This PDF file contains the front matter associated with SPIE Proceedings Volume 8802 including the Title Page, Copyright information, Table of Contents, Introduction, and Conference Committee listing.

Optical coherence tomography (OCT) has enabled clinical applications that revolutionized in vivo medical diagnostics. Nevertheless, its current limitations owing to cost, size, complexity, and the need for accurate alignment must be overcome by radically novel approaches. Exploiting integrated optics, the central components of a spectral-domain OCT (SD-OCT) system can be integrated on a chip. Arrayed-waveguide grating (AWG) spectrometers with their high spectral resolution and compactness are excellent candidates for on-chip SD-OCT systems. However, specific design-related issues of AWG spectrometers limit the performance of on-chip SD-OCT systems. Here we present advanced AWG designs which could overcome the limitations arising from free spectral range, polarization dependency, and curved focal plane of the AWG spectrometers. Using these advanced AWG designs in an SD-OCT system can provide not only better overall performance but also some unique aspects that a commercial system does not have. Additionally, a partially integrated OCT system comprising an AWG spectrometer and an integrated beam splitter, as well as the in vivo imaging using this system are demonstrated.

Full range imaging is of high interest in frequency domain (FD) optical coherence tomography (OCT), and dispersion encoded full range (DEFR) OCT has emerged as an effective technique with only minor additional hardware requirements. We present an advanced DEFR OCT algorithm, which increases the processing speed considerably by using only one Fourier transform per A-scan and convolution in z-space. While the initial DEFR algorithm effectively removes mirror artifacts, DC and autocorrelation artifacts are still prone to corrupt the reconstructed image. To address this issue, the presented advanced DEFR algorithm uses an additional Fourier transform per A-scan and removes DC and autocorrelation artifacts within the same regime, significantly improving the quality of the reconstructed image. The DEFR algorithm is inherently phase stable and hence provides access to Doppler measurements using standard Doppler processing. Online DEFR evaluation with more than 20 frames per second is achieved using GPU based processing.

Bone grafting is a commonly performed surgical procedure to augment bone regeneration in a variety of orthopaedic and maxillofacial procedures, with autologous bone being considered as the "gold standard" bone-grafting material, as it combines all properties required in a bone-graft material: osteoinduction (bone morphogenetic proteins – BMPs - and other growth factors), osteogenesis (osteoprogenitor cells) and osteoconduction (scaffold). The problematic elements of bone regenerative materials are represented by their quality control methods, the adjustment of the initial bone regenerative material, the monitoring (noninvasive, if possible) during their osteoconduction and osteointegration period and biomedical evaluation of the new regenerated bone. One of the research directions was the interface investigation of the regenerative bone materials and their behavior at different time periods on the normal femoral rat bone. 12 rat femurs were used for this investigation. In each ones a 1 mm diameter hole were drilled and a bone grafting material was inserted in the artificial defect. The femurs were removed after one, three and six months. The defects repaired by bone grafting material were evaluated by optical coherence tomography working in Time Domain Mode at 1300 nm. Three dimensional reconstructions of the interfaces were generated. The validations of the results were evaluated by microCT. Synchrotron Radiation allows achieving high spatial resolution images to be generated with high signal-to-noise ratio. In addition, Synchrotron Radiation allows acquisition of volumes at different energies and volume subtraction to enhance contrast. Evaluation of the bone grafting material/bone interface with noninvasive methods such as optical coherence tomography could act as a valuable procedure that can be use in the future in the usual clinical techniques. The results were confirmed by microCT. Optical coherence tomography can be performed in vivo and can provide a qualitative and quantitative evaluation of the bone augmentation procedure.

