Rainer A. Leitgeb

Doppler Optical Coherence Tomography

Optical Coherence Tomography (OCT) has revolutionized ophthalmology. Since its introduction in the early 1990s it has continuously improved in terms of speed, resolution and sensitivity. The technique has also seen a variety of extensions aiming to assess functional aspects of the tissue in addition to morphology. One of these approaches is Doppler OCT (DOCT), which aims to visualize and quantify blood flow. Such extensions were already implemented in time domain systems, but have gained importance with the introduction of Fourier domain OCT. Nowadays phase-sensitive detection techniques are most widely used to extract blood velocity and blood flow from tissues. A common problem with the technique is that the Doppler angle is not known and several approaches have been realized to obtain absolute velocity and flow data from the retina. Additional studies are required to elucidate which of these techniques is most promising. In the recent years, however, several groups have shown that data can be obtained with high validity and reproducibility. In addition, several groups have published values for total retinal blood flow. Another promising application relates to non-invasive angiography. As compared to standard techniques such as fluorescein and indocyanine-green angiography the technique offers two major advantages: no dye is required and depth resolution is required is provided. As such Doppler OCT has the potential to improve our abilities to diagnose and monitor ocular vascular diseases.

Line-field parallel swept source MHz OCT for structural and functional retinal imaging

We demonstrate three-dimensional structural and functional retinal imaging with line-field parallel swept source imaging (LPSI) at acquisition speeds of up to 1 MHz equivalent A-scan rate with sensitivity better than 93.5 dB at a central wavelength of 840 nm. The results demonstrate competitive sensitivity, speed, image contrast and penetration depth when compared to conventional point scanning OCT. LPSI allows high-speed retinal imaging of function and morphology with commercially available components. We further demonstrate a method that mitigates the effect of the lateral Gaussian intensity distribution across the line focus and demonstrate and discuss the feasibility of high-speed optical angiography for visualization of the retinal microcirculation.

Anisotropic aberration correction using region of interest based digital adaptive optics in Fourier domain OCT

In this paper a numerical technique is presented to compensate for anisotropic optical aberrations, which are usually present across the lateral field of view in the out of focus regions, in high resolution optical coherence tomography and microscopy (OCT/OCM) setups. The recorded enface image field at different depths in the tomogram is digitally divided into smaller sub-regions or the regions of interest (ROIs), processed individually using subaperture based digital adaptive optics (DAO), and finally stitched together to yield a final image with a uniform diffraction limited resolution across the entire field of view (FOV). Using this method, a sub-micron lateral resolution is achieved over a depth range of 218 [Formula: see text]for a nano-particle phantom sample imaged using a fiber based point scanning spectral domain (SD) OCM system with a limited depth of focus (DOF) of ~7 [Formula: see text]at a numerical aperture (NA) of 0.6. Thus, an increase in DOF by ~30x is demonstrated in this case. The application of this method is also shown in ex vivo mouse adipose tissue.

Comparative study between a spectral domain and a high-speed single-beam swept source OCTA system for identifying choroidal neovascularization in AMD

This comparative study between a SD- and SS-OCTA system for visualizing neovascular patterns in AMD, also assessed the influence of cataract on OCTA imaging. 25 eyes with active CNV (AMD) were documented by FA, ICGA and SD-OCT. Two OCTA devices were used: A custom built SS-OCTA (1050u2009nm, 400,000 A-scans/s, 5u2009×u20095u2009mm, no image segmentation); AngioVue (OptoVue, CA, USA) SD-OCTA (840u2009nm, 70.000 A-scans/s, 3u2009×u20093u2009mm, SSADA technology). Two retina experts graded CNV types and vascular patterns. Cataract influence on OCTA image quality was reported for the superficial retinal plexus (6 eyes). The SS-OCTA prototype showed more CNV lesions compared to the SD-OCTA system (pu2009=u20090.01). Overall sensitivity of SD- and SS-OCTA systems to detect CNV lesions was.32 and.68, respectively. The SS-OCTA system was able to detect discrete lesion characteristics better than the SD-OCTA. No significant difference was found in the ability to identify CNV in treatment-naïve eyes. There was no significant influence of cataract. The SS-OCTA prototype detected CNV-associated vascular patterns more reliably than the SD-OCTA system. This is attributed to the SS-OCTA system’s longer center wavelength and higher A-scan rate yielding higher definition and contrast of small neovascular structures. The SS-OCTA system used showed no advantage regarding cataract influence.

Phase-stable swept source OCT angiography in human skin using an akinetic source

We demonstrate noninvasive structural and microvascular contrast imaging of human skin in vivo, using phase difference swept source OCT angiography (pOCTA). The pOCTA system employs an akinetic, all-semiconductor, highly phase-stable swept laser source which operates at 1340 nm central wavelength, with 37 nm bandwidth (at 0 dB region) and 200 kHz A-scan rate. The phase sensitive detection does not need any external phase stabilizing implementations, due to the outstanding high phase linearity and sweep phase repeatability within 2 mrad. We compare the performance of phase based OCTA to speckle based OCTA for visualizing human vascular networks. pOCTA shows better contrast especially for deeper vascular details as compared to speckle based OCTA. The phase stability of the akinetic source allows the OCTA system to show decent vascular contrast only with 2 B-scans. We compare the performance of using 2 versus 4 B-scans for calculating the vascular contrast. Finally, the performance of a 100 nm bandwidth akinetic laser at 1310 nm is investigated for both OCT and OCTA.

