as images of human retina in vivo prepared with three different techniques are shown.

Phase sensitive OCT enables the measurement of thermal expansion in laser irradiated material at high lateral and temporal resolution. In principle, a calculation of the 3D temperature distribution and its temporal evolution should be possible by evaluating the local expansion. This could be utilized for a non-invasive and very fast temperature measurement, e.g. to realize an online dosimetry for photocoagulation. The possibilities of quantitative investigations at high axial and lateral resolution are demonstrated by imaging the reversible thermal expansion in laser irradiated multilayer silicone phantoms.

Direct measurement of absolute vibration parameters from different locations within the mammalian organ of Corti is crucial for understanding the hearing mechanics such as how sound propagates through the cochlea and how sound stimulates the vibration of various structures of the cochlea, namely, basilar membrane (BM), recticular lamina, outer hair cells and tectorial membrane (TM). In this study we demonstrate the feasibility a modified phase-sensitive spectral domain optical coherence tomography system to provide subnanometer scale vibration information from multiple angles within the imaging beam. The system has the potential to provide depth resolved absolute vibration measurement of tissue microstructures from each of the delay-encoded vibration images with a noise floor of ~0.3nm at 200Hz.

A polarization sensitive optical coherence tomography based automated algorithm for segmentation of the chorio-scleral interface is presented. The algorithm employs a two-step segmentation approach. At first, local birefringence based segmentation with low precision is performed to roughly distinguish the choroid and sclera. Successively, a depth oriented slope fitting to phase retardation is applied in both the choroid and sclera. The interface is determined as the cross-point of the two phase retardation slope lines. The algorithm shows potential for functional, objective, and volumetric choroid thickness measurement.

We demonstrate Optical Coherence Microscopy (OCM) for in vivo imaging of the rat cerebral cortex. Imaging does not require addition of dyes or contrast agents, and is achieved through intrinsic scattering contrast and image processing alone. Furthermore, we demonstrate in vivo, quantitative measurements of optical properties and angiography in the rat cerebral cortex. Imaging depths greater than those achieved by conventional two-photon microscopy are demonstrated.

Holoscopy is a new imaging approach combining Digital Holography and Full-field Fourier-domain Optical Coherence Tomography. The interference pattern between the light scattered by a sample and a defined reference wave is recorded digitally. By numerical processing of the recorded interference pattern, the back-scattering field of the sample is reconstructed with a diffraction limited lateral resolution over the whole measurement depth since numerical refocusing overcomes the limitation of the focal depth. We present two setup configurations - a low resolution setup based on a Michelson interferometer and a high resolution setup based on a Mach-Zehnder interferometer. Successful measurements were demonstrated with a numerical aperture (NA) of 0.05 and 0.14, respectively and will be presented. Additionally, the effects of filtering spatial frequencies in terms of separating sample signals from artifacts caused by setup reflections is discussed and its improvement on the image quality is shown.

Computer-aided diagnosis of ophthalmic diseases using optical coherence tomography (OCT) relies on the extraction of thickness and size measures from the OCT images, but such defined layers are usually not observed in emerging OCT applications aimed at "optical biopsy" such as pulmonology or gastroenterology. Mathematical methods such as Principal Component Analysis (PCA) or textural analyses including both spatial textural analysis derived from the two-dimensional discrete Fourier transform (DFT) and statistical texture analysis obtained independently from center-symmetric auto-correlation (CSAC) and spatial grey-level dependency matrices (SGLDM), as well as, quantitative measurements of the attenuation coefficient have been previously proposed to overcome this problem. We recently proposed an alternative approach consisting of a region segmentation according to the intensity variation along the vertical axis and a pure statistical technology for feature quantification. OCT images were first segmented in the axial direction in an automated manner according to intensity. Afterwards, a morphological analysis of the segmented OCT images was employed for quantifying the features that served for tissue classification. In this study, a PCA processing of the extracted features is accomplished to combine their discriminative power in a lower number of dimensions. Ready discrimination of gastrointestinal surgical specimens is attained demonstrating that the approach further surpasses the algorithms previously reported and is feasible for tissue classification in the clinical setting.

