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A less-complex 2.8-mm beam diameter spectral domain optical coherence tomography system with an adaptive optics module presented. In this system a Shack-Hartmann wavefront sensor used for aberration sensing and the Deformable mirror used for aberration correction. We demonstrated the diffraction-limited resolution performance of this system on model retina. On the model, measured speckle size with present system is 2.2 times smaller than a 1.2-mm beam diameter OCT system. Further, on the model eye SNR gain of 6.7 dB was quantified with the present system over a 1.2-mm beam diameter OCT system. Relatively small size of 25 cm by 50 cm, less complexity, large field of view of the present system as compared to the conventional AO-OCT systems, would make it suitable for ophthalmic clinical applications.

We present an adaptive-optics optical coherence tomography (AO-OCT) system with 3.4-mm beam diameter. A deformable mirror is used for the correction of two radial Zernike orders (defocus, vertical and oblique astigmatism). The aberrations are corrected sequentially with a Shack-Hartmann wave-front sensor and the deformable mirror. This system fills a gap between a standard clinical 1.2-mm beam diameter OCT system and a 6-mm beam diameter AO-OCT system. We also present 8° by 8° en face OCT images from a patient with macular degeneration. This system has a 25 cm by 50 cm footprint, which makes it considerably smaller to conventional 6-mm beam diameter AO-OCT system. Because of its larger field of view and smaller size, it is likely to be useful in the ophthalmic clinics for high-resolution imaging of the human eye retina.

A spectrometer design with a multiple line line-scan camera and beam displacer is presented for ultra-high resolution optical coherence tomography measurements of the human retina at 840 nm. The beam displacer offsets the two orthogonal polarization states on the same line-scan camera, which reduces k-space mapping complexity, as data in both polarization channels can be mapped with the same procedure. Its coherence length is 2.8 μm in tissue (n = 1.38). Birefringence values of 1°/μm and higher were found in a circle with a radius of 2.5° eccentricity centered on the fovea, and in the raphe, pointing at a higher packing density of microtubules and a lower concentration of glia. Birefringence measurements may be more helpful in the modeling of individual structure-function maps than thickness measurements, as they are not affected by glial content.

We developed an optical coherence tomography (OCT) prototype with a sample arm that uses a 3.4 mm beam, which is considerably larger than the 1.2 to 1.5 mm beam that is used in commercialized OCT systems. The system is equipped with adaptive optics (AO), and to distinguish it from traditional AO-OCT systems with a larger 6 mm beam we have coined this concept AO-assisted OCT. Compared to commercialized OCT systems, the 3.4 mm aperture combined with AO improves light collection efficiency and imaging lateral resolution. In this paper, the performance of the AOa-OCT system was compared to a standard OCT system and demonstrated for imaging of age-related macular degeneration (AMD). Measurements were performed on the retinas of three human volunteers with healthy eyes and on one eye of a patient diagnosed with AMD. The AO-assisted OCT system imaged retinal structures of healthy human eyes and a patient eye affected by AMD with higher lateral resolution and a 9° by 9° field of view. This combination of a large isoplanatic patch and high lateral resolution can be expected to fill a gap between standard OCT with a 1.2 mm beam and conventional AO-OCT with a 6 mm beam and a 1.5° by 1.5° isoplanatic patch.

We present the use of sub-micron resolution optical coherence tomography (OCT) in quality inspection for printed electronics. The device used in the study is based on a supercontinuum light source, Michelson interferometer and high-speed spectrometer. The spectrometer in the presented spectral-domain optical coherence tomography setup (SD-OCT) is centered at 600 nm and covers a 400 nm wide spectral region ranging from 400 nm to 800 nm. Spectra were acquired at a continuous rate of 140,000 per second. The full width at half maximum of the point spread function obtained from a Parylene C sample was 0:98 m. In addition to Parylene C layers, the applicability of sub-micron SD-OCT in printed electronics was studied using PET and epoxy covered solar cell, a printed RFID antenna and a screen-printed battery electrode. A commercial SD-OCT system was used for reference measurements.