Retinal oxygen extraction in humans

Adequate function of the retina is dependent on proper oxygen supply. In humans, the inner retina is oxygenated via the retinal circulation. We present a method to calculate total retinal oxygen extraction based on measurement of total retinal blood flow using dual-beam bidirectional Doppler optical coherence tomography and measurement of oxygen saturation by spectrophotometry. These measurements were done on 8 healthy subjects while breathing ambient room air and 100% oxygen. Total retinal blood flow was 44.3u2009±u20099.0u2009μl/min during baseline and decreased to 18.7u2009±u20094.2u2009μl/min during 100% oxygen breathing (Pu2009<u20090.001) resulting in a pronounced decrease in retinal oxygen extraction from 2.33u2009±u20090.51u2009μl(O2)/min to 0.88u2009±u20090.14u2009μl(O2)/min during breathing of 100% oxygen. The method presented in this paper may have significant potential to study oxygen metabolism in hypoxic retinal diseases such as diabetic retinopathy.

Combined multi-modal photoacoustic tomography, optical coherence tomography (OCT) and OCT angiography system with an articulated probe for in vivo human skin structure and vasculature imaging

Cutaneous blood flow accounts for approximately 5% of cardiac output in human and plays a key role in a number of a physiological and pathological processes. We show for the first time a multi-modal photoacoustic tomography (PAT), optical coherence tomography (OCT) and OCT angiography system with an articulated probe to extract human cutaneous vasculature in vivo in various skin regions. OCT angiography supplements the microvasculature which PAT alone is unable to provide. Co-registered volumes for vessel network is further embedded in the morphologic image provided by OCT. This multi-modal system is therefore demonstrated as a valuable tool for comprehensive non-invasive human skin vasculature and morphology imaging in vivo.

Blood flow velocity vector field reconstruction from dual-beam bidirectional Doppler OCT measurements in retinal veins.

In this paper, we demonstrate the possibility to reconstruct the actual blood flow velocity vector field in retinal microvessels from dual-beam bidirectional Doppler optical coherence tomography measurements. First, for a better understanding of measured phase patterns, several flow situations were simulated on the basis of the known dual beam measurement geometry. We were able to extract the vector field parameters that determine the measured phase pattern, allowing for the development of an algorithm to reconstruct the velocity vector field from measured phase data. In a next step, measurements were performed at a straight vessel section and at a venous convergence; the obtained phase data were evaluated by means of the new approach. For the straight vessel section, the reconstructed flow velocity vector field yielded a parabolic flow. For the venous convergence, however, the reconstructed vector field deviated from a parabolic profile, but was in very good accordance with the simulated vector field for the given vessel geometry. The proposed algorithm allows predictions of the velocity vector field. Moreover, the algorithm is also sensitive to directional changes of the flow velocity as small as <1°, thereby offering insight in the flow characteristics of the non-Newtonian fluid blood in microvessels.

Visualization of micro-capillaries using optical coherence tomography angiography with and without adaptive optics.

The purpose of this work is to investigate the benefits of adaptive optics (AO) technology for optical coherence tomography angiography (OCTA). OCTA has shown great potential in non-invasively enhancing the contrast of vessels and small capillaries. Especially the capability of the technique to visualize capillaries with a lateral extension that is below the transverse resolution of the system opens unique opportunities in diagnosing retinal vascular diseases. However, there are some limitations of this technology such as shadowing and projection artifacts caused by overlying vasculature or the inability to determine the true extension of a vessel. Thus, the evaluation of the vascular structure and density based on OCTA alone can be misleading. In this paper we compare the performance of AO-OCT, AO-OCTA and OCTA for imaging retinal vasculature. The improved transverse resolution and the reduced depth of focus of AO-OCT and AO-OCTA greatly reduce shadowing artifacts allowing for a better differentiation and segmentation of different vasculature layers of the inner retina. The comparison is done on images recorded in healthy volunteers and in diabetic patients with distinct pathologies of the retinal microvasculature.

Super-resolved thickness maps of thin film phantoms and in vivo visualization of tear film lipid layer using OCT

In optical coherence tomography (OCT), the axial resolution is directly linked to the coherence length of the employed light source. It is currently unclear if OCT allows measuring thicknesses below its axial resolution value. To investigate spectral-domain OCT imaging in the super-resolution regime, we derived a signal model and compared it with the experiment. Several island thin film samples of known refractive indices and thicknesses in the range 46 - 163 nm were fabricated and imaged. Reference thickness measurements were performed using a commercial atomic force microscope. In vivo measurements of the tear film were performed in 4 healthy subjects. Our results show that quantitative super-resolved thickness measurement can be performed using OCT. In addition, we report repeatable tear film lipid layer visualization. Our results provide a novel interpretation of the OCT axial resolution limit and open a perspective to deeper extraction of the information hidden in the coherence volume.