Wide Dynamic Range Digital Aberration Measurement and Fast Anterior-Segment OCT Imaging †.

Ocular aberrometry with a wide dynamic range for assessing vision performance and anterior segment imaging that provides anatomical details of the eye are both essential for vision research and clinical applications. Defocus error is a major limitation of digital wavefront aberrometry (DWA), as the blurring of the detected point spread function (PSF) significantly reduces the signal-to-noise ratio (SNR) beyond the ±3 D range. With the aid of Badal-like precompensation of defocus, the dynamic defocus range of the captured aberrated PSFs can be effectively extended. We demonstrate a dual-modality MHz VCSEL-based swept-source OCT (SS-OCT) system with easy switching between DWA and OCT imaging modes. The system is capable of measuring aberrations with defocus dynamic range of 20 D as well as providing fast anatomical imaging of the anterior segment at an A-scan rate of 1.6 MHz.

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.

Roadmap on digital holography [Invited].

This Roadmap article on digital holography provides an overview of a vast array of research activities in the field of digital holography. The paper consists of a series of 25 sections from the prominent experts in digital holography presenting various aspects of the field on sensing, 3D imaging and displays, virtual and augmented reality, microscopy, cell identification, tomography, label-free live cell imaging, and other applications. Each section represents the vision of its author to describe the significant progress, potential impact, important developments, and challenging issues in the field of digital holography.

Morpho-molecular ex vivo detection and grading of non-muscle-invasive bladder cancer using forward imaging probe based multimodal optical coherence tomography and Raman spectroscopy.

Non-muscle-invasive bladder cancer affects millions of people worldwide, resulting in significant discomfort to the patient and potential death. Today, cystoscopy is the gold standard for bladder cancer assessment, using white light endoscopy to detect tumor suspected lesion areas, followed by resection of these areas and subsequent histopathological evaluation. Not only does the pathological examination take days, but due to the invasive nature, the performed biopsy can result in significant harm to the patient. Nowadays, optical modalities, such as optical coherence tomography (OCT) and Raman spectroscopy (RS), have proven to detect cancer in real time and can provide more detailed clinical information of a lesion, e.g. its penetration depth (stage) and the differentiation of the cells (grade). In this paper, we present an ex vivo study performed with a combined piezoelectric tube-based OCT-probe and fiber optic RS-probe imaging system that allows large field-of-view imaging of bladder biopsies, using both modalities and co-registered visualization, detection and grading of cancerous bladder lesions. In the present study, 119 examined biopsies were characterized, showing that fiber-optic based OCT provides a sensitivity of 78% and a specificity of 69% for the detection of non-muscle-invasive bladder cancer, while RS, on the other hand, provides a sensitivity of 81% and a specificity of 61% for the grading of low- and high-grade tissues. Moreover, the study shows that a piezoelectric tube-based OCT probe can have significant endurance, suitable for future long-lasting in vivo applications. These results also indicate that combined OCT and RS fiber probe-based characterization offers an exciting possibility for label-free and morpho-chemical optical biopsies for bladder cancer diagnostics.

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.

Numerically focused full-field swept-source optical coherence microscopy with structured illumination.

This paper presents an experimental investigation of the possibility of transverse resolution improvement combined with effective numerically focused 3D imaging in full-field swept-source optical coherence microscopy (OCM) by using structured illumination and specific numerical post-processing. The possibility of transverse resolution improvement of the OCM coherence signal combined with the possibility of numerical focusing is demonstrated by imaging a resolution test target in the optical focus and defocus regions. The possibility of numerically focused 3D imaging with high transverse resolution is further demonstrated by imaging a 3D phantom and a biological sample. The results obtained demonstrate the feasibility and prospects of the combination of structured illumination and numerical focusing in Fourier domain OCM.

Numerical focusing methods for full field OCT: a comparison based on a common signal model.

In this paper a theoretical model of the full field swept source (FF SS) OCT signal is presented based on the angular spectrum wave propagation approach which accounts for the defocus error with imaging depth. It is shown that using the same theoretical model of the signal, numerical defocus correction methods based on a simple forward model (FM) and inverse scattering (IS), the latter being similar to interferometric synthetic aperture microscopy (ISAM), can be derived. Both FM and IS are compared quantitatively with sub-aperture based digital adaptive optics (DAO). FM has the least numerical complexity, and is the fastest in terms of computational speed among the three. SNR improvement of more than 10 dB is shown for all the three methods over a sample depth of 1.5 mm. For a sample with non-uniform refractive index with depth, FM and IS both improved the depth of focus (DOF) by a factor of 7x for an imaging NA of 0.1. DAO performs the best in case of non-uniform refractive index with respect to DOF improvement by 11x.

