Akinetic all-semiconductor programmable swept-source at 1550 nm and 1310 nm with centimeters coherence length.

We demonstrate, for the first time, OCT imaging capabilities of a novel, akinetic (without any form of movement in the tuning mechanism), all-semiconductor, all-electronic tunable, compact and flexible swept source laser technology at 1550 nm and 1310 nm. To investigate its OCT performance, 2D and 3D ex vivo and in vivo OCT imaging was performed at different sweep rates, from 20 kHz up to 200 kHz, with different axial resolutions, about 10 µm to 20 µm, and at different coherence gate displacements, from zero delay to >17 cm. Laser source phase linearity and phase repeatability standard deviation of <2 mrad (<160 pm) were observed without external phase referencing, indicating that the laser operated close to the shot noise limit (~2 × factor); constant percentile wavelengths variations of sliding RIN and ortho RIN <0.2% could be demonstrated, ~5 times better as compared to other swept laser technologies.

Temporal changes of human cone photoreceptors observed in vivo with SLO/OCT.

In this study we use our previously introduced scanning laser ophthalmoscope (SLO) / transverse scanning optical coherence tomography (TS-OCT) instrument to investigate long term changes in cone photoreceptors. The instrument is capable to provide 3D information of the human cone photoreceptors with negligible eye motion artifacts due to an implemented 3D motion correction on a cellular level. This allows for an in vivo investigation of exactly the same location on the retina with cellular resolution over several days. Temporal changes in the backscattered intensity are observed and quantified within the junction between inner and outer segments of cone photoreceptors, the cone outer segments, the end tips of cone photoreceptors and the retinal pigment epithelium. Furthermore, the length of individual cone outer segments is measured and observed over time. We show, to the best of our knowledge for the first time, that bright reflection spots which are located within the outer segment of cone photoreceptors change their position when observed over extended time periods. The average measured bright reflection spot motion speed corresponds well to the expected cone growth speed. We believe that this observation can be associated with the first direct in vivo imaging of the cone renewal process.

Optophysiology: depth-resolved probing of retinal physiology with functional ultrahigh-resolution optical coherence tomography.

Noncontact, depth-resolved, optical probing of retinal response to visual stimulation with a <10-microm spatial resolution, achieved by using functional ultrahigh-resolution optical coherence tomography (fUHROCT), is demonstrated in isolated rabbit retinas. The method takes advantage of the fact that physiological changes in dark-adapted retinas caused by light stimulation can result in local variation of the tissue reflectivity. fUHROCT scans were acquired from isolated retinas synchronously with electrical recordings before, during, and after light stimulation. Pronounced stimulus-related changes in the retinal reflectivity profile were observed in the inner/outer segments of the photoreceptor layer and the plexiform layers. Control experiments (e.g., dark adaptation vs. light stimulation), pharmacological inhibition of photoreceptor function, and synaptic transmission to the inner retina confirmed that the origin of the observed optical changes is the altered physiological state of the retina evoked by the light stimulus. We have demonstrated that fUHROCT allows for simultaneous, noninvasive probing of both retinal morphology and function, which could significantly improve the early diagnosis of various ophthalmic pathologies and could lead to better understanding of pathogenesis.

In vivo retinal optical coherence tomography at 1040 nm - enhanced penetration into the choroid.

For the first time in vivo retinal imaging has been performed with a new compact, low noise Yb-based ASE source operating in the 1 microm range (NP Photonics, lambdac = 1040 nm, Deltalambda = 50 nm, Pout = 30 mW) at the dispersion minimum of water with ~7 microm axial resolution. OCT tomograms acquired at 800 nm are compared to those achieved at 1040 nm showing about 200 microm deeper penetration into the choroid below the retinal pigment epithelium. Retinal OCT at longer wavelengths significantly improves the visualization of the retinal pigment epithelium/choriocapillaris/choroids interface and superficial choroidal layers as well as reduces the scattering through turbid media and therefore might provide a better diagnosis tool for early stages of retinal pathologies such as age related macular degeneration which is accompanied by choroidal neovascularization, i.e., extensive growth of new blood vessels in the choroid and retina.

Adaptive-optics ultrahigh-resolution optical coherence tomography.

