Barry Cense

Imaging retinal nerve fiber bundles using optical coherence tomography with adaptive optics.

Early detection of axonal tissue loss in retinal nerve fiber layer (RNFL) is critical for effective treatment and management of diseases such as glaucoma. This study aims to evaluate the capability of ultrahigh-resolution optical coherence tomography with adaptive optics (UHR-AO-OCT) for imaging the RNFL axonal bundles (RNFBs) with 3×3×3μm(3) resolution in the eye. We used a research-grade UHR-AO-OCT system to acquire 3°×3° volumes in four normal subjects and one subject with an arcuate retinal nerve fiber layer defect (n=5; 29-62years). Cross section (B-scans) and en face (C-scan) slices extracted from the volumes were used to assess visibility and size distribution of individual RNFBs. In one subject, we reimaged the same RNFBs twice over a 7month interval and compared bundle width and thickness between the two imaging sessions. Lastly we compared images of an arcuate RNFL defect acquired with UHR-AO-OCT and commercial OCT (Heidelberg Spectralis). Individual RNFBs were distinguishable in all subjects at 3° retinal eccentricity in both cross-sectional and en face views (width: 30-50μm, thickness: 10-15μm). At 6° retinal eccentricity, RNFBs were distinguishable in three of the five subjects in both views (width: 30-45μm, thickness: 20-40μm). Width and thickness RNFB measurements taken 7months apart were strongly correlated (p<0.0005). Mean difference and standard deviation of the differences between the two measurement sessions were -0.1±4.0μm (width) and 0.3±1.5μm (thickness). UHR-AO-OCT outperformed commercial OCT in terms of clarity of the microscopic retina. To our knowledge, these are the first measurements of RNFB cross section reported in the living human eye.

Simultaneous high-resolution retinal imaging and high-penetration choroidal imaging by one-micrometer adaptive optics optical coherence tomography

Adaptive optics optical coherence tomography (AO-OCT) provides three-dimensional high-isotropic-resolution retinal images in vivo. We developed AO-OCT with a 1.03-mum probing beam and demonstrated high-penetration, high-resolution retinal imaging. Axial scans are acquired with a speed of 47,000 lines/s. AO closed loop is configured with a single deformable mirror. Seven eyes of 7 normal subjects were examined. Signal enhancement was found for all subjects. A rippled interface between nerve fiber layer and ganglion cell layer, boundary between ganglion cell layer and inner plexiform layer, and chorioscleral interface were identified. Simultaneous high-resolution and high-penetration choroidal imaging may be useful for microstructural investigation of photoreceptors and glaucomatous nerve-fiber abnormalities.

Henle fiber layer phase retardation measured with polarization-sensitive optical coherence tomography

We developed a method based on polarization-sensitive optical coherence tomography (PS-OCT) to quantify the double pass phase retardation (DPPR) induced by Henle fiber layer in three subjects. Measurements of the retina were performed at a mean wavelength of 840 nm using two polarization states that were perpendicular in a Poincaré sphere representation and phase retardation contributions from tissue layers above and below the Henle fiber layer were excluded using appropriately placed reference and measurement points. These points were semi-automatically segmented from intensity data. Using a new algorithm to determine DPPR, the Henle fiber layer in three healthy subjects aged 50-60 years showed elevated DPPR in a concentric ring about the fovea, with an average maximum DPPR for the three subjects of 22.0° (range: 20.4° to 23.0°) occurring at an average retinal eccentricity of 1.8° (range: 1.5° to 2.25°). Outside the ring, a floor of approximately 6.8° was measured, which we show can mainly be attributed to phase noise that is induced in the polarization states. We also demonstrate the method can determine fast axis orientation of the retardation, which is found consistent with the known radial pattern of Henle fibers.

Towards model-based adaptive optics optical coherence tomography

The transfer function for optical wavefront aberrations in single-mode fiber based optical coherence tomography is determined. The loss in measured OCT signal due to optical wavefront aberrations is quantified using Fresnel propagation and the calculation of overlap integrals. A distinction is made between a model for a mirror and a scattering medium model. The model predictions are validated with measurements on a mirror and a scattering medium obtained with an adaptive optics optical coherence tomography setup. Furthermore, a one-step defocus correction, based on a single A-scan measurement, is derived from the model and verified. Finally, the pseudo-convex structure of the optical coherence tomography transfer function is validated with the convergence of a hill climbing algorithm. The implications of this model for wavefront sensorless aberration correction are discussed.

Developmental and morphological studies in Japanese medaka with ultra-high resolution optical coherence tomography

We propose ultra-high resolution optical coherence tomography to study the morphological development of internal organs in medaka fish in the post-embryonic stages at micrometer resolution. Different stages of Japanese medaka were imaged after hatching in vivo with an axial resolution of 2.8 µm in tissue. Various morphological structures and organs identified in the OCT images were then compared with the histology. Due to the medakas close resemblance to vertebrates, including humans, these morphological features play an important role in morphogenesis and can be used to study diseases that also occur in humans.

