Wolfgang Drexler

Robust segmentation of intraretinal layers in the normal human fovea using a novel statistical model based on texture and shape analysis

A novel statistical model based on texture and shape for fully automatic intraretinal layer segmentation of normal retinal tomograms obtained by a commercial 800nm optical coherence tomography (OCT) system is developed. While existing algorithms often fail dramatically due to strong speckle noise, non-optimal imaging conditions, shadows and other artefacts, the novel algorithms accuracy only slowly deteriorates when progressively increasing segmentation task difficulty. Evaluation against a large set of manual segmentations shows unprecedented robustness, even in the presence of additional strong speckle noise, with dynamic range tested down to 12dB, enabling segmentation of almost all intraretinal layers in cases previously inaccessible to the existing algorithms. For the first time, an error measure is computed from a large, representative manually segmented data set (466 B-scans from 17 eyes, segmented twice by different operators) and compared to the automatic segmentation with a difference of only 2.6% against the inter-observer variability.

Automated choroidal segmentation of 1060 nm OCT in healthy and pathologic eyes using a statistical model

A two stage statistical model based on texture and shape for fully automatic choroidal segmentation of normal and pathologic eyes obtained by a 1060 nm optical coherence tomography (OCT) system is developed. A novel dynamic programming approach is implemented to determine location of the retinal pigment epithelium/ Bruch’s membrane /choriocapillaris (RBC) boundary. The choroid–sclera interface (CSI) is segmented using a statistical model. The algorithm is robust even in presence of speckle noise, low signal (thick choroid), retinal pigment epithelium (RPE) detachments and atrophy, drusen, shadowing and other artifacts. Evaluation against a set of 871 manually segmented cross-sectional scans from 12 eyes achieves an average error rate of 13%, computed per tomogram as a ratio of incorrectly classified pixels and the total layer surface. For the first time a fully automatic choroidal segmentation algorithm is successfully applied to a wide range of clinical volumetric OCT data.

Photonic integrated Mach-Zehnder interferometer with an on-chip reference arm for optical coherence tomography

Optical coherence tomography (OCT) is a noninvasive, three-dimensional imaging modality with several medical and industrial applications. Integrated photonics has the potential to enable mass production of OCT devices to significantly reduce size and cost, which can increase its use in established fields as well as enable new applications. Using silicon nitride (Si3N4) and silicon dioxide (SiO2) waveguides, we fabricated an integrated interferometer for spectrometer-based OCT. The integrated photonic circuit consists of four splitters and a 190 mm long reference arm with a foot-print of only 10 × 33 mm(2). It is used as the core of a spectral domain OCT system consisting of a superluminescent diode centered at 1320 nm with 100 nm bandwidth, a spectrometer with 1024 channels, and an x-y scanner. The sensitivity of the system was measured at 0.25 mm depth to be 65 dB with 0.1 mW on the sample. Using the system, we imaged human skin in vivo. With further optimization in design and fabrication technology, Si3N4/SiO2 waveguides have a potential to serve as a platform for passive photonic integrated circuits for OCT.

Automated three-dimensional choroidal vessel segmentation of 3D 1060 nm OCT retinal data

A fully automated, robust vessel segmentation algorithm has been developed for choroidal OCT, employing multiscale 3D edge filtering and projection of “probability cones” to determine the vessel “core”, even in the tomograms with low signal-to-noise ratio (SNR). Based on the ideal vessel response after registration and multiscale filtering, with computed depth related SNR, the vessel core estimate is dilated to quantify the full vessel diameter. As a consequence, various statistics can be computed using the 3D choroidal vessel information, such as ratios of inner (smaller) to outer (larger) choroidal vessels or the absolute/relative volume of choroid vessels. Choroidal vessel quantification can be displayed in various forms, focused and averaged within a special region of interest, or analyzed as the function of image depth. In this way, the proposed algorithm enables unique visualization of choroidal watershed zones, as well as the vessel size reduction when investigating the choroid from the sclera towards the retinal pigment epithelium (RPE). To the best of our knowledge, this is the first time that an automatic choroidal vessel segmentation algorithm is successfully applied to 1060 nm 3D OCT of healthy and diseased eyes.

Visible light optical coherence tomography

We demonstrate for the first time optical coherence tomography (OCT) in the visible wavelength range with unprecedented sub-micrometer axial resolution, achieved by employing a photonic crystal fiber in combination with a sub-15fs Ti:sapphire laser (FEMTOLASERS). The shaped emission spectrum produced by the photonic crystal fiber ranges from 535 nm to 700 nm (centered at ~600 nm) resulting in ~0.9 micrometers axial OCT resolution in air corresponding to ~0.6 micrometers in biological tissue. Preliminary demonstration of the sub-micrometer resolution achieved with this visible light OCT setup is demonstrated on a 2.2 micrometers thick nitrocellulose membrane. The visible wavelength range not only enables extremely high axial resolution for OCT imaging, but also offers an attractive region for spectroscopic OCT.