Line-field parallel swept source interferometric imaging at up to 1 MHz.

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.

The Effect of Photobiomodulation on Bone Mineral Density, Serum Vitamin D, and Bone Formation Markers in Individuals with Complete Spinal Cord Injuries with Osteoporosis.

Study design: A quasi-experimental study utilized a matched-pair design, administering photobiomodulation at four-sites on one side of the body and assigning control to the other side at corresponding sites. Objectives: This study aimed to assess photobiomodulation treatment effects on bone mineral density (BMD) measurement using dual-energy X-ray-absorptiometry in individuals with complete spinal cord injury (C.SCI) and osteoporosis. Methods: Eight patients received treatment at four-sites: forearm-mid-distal (MID), proximal-femur, distal-femur, and proximal-tibia, totaling 32 sites. Using an 830 nm gallium-aluminum-arsenide semiconductor laser irradiation was administered three times weekly for 8 weeks. Different doses (energy density) were determined depending on bone depth from skin surface, as assessed by sonography and adjusted through irradiation time to be 8, 10, and 12 J/cm2 for depths <1 cm, between 1 and 1.5 cm, and >1.5 cm, respectively, using 200 mW power to deliver the optimal isodose of laser at each depth of bone within each therapeutic site. BMD was measured at baseline, week 8 of treatment, and week 15 of follow-up. Serum 25-(OH)-vitamin D and bone formation markers including osteocalcin and bone-alkaline-phosphatase (B-ALP) were also assessed at baseline and week 8 of treatment. Results: Significant increases in BMD were noted in proximal-femur and forearm-MID at both week 8 and week 15. Serum 25-(OH)-vitamin D levels significantly increased after treatment. However, no notable changes were observed in distal-femur and proximal-tibia BMD or in osteocalcin and B-ALP levels. Conclusions: Photobiomodulation (830 nm) laser demonstrated efficacy in improving BMD at proximal-femur and forearm-MID in individuals with C.SCI. Moreover, the observed positive influence on vitamin D levels suggests a potential photobiomodulation role, warranting further investigation.

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.

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.

Visualization of Cataract Surgery Steps With 4D Microscope-Integrated Swept-Source Optical Coherence Tomography in Ex Vivo Porcine Eyes.

Purpose: To investigate the visualization capabilities of high-speed swept-source optical coherence tomography (SS-OCT) in cataract surgery. Methods: Cataract surgery was simulated in wet labs with ex vivo porcine eyes. Each phase of the surgery was visualized with a novel surgical microscope-integrated SS-OCT with a variable imaging speed of over 1 million A-scans per second. It was designed to provide four-dimensional (4D) live-volumetric videos, live B-scans, and volume capture scans. Results: Four-dimensional videos, B-scans, and volume capture scans of corneal incision, ophthalmic viscosurgical device injection, capsulorrhexis, phacoemulsification, intraocular lens (IOL) injection, and position of unfolded IOL in the capsular bag were recorded. The flexibility of the SS-OCT system allowed us to tailor the scanning parameters to meet the specific demands of dynamic surgical steps and static pauses. The entire length of the eye was recorded in a single scan, and unfolding of the IOL was visualized dynamically. Conclusions: The presented novel visualization method for fast ophthalmic surgical microscope-integrated intraoperative OCT imaging in cataract surgery allowed the visualization of all major steps of the procedure by achieving large imaging depths covering the entire eye and high acquisition speeds enabling live volumetric 4D-OCT imaging. This promising technology may become an integral part of routine and advanced robotic-assisted cataract surgery in the future. Translational Relevance: We demonstrate the visualization capabilities of a cutting edge swept-source OCT system integrated into an ophthalmic surgical microscope during cataract surgery.

Microaneurysm detection using high-speed megahertz optical coherence tomography angiography in advanced diabetic retinopathy.

