This PDF file contains the front matter associated with SPIE Proceedings Volume 9312, including the Title Page, Copyright information, Table of Contents, Invited Panel Discussion, and Conference Committee listing.

Full volumetric high speed OCT imaging of the retina with multiple settings varying in volume size and volume rate is presented. The volume size ranges from 255x255 A-scans to 160x40 A-scans with 450 samples per depth scan. The volume rates vary between 20.8 V/s for the largest volumes to 195.2 V/s for the smallest. The system is based on a 1060nm Fourier domain mode locked (FDML) laser with 1.6MHz line rate. Scanning along the fast axis is performed with a 2.7 kHz or 4.3 kHz resonant scanner operated in bidirectional scanning mode, while a standard galvo scanner is used for the slow axis. The performance is analyzed with respect to various potential applications, like intraoperative OCT.

MHz OCT allows mitigating undesired influence of motion artifacts during retinal assessment, but comes in state-of-the-art point scanning OCT at the price of increased system complexity. By changing the paradigm from scanning to parallel OCT for in vivo retinal imaging the three-dimensional (3D) acquisition time is reduced without a trade-off between speed, sensitivity and technological requirements. Furthermore, the intrinsic phase stability allows for applying digital refocusing methods increasing the in-focus imaging depth range. Line field parallel interferometric imaging (LPSI) is utilizing a commercially available swept source, a single-axis galvo-scanner and a line scan camera for recording 3D data with up to 1MHz A-scan rate. Besides line-focus illumination and parallel detection, we mitigate the necessity for high-speed sensor and laser technology by holographic full-range imaging, which allows for increasing the imaging speed by low sampling of the optical spectrum. High B-scan rates up to 1kHz further allow for implementation of lable-free optical angiography in 3D by calculating the inter B-scan speckle variance. We achieve a detection sensitivity of 93.5 (96.5) dB at an equivalent A-scan rate of 1 (0.6) MHz and present 3D in vivo retinal structural and functional imaging utilizing digital refocusing. Our results demonstrate for the first time competitive imaging sensitivity, resolution and speed with a parallel OCT modality. LPSI is in fact currently the fastest OCT device applied to retinal imaging and operating at a central wavelength window around 800 nm with a detection sensitivity of higher than 93.5 dB.

Ophthalmic surgical maneuvers are currently limited by the ability of surgeons to visualize and manipulate semitransparent tissue layers as thin as tens of microns. We describe several iterative advances in iOCT technology, including a novel iOCT system, real-time heads-up display (HUD) feedback, visualization of intraoperative maneuvers, and OCT-compatible surgical instrumentation. Simulated surgical maneuvers were performed on freshly enucleated porcine eyes. Subretinal space cannulation with injection was performed and imaged using spatial compounding. The optical properties of semitransparent materials were quantified to identify OCT-compatible substrates, and surgical instrument prototypes were machined, including corneal, surgical picks, and retinal forceps.

Accurate metrology of the anterior chamber of the eye is useful for a number of diagnostic and clinical applications. In particular, accurate corneal topography and corneal thickness data is desirable for fitting contact lenses, screening for diseases and monitoring corneal changes. Anterior OCT systems can be used to measure anterior chamber surfaces, however accurate curvature measurements for single point scanning systems are known to be very sensitive to patient movement. To overcome this problem we have developed a parallel 3D spectral metrology system that captures simultaneous A-scans on a 2D lateral grid. This approach enables estimates of the elevation and curvature of anterior and posterior corneal surfaces that are robust to sample movement. Furthermore, multiple simultaneous surface measurements greatly improve the ability to register consecutive frames and enable aggregate measurements over a finer lateral grid. A key element of our approach has been to exploit standard low cost optical components including lenslet arrays and a 2D sensor to provide a path towards low cost implementation. We demonstrate first prototypes based on 6 Mpixel sensor using a 250 μm pitch lenslet array with 300 sample beams to achieve an RMS elevation accuracy of 1μm with 95 dB sensitivity and a 7.0 mm range. Initial tests on Porcine eyes, model eyes and calibration spheres demonstrate the validity of the concept. With the next iteration of designs we expect to be able to achieve over 1000 simultaneous A-scans in excess of 75 frames per second.

