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AimTo assess the detection rate of retinal neovascularisation (NV) in eyes with proliferative diabetic retinopathy (PDR) using widefield optical coherence tomography angiography (WF-OCTA) in comparison to ultrawidefield fluorescein angiography (UWF-FA).MethodsSingle-capture 65°-WF-OCTA-imaging was performed in patients with NV at the disc or elsewhere (NVE) detected on UWF-FA using a modified PlexElite system and B-scans were examined for blood flow signals breaching the internal limiting membrane. Sensitivity of WF-OCTA and UWF colour fundus (UWF-CF) photography for correct diagnosis of PDR was determined and interdevice agreement (Fleiss’ κ) between WF-OCTA and UWF-FA for detection of NV in the total gradable area and each retinal quadrant was evaluated.ResultsFifty-nine eyes of 41 patients with PDR detected on UWF-FA were included. Sensitivity of detecting PDR on WF-OCTA scans was 0.95 in contrast to 0.78 on UWF-CF images. Agreement in detecting NVE between WF-OCTA and UWF-FA was high in the superotemporal (κ=0.98) and inferotemporal (κ=0.94) and weak in the superonasal (κ=0.24) and inferonasal quadrants (κ=0.42). On UWF-FA, 63% of NVEs (n=153) were located in the temporal quadrants with 93% (n=142) of them being detected on WF-OCTA scans.ConclusionThe high reliability of non-invasive WF-OCTA imaging in detecting PDR can improve clinical examination with the potential to replace FA as a single diagnostic tool.

Intraoperative optical coherence tomography is still not overly pervasive in routine ophthalmic surgery, despite evident clinical benefits. That is because today’s spectral-domain optical coherence tomography systems lack flexibility, acquisition speed, and imaging depth. We present to the best of our knowledge the most flexible swept-source optical coherence tomography (SS-OCT) engine coupled to an ophthalmic surgical microscope that operates at MHz A-scan rates. We use a MEMS tunable VCSEL to implement application-specific imaging modes, enabling diagnostic and documentary capture scans, live B-scan visualizations, and real-time 4D-OCT renderings. The technical design and implementation of the SS-OCT engine, as well as the reconstruction and rendering platform, are presented. All imaging modes are evaluated in surgical mock maneuvers using ex vivo bovine and porcine eye models. The applicability and limitations of MHz SS-OCT as a visualization tool for ophthalmic surgery are discussed.

Increasing the FOV of OCTA images while keeping the acquisition time moderate requires high A-scan rates. Therefore, OCTA images appear to be noisier. Deep learning methods can be used for noise reduction. In OCTA volumes small vessels with an orientation perpendicular to the image plane are often removed by deep learning denoising algorithms, due to their small appearance. To overcome this a 3-dimensional Unet was developed to utilize volumetric information. With the knowledge of also the third dimension, the algorithm is able to distinguish between noise and vessel contrast and is therefore less likely to remove vessels.

We present a flexible OCT engine for acquiring full eye-length, anterior and posterior segment B-scans, as well as 4D live volumes with an effective A-scan rate of up to 2MHz. It is enabled by a MEMS tunable VCSEL with flexible A-scan rates, broad spectral bandwidth and a long instantaneous coherence length. Our GPU based, custom reconstruction and rendering software is able to process and display live volume series at rates of up to 17 volumes per second. We show B-scans and volume series of model eyes.

