Benjamin Potsaid

Quantitative Optical Coherence Tomography Angiography of Choroidal Neovascularization in Age-Related Macular Degeneration

PURPOSE To detect and quantify choroidal neovascularization (CNV) in patients with age-related macular degeneration (AMD) using optical coherence tomography (OCT) angiography. DESIGN Observational, cross-sectional study. PARTICIPANTS A total of 5 normal subjects and 5 subjects with neovascular AMD were included. METHODS A total of 5 eyes with neovascular AMD and 5 normal age-matched controls were scanned by a high-speed (100 000 A-scans/seconds) 1050-nm wavelength swept-source OCT. The macular angiography scan covered a 3 × 3-mm area and comprised 200 × 200 × 8 A-scans acquired in 3.5 seconds. Flow was detected using the split-spectrum amplitude-decorrelation angiography (SSADA) algorithm. Motion artifacts were removed by 3-dimensional (3D) orthogonal registration and merging of 4 scans. The 3D angiography was segmented into 3 layers: inner retina (to show retinal vasculature), outer retina (to identify CNV), and choroid. En face maximum projection was used to obtain 2-dimensional angiograms from the 3 layers. The CNV area and flow index were computed from the en face OCT angiogram of the outer retinal layer. Flow (decorrelation) and structural data were combined in composite color angiograms for both en face and cross-sectional views. MAIN OUTCOME MEASURES The CNV angiogram, CNV area, and CNV flow index. RESULTS En face OCT angiograms of CNV showed sizes and locations that were confirmed by fluorescein angiography (FA). Optical coherence tomography angiography provided more distinct vascular network patterns that were less obscured by subretinal hemorrhage. The en face angiograms also showed areas of reduced choroidal flow adjacent to the CNV in all cases and significantly reduced retinal flow in 1 case. Cross-sectional angiograms were used to visualize CNV location relative to the retinal pigment epithelium and Bruchs layer and classify type I and type II CNV. A feeder vessel could be identified in 1 case. Higher flow indexes were associated with larger CNV and type II CNV. CONCLUSIONS Optical coherence tomography angiography provides depth-resolved information and detailed images of CNV in neovascular AMD. Quantitative information regarding CNV flow and area can be obtained. Further studies are needed to assess the role of quantitative OCT angiography in the evaluation and treatment of neovascular AMD.

Ultrahigh speed Spectral / Fourier domain OCT ophthalmic imaging at 70,000 to 312,500 axial scans per second

We demonstrate ultrahigh speed spectral / Fourier domain optical coherence tomography (OCT) using an ultrahigh speed CMOS line scan camera at rates of 70,000 - 312,500 axial scans per second. Several design configurations are characterized to illustrate trade-offs between acquisition speed, resolution, imaging range, sensitivity and sensitivity roll-off performance. Ultrahigh resolution OCT with 2.5 - 3.0 micron axial image resolution is demonstrated at approximately 100,000 axial scans per second. A high resolution spectrometer design improves sensitivity roll-off and imaging range performance, trading off imaging speed to 70,000 axial scans per second. Ultrahigh speed imaging at >300,000 axial scans per second with standard image resolution is also demonstrated. Ophthalmic OCT imaging of the normal human retina is investigated. The high acquisition speeds enable dense raster scanning to acquire densely sampled volumetric three dimensional OCT (3D-OCT) data sets of the macula and optic disc with minimal motion artifacts. Imaging with approximately 8 - 9 micron axial resolution at 250,000 axial scans per second, a 512 x 512 x 400 voxel volumetric 3D-OCT data set can be acquired in only approximately 1.3 seconds. Orthogonal registration scans are used to register OCT raster scans and remove residual axial eye motion, resulting in 3D-OCT data sets which preserve retinal topography. Rapid repetitive imaging over small volumes can visualize small retinal features without motion induced distortions and enables volume registration to remove eye motion. Cone photoreceptors in some regions of the retina can be visualized without adaptive optics or active eye tracking. Rapid repetitive imaging of 3D volumes also provides dynamic volumetric information (4D-OCT) which is shown to enhance visualization of retinal capillaries and should enable functional imaging. Improvements in the speed and performance of 3D-OCT volumetric imaging promise to enable earlier diagnosis and improved monitoring of disease progression and response to therapy in ophthalmology, as well as have a wide range of research and clinical applications in other areas.