A new high-resolution polarization sensitive optical coherence tomography system was developed for imaging rodent retina. Various light-tissue interactions such as birefringence and depolarization can change the polarization state of light. In the eye, there are several tissues that have these properties, for example retinal pigment epithelium (depolarization) and sclera (birefringence). These layers play key roles in diseases like age-related macular degeneration or glaucoma. Animal models are an important component for understanding disease pathogenesis. The gold standard for the evaluation of preclinical experiments is histology, which is an invasive and terminal procedure. Since OCT is non-invasive, it has the potential to be an alternative to histology with the benefit of long-term study of the disease progression in the same animal. In this study, a superluminescent diode with spectrum width 100 nm and mean wavelength 840 nm is used as a light source in order to enable high axial resolution. Spectrometers are custom built to enable high imaging speed that allows acquiring 3D data sets with 1024x200x1536 voxels in 3.44 s. From the acquired data, images displaying phase retardation induced by birefringence and orientation of birefringent axis were calculated. In first measurements, we were able to identify the RPE-choroid complex (depolarization effect) and the sclera (strong birefringence) in the retina of Long-Evans and Sprague-Dawley rats. Our preliminary results demonstrate the feasibility of the system for high speed/resolution imaging of the rodent retina. This is useful for longitudinal studies of disease models of retinal disease in rats and mice

Ultra-high resolution optical Doppler coherence tomography (μODT) is a promising tool for brain functional imaging. However, its sensitivity for detecting slow flows in capillary beds may limit its utility in visualizing and quantifying subtle changes in brain microcirculation. To address this limitation, we developed a novel method called contrast-enhanced μODT (c-μODT) in which intralipid is injected into mouse tail vein to enhance μODT detection sensitivity. We demonstrate that after intralipid injection, the flow detection sensitivity of μODT is dramatically enhanced by 230% as quantified by the fill factor (FF) of microvasculature. More importantly, we show that c-μODT preserves the quantitative properties for flow imaging, i.e., showing a comparable change ratio of hypercapnia-induced flow increase in the capillary network before and after injecting intralipid.

Arteriolo-arteriolar anastomosis’s role in regulating blood perfusion through penetrating arterioles during stroke is yet to be discovered. We apply ultra-high sensitive optical microangiography (UHS-OMAG) and Doppler optical microangiography (DOMAG) techniques to evaluate vessel diameter and red blood cell velocity changes in large number of pial and penetrating arterioles in relation with arteriolo-arteriolar anastomosis (AAA) during and after focal stroke. Thanks to the high sensitivity of UHS-OMAG, we were able to image pial microvasculature up to capillary level through a cranial window (9 mm₂), and DOMAG provided clear image of penetrating arterioles up to 500μm depth. Results showed that penetrating arterioles close to a strong AAA connection dilate whereas penetrating arterioles constrict significantly in weaker AAA regions. These results suggest that AAA plays a major role in active regulation of the pial arterioles, and weaker AAA connections lead to poor blood perfusion to penumbra through penetrating arterioles.

We report three-dimensional (3D) imaging of microcirculation within human cavity tissues in vivo using a high-speed swept-source optical coherence tomography (SS-OCT) at 1.3 μm with a modified probe interface. Volumetric structural OCT images of the inner tissues of oral and nasal cavities are acquired with a field of view of 2 mm x 2 mm. Two types of disposable and detachable probe attachments are devised and applied to the port of the imaging probe of OCT system, enabling forward and side imaging scans for selective and easy access to specific cavity tissue sites. Blood perfusion is mapped with OCT-based microangiography from 3D structural OCT images, in which a novel vessel extraction algorithm is used to decouple dynamic light scattering signals, due to moving blood cells, from the background scattering signals due to static tissue elements. Characteristic tissue anatomy and microvessel architectures of various cavity tissue regions of a healthy human volunteer are identified with the 3D OCT images and the corresponding 3D vascular perfusion maps at a level approaching capillary resolution. The initial finding suggests that the proposed method may be engineered into a promising tool for evaluating and monitoring tissue microcirculation and its alteration within a wide-range of cavity tissues in the patients with various pathological conditions.

Shear wave optical coherence elastography (SW-OCE) is a quantitative approach to assess tissue structures and elasticity with high resolution, based on OCT. Shear wave imaging (SWI) is the foundation of shear wave elasticity imaging (SWEI), which is a quantitative approach to assess tissue structures and pathological status. In order to enhance elastography resolution to micron scale, the shear waves needs to be highly localized, with short wavelength and high frequency (second order of kHz), which also places stricter requirement on the temporal resolution requirements of SWI device. In this paper, we introduced two approaches to remotely induce high frequency shear waves within tissue samples: ultrasound acoustic radiation force impulse (ARFI), and high energy nanosecond pulsed laser. The maximum frequency of pulsed laser induced shear waves in tissue-mimicking phantoms can go up to 25 kHz, which is not possible to be captured and tracked by other SWI modalities. We use a custom-built SWI-OCT system to visualize and capture the nanometer scale shear waves, achieving a spatial resolution up to 15 um and frame rate of up to 92 kHz. The dynamic wave propagation data was then used for the reconstruction of localized wave velocity and elasticity. This study demonstrates the non-contact shear wave generation with pulsed laser source, and ultra-fast, high-resolution sectional acoustical wave tracking with remarkable sensitivity, promising a future clinical application for a high-resolution quantitative mapping of elasticity in vivo, non-contact and real time in OCT-accessible tissue, especially in ocular tissues.