Wide field of view (FOV) retinal imaging with high resolution has been demonstrated for quantitative analysis of retinal microstructures. An adaptive optics scanning laser ophthalmoscope (AO-SLO) that was built in our laboratory was improved by a customized scanning protocol for scanning wide region. A post-processing program was developed for generating wide FOV retinal images. The high resolution retinal image with 1.7 degree by 3.0 degree FOV were obtained.

The effect of using collimator lenses with different focal lengths on the performance of a spectral-domain adaptive optics optical coherence tomography (AO-OCT) system has been studied. In vivo OCT scans of a healthy human retina were taken separately with different collimator lenses. Although shorter focal length lenses provide a smaller beam diameter at the pupil of the eye, and therefore a larger diffraction-limited spot size, on the return path the shorter focal length collimators demonstrate a better performance focusing the sinc-function-like intensity distribution returning from the eye on the fiber tip. The results might have applications in the OCT imaging of challenging cases.

Ultrahigh speed line scan detectors based on CMOS technology have been recently demonstrated in ultrahigh resolution spectral-domain optical coherence tomography (UHR-SD-OCT) for retinal imaging. While successful, fundamental tradeoffs exist been image acquisition time, image sampling density, and sensitivity, all of which impact the extent of motion artifacts, visualization of fine spatial detail, and detection of faint reflections. Here we investigate these tradeoffs for imaging retinal nerve fiber bundles (RNFBs) using UHR-SD-OCT with adaptive optics (AO). Volume scans of 3°x3° and 1.5°x1.5° were acquired at retinal locations of 3° nasal and 6° superior to the fovea on a healthy subject. Dynamic AO compensation across a 6 mm pupil provided near-diffraction-limited performance. The acquisition rates were 22.5k lines/s and 125k lines/s with A-lines spaced at 0.9 μm and 1.8 μm and B-scans at 1.8 μm and 9 μm. Focus was optimized for visualizing the retinal nerve fiber bundles (RNFBs). En face projection and crosssectional views of the RNFBs were extracted from the volumes and compared to images acquired with established conventional CCD-based line-scan camera. The projection view was found highly sensitive to eye motion artifacts, yet could only be partially compensated with coarser sampling, since fine sampling was necessary to observe the microscopic features in the RNFBs. For the cross-sectional view, speckle noise rather than eye motion artifacts limited bundle clarity. The highest B-scan density (1.8 μm spacing) coupled with B-scan averaging proved the best combination. Regardless of view, the higher line rate provided better RNFB clarity.

The combination of adaptive optics (AO) and optical coherence tomography (OCT) has been successfully applied to in vivo retinal imaging, motivated by the potential of unprecedented 3D resolution. The eye, however, not only suffers from monochromatic aberrations, which are corrected by AO, but also substantial chromatic aberrations, which are not. To correct chromatic aberrations, achromatizing lenses have been recently employed in ultrahigh resolution AO-OCT instruments. These lenses, like their earlier predecessors for vision improvement, effectively correct the eye's longitudinal chromatic aberration (LCA), but make no attempt at the complementary transverse chromatic aberration (TCA). This raises an important concern as to the degrading impact of TCA on the 3D resolution of AO-OCT and OCT retina cameras. To address this, we undertook a theoretical analysis of TCA for high-resolution retinal imaging. The theoretical analysis included the two primary contributors of TCA for retinal imaging: (1) errors in the lateral positioning of the eye and (2) off-axis imaging. The analysis predicted the extent to which TCA impacts retinal imaging and the conditions under which it can be held at acceptable levels for AO-OCT and OCT. Several near-infrared bands were chosen that correspond to common OCT light sources.

Ultra-high isotropic resolution imaging of retinal structures was made possible with an adaptive optics system using dual deformable mirrors and a Fourier-domain optical coherence tomography (Fd-OCT) system with correction for longitudinal chromatic aberration. This system was used to image microscopic retinal structures of healthy as well as diseased retinas in vivo. The improved resolution and contrast enhanced visualization of morphological structures in the retina can be clearly seen. The benefits of this instrument are apparent from comparison of new images with those acquired using a previous generation AO-OCT instrument. Big change in the appearance of speckle field (reduction in speckle size) can be observed as well. Additionally, further improvements in volumetric data acquisition and image representation will be discussed. This includes creation of large Field of View (FOV) AO-OCT volume from multiple sub-volumes and its visualization. Also techniques and results of reducing speckle contrast by averaging multiple B-scans will be presented.