Ultrahigh speed 1050nm swept source / Fourier domain OCT retinal and anterior segment imaging at 100,000 to 400,000 axial scans per second

We demonstrate ultrahigh speed swept source/Fourier domain ophthalmic OCT imaging using a short cavity swept laser at 100,000 - 400,000 axial scan rates. Several design configurations illustrate tradeoffs in imaging speed, sensitivity, axial resolution, and imaging depth. Variable rate A/D optical clocking is used to acquire linear-in-k OCT fringe data at 100 kHz axial scan rate with 5.3 um axial resolution in tissue. Fixed rate sampling at 1 GSPS achieves a 7.5mm imaging range in tissue with 6.0 um axial resolution at 100 kHz axial scan rate. A 200 kHz axial scan rate with 5.3 um axial resolution over 4mm imaging range is achieved by buffering the laser sweep. Dual spot OCT using two parallel interferometers achieves 400 kHz axial scan rate, almost 2X faster than previous 1050 nm ophthalmic results and 20X faster than current commercial instruments. Superior sensitivity roll-off performance is shown. Imaging is demonstrated in the human retina and anterior segment. Wide field 12x12 mm data sets include the macula and optic nerve head. Small area, high density imaging shows individual cone photoreceptors. The 7.5 mm imaging range configuration can show the cornea, iris, and anterior lens in a single image. These improvements in imaging speed and depth range provide important advantages for ophthalmic imaging. The ability to rapidly acquire 3D-OCT data over a wide field of view promises to simplify examination protocols. The ability to image fine structures can provide detailed information on focal pathologies. The large imaging range and improved image penetration at 1050 m wavelengths promises to improve performance for instrumentation which images both the retina and anterior eye. These advantages suggest that swept source OCT at 1050 nm wavelengths will play an important role in future ophthalmic instrumentation.

Motion correction in optical coherence tomography volumes on a per A-scan basis using orthogonal scan patterns

High speed Optical Coherence Tomography (OCT) has made it possible to rapidly capture densely sampled 3D volume data. One key application is the acquisition of high quality in vivo volumetric data sets of the human retina. Since the volume is acquired in a few seconds, eye movement during the scan process leads to distortion, which limits the accuracy of quantitative measurements using 3D OCT data. In this paper, we present a novel software based method to correct motion artifacts in OCT raster scans. Motion compensation is performed retrospectively using image registration algorithms on the OCT data sets themselves. Multiple, successively acquired volume scans with orthogonal fast scan directions are registered retrospectively in order to estimate and correct eye motion. Registration is performed by optimizing a large scale numerical problem as given by a global objective function using one dense displacement field for each input volume and special regularization based on the time structure of the acquisition process. After optimization, each volume is undistorted and a single merged volume is constructed that has superior signal quality compared to the input volumes. Experiments were performed using 3D OCT data from the macula and optic nerve head acquired with a high-speed ultra-high resolution 850 nm spectral OCT as well as wide field data acquired with a 1050 nm swept source OCT instrument. Evaluation of registration performance and result stability as well as visual inspection shows that the algorithm can correct for motion in all three dimensions and on a per A-scan basis. Corrected volumes do not show visible motion artifacts. In addition, merging multiple motion corrected and registered volumes leads to improved signal quality. These results demonstrate that motion correction and merging improves image quality and should also improve morphometric measurement accuracy from volumetric OCT data.