Gynecologic applications of optical coherence tomography (OCT) are usually performed in combination with routine diagnostic procedures: laparoscopy and colposcopy. In combination with laparoscopy OCT is employed for inspection of fallopian tubes in cases of unrecognized infertility while in colposcopy it is used to identify cervix pathologies including cancer. In this paper we discuss methods for increasing diagnostic efficacy of OCT application in these procedures. For OCT-laparoscopy we demonstrate independent criteria for pathology recognition which allow to increase accuracy of diagnostics. For OCT-colposcopy we report on application of device for controlled compression allowing to sense the elasticity of the inspected cervix area and distinguish between neoplasia and inflammatory processes.

A Fourier domain optical coherence tomography system equipped with two spectrometers in balance detection is presented. The set-up was successfully used in reducing the autocorrelation terms and fixed pattern noise. It is concluded that balance detection performs better than single camera techniques, is more tolerant to movement, exhibits longer-term stability and can operate dynamically in real time. The cameras used here exhibit a saturation power larger than the power threshold where excess photon noise exceeds shot noise. We demonstrate that balance detection can reduce the noise in real time operation, in comparison with single camera configurations. However, simple deduction of an average spectrum in single camera configurations provides less noise than the balance detection.

Optical coherence elastography (OCE) provides deformation or material properties mapping of soft tissue, which is important for morphological and pathological studies of the tissue. An OCE technique is developed based on digital image correlation. System calibration and measurement error evaluation are performed. The displacement measurement of 0.6 μm to over 100 μm was obtained through a phantom experiment. The capability of this OCE technique for differentiation of stiffness was evaluated by imaging a two-components phantom. OCE imaging of an aneurysm sample shows promising results for characterization of composites of aneurismal wall in the future.

We discuss an elastography method based on comparison of correlation stability for different parts of sequentially obtained OCT images of the studied strained tissue. The basic idea is that in stiffer regions of a deformed tissue the OCT image is distorted to a smaller degree. Thus, cross-correlation maps obtained using a sliding correlation window for compensation of trivial translational motion of the image parts can reflect the spatial inhomogeneity of the tissue stiffness distribution. An important advantage of the proposed approach is that it allows one to avoid the stage of local strain reconstruction via error-sensitive procedures of numerical differentiation of experimentally determined displacements. Another advantage is that the correlation-stability approach requires that for deformed softer tissue regions, cross-correlation should already be strongly decreased, which intrinsically implies much wider strain range of the method operability compared to other approaches and is favorable for its free-hand implementation. Generally speaking, the approach can be implemented using the cross-correlation both image features reflecting morphological structure of the tissue and speckle-level cross-correlation. Examples of numerical simulations and experimental demonstrations using both phantom samples and in vivo obtained OCT images are presented.

Based on single-objective construction utilizing high brightness Ce³⁺:YAG single-clad crystal fiber light source, this Mirau-based full-field time-domain optical coherence tomography with circular polarization incident light represents deeper penetration in scattering medium. Using objective-changeable ability of home-designed Mirau objective, this system provides different applications, like biological tissue and single cells, by different spatial resolution with corresponding dynamics. High quality image relying on less ghost image and near common-path interference was demonstrated under this compact and power-stable system.

We propose a dynamic full-field optical coherence microscope imaging method using a scientific complementary metal oxide semiconductor camera in conjunction with a demodulation scheme based on Riesz transform and monogenic signals.

We demonstrate a direct Shack-Hartmann wavefront sensing method that allows depth-resolved measurements. A coherence-gate Shack-Hartmann wavefront sensor (CG/SH-WFS) is implemented by adding low coherence reflectometry gating to a SH-WFS. The depth resolution is determined by the coherence gate, much narrower than the depth range of the SH-WFS. Distinctive wavefronts are measured from five layers in a multiple-layer target. This paves the way towards depth-resolved closed-loop adaptive optics assisted microscopy and imaging of the retina.

We use a deformable mirror (DM) in an adaptive optics dual channel optical coherence tomography/en-face eye fundus setup to control focus on the sample by adding aberrations to the wavefront. A program was created to sweep the equivalent focus created by the DM. Using this device we are able to sweep the focus between two extremes. This system is also used to measure and monitor any existing aberrations in the system, caused by the optical elements or the target object.

