Thermally tuned VCSEL at 850†nm as a low-cost alternative source for full-eye SS-OCT.

Swept-source optical coherence tomography (SS-OCT) demonstrates superior performance in comparison to spectral domain OCT with regard to depth ranging. The main driver of cost for SS-OCT systems is, however, the price of the source. Here we show a low-cost alternative swept source that uses a thermally tuned vertical-cavity surface-emitting laser (VCSEL) at 850 nm. Its center wavelength can be tuned by adjusting the operating temperature through modulation of the injection current. At 2 kHz sweep rate, the depth range of the system was 5 cm, with a sensitivity roll-off of under -3 dB across this range. The system achieved a sensitivity of 97 dB with a sample beam power of 0.3 mW and an axial resolution of 50 µm in air. To demonstrate the system performance in vivo, an eye of a healthy volunteer was measured, and full-eye scans were acquired at 25 and 50 kHz from the cornea to the retina. Based on our results, we believe that this technology can be used as a cost-effective alternative OCT for point-of-care diagnostics.

Three-dimensional assessment of para- and perifoveal photoreceptor densities and the impact of meridians and age in healthy eyes with adaptive-optics optical coherence tomography (AO-OCT).

An adaptive optics optical coherence tomography (AO-OCT) system is used to assess sixty healthy eyes of thirty subjects (age 22 to 75) to evaluate how the outer retinal layers, foveal eccentricity and age effect the mean cone density. The cone mosaics of different retinal planes (the cone inner segment outer segment junction (IS/OS), the cone outer segment combined with the IS/OS (ISOS+), the cone outer segment tips (COST), and the full en-face plane (FEF)) at four main meridians (superior, nasal, inferior, temporal) and para- and perifoveal eccentricities (ecc 2.5° and 6.5°) were analyzed quantitatively. The mean overall cone density was 19,892/mm2 at ecc 2.5° and 13,323/mm2 at ecc 6.5°. A significant impact on cone density was found for eccentricity (up to 6,700/mm2 between ecc 2.5° and 6.5°), meridian (up to 3,700/mm2 between nasal and superior meridian) and layer (up to 1,400/mm2 between FEF and IS/OS). Age showed only a weak negative effect. These factors as well as inter-individual variability have to be taken into account when comparing cone density measurements between healthy and pathologically changed eyes, as their combined effect on density can easily exceed several thousand cones per mm2 even in parafoveal regions.

Synthetic subaperture-based angle-independent Doppler flow measurements using single-beam line field optical coherence tomography in vivo.

We demonstrate a synthetic subaperture-based angle-independent Doppler flow calculation, using a line field spectral domain optical coherence tomography system. The high speed of the system features a high phase stability over the volume, which is necessary to apply synthetic subapertures in the aperture plane. Thus, the flow component for each subaperture can be reconstructed in postprocessing. Capillary phantom and in vivo retinal imaging experiments were performed to validate and demonstrate angle-independent Doppler flow calculation.

THREE-DIMENSIONAL ANALYSIS OF RETINAL MICROANEURYSMS WITH ADAPTIVE OPTICS OPTICAL COHERENCE TOMOGRAPHY.

PURPOSE: To characterize retinal microaneurysms (MAs) in patients with diabetes using adaptive optics optical coherence tomography (AOOCT) and compare details found in AOOCT with those found in commercially available retinal imaging techniques. METHODS: Patients with diabetes and MA in the macular area were included in this pilot study. The area of interest, identified in standard fluorescein angiography, was imaged using an AO fundus camera and AOOCT. Microaneurysms were characterized in AOOCT (visibility, reflectivity, feeding/draining vessels, and intraretinal location) and compared with findings in AO fundus camera, OCT angiography, and fluorescein angiography. RESULTS: Fifty-three MAs were imaged in 15 eyes of 10 patients. Feeding and/or draining vessels from both capillary plexus could be identified in 34 MAs in AOOCT images. Of 45 MAs imaged with OCT angiography, 18 (40%) were visible in the superior plexus, 12 (27%) in the deep capillary plexus, and 15 MAs (33%) could not be identified at all. Intraluminal hyperreflectivity, commonly seen in AO fundus camera, corresponded only in 8 of 27 cases (30%) to intraluminal densities seen in AOOCT. CONCLUSION: Adaptive optics OCT imaging revealed that MAs located in the inner nuclear layer were connected to the intermediate and/or deep capillary plexus. Intraluminal hyperreflectivity seen on AO fundus camera images originated from a strong reflection from the vessel wall and only in a third of the cases from intraluminal clots. Currently, AOOCT is the most expedient in vivo imaging method to capture morphologic details of retinal microvasculature in 3D and in the context of the surrounding retinal anatomy.