Adaptive optics (AO) coupled with ultra-fast spectral-domain optical coherence tomography (SD-OCT) has achieved the necessary 3D resolution, sensitivity, and speed for imaging the microscopic retina at the cellular level. While this technology has been rigorously applied to evaluating the 3D morphology of cone photoreceptors, similar detailed studies of cell-sized structures in the inner retina have yet to be undertaken. In this paper, we improve the technical performance of our AO ultrafast SD-OCT and investigate its use for imaging the microscopic inner retina, in particular the nerve fiber layer (NFL) and retinal capillary network. To maximize lateral resolution within the inner retina, focus was controlled with a high stroke, 37-actuator bimorph mirror (AOptix) that also served as the wavefront corrector of the AO. The AO system operated at a closed-loop rate of 25 Hz. The SD-OCT sub-system consisted of a superluminescent diode (l= 842 nm, Dl= 50 nm) and a 512 pixel line scan charge-coupled device (CCD) that acquired 72,000 A-scans/sec. Three different B-scan lengths (36, 60, and 120 A-scans/B-scan), which correspond to B-scan exposure durations of 0.5, 0.83, and 1.67 ms, were evaluated to determine the maximum B-scan length that could be tolerated without noticeable loss in image quality due to eye motion in the well fixated eye. Additional technical improvements included sub-pixel registration to remove instrument error and axial registration of the volume images. Small volume images were acquired at 2 and 7 degrees retinal eccentricity with focus systematically shifted through the retina. Small capillaries, some approaching the smallest in the human eye, were readily detected with AO SD-OCT. Appearance of the nerve fiber layer varied noticeably with depth. The most inner portion (presumably the inner limiting membrane) appeared as a thin irregular surface with little characteristic speckle noise. Within the NFL, complex striation patterns (presumably NFL bundles) were observed throughout the entire thickness with pattern density highest in the inner portion (~15 mm) and large corrugations (~35 mm) at the interface with the ganglion cell layer below. Speckle noise was significant throughout the NFL.

We evaluate a novel non-invasive technique for observing fast physiological processes, such as phototransduction, in single photoreceptor cells in the living human eye. The method takes advantage of the interference of multiple reflections within the outer segments of cones. This self-interference phenomenon is highly sensitive to phase changes such as those caused by variations in refractive index and scatter within the photoreceptor cell. A high-speed flood-illumination retina camera equipped with adaptive optics (AO) is used to observe this interference pattern, and to monitor the changes in those patterns in response to visible stimuli. AO and high frame rates are necessary for resolving individual cones and their fast temporal dynamics, respectively. Preliminary results suggest that a frame rate of 192 fps, corresponding to a full field 1024x512 pixel rate of 100 MHz, may be sufficient for observing these early stages of phototransduction. This pixel rate is at least 80 and 10 times faster than current flood-illumination and SLO pixel rates, respectively. To our knowledge this is the first demonstration of in vivo single photoreceptor functional imaging, and the first demonstration of in vivo optical detection of phototransduction.

Ultrahigh axial resolution in adaptive optics - optical coherence tomography (AO-OCT) is fundamentally limited by the intrinsic chromatic aberrations of the human eye. Variation in refractive index of the ocular media with wavelength causes the spectral content of broadband light sources to focus at different depths in the retina for light entering the eye and at the imaging detector for light exiting. This effect has not been previously reported for ultrahigh-resolution OCT (without AO) likely because the effect is masked by the relatively long depth of focus dictated by the small pupils used in these systems. With AO, the pupil size is much larger and depth of focus substantially narrower. As such the chromatic aberrations of the eye can counteract the lateral resolution benefit of AO when used with broadband light sources. To more fully tap the potential of AO-OCT, compensation of the eye's chromatic and monochromatic aberrations must occur concurrently. One solution is to insert an achromatizing lens in front of the eye whose chromatic aberrations are equal but opposite in sign to that of the eye. In this paper we evaluate the efficacy of a novel design that uses a custom achromatizing lens placed near the fiber collimating optic. AO-OCT images are acquired on several subjects with and without the achromatizing lens and in combination with two light sources of different spectral width. The combination of the achromatizing lens and broadband light source yielded the sharpest images of the retina and the smallest speckle.