A method for improvement of lateral resolution in Optical Coherence Tomography (OCT) is presented. The resolution improvement achieved with this method does not depend on the delivery optics. Moreover the depth of focus is not restricted. The method is based on the lateral oversampling of the image. The laterally oversampled signals are backscattered signals from shifted and overlapped resolution volumes. Signals from successive volumes are correlated due to the region shared by adjacent resolution volumes. By utilizing the cross correlation of signals from such overlapped volumes, resolution can be improved by various degrees depending on which pairs of signals are used. To maximize the resolution improvement for a given oversampling factor, signals from the farthest spaced and overlapped resolution volumes should be processed. The cost of the resolution refinement is the increasing statistical error because the magnitude of the cross-correlation function becomes smaller. 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 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. 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.

Optical coherence tomography (OCT) can be utilized for the spatially and temporally resolved visualization of alveolar tissue and its dynamics in rodent models, which allows the investigation of lung dynamics on the microscopic scale of single alveoli. The findings could provide experimental input data for numerical simulations of lung tissue mechanics and could support the development of protective ventilation strategies. Real four-dimensional OCT imaging permits the acquisition of several OCT stacks within one single ventilation cycle. Thus, the entire four-dimensional information is directly obtained. Compared to conventional virtual four-dimensional OCT imaging, where the image acquisition is extended over many ventilation cycles and is triggered on pressure levels, real four-dimensional OCT is less vulnerable against motion artifacts and non-reproducible movement of the lung tissue over subsequent ventilation cycles, which widely reduces image artifacts. However, OCT imaging of alveolar tissue is affected by refraction and total internal reflection at air-tissue interfaces. Thus, only the first alveolar layer beneath the pleura is visible. To circumvent this effect, total liquid ventilation can be carried out to match the refractive indices of lung tissue and the breathing medium, which improves the visibility of the alveolar structure, the image quality and the penetration depth and provides the real structure of the alveolar tissue. In this study, a combination of four-dimensional OCT imaging with total liquid ventilation allowed the visualization of the alveolar structure in rat lung tissue benefiting from the improved depth range beneath the pleura and from the high spatial and temporal resolution.

Optical coherence tomographic images of ascending thoracic human aortas from aneurysms exhibit disorders on the smooth muscle cell structure of the media layer of the aortic vessel as well as elastin degradation. Ex-vivo measurements of human samples provide results that correlate with pathologist diagnosis in aneurysmatic and control aortas. The observed disorders are studied as possible hallmarks for aneurysm diagnosis. To this end, the backscattering profile along the vessel thickness has been evaluated by fitting its decay against two different models, a third order polynomial fitting and an exponential fitting. The discontinuities present on the vessel wall on aneurysmatic aortas are slightly better identified with the exponential approach. Aneurysmatic aortic walls present uneven reflectivity decay when compared with healthy vessels. The fitting error has revealed as the most favorable indicator for aneurysm diagnosis as it provides a measure of how uniform is the decay along the vessel thickness.

In this paper we demonstrate applicability of intensity-based optical coherence tomography technique for noninvasive visualization of 3D retinal microcapillary network. The study was performed with ultra high resolution and high speed (180,000 Ascans/sec) spectral optical coherence tomography (SOCT). New scanning protocols and data processing algorithms have been introduced to visualize microcapillary network. Moreover, results obtained in the eyes of healthy volunteers and patients with eye diseases were compared with fluorescein angiography. Presented report shows that SOCT is well suited for visualization of 3D retinal capillary network in the healthy and pathologic eyes as well. Obtained results demonstrate high correspondence with fluorescein angiography, without using any contrast agents. Our data suggest that intensity-based SOCT has potential in the early diagnosis of the retinal vascular diseases.