High resolution spectroscopic optical coherence tomography in the 900-1100 nm wavelength range

We demonstrate for the first time optical coherence tomography (OCT) in the 900-1100 nm wavelength range. A photonic crystal fiber (PCF) in combination with a sub-15fs Ti:sapphire laser is used to produce an emission spectrum with an optical bandwidth of 35 nm centered at ~1070 nm. Coupling the light from the PCF based source to an optimized free space OCT system results in ~15 micrometers axial resolution in air, corresponding to ~10 micrometers in biological tissue. The near infrared wavelength range around 1100 nm is very attractive for high resolution ophthalmologic OCT imaging of the anterior and posterior eye segment with enhanced penetration. The emission spectrum of the PCF based light source can also be reshaped and tuned to cover the wavelength region around 950-970 nm, where water absorption has a local peak. Therefore, the OCT system described in this paper can also be used for spatially resolved water absorption measurements in non-transparent biological tissue. A preliminary qualitative spectroscopic Oct measurement in D2O and H2 O phantoms is described in this paper.

Multimodal imaging fiber probe for biomedical applications (Conference Presentation)

Multimodal label-free optical microscopy for in vivo and in situ imaging of human tissue represents a challenge especially when nonlinear optical techniques are used. One possible solution to address this challenge is the use of specific hand-held and endomicroscopy probes, based on optical fibers, capable to image at the same time the chemical composition and the morphological structure of the tissues. Nonlinear optical imaging techniques, including TPEF, SHG, spectral focusing CARS, combined with spectral domain OCT are capable to give functional, molecular and morphological information. Since nonlinear optical microscopy and SD-OCT require ultrashort pulses to efficiently image the targeted sample, the development of such probes requires specific attention to high peak power and ultrashort pulse delivery at the focal plane. Different optical fiber technologies for femtosecond pulse delivery are experimentally investigated in order to suggest an optical fiber that fulfill at the same time the requirements for above mentioned imaging modalities. We investigated three different approaches that are normally considered for ultrashort pulse delivery: large-mode area (LMA) fiber, hollow-core photonic bandgap fiber and kagome hollow-core fiber from GLOphotonics. We tested this three fibers on our label-free multimodal imaging platform which is capable to simultaneously acquire TPEF, SHG, spectral focusing CARS and SD-OCT. From our investigation, we identify the fiber which better satisfy the requirements of all the above mentioned imaging modalities in terms of dispersion profile and transmission of high energy pulses. Imaging capabilities are shown on a biological tissue of interest.

Three-dimensional ultrahigh resolution optical coherence tomography of retinal pathologies

The clinical feasibility of three-dimensional (3D) ultrahigh resolution (UHR) optical coherence tomography (OCT) has been investigated to visualize macular pathologies in more than 140 eyes. Three-dimensional retinal imaging was performed with high axial resolution of 3 μm employing a compact, commercially available ultrabroad bandwidth (160 nm) Titanium: sapphire laser at video-rate with up to 50 B-scans/second, each tomogram consisting of 512x1024 pixels, resulting in 25 Megavoxels/second. 3D UHR OCT allows identifying the contour of the hyaloid membrane, epiretinal membranes, inner limiting membrane, the topography of tractive forces from the retinal surface down to the level of the photoreceptor segments. Photoreceptor inner and outer segments are clearly delineated in configuration and size in micrometer with a characteristic peak in the subfoveal area. The pattern of the retinal vasculature is distinctly recognized by the hyperreflectivity of the vascular walls and the resulting reflectance shadow exhibiting a three-dimensional angiographic image of the entire vascular net without the use of fluorescent markers. 3D UHR OCT offers unprecedented, realistic threedimensional imaging of pathologies at all epi-, intra- and subretinal levels. Ultrastructural changes are identified and displayed using a dynamic video technique.

In vivo retinal optical coherence tomography at 1030 nm with enhanced penetration into the choroid

In vivo retinal imaging with ~ 8 μm axial resolution at 1030 nm is demonstrated for the first time, enabling enhanced penetration into the choroid. A new high power, broad bandwidth light source based on amplified spontaneous emission (NP Photonics, λc = 1030 nm, Δλ= 50 nm, Pout = 25 mW) has been interfaced to a time domain ophthalmic OCT system. In vivo retinal OCT tomograms performed at 800 nm are compared to those achieved at 1030 nm. Retinal OCT at longer wavelengths, e.g. 1030 nm significantly improves the visualization of the retinal pigment epithelium/choriocapillaris/choroid interface and might therefore provide new insight into choroidal/choriocapillary changes in age-related macular degeneration and other diseases of the retinal pigment epithelium (RPE)-choroid complex. 1030 nm OCT could also become a valuable tool in monitoring treatment effects on the choroids as in Verteporfin therapy.

Sensitivity estimation of spectroscopic optical coherence tomography

This study aims to investigate the sensitivity of spectroscopic optical coherence tomography (OCT) to small changes in the absorption properties of the imaged object as well as to evaluate its ability to resolve spatial variations in the objects absorption coefficient. Spectroscopic OCT would have the advantage to provide spatially resolved spectroscopic information at multiple wavelengths across the available bandwidth of the light source in a single measurement. An ultrahigh resolution OCT system based on a Ti:sapphire source emitting in the range of 700 nm to 900 nm with an optical bandwidth of up to 165 nm was used to measure optical absorption of specially designed, non-scattering phantoms. High speed and high resolution digitization in combination with a Morlet wavelet transform was utilized to derive spectroscopic information from the full interference OCT data. Using a non scattering phantom, the preliminary results of the present work reveal the challenges that have to be overcome in order to extract spatially resolved quantitative spectroscopic information by OCT.