Non-invasive in vivo functional optical imaging is emonstrated using high-speed, ultrahigh resolution optical coherence tomography (UHR-OCT). A high-speed, UHR-OCT system using spectral/Fourier domain detection was developed for functional imaging experiments in the rodent retina. Using a spectrally multiplexed superluminescent diode light source, imaging was performed with 2.8 μm resolution at a rate of 24,000 axial scans per second. OCT measurement protocols were designed to minimize noise sources that cause undesired fluctuations in the measured OCT signal. A white light stimulus was applied to the retina and the average reflectivity from each intraretinal layer was monitored over time using OCT. A white light stimulus induces a response consisting of an increase in the reflectance of the photoreceptor outer segments. To our knowledge, this is the first in vivo demonstration of functional imaging using OCT in the retina. Further systematic investigation will be required to fully characterize the observed optical changes. Eventually, this may prove to be an objective method for measuring photoreceptor function in the human retina.
High performance, short coherence length light sources with broad bandwidths and high output powers are critical for high speed, ultrahigh resolution OCT imaging. We demonstrate an all-fiber continuous-wave Raman light source based on a photonic crystal fiber, pumped by a continuous-wave Yb-fiber laser, which generates 330 mW output power and 140 nm bandwidths. The light source is compact, robust, turnkey and requires no optical alignment. In vivo high speed, ultrahigh resolution OCT imaging of tissues with < 5 μm axial resolution at 1.3 μm center wavelength is demonstrated.
We present clinical data obtained with the aid of a novel instrumentation using, high speed, ultrahigh resolution Spectral/Fourier domain Optical Coherence Tomography (SOCT). This method allows performing video rate, ultrahigh resolution cross-sectional images with 98 dB of sensitivity, 100 times faster that previously reported UHR OCT system with comparable axial resolution of 3 um. Ultrahigh resolution imaging enables improved visualization of retinal architectural morphology compared to standard resolution OCT. High speed, ultrahigh resolution OCT using Spectral/Fourier domain detection promises to significantly enhance the utility of OCT for clinical applications. High speed imaging enables high density data sets to be acquired which can increase the quality of reconstructed cross-sectional images and can help to visualize small focal pathologic changes. This technique helps reconstructing true retinal topography without motion artifacts. Submitted manuscript describes the technology, its clinical performance and present preliminary data obtained for various retinal pathologies.
Ultrahigh resolution OCT using broadband light sources achieves improved axial image resolutions of ~2-3 um compared to standard 10 um resolution OCT used in current commercial instruments. High-speed OCT using Fourier/spectral domain detection enables dramatic increases in imaging speeds. 3D OCT retinal imaging is performed in human subjects using high-speed, ultrahigh resolution OCT, and the concept of an OCT fundus image is introduced. Three-dimensional data and high quality cross-sectional images of retinal pathologies are presented. These results show that 3D OCT may be used to improve coverage of the retina, precision of cross-sectional image registration, quality of cross-sectional images, and visualization of subtle changes in retinal topography. 3D OCT imaging and mapping promise to help elucidate the structural changes associated with retinal disease as well as to improve early diagnosis and monitoring of disease progression and response to treatment.
We demonstrate a high-speed tunable, continuous wave laser source for Fourier domain OCT. The laser source is based on a fiber coupled, semiconductor optical amplifier and a tunable ultrahigh finesse, fiber Fabry Perot filter for frequency tuning. The light source provides frequency scan rates of up to 20,000 sweeps per second over a wavelength range of >70 nm FWHM at 1330 nm, yielding an axial resolution of ~14 μm in air. The linewidth is narrow and corresponds to a coherence length of several mm, enabling OCT imaging over a large axial range.
