Dae Yu Kim

In vivo volumetric imaging of human retinal circulation with phase-variance optical coherence tomography.

We present in vivo volumetric images of human retinal micro-circulation using Fourier-domain optical coherence tomography (Fd-OCT) with the phase-variance based motion contrast method. Currently fundus fluorescein angiography (FA) is the standard technique in clinical settings for visualizing blood circulation of the retina. High contrast imaging of retinal vasculature is achieved by injection of a fluorescein dye into the systemic circulation. We previously reported phase-variance optical coherence tomography (pvOCT) as an alternative and non-invasive technique to image human retinal capillaries. In contrast to FA, pvOCT allows not only noninvasive visualization of a two-dimensional retinal perfusion map but also volumetric morphology of retinal microvasculature with high sensitivity. In this paper we report high-speed acquisition at 125 kHz A-scans with pvOCT to reduce motion artifacts and increase the scanning area when compared with previous reports. Two scanning schemes with different sampling densities and scanning areas are evaluated to find optimal parameters for high acquisition speed in vivo imaging. In order to evaluate this technique, we compare pvOCT capillary imaging at 3x3 mm2 and 1.5x1.5 mm2 with fundus FA for a normal human subject. Additionally, a volumetric view of retinal capillaries and a stitched image acquired with ten 3x3 mm2 pvOCT sub-volumes are presented. Visualization of retinal vasculature with pvOCT has potential for diagnosis of retinal vascular diseases.

Optical imaging of the chorioretinal vasculature in the living human eye

Detailed visualization of microvascular changes in the human retina is clinically limited by the capabilities of angiography imaging, a 2D fundus photograph that requires an intravenous injection of fluorescent dye. Whereas current angiography methods enable visualization of some retinal capillary detail, they do not adequately reveal the choriocapillaris or other microvascular features beneath the retina. We have developed a noninvasive microvascular imaging technique called phase-variance optical coherence tomography (pvOCT), which identifies vasculature three dimensionally through analysis of data acquired with OCT systems. The pvOCT imaging method is not only capable of generating capillary perfusion maps for the retina, but it can also use the 3D capabilities to segment the data in depth to isolate vasculature in different layers of the retina and choroid. This paper demonstrates some of the capabilities of pvOCT imaging of the anterior layers of choroidal vasculature of a healthy normal eye as well as of eyes with geographic atrophy (GA) secondary to age-related macular degeneration. The pvOCT data presented permit digital segmentation to produce 2D depth-resolved images of the retinal vasculature, the choriocapillaris, and the vessels in Sattler’s and Haller’s layers. Comparisons are presented between en face projections of pvOCT data within the superficial choroid and clinical angiography images for regions of GA. Abnormalities and vascular dropout observed within the choriocapillaris for pvOCT are compared with regional GA progression. The capability of pvOCT imaging of the microvasculature of the choriocapillaris and the anterior choroidal vasculature has the potential to become a unique tool to evaluate therapies and understand the underlying mechanisms of age-related macular degeneration progression.

Noninvasive Imaging of the Foveal Avascular Zone with High-Speed, Phase-Variance Optical Coherence Tomography

PURPOSE To demonstrate the application of phase-variance optical coherence tomography (pvOCT) for contrast agent-free in vivo imaging of volumetric retinal microcirculation in the human foveal region and for extraction of foveal avascular zone dimensions. METHODS A custom-built, high-speed Fourier-domain OCT retinal imaging system was used to image retinas of two healthy subjects and eight diabetic patients. Through the acquisition of multiple B-scans for each scan location, phase differences between consecutive scans were extracted and used for phase-variance contrast, identifying motion signals from within blood vessels and capillaries. The en face projection view of the inner retinal layers segmented out from volumetric pvOCT data sets allowed visualization of a perfusion network with the foveal avascular zone (FAZ). In addition, the authors presented 2D retinal perfusion maps with pseudo color-coded depth positions of capillaries. RESULTS Retinal vascular imaging with pvOCT provides accurate measurements of the FAZ area and its morphology and a volumetric perfusion map of microcapillaries. In this study using two images from each fundus fluorescein angiography (FA) and pvOCT, the measured average areas of the FAZ from two healthy subjects were below 0.22 mm(2), and each of eight diabetic patients had an enlarged FAZ area, larger than 0.22 mm(2). Moreover, the FAZ areas demonstrated a significant correlation (r = 0.91) between measurements from FA and pvOCT. CONCLUSIONS The high-speed pvOCT allows contrast agent-free visualization of capillary networks in the human foveal region that is analogous to fundus FA imaging. This could allow for noninvasive diagnosis and progression monitoring of diabetic retinopathy in clinical settings.