Two deformable mirrors (2DM) were used in an adaptive optics - optical coherence tomography (AO-OCT) system to image in vivo microscopic retinal structures of healthy and diseased retinas. As a result, multiple morphological structures not previously seen in vivo have been visualized. Among those presented are three-dimensional representations of the fovea and optic nerve head (ONH), revealing cellular structures and micro-vasculature. Drusen in macular degeneration and photoreceptor dystrophies are also presented. Different methods for displaying volumetric AO-OCT data to facilitate visualization of certain morphological details are compared.

Spectral-Domain Optical Coherence Tomography (SDOCT) allows for in-vivo video-rate investigation of biomedical tissue depth structure intended for non-invasive optical diagnostics. It has been suggested that OCT can be used for di-agnosis of glaucoma by measuring the thickness of the Retinal Nerve Fiber Layer (RNLF). We present an automated method for determining the RNFL thickness from a 3-D dataset based on edge detection using a deformable spline algo-rithm. The RNFL thickness map is combined with an integrated reflectance map and retinal cross-sectional images to provide the ophthalmologist with a familiar image for interpreting the OCT data. The video-rate capabilities of our SDOCT system allow for mapping the true retinal topography since motion artifacts are significantly reduced as com-pared to slower time-domain systems. Combined with Doppler Velocimetry, SDOCT also provides information on retinal blood flow dynamics. We analyzed the pulsatile nature of the bidirectional flow dynamics in an artery-vein pair for a healthy volunteer at different locations and for different blood vessel diameters. The Doppler phase shift is determined as the phase difference at the same point of adjacent depth profiles, and is integrated over the area delimited by two circles corresponding to the blood vessels location. Its temporal evolution clearly shows the blood flow pulsatile nature, the cardiac cycle, in both artery and vein. The artery is identified as having a stronger variation of the integrated phase shift. We observe that artery pulsation is always easily detectable, while vein pulsation seems to depend on the veins diameter.

Spectral-Domain Optical Coherence Tomography (SDOCT) allows for in-vivo video-rate investigation of biomedical tissue depth structure with the purpose of non-invasive optical diagnostics. In ophthalmic applications, it has been suggested that Optical Coherence Tomography (OCT) can be used for diagnosis of glaucoma by measuring the thickness of the Retinal Nerve Fiber Layer (RNLF). We present here an automated method for determining the RNFL thickness map from a 3-D dataset. Boundary detection has been studied since the early days of computer vision and image processing, and different approaches have been proposed. The procedure described here is based on edge detection using a deformable spline (snake) algorithm. As the snake seeks to minimize its overall energy, its shape will converge on the image contour, the boundaries of the nerve fiber layer. In general, the snake is not allowed to travel too much, and therefore, proper initialization is required. The snake parameters, elasticity, rigidity, viscosity, and external force weight are set to allow the snake to follow the boundary for a large number of retinal topographies. The RNFL thickness map is combined with an integrated reflectance map of the retina and retinal cross-sectional images (OCT movie), to provide the ophthalmologist with a familiar image for interpreting the OCT data. The video-rate capabilities of our SDOCT system allow for mapping the true retinal topography since the motion artifacts are significantly reduced as compared to slower time-domain systems.

Spectral-Domain Polarization-Sensitive Optical Coherence Tomography (SD-PS-OCT) is a technique developed to measure the thickness and birefringence of the nerve fiber layer in vivo as a tool for the early diagnosis of glaucoma. A clinical SD-PS-OCT system was developed and scans were made around the optic nerve head (ONH) using ten concentric circles of increasing diameter. One healthy volunteer was imaged. Retinal nerve fiber layer thickness and birefringence information was extracted from the data. Polarization-sensitive OCT images were acquired at video rate (29 frames per second (fps), 1000 A-lines / frame) and at 7 fps (1000 A-lines / frame). The last setting improved the signal to noise ratio by approximately 6 dB. Birefringence measurements on the healthy volunteer gave similar results as earlier reported values that were obtained with a time-domain setup. The measurement time was reduced from more than a minute to less than a second.