An ultrahigh resolution spectral domain optical coherence tomography (OCT) system capable of performing high speed imaging in the ophthalmology clinic has been developed. An OCT system using spectral/Fourier domain enables high speed imaging rates of up to 25,000 axial scans (A-scan) per second. Using a low threshold femtosecond Ti:sapphire laser light source, which can generate bandwidths of ~125 nm at 800 nm, cross-sectional imaging of the retina with ~3 μm axial resolution is possible. High speed imaging has been performed in the ophthalmology clinic on patients with various retinal pathologies using the ultrahigh resolution spectral domain OCT system. High pixel density OCT images containing 1024 pixels and 2048 transverse lines (A-scans) can be acquired in 0.08 seconds, which represents a ~100 fold improvement in imaging speed over previously reported time-domain ultrahigh resolution OCT systems. High speed imaging also enables three dimensional scanning and mapping of intraretinal architectural morphology with unprecedented resolution. High speed ultrahigh resolution OCT is a powerful tool for visualizing retinal pathologies, especially those involving the details of the photoreceptor segments; it will enable three-dimensional retinal imaging and the rendering of image information from volumetric data, and it has the potential to improve the early diagnosis of retinal diseases.
In vivo ultrahigh resolution ophthalmic OCT has been performed in more than 300 eyes of 200 patients with several retinal pathologies, demonstrating unprecedented visualization of all major intraretinal layers, in particular the photoreceptor layer. Visualization as well as quantification of the inner and outer segment of the photoreceptor layer especially in the foveal region has been acvhieved. In normal subjects the photoreceptor layer thickness in the center of the fovea is about of 90 μm, approximately equally distributed to the inner and the outer photoreceptor segment. In the parafoveal region this thickness is reduced to ~50 μm (~30 μm for the inner and ~20 μm for the outer segment). This is in good agreement with well known increase of cone outer segments in the central foveal region. Photoreceptor layer impairment in different macular pathologies like macular hole, central serous chorioretinopathy, age related macular degeneration, foveomacular dystrophies, Stargardt dystrophy as well as retinitis pigmentosa has been investigated. Photoreceptor layer loss significantly correlated with visual acuity (R2 = 0.6, p < 0.001) and microperimetry findings for the first time in 22 eyes with Stargardt dystrophy. Visualization and quantification of photoreceptor inner and outer segment using ultrahigh resolution OCT has the potential to improve early ophthalmic diagnosis, contributes to a better understanding of pathogenesis of retinal diseases as well as might have impact in the development and monitoring of novel therapy approaches.
Ultrahigh resolution ophthalmic OCT has been performed in more than 250 eyes of 160 patients, demonstrating unprecedented visualization of intraretinal morphology of several retinal pathologies. and therefore the potential to enhance sensitivity and specificity for early ophthalmic diagnosis as well as to monitor the efficacy of therapy. In addition, it might contribute to a better understanding of ocular pathogenesis. This is demonstrated by investigating both normal retinal morphology in an animal model and the impairment of the photoreceptor layer in different macular pathologies.
We demonstrate methods for achieving high resolution imaging using alternate scanning techniques in optical coherence tomography and optical coherence microscopy. These techniques enable high transverse resolutions and overcome depth of field limitations. Cellular level resolutions in human tissue may be achieved.
Ultrahigh resolution OCT is used to visualize experimentally induced osteoarthritis in a rat knee model. Using a Cr4+:Forsterite laser, ultrahigh image resolutions of 5um are achieved. Progression of osteoarthritic remodeling and cartilage degeneration are quantified. The utility of OCT for the assessment of cartilage integrity is demonstrated.
KEYWORDS: Optical coherence tomography, In vivo imaging, Image resolution, Imaging systems, Femtosecond phenomena, Neodymium glass lasers, Light sources, Single mode fibers, Skin, Real time imaging
We demonstrate compact ultrahigh resolution OCT systems for in vivo studies, with broadband light sources based on a commercially available Nd:Glass femtosecond laser and nonlinear fiber continuum generation. In vivo OCT images of hamster cheek pouch and human skin acquired at 4 frames per second and with 5.5 μm axial resolution are presented. These systems are robust, compact and portable.