Optical coherence tomography (OCT) is one of the most innovative and successfully translated imaging techniques with substantial clinical and economic impacts and acceptance.1,2 OCT is a non-invasive optical analog to ultrasound (US) with significantly higher resolution ( millions of A-scans/s) imaging with tissue penetration of up to 2 mm, closely matching that of conventional histopathology. The year 2021 marks not only the 30th birthday of OCT (assuming its initiation with the Science paper by Huang et al.3 in 1991) but also the 35th birthday of low-coherence interferometry and optical ranging in biological systems.4,5 In the last three decades, more than 75,000 OCT related papers have been published (about two thirds in ophthalmology) with continuous yearly increases of published articles.6 Breaking through the 1000 publications/year barrier was initiated in 2005/2006 with the introduction of spectral domain OCT (SD OCT). In 2020, the OCT-related scientific output was more than 7800 papers, resulting in nearly one paper every single hour on every single day of the year. Extrapolating this publishing performance, a saturation of yearly publication output at about 9500 can be expected around 2030. After 30 years, it is interesting and important to benchmark this performance with other medical imaging techniques:6 multiphoton microscopy (MPM) [including second harmonic generation (SHG) and third harmonic generation (THG)], developed about three decades before OCT,7,8 has about 50,000 publications so far; photoacoustic imaging (PAI), established in the 1970s,9,10 has about 15,000 papers; and confocal microscopy, developed in the 1940s,11,12 has about 145,000. Developed in the 1940s,13 US imaging has contributed to about 160,000 papers; positron emission tomography (PET), initiated in the 1970s,14,15 has about 175,000; computed tomography (CT), developed in the 1930s,16 has about 750,000; and magnetic resonance imaging (MRI), developed in the late 1940s,17 has close to 1,000,000 publications. This dominance in publications of radiology and nuclear medicine imaging technologies is also one of the reasons why medical imaging is, in general, associated with MRI, CT, PET, or US. It is important to note, though, that from a medical imaging market perspective, optical imaging technologies dominate with 66% versus 34% for radiology and nuclear medicine imaging technologies. In addition, in the United States alone, about 450,000 physicians use primarily optical imaging techniques; 60,000 use primarily radiologic imaging; and about 130,000 use both.18 In the last three decades, OCT has revolutionized ophthalmic diagnosis, therapy monitoring, and guidance. Every second, a human gets a retinal OCT scan; therefore it is the fastest adopted imaging technology in the history of ophthalmology. This is mainly due to the ease of optical accessibility of the human eye, OCT’s exquisite depth sectioning performance at the micrometer level, and a significantly better performance compared with the previous gold standard in this field, ultrasonography. Furthermore, it is also due to the fact that the human retina cannot be biopsied and finally to the continuous clinically relevant improvements of this technology, due to an exquisite ecosystem between industry and academia in terms of resolution, speed, wide-field imaging, and longer wavelength for choroidal imaging. Motion contrast-based angiography, cellular level retinal visualization, visible light OCT for oximetry and unprecedented retinal layer detection, functional and contrast enhanced extensions, and artificial intelligence (AI)-enhanced performance also contributed to this success. Most of these superb technological developments can be directly translated to the original motivation and idea of OCT: to enable optical biopsy, i.e., the in situ imaging of tissue microstructure with a resolution approaching that of histology but without the need for tissue excision and preparation, allowing for quasi-instantaneous diagnostic feedback for physicians, and thereby reducing healthcare costs. There is no doubt that outside ophthalmology, OCT faces significantly bigger challenges with extremely well performing, long-established diagnostic techniques. Hence, OCT has successfully penetrated into different medical fields outside of ophthalmology, but in the last 30 years, it has not been as successful as in ophthalmic diagnosis. Despite the unprecedented success of this imaging technique in ophthalmology so far, there are still numerous remaining challenges in this field to be addressed (e.g., 4D intrasurgical OCT, portable, handheld OCT, and OCT-based digital adaptive optics) but one of the biggest perspectives for OCT is to further push performance frontiers of all involved technologies to converge to the original motivation of OCT, which is to enable in situ optical biopsy, especially for early cancer diagnosis and for a better understanding of oncogenesis. Consequently, this perspective will focus on the following areas that will pave the way for enabling even further enhanced medical diagnosis using OCT in the future. Imaging speed is absolutely essential in medical diagnosis: on the one hand, to minimize the exam time for the patient, but foremost to enable motion artifact free, properly sampled data sets. The speed of today’s systems already supports three- and even four-dimensional imaging as well as wide fields of view and functional extensions of OCT, such as OCT angiography. In the future, different technologies will enable increased OCT imaging speed with one of the fundamental decisions being at which scanning speed single-beam raster scanning will be abandoned and scanning beam parallelization will be used. Further challenges of OCT’s unmatched axial and transverse resolution will also be discussed. Similar to combining different radiology and nuclear medicine imaging technologies in current clinical diagnosis, multimodal optical imaging not only enables the “best of both/all worlds” but also compensates for the deficits of OCT (metabolic, molecular sensitivity, penetration depth, and limited contrast). Multimodal imaging applications combining techniques complementary to OCT will more and more be transferred from significantly improved microscopy setups—acting as fast quasi-histological optical biopsies next to the operating room—to the miniaturized endoscopic level with OCT acting like a global positioning system (GPS) by prescreening the tissue at a wider field of view (FOV) with microscopic resolution. Aside from OCTA, no other functional or contrast enhancing OCT extension has accomplished comparable clinical impact in the last three decades. Some more recently developed ones that might accomplish this challenging task, including quantitative OCTA (especially in neuro-ophthalmology), optical coherence elastography (OCE), dynamic contrast OCT, oximetry using visible light OCT, optophysiology—also referred to optoretinography—and AI-enhanced OCT, will be covered in this perspective. In addition, OCT miniaturization for portable, compact, handheld OCT applications, as well as for home-OCT and self-OCT, will be discussed. Finally, industrial translation of OCT, including medical device regulatory challenges, will be reviewed.