Merging of ultrahigh-resolution optical coherence tomography (UHR OCT) and adaptive optics (AO), resulting in high axial (3 microm) and improved transverse resolution (5-10 microm) is demonstrated for the first time to our knowledge in in vivo retinal imaging. A compact (300 mm x 300 mm) closed-loop AO system, based on a real-time Hartmann-Shack wave-front sensor operating at 30 Hz and a 37-actuator membrane deformable mirror, is interfaced to an UHR OCT system, based on a commercial OCT instrument, employing a compact Ti:sapphire laser with 130-nm bandwidth. Closed-loop correction of both ocular and system aberrations results in a residual uncorrected wave-front rms of 0.1 microm for a 3.68-mm pupil diameter. When this level of correction is achieved, OCT images are obtained under a static mirror configuration. By use of AO, an improvement of the transverse resolution of two to three times, compared with UHR OCT systems used so far, is obtained. A significant signal-to-noise ratio improvement of up to 9 dB in corrected compared with uncorrected OCT tomograms is also achieved.

Advances in broad bandwidth light sources for ultrahigh resolution optical coherence tomography.

Novel ultra-broad bandwidth light sources enabling unprecedented sub-2 microm axial resolution over the 400 nm-1700 nm wavelength range have been developed and evaluated with respect to their feasibility for clinical ultrahigh resolution optical coherence tomography (UHR OCT) applications. The state-of-the-art light sources described here include a compact Kerr lens mode locked Ti:sapphire laser (lambdaC = 785 nm, delta lambda = 260 nm, P(out) = 50 mW) and different nonlinear fibre-based light sources with spectral bandwidths (at full width at half maximum) up to 350 nm at lambdaC = 1130 nm and 470 nm at lambdaC = 1375 nm. In vitro UHR OCT imaging is demonstrated at multiple wavelengths in human cancer cells, animal ganglion cells as well as in neuropathologic and ophthalmic biopsies in order to compare and optimize UHR OCT image contrast, resolution and penetration depth.

Precision of extracting absorption profiles from weakly scattering media with spectroscopic time-domain optical coherence tomography.

The feasibility of spectroscopic optical coherence tomography (SOCT) to quantify spatially localized absorption profiles of chromophores embedded in weakly scattering media with a single measurement over the full spectral bandwidth of the light source was investigated by using a state-of-the-art ultra-broad bandwidth Ti:Al(2)O(3) laser (lambdac = 800 nm, Deltalambda = 260 nm, P(out) = 120 mW ex-fiber). The precision of the method as a function of the chromophore absorption, the sample thickness, and different parameters related to the measurement procedure was evaluated both theoretically and experimentally in single and multilayered phantoms. It is demonstrated that in weakly scattering media SOCT is able to extract mua(lambda) as small as 0.5 mm-1 from 450 mum thick phantoms with a precision of ~2% in the central and ~8% at the edges of the used wavelength region. As expected, in phantoms with the same absorption properties and thickness ~180 mum the precision of SOCT decreases to >10% in the central wavelength region.

Compact, low-cost Ti:Al2O3 laser for in vivo ultrahigh-resolution optical coherence tomography.

A compact, low-cost, prismless Ti:Al2O3 laser with 176-nm bandwidth (FWHM) and 20-mW output power was developed. Ultrahigh-resolution ophthalmic optical coherence tomography (OCT) ex vivo imaging in an animal model with approximately 1.2-microm axial resolution and in vivo imaging in patients with macular pathologies with approximately 3-microm axial resolution were demonstrated. Owing to the pump laser, this light source significantly reduces the cost of broadband OCT systems. Furthermore, the source has great potential for clinical application of spectroscopic and ultrahigh-resolution OCT because of its small footprint (500 mm x 180 mm including the pump laser), user friendliness, stability, and reproducibility.

Compact, broad-bandwidth fiber laser for sub-2-microm axial resolution optical coherence tomography in the 1300-nm wavelength region.

A novel, compact, user friendly fiber laser with a broad emission bandwidth (MenloSystems, lambdac = 1375 nm, deltalambda = 470 nm, Pout = 4 mW) was used to achieve unprecedented sub-2-microm axial resolution optical coherence tomography (OCT) in nontransparent biological tissue in the 1300-nm wavelength region. Fresh human skin and arterial biopsies were imaged ex vivo with approximately 1.4-microm axial and approximately 3-microm lateral resolution and 95-dB sensitivity, demonstrating the great potential for clinical OCT applications of this stable, low-cost, and turn-on-key fiber laser.

Enhanced visualization of choroidal vessels using ultrahigh resolution ophthalmic OCT at 1050 nm.