In this report we demonstrate results of measuring wavefront aberrations from different depths in a fabricated phantom using a coherence-gated Shack-Hartman wavefront sensing technique (CG-SH/WFS). The SH/WFS is equipped with a Mach-Zehnder interferometer and the coherence gate operates on principles of swept source (SS) interferometry. The CG-SH/WFS is able to differentiate wavefront signals from different depths separated by a depth resolution of 7.1 micron. The CG-SH/WFS delivers a similar SH spot pattern as that provided by a conventional SH/WFS. Due to the coherence gate, the sensor is capable of eliminating stray reflections. Hereby we present the results of measuring depth-resolved wavefront aberrations. The method is robust and all depth-resolved aberrations are recorded simultaneously without any mechanical movement. This technique has the potential of providing depth resolved correction in adaptive optics assisted ophthalmology imaging and in nonlinear microscopy.

We present a quantitative optical coherence elastographic method for noncontact assessment of the myocardium elasticity. The method is based on shear wave imaging optical coherence tomography (SWI-OCT), where a focused air-puff system is used to induce localized tissue deformation through a low-pressure short-duration air stream and a phase-sensitive OCT system is utilized to monitor the propagation of the induced tissue displacement with nanoscale sensitivity. The 1-D scanning of M-mode OCT imaging and the application of optical phase retrieval and mapping techniques enable the reconstruction and visualization of 2-D depth-resolved shear wave propagation in tissue with ultra-high frame rate. The feasibility of this method in quantitative elasticity measurement is demonstrated on tissue-mimicking phantoms with the estimated Young’s modulus compared with uniaxial compression tests. We also performed pilot experiments on ex vivo mouse cardiac muscle tissues with normal and genetically altered cardiomyocytes. Our results indicate this noncontact quantitative optical coherence elastographic method can be a useful tool for the cardiac muscle research and studies.

We demonstrate a novel label-free OCT method allowing optical detection and differentiation of moving micro-objects, such as blood cells. In this study we use phase-sensitive Fd-OCT/OCM system with broadband light source (axial resolution: 3 μm in tissue and lateral resolution 4−8 μm) and fluidic sample setup. The novel part of this method is that the optical identification is based on optical signal coming from optically uniform scattering media localized beneath the flowing/moving objects and not from the objects itself. This signal reveals as an enhancement in speckle pattern on intensity images and non-zero phase change on phase images (phase-change). Statistical parameters of such signals depend on the features of the object, like its size, shape, internal structure, etc. In order to demonstrate the effectiveness and reliability of proposed method, we performed an experiment to differentiate erythrocytes from leukocytes. Obtained OCT cross-sectional images present signal enhancement in the scattering base, both on intensity and phase-change images. This modulation signals, corresponding to erythrocytes and leukocytes, are significantly different and could be easily distinguished qualitatively. Statistical parameters used for the analysis also represent satisfactory separation to distinguish between different kinds of cells. Above-mentioned results of differentiation are presented in this paper.

We present a Graph Cut based image segmentation that was implemented on a Graphics Processing Unit for acceleration of processing retinal images acquired with OCT. We applied this work to generate a retinal thickness map, and for retinal layer segmentation to enhance the visualization of vasculature networks from distinct retinal capillary beds during acquisition using speckle variance OCT.

We present a new design for a wavefront sensorless adaptive optics (WS-AO) Fourier domain optical coherence tomography (FD-OCT) system for small animal retinal imaging in vivo. Without the optical complications necessary for inclusion of a wavefront sensor in the optical system, this version of WS-AO FD-OCT system has a simplified optical design, including elimination of long focal length scanning optics and optical conjugation of vertical and horizontal scanners. This modification provides a modular large Field of View for retinal screening (25 degree visual angle), while also allowing a “zoom” capability for allocating all the scanning resources to a smaller region of interest, allowing high resolution aberration-corrected imaging. In the present system we used a 0 Dpt contact lens to stabilize the mouse eye position and to allow long duration imaging. Defocus (axial focus position) in our system is controlled by the collimation of the OCT sample arm entrance beam.

Interest in eye growth regulation has burgeoned with the rise in myopia prevalence world-wide. Eye length and eye shape are fundamental metrics for related research, but current in vivo measurement techniques are generally limited to the optical axis of the eye. We describe a high resolution, time domain low coherence interferometry based optometer for measuring the eye length of small animals over a wide field of view. The system is based upon a Michelson interferometer using a superluminescent diode as a source, including a sample arm and a reference arm. The sample arm is split into two paths by a polarisation beam splitter; one focuses the light on the cornea and the other focuses the light on the retina. This method has a high efficiency of detection for reflections from both surfaces. The reference arm contains a custom high speed linear motor with 25 mm stroke and equipped with a precision displacement encoder. Light reflected from the cornea and the retina is combined with the reference beam to generate low coherence interferograms. Two galvo scanners are employed to steer the light to different angles so that the eye length over a field of view of 20° × 20° can be measured. The system has an axial resolution of 6.8 μm (in air) and the motor provides accurate movement, allowing for precise and repeatable measurement of coherence peak positions. Example scans from a tree shrew are presented.