Tunable laser sources with sweep-rates higher than 1MHz recently became commercially available. Today’s commercial ophthalmic OCT systems use sweep-rates in the 100-200kHz regime. These much faster laser sources can be used to either significantly reduce the imaging time or significantly increase the field of view (FOV). In this study we investigate the clinical value of OCT with MHz-rate swept source lasers. We implemented a versatile ophthalmic OCT system using a Frequency-Domain-Mode-Locked (FDML) laser with a sweep-rate of 1.7MHz, to address a variety of ophthalmic OCT imaging applications, exhibiting large imaging depth for wide field retinal OCT and OCT angiography (OCTA) with a field of view of up to 90 degrees, as well as for anterior segment imaging, and microscopic OCTA of the choriocapillaris with repetition rates of more than 1kHz.

Side lobe artifacts on point spread functions can be traced back to (1) fringe visibility variation across the spectrum, (2) errors in sampling instances, and (3) window functions. We demonstrate signal processing methods for correcting for all three of these issues. These methods require a system calibration step. If the systems slowly age, the recalibration step could be performed in the field with a fixtured target.

1. INTRODUCTION The choriocappilaris layer is considered to be one of the first retinal layers affected in age related macular degeneration and other retinal diseases [1]. Imaging this fine vascular layer below the retinal pigment epithelium (RPE) with optical coherence tomography angiography (OCTA) has been very challenging due to the high scattering and absorption of the RPE. In OCTA higher inter B-scan times increase the sensitivity for slow motion and hence improve the contrast of fine vessels. However, it was demonstrated that for the choriocappilaris the opposite is the case [2]. Novel swept source laser technology enables acquiring images at A-scan-rates of 1.7 million A-scans per second, which is approx. 17 times faster than the fastest commercially available OCT devices [3, 4]. OCTA images of the human macula with different inter B-scan times were acquired and compared. The same prototype system was also used to acquire single shot wide-field OCTA images with up to 60 degree field of view.

We exploit the intrinsic phase stability of akinetic swept source optical coherence tomography to demonstrate digital defocus correction in-vivo at a center wavelength of 1060nm. The high speed of 500kHz enables digital adaptive optics (AO) correction across a field of view of 1.8x1.5deg, currently limited by the employed galvo scanners. The source operates in a previously presented dual resolution mode OCT system (wide field >40deg, AO >3deg) with hardware based adaptive optics. The latter allows to efficiently combine hardware and digital AO, and to further optimize the AO imaging results. We demonstrate the digitally assisted AO performance for both structural imaging as well as for OCT angiography imaging across the full retina down to the choriocapillaris.