In this paper, we systematically presented a series of graphics processing unit (GPU) based data processing methods for ultrahigh speed, real-time Fourier Domain optical coherence tomography (FD-OCT): GPU based algorithms including high-speed linear/cubic interpolation, non-uniform fast Fourier transform (NUFFT), numerical dispersion compensation, and multi-GPU implementation were developed to improve the image quality and stability of the system. Full-range complex-conjugate-free FD-OCT was also implemented on the GPU architecture to double the imaging range and to improve SNR. The maximum processing speed of >3.0 Giga-Voxel/second (>6.0 Mega-A-scan/ second of 1024-pixel FD-OCT) was achieved using NVIDIA's latest GPU modules. The GPU-based volume rendering enabled real-time 4D (3D+time) FD-OCT imaging, and a 5 volume/second 4D FD-OCT system was demonstrated. These GPU technologies were highly effective in circumventing the imaging reconstruction and visualization bottlenecks exist among current ultra-high speed FD-OCT systems and could significantly facilitate the interventional OCT imaging.

The problem of restoration Optical Coherence Tomography (OCT) images, acquired with tightly focused probing beam, in out-of-focus region for improving lateral resolution of the OCT has been considered. Phase stability issue has been discussed and phase equalization algorithm has been proposed. After phase equalization, the algorithm of digital refocusing, based on some methods from the DH, have been applied to the simulated as well as to experimental OCT data, acquired with tightly focused scanning beam to restore micrometer lateral resolution in the whole investigated volume.

Standard FD-OCT systems suffer from a limited useful depth range due to the inherent complex conjugate artifacts and continuous fall-off in sensitivity with distance from the zero delay. The techniques of dispersion encoded full range (DEFR) frequency-domain optical coherence tomography (FD-OCT) and its enhanced version fast DEFR use the dispersion mismatch between sample and reference arm to double the imaging depth range by iteratively suppressing complex conjugate artifacts. Previously the computational complexity of DEFR prevented its application to fields where real-time visualization or large volumetric datasets are needed. A graphics processing unit (GPU) with hundreds of processing cores provides highly parallel computation capability to FD-OCT in which processing for each A-line is identical and independent. In this paper, we adopted GPUs to accelerate DEFR, thereby significantly improving reconstruction speed by a factor of >90 in respect to CPU based processing. A maximum display line rate of ~21 k-lines/ s for 2048 points/A-line using 10 iterations of the fast DEFR algorithm has been successively achieved, thereby enabling the application of DEFR in fields where real time visualization is required. By comparison in the conjugate artifact suppressed cross-sectional image of a mouse eye, there is no significant qualitative difference between the corresponding CPU- and GPU-processed images.

This paper presents the combination of phase sensitive optical coherence tomography (PhS-OCT) imaging system and surface wave method to achieve quantitative evaluation and elastography of the mechanical properties of in vivo human skin. PhS-OCT measures the surface acoustic waves (SAWs) generated by impulse stimulation from a home-made shaker, and provide the B-frame images for the sample. The surface wave phase velocity dispersion curves were calculated, from which the elasticity of different skin layers were determined. The combination of phase velocities from adjacent two locations generates a quantitative elastography of sample. The experimental results agree well with theoretical expectations and may offer potential use in clinical situations.

We have developed swept source optical coherence tomography (OCT) system with an optical comb swept source system. The swept source system comprised of two super-structured grating distributed Bragg reflector lasers covering a wavelength range from 1561-1693 nm. A method to scan these lasers to obtain an interference signal without stitching noises, which are inherent in these lasers, and to connect two lasers without concatenation noise is explained. Method to reduce optical aliasing noises in this optical comb swept laser OCT is explained and demonstrated based on the characteristic of the optical aliasing noises in this particular OCT system. By reduction of those noises, a sensitivity of 124 dB was realized. The A-scan rate, resolution and depth range were 3.1 kHz, 16 μm (in air) and 12 mm, respectively. Deep imaging penetration into tissue is demonstrated for two selected samples.

The concentration of photothermal (light-to-heat converters) compounds as a function of depth is determined in solid agar gel phantoms. The system contains an 808nm pump laser, which excites the photothermal compound, and a phase sensitive spectral domain optical coherence tomography system, which detects the changes in the optical pathlength of the sample induced by the temperature increase. The derivation of the model is described, and its parameters are empirically determined. The concentration of photothermal compounds are observed from double layer agar gel phantoms.