Fourier Domain (FD) Optical Coherence Tomography (OCT) interferograms require a Fourier transformation in order to be converted to A-Scans representing the backscattering intensity from the different depths of the tissue microstructure. Most often, this transformation is performed using a discrete Fourier transform, i.e. the well-known Fast Fourier Transform (FFT). However, there are many alternatives for performing the necessary spectral conversion. Autoregressive (AR) spectral estimation techniques are one such example. The parametric nature of AR techniques offers several advantages, compared to the commonly-used FFT, including better convergence and less susceptibility to noise. They can also be adjusted to represent more or less of the signal detail depending on the order of the autoregression. These features make them uniquely suited for processing the FD OCT data. The advantages of the proposed methodology are illustrated on in vivo skin imaging data and the resolution is verified on single back-reflections from a glass surface. AR spectral estimation can be used to convert the interferograms to A-Scans while at the same time reducing the artifacts caused by high intensity back-reflections (by -20 dB) and diminishing the speckle (by -12 dB) all without the degradation in the resolution associated with other techniques.

As optical coherence tomography (OCT) grows to be a mature and successful field, it is important for the research community to develop a stronger practice of sharing code and data. A prolific culture of sharing can enable new and emerging laboratories to enter the field, allow research groups to gain new exposure and notoriety, and enable benchmarking of new algorithms and methods. Our long-term vision is to build tools to facilitate a stronger practice of sharing within this community. In line with this goal, our first aim was to understand the perceptions and practices of the community with respect to sharing research contributions (i.e., as code and data). We surveyed 52 members of the OCT community using an online polling system. Our main findings indicate that while researchers infrequently share their code and data, they are willing to contribute their research resources to a shared repository, and they believe that such a repository would benefit both their research and the OCT community at large. We plan to use the results of this survey to design a platform targeted to the OCT research community – an effort that ultimately aims to facilitate a more prolific culture of sharing.

The development of Optical Coherence Tomography (OCT) systems started in the 1990's. The technology early found its application in Ophthalmology. Today more than 75% of the OCT market comes from the ophthalmic sector. However the growth of the ophthalmology OCT market has been slowing down for the last years. In this article, we present the results of our prospective study on the drivers of the OCT market growth in the coming years, based on bibliographical research and interviews with key players. In parallel of being used for ophthalmology, OCT has been developed and tested in new medical domains like cardiology, dermatology, gastroenterology, etc. OCT addresses key societal challenges such as the diagnosis of coronary artery diseases or skin cancer. There is a strong demand for fast, high-resolution, label-free and in vivo imaging tools in these fields. For the last 5 years, RD efforts have been focused on improving the performance and the compactness of OCT components and sub-systems. Advances in integrated photonics will enable the miniaturization of components and sub-systems and thus pave the way to Point-of-Care applications. Moreover the developments of new functionalities of OCT systems are undertaken to reach more complex diagnosis. OCT will no longer be a simple imaging device, it is on the verge of becoming a quantitative measurement tool. Our study shows that the emergence of new applications along with the improvements of components performance and the progress of functional OCT will drive the OCT market growth in the coming years.

We present the methodology for spectroscopic examination of absorbing media being the combination of Spectral Optical Coherence Tomography and Fourier Transform Spectroscopy. The method bases on the joint Spectral and Time OCT computational scheme and simplifies data analysis procedure as compared to the mostly used windowing-based Spectroscopic OCT methods. The proposed experimental setup is self-calibrating in terms of wavelength-pixel assignment. The performance of the method in measuring absorption spectrum was checked with the use of the reflecting phantom filled with the absorbing agent (indocyanine green). The results show quantitative accordance with the controlled exact results provided by the reference method.

Objectives. Prostate cancer is the most frequently diagnosed malignancy in men. Digital rectal examination (DRE) - a known clinical tool based on alteration in the mechanical properties of tissues due to cancer has traditionally been used for screening prostate cancer. Essentially, DRE estimates relative stiffness of cancerous and normal prostate tissue. Optical coherence elastography (OCE) are new optical imaging techniques capable of providing cross-sectional imaging of tissue microstructure as well as elastogram in vivo and in real time. In this preliminary study, OCE was used in the setting of the human prostate biopsies ex vivo, and the images acquired were compared with those obtained using standard histopathologic methods. Methods. 120 prostate biopsies were obtained by TRUS guided needle biopsy procedures from 9 patients with clinically suspected cancer of the prostate. The biopsies were approximately 0.8mm in diameter and 12mm in length, and prepared in Formalin solution. Quantitative assessment of biopsy samples using OCE was obtained in kilopascals (kPa) before histopathologic evaluation. The results obtained from OCE and standard histopathologic evaluation were compared provided the cross-validation. Sensitivity, specificity, and positive and negative predictive values were calculated for OCE (histopathology was a reference standard). Results. OCE could provide quantitative elasticity properties of prostate biopsies within benign prostate tissue, prostatic intraepithelial neoplasia, atypical hyperplasia and malignant prostate cancer. Data analysed showed that the sensitivity and specificity of OCE for PCa detection were 1 and 0.91, respectively. PCa had significantly higher stiffness values compared to benign tissues, with a trend of increasing in stiffness with increasing of malignancy. Conclusions. Using OCE, microscopic resolution elastogram is promising in diagnosis of human prostatic diseases. Further studies using this technique to improve the detection and staging of malignant cancer of the prostate are ongoing.