We demonstrate real time, ultrahigh resolution OCT imaging using a portable mode-locked Cr:forsterite laser. OCT imaging at 5.5 um axial resolution was performed of normal and cancerous human prostate tissue and correlated with histology.
Ultrahigh resolution OCT imaging is demonstrated using compact broadband light sources based on a commercially available Nd:Glass femtosecond laser with nonlinear fiber continuum generation. A tapered single mode fiber is used to generate broadband light centered at 1300 nm. Broadband light near 1064 nm can also be generated using a high numerical aperture single mode germanium doped fiber. These light sources enable ultrahigh resolution OCT imaging with 5-6 μm axial resolution at both 1064 nm and 1300 nm.
An ultrahigh resolution ophthalmic optical coherence tomography (OCT) system has been developed. Using a femtosecond Ti:sapphire laser light source, which generates bandwidths of ~150 nm at 800 nm, real-time, cross-sectional imaging of the retina with ~3 μm axial resolution is possible. Ultrahigh resolution OCT images of retinal morphology were obtained in normal subjects and patients with retinal disease. Intraretinal architectural morphology associated with macular diseases such as macular edema, epiretinal membranes, and macular holes can be visualized with unprecedented resolution. Ultrahigh resolution ophthalmic OCT promises to improve the early diagnosis of retinal diseases as well as enable monitoring of disease progression and the efficacy of therapeutic intervention.
Quantitative, three-dimensional mapping of retinal architectural morphology was achieved using an ultrahigh resolution ophthalmic OCT system. This OCT system utilizes a broad bandwidth titanium-sapphire laser light source generating bandwidths of up to 300 nm near 800 nm center wavelength. The system enables real-time cross-sectional imaging of the retina with ~3 micrometers axial resolution. The macula and the papillomacular axis of a normal human subject were systematically mapped using a series of linear scans. Edge detection and segmentation algorithms were developed to quantify retinal and intraretinal thicknesses. Topographic mapping of the total retinal thickness and the total ganglion cell/inner plexiform layer thickness was achieved around the macula. A topographic mapping quantifying the progressive thickening of the nerve fiber layer (NFL) nasally approaching the optic disk was also demonstrated. The ability to create three-dimensional topographic mapping of retinal architectural morphology at ~3 micrometers axial resolution will be relevant for the diagnosis of many retinal diseases. The topographic quantification of these structures can serve as a powerful tool for developing algorithms and clinical scanning protocols for the screening and staging of ophthalmic diseases such as glaucoma.
A miniature fiber Doppler imaging catheter for integrated functional and structural optical coherence tomography (OCT) imaging has been developed. The Doppler catheter can be used to map blood flow profile within a vessel as well as image vessel wall structures. The prototype Doppler catheter was demonstrated in measuring the intraluminal velocity profile in a vessel phantom (conduit). A simple mathematical model can be used to estimate the flow profile outside of normal OCT beam penetration. By extending the spatial range of the flow measurements to approximately two times the normal OCT image penetration depth, the total flow rate can then be calculated from the estimated velocity profiles. The measured total flow rate in the vessel phantom obtained from the Doppler imaging catheter correlates well with the calibrated flow values. The Doppler OCT catheter's ability to simultaneously obtain both structural and functional information makes it a potentially powerful device of cardiovascular imaging.
We demonstrate ultrahigh resolution optical coherence tomography using the continuum generation in an air-silica microstructure fiber. A broadband OCT system was developed, supporting a bandwidth of 370 nm at 1.3 micrometers center wavelength. We achieved longitudinal resolutions of 2.5 micrometers in air, or approximately 2 micrometers in tissue. This is to our knowledge the highest longitudinal OCT resolution demonstrated at this wavelength range and the first application of this new light source for OCT. We will also describe the application of this technique for imaging biological tissue in vivo.
We demonstrate in vivo optical coherence tomography imaging of neoplasia in patients using an integrated OCT colposcope. OCT images of epithelial structure were correlated with histological findings in patients with cervical intraepithelial neoplasia and cancer.