Comparison of phase-shifting techniques for in vivo full-range, high-speed Fourier-domain optical coherence tomography.

Single spectrometer-based complex conjugate artifact removal methods are evaluated for in vivo imaging with complementary metal-oxide semiconductor line scan camera based high-speed Fourier-domain optical coherence tomography (FD-OCT) at 100,000 axial scans per second. Performance of three different phase-shifting methods with the same OCT engine is evaluated using modified data acquisition schemes, depending on the requirements of each phase-shifting technique. The suppression ratio of complex conjugate artifact images using a paperboard is assessed for all tested methods. Several other characteristics, including a list of additional hardware requirements (beyond standard FD-OCT components) and data acquisition schemes for each of the methods is presented. In vivo full-range images of human fingerpad and nail are shown and compared with standard FD-OCT images. Additionally, a complex-conjugate-free human retinal volume acquired at the speed of 100,000 A-scans/s is presented.

Progress on Developing Adaptive Optics–Optical Coherence Tomography for In Vivo Retinal Imaging: Monitoring and Correction of Eye Motion Artifacts

Recent progress in retinal image acquisition techniques, including optical coherence tomography (OCT) and scanning laser ophthalmoscopy (SLO), combined with improved performance of adaptive optics (AO) instrumentation, has resulted in improvement in the quality of in vivo images of cellular structures in the human retina. Here, we present a short review of progress on developing AO-OCT instruments. Despite significant progress in imaging speed and resolution, eye movements present during acquisition of a retinal image with OCT introduce motion artifacts into the image, complicating analysis and registration. This effect is especially pronounced in high-resolution datasets acquired with AO-OCT instruments. Several retinal tracking systems have been introduced to correct retinal motion during data acquisition. We present a method for correcting motion artifacts in AO-OCT volume data after acquisition using simultaneously captured adaptive optics-scanning laser ophthalmoscope (AO-SLO) images. We extract transverse eye motion data from the AO-SLO images, assign a motion adjustment vector to each AO-OCT A-scan, and re-sample from the scattered data back onto a regular grid. The corrected volume data improve the accuracy of quantitative analyses of microscopic structures.

In vivo imaging of human vasculature in the chorioretinal complex using phase-variance contrast method with phase-stabilized 1-μm swept-source optical coherence tomography

Abstract. We present a noninvasive phase-variance (pv)–based motion contrast method for depth-resolved imaging of the human chorioretinal complex microcirculation with a newly developed phase-stabilized high speed (100-kHz A-scans/s) 1-μm swept-source optical coherence tomography (SSOCT) system. Compared to our previous spectral-domain (spectrometer based) pv-spectral domain OCT (SDOCT) system, this system has the advantages of higher sensitivity, reduced fringe wash-out for high blood flow speeds and deeper penetration in choroid. High phase stability SSOCT imaging was achieved by using a computationally efficient phase stabilization approach. This process does not require additional calibration hardware and complex numerical procedures. Our phase stabilization method is simple and can be employed in a variety of SSOCT systems. Examples of vasculature in the chorioretinal complex imaged by pv-SSOCT from normal as well as diseased eyes are presented and compared to retinal images of the same subjects acquired with fluorescein angiography and indocyanine green angiography. Observations of morphology of vascular perfusion in chorioretinal complex visualized by our method are listed.

