Ophthalmic Optical Coherence Tomography System Research Articles

Robotic Optical Coherence Tomography of Human Subjects with Posture-Invariant Head and Eye Alignment in Six Degrees of Freedom.

Ophthalmic optical coherence tomography (OCT) has achieved remarkable clinical success but remains sequestered in ophthalmology specialty offices. Recently introduced robotic OCT systems seek to expand patient access but fall short of their full potential due to significant imaging workspace and motion planning restrictions. Here, we present a next-generation robotic OCT system capable of imaging in any head orientation or posture that is mechanically reachable. This system overcomes prior restrictions by eliminating fixed-base tracking components, extending robot reach, and planning alignment in six degrees of freedom. With this robotic system, we show repeatable subject imaging independent of posture (standing, seated, reclined, and supine) under widely varying head orientations for multiple human subjects. For each subject, we obtained a consistent view of the retina, including the fovea, retinal vasculature, and edge of the optic nerve head. We believe this robotic approach can extend OCT as an eye disease screening, diagnosis, and monitoring tool to previously unreached patient populations.

Wide-field Ophthalmic Space-Division Multiplexing Optical Coherence Tomography.

High-speed ophthalmic optical coherence tomography systems are of interest because they allow rapid, motion-free, and wide-field retinal imaging. Space-division multiplexing optical coherence tomography (SDM-OCT) is a high-speed imaging technology which takes advantage of the long coherence length of microelectromechanical vertical cavity surface emitting laser (MEMs VCSEL) sources to multiplex multiple images along a single imaging depth. We demonstrate wide-field retinal OCT imaging, acquired at an effective A-scan rate of 800,000 A-scans/sec with volumetric images covering up to 12.5 mm × 7.4 mm on the retina acquired in less than 1 second. A clinical feasibility study was conducted to compare the ophthalmic SDM-OCT with commercial OCT systems, illustrating the high-speed capability of SDM-OCT in a clinical setting.

Adaptive optics optical coherence tomography at 1 MHz.

Image acquisition speed of optical coherence tomography (OCT) remains a fundamental barrier that limits its scientific and clinical utility. Here we demonstrate a novel multi-camera adaptive optics (AO-)OCT system for ophthalmologic use that operates at 1 million A-lines/s at a wavelength of 790 nm with 5.3 μm axial resolution in retinal tissue. Central to the spectral-domain design is a novel detection channel based on four high-speed spectrometers that receive light sequentially from a 1 × 4 optical switch assembly. Absence of moving parts enables ultra-fast (50ns) and precise switching with low insertion loss (-0.18 dB per channel). This manner of control makes use of all available light in the detection channel and avoids camera dead-time, both critical for imaging at high speeds. Additional benefit in signal-to-noise accrues from the larger numerical aperture afforded by the use of AO and yields retinal images of comparable dynamic range to that of clinical OCT. We validated system performance by a series of experiments that included imaging in both model and human eyes. We demonstrated the performance of our MHz AO-OCT system to capture detailed images of individual retinal nerve fiber bundles and cone photoreceptors. This is the fastest ophthalmic OCT system we know of in the 700 to 915 nm spectral band.

In vivo Ultrahigh-Resolution Ophthalmic Optical Coherence Tomography Using Gaussian-Shaped Supercontinuum

We have demonstrated the in vivo ultrahigh-resolution optical coherence tomography (OCT) imaging of the human eye using a Gaussian-shaped supercontinuum source. Using an ultrashort-pulse Ti:sapphire laser and a polarization-maintaining single-mode fiber, a linearly polarized, high-power, low-noise, Gaussian-shaped supercontinuum is generated in the wavelength region from 700 to 950 nm. For ophthalmic imaging, a wideband Gaussian-shaped supercontinuum with a bandwidth of 140 nm is generated at a center wavelength of 830 nm. The observed axial resolutions are 2.9 µm in air and 2.1 µm in tissue. The generated supercontinuum is combined with a modified ophthalmic OCT system, and sidelobe-free ultrahigh-resolution OCT images of the human retina and cornea are obtained.