Bio-ceramics such as hydroxyapatite (HAp) are widely used materials in medical applications, especially as an interface between implants and living tissues. There are many ways of creating structures from HAp like electrochemical assisted deposition, biomimetic, electrophoresis, pulsed laser deposition or sol-gel processing. Our research is based on analyzing the parameters of the sol-gel method for creating thin layers of HAp. In order to achieve this, we propose to use Optical Coherence Tomography (OCT) for non-destructive and non-invasive evaluation. Our system works in the IR spectrum range, which is helpful due to the wide range of nanocomposites being opaque in the VIS range. In order to use our method we need to measure two samples, one which is a reference HAp solution and second: a similar HAp solution with nanoparticles introduced inside. We use silver nanoparticles below 300 nm. The aim of this research is to analyze the concentration and dispersion of nanodopants in the bio-ceramic matrix. Furthermore, the quality of the HAp coating and deposition process repetition have been monitored. For this purpose the polarization sensitive OCT with additional spectroscopic analysis is being investigated. Despite the other methods, which are suitable for nanocomposite materials evaluation, the OCT with additional features seems to be one of the few which belong to the NDE/NDT group. Here we are presenting the OCT system for evaluation of the HAp with nano-particles, as well as HAp manufacturing process. A brief discussion on the usefulness of OCT for bio-ceramics materials examination is also being presented.

The hemodynamic environment is known to play a crucial role in the progression, rupture, and treatment of intracranial aneurysms. Currently there is difficulty assessing and measuring blood flow profiles in vivo. An emerging high resolution imaging modality known as split spectrum Doppler optical coherence tomography (ssDOCT) has demonstrated the capability to quantify hemodynamic patterns as well as arterial microstructural changes. In this study, we present a novel in vitro method to acquire precise blood flow patterns within a patient- specific aneurysm silicone flow models using ssDOCT imaging. Computational fluid dynamics (CFD) models were generated to verify ssDOCT results.

In this work, we demonstrated that bulk motion could lead to increased background in OCT microangiography image. Based on our motion analysis, we developed an adaptive thresholding method to reduce artifact in OCT microangiography caused by transient bulk motion. Motion artifact reduced microangiography was demonstrated in a 1.3μm spectral domain OCT system using graphic processing unit (GPU) for real-time signal processing. We conducted in vivo microvasculature imaging on human skin. Our results clearly show that the adaptive thresholding is highly effective in motion artifact removal.

Degradation of the wall of human ascending thoracic aorta has been assessed through Optical Coherence Tomography (OCT). OCT images of the media layer of the aortic wall exhibit micro-structure degradation in case of diseased aortas from aneurysmal vessels or in aortas prone to aortic dissections. The degeneration in vessel walls appears as low-reflectivity areas due to the invasive appearance of acidic polysaccharides and mucopolysaccharides within a typical ordered microstructure of parallel lamellae of smooth muscle cells, elastin and collagen fibers. An OCT indicator of wall degradation can be generated upon the spatial quantification of the extension of degraded areas in a similar way as conventional histopathology. This proposed OCT marker offers a real-time clinical insight of the vessel status to help cardiovascular surgeons in vessel repair interventions. However, the delineation of degraded areas on the B-scan image from OCT is sometimes difficult due to presence of speckle noise, variable SNR conditions on the measurement process, etc. Degraded areas could be outlined by basic thresholding techniques taking advantage of disorders evidences in B-scan images, but this delineation is not always optimum and requires complex additional processing stages. This work proposes an optimized delineation of degraded spots in vessel walls, robust to noisy environments, based on the analysis of the second order variation of image intensity of backreflection to determine the type of local structure. Results improve the delineation of wall anomalies providing a deeper physiological perception of the vessel wall conditions. Achievements could be also transferred to other clinical scenarios: carotid arteries, aorto-iliac or ilio-femoral sections, intracranial, etc.