Introduction and Validation of Low-Cost Ocular Biometry in Healthy and Cataractous Eyes Using a Thermally Tunable Swept-Source Laser.

PURPOSE: To introduce and validate a novel substantially lower-priced and rapid swept-source investigational optical biometer in healthy and cataractous eyes, using a thermally tuned laser diode used extensively in cell phones and data communication as an alternative swept source. DESIGN: Prospective accuracy, validity, and reliability analysis. METHODS: A total of 60 eyes of 59 subjects (29 eyes of 29 healthy subjects and 31 eyes of 30 cataract patients) were enrolled in a prospective comparative study at the Vienna General Hospital between August 2021 and April 2023. Averaged intraocular distances were acquired in 2.5 seconds from datasets consisting of 5000 consecutive A-scans at a single position by a low-cost swept-source optical biometry (SSOB) system. Instrument repeatability was assessed via standard deviations (SDs) and coefficients of variation (CoVs) of parameters such as axial length (AL), anterior chamber depth (ACD), lens thickness (LT), and central corneal thickness (CCT). Healthy subjects and cataract patients were subsequently measured on the same day with the SSOB and a referential partial coherence interferometry (PCI) biometer (IOLMaster 500) to establish AL inter-device correlation (r) for instrument calibration. AL and ACD as shared parameters between both biometers were evaluated for their limits of agreements (LoA) using Bland-Altman analysis. RESULTS: Repeated measurements of AL, ACD, LT, and CCT revealed SDs of 18 µm, 12 µm, 12 µm, and 10 µm, respectively. All parameters except for CCT had a COV <1%. Except for 1 eye with white cataract, 59 eyes of 59 study participants with various degrees and types of cataract could be measured with both devices. The AL inter-device correlation was excellent (r > 0.99). The 95% LoAs between both biometers were -0.14 to 0.13 mm for AL and -0.28 to 0.25 mm for ACD. CONCLUSIONS: Optical biometry using a thermally tunable VCSEL swept-source light source has the potential to provide clinically relevant biometric parameters at an unprecedented 100-fold lower price point than currently used state-of-the-art optical biometers, paving the way for compact devices in remote care settings.

Exploring single-mode VCSEL wavelength tuning for low-cost 3D optical coherence tomography and OCT angiography.

Low-cost optical coherence tomography has recently emerged as a growing field due to the increased need for general availability of OCT devices outside of the clinics. One of the main obstacles in creating low-cost SS-OCT systems is the price of the laser. In this work, we study the influence of different tuning parameters (e.g., frequency, duty cycle, modulation curve, temperature) on the resulting bandwidth of the previously proposed low-cost single-mode thermally-tunable vertical-cavity surface-emitting laser (VCSEL) source at 850 nm. With optimal parameters, the laser achieves a tuning bandwidth of 10.2 nm at a 50 kHz A-scan rate. In addition, we show the first 3D rendered volume scans of both anterior and posterior segment using a custom VCSEL-based low-cost OCT setup. With the help of deep-learning-based denoising, it was possible to critically reduce the noise in single scans. Moreover, by investigating the phase stability, it became apparent that phase stability between sweeps increases with rising modulation frequencies, making the auxiliary interferometer obsolete. Thus, the system's 50 kHz tuning regimen is also suitable for functional extensions such as OCT angiography.