We present retinal photoreceptor imaging with a line-field parallel spectral domain OCT modality, utilizing a commercially available 2D CMOS detector array operating at and imaging speed of 500 B-scans/s. Our results demonstrate for the first time in vivo structural and functional retinal assessment with a line-field OCT setup providing sufficient sensitivity, lateral and axial resolution and 3D acquisition rates in order to resolve individual photoreceptor cells. The phase stability of the system is manifested by the high phase-correlation across the lateral FOV on the level of individual photoreceptors. The setup comprises a Michelson interferometer illuminated by a broadband light source, where a line-focus is formed via a cylindrical lens and the back-propagated light from sample and reference arm is detected by a 2D array after passing a diffraction grating. The spot size of the line-focus on the retina is 5μm, which corresponds to a PSF of 50μm and an oversampling factor of 3.6 at the detector plane, respectively. A full 3D stack was recorded in only 0.8 s. We show representative enface images, tomograms and phase-difference maps of cone photoreceptors with a lateral FOV close to 2°. The high-speed capability and the phase stability due to parallel illumination and detection may potentially lead to novel structural and functional diagnostic tools on a cellular and microvascular imaging level. Furthermore, the presented system enables competitive imaging results as compared to respective point scanning modalities and facilitates utilizing software based digital aberration correction algorithms for achieving 3D isotropic resolution across the full FOV.

Purpose. To visualize corneal microstructure such as tear film, epithelium, and Bowman’s layer in three dimensions with spectral domain optical coherence tomography (SDOCT) exhibiting 1.3 m axial resolution at 100,000 A-scans/s. This enables measurement of epithelial and Bowman layer thickness across an area of 8.4 mm 8.4 mm and measuring the tear film thickness at the central cornea. Methods. We designed a high-performance SDOCT system, which uses a broad bandwidth TiSapph Laser and a high-speed complementary metal-oxide-semiconductor detector technology, providing a resolution in tissue of 1.3 m and an acquisition speed of 100,000 A-scans/s. Such speed and resolution is a prerequisite if precise anatomy is to be determined. The high resolution gives access to corneal microstructure such as the epithelium layer as well as the boundaries of Bowman’s layer and stroma. Even more interestingly, the tear film can be distinguished on the surface of the cornea. The Bowman’s layer and epithelial thickness for both eyes of nine subjects have been measured out of which two subjects underwent photorefractive keratectomy treatment. Results. Three-dimensional volumes of the human cornea have been recorded in vivo at an A-scan rate of 100,000 scans/s. Epithelial thickness was measured to be 55.8 3.3 m and Bowman’s layer thickness 18.7 2.5 m in normal eyes. Epithelial thickness in the eyes after refractive surgery was measured to be 68.2 5.0 m. The Bowman layer was degenerated in these eyes. The average tear film thickness of four eyes was 5.1 0.5 m. Conclusions. Using a high-performance SDOCT system with high-imaging speed and ultrahigh resolution, we produced precise thickness maps of the epithelium and for the first time of the Bowman’s layer. Such a system will give insight into high-fidelity three-dimensional corneal microstructure helping to precisely plan refractive surgery. It may furthermore yield new perspectives on studying and understanding tear film dynamics. (Optom Vis Sci 2012;89:E795–E802)

Doppler optical coherence tomography has the capability to measure blood flow quantitatively and in vivo. As only the axial component of the velocity can be assessed, the measurements have to be corrected for the angle of the vessels. We present a novel approach to extract quantitative flow data from circumpapillary scans in vivo on the human retina by registering the circular scan to a reference volume scan and extracting the angle directly from the volume. In addition, we perform phase unwrapping and interpolation of the flow under the assumption of a parabolic flow profile. We demonstrate the repeatability of the methods by applying it to different retinal vessels, achieving coefficients of variation of the average velocity of 3 to 8%. Results on the pulsatility and resistance index are also presented.

Doppler Fourier domain optical coherence tomography (D-FDOCT) can be used to visualise and measure ocular blood flow in the retina of the human eye. This has the potential to diagnose illnesses such as macula degeneration or diabetic retinopathy early on because these medical conditions cause a pathological change in the retinal vasculature and perfusion. Here we are presenting a method to separate quantitative blood flow information from static tissue. Our approach is demonstrated on retinal D-FDOCT volume scans taken at the optic nerve head (see figure) and near the fovea with a high speed CMOS-based FDOCT system. The advantage of this method is the small post-processing effort together with the immediate availability of segmented quantitative Doppler flow maps. The performance of the filtering technique is also compared to spatial frequency filtering methods.