Staging of Macular Telangiectasia: Power-Doppler Optical Coherence Tomography and Macular Pigment Optical Density

PURPOSE Two methods were used to study the stages of macular telangiectasia (MACTEL): Power-Doppler optical coherence tomography (PD-OCT), which allows imaging of the retinal circulation in three dimensions, and macular pigment optical density (MPOD), which quantifies the distribution of macular carotenoids. METHODS Among 49 patients with MacTel identified, 12 eyes (6 patients) with MacTel and 7 age-matched control eyes (7 patients) were imaged with a custom-built Fourier-domain OCT instrument to acquire PD-OCT images. MPOD was measured using heterochromatic flicker photometry in 10 eyes (5 patients) with MacTel and compared with 44 age-matched control eyes (44 patients). Clinical staging of MacTel was based on best-corrected visual acuity, fundus biomicroscopy, fluorescein angiography, and OCT. RESULTS Stage 1 eyes (n = 2) had subtle punctate vascular signal confined to the inner portion of the outer plexiform layer (OPL) on PD-OCT. Stage 2 (n = 2) showed larger oblique vascular signal extending into deeper OPL. Stage 3 (n = 5) had disruption of outer retinal layers with abnormal vasculature extending into the outer nuclear layer. Stage 4 (n = 3) showed diffuse blurring of the retinal layers with vascular channels extending the full thickness of the retina. MPOD values in four eyes with stage 1 or 2 MacTel correlated well with age-matched controls. Six eyes with stage 3 or 4 MacTel had loss of MPOD especially at the fovea. CONCLUSIONS PD-OCT shows penetration of the retinal capillaries into the deeper retinal layers in early stages of MacTel, with full thickness vascular proliferation in advanced disease. MPOD is commonly depleted but may appear normal in early stage MacTel.

Complex conjugate artifact-free adaptive optics optical coherence tomography of in vivo human optic nerve head

Abstract. We acquired in vivo images of the human optic nerve head (ONH) using an adaptive optics—optical coherence tomography (AO-OCT) system. In order to improve imaging of the lamina cribrosa in the ONH with high lateral resolution and sensitivity, we implemented a complex conjugate artifact-free Fourier domain OCT (Fd-OCT) acquisition scheme with a reference arm-based phase shifting method. This allowed positioning of the lamina cribrosa structures near the zero path length difference where AO-OCT imaging achieves highest sensitivity. Implementation of our complex conjugate artifact removal (CCR) method required constant phase shifts between consecutive axial scans (A-scans), generated by continuous beam path-length changes from offsetting the pivot point of the scanning mirror placed in the reference arm. Fourier transform along the transverse axis and a filtering algorithm allowed reconstruction of CCR AO-OCT images. The suppression ratio of the mirror artifact was approximately 22 dB (at 18,000 A-scans per second acquisition speed) with a paperboard test target and an optimum phase-shift value. Finally, we reconstructed the three-dimensional structure of human ONH with enhanced depth range and sensitivity using CCR AO-OCT.

Retinal Imaging with a Combined Adaptive Optics: Optical Coherence Tomography and Adaptive Optics: Scanning Laser Ophthalmoscopy System

We describe results of retinal imaging with a novel instrument that combines adaptive optics - Fourier-domain optical coherence tomography (AO-OCT) with an adaptive optics scanning laser ophthalmoscope (AO-SLO). One of the benefits of combining Fd-OCT with SLO includes automatic co-registration between the two imaging modalities and the potential for correcting lateral and transversal eye motion resulting in motion artifact-free volumetric retinal imaging. Additionally this allows for direct comparison between retinal structures that can be imaged with both modalities (e.g., photoreceptor mosaics or microvasculature maps). This dual imaging modality could provide insight into some retinal properties that could not be accessed by a single imaging system. Additionally, extension of OCT and SLO beyond structural imaging may open new avenues for diagnostics and testing in ophthalmology. In particular, non-invasive vasculature mapping with these modalities holds promise of replacing fluorescein angiography in vascular identification. Several new improvements of our system are described, including results of testing a novel 97-actuator deformable mirror and AO-SLO light intensity modulation.

Visualization of human retinal micro-capillaries with phase contrast high-speed optical coherence tomography

We present high-speed Fourier-domain optical coherence tomography (Fd-OCT) with the phase variance based motion contrast method for visualizing retinal micro-circulation in vivo. This technique allows non-invasive visualization of a two-dimensional retinal perfusion map and concurrent volumetric morphology of retinal microvasculature with high sensitivity. The high-speed acquisition rate at 125kHz A-scans enables reduction of motion artifacts with increased scanning area if compared to previously reported results. Several scanning schemes with different sampling densities and scanning areas are evaluated to find optimal parameters for in vivo imaging. In order to evaluate this technique, we compare OCT micro-capillary imaging using the phase variance technique with fundus fluorescein angiography (FA). Additionally, volumetric visualization of blood flow for a normal subject is presented.