We have demonstrated dynamic analysis of the physiological function of eccrine sweat glands underneath skin surface by optical coherence tomography (OCT). We propose a method for extraction of the target eccrine sweat gland by use of the connected component extraction process and the adaptive threshold method, where the en-face OCT images are constructed by the SS-OCT. Furthermore, we demonstrate precise measurement of instantaneous volume of the sweat gland in response to the external stimulus. The dynamic change of instantaneous volume of eccrine sweat gland in mental sweating is performed by this method during the period of 300 sec with the frame intervals of 3.23 sec.

The generation of a synthetic MR-OCT signal is presented and compared to a real acquired signal. Multiple reference optical coherence tomography (MR-OCT) is a novel time-domain interferometric system. The MR-OCT principle is adding a partial mirror to extend the axial scan range, which effectively extends the scan depth for imaging. The actuation of the scan mirror required for time-domain OCT, was demonstrated to operate with a low cost miniature voice coil, such as a speaker extracted from a smartphone or CD/DVD pick-up system. Building a compact and cost-effective optical imaging system will enable affordable medical diagnosis at low-resource setting applications. The partial mirror recirculates multiple reflections (orders) into the interferometric system and the increase of optical path delay does increase the beat frequency of the interference signal. The synthesis of such an interference signal using a numerical method is described in this manuscript.

We developed a low cost, high resolution optical coherence tomography system utilizing a narrowband laser diode (LD), which is usually used in optical pickup for compact disc. To achieve high axial resolution even with the narrow bandwidth of the LD, we have constructed a free space interferometer including a phase-diversity detection system and a high numerical aperture (NA) objective. The axial and lateral resolution in the air was about 2.6 μm and 1 μm, respectively. The tomographic imaging of biological tissue was demonstrated, and the results showed that our OCT system enabled cellular-level imaging.

An electronically controlled optical swept source (SS) at 1550 nm using mode locking in a dispersive ring cavity is described. Active mode-locking was achieved by directly modulating the current of a semiconductor optical amplifier (SOA) used as a gain medium. In the static regime, parameters such as linewidth, tuning bandwidth and contrast were measured, while the axial range was determined dynamically. Two types of fiber, dispersion compensation and single mode, are employed in the laser ring cavity. It is demonstrated that the relative lengths of the two types of fiber have little effect on the linewidth, while more control on the linewidth is obtained via the frequency of the signal driving the SOA. Linewidths less than 60 pm and over 1 nm were measured in the static regime while driving the SOA at 50 – 500 MHz. The narrowest linewidths were achieved where the proportion of dispersion compensation fiber in the cavity is 80- 90% of the total length. The optical source is developed to respond to the demands of OCT applications in general as well as address the need for low cost tunable lasers for configurations where a large tuning bandwidths and long coherence length might not be necessary.

Near-infrared external cavity lasers with high tuning rates (“swept lasers”) have come to dominate the field of nearinfrared low-coherence imaging of biological tissues. Compared with time-domain OCT, swept-source OCT a) replaces slow mechanical scanning of a bulky reference mirror with much faster tuning of a laser cavity filter element and b) provides a ×N (N being the number of axial pixels per A-scan) speed advantage with no loss of SNR. We will argue that this striking speed advantage has not yet been fully exploited within biophotonics but will next make its effects felt in the mid-infrared. This transformation is likely to be driven by recent advances in external cavity quantum cascade lasers, which are the mid-IR counterpart to the OCT swept-source. These mid-IR sources are rapidly emerging in the area of infrared spectroscopy. By noting a direct analogy between time-domain OCT and Fourier Transform Infrared (FTIR) spectroscopy we show analytically and via simulations that the mid-IR swept laser can acquire an infrared spectrum ×N (N being the number of spectral data points) faster than an FTIR instrument, using identical detected flux levels and identical receiver noise. A prototype external cavity mid-IR swept laser is demonstrated, offering a comparatively low sweep rate of 400 Hz over 60 cm^-1 with 2 cm-¹ linewidth, but which provides evidence that sweep rates of over a 100 kHz should be readily achievable simply by speeding up the cavity tuning element. Translating the knowledge and experience gained in near-IR OCT into mid-IR source development may result in sources offering significant benefits in certain spectroscopic applications.

An experimental and theoretical analysis of the dynamics of a Fourier domain mode locked laser, currently one of the fastest swept source lasers applied in optical coherence tomography, is performed. A novel time- resolved technique to measure the laser output electric field allows access to the phase dynamics of the laser and thus the coherence properties. A delay-differential equation model for the laser is used to analyse the system theoretically and via direct simulation. Numerical simulations of the laser output are in excellent agreement with experimentally measured data.

Tunable semiconductor laser for 1025-1095 nm spectral range is developed based on the InGaAs semiconductor optical amplifier and a narrow band-pass acousto-optic tunable filter in a fiber ring cavity. Mode-hop-free sweeping with tuning speeds of up to 10⁴ nm/s was demonstrated. Instantaneous linewidth is in the range of 0.06-0.15 nm, side-mode suppression is up to 50 dB and polarization extinction ratio exceeds 18 dB. Optical power in output single mode fiber reaches 20 mW. The laser was used in OCT system for imaging a contact lens immersed in a 0.5% intra-lipid solution. The cross-section image provided the imaging depth of more than 5mm.