We demonstrate a high-resolution line field en-face time domain optical coherence tomography (OCT) system using an off-axis holography configuration. Line field en-face OCT produces high speed en-face images at rates of up to 100 Hz. The high frame rate favors good phase stability across the lateral field-of-view which is indispensable for digital adaptive optics (DAO). Human retinal structures are acquired in-vivo with a broadband light source at 840 nm, and line rates of 10 kHz to 100 kHz. Structures of different retinal layers, such as photoreceptors, capillaries, and nerve fibers are visualized with high resolution of 2.8 µm and 5.5 µm in lateral directions. Subaperture based DAO is successfully applied to increase the visibility of cone-photoreceptors and nerve fibers. Furthermore, en-face Doppler OCT maps are generated based on calculating the differential phase shifts between recorded lines.

Проблемой оптической когерентной томографии на основе спектрометра является исчезновение интерференционных полос при быстром потоке, что сказывается на качестве визуализации потоков. Решение этой проблемы представляет интерес как для оптической ангиографии без дополнительного контраста, так и для количественного анализа потока. Мы разработали метод, который можно использовать для контраста очень быстрых потоков, поддерживая при этом относительно низкую скорость A-сканов. Метод основан на применении сдвига фазы π во время получения изображений, так что интерференционные полосы, вызванные движением структур образца, восстанавливаются в зависимости от продольной скорости. Это позволяет использовать медленные камеры для измерения быстрых кровотоков внутри больших сосудов в области диска зрительного нерва, сохраняя при этом хорошую чувствительность. Более того, метод можно применять для контрастирования быстро движущихся структур, ослабляя сигналы от статических и медленнее движущихся тканей. Недостатком по-прежнему является узкий скоростной диапазон, который не оптимален для проведения оптической ангиографии всего сосудистого сплетения. Тем не менее метод может быть полезен для наблюдения за быстрой динамикой изменений, например в оптической эластографии. Мы представляем различные варианты этого метода, основанного на внутрикадровой фазовой модуляции, а также на данных последовательного сканирования в Aи B-режимах, которые затем попарно суммируются. Сдвиг фазы π между суммируемыми сканами равноценен фактически вычитанию обоих сканов в комплексном пространстве. Анализ различий комплексного сигнала между последовательными B-сканами позволяет, в частности, контрастировать очень медленные потоки капиллярной сети. Установив теоретические основы, мы демонстрируем контрольно-проверочные измерения с пьезозеркалом, а также in vivo измерения сетчатки глаза человека для различных внутрикадровых схем сдвига фазы. Мы показываем способность контрастировать парафовеальные капиллярные структуры, применяя метод дифференциального B-сканирования, и обсуждаем ограничения этого метода. Установлено, что добиться улучшения чувствительности возможно за счет увеличения количества B-сканов, используемых для вычисления отличий сигнала, а также путем увеличения частоты выборки. При in vivo визуализации необходимо следить за тем, чтобы общее время измерения оставалось низким, обычно несколько секунд. Метод может зарекомендовать себя как полезный диагностический инструмент, поскольку некоторые заболевания сетчатки глаза проявляются на ранней стадии капиллярных нарушений., Spectrometer based optical coherence tomography suffers from fringe washout for fast flow, a drawback for flow visualization, which is of interest for both lable-free optical angiography and flow quantification. We presented a method, which can be used to contrast very fast flows, while maintaining relatively low A-scan rates. It is based on introducing a phase shift of π during acquisition such that the interference fringes associated to moving sample structures are recovered depending on the axial velocity. This enables the use of slower line scan cameras for measuring the fast blood flows within the large vessels in the region of the optic nerve head, while keeping good sensitivity. Furthermore it can be used to contrast the fast moving structures by attenuating the static and slower moving tissue signals. A drawback is still the narrow velocity bandwidth, which is not optimal for providing optical angiography for the full vascular plexus. Nevertheless, it could be of value for following fast dynamic changes, as for example in optical elastography. We introduce different variants of this method, based on intra-frame phase switching, as well as between consecutive A-scans and B-scans, which are then pairwise summed. A phase shift of π between summed scans is in fact equivalent to subtraction of both in general complex valued scans. Analyzing complex signal differences between successive B-scans allows in particular contrasting very slow flows of the capillary network. After setting the theoretical framework we show proof-of-principle measurements with a piezo mirror, as well as in vivo measurements of the human retina for the different intraframe phase shifting schemes. We further show the capability to contrast the parafoveal capillary structure with the differential inter B-scan method and discuss its limitations. Improvement of the sensitivity might be achieved by increasing the number of B-scans to be used for calculating the signal differences, as well as by increasing the sampling density. Care must then be taken for in vivo imaging to keep the total measurement time still sufficiently small, typically a few seconds. The method may proof as a valuable diagnostic tool, as several retinal diseases will manifest at an early stage in capillary disorders.