Impact of motion-associated noise on intrinsic optical signal imaging in humans with optical coherence tomography

A growing body of evidence suggests that phototransduction can be studied in the human eye in vivo by imaging of fast intrinsic optical signals (IOS). There is consensus concerning the limiting influence of motion-associated imaging noise on the reproducibility of IOS-measurements, especially in those employing spectral-domain optical coherence tomography (SD-OCT). However, no study to date has conducted a comprehensive analysis of this noise in the context of IOS-imaging. In this study, we discuss biophysical correlates of IOS, and we address motion-associated imaging noise by providing correctional post-processing methods. In order to avoid cross-talk of adjacent IOS of opposite signal polarity, cellular resolution and stability of imaging to the level of individual cones is likely needed. The optical Stiles-Crawford effect can be a source of significant IOS-imaging noise if alignment with the peak of the Stiles-Crawford function cannot be maintained. Therefore, complete head stabilization by implementation of a bite-bar may be critical to maintain a constant pupil entry position of the OCT beam. Due to depth-dependent sensitivity fall-off, heartbeat and breathing associated axial movements can cause tissue reflectivity to vary by 29% over time, although known methods can be implemented to null these effects. Substantial variations in reflectivity can be caused by variable illumination due to changes in the beam pupil entry position and angle, which can be reduced by an adaptive algorithm based on slope-fitting of optical attenuation in the choriocapillary lamina.

Sub-micron resolution high-speed spectral domain optical coherence tomography in quality inspection for printed electronics

We present the use of sub-micron resolution optical coherence tomography (OCT) in quality inspection for printed electronics. The device used in the study is based on a supercontinuum light source, Michelson interferometer and high-speed spectrometer. The spectrometer in the presented spectral-domain optical coherence tomography setup (SD-OCT) is centered at 600 nm and covers a 400 nm wide spectral region ranging from 400 nm to 800 nm. Spectra were acquired at a continuous rate of 140,000 per second. The full width at half maximum of the point spread function obtained from a Parylene C sample was 0:98 m. In addition to Parylene C layers, the applicability of sub-micron SD-OCT in printed electronics was studied using PET and epoxy covered solar cell, a printed RFID antenna and a screen-printed battery electrode. A commercial SD-OCT system was used for reference measurements.

Optical coherence tomography with a 2.8-mm beam diameter and sensorless defocus and astigmatism correction

Abstract. An optical coherence tomography (OCT) system with a 2.8-mm beam diameter is presented. Sensorless defocus correction can be performed with a Badal optometer and astigmatism correction with a liquid crystal device. OCT B-scans were used in an image-based optimization algorithm for aberration correction. Defocus can be corrected from −4.3u2009u2009D to +4.3u2009u2009D and vertical and oblique astigmatism from −2.5u2009u2009D to +2.5u2009u2009D. A contrast gain of 6.9 times was measured after aberration correction. In comparison with a 1.3-mm beam diameter OCT system, this concept achieved a 3.7-dB gain in dynamic range on a model retina. Both systems were used to image the retina of a human subject. As the correction of the liquid crystal device can take more than 60 s, the subject’s spectacle prescription was adopted instead. This resulted in a 2.5 times smaller speckle size compared with the standard OCT system. The liquid crystal device for astigmatism correction does not need a high-voltage amplifier and can be operated at 5 V. The correction device is small (9u2009u2009mm×30u2009u2009mm×38u2009u2009mm) and can easily be implemented in existing designs for OCT.

Influence of coherence length, signal-to-noise ratio, log transform, and low-pass filtering on layer thickness assessment with OCT in the retina.

Optical coherence tomography (OCT) images of the retina are inevitably affected by the finite width of the coherence function and noise. To make low-reflective layers visible, the raw OCT signal is log transformed; to reduce the effect of noise the images can be low-pass filtered. We determined the effects of these operations on layer thickness assessment, as a function of signal-to-noise ratio (SNR), by performing measurements in a phantom eye and modeling. The log transform appeared to be the key factor in a SNR-dependent overestimation of peak widths and a less predictive bias in the widths of low-reflective layers.

Adaptive optics-assisted optical coherence tomography for imaging of patients with age related macular degeneration

We developed an optical coherence tomography (OCT) prototype with a sample arm that uses a 3.4 mm beam, which is considerably larger than the 1.2 to 1.5 mm beam that is used in commercialized OCT systems. The system is equipped with adaptive optics (AO), and to distinguish it from traditional AO-OCT systems with a larger 6 mm beam we have coined this concept AO-assisted OCT. Compared to commercialized OCT systems, the 3.4 mm aperture combined with AO improves light collection efficiency and imaging lateral resolution. In this paper, the performance of the AOa-OCT system was compared to a standard OCT system and demonstrated for imaging of age-related macular degeneration (AMD). Measurements were performed on the retinas of three human volunteers with healthy eyes and on one eye of a patient diagnosed with AMD. The AO-assisted OCT system imaged retinal structures of healthy human eyes and a patient eye affected by AMD with higher lateral resolution and a 9° by 9° field of view. This combination of a large isoplanatic patch and high lateral resolution can be expected to fill a gap between standard OCT with a 1.2 mm beam and conventional AO-OCT with a 6 mm beam and a 1.5° by 1.5° isoplanatic patch.