Cedric Blatter

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.

Resonant Doppler flow imaging and optical vivisection of retinal blood vessels

For Fourier domain optical coherence tomography any sample movement during camera integration causes blurring of interference fringes and as such reduction of sensitivity for flow detection. The proposed method overcomes this problem by phase-matching a reference signal to the sample motion. The interference fringes corresponding to flow signal will appear frozen across the detector whereas those of static sample structures will be blurred resulting in enhanced contrast for blood vessels. An electro-optic phase modulator in the reference arm, driven with specific phase cycles locked to the detection frequency, allows not only for qualitative but also for quantitative flow detection already from the relative signal intensities. First applications to extract in-vivo retinal flow and to visualize 3D vascularization, i.e. optical vivisection, are presented.

Ultrahigh-speed non-invasive widefield angiography

Retinal and choroidal vascular imaging is an important diagnostic benefit for ocular diseases such as age-related macular degeneration. The current gold standard for vessel visualization is fluorescence angiography. We present a potential non-invasive alternative to image blood vessels based on functional Fourier domain optical coherence tomography (OCT). For OCT to compete with the field of view and resolution of angiography while maintaining motion artifacts to a minimum, ultrahigh-speed imaging has to be introduced. We employ Fourier domain mode locking swept source technology that offers high quality imaging at an A-scan rate of up to 1.68 MHz. We present retinal angiogram over ∼48  deg acquired in a few seconds in a single recording without the need of image stitching. OCT at 1060 nm allows for high penetration in the choroid and efficient separate characterization of the retinal and choroidal vascularization.

In situ structural and microangiographic assessment of human skin lesions with high-speed OCT

We demonstrate noninvasive structural and microvascular contrast imaging of different human skin diseases in vivo using an intensity difference analysis of OCT tomograms. The high-speed swept source OCT system operates at 1310 nm with 220 kHz A-scan rate. It provides an extended focus by employing a Bessel beam. The studied lesions were two cases of dermatitis and two cases of basal cell carcinoma. The lesions show characteristic vascular patterns that are significantly different from healthy skin. In case of inflammation, vessels are dilated and perfusion is increased. In case of basal cell carcinoma, the angiogram shows a denser network of unorganized vessels with large vessels close to the skin surface. Those results indicate that assessing vascular changes yields complementary information with important insight into the metabolic demand.

Vectorial reconstruction of retinal blood flow in three dimensions measured with high resolution resonant Doppler Fourier domain optical coherence tomography

Resonant Doppler Fourier domain optical coherence tomography (FDOCT) is a functional imaging tool for extracting tissue flow. The method is based on the effect of interference fringe blurring in spectrometer-based FDOCT, where the path difference between structure and reference changes during camera integration. If the reference path length is changed in resonance with the Doppler frequency of the sample flow, the signals of resting structures will be suppressed, whereas the signals of blood flow are enhanced. This allows for an easy extraction of vascularization structure. Conventional flow velocity analysis extracts only the axial flow component, which strongly depends on the orientation of the vessel with respect to the incident light. We introduce an algorithm to extract the vessel geometry within the 3-D data volume. The algorithm calculates the angular correction according to the local gradients of the vessel orientations. We apply the algorithm on a measured 3-D resonant Doppler dataset. For validation of the reproducibility, we compare two independently obtained 3-D flow maps of the same volunteer and region.

Imaging of the parafoveal capillary network and its integrity analysis using fractal dimension

Using a spectral domain OCT system, equipped with a broadband Ti:sapphire laser, we imaged the human retina with 5 µm x 1.3 µm transverse and axial resolution at acquisition rate of 100 kHz. Such imaging speed significantly reduces motion artifacts. Combined with the ultra-high resolution, this allows observing microscopic retinal details with high axial definition without the help of adaptive optics. In this work we apply our system to image the parafoveal capillary network. We demonstrate how already on the intensity level the parafoveal capillaries can be segmented by a simple structural high pass filtering algorithm. This data is then used to quantitatively characterize the capillary network of healthy and diseased eyes. We propose to use the fractal dimension as index for capillary integrity of pathologic disorders.

Extended focus high-speed swept source OCT with self-reconstructive illumination

We present a Bessel beam illumination FDOCT setup using a FDML Swept Source at 1300 nm with up to 440 kHz A-scan rate, and discuss its advantages for structural and functional imaging of highly scattering samples. An extended focus is achieved due to the Bessel beam that preserves its lateral extend over a large depth range. Furthermore, Bessel beams exhibit a self-reconstruction property that allows imaging even behind obstacles such as hairs on skin. Decoupling the illumination from the gaussian detection increases the global sensitivity and enables dark field imaging. Dark field imaging is useful to avoid strong reflexes from the sample surface that adversely affect the sensitivity due to the limited dynamic range of high speed 8 bit acquisition cards. In addition the possibility of contrasting capillaries with high sensitivity is shown, using inter-B-scan speckle variance analysis. We demonstrate intrinsic advantages of the extended focus configuration, in particular the reduction of the phase decorrelation effect below vessels leading to improved axial vessel definition.

Dove prism based rotating dual beam bidirectional Doppler OCT

Traditional Doppler OCT is highly sensitive to motion artifacts due to the dependence on the Doppler angle. This limits its accuracy in clinical practice. To overcome this limitation, we use a bidirectional dual beam technique equipped with a novel rotating scanning scheme employing a Dove prism. The volume is probed from two distinct illumination directions with variable controlled incidence plane, allowing for reconstruction of the true flow velocity at arbitrary vessel orientations. The principle is implemented with Swept Source OCT at 1060nm with 100,000 A-Scans/s. We apply the system to resolve pulsatile retinal absolute blood velocity by performing segment scans around the optic nerve head and circumpapillary scan time series.

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.

Intrasweep phase-sensitive optical coherence tomography for noncontact optical photoacoustic imaging

We introduce a method to extract the photoacoustic (PA) signal from the phase time evolution of an optical coherence tomography (OCT) swept source spectral sweep. This all-optical detection is achieved in a noncontact fashion directly on the sample surface by using its specular reflection. High-speed measurement and referencing allow for close to shot noise limited phase-sensitive detection. It offers a simple way to perform OCT and PA imaging by sharing the same system components.