Spectrometer based optical coherence tomography suffers from fringe washout for fast flow, a drawback for flow visualization, which is of interest for both lable-free optical angiography and flow quantification. We presented a method, which can be used to contrast very fast flows, while maintaining relatively low A-scan rates. It is based on introducing a phase shift of π during acquisition such that the interference fringes associated to moving sample structures are recovered depending on the axial velocity. This enables the use of slower line scan cameras for measuring the fast blood flows within the large vessels in the region of the optic nerve head, while keeping good sensitivity. Furthermore it can be used to contrast the fast moving structures by attenuating the static and slower moving tissue signals. A drawback is still the narrow velocity bandwidth, which is not optimal for providing optical angiography for the full vascular plexus. Nevertheless, it could be of value for following fast dynamic changes, as for example in optical elastography. We introduce different variants of this method, based on intra-frame phase switching, as well as between consecutive A-scans and B-scans, which are then pairwise summed. A phase shift of π between summed scans is in fact equivalent to subtraction of both in general complex valued scans. Analyzing complex signal differences between successive B-scans allows in particular contrasting very slow flows of the capillary network. After setting the theoretical framework we show proof-of-principle measurements with a piezo mirror, as well as in vivo measurements of the human retina for the different intraframe phase shifting schemes. We further show the capability to contrast the parafoveal capillary structure with the differential inter B-scan method and discuss its limitations. Improvement of the sensitivity might be achieved by increasing the number of B-scans to be used for calculating the signal differences, as well as by increasing the sampling density. Care must then be taken for in vivo imaging to keep the total measurement time still sufficiently small, typically a few seconds. The method may proof as a valuable diagnostic tool, as several retinal diseases will manifest at an early stage in capillary disorders.

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.

We use phase-sensitive optical coherence tomography to measure relative motions within the human eye. From a sequence of tomograms, the phase difference between successive tomograms reveals the local axial motion of the tissue at every location within the image. The pulsation of the retina and of the lamina cribrosa amounts to, at most, a few micrometers per second, while the bulk velocity of the eye, even with the head resting in an ophthalmic instrument, is a few orders of magnitude faster. The bulk velocity changes continuously as the tomograms are acquired, whereas localized motions appear at acquisition times determined by the repeated scan of the tomogram. This difference in timing allows the bulk motion to be separated from any localized motions within a temporal bandwidth below the tomogram frame rate. In the human eye, this reveals a map of relative motions with a precision of a few micrometers per second.

We use phase-sensitive optical coherence tomography (OCT) to measure the deformation of the optic nerve head during the pulse cycle, motivated by the possibility that these deformations might be indicative of the progression of glaucoma. A spectral-domain OCT system acquired 100k A-scans per second, with measurements from a pulse-oximeter recorded simultaneously, correlating OCT data to the subject’s pulse. Data acquisition lasted for 2 seconds, to cover at least two pulse cycles. A frame-rate of 200–400 B-scans per second results in a sufficient degree of correlated speckle between successive frames that the phase-differences between fames can be extracted. Bulk motion of the entire eye changes the phase by several full cycles between frames, but this does not severely hinder extracting the smaller phase-changes due to differential motion within a frame. The central cup moves about 5 μm/s relative to the retinal-pigment-epithelium edge, with tissue adjacent to blood vessels showing larger motion.

We present a holographic imaging device with a low-coherence light source that uses the reflection of the objective lens as reference illumination. This results in a simple setup and allows applications to microscopy with only small modifications of the setup for aberration measurements. In addition, it opens the prospects to in vivo ophthalmic imaging. We present in vitro experiments using a resolution test target to quantify the system performance. We demonstrate that we can achieve diffraction-limited resolution and show the possibility of aberration correction. We also present preliminary results using a scattering sample.