In this report we investigate the possibility of narrowing the depth range of a physical Shack-Hartmann wavefront sensor (SH-WFS) using coherence gating technique in spectral domain. A time-domain low coherence interferometry (LCI) setup [1] has already been demonstrated capable of generating similar Shack-Hartmann spots pattern to that delivered by a conventional SH-WFS. Stray reflections are eliminated in the images due to a narrow coherence gating introduced by the interferometric technique. Hereby we present another approach by employing a wavelength tuneable light source to obtain Shack-Hartmann spot patterns with coherence gating in a 3D volume without axial scanning. Signal strength is enhanced in contrast with a conventional SH-WFS and signal to noise ratio is improved compared to the previous time-domain setup. This novel technique has the potential of providing depth resolved wavefront aberration information, which can guide better wavefront correction in adaptive optics assisted ophthalmology imaging and confocal microscopy instruments.

In the last decade a large number of new intracoronary devices (i.e. drug-eluting stents, DES) have been developed to reduce the risks related to bare metal stent (BMS) implantation. The use of this new generation of DES has been shown to substantially reduce, compared with BMS, the occurrence of restenosis and recurrent ischemia that would necessitate a second revascularization procedure. Nevertheless, safety issues on the use of DES persist and full understanding of mechanisms of adverse clinical events is still a matter of concern and debate. Intravascular Optical Coherence Tomography (IV-OCT) is an imaging technique able to visualize the microstructure of blood vessels with an axial resolution <20 μm. Due to its very high spatial resolution, it enables detailed in-vivo assessment of implanted devices and vessel wall. Currently, the aim of several major clinical trials is to observe and quantify the vessel response to DES implantation over time. However, image analysis is currently performed manually and corresponding images, belonging to different IV-OCT acquisitions, can only be matched through a very labor intensive and subjective procedure. The aim of this study is to develop and validate a new methodology for the automatic registration of IV-OCT datasets on an image level. Hereto, we propose a landmark based rigid registration method exploiting the metallic stent framework as a feature. Such a tool would provide a better understanding of the behavior of different intracoronary devices in-vivo, giving unique insights about vessel pathophysiology and performance of new generation of intracoronary devices and different drugs.

In most dual-band OCT systems, there is a spectral gap between both bands. This might be as large as one third of the total spectral region. Therefore, a simple Fourier transformation of the data does not give the resolution that could be possible considering the overall spectral width. Instead, the full width of the peak is comparable to the width resulting from a single band and is additionally modulated. We compare several methods to achieve a high resolution in spite of the missing data. Because in a dual-band system the image quality resulting from the full information is not known we test and optimize different algorithms by using the data from a single band system and excluding an equal part of the spectrum. While methods using non-equidistant sample points like Vandermonde and Lomb transformation work well with small spectral gaps, they result in large image artifacts for broader gaps, which are typical for dual-band OCT systems. Simulations show that fitting the available data with a limited set of sine and cosines functions might give good results but for larger gaps and appropriate amount of basis-functions this method fails, too. Dividing both bands into overlapping smaller bands and looking at the phase of short-time Fourier transformations (STFT) resulting from a single scatterer, it becomes clear that the amplitude of all Fourier coefficients for the total band can be estimated by the change of the phase of the STFTs in and between both bands. Therefore, we developed an algorithm of weighting the data based on the phase distribution of the STFT data. As a single value specifying the phase distribution we choose the absolute sum of the STFTs divided by the sum of the amplitudes of the STFTs. Because typical OCT data are not caused by single scatterers, we adapted this algorithm with a cluster analysis to predict the appropriate amplitude expected for a full spectrum from the phase distribution of the STFTs inside both bands and between both bands. Although the image is noisier and fainter compared to an image from the full spectrum, the resulting image has the best resolution from all methods investigated.

We report a 45 kHz spectroscopic OCT system based on a swept laser source utilizing two wavelength bands. The source is generated by single-band swept laser input and a fiber optical parametric amplifier. The time-multiplexing architecture reduces the complexity of the coupling and detecting configuration in comparison with the previous dual-band swept-source setup. This high-speed spectroscopic OCT combines the advantages of the speed of the swept laser and contrast enhancement, in comparison with the time or spectral-domain spectroscopic OCT system. In the experiment, spectroscopic OCT imaging around 1550 nm is achieved for the first time. The difference in images at 1500 nm and 1600 nm clearly shows different back scattering and penetration properties which can be used for tissue classification and water content measurement.