Microfluidic devices are becoming increasingly popular for many applications, enabling biological and chemical reactions to be performed with nano- and picoliter sample volumes. Accurate measurement and monitoring of fluid flow behavior in the small channels of microfluidic systems is important for evaluating the performance of existing devices, and in the modeling and design of new microfluidic networks. We present here the results of experiments using spectral-domain optical Doppler tomography (SD-ODT) to measure fluid flow in single-layer microfluidic devices. The principles behind flow imaging with SD-ODT are reviewed, a method for velocity calibration is described, and cross-sectional and en-face images of fluid velocity in microfluidic channels are presented.

Changes in retinal nerve fiber layer thickness and birefringence may both precede clinically detectable glaucomatous vision loss. Early detection of retinal nerve fiber layer changes may enable treatment to prevent permanent loss of vision. Polarization sensitive optical coherence tomography (PS-OCT) can provide objective information on retinal nerve fiber layer thickness and birefringence. PS-OCT scans around the optic nerve head (ONH) of two healthy young volunteers were made using 10 concentric circles of increasing radius. Both the mean retinal nerve fiber layer thickness and mean retinal nerve fiber birefringence for each of 48 sectors on a circle were determined with data analysis. Birefringence of healthy RNFL is constant as a function of scan radius but varies as a function of position around the ONH, with higher values occurring superior and inferior to the ONH. Measured double pass phase retardation per unit depth values around the ONH range between 0.10 and 0.35°/μm, equivalent to birefringence values of 1.2•10 -4 and 4.1•10 -4 respectively, measured at a wavelength of 840 nm. Consequently, conversion of phase retardation measurements (as obtained with scanning laser polarimetry) to RNFL thickness measurements, assuming a constant birefringence value, will yield thickness values that are incorrect.

Osteoarthritis is a prevalent medical condition that presents a diagnostic and therapeutic challenge to physicians today because of the inability to assess the integrity of the articular cartilage early in the disease. Polarization sensitive optical coherence tomography (PS-OCT) is a high resolution, non-contact imaging modality that provides cross-sectional images with additional information regarding the integrity of the collagen matrix. Using PS-OCT to image provides information regarding thickness of the articular cartilage and gives an index of biochemical changes based on alterations in optical properties (i.e. birefringence) of the tissue. We demonstrate initial experiments performed on specimens collected following total knee replacement surgery. Articular cartilage was imaged using a 1310 nm PS-OCT system where both intensity and phase images were acquired. PS-OCT images were compared with histology, and the changes in tissue optical properties were characterized. Analysis of the intensity images demonstrates differences between healthy and diseased cartilage surface and thickness. Phase maps of the tissue demonstrated distinct differences between healthy and diseased tissue. PS-OCT was able to image a gradual loss of birefringence as the tissue became more diseased. In this way, determining the rate of change of the phase provides a quantitative measure of pathology. Thus, imaging and evaluation of osteoarthritis using PS-OCT can be a useful means of quantitative assessment of the disease.

We have developed a scanning fiber-optic probe compatible with high-speed polarization-sensitive OCT imaging. The effect of sample arm fiber motion on the polarization state of light incident on a sample is demonstrated by the evolution of incident Stokes vectors during the course of acquiring a single image. By referencing the polarization state of light backscattered from within a sample to the measured surface state, effects of motion-induced birefringence can be isolated. Conventional and polarization-sensitive images of human tissues are presented.

A vector-based analysis is presented for polarization-sensitive optical coherence tomography (PS-OCT) that yields diattenuation, birefringence, and relative optic axis orientation. Experimental confirmation is demonstrated by comparing the calculated diattenuation of chicken tendon and muscle to independent measurement. The diattenuation of the retinal nerve fiber layer of the superior region of a human retina is also calculated.