For the study of disease mechanisms and the development of novel therapeutic strategies for retinal pathologies in human, rodent models play an important role. Nowadays, optical coherence tomography (OCT) allows three-dimensional investigation of retinal events over time. However, a detailed analysis of how different retinal degenerations are reflected in OCT images is still lacking in the biomedical field. Therefore, we use OCT to visualize retinal degeneration in specific mouse models in order to study disease progression in vivo and improve image interpretation of this noninvasive modality. We use a self-developed spectral domain OCT system for simultaneous dual-band imaging in the 0.8 μm- and 1.3 μm-wavelength range – the two most common spectral bands in biomedical OCT. A fiber-coupled ophthalmic scanning unit allows flexible imaging of the eye with a high axial resolution of 3 - 4 μm in tissue. Four different mouse models consisting of one genetic (rhodopsin-deficient and three induced retinal degenerations (sodium iodate-induced damage, light-induced photoreceptor damage and Kainate neurotoxin damage) were investigated. OCT imaging was performed daily or weekly, depending on the specific degeneration model, over a time period of up to 9 weeks. Individual retinal layers that were affected by the specific degeneration could successfully be identified and monitored over the observation time period. Therefore, longitudinal OCT studies deliver reliable information about the retinal microstructure and the time course of retinal degeneration processes in vivo.

Retinal imaging with optical coherence tomography (OCT) has rapidly advanced in ophthalmic applications with the broad availability of Fourier domain (FD) technology in commercial systems. The high sensitivity afforded by FD-OCT has enabled imaging of the choroid, a layer of blood vessels serving the outer retina. Improved visualization of the choroid and the choroid-sclera boundary has been investigated using techniques such as enhanced depth imaging (EDI), and also with OCT systems operating in the 1060-nm wavelength range. We report on a comparison of imaging the macular choroid with commercial and prototype OCT systems, and present automated 3D segmentation of the choroid-scleral layer using a graph cut algorithm. The thickness of the choroid is an important measurement to investigate for possible correlation with severity, or possibly early diagnosis, of diseases such as age-related macular degeneration.

The unbiased complex algorithm for flow velocity measurements with enhanced joint spectral and time domain OCT (enhSTdOCT) is verified statistically and experimentally to find the optimal parameters for maximal velocity noise reduction.

We propose a new numerical method for speckle reduction in Fourier domain OCT based on incoherent averaging of fractional Fourier domains of a single A-scan. Fractional Fourier transforms represent projections in the time-frequency space and thus, this method simultaneously compensates for group velocity dispersion.

Recent studies in animal models provided proof-of-principle evidence for cell transplantation as a potential future therapeutic approach for retinal pathologies in humans such as Retinitis pigmentosa or age-related macular degeneration. In this case, donor cells are injected into the eye in order to protect or replace degenerating photoreceptors or retinal pigment epithelium. However, currently there is no three-dimensional imaging technique available that allows tracking of cell migration and integration into the host tissue under in vivo conditions. Therefore, we investigate about magnetomotive optical coherence tomography (OCT) of substances labeled with iron oxide nanoparticles as a potential method for noninvasive, three-dimensional cell tracking in the retina. We use a self-developed spectral domain OCT system for high-resolution imaging in the 800 nm-wavelength region. A suitable AC magnetic field for magnetomotive imaging was generated using two different setups, which consist of an electrically driven solenoid in combination with a permanent magnet, and a mechanically driven all-permanent magnet configuration. In the sample region the maximum magnetic flux density was 100 mT for both setups, with a field gradient of 9 T/m and 13 T/m for the solenoid and the allpermanent magnet setup, respectively. Magnetomotive OCT imaging was performed in elastic tissue phantoms and single cells labeled with iron oxide nanoparticles. Particle-induced sub-resolution movement of the elastic samples and the single cells could successfully be detected and visualized by means of phase-resolved Doppler OCT analysis. Therefore, this method is a potential technique to enhance image contrast of specific cells in OCT.