We analyse the dynamical behaviour of a short cavity OCT swept-source laser experimentally and theoretically. Mode-hopping, sliding frequency mode-locking and chaos are all observed during the laser sweep period. Hetero- dyne measurements of laser dynamics allows some insight into the behaviour of the laser, while interferometric techniques allow the full phase reconstruction of the laser electric field. A delay differential equation enables modelling of the laser output, and laser parameters can be altered to provide optimisation conditions for future laser designs.

OCT as a coherent imaging technique inherently suffers from speckle. We present a new dual parametric compounding approach to reduce speckle. The approach is to acquire several OCT volumes with different numerical apertures (NAs). Then in post processing, a first spatial compounding step is performed by averaging of adjacent B-frames. In a second step data from the different volume is averaged. Retinal imaging data comparing this idea with standard spatial compounding is presented and analyzed and necessary parameters such as the required variation of the NA and number of different NAs are discussed

We present further improvements on the Master Slave (MS) interferometry method since our first communication [1]. In this paper, we present more data collection and additionally demonstrate an important feature of the MS method, that of tolerance to dispersion. MS interferometry produces the interference of a selected point in depth based on principles of spectral domain (SD) interferometry, but without the need of a Fast Fourier transformation (FFT). The method can be used to directly produce en-face optical coherence tomography (OCT) images but also as a tool to accurately measure distances in low coherence interferometry for sensing applications [1]. In the MS-OCT method, cross-correlation is applied to both methods of SD-OCT, spectrometer based (SP) or swept source (SS) OCT. The channelled spectrum provided by an OCT system is correlated with the signal produced by reading a stored mask. Several such masks can be used simultaneously. The masks operate as adaptive filters. Each mask (filter) determines recognition in the measured channelled spectrum delivered by the interferometer, of the pattern corresponding to each optical path difference to be recognized. The method presents net advantages in comparison with the classical method of producing axial reflectivity profiles by FFT: no need for resampling of data, possibility to tailor the trade-off between depth resolution and sensitivity. Here, using a swept source, the MS method is used to obtain axial reflectivity profiles, which are compared to the axial profiles obtained by calibration of data and FFT. The tolerance to dispersion of the MS method was assumed in [1] but not demonstrated. Here, measurements are performed to demonstrate its axial resolution independence on dispersion.

We show that in Fourier domain Optical Coherence Tomography (FdOCT) it is possible to determine the wavelength of light for each point of the detected spectrum using any measurable physical quantity that has linear dependency on wavenumber. The presented approach is robust as the actual values of the measured quantity have no importance for the algorithm. As example we calibrate a SOCT spectrometer using Doppler frequency induced in time-dependent spectral fringes by a mirror moving in one of the arm of the interferometer. The results of calibration are validated using narrow spectral lines generated by optical parametric oscillator.

Optical Coherence Tomography (OCT) systems, as all low coherence interferometry equipments, are mainly grouped in two categories: Time Domain and Frequency Domain, depending on the methodology of data analysis. When measuring samples with high reflectivity, using Frequency Domain systems, detrimental features on OCT images can appear as a replication of a feature at multiple depths on the resulting image, referred as harmonics by the community. This work presents the potential to access better axial resolution and accuracy results on profile measurements analyzing higher harmonics. A variety of measurements of samples with different features, such as roughness, angles and movement evaluation were performed in order to demonstrate the advantages of this approach as a low cost way to have better visualization of reliefs close to the system nominal axial resolution.

We developed a spectral domain OCT system combining two NIR, CW light sources of different spectral range. Its resolving power is validated by visualizing the cellular structures of zebra fish larvae in vivo. An NIR extended illumination from 755-1100 nm is achieved. The axial resolution is 1.27 μm in air, corresponding to 0.93μm in tissue (n=1.36), which is the highest axial resolution using NIR, CW laser sources up to date to the best of our knowledge. In vivo imaging is conducted to demonstrate the resolving power of proposed one-micron resolution OCT system. The top and bottom surfaces of individual disk-like red blood cell is reliably visualized, as well as flat, spindle shaped endothelial cells lining along the luminal surface of the blood vessel wall. This study provides a viable solution for cellular and subcellular level OCT imaging system which is also very competitive in cost.

Many fiber based probes used in Optical Coherence Tomography (OCT) are comprised of a spacer, GRadient INdex (GRIN) lens, and a microprism. This design has the benefit of being relatively simple given the need for only three optical components. However, because of constraints to optical performance specifications, such as the probe working distance and spot size, the spacer and GRIN lens will have demanding and difficult tolerances for component length. These tolerances are a detriment to high volume manufacturing. In this paper we present an alternative monolithic, single component design form which is more robust and eliminates the manufacturing constraints of the present design form, thereby making it ideally suited for high volume manufacturing.