In this article the ability of ultrahigh resolution ophthalmic optical coherence tomography (OCT) to image small choroidal blood vessels below the highly reflective and absorbing retinal pigment epithelium is demonstrated for the first time. A new light source (lambdac= 1050 nm, Deltalambda = 165 nm, Pout= 10 mW), based on a photonic crystal fiber pumped by a compact, self-starting Ti:Al2O3 laser has therefore been developed. Ex-vivo ultrahigh resolution OCT images of freshly excised pig retinas acquired with this light source demonstrate enhanced penetration into the choroid and better visualization of choroidal vessels as compared to tomograms acquired with a state-of-the art Ti:Al2O3 laser (Femtolasers Compact Pro, lc= 780 nm, Deltalambda= 160 nm, Pout= 400 mW), normally used in clinical studies for in vivo ultrahigh resolution ophthalmic OCT imaging. These results were also compared with retinal tomograms acquired with a novel, spectrally broadened fiber laser (MenloSystems, lambdac= 1350 nm, Deltalambda= 470 nm, Pout = 4 mW) permitting even greater penetration in the choroid. Due to high water absorption at longer wavelengths retinal OCT imaging at ~1300 nm may find applications in animal ophthalmic studies. Detection and follow-up of choroidal neovascularization improves early diagnosis of many retinal pathologies, e.g. age-related macular degeneration or diabetic retinopathy and can aid development of novel therapy approaches.

Submicrometer axial resolution optical coherence tomography.

Optical coherence tomography (OCT) with unprecedented submicrometer axial resolution achieved by use of a photonic crystal fiber in combination with a compact sub-10-fs Ti:sapphire laser (Femtolasers Produktions) is demonstrated for what the authors believe is the first time. The emission spectrum ranges from 550 to 950 nm (lambda(c)=725 nm , P(out)=27 mW) , resulting in a free-space axial OCT resolution of ~0.75 mum , corresponding to ~0.5 mum in biological tissue. Submicrometer-resolution OCT is demonstrated in vitro on human colorectal adenocarcinoma cells HT-29. This novel light source has great potential for development of spectroscopic OCT because its spectrum covers the absorption bands of several biological chromophores.

Resolution-improved dual-beam and standard optical coherence tomography: a comparison.

BACKGROUND: The purpose of the study was to demonstrate the improved axial resolution and longitudinal stability of dual-beam optical coherence tomography (OCT) in comparison to conventional OCT setups used in commercially available OCT instruments. METHODS: The conventional OCT technique is based on an interferometric setup that is rather sensitive to axial eye motions. We have developed a special dual-beam OCT technique which eliminates the influence of axial eye motions. This is achieved by using the anterior corneal surface as the reference surface for the interferometric ranging. To improve the signal quality, the different wavefront curvatures of beams reflected at cornea and retina are matched by a diffractive optical element. To improve the axial resolution, a broadband synthesized light source with an effective bandwidth of 50 nm is used, and the group dispersion of the ocular media is compensated. Tomographic images were recorded in the fovea and the optic nerve head of healthy volunteers. For comparison purposes, approximately the same locations in the same eyes were imaged by a commercially available OCT instrument. RESULTS: Compared to the standard OCT technique, the dual-beam OCT images show considerably improved axial resolution. Especially in tomograms recorded at the fovea, dual-beam OCT resolves microstructural details that are not visible in the standard OCT images. Furthermore, the axial stability of dual-beam OCT enables the recording of exact geometrical contours of fundus layers. CONCLUSIONS: Dual-beam OCT is able to provide structural information on the ocular fundus that is not obtained with standard OCT. The long recording times of our instrument limit the transverse resolution to 100-150 microm at present.

Polarization-sensitive optical coherence tomography of dental structures.

Optical coherence tomography (OCT) has been developed during the last 10 years as a new noninvasive imaging tool and has been applied to diagnose different ocular and skin diseases. This technique has been modified for cross-sectional imaging of dental structures. In this first preliminary study the technique was applied to obtain tomographic images of extracted sound and decayed human teeth in order to evaluate its possible diagnostic potential for dental applications. Classical OCT images based on reflectivity measurements and phase retardation images using polarization-sensitive OCT were recorded. It was demonstrated that polarization-sensitive OCT can provide additional information which is probably related to the mineralization status and/or the scattering properties of the dental material. One of the attractive features of OCT is that it uses near-infrared light instead of ionizing radiation. Furthermore, high transversal and depth resolution on the order of 10 microm can be obtained. Present limitations, e.g. the limited penetration depth, and possible solutions are discussed.

