Complex conjugate resolved heterodyne swept source optical coherence tomography using coherence revival

We describe a simple and low-cost technique for resolving the complex conjugate ambiguity in Fourier domain optical coherence tomography (OCT) that is applicable to many swept source OCT (SSOCT) systems. First, we review the principles of coherence revival, wherein an interferometer illuminated by an external cavity tunable laser (ECTL) exhibits interference fringes when the two arms of the interferometer are mismatched by an integer multiple of the laser cavity length. Second, we report observations that the spectral interferogram obtained from SSOCT systems employing certain ECTLs are automatically phase modulated when the arm lengths are mismatched this way. This phase modulation results in a frequency-shifted interferogram, effectively creating an extended-depth heterodyne SSOCT system without the use of acousto-optic or electro-optic modulators. We suggest that this phase modulation may be caused by the ECTL cavity optical pathlength varying slightly over the laser sweep, and support this hypothesis with numerical simulations. We also report on the successful implementation of this technique with two commercial swept source lasers operating at 840nm and 1040nm, with sweep rates of 8kHz and 100kHz respectively. The extended imaging depth afforded by this technique was demonstrated by measuring the sensitivity fall-off profiles of each laser with matched and mismatched interferometer arms. The feasibility of this technique for clinical systems is demonstrated by imaging the ocular anterior segments of healthy human volunteers.     

Handheld ultrahigh speed swept source optical coherence tomography instrument using a MEMS scanning mirror

We developed an ultrahigh speed, handheld swept source optical coherence tomography (SS-OCT) ophthalmic instrument using a 2D MEMS mirror. A vertical cavity surface-emitting laser (VCSEL) operating at 1060 nm center wavelength yielded a 350 kHz axial scan rate and 10 µm axial resolution in tissue. The long coherence length of the VCSEL enabled a 3.08 mm imaging range with minimal sensitivity roll-off in tissue. Two different designs with identical optical components were tested to evaluate handheld OCT ergonomics. An iris camera aided in alignment of the OCT beam through the pupil and a manual fixation light selected the imaging region on the retina. Volumetric and high definition scans were obtained from 5 undilated normal subjects. Volumetric OCT data was acquired by scanning the 2.4 mm diameter 2D MEMS mirror sinusoidally in the fast direction and linearly in the orthogonal slow direction. A second volumetric sinusoidal scan was obtained in the orthogonal direction and the two volumes were processed with a software algorithm to generate a merged motion-corrected volume. Motion-corrected standard 6 x 6 mm² and wide field 10 x 10 mm² volumetric OCT data were generated using two volumetric scans, each obtained in 1.4 seconds. High definition 10 mm and 6 mm B-scans were obtained by averaging and registering 25 B-scans obtained over the same position in 0.57 seconds. One of the advantages of volumetric OCT data is the generation of en face OCT images with arbitrary cross sectional B-scans registered to fundus features. This technology should enable screening applications to identify early retinal disease, before irreversible vision impairment or loss occurs. Handheld OCT technology also promises to enable applications in a wide range of settings outside of the traditional ophthalmology or optometry clinics including pediatrics, intraoperative, primary care, developing countries, and military medicine.OCIS codes: (170.4460) Ophthalmic optics and devices, (170.5755) Retina scanning, (170.3880) Medical and biological imaging, (170.4500) Optical coherence tomography, (170.4470) Ophthalmology     

Complete complex conjugate resolved heterodyne swept source optical coherence tomography using a dispersive optical delay line: erratum

We correct an error in our previous paper [Biomed. Opt. Express 2, 1218 (2011)] which led to an erroneous conclusion that a dispersive optical delay line (DODL) used in a swept source optical coherence tomography (SSOCT) system generated a pure phase modulation allowing for complex conjugate artifact removal in Fourier domain OCT via optical heterodyning. We now understand that an alternate phenomenon known as coherence revival was responsible for the observed phase modulation, while the DODL provided a compact means of generating a large group delay with readily adjustable group velocity dispersion compensation.     