Retinal, anterior segment and full eye imaging using ultrahigh speed swept source OCT with vertical-cavity surface emitting lasers

We demonstrate swept source OCT utilizing vertical-cavity surface emitting laser (VCSEL) technology for in vivo high speed retinal, anterior segment and full eye imaging. The MEMS tunable VCSEL enables long coherence length, adjustable spectral sweep range and adjustable high sweeping rate (50–580 kHz axial scan rate). These features enable integration of multiple ophthalmic applications into one instrument. The operating modes of the device include: ultrahigh speed, high resolution retinal imaging (up to 580 kHz); high speed, long depth range anterior segment imaging (100 kHz) and ultralong range full eye imaging (50 kHz). High speed imaging enables wide-field retinal scanning, while increased light penetration at 1060 nm enables visualization of choroidal vasculature. Comprehensive volumetric data sets of the anterior segment from the cornea to posterior crystalline lens surface are also shown. The adjustable VCSEL sweep range and rate make it possible to achieve an extremely long imaging depth range of ~50 mm, and to demonstrate the first in vivo 3D OCT imaging spanning the entire eye for non-contact measurement of intraocular distances including axial eye length. Swept source OCT with VCSEL technology may be attractive for next generation integrated ophthalmic OCT instruments.

Total retinal blood flow measurement with ultrahigh speed swept source/Fourier domain OCT.

Doppler OCT provides depth-resolved information on flow in biological tissues. In this article, we demonstrate ultrahigh speed swept source/Fourier domain OCT for visualization and quantitative assessment of retinal blood flow. Using swept laser technology, the system operated in the 1050-nm wavelength range at a high axial scan rate of 200 kHz. The rapid imaging speed not only enables volumetric imaging with high axial scan densities, but also enables measurement of high flow velocities in the central retinal vessels. Deep penetration in the optic nerve and lamina cribrosa was achieved by imaging at 1-µm wavelengths. By analyzing en-face images extracted from 3D Doppler data sets, absolute flow in single vessels as well as total retinal blood flow was measured using a simple and robust protocol that does not require measurement of Doppler angles. The results from measurements in healthy eyes suggest that ultrahigh speed swept source/Fourier domain OCT could be a promising technique for volumetric imaging of retinal vasculature and quantitation of retinal blood flow in a wide range of retinal diseases.

Choriocapillaris and Choroidal Microvasculature Imaging with Ultrahigh Speed OCT Angiography

We demonstrate in vivo choriocapillaris and choroidal microvasculature imaging in normal human subjects using optical coherence tomography (OCT). An ultrahigh speed swept source OCT prototype at 1060 nm wavelengths with a 400 kHz A-scan rate is developed for three-dimensional ultrahigh speed imaging of the posterior eye. OCT angiography is used to image three-dimensional vascular structure without the need for exogenous fluorophores by detecting erythrocyte motion contrast between OCT intensity cross-sectional images acquired rapidly and repeatedly from the same location on the retina. En face OCT angiograms of the choriocapillaris and choroidal vasculature are visualized by acquiring cross-sectional OCT angiograms volumetrically via raster scanning and segmenting the three-dimensional angiographic data at multiple depths below the retinal pigment epithelium (RPE). Fine microvasculature of the choriocapillaris, as well as tightly packed networks of feeding arterioles and draining venules, can be visualized at different en face depths. Panoramic ultra-wide field stitched OCT angiograms of the choriocapillaris spanning ∼32 mm on the retina show distinct vascular structures at different fundus locations. Isolated smaller fields at the central fovea and ∼6 mm nasal to the fovea at the depths of the choriocapillaris and Sattlers layer show vasculature structures consistent with established architectural morphology from histological and electron micrograph corrosion casting studies. Choriocapillaris imaging was performed in eight healthy volunteers with OCT angiograms successfully acquired from all subjects. These results demonstrate the feasibility of ultrahigh speed OCT for in vivo dye-free choriocapillaris and choroidal vasculature imaging, in addition to conventional structural imaging.