Enhancing the signal-to-noise ratio in ophthalmic optical coherence tomography by image registration—method and clinical examples

Optical coherence tomography (OCT) has already proven an important clinical tool for imaging and diagnosing retinal diseases. Concerning the standard commercial ophthalmic OCT systems, speckle noise is a limiting factor with respect to resolving relevant retinal features. We demonstrate successful suppression of speckle noise from mutually aligning a series of in vivo OCT recordings obtained from the same retinal target using the Stratus system from Humphrey-Zeiss. Our registration technique is able to account for the axial movements experienced during recording as well as small transverse movements of the scan line from one scan to the next. The algorithm is based on a regularized shortest path formulation for a directed graph on a map formed by interimage (B-scan) correlations. The resulting image enhancement typically increases the contrast-to-noise ratio (CNR) with a factor of three or more and facilitates segmentation and quantitative characterization of pathologies. The method is currently successfully being applied by medical doctors in a number of specific retinal case studies.

Compact, low-cost Ti:Al_2O_3 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.

Ultrahigh-resolution ophthalmic optical coherence tomography.

Here we present new technology for optical coherence tomography (OCT) that enables ultrahigh-resolution, non-invasive in vivo ophthalmologic imaging of retinal and corneal morphology with an axial resolution of 2–3 μm. This resolution represents a significant advance in performance over the 10–15-μm resolution currently available in ophthalmic OCT systems and, to our knowledge, is the highest resolution for in vivo ophthalmologic imaging achieved to date. This resolution enables in vivo visualization of intraretinal and intra-corneal architectural morphology that had previously only been possible with histopathology. We demonstrate image processing and segmentation techniques for automatic identification and quantification of retinal morphology. Ultrahigh-resolution OCT promises to enhance early diagnosis and objective measurement for tracking progression of ocular diseases, as well as monitoring the efficacy of therapy. Current clinical practice emphasizes the development of techniques to diagnose disease in its early stages, when treatment is most effective and irreversible damage can be prevented or delayed. In ophthalmology, the precise visualization of pathology is especially critical for the diagnosis and staging of ocular diseases. Therefore, new imaging techniques have been developed to augment conventional fundoscopy and slit-lamp biomicroscopy. Ultrasonography is routinely used in ophthalmology, but requires physical contact with the eye and has axial resolutions of approximately 200 μm (ref. 1). High-frequency ultrasound enables approximately 20 μm axial resolutions, but due to limited penetration, only anterior eye structures can be imaged2. Confocal microscopy has been used to image the cornea with sub-micrometer transverse resolution3. Scanning laser ophthalmoscopy enables en face fundus imaging with micron-scale transverse and approximately 300-μm axial resolution4,5. None of these techniques, however, permits high-resolution, cross-sectional imaging of the retina in vivo. Recently, optical coherence tomography (OCT) has emerged as a promising new technique for high-resolution, cross-sectional imaging6,7. OCT is attractive for ophthalmic imaging because image resolutions are 1–2 orders of magnitude higher than conventional ultrasound, imaging can be performed non-invasively and in real time, and quantitative morphometric information can be obtained. OCT is somewhat analogous to ultrasound imaging except that it uses light instead of sound. High-resolution, cross-sectional images are obtained by measuring the echo time delay of reflected infrared light using a technique known as low coherence interferometry8,9. OCT imaging was first demonstrated in the human retina in vitro6 and in vivo10,11. Recently, it has been extended to a wide range of other non-transparent tissues to function as a type of optical biopsy12–15. To date, however, the most important clinical applications of OCT have been retinal imaging in ophthalmic diagnosis7,16–22. Current ophthalmic OCT systems have 10–15-μm axial resolution and provide more detailed structural information than any other non-invasive ophthalmic imaging technique6,7,10,11. However, the resolution of current clinical ophthalmic OCT technology is significantly below what is theoretically possible. Improving the resolution of OCT ophthalmic imaging would enable structural imaging of retinal pathology at an intraretinal level, as well as improve the accuracy of morphometric quantification. The axial resolution of conventional ophthalmic OCT systems is limited to 10–15 μm by the bandwidth of light sources used for imaging. Short-pulse, solid-state lasers can generate ultrabroad bandwidth, low-coherence light13. A broadband Cr:Forsterite laser operating in the near infrared (1,300 nm) has permitted cellular-level OCT imaging in developmental biology specimens with 6-μm axial resolution13. For ophthalmic imaging, light sources operating at 800 nm are necessary to avoid absorption in the ocular media. Recently, a state-of-the-art broadband Ti:Al2O3 laser has been developed for ultrahigh (~1 μm) axial resolution, spectroscopic OCT imaging in non-transparent tissue at 800-nm center wavelength23,24. We describe here ultrahigh-resolution ophthalmic OCT based on this state-of-the-art optical technology and demonstrate its potential to provide enhanced structural and quantitative information for ophthalmologic imaging.