Logarithmic intensity and speckle-based motion contrast methods for human retinal vasculature visualization using swept source optical coherence tomography

We formulate a theory to show that the statistics of OCT signal amplitude and intensity are highly dependent on the sample reflectivity strength, motion, and noise power. Our theoretical and experimental results depict the lack of speckle amplitude and intensity contrasts to differentiate regions of motion from static areas. Two logarithmic intensity-based contrasts, logarithmic intensity variance (LOGIV) and differential logarithmic intensity variance (DLOGIV), are proposed for serving as surrogate markers for motion with enhanced sensitivity. Our findings demonstrate a good agreement between the theoretical and experimental results for logarithmic intensity-based contrasts. Logarithmic intensity-based motion and speckle-based contrast methods are validated and compared for in vivo human retinal vasculature visualization using high-speed swept-source optical coherence tomography (SS-OCT) at 1060 nm. The vasculature was identified as regions of motion by creating LOGIV and DLOGIV tomograms: multiple B-scans were collected of individual slices through the retina and the variance of logarithmic intensities and differences of logarithmic intensities were calculated. Both methods captured the small vessels and the meshwork of capillaries associated with the inner retina in en face images over 4 mm(2) in a normal subject.     

Handheld,rapidly switchable,anterior/posterior segment swept source optical coherence tomography probe

We describe the first handheld, swept source optical coherence tomography (SSOCT) system capable of imaging both the anterior and posterior segments of the eye in rapid succession. A single 2D microelectromechanical systems (MEMS) scanner was utilized for both imaging modes, and the optical paths for each imaging mode were optimized for their respective application using a combination of commercial and custom optics. The system has a working distance of 26.1 mm and a measured axial resolution of 8 μm (in air). In posterior segment mode, the design has a lateral resolution of 9 μm, 7.4 mm imaging depth range (in air), 4.9 mm 6dB fall-off range (in air), and peak sensitivity of 103 dB over a 22° field of view (FOV). In anterior segment mode, the design has a lateral resolution of 24 μm, imaging depth range of 7.4 mm (in air), 6dB fall-off range of 4.5 mm (in air), depth-of-focus of 3.6 mm, and a peak sensitivity of 99 dB over a 17.5 mm FOV. In addition, the probe includes a wide-field iris imaging system to simplify alignment. A fold mirror assembly actuated by a bi-stable rotary solenoid was used to switch between anterior and posterior segment imaging modes, and a miniature motorized translation stage was used to adjust the objective lens position to correct for patient refraction between −12.6 and + 9.9 D. The entire probe weighs less than 630 g with a form factor of 20.3 x 9.5 x 8.8 cm. Healthy volunteers were imaged to illustrate imaging performance.OCIS codes: (110.4500) Optical coherence tomography, (170.4460) Ophthalmic optics and devices, (080.3620) Lens system design, (170.0110) Imaging systems, (170.5755) Retina scanning, (170.4470) Ophthalmology     

Tuning of successively scanned two monolithic Vernier-tuned lasers and selective data sampling in optical comb swept source optical coherence tomography

Monolithic Vernier tuned super-structure grating distributed Bragg reflector (SSG-DBR) lasers are expected to become one of the most promising sources for swept source optical coherence tomography (SS-OCT) with a long coherence length, reduced sensitivity roll-off, and potential capability for a very fast A-scan rate. However, previous implementations of the lasers suffer from four main problems: 1) frequencies deviate from the targeted values when scanned, 2) large amounts of noise appear associated with abrupt changes in injection currents, 3) optically aliased noise appears due to a long coherence length, and 4) the narrow wavelength coverage of a single chip limits resolution. We have developed a method of dynamical frequency tuning, a method of selective data sampling to eliminate current switching noise, an interferometer to reduce aliased noise, and an excess-noise-free connection of two serially scanned lasers to enhance resolution to solve these problems. An optical frequency comb SS-OCT system was achieved with a sensitivity of 124 dB and a dynamic range of 55-72 dB that depended on the depth at an A-scan rate of 3.1 kHz with a resolution of 15 μm by discretely scanning two SSG-DBR lasers, i.e., L-band (1.560-1.599 μm) and UL-band (1.598-1.640 μm). A few OCT images with excellent image penetration depth were obtained.OCIS codes: (170.4500) Optical coherence tomography, (170.3880) Medical and biological imaging, (170.4470) Ophthalmology     

High-speed spectral domain optical coherence tomography using non-uniform fast Fourier transform

The useful imaging range in spectral domain optical coherence tomography (SD-OCT) is often limited by the depth dependent sensitivity fall-off. Processing SD-OCT data with the non-uniform fast Fourier transform (NFFT) can improve the sensitivity fall-off at maximum depth by greater than 5dB concurrently with a 30 fold decrease in processing time compared to the fast Fourier transform with cubic spline interpolation method. NFFT can also improve local signal to noise ratio (SNR) and reduce image artifacts introduced in post-processing. Combined with parallel processing, NFFT is shown to have the ability to process up to 90k A-lines per second. High-speed SD-OCT imaging is demonstrated at camera-limited 100 frames per second on an ex-vivo squid eye.     