Properties and applications of Spectral Domain OCT have recently been explored, demonstrating improved signal to noise ratios and the potential for high-speed acquisition. In this presentation, we demonstrate in-vivo measurements of a human retina using a Spectral Domain system with acquisition rates of 10,000, 20,000, and 30,000 A-lines per second and 580 μW incident on the eye. Images consisting of 1000 depth profiles and ranging in width from 4 to 12 mm were acquired. The dynamic ranges within an image at 104, 2x104, and 3x104 lps were 40 dB, 39 dB and 28 dB respectively. These values are comparable to that of time domain Optical Coherence tomography yet are achieved at acquisition rates over 50 times faster, demonstrating video-rate OCT imaging at up to 30 frames/sec with 1000 A-lines per image. This work is more thoroughly described in the following publications: 1) B. R. White, M. C. Pierce, N. Nassif, B. Cense, B. H. Park, G. J. Tearney, B. E. Bouma, T. C. Chen,J. F. de Boer, "In vivo dynamic human retinal blood flow imaging using ultra-high speed spectral domain optical doppler tomography," Opt. Express 11, 3490-3497 (2003). 2) N. A. Nassif, B. Cense, B. H. Park, M. C. Pierce, S. H. Yun, B. E. Bouma, G. J. Tearney, T. C. Chen, and J. F. de Boer, "In vivo high-resolution video-rate spectral-domain optical coherence tomography of the human retina and optic nerve," Opt. Express 12, 367-376 (2004). 3) N. Nassif, B. Cense, B. H. Park, S. H. Yun, T. C. Chen, B. E. Bouma, G. J. Tearney,J. F. de Boer, "In-vivo human retinal imaging by ultra high-speed spectral domain optical coherence tomography," Optics Letters 29, 480-482 (2004).

A novel method for reducing the appearance of speckle within a single image acquisition in optical coherence tomography is presented. Local variations in the optical path length of beamlets within the beam diameter are introduced by vibrating a thin water film placed in a collimated section of the sample arm beam path. Consequent averaging of small numbers of adjacent depth scans results in a reduced appearance of speckle with no change in the axial point spread function. Reduced speckle images of a layered agar sample and thin reflective surfaces are shown.

We present in vivo depth-resolved birefringence measurements of the human retinal nerve fiber layer (RNFL) by use of polarization-sensitive optical coherence tomography (PS-OCT). Because glaucoma causes nerve fiber layer damage, which may cause loss of retinal birefringence, PS-OCT is a potentially useful technique for the early detection of glaucoma. We built a fiber-based PS-OCT setup that produces real-time images of the human retina in vivo, co-registered with video images of the location of PS-OCT scans on the retina. Preliminary measurements of a healthy volunteer showed that the double-pass phase retardation per unit depth of the RNFL varies with location with values in between 0.18 and 0.37°/μm. A trend in the preliminary measurements shows that thicker nerve fiber layer tissue is more birefringent than thin nerve fiber layer tissue.

We demonstrate real-time acquisition, processing, and display of tissue structure, birefringence, and blood flow in a multi-functional optical coherence tomography (MF-OCT) system. This is accomplished by efficient data processing of the phase-resolved inteference patterns without dedicated hardware or extensive modification to the high-speed fiber-based OCT system. The system acquires images of 2048 depth scans per second, covering an area of 5 mm in width x 1.2 mm in depth with real-time display updating images in a rolling manner 32 times each second.

Recent extensions to conventional OCT imaging include polarization-sensitive optical coherence tomography (PS-OCT) and optical Doppler tomography (ODT), enabling further information to be acquired in addition to tissue structure. We demonstrate here that structure, birefringence and blood flow measurements may be carried out simultaneously, using both techniques of polarization-sensitive OT and phase- resolved ODT. Images of in vivo human skin acquired with a high-speed fiber-based system are presented. The concurrent processing of data is performed with no penalty to signal- to-noise ratio, and without degradation of either the individual structure, birefringence or flow images.

Glaucoma causes irreversible damage to nerves in the retinal nerve fiber layer. A technique that could measure both the condition and thickness of the retinal nerve fiber layer (RNFL) would be very useful for the early detection and treatment of glaucoma. Polarization Sensitive Optical Coherence Tomography (PS-OCT) is a modality that measures the depth resolved optical birefringence of biological tissue. Since damage to the nerve fiber layer could decrease its birefringence, PS-OCT has the potential to enhance specificity in determining RNFL thickness and integrity in OCT images. In order to measure the RNFL birefringence on humans in vivo, a fiber-based PS-OCT set-up was built with which quasi real time images of the human retina were made. Preliminary measurements on a healthy retina show that the birefringence of the RNFL around the optic nerve head was equal to 34+/- 3 degree(s)/100 micrometers . In conclusion, to our knowledge, we present the first depth resolved birefringence measurements of the human RNFL in vivo.