Investigation of dispersion effects in ocular media by multiple wavelength partial coherence interferometry.

We report on quantitative measurements of group refractive indices and group dispersion in water and in human ocular media such as the cornea, the aqueous humor, the lens, artificial intraocular lenses, as well as a total value averaged over the media along the axial eye length of normal subjects and pseudophakic patients in vivo using dual beam partial coherence interferometry. Different optical thickness values due to the dispersion of the cornea are demonstrated using two spectrally displaced light sources. The displacement can be used to indirectly calculate the group dispersion of the human cornea in the spectral region between 810 nm and 860 nm. If the object under investigation is dispersive, resolution is limited due to a broadening of the detected signals. This broadening increases with group dispersion, i.e., the extent to which the group refractive index of the medium varies with wavelength and thickness of the tissue under investigation as well as with the spectral bandwidth of the light source. Measurements of the group dispersion in the cornea, lens and vitreous of pseudophakic and normal human eyes, show that the cornea and the lens are more dispersive than water-by a factor of about 5 and 2, respectively-in the investigated spectral region. The cornea is approximately threefold more dispersive than the human crystalline lens, the aqueous humor is less dispersive than water and the group dispersion of all ocular components together, averaged over the axial length of normal and pseudophakic eyes, was only slightly higher compared to that of water. Since the highly dispersive cornea and lens together have only a thickness of about one sixth of that of the axial eye length, it seems that their contribution to the group dispersive effect along the whole axial eye length is only small.

Signal and resolution enhancements in dual beam optical coherence tomography of the human eye.

In the past 10 years, a dual beam version of partial coherence interferometry has been developed for measuring intraocular distances in vivo with a precision on the order of 0.3 to 3 µm. Two improvements of this technology are described. A special diffractive optical element allows matching of the wavefronts of the divergent beam reflected at the cornea and the parallel beam reflected at the retina and collimated by the optic system of the eye. In this way, the power of the light oscillations of the interfering beams incident on the photodetector is increased and the signal-to-noise ratio of in vivo measurements to the human retina is improved by 20 to 25 dB. By using a synthesized light source consisting of two spectrally displaced superluminescent diodes with an effective bandwidth of 50 nm, and by compensating for the dispersive effects of the ocular media, it was possible to record the first optical coherence tomogram of the retina of a human eye in vivo with an axial resolution of ∼6 to 7 µm. This is a twofold improvement over the current technology. © 1998 Society of Photo-Optical Instrumentation Engineers.

Submicrometer precision biometry of the anterior segment of the human eye.

PURPOSE: To demonstrate the feasibility of measuring the anterior structures of the human eye by partial coherence interferometry and to determine its precision for eyes under normal and cycloplegic conditions. METHODS: The dual-beam version of partial coherence interferometry, a recently developed noninvasive optical ranging technique, enables high resolution measurements of several intraocular distances with unprecedented precision. A modified, more sensitive scanning version of this technique was used to assess the central and peripheral corneal thickness, the anterior chamber depth, and the lens thickness of 20 healthy, emmetropic to moderately myopic eyes. Furthermore the anterior structures of three eyes were measured under cycloplegia (1% cyclopentolate) to investigate the influence on the precision of this technique after suppression of residual accommodations. RESULTS: The mean geometric precision (standard deviation) of the measurement of the central corneal thickness was 0.29 micron (range, 0.22 micron to 0.38 micron) and 0.43 micron (range, 0.27 micron to 0.56 micron) for the peripheral corneal thickness at a distance 2 mm from its apex. The precision for measuring the anterior chamber depth and the lens thickness for fixation at infinity was 8.7 microns (range, 3.9 microns to 16.8 microns) and 8.9 microns (rang, 2.9 microns to 14.4 microns) for noncycloplegic eyes and 1.9 microns (range, 1.7 microns to 2 microns) and 1.4 microns (range, 0.7 micron to 1.8 microns) for cycloplegic eyes, respectively. CONCLUSIONS: The dual-beam partial coherence interferometry enables fast, noninvasive, submicrometer precision biometry of the anterior segment of the eye. The precision of determining the anterior chamber depth and the lens thickness is more than one order of magnitude better than that of the currently used ultrasound and optical techniques, and it can be improved by a factor of 5 by using cycloplegia.