Single input state polarization sensitive swept source optical coherence tomography based on an all single mode fiber interferometer

We present a newly developed single mode fiber based swept source polarization sensitive optical coherence tomography system using a single input state at 1040 nm. Two non-polarizing fiber based beam splitters are combined to form a Mach-Zehnder interferometer, while two polarizing beam splitters are used to obtain a polarization sensitive detection. Both types of beam splitters solely feature conventional single mode fibers. Polarization control paddles are used to set and maintain the polarization states in the fibers of the interferometer and detection unit. By use of a special paddle alignment scheme we are able to eliminate any bulk optic wave plates and polarization maintaining fibers in the interferometer and detection paths while preserving the advantages of a single input state system that illuminates the sample with circularly polarized light. To demonstrate the capabilities of our system, we performed retinal measurements on healthy human volunteers.OCIS codes: (170.0170) Medical optics and biotechnology, (170.0110) Imaging systems, (170.2655) Functional monitoring and imaging, (170.4500) Optical coherence tomography, (170.4470) Ophthalmology, (060.2430) Fibers, single-mode     

Full-depth epidermis tomography using a Mirau-based full-field optical coherence tomography

With a Gaussian-like broadband light source from high brightness Ce³⁺:YAG single-clad crystal fiber, a full-field optical coherence tomography using a home-designed Mirau objective realized high quality images of in vivo and excised skin tissues. With a 40 × silicone-oil-immersion Mirau objective, the achieved spatial resolutions in axial and lateral directions were 0.9 and 0.51 μm, respectively. Such a high spatial resolution enables the separation of lamellar structure of the full epidermis in both the cross-sectional and en face planes. The number of layers of stratum corneum and its thickness were quantitatively measured. This label free and non-invasive optical probe could be useful for evaluating the water barrier of skin tissue in clinics. As a preliminary in vivo experiment, the blood vessel in dermis was also observed, and the flowing of the red blood cells and location of the melanocyte were traced.OCIS codes: (060.2380) Fiber optics sources and detectors, (170.4500) Optical coherence tomography, (160.1435) Biomaterials, (170.3880) Medical and biological imaging, (180.3170) Interference microscopy     

Frequency multiplexed long range swept source optical coherence tomography

We present a novel swept source optical coherence tomography configuration, equipped with acousto-optic deflectors that can be used to simultaneously acquire multiple B-scans originating from different depths. The sensitivity range of the configuration is evaluated while acquiring five simultaneous B-scans. Then the configuration is employed to demonstrate long range B-scan imaging by combining two simultaneous B-scans from a mouse head sample.OCIS codes: (120.3180) Interferometry, (110.4500) Optical coherence tomography, (170.1065) Acousto-optics, (170.0110) Imaging systems, (110.6880) Three-dimensional image acquisition, (140.3600) Lasers, tunable     

In vivo layer visualization of rat olfactory bulb by a swept source optical coherence tomography and its confirmation through electrocoagulation and anatomy

Here, we report in vivo 3-D visualization of the layered organization of a rat olfactory bulb (OB) by a swept source optical coherence tomography (SS-OCT). The SS-OCT operates at a wavelength of 1334 nm with respective theoretical depth and lateral resolutions of 6.7 μm and 15.4 μm in air and hence it is possible to get a 3D structural map of OB in vivo at the micron level resolution with millimeter-scale imaging depth. Up until now, with methods such as MRI, confocal microscopy, OB depth structure in vivo had not been clearly visualized as these do not satisfy the criterion of simultaneously providing micron-scale spatial resolution and imaging up to a few millimeter in depth. In order to confirm the OB's layered organization revealed by SS-OCT, we introduced the technique of electrocoagulation to make landmarks across the layered structure. To our knowledge this is such a first study that combines electrocoagulation and OCT in vivo of rat OB. Our results confirmed the layered organization of OB, and moreover the layers were clearly identified by electrocoagulation landmarks both in the OCT structural and anatomical slice images. We expect such a combined study is beneficial for both OCT and neuroscience fields.     