Ultrahigh-Speed Swept-Source OCT Angiography in Exudative AMD

BACKGROUND AND OBJECTIVE To investigate the potential of ultrahigh-speed swept-source optical coherence tomography angiography (OCTA) to visualize retinal and choroidal vascular changes in patients with exudative age-related macular degeneration (AMD). PATIENTS AND METHODS Observational, prospective cross-sectional study. An ultrahigh-speed swept-source prototype was used to perform OCTA of the retinal and choriocapillaris microvasculature in 63 eyes of 32 healthy controls and 19 eyes of 15 patients with exudative AMD. MAIN OUTCOME MEASURE qualitative comparison of the retinal and choriocapillaris microvasculature in the two groups. RESULTS Choroidal neovascularization (CNV) was clearly visualized in 16 of the 19 eyes with exudative AMD, located above regions of severe choriocapillaris alteration. In 14 of these eyes, the CNV lesions were surrounded by regions of choriocapillaris alteration. CONCLUSION OCTA may offer noninvasive monitoring of the retinal and choriocapillaris microvasculature in patients with CNV, which may assist in diagnosis and monitoring.

Optical coherence tomography angiography of optic nerve head and parafovea in multiple sclerosis

Aims To investigate swept-source optical coherence tomography (OCT) angiography in the optic nerve head (ONH) and parafoveal regions in patients with multiple sclerosis (MS). Methods Fifty-two MS eyes and 21 healthy control (HC) eyes were included. There were two MS subgroups: 38 MS eyes without an optic neuritis (ON) history (MS −ON), and 14 MS eyes with an ON history (MS +ON). The OCT images were captured by high-speed 1050 nm swept-source OCT. The ONH flow index (FI) and parafoveal FI were quantified from OCT angiograms. Results The mean ONH FI was 0.160±0.010 for the HC group, 0.156±0.017 for the MS−ON group, and 0.140±0.020 for the MS+ON group. The ONH FI of the MS+ON group was reduced by 12.5% compared to HC eyes (p=0.004). A higher percentage of MS+ON eyes had abnormal ONH FI compared to HC patients (43% vs 5%, p=0.01). Mean parafoveal FIs were 0.126±0.007, 0.127±0.010, and 0.129±0.005 for the HC, MS−ON, and MS +ON groups, respectively, and did not differ significantly among them. The coefficient of variation (CV) of intravisit repeatability and intervisit reproducibility were 1.03% and 4.53% for ONH FI, and 1.65% and 3.55% for parafoveal FI. Conclusions Based on OCT angiography, the FI measurement is feasible, highly repeatable and reproducible, and it is suitable for clinical measurement of ONH and parafoveal perfusion. The ONH FI may be useful in detecting damage from ON and quantifying its severity.

Handheld ultrahigh speed swept source optical coherence tomography instrument using a MEMS scanning mirror

We developed an ultrahigh speed, handheld swept source optical coherence tomography (SS-OCT) ophthalmic instrument using a 2D MEMS mirror. A vertical cavity surface-emitting laser (VCSEL) operating at 1060 nm center wavelength yielded a 350 kHz axial scan rate and 10 µm axial resolution in tissue. The long coherence length of the VCSEL enabled a 3.08 mm imaging range with minimal sensitivity roll-off in tissue. Two different designs with identical optical components were tested to evaluate handheld OCT ergonomics. An iris camera aided in alignment of the OCT beam through the pupil and a manual fixation light selected the imaging region on the retina. Volumetric and high definition scans were obtained from 5 undilated normal subjects. Volumetric OCT data was acquired by scanning the 2.4 mm diameter 2D MEMS mirror sinusoidally in the fast direction and linearly in the orthogonal slow direction. A second volumetric sinusoidal scan was obtained in the orthogonal direction and the two volumes were processed with a software algorithm to generate a merged motion-corrected volume. Motion-corrected standard 6 x 6 mm(2) and wide field 10 x 10 mm(2) volumetric OCT data were generated using two volumetric scans, each obtained in 1.4 seconds. High definition 10 mm and 6 mm B-scans were obtained by averaging and registering 25 B-scans obtained over the same position in 0.57 seconds. One of the advantages of volumetric OCT data is the generation of en face OCT images with arbitrary cross sectional B-scans registered to fundus features. This technology should enable screening applications to identify early retinal disease, before irreversible vision impairment or loss occurs. Handheld OCT technology also promises to enable applications in a wide range of settings outside of the traditional ophthalmology or optometry clinics including pediatrics, intraoperative, primary care, developing countries, and military medicine.