Although the Doppler Optical Coherence Tomography techniques have already enabled imaging of blood flow in large vessels in biological tissues, the generation of velocity maps of the capillary network is still a challenge. Since several important physiological and pathological phenomena occur in the microcirculation, the possibility of flow imaging and velocity assessment in microcapillaries may be important for medical diagnostics. Understanding of the origin of the Doppler signal in capillary vessels and limitations of such measurements is essential for further development of Doppler OCT methods. In the OCT flow maps of a microcapillary network randomly varying Doppler signals are observed. To answer the question how accurate is the Doppler OCT flow measurement for blood motion in small vessels, we have investigated the possibility to obtain velocity profiles of blood in vitro in well controlled experimental configuration. We have used a rectangular microchannel (100 μm wide, 40 μm deep) as a microcapillary phantom. Imaging was performed with a Fourier domain OCT setup with a CMOS camera. Data analysis was performed using joint Spectral and Time Domain OCT method (STdOCT).

We demonstrate theoretically and experimentally that the phase retardance and relative optic-axis orientation of a sample can be calculated without prior knowledge of the actual value of the phase modulation amplitude when using a polarization-sensitive optical coherence tomography system based on continuous polarization modulation (CPM-PS-OCT). We also demonstrate that the sample Jones matrix can be calculated at any values of the phase modulation amplitude in a reasonable range depending on the system effective signal-to-noise ratio. This has fundamental importance for the development of clinical systems by simplifying the polarization modulator drive instrumentation and eliminating its calibration procedure. This was validated on measurements of a three-quarter waveplate and an equine tendon sample by a fiber-based swept-source CPM-PS-OCT system.

A novel method for lateral resolution improvement of Optical Coherence Tomography (OCT) images, which is independent of the focusing of the delivery optics and the depth of field, is presented. This method was inspired by radar range oversampling techniques. It is based on the lateral oversampling of the image and the estimation of the locations of the multiple scatterers which contribute to the signal. The information in the oversampled images is used to estimate the locations of multiple scatterers assuming each contributes a weighted portion to the detected signal, the weight determined by the location of the scatterer and the point spread function (PSF) of the system. A priori knowledge of the PSF is not required since optimization techniques can be employed to achieve the best possible enhancement of the image resolution. Preliminary results of such an approach on laterally oversampled OCT images have shown that it is possible to achieve a two-fold lateral resolution improvement. Moreover by performing deconvolution with the new improved PSF the lateral resolution can be further improved by another factor of two for a total of 4x improvement. Such improvement can be significant, especially in cases where the Numerical Aperture (NA) of the delivery optics is limited, such as, for example, in the case of ophthalmic imaging where the optics of the eye itself limit the lateral resolution.

Phase-resolved optical frequency domain imaging (OFDI) has emerged as a promising technique for blood flow measurement in human tissues. Phase stability is essential for this technique to achieve high accuracy in flow velocity measurement. In OFDI systems that use k-clocking for the data acquisition, phase-error occurs due to jitter in the data acquisition electronics. We presented a statistical analysis of jitter represented as point shifts of the k-clocked spectrum. We demonstrated a real-time phase-error correction algorithm for phase-resolved OFDI. A 50 KHz wavelength-swept laser (Axsun Technologies) based balanced-detection OFDI system was developed centered at 1310 nm. To evaluate the performance of this algorithm, a stationary gold mirror was employed as sample for phase analysis. Furthermore, we implemented this algorithm for imaging of human skin. Good-quality skin structure and Doppler image can be observed in real-time after phase-error correction. The results show that the algorithm can effectively correct the jitter-induced phase error in OFDI system.