Guidance of aortic ablation using optical coherence tomography

Purpose: There is a significant need for an imaging modality that is capable of providing guidance for intravascular procedures, as current technologies suffer from significant limitations. In particular, laser ablation of in-stent restenosis, revascularization of chronic total occlusions, and pulmonary vein ablation could benefit from guidance. Optical coherence tomography (OCT), a recently introduced technology, is similar to ultrasound except that it measures the back-reflection of infrared light instead of sound. This study examines the ability of OCT to guide vascular laser ablation. Methods: Aorta samples underwent laser ablation using an argon laser at varying power outputs and were monitored with OCT collecting images at 4frames. Samples were compared to the corresponding histopathology. Results: Arterial layers could be differentiated in the images sequences. This allowed correlation of changes in the OCT image with power and duration in addition to histopathology. Conclusions: OCT provides real-time guidance of arterial ablation. At 4 frames, OCT was successfully able to show the microstructural changes in the vessel wall during laser ablation. Since current ablation procedures often injure surrounding tissue, the ability to minimize collateral damage to the adjoining tissue represents a useful advantage of this system. This study suggests a possible role for OCT in the guidance of intravascular procedures.     

Improved velocimetry in optical coherence tomography using Bayesian analysis

OCT is a popular cross-sectional microscale imaging modality in medicine and biology. While structural imaging using OCT is a mature technology in many respects, flow and motion estimation using OCT remains an intense area of research. In particular, there is keen interest in maximizing information extraction from the complex-valued OCT signal. Here, we introduce a Bayesian framework into the data workflow in OCT-based velocimetry. We demonstrate that using prior information in this Bayesian framework can significantly improve velocity estimate precision in a correlation-based, model-based framework for Doppler and transverse velocimetry. We show results in calibrated flow phantoms as well as in vivo in a Drosophila melanogaster (fruit fly) heart. Thus, our work improves upon the current approaches in terms of improved information extraction from the complex-valued OCT signal.OCIS codes: (110.4500) Optical coherence tomography, (000.5490) Probability theory, stochastic processes, and statistics, (110.4153) Motion estimation and optical flow, (170.3880) Medical and biological imaging, (290.5820) Scattering measurements, (030.6140) Speckle     

Diagnosis of Barrett's esophagus using optical coherence tomography

The presence of Barrett's esophagus (BE) is determined by histopathologic analysis of biopsy specimens obtained during upper endoscopy. The accuracy of endoscopy for the diagnosis of BE is surprisingly poor, however. Optical coherence tomography (OCT) is an optical technology that has shown promise as a powerful new tool to study BE. Of all the methods of optical biopsy discussed in this issue,perhaps OCT comes closest to this goal in that it provides a two dimensional image that correlates with traditional histopathologic excisional biopsy.     

Diagnosis of Barrett's esophagus using optical coherence tomography

OCT is a promising optical technology that permits real-time, high-resolution, cross-sectional imaging of tissue during endoscopy. It has been shown to be a highly sensitive and specific means of identifying the presence of SIM. Preliminary studies suggest that OCT is capable of grading dysplasia occurring within BE and has the potential to assist with the staging of superficial malignancies, particularly squamous cell cancers. In the near future, the capabilities of OCT systems are expected to improve with systems capable of much higher resolution and with Doppler capability becoming available.     

Segmentation of Doppler optical coherence tomography signatures using a support-vector machine

When processing Doppler optical coherence tomography images, there is a need to segment the Doppler signatures of the vessels. This can be used for visualization, for finding the center point of the flow areas or to facilitate the quantitative analysis of the vessel flow. We propose the use of a support-vector machine classifier in order to segment the flow. It uses the phase values of the Doppler image as well as texture information. We show that superior results compared to conventional simple threshold-based methods can be achieved in conditions of significant phase noise, which inhibit the use of a simple threshold of the phase values.     

Efficient and facile delivery of gold nanoparticles in vivo using dissolvable microneedles for contrast-enhanced optical coherence tomography

Obtaining sufficient contrast is an indispensable requirement for detecting early stage cancer using optical coherence tomography (OCT), an emerging diagnostic tool that detects abnormal lesions with micrometer resolutions in real time. PEGylated gold nanoparticles (Au NPs; 87 nm in diameter) were formulated in aqueous dissolvable microneedles (dMNs; 200 μm height) for efficient, precisely controlled, and convenient delivery of Au NPs into hamster oral tissue in vivo. The Au NPs were then further briefly dissipated by ultrasound (US). The results showed 33% and 20% increase in average optical scattering intensity (contrast level) in dysplastic and normal tissues, respectively, and pinpointed pathological structures of early stage oral cancer were also identified by the highly convenient and efficient administration of Au NPs in a novel delivery platform.     