Digital adaptive optics based on digital lateral shearing of the computed pupil field for point scanning retinal swept source OCT.

A novel non-iterative digital adaptive optics technique is presented in which the wavefront error is calculated using the phase difference between the pupil field and its digital copies translated by a pixel along the horizontal and vertical direction in the pupil plane. This method provides slope data per pixel, thus can generate > 50k local slope data samples for a circular pupil of diameter 256 pixels with high accuracy and dynamic range. It offers more than 12x faster computational speed in comparison to the sub-aperture based digital adaptive optics method. Furthermore, it is independent of any system parameters, the light distribution in the pupil plane, or the intensity of the image. The technique is useful in applications such as interferometric or digital holography based microscopy, metrology, and as digital wavefront sensor in adaptive optics, where focusing of light in the sample is involved that creates a guide star or where the sample itself exhibits guide star-like structures. This technique is implemented in a point scanning swept-source OCT at 1060 nm, and a large wavefront error with a peak to valley of 20 radians and root mean square error of 0.71 waves is detected and corrected in case of a micro-beads phantom sample. Also, human photoreceptor images are recovered from aberrated retinal OCT volumes acquired at eccentricities of 2 and 2.5 degrees from the fovea in vivo.

Reconstruction of visible light optical coherence tomography images retrieved from discontinuous spectral data using a conditional generative adversarial network.

Achieving high resolution in optical coherence tomography typically requires the continuous extension of the spectral bandwidth of the light source. This work demonstrates an alternative approach: combining two discrete spectral windows located in the visible spectrum with a trained conditional generative adversarial network (cGAN) to reconstruct a high-resolution image equivalent to that generated using a continuous spectral band. The cGAN was trained using OCT image pairs acquired with the continuous and discontinuous visible range spectra to learn the relation between low- and high-resolution data. The reconstruction performance was tested using 6000 B-scans of a layered phantom, micro-beads and ex-vivo mouse ear tissue. The resultant cGAN-generated images demonstrate an image quality and axial resolution which approaches that of the high-resolution system.

Assessment of Detailed Photoreceptor Structure and Retinal Sensitivity in Diabetic Macular Ischemia Using Adaptive Optics-OCT and Microperimetry.

Purpose: The purpose of this study was to assess density and morphology of cone photoreceptors (PRs) and corresponding retinal sensitivity in ischemic compared to nonischemic retinal capillary areas of diabetic eyes using adaptive optics optical coherence tomography (AO-OCT) and microperimetry (MP). Methods: In this cross-sectional, observational study five eyes of four patients (2 eyes with proliferative diabetic retinopathy (DR) and 3 eyes moderate nonproliferative DR) were included. PR morphology and density was manually assessed in AO-OCT en face images both at the axial position of the inner-segment outer segment (IS/OS) and cone outer segment tips (COSTs). Retinal sensitivity was determined by fundus-controlled microperimetry in corresponding areas (MP-3, Nidek). Results: In AO-OCT, areas affected by capillary nonperfusion showed severe alterations of cone PR morphology at IS/OS and COST compared to areas with intact capillary perfusion (84% and 87% vs. 9% and 8% of area affected for IS/OS and COST, respectively). Mean reduction of PR signal density in affected areas compared to those with intact superficial capillary plexus (SCP) and deep capillary plexus (DCP) perfusion of similar eccentricity was -38% at the level of IS/OS (P = 0.01) and -39% at the level of COST (P = 0.01). Mean retinal sensitivity was 10.8 ± 5.4 in areas affected by DCP nonperfusion and 28.2 ± 1.5 outside these areas (P < 0.001). Conclusions: Cone PR morphology and signal density are severely altered in areas of capillary nonperfusion. These structural changes are accompanied by a severe reduction of retinal sensitivity, indicating the importance of preventing impaired capillary circulation in patients with DR.