Many studies have been performed which compare ex-vivo OCT imaging to histopathology in a wide range of tissues and organ systems. While some tissues, such as arterial pathology or cartilage, are relatively stable post mortem, others, such as epithelial tissues, exhibit rapid degradation. It is important to preserve these tissues with minimal changes in morphology relative to their in vivo state in order to enable meaningful ex vivo OCT imaging studies. In this paper, we investigate the differences between in vivo and ex vivo OCT imaging and the effect of different tissue preservation solutions on tissue degradation and image quality. Ultrahigh resolution OCT imaging was preformed using a Ti:Al2O3 light source with 2 micrometers axial and 5 micrometers transverse resolution, using the hamster cheek pouch as a model for epithelial tissue. Tissue preservation solutions examined included: low temperature saline, room temperature saline, phosphate buffered sucrose, University of Wisconsin solution, and 10% formalin. Results of in vivo versus ex vivo ultrahigh resolution OCT imaging indicate that changes in optical properties and image degradation occur on a rapid time scale (in minutes) for all preservation solutions except formalin.
We demonstrate a low cost, high-speed scanning delay line using a Herriott cell cavity and electromagnetic actuation. Path length scanning at 2 kHz repetition rate is demonstrated for real time OCT imaging.
Optical coherence tomography (OCT) is an emerging technology capable of imaging tissue architectural morphology at micron scale resolution . OCT was first developed to image the relatively transparent suctures in the eye 2,3 and later applied extensively in highly scattering tissues for moiphologic and functional imaging with unprecedented resolution 48 Real-time, in vivo imaging and ultrahigh (1 tm) resolution imaging have also been demonstrated. A variety of applications of OCT imaging have been made possible by designing novel OCT delivery/collection probes. Examples include a forward imaging hand-held probe for assessing tissue during open field surgery 11,12 and a transverse scanning OCT endoscope/catheter for imaging hollow organs such as the gastrointestinal tract and cardiovascular system 1318 oT applications have been limited to the surfaces or lumina of organ systems because the penetration depth of OCT is 2-3 mm and also because high transverse resolution is only achievable within a short confocal length. To date, it has not been possible to image structures inside solid tissues or organs. However, there are many clinical scenarios where high resolution internal imaging of solid tissues is required. One such application of OCT is to image pathology and guide biopsy in solid tissues. Other applications include optical imaging where excisional biopsy is hazardous, and surgical guidance such as in cryosurgery or interstitial photodvnmic therapy.
Using state of the art laser technology, third generation ophthalmologic optical coherence tomography (OCT) has been developed which enables ultrahigh resolution, non-invasive in vivo imaging of retinal morphology with an unprecedented axial resolution of 3 micrometers . This represents a quantum leap in performance over the 10-15 micrometers resolution currently available in ophthalmic OCT systems and, to our knowledge, is the highest resolution in vivo ophthalmologic imaging achieved to date. This resolution enables optical biopsy, i.e. the in vivo visualization of intraretinal architectural morphology which had previously only been possible with histopathology. Image processing and segmentation techniques are demonstrated for automatic identification and quantification of retinal morphology. Ultrahigh resolution ophthalmic OCT has the potential to enhance the sensitivity and specificity for early diagnosis of several ocular diseases, e.g. glaucoma, which requires precise imaging and measurement of retinal nerve fiber layer thickness, as well as improve monitoring of disease progression and efficacy of therapy.
We demonstrate ultrahigh resolution optical coherence tomography using the continuum generation in an air-silica microstructure fiber. A broadband OCT system was developed, supporting a bandwidth of 370 nm at 1.3 micrometers center wavelength. We achieved longitudinal resolutions of 2.5 micrometers in air, or ~2 micrometers in tissue. This is to our knowledge with the highest longitudinal OCT resolution demonstrated at this wavelength range and the first application of this new light source for OCT. We will also describe the application of this technique for imaging biological tissue in vivo.
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