Cornea characterization using a combined multiphoton microscopy and optical coherence tomography system

We present a multimodal imaging system which combines multiphoton microscopy and optical coherence tomography to visualize the morphological structures, and to quantify the refractive index (RI) and thickness of cornea. The morphological similarities and differences at different corneal layers across various species are identified. In the piscine and human corneas, the stromata exhibit thin fibers that indicate an overall collagen direction. Human corneas display collagen micro-folds which cause increased light attenuation. In the murine, porcine and bovine corneas, the stromata show interwoven collagen patterns. The Bowman’s layer and the Descemet’s membrane are also distinguished in some species. The RI and thicknesses are quantified for the epithelium and the stromal layers respectively, where the epithelium is found to have slightly higher RI than the stroma. The average epithelial and stromal RI are, respectively, 1.371 ± 0.016 and 1.360 ± 0.008 for the murine corneas; 1.502 ± 0.057 and 1.335 ± 0.011 for the piscine corneas; 1.433 ± 0.023 and 1.357 ± 0.013 for the human corneas; 1.476 ± 0.091 and 1.343 ± 0.013 for the porcine corneas; and 1.400 ± 0.007 and 1.376 ± 0.003 for the bovine corneas. The multimodal system can potentially provide a comprehensive characterization of the cornea.OCIS codes: (180.4315) Nonlinear microscopy, (110.4500) Optical coherence tomography     

Real-time speckle variance swept-source optical coherence tomography using a graphics processing unit

Advances in swept source laser technology continues to increase the imaging speed of swept-source optical coherence tomography (SS-OCT) systems. These fast imaging speeds are ideal for microvascular detection schemes, such as speckle variance (SV), where interframe motion can cause severe imaging artifacts and loss of vascular contrast. However, full utilization of the laser scan speed has been hindered by the computationally intensive signal processing required by SS-OCT and SV calculations. Using a commercial graphics processing unit that has been optimized for parallel data processing, we report a complete high-speed SS-OCT platform capable of real-time data acquisition, processing, display, and saving at 108,000 lines per second. Subpixel image registration of structural images was performed in real-time prior to SV calculations in order to reduce decorrelation from stationary structures induced by the bulk tissue motion. The viability of the system was successfully demonstrated in a high bulk tissue motion scenario of human fingernail root imaging where SV images (512 × 512 pixels, n = 4) were displayed at 54 frames per second.     

Complete complex conjugate resolved heterodyne swept-source optical coherence tomography using a dispersive optical delay line

Swept-source optical coherence tomography (SSOCT) provides a substantial sensitivity advantage over its time-domain counterpart, but suffers from a reduced imaging depth range due to sensitivity falloff and complex conjugate ambiguity. Heterodyne complex conjugate-resolved SSOCT (HCCR-SSOCT) has been previously demonstrated as a technique to completely resolve the complex conjugate ambiguity, effectively doubling the falloff limited imaging depth, without the reduction in imaging speed associated with other CCR techniques. However, previous implementations of this technique have employed expensive and lossy optical modulators to provide the required differential phase modulation. In this paper, we demonstrate the use of a dispersive optical delay line (D-ODL) as the reference arm of an OCT system to realize HCCR-SSOCT. This technique maintains the existing advantages of HCCR-SSOCT in that it completely resolves the complex conjugate artifact and does not reduce imaging speed, while conferring the additional advantages of being low cost, maintaining system sensitivity and resolution, not requiring any additional signal processing, and working at all wavelengths and imaging speeds. The D-ODL also allows for hardware correction of unbalanced dispersion in the reference and sample arm, adding further flexibility to system design. We demonstrate the technique using an SSOCT system operating at 100kHz with a central wavelength of 1040nm. Falloff measurements performed using a standard OCT configuration and the proposed D-ODL demonstrate a doubling of the effective imaging range with no sensitivity or resolution penalty. Feasibility of the technique for in vivo imaging was demonstrated by imaging the ocular anterior segments of healthy human volunteers.