When processing Doppler optical coherence tomography images, there is a need to segment the Doppler signatures of the vessels. This can be used for visualization, for finding the center point of the flow areas or to facilitate the quantitative analysis of the vessel flow. We propose the use of a support-vector machine classifier in order to segment the flow. It uses the phase values of the Doppler image as well as texture information. We show that superior results compared to conventional simple threshold-based methods can be achieved in conditions of significant phase noise, which inhibit the use of a simple threshold of the phase values.

We present a single spectrometer functional spectral domain optical coherence tomography system, which allows for encoding additional information within the spatial frequencies. The method is based on a differentiation between orthogonal polarization channels through spatial modulation introduced by an electro-optic modulator. This method is used to perform Ultrahigh- speed retinal polarization sensitive optical coherence tomography (PSOCT). With this setup, we realized for the first time polarization sensitive OCT measurements of the human retina in-vivo, with camera line rates of up to 160.000 A-scans per second. Compared to PSOCT systems, operating at traditional line rates, this significantly improves patient comfort during the measurements and gives the possibility to resolve microscopic retinal details, while still gaining information of the polarization characteristics of the tissue. In this proceeding we present preliminary results acquired with this ultra-high speed PSOCT system.

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.

We present a method for the automated extraction of Doppler OCT flow information by using a support vector machine that combines different features for classification. We employ histogram equalization that makes it possible to distinguish vessels from bulk tissue by texture analysis. This method is particularly applicable to settings with significant phase noise as it is more robust to multiple scattering components than simple threshold-based methods.

We developed a high speed Doppler tomography system together with flow extraction algorithms that provide a flexible tool to assess retinal perfusion. The aim of the present study is to stimulate perfusion by flickering with light of adjustable color and to measure changes depending on light frequency and flicker location. We observed relative changes in arterial flow velocity during flicker stimulation up to 50%. We found in arteries close to the optic nerve head the highest flicker response at a frequency of 8Hz. We believe that a multimodal functional imaging concept is of high value for an accurate and early diagnosis and understanding of retinal pathologies and pathogenesis.

We present a polarization sensitive spectral domain optical coherence tomography system that is capable to retrieve with a single camera both retardation and optical axis orientation. The method is based on a differentiation between orthogonal polarization channels through spatial modulation introduced by an electro-optic modulator. Proof-of principle using a chromatic quarter wave plate designed for 1300nm as a sample and acquisitions of a piece of borealis, a highly birefringend plastic is provided. Results of the method for in-vivo imaging of a fingertip are presented.

Polarization sensitive spectral domain optical coherence tomography is introduced, capable to retrieve with a single camera retardation and axis orientation at 100.000 A-scans/second. Orthogonal polarization channels are distinguished through spatial modulation by an electro-optic modulator.

Novel CMOS detector technology allows for high-speed volumetric tissue imaging with Fourier domain optical coherence tomography. Acquisition speeds of 200kHz reveal comprehensive image details due to the virtual lack of motion artifacts. We applied this system to the retina and achieved high resolution imaging with 5µm x 3µm transverse and axial resolution. Such resolution allows observing microscopic details such as photoreceptor cone mosaic, nerve fiber bundles, and the capillary bed without applying adaptive optics instrumentation. Fast image series reveal perfusion dynamics of full retinal volumes and allow for tracking of individual photoreceptors to study their dynamics. We observed that for in-vivo imaging speed is crucial for reproducible maps of microscopic tissue details.

Applying novel detector development based on CMOS technology to Fourier domain optical coherence tomography we achieve depth profile rates up to 200,000 scans/sec. This speed allows for dramatic improvement for imaging small retinal details, such as photo-receptors and capillaries. We demonstrate the impact of this achievable speed to Doppler tomography and discuss advantages as well as short-comings of high speed 3D Doppler imaging of the human retina. Experimental data of 3D static D-FDOCT sets from fovea and nerve head region are shown together with first 4D imaging of retinal capillary flow.