Three-dimensional composition of the photoreceptor cone layers in healthy eyes using adaptive-optics optical coherence tomography (AO-OCT).

PURPOSE: To assess the signal composition of cone photoreceptors three-dimensionally in healthy retinas using adaptive optics optical coherence tomography (AO-OCT). METHODS: Study population. Twenty healthy eyes of ten subjects (age 23 to 67). Procedures. After routine ophthalmological assessments, eyes were examined using AO-OCT. Three-dimensional volumes were acquired at 2.5° and 6.5° foveal eccentricity in four main meridians (superior, nasal, inferior, temporal). Cone densities and signal compositions were investigated in four different planes: the cone inner segment outer segment junction (IS/OS), the cone outer segment combined with the IS/OS (ISOS+), the cone outer segment tips (COST) and full en-face plane (FEF) combining signals from all mentioned cone layers. Additionally, reliability of a simple semi-automated approach for assessment of cone density was tested. Main outcome measures. Cone density of IS/OS, IS/OS+, COST and FEF. Qualitative depiction and composition of each cone layer. Inter-rater agreement of cone density measurements. RESULTS: Mean overall cone density at all eccentricities was highest at the FEF plane (21.160/mm2), followed by COST (20.450/mm2), IS/OS+ (19.920/mm2) and IS/OS (19.530/mm2). The different meridians and eccentricities had a significant impact on cone density, with lower eccentricity resulting in higher cone densities (p≤.001), which were highest at the nasal, then temporal, then inferior and then superior meridian. Depiction of the cone mosaic differed between all 4 layers regarding signal size and packing density. Therefore, different cone layers showed evident but not complete signal overlap. Using the semi-automated technique for counting of cone signals achieved high inter-rater reliability (ICC > .99). CONCLUSIONS: In healthy individuals qualitative and quantitative changes in cone signals are found not only in different eccentricities and meridians, but also within different photoreceptor layers. The variation between cone planes has to be considered when assessing the integrity of cone photoreceptors in healthy and diseased eyes using adaptive optics technology.

In vivo human retinal swept source optical coherence tomography and angiography at 830 nm with a CMOS compatible photonic integrated circuit.

Photonic integrated circuits (PIC) provide promising functionalities to significantly reduce the size and costs of optical coherence tomography (OCT) systems. This paper presents an imaging platform operating at a center wavelength of 830 nm for ophthalmic application using PIC-based swept source OCT. An on-chip Mach-Zehnder interferometer (MZI) configuration, which comprises an input power splitter, polarization beam splitters in the sample and the reference arm, and a 50/50 coupler for signal interference represents the core element of the system with a footprint of only [Formula: see text]. The system achieves 94 dB imaging sensitivity with 750 [Formula: see text]W on the sample, 50 kHz imaging speed and 5.5 [Formula: see text]m axial resolution (in soft tissue). With this setup, in vivo human retinal imaging of healthy subjects was performed producing B-scans, three-dimensional renderings as well as OCT angiography. These promising results are significant prerequisites for further integration of optical and electronic building blocks on a single swept source-OCT PIC.

Toward optical coherence tomography on a chip: in vivo three-dimensional human retinal imaging using photonic integrated circuit-based arrayed waveguide gratings.

In this work, we present a significant step toward in vivo ophthalmic optical coherence tomography and angiography on a photonic integrated chip. The diffraction gratings used in spectral-domain optical coherence tomography can be replaced by photonic integrated circuits comprising an arrayed waveguide grating. Two arrayed waveguide grating designs with 256 channels were tested, which enabled the first chip-based optical coherence tomography and angiography in vivo three-dimensional human retinal measurements. Design 1 supports a bandwidth of 22 nm, with which a sensitivity of up to 91 dB (830 µW) and an axial resolution of 10.7 µm was measured. Design 2 supports a bandwidth of 48 nm, with which a sensitivity of 90 dB (480 µW) and an axial resolution of 6.5 µm was measured. The silicon nitride-based integrated optical waveguides were fabricated with a fully CMOS-compatible process, which allows their monolithic co-integration on top of an optoelectronic silicon chip. As a benchmark for chip-based optical coherence tomography, tomograms generated by a commercially available clinical spectral-domain optical coherence tomography system were compared to those acquired with on-chip gratings. The similarities in the tomograms demonstrate the significant clinical potential for further integration of optical coherence tomography on a chip system.