Optical coherence tomography (OCT) is a non-invasive method for 3D and cross-sectional imaging of biological and non-biological objects. The OCT measurements are provided in non-contact and absolutely safe way for the tested sample. Nowadays, the OCT is widely applied in medical diagnosis especially in ophthalmology, as well as dermatology, oncology and many more. Despite of great progress in OCT measurements there are still a vast number of issues like tissue recognition or imaging contrast enhancement that have not been solved yet. Here we are going to present the polarization sensitive spectroscopic OCT system (PS-SOCT). The PS-SOCT combines the polarization sensitive analysis with time-frequency analysis. Unlike standard polarization sensitive OCT the PS-SOCT delivers spectral information about measured quantities e.g. tested object birefringence changes over the light spectra. This solution overcomes the limits of polarization sensitive analysis applied in standard PS-OCT. Based on spectral data obtained from PS-SOCT the exact value of birefringence can be calculated even for the objects that provide higher order of retardation. In this contribution the benefits of using the combination of time-frequency and polarization sensitive analysis are being expressed. Moreover, the PS-SOCT system features, as well as OCT measurement examples are presented.

The lateral resolution of a Spectral Domain Optical Coherence Tomography (SD-OCT) image is limited by the focusing properties of the OCT imaging probe optics, the wavelength range which SD-OCT system operates at, spherical and chromatic aberrations induced by the imaging optics, the optical properties of the imaged object, and in the special case of in-vivo retinal imaging by the optics of the eye. This limitation often results in challenges with resolving fine details and structures of the imaged sample outside of the Depth-Of-Focus (DOF) range. We propose a novel technique for generating Laterally Resolved OCT (LR-OCT) images using OCT measurements acquired with intentional imbrications. The proposed, novel method is based on a Maximum A Posteriori (MAP) reconstruction framework which takes advantage of a Stochastic Fully Connected Conditional Random Field (SFCRF) model to compensate for the artifacts and noise when reconstructing a LR-OCT image from imbricated OCT measurement. The proposed lateral resolution enhancement method was tested on synthetic OCT measurement as well as on a human cornea SDOCT image to evaluate the usefulness of the proposed approach in lateral resolution enhancement. Experimental results show that applying this method to OCT images, noticeably improves the sharpness of morphological features in the OCT image and in lateral direction, thus demonstrating better delineation of fine dot shape details in the synthetic OCT test, as well as better delineation of the keratocyte cells in the human corneal OCT test image.

The axial resolution of Spectral Domain Optical Coherence Tomography (SD-OCT) images degrades with scanning depth due to the limited number of pixels and the pixel size of the camera, any aberrations in the spectrometer optics and wavelength dependent scattering and absorption in the imaged object [1]. Here we propose a novel algorithm which compensates for the blurring effect of these factors of the depth-dependent axial Point Spread Function (PSF) in SDOCT images. The proposed method is based on a Maximum A Posteriori (MAP) reconstruction framework which takes advantage of a Stochastic Fully Connected Conditional Random Field (SFCRF) model. The aim is to compensate for the depth-dependent axial blur in SD-OCT images and simultaneously suppress the speckle noise which is inherent to all OCT images. Applying the proposed depth-dependent axial resolution enhancement technique to an OCT image of cucumber considerably improved the axial resolution of the image especially at higher imaging depths and allowed for better visualization of cellular membrane and nuclei. Comparing the result of our proposed method with the conventional Lucy-Richardson deconvolution algorithm clearly demonstrates the efficiency of our proposed technique in better visualization and preservation of fine details and structures in the imaged sample, as well as better speckle noise suppression. This illustrates the potential usefulness of our proposed technique as a suitable replacement for the hardware approaches which are often very costly and complicated.

In this Hot Topics presentation, Brett Bouma notes how diagnostic procedures using optical coherence tomography (OCT) technology have become the gold standard for detecting diseases of the eye, heart and gastrointestinal tract, looking for disease in the body -- without incisions. Advances in endoscopic OCT have included a 20-fold increase in image speed, now producing 3,000 frames per second. Other advances include new probes such as tethered capsules, polarization sensitive imaging, and uses in biopsy guidance. The technique has been in use since the 1990s in animals and in humans since 2002. But the clinical community was skeptical until studies in 2003 showed ways to obtain dramatically higher speed imaging of tissues over a wider field of view. Brett Bouma is a professor of dermatology and health sciences and technology at Harvard Medical School and an associate physicist in the Wellman Center for Photomedicine at the Massachusetts General Hospital (MGH). His doctoral research, at the University of Illinois, Chicago, focused on understanding the interaction of ultrafast laser pulses with optical materials and plasmas. Since starting a lab at MGH in 1998, he has focused his research on the development and clinical application of novel optical technologies for diagnosis and therapy.