Myeong Jin Ju

Lens-based wavefront sensorless adaptive optics swept source OCT.

Optical coherence tomography (OCT) has revolutionized modern ophthalmology, providing depth resolved images of the retinal layers in a system that is suited to a clinical environment. Although the axial resolution of OCT system, which is a function of the light source bandwidth, is sufficient to resolve retinal features at a micrometer scale, the lateral resolution is dependent on the delivery optics and is limited by ocular aberrations. Through the combination of wavefront sensorless adaptive optics and the use of dual deformable transmissive optical elements, we present a compact lens-based OCT system at an imaging wavelength of 1060u2009nm for high resolution retinal imaging. We utilized a commercially available variable focal length lens to correct for a wide range of defocus commonly found in patient’s eyes, and a novel multi-actuator adaptive lens for aberration correction to achieve near diffraction limited imaging performance at the retina. With a parallel processing computational platform, high resolution cross-sectional and en face retinal image acquisition and display was performed in real time. In order to demonstrate the system functionality and clinical utility, we present images of the photoreceptor cone mosaic and other retinal layers acquired in vivo from research subjects.

Wavefront sensorless adaptive optics OCT with the DONE algorithm for in vivo human retinal imaging [Invited]

In this report, which is an international collaboration of OCT, adaptive optics, and control research, we demonstrate the Data-based Online Nonlinear Extremum-seeker (DONE) algorithm to guide the image based optimization for wavefront sensorless adaptive optics (WFSL-AO) OCT for in vivo human retinal imaging. The ocular aberrations were corrected using a multi-actuator adaptive lens after linearization of the hysteresis in the piezoelectric actuators. The DONE algorithm succeeded in drastically improving image quality and the OCT signal intensity, up to a factor seven, while achieving a computational time of 1 ms per iteration, making it applicable for many high speed applications. We demonstrate the correction of five aberrations using 70 iterations of the DONE algorithm performed over 2.8 s of continuous volumetric OCT acquisition. Data acquired from an imaging phantom and in vivo from human research volunteers are presented.

Retinal optical coherence tomography at 1 μm with dynamic focus control and axial motion tracking

Abstract. High-resolution optical coherence tomography (OCT) retinal imaging is important to noninvasively visualize the various retinal structures to aid in better understanding of the pathogenesis of vision-robbing diseases. However, conventional OCT systems have a trade-off between lateral resolution and depth-of-focus. In this report, we present the development of a focus-stacking OCT system with automatic focus optimization for high-resolution, extended-focal-range clinical retinal imaging by incorporating a variable-focus liquid lens into the sample arm optics. Retinal layer tracking and selection was performed using a graphics processing unit accelerated processing platform for focus optimization, providing real-time layer-specific en face visualization. After optimization, multiple volumes focused at different depths were acquired, registered, and stitched together to yield a single, high-resolution focus-stacked dataset. Using this system, we show high-resolution images of the retina and optic nerve head, from which we extracted clinically relevant parameters such as the nerve fiber layer thickness and lamina cribrosa microarchitecture.

Multiscale sensorless adaptive optics OCT angiography system for in vivo human retinal imaging

Abstract. We present a multiscale sensorless adaptive optics (SAO) OCT system capable of imaging retinal structure and vasculature with various fields-of-view (FOV) and resolutions. Using a single deformable mirror and exploiting the polarization properties of light, the SAO-OCT-A was implemented in a compact and easy to operate system. With the ability to adjust the beam diameter at the pupil, retinal imaging was demonstrated at two different numerical apertures with the same system. The general morphological structure and retinal vasculature could be observed with a few tens of micrometer-scale lateral resolution with conventional OCT and OCT-A scanning protocols with a 1.7-mm-diameter beam incident at the pupil and a large FOV (15u2009deg×u200915u2009deg). Changing the system to a higher numerical aperture with a 5.0-mm-diameter beam incident at the pupil and the SAO aberration correction, the FOV was reduced to 3u2009deg×u20093u2009deg for fine detailed imaging of morphological structure and microvasculature such as the photoreceptor mosaic and capillaries. Multiscale functional SAO-OCT imaging was performed on four healthy subjects, demonstrating its functionality and potential for clinical utility.

Strip-based registration of serially acquired optical coherence tomography angiography

Abstract. The visibility of retinal microvasculature in optical coherence tomography angiography (OCT-A) images is negatively affected by the small dimension of the capillaries, pulsatile blood flow, and motion artifacts. Serial acquisition and time-averaging of multiple OCT-A images can enhance the definition of the capillaries and result in repeatable and consistent visualization. We demonstrate an automated method for registration and averaging of serially acquired OCT-A images. Ten OCT-A volumes from six normal control subjects were acquired using our prototype 1060-nm swept source OCT system. The volumes were divided into microsaccade-free en face angiogram strips, which were affine registered using scale-invariant feature transform keypoints, followed by nonrigid registration by pixel-wise local neighborhood matching. The resulting averaged images were presented of all the retinal layers combined, as well as in the superficial and deep plexus layers separately. The contrast-to-noise ratio and signal-to-noise ratio of the angiograms with all retinal layers (reported as average±standard deviation) increased from 0.52±0.22 and 19.58±4.04u2009u2009dB for a single image to 0.77±0.25 and 25.05±4.73u2009u2009dB, respectively, for the serially acquired images after registration and averaging. The improved visualization of the capillaries can enable robust quantification and study of minute changes in retinal microvasculature.