Ex-vivo Alzheimer's disease brain tissue investigation: a multiscale approach using 1060-nm swept source optical coherence tomography for a direct correlation to histology.

Significance: Amyloid-beta ( A - ß ) plaques are pathological protein deposits formed in the brain of Alzheimer's disease (AD) patients upon disease progression. Further research is needed to elucidate the complex underlying mechanisms involved in their formation using label-free, tissue preserving, and volumetric techniques. Aim: The aim is to achieve a one-to-one correlation of optical coherence tomography (OCT) data to histological micrographs of brain tissue using 1060-nm swept source OCT. Approach: A - ß plaques were investigated in ex-vivo AD brain tissue using OCT with the capability of switching between two magnifications. For the exact correlation to histology, a 3D-printed tool was designed to generate samples with parallel flat surfaces. Large field-of-view (FoV) and sequentially high-resolution volumes at different locations were acquired. The large FoV served to align the OCT to histology images; the high-resolution images were used to visualize fine details. Results: The instrument and the presented method enabled an accurate correlation of histological micrographs with OCT data. A - ß plaques were identified as hyperscattering features in both FoV OCT modalities. The plaques identified in volumetric OCT data were in good agreement with immunohistochemically derived micrographs. Conclusion: OCT combined with the 3D-printed tool is a promising approach for label-free, nondestructive, volumetric, and fast tissue analysis.

Analysis of longitudinal sections of retinal vessels using Doppler OCT.

We present a new method for imaging retinal vessels that provides both structural and hemodynamic information. Our technique is based on a single beam OCT system with an integrated retinal tracker that enables recording of arbitrary scan patterns. We record longitudinal sections along the traces of retinal vessels. The tracker function enables the acquisition of multiple longitudinal sections along the same trace to provide high-quality averaged OCT scans as well as temporal changes of flow dynamics. The vessel walls are clearly identified as narrow, bright lines from which the vessel diameter can be retrieved as a function of position along the vessel. Furthermore, the Doppler angle can be obtained at each position along the vessel trace, enabling measurement of absolute blood flow by Doppler OCT analysis. The method is demonstrated in flow phantoms and in-vivo on retinal vessel bifurcations in healthy volunteers. In 7 of 9 imaged bifurcations, measured in- and outflow deviate by less than 11%, demonstrating the consistency of the method.

Improved Diagnostic Imaging of Brain Tumors by Multimodal Microscopy and Deep Learning.

Fluorescence-guided surgery is a state-of-the-art approach for intraoperative imaging during neurosurgical removal of tumor tissue. While the visualization of high-grade gliomas is reliable, lower grade glioma often lack visible fluorescence signals. Here, we present a hybrid prototype combining visible light optical coherence microscopy (OCM) and high-resolution fluorescence imaging for assessment of brain tumor samples acquired by 5-aminolevulinic acid (5-ALA) fluorescence-guided surgery. OCM provides high-resolution information of the inherent tissue scattering and absorption properties of tissue. We here explore quantitative attenuation coefficients derived from volumetric OCM intensity data and quantitative high-resolution 5-ALA fluorescence as potential biomarkers for tissue malignancy including otherwise difficult-to-assess low-grade glioma. We validate our findings against the gold standard histology and use attenuation and fluorescence intensity measures to differentiate between tumor core, infiltrative zone and adjacent brain tissue. Using large field-of-view scans acquired by a near-infrared swept-source optical coherence tomography setup, we provide initial assessments of tumor heterogeneity. Finally, we use cross-sectional OCM images to train a convolutional neural network that discriminates tumor from non-tumor tissue with an accuracy of 97%. Collectively, the present hybrid approach offers potential to translate into an in vivo imaging setup for substantially improved intraoperative guidance of brain tumor surgeries.