We report design and construction of an FPGA-based high-speed swept-source polarization-sensitive optical coherence tomography (SS-PS-OCT) system for clinical retinal imaging. Clinical application of the SS-PS-OCT system is accurate measurement and display of thickness, phase retardation and birefringence maps of the retinal nerve fiber layer (RNFL) in human subjects for early detection of glaucoma. The FPGA-based SS-PS-OCT system provides three incident polarization states on the eye and uses a bulk-optic polarization sensitive balanced detection module to record two orthogonal interference fringe signals. Interference fringe signals and relative phase retardation between two orthogonal polarization states are used to obtain Stokes vectors of light returning from each RNFL depth. We implement a Levenberg-Marquardt algorithm on a Field Programmable Gate Array (FPGA) to compute accurate phase retardation and birefringence maps. For each retinal scan, a three-state Levenberg-Marquardt nonlinear algorithm is applied to 360 clusters each consisting of 100 A-scans to determine accurate maps of phase retardation and birefringence in less than 1 second after patient measurement allowing real-time clinical imaging-a speedup of more than 300 times over previous implementations. We report application of the FPGA-based SS-PS-OCT system for real-time clinical imaging of patients enrolled in a clinical study at the Eye Institute of Austin and Duke Eye Center.

The effectiveness of speckle reduction using traditional frame averaging technique was limited in ultrahigh speed optical coherence tomography (OCT). As the motion between repeated frames was very small, the speckle pattern of the frames might be identical. This problem could be solved by averaging frames acquired at slightly different locations. The optimized scan range depended on the spot size of the laser beam, the smoothness of the boundary, and the homogeneity of the tissue. In this study we presented a method to average frames obtained within a narrow range along the slow-axis. A swept-source OCT with 100,000 Hz axial scan rate was used to scan the retina in vivo. A series of narrow raster scans (0-50 micron along the slow axis) were evaluated. Each scan contained 20 image frames evenly distributed in the scan range. The imaging frame rate was 417 HZ. Only frames with high correlation after rigid registration were used in averaging. The result showed that the contrast-to-noise ratio (CNR) increased with the scan range. But the best edge reservation was obtained with 15 micron scan range. Thus, for ultrahigh speed OCT systems, averaging frames from a narrow band along the slow-axis could achieve better speckle reduction than traditional frame averaging techniques.

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 sources. Although ultrahigh longitudinal resolution was achieved in several center wavelength regions, its low penetration depth is a serious limitation for other applications. To realize ultrahigh resolution and deep penetration depth simultaneously, it is necessary to choose the proper wavelength to maximize the light penetration and enhance the image contrast at deeper depths. Recently, we have demonstrated the wavelength dependence of penetration depth and imaging contrast for ultrahigh resolution OCT at 0.8 μm, 1.3 μm, and 1.7 μm wavelength ranges. In this paper, additionally we used SC sources at 1.06 μm and 1.55 μm, and we have investigated the wavelength dependence of UHR-OCT at five wavelength regions. The image contrast and penetration depth have been discussed in terms of the scattering coefficient and water absorption of samples. Almost the same optical characteristics in longitudinal and lateral resolution, sensitivity, and incident optical power at all wavelength regions were demonstrated. We confirmed the enhancement of image contrast and decreased ambiguity of deeper epithelioid structure at longer wavelength region.

We developed the ultra high-speed processing of FD-OCT images using a low-cost graphics processing unit (GPU) with many stream processors to realize highly parallel processing. The processing line rates of half range FD-OCT and full range FD-OCT were 1.34 MHz and 0.70 MHz for a spectral interference image of 1024 FFT size x 2048 lateral A-scans, respectively. A display rate of 22.5 frames per second for processed full range images was achieved in our OCT system using an InGaAs line scan camera operated at 47 kHz.

Several factors are spurring the development of hardware and software to accomplish high-speed processing for Optical Coherence Tomography (OCT). The two most prevalent architectures incorporate either an FPGA or a GPU. While GPUs have faster clock-speed the fact an FPGA can be pipelined makes a direct comparison based simply on system specifications difficult. We have undertaken an effort to make a direct comparison on the same host and consider the total time from digitization to rendering of the image. In addition to making quantitative comparisons between the two architectures we hope to derive useful benchmarks that will inform the design of an optimal high-speed processing system.

We are developing a new light source for swept-source OCT, namely, an external-cavity LD equipped with a KTN electro-optic deflector. Being free from mechanical resonance, our 1.3-μm laser exhibits scanning range of almost 100 nm up to 200-kHz under a ±300 V deflector driving voltage. Using a semi-empirically derived equation, we find that KTN's convex lens power degrades the coherence length, and this can be compensated with a cylindrical concave lens. Such compensation was experimentally confirmed by observing reduction of elliptical beam divergence. OCT images of a human fingernail are obtained using the swept source.