Automated identification of cone photoreceptors in adaptive optics optical coherence tomography images using transfer learning

Automated measurements of the human cone mosaic requires the identification of individual cone photoreceptors. The current gold standard, manual labeling, is a tedious process and can not be done in a clinically useful timeframe. As such, we present an automated algorithm for identifying cone photoreceptors in adaptive optics optical coherence tomography (AO-OCT) images. Our approach fine-tunes a pre-trained convolutional neural network originally trained on AO scanning laser ophthalmoscope (AO-SLO) images, to work on previously unseen data from a different imaging modality. On average, the automated method correctly identified 94% of manually labeled cones when compared to manual raters, from twenty different AO-OCT images acquired from five normal subjects. Voronoi analysis confirmed the general hexagonal-packing structure of the cone mosaic as well as the general cone density variability across portions of the retina. The consistency of our measurements demonstrates the high reliability and practical utility of having an automated solution to this problem.

Investigation of the effect of directional (off-axis) illumination on the reflectivity of retina layers in mice using swept-source optical coherence tomography

Changes in visibility of the Henle fiber layer and photoreceptor bands of the human retina with illumination directionality have been reported in OCT clinical imaging. These are a direct consequence of the changes in back scattering due to fibrous tissue orientation and to waveguiding properties of the photoreceptors respectively. Here we report the preliminary results of a study on the effects of retinal images acquired with OCT of illumination directionality in the mouse retina. The quantitative assessment of the reflectivity of retinal layers of a BALB/c and WT pigmented mice was performed in-vivo using a swept-source optical coherence tomography system. The intensities of backscattered signals from different outer retinal layers were measured and compared.

Correlation between polarization sensitive optical coherence tomography and SHG microscopy in articular cartilage

Polarization-sensitive optical coherence tomography (PS-OCT) and second harmonic generation (SHG) microscopy are two imaging modalities with different resolutions, field-of-views (FOV), and contrasts, while they both have the capability of imaging collagen fibers in biological tissues. PS-OCT can measure the tissue birefringence which is induced by highly organized fibers while SHG can image the collagen fiber organization with high resolution. Articular cartilage, with abundant structural collagen fibers, is a suitable sample to study the correlation between PS-OCT and SHG microscopy. Qualitative conjecture has been made that the phase retardation measured by PS-OCT is affected by the relationship between the collagen fiber orientation and the illumination direction. Anatomical studies show that the multilayered architecture of articular cartilage can be divided into four zones from its natural surface to the subchondral bone: the superficial zone, the middle zone, the deep zone, and the calcified zone. The different zones have different collagen fiber orientations, which can be studied by the different slopes in the cumulative phase retardation in PS-OCT. An algorithm is developed based on the quantitative analysis of PS-OCT phase retardation images to analyze the microstructural features in swine articular cartilage tissues. This algorithm utilizes the depth-dependent slope changing of phase retardation A-lines to segment structural layers. The results show good consistency with the knowledge of cartilage morphology and correlation with the SHG images measured at selected depth locations. The correlation between PS-OCT and SHG microscopy shows that PS-OCT has the potential to analyze both the macro and micro characteristics of biological tissues with abundant collagen fibers and other materials that may cause birefringence.

Real time optimization algorithm for wavefront sensorless adaptive optics OCT (Conference Presentation)

Optical Coherence Tomography (OCT) has revolutionized modern ophthalmology, providing depth resolved images of the retinal layers in a system that is suited to a clinical environment. A limitation of the performance and utilization of the OCT systems has been the lateral resolution. Through the combination of wavefront sensorless adaptive optics with dual variable optical elements, we present a compact lens based OCT system that is capable of imaging the photoreceptor mosaic. We utilized a commercially available variable focal length lens to correct for a wide range of defocus commonly found in patient eyes, and a multi-actuator adaptive lens after linearization of the hysteresis in the piezoelectric actuators for aberration correction to obtain near diffraction limited imaging at the retina. A parallel processing computational platform permitted real-time image acquisition and display. The Data-based Online Nonlinear Extremum seeker (DONE) algorithm was used for real time optimization of the wavefront sensorless adaptive optics OCT, and the performance was compared with a coordinate search algorithm. Cross sectional images of the retinal layers and en face images of the cone photoreceptor mosaic acquired in vivo from research volunteers before and after WSAO optimization are presented. Applying the DONE algorithm in vivo for wavefront sensorless AO-OCT demonstrates that the DONE algorithm succeeds in drastically improving the signal while achieving a computational time of 1 ms per iteration, making it applicable for high speed real time applications.

GPU accelerated optical coherence tomography angiography using strip-based registration (Conference Presentation)

High quality visualization of the retinal microvasculature can improve our understanding of the onset and development of retinal vascular diseases, which are a major cause of visual morbidity and are increasing in prevalence. Optical Coherence Tomography Angiography (OCT-A) images are acquired over multiple seconds and are particularly susceptible to motion artifacts, which are more prevalent when imaging patients with pathology whose ability to fixate is limited. The acquisition of multiple OCT-A images sequentially can be performed for the purpose of removing motion artifact and increasing the contrast of the vascular network through averaging. Due to the motion artifacts, a robust registration pipeline is needed before feature preserving image averaging can be performed. In this report, we present a novel method for a GPU-accelerated pipeline for acquisition, processing, segmentation, and registration of multiple, sequentially acquired OCT-A images to correct for the motion artifacts in individual images for the purpose of averaging. High performance computing, blending CPU and GPU, was introduced to accelerate processing in order to provide high quality visualization of the retinal microvasculature and to enable a more accurate quantitative analysis in a clinically useful time frame. Specifically, image discontinuities caused by rapid micro-saccadic movements and image warping due to smoother reflex movements were corrected by strip-wise affine registration estimated using Scale Invariant Feature Transform (SIFT) keypoints and subsequent local similarity-based non-rigid registration. These techniques improve the image quality, increasing the value for clinical diagnosis and increasing the range of patients for whom high quality OCT-A images can be acquired.