Morphologic and Functional Assessment of Photoreceptors After Macula-Off Retinal Detachment With Adaptive-Optics OCT and Microperimetry.

PURPOSE: Limited information is available on morphologic and functional regeneration of photoreceptors after retinal detachment (RD) surgery. This observational clinical study compared morphologic and functional changes of cones after vitrectomy for macula-off retinal detachment. DESIGN: Prospective, fellow-eye comparative case series. METHODS: StudyPopulation: Five eyes after vitrectomy with gas for macula-off retinal detachment (retinal detachment eyes, RDE) and 5 healthy fellow eyes (HFE) of 5 patients (mean age 59.8 years, macula-off duration 0.5 days to 5.5 days). ObservationProcedures: Eyes were examined with adaptive-optics optical coherence tomography (AO-OCT), spectral-domain OCT (SDOCT), and microperimetry (MP) at 6 (baseline, BL) and 56 weeks (follow-up, FUP) after 23 gauge pars plana vitrectomy and SF6 gas tamponade. Eight corresponding regions at foveal eccentricities of 2.5° (ecc 2.5°) and 6.5° (ecc 6.5°) were analyzed in every eye. AO-OCT en face images and SD-OCT B-scans were graded regarding irregularity and loss of photoreceptor signals ranging from none to severe changes. The number of detectable cones at height of the inner-outer segment junction (IS/OS) and cone outer segment tips (COST) was counted manually in AO-OCT images. MP with a custom grid was used to assess retinal sensitivity at these locations. MainOutcomeMeasures: Cone density, cone pattern regularity and signal attenuation, retinal sensitivity. RESULTS: In comparison to HFE, RDE showed highly irregular cone patterns in AO-OCT and irregular outer retinal bands in SDOCT. Despite significant improvement of cone pattern regularity compared to BL (P < .001), 63% of AO images showed remaining cone pattern irregularity and 45.5% of SDOCT B-scans showed severe signal reduction at FUP. In HFE, mean cone density retrieved from IS/OS and COST remained around 20,000/mm2 (ecc 2.5°) and 16,000/mm2 (ecc 6.5°) at BL and FUP. Cone density of RDE was significantly reduced and ranged between 200/mm2 and 15,600/mm2 (P < .001) at BL. Despite improvement at FUP (P < .001), mean cone density at IS/OS and COST was still lower compared to HFE and ranged between 7790 and 9555 cones/mm2 (P < .001). Mean retinal sensitivity of all measured locations remained 18 dB in HFE and was significantly lower in RDE, with 14.30 dB at BL and 14.64 dB at FUP. Both SDOCT grading and microperimetry sensitivity showed strong correlation with AO-OCT grading and cone density (rho values > 0.750). CONCLUSIONS: The combination of AO-OCT, SDOCT, and microperimetry is a powerful tool to capture cone regeneration after vitreoretinal surgery. Our study shows that cone morphology and function improve within 56 weeks after RD surgery but structural and functional impairment is still present.

Three-Dimensional Adaptive Optics-Assisted Visualization of Photoreceptors in Healthy and Pathologically Aged Eyes.