In this work the use of two identical QD SOAs to enhance the performance of swept laser system for OCT applications is discussed, resulting in an increase in bandwidth up to 94nm. The combination of GaAs based QD SOAs and InP based QW SOAs for realizing broad bandwidth sources for OCT system is described. For the swept laser source a 154nm spectral bandwidth from 1193nm to 1347nm and an average power of 8mW is obtained and for the filtered ASE source a 225 nm bandwidth is demonstrated.

We present a Fourier domain optical coherence tomography set-up built around an optical configuration that exhibits Talbot bands. To produce Talbot bands, the two interferometer beams, object and reference are laterally shifted in their way towards the diffraction grating. This allows attenuation of mirror terms and optimisation of the sensitivity profile. We imaged the human skin in-vivo, and quantified the profile of the sensitivity profile in tissue by measuring the ratio between the strengths of signals originating in the reticular dermis and in the stratum corneum for different values of the lateral shift of the two interfering beams.

Spectral domain optical coherence microscopy (OCM) is an interferometric imaging technique for three-dimensional reconstruction of biological samples. Phase sensitive implementation of OCM has generally been in common path interferometer configuration to obtain high phase stability, which limits the numerical aperture of the imaging optics and the transverse resolution. Here, we describe the implementation of optical coherence phase microscope in asymmetric Linnik interferometer configuration, which provides phase stability of 0.5 milliradians along with high spatial resolution. Three-dimensional structural images and dynamic displacement images obtained from spontaneously active cardiomyocytes demonstrate that the phase information could potentially be used for quantitative analysis of contraction dynamics, spatially resolved to sub-cellular structures.

We report on the software design of an ultra-parallel ultra-high speed spectral domain optical coherence tomography (SD-OCT) system. In our system, optical de-multiplexers divide an interferogram into 320 light every 18.7 GHz frequency, instead of a refractive grating for spectroscopy so far used in conventional SD-OCT. These optical elements enable to get rid of a re-sampling process and contribute to reduce the load of computing. The fast Fourier transform (FFT) is performed by field-programmable gate array (FPGA) and real-time 3D OCT images are created on graphics processing unit (GPU). Our system achieves a real-time 3D OCT image display (4D display) with an A-scan, B-scan, and volume rate of 10 MHz, 4 kHz, and 12 volumes per second, respectively.

We report all-PM-fiber ring external cavity, extremely wide tunable/swept lasers and MOPA sources basing on a newly developed SOAs and acousto-optic filter. Tuning ranges of 100 nm, 90 nm and 70 nm have been achieved at output powers of 1.0 mW, 5.0 mW and 10.0 mW, respectively. Instantaneous linewidth below 0.04 nm and sweeping rate up to 10⁴ nm/s had been demonstrated. Power boosting up to 50 mW (PMF) and up to 250 mW (MMF) with tunability of around 50 nm had been also demonstrated by using MOPA systems basing on developed laser and different types of boosting SOAs.

We discuss two methods which use the intrinsic dispersion imbalance between interferometer arms in order to address and manipulate the complex conjugate terms in spectral domain optical coherence tomography. Using projections of the time-frequency plane, we can manipulate small induced dispersion and obtain similar modification of the complex conjugate term as large amount of chromatic dispersion. The algorithm described spreads the energy of the complex conjugate term over the entire A-scan. The method is applied to simulated OCT depth signals and offered a mirror term suppression of 20 dB. The second method shows how we can use the time-frequency distribution to filter the mirror terms for a pre-configured depth range about zero path length.

OCT is highly potential for dynamic analysis of physiological functions of mental sweating and peripheral vessels as demonstrated by the authors. Both mental sweating and the peripheral vessels reflect the activity of the sympathetic nerve of the autonomic nervous system (ANS). The sympathetic nerve also exhibits the LF/HF ratio of the heart rate variability (HRV). In this paper, we demonstrate dynamic analysis of mental sweating and the peripheral vessels for the external stimulus by SS-OCT. In the experiment, the Kraepelin test as a continuous stimulus was applied to the volunteer to discuss in detail dynamics of the physiological function of such small organs in response to the HRV.