Probing the retina with flicker light of defined frequencies allowed to offset the detection for intrinsic signals from proband motion artifacts as well as blood flow. In addition the fast imaging sequence capability of FDOCT is promising for the assessment of fast physiologic changes within retinal structures. For the present study two measurement protocols are evaluated: first, taking fast tomogram series across a flickered region, and then constructing via frequency analysis and bandpass filtering a functional OCT tomogram similar to fMRI. The second protocol consists of a fast local A-scan series at 17kHz rate with 1Hz flicker. 'Light-on' time is 250ms. 'Lights off' time is 750ms. 500ms before 'light-on' is used for calculating the baseline. Finally the average over 5 cycles is taken. A clear negative response is found at the outer photoreceptor segment for both 'light-on' and 'light-off' edge. The response appears to be stronger for the 'light off' edge. The shape of the responses is analysed and might eventually be used in linear regression models to enhance the sensitivity of our fOCT approach.

Doppler OCT systems allow nowadays to visualize quantitative and qualitative angiographic maps of retinal tissue. We equipped the instrument with a pulse oximeter and recorded the pulse synchronously with the resonant Doppler flow data. Recombination of tomograms according to the heart beat cycles yields full volumes for each cycle instant. We believe such multi-dimensional functional information and the ability to monitor dynamic processes over time to open exciting perspectives that ultimately contribute to a better understanding of retinal physiology and patho-physiology in-vivo.

The trend in biomedical imaging is towards high resolution imaging of dynamic physiologic or metabolic processes. Fourier domain optical coherence tomography employing novel CMOS detector technology allows for a big step in this direction. Acquisition speeds of 200kHz reveal comprehensive tissue details on the level of histology but in-vivo due to virtual lack of motion artifacts. We applied this system to the retina and achieved high resolution imaging with 5μm × 3μm transverse and axial resolution. Such resolution allows observing microscopic details such as photoreceptor cone mosaic, nerve fiber bundles, and the capillary bed. Fast image series assess perfusion dynamics of full retinal volumes and allow for tracking of individual photoreceptors to study their dynamics. Finally the availability of signal phase uniquely allows for quantitative perfusion imaging within small retinal vessels and capillaries.

We present a novel medical imaging modality based on optical coherence tomography (OCT) that enables in vivo 3D tomography at acquisition rates up to 1 MHz. Line field parallel swept source interferometric imaging (LPSI) combines line-field swept source OCT with modulation of the interferometric signal in spatial direction for full range imaging. This method enables high speed imaging with cost-effective and commercially available technology. We explain the realization of the LPSI setup, acquisition, and postprocessing and finally demonstrate 3D in vivo imaging of human nail fold. To the best of our knowledge, sensitivity and depth penetration are competitive with respective point scanning OCT methods at a comparable wavelength. Measured maximum sensitivity is 98.5 dB for 100 kHz and 90 dB for 1 MHz. Together with the significantly relaxed technological requirements regarding detection and swept source technology, LPSI might be a promising concept for future diagnostic OCT imaging.

Purpose To visualize the precorneal tear film with ultrahigh-resolution spectral domain optical coherence tomography, enabling quantification of tear film thickness in healthy subjects. Methods A custom-built spectral domain optical coherence tomography system comprising a broadband titanium:sapphire laser operating at 800 nm and a high-speed charge coupled device (CCD) camera with a read-out rate of 47 kHz was used for measurement of precorneal tear film thickness. The system provides a theoretical axial resolution of 1.2 μm in tissue. The signal-to-noise ratio close to the zero delay was measured with 94 dB. A total of 26 healthy subjects were included in this study. Measurement was started immediately after blinking and averaged over a period of 1 second. In a subset of eight healthy subjects, the reproducibility of the approach was studied by measuring the tear film thickness every 10 minutes over 1 hour. Results The average central tear film thickness of the measured population was 4.79 ± 0.88 μm. Reproducibility was very high, with an intraclass correlation coefficient of 0.97. A breakup of the tear film was observed in one subject after 14 seconds. Conclusions Our data indicate that the human precorneal tear film can be measured with excellent reproducibility using ultrahigh-resolution optical coherence tomography. This technique may be a valuable tool in the management of dry eye syndrome.