We present detection of water and lipid at a micron scale by evaluating their unique dispersion properties. Using a triband swept source configuration, we measure β₂ and β₃ and show how to identify the two materials at a sample thickness of 40μm and 90μm, respectively. This report reveals exciting new prospects for label free differentiation and segmentation using optical coherence tomography.

We demonstrated intravascular OCT imaging with frame rate up to 3.2 kHz (192,000 rpm scanning). This was achieved by using a custom-built catheter in which the circumferential scanning was actuated by a 1.0 mm diameter synchronous motor. The OCT system was based on a Fourier Domain Mode Locked laser operating at an A-line rate of 1.6 MHz. The diameter of the catheter was 1.1 mm at the tip. Ex vivo images of human coronary artery (~78.4 mm length) were acquired at a pullback speed of 100 mm/s. True 3D volumetric imaging of the entire artery, with adequate sampling in all dimensions, was performed in < 1 second acquisition time.

Keratoconus (KC) is a progressive degenerative corneal disease that can lead to a strong deformation of the cornea and loss of clarity, causing distorted or blurred vision. Surgical treatment for severe cases requires precise evaluation of the corneal curvature, thickness, layer structure, and clarity. Current clinical instruments for assessing the corneal shape cannot resolve the internal structure, and high-resolution microscopy techniques are limited to a small field of view. We have implemented a swept-source OCT (SS-OCT) system that enables high-speed imaging (100 kA-scans/s) of the entire cornea and provides ~5.1μm axial resolution in corneal tissue. With an imaging range of 5.6 mm (in air), we can cover the full length from the cornea’s apex to the anterior surface of the lens. We have acquired volumetric corneal images from human subjects with different stages of KC and from subjects who underwent surgery or cross-linking therapy. We developed an automatic algorithm for segmenting the outer and inner surfaces of the cornea in the images which will enable precise measurement of the corneal curvature and thickness. This makes SS-OCT an ideal instrument for comprehensive examination of keratoconic corneas.

This paper presents the successful creation of new phantom for optical coherence tomography (OCT) aimed on perfusion simulation. The phantom is created from syringe pump and polypropylene hollow fiber with porous walls embeded in the glass capillary to provide small outer environment. Its function was tested by gold nanorods as a flowing medium and imaged by commercial swept-source OCT system. Results showed that the fiber is permeable for used gold nanorods which are frequently declared as possible contrast agents for OCT and this permeability can be displayed by OCT.

In food and feed production an emerging issue is the use of nanoparticles as additives to control specific properties of the products. In this context, one focus in food chemistry is the development and evaluation of measurement techniques, which could allow the detection and quantification of nanoparticles in food products. For this purpose, special noninvasive and non-destructive reference methods are required, which allow subsequent analysis with other measurement techniques. Additionally, non-invasive and fast imaging techniques are potentially appropriate for applications in the food production. Optical coherence tomography is sensitive to the backscattering of particles and is regarded as a promising technique due to its spatial resolution, the high sensitivity and the high-speed capability. In this study, the ability of OCT as a potential reference method for the detection of nanoparticles in thin-film polymer samples was investigated by determining the correlation between nanoparticle concentration and signal intensity.

Optical coherence tomography (OCT) imaging has been widely employed in assessing cardiovascular disease. Atherosclerosis is one of the major cause cardio vascular diseases. However visual detection of atherosclerotic plaque from OCT images is often limited and further complicated by high frame rates. We developed a texture based segmentation method to automatically detect plaque and non plaque regions from OCT images. To verify our results we compared them to photographs of the vascular tissue with atherosclerotic plaque that we used to generate the OCT images. Our results show a close match with photographs of vascular tissue with atherosclerotic plaque. Our texture based segmentation method for plaque detection could be potentially used in clinical cardiovascular OCT imaging for plaque detection.