The difference in the genetic make up of the constituent molecules in collagen fibers in tendon and articular cartilage is what makes them mechanically and functionally different. A comparative study carried out on the differences in the angle-resolved back-scattering properties obtained from optical coherence tomography based studies on the two different types of scatterers: collagen I and collagen II fibers in bovine tendon and bovine articular cartilage sample, respectively, is reported here. Tendon sample shows greater anisotropy in the angle-resolved scattering profile compared to that obtained from articular cartilage sample. Rayleigh-Gans scattering approximation is used to provide the qualitative support needed to substantiate differences in the light scattering profiles obtained from the two tissues based on the size and type of the scatterers involved.

An efficient technique of linear in-wavenumber optical spectrum registration in SD-OCT is proposed. Methods of partial phase correction of registered optical spectrum for in-wavenumber linearization are described and investigated. The decrease sensitivity decay with depth increasing degeneration is presented. The experimental results for sample media are presented.

We demonstrate a compact all-fiber probe for a common path optical coherence tomography (CPOCT) system. By forming a focusing lens directly on the tip of an optical fiber, a compact fiber probe could be constructed. The microlens is produced by forming a droplet with UV-curing adhesive on the cleaved tip of multimode fiber. It fulfills two functions acting as both the reference plane and the imaging lens. To simultaneously achieve a relative long working distance and a good lateral resolution, we employed a large core size multimode fiber. A working distance of 280μm, and a transverse resolution of 14μm were achieved with the implemented MMF lensed fiber. The performance of the CPOCT system with the proposed MMF lensed fiber is presented by showing the OCT images of an onion tissue as biological sample.

An efficient technique of simultaneous obtaining of quadrature spectral components of interference signal in spectrometer-based OCT using a single-line linear photodiode array is proposed. The components are obtained in air-spaced non-polarization interferometer by partition of reference beam onto two parts and using an achromatic phase shifter. Several setups are described and compared.

A miniature endoscope probe for forward viewing in a 50 kHz swept source optical coherence tomography (SS-OCT) configuration was developed. The work presented here is an intermediate step in our research towards in vivo endoscopic laryngeal cancer screening. The endoscope probe consists of a miniature tubular lead zirconate titanate (PZT) actuator, a single mode fiber (SMF) cantilever and a GRIN lens, with a diameter of 2.4 mm. The outer surface of the PZT actuator is divided into four quadrants that form two pairs of orthogonal electrodes (X and Y). When sinusoidal waves of opposite polarities are applied to one electrode pair, the PZT tube bends transversally with respect to the two corresponding quadrants, and the fiber optic cantilever is displaced perpendicular to the PZT tube. The cantilever's resonant frequency was found experimentally as 47.03 Hz. With the GRIN lens used, a lateral resolution of ~ 13 μm is expected. 2D en face spiral scanning pattern is achieved by adjusting the phase between the pairs of X and Y electrodes drive close to 90 degrees. Furthermore, we demonstrate the imaging capability of the probe by obtaining B-scan images of diseased larynx tissue and compare them with those obtained in a 1310 nm SS-OCT classical non-endoscopic system.

As optical coherence tomography (OCT) becomes widespread, validation and characterization of systems becomes important. Reference standards are required to qualitatively and quantitatively measure the performance between difference systems. This would allow the performance degradation of the system over time to be monitored. In this report, the properties of the femtosecond inscribed structures from three different systems for making suitable OCT characterization artefacts (phantoms) are analyzed. The parameter test samples are directly inscribed inside transparent materials. The structures are characterized using an optical microscope and a swept-source OCT. The high reproducibility of the inscribed structures shows high potential for producing multi-modality OCT calibration and characterization phantoms. Such that a single artefact can be used to characterize multiple performance parameters such the resolution, linearity, distortion, and imaging depths.

In this work we study the factors affecting the linewidth of a swept laser source. A ring fiber laser source based on EDFA and a Fabry-Perort resonator is used for this purpose. With this setup a swept source with a linewidth of better than 0.1 nm is obtained over a tuning range of about 47 nm limited by the spectral gain of the EDFA amplifier used. The factors affecting the source linewidth are then examined by modeling the EFDA amplifier and the swept source and then compared to the practical measured results of an EDFA swept laser source. The measurements and simulations both show that the swept laser linewidth is about 10 times narrower than the Fabry-Perot filter 3dB linewidth.