Purpose: To visualize and characterize photoreceptor (PR) layers on a subcellular level in healthy and pathologically aged eyes using adaptive-optics optical coherence tomography technology (AO-OCT). Methods: AO-OCT scanning was performed within a 2° × 2° field of view, focused on the PR layer at different retinal regions in healthy aged eyes (n = 32 eyes/16 subjects; 62- to 85-years old), eyes with early to intermediate AMD (n = 16 eyes/8 subjects, 65- to 83-years old), and eyes with advanced nonneovascular AMD (n = 16 eyes/8 subjects, 61- to 84-years old). Areas of interest were determined by AO-fundus camera, which is part of the AO-OCT system and spectral-domain (SD)-OCT. PR integrity was evaluated in AO-OCT en face and cross-sectional images at the level of inner/outer segment junction (IS/OS) and cone/PR end tips (COST/ETPR). Results: AO-OCT in healthy eyes showed clearly distinguishable and regular IS/OS and COST patterns and an inverse relation between cone density and eccentricity. In early to intermediate AMD, PR in between drusen showed more irregular patterns (P < 0.001) and slightly lower PR density (P ≤ 0.002). Drusen caused attenuated and distorted signals and a loss of PR mosaic. In advanced AMD, IS/OS and COST patterns were affected to different degrees between surrounding area, junctional zone, and atrophic area (P < 0.001), ranging from reduced PR densities to total signal loss. Conclusions: AO-OCT imaging allows the three-dimensional visualization of different PR layers in patients with AMD and age-matched healthy subjects. Thereby, AO-OCT provides a unique insight into PR morphology and shows potential to fill the gap between conventional OCT and histologic examination of the retina.

Revealing brain pathologies with multimodal visible light optical coherence microscopy and fluorescence imaging.

We present a multimodal visible light optical coherence microscopy (OCM) and fluorescence imaging (FI) setup. Specification and phantom measurements were performed to characterize the system. Two applications in neuroimaging were investigated. First, curcumin-stained brain slices of a mouse model of Alzheimer's disease were examined. Amyloid-beta plaques were identified based on the fluorescence of curcumin, and coregistered morphological images of the brain tissue were provided by the OCM channel. Second, human brain tumor biopsies retrieved intraoperatively were imaged prior to conventional neuropathologic work-up. OCM revealed the three-dimensional structure of the brain parenchyma, and FI added the tumor tissue-specific contrast. Attenuation coefficients computed from the OCM data and the florescence intensity values were analyzed and showed a statistically significant difference for 5-aminolevulinic acid (5-ALA)-positive and -negative brain tissues. OCM findings correlated well with malignant hot spots within brain tumor biopsies upon histopathology. The combination of OCM and FI seems to be a promising optical imaging modality providing complementary contrast for applications in the field of neuroimaging.

Dynamic Changes of Retinal Microaneurysms in Diabetes Imaged With In Vivo Adaptive Optics Optical Coherence Tomography.

Purpose: To prospectively monitor microaneurysms (MAs) in three dimensions using adaptive optics optical coherence tomography (AOOCT). Methods: Patients with diabetes mellitus and parafoveal MAs were included in this longitudinal study. At baseline, MAs were identified in standard fluorescein angiography (FA) and subsequently imaged with an AOOCT prototype, incorporated into an AO fundus camera (RTX1, Imagine Eyes) device. Imaging was repeated every 3 months in each patient to explore the potential structural change of MAs over time including size, shape, intraretinal position, (intra-) luminal reflectivity, and other qualitative morphologic characteristics. Results: We imaged 18 MAs in seven eyes (two left eyes) of five patients (mean age: 69 ± 7 years) over 18 months. All MAs appeared as saccular in the en face imaging plane at baseline, and no change in shape was observed in any of the MAs during follow-up. Evaluation of the AOOCT volumes revealed dynamic changes of MAs during follow-up including intermittent growth (n = 2), progressive involution (n = 3), total disappearance (n = 2), and MA division (n = 1). Intraluminal hyperreflective material was visualized in 11 out of 18 MAs, which remained stable (n = 3), increased (n = 2), regressed (n = 1), or fluctuated (n = 5). Three MAs without intraluminal spots at baseline progressively developed distinct hyperreflectivities. Conclusions: AOOCT illustrates the structurally dynamic evolution of MAs in vivo in three dimensions. Despite a consistent saccular shape in the en face view, AOOCT volumes revealed a heterogeneous behavior in regard to size and reflective status of MAs over time.

Holographic line field en-face OCT with digital adaptive optics in the retina in vivo.

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.