PURPOSE: To compare detection rates of microaneurysms (MAs) on high-speed megahertz optical coherence tomography angiography (MHz-OCTA), fluorescein angiography (FA) and colour fundus photography (CF) in patients with diabetic retinopathy (DR). METHODS: For this exploratory cross-sectional study, MHz-OCTA data were acquired with a swept-source OCT prototype (A-scan rate: 1.7 MHz), and FA and CF imaging was performed using Optos® California. MA count was manually evaluated on en face MHz-OCTA/FA/CF images within an extended ETDRS grid. Detectability of MAs visible on FA images was evaluated on corresponding MHz-OCTA and CF images. MA distribution and leakage were correlated with detectability on OCTA and CF imaging. RESULTS: 47 eyes with severe DR (n = 12) and proliferative DR (n = 35) were included. MHz-OCTA and CF imaging detected on average 56% and 36% of MAs, respectively. MHz-OCTA detection rate was significantly higher than CF (p < 0.01). The combination of MHz-OCTA and CF leads to an increased detection rate of 70%. There was no statistically significant association between leakage and MA detectability on OCTA (p = 0.13). For CF, the odds of detecting leaking MAs were significantly lower than non-leaking MAs (p = 0.012). Using MHz-OCTA, detection of MAs outside the ETDRS grid was less likely than MAs located within the ETDRS grid (outer ring, p < 0.01; inner ring, p = 0.028). No statistically significant difference between rings was observed for CF measurements. CONCLUSIONS: More MAs were detected on MHz-OCTA than on CF imaging. Detection rate was lower for MAs located outside the macular region with MHz-OCTA and for leaking MAs with CF imaging. Combining both non-invasive modalities can improve MA detection.

Subaperture correlation based digital adaptive optics for full field optical coherence tomography.

This paper proposes a sub-aperture correlation based numerical phase correction method for interferometric full field imaging systems provided the complex object field information can be extracted. This method corrects for the wavefront aberration at the pupil/ Fourier transform plane without the need of any adaptive optics, spatial light modulators (SLM) and additional cameras. We show that this method does not require the knowledge of any system parameters. In the simulation study, we consider a full field swept source OCT (FF SSOCT) system to show the working principle of the algorithm. Experimental results are presented for a technical and biological sample to demonstrate the proof of the principle.

Angle independent flow assessment with bidirectional Doppler optical coherence tomography.

Bidirectional Doppler optical coherence tomography is a stable and accurate method to extract the absolute velocity of vessels close to perpendicular to the optical axis by illuminating the sample under two different angles. However it requires knowledge of the vessel angle in the en face plane. In this Letter, we demonstrate that a direct calculation of the flow out of bidirectional Doppler cross sections perpendicular to the illumination plane is independent of that angle and of the Doppler angle, thereby improving the accuracy and flexibility of that technique. We validate our approach with an in vitro experiment and in vivo measurements of a human retinal vessel and discuss the practical limitations of this approach. The method yields accurate flow values for most vascular plexuses without precise knowledge of the vessel orientation. The precision gradually decreases for larger en face angles.

Comparison of corneal aberrations from anterior segment swept source OCT versus Placido-topography combined spectral domain OCT in cataract patients.

BACKGROUND: To comprehensively evaluate the agreement of component corneal aberrations from the newly updated wavefront analysis software of a swept-source optical coherence tomographer (SS-OCT) and a referential Placido-topography combined OCT device in elderly cataract patients. METHODS: Retrospective study including 103 eyes from 103 elderly patients scheduled for cataract surgery that were measured on the same day with a SS-OCT (Heidelberg Engineering, Germany) device and a Placido-topography combined OCT device (CSO, Italy). Anterior, total, and posterior corneal wavefront aberrations were evaluated for their mean differences and limits of agreement (LoA) via Bland-Altman plots. Vector analysis was additionally employed to compare corneal astigmatism measurements in dioptric vector space. RESULTS: Mean differences of all corneal aberrometric parameters did not exceed 0.05 µm. Total corneal aberrations were not significantly different from 0 except for vertical coma (- 0.04 µm; P = 0.003), spherical aberration (- 0.01 µm, P < 0.001), and root mean square (RMS) higher-order aberration (HOA) (0.03 µm, P = 0.04). The 95% LoA for total corneal aberration parameters between both devices were - 0.46 to 0.42 µm for horizontal astigmatism, - 0.37 to 0.41 µm for oblique astigmatism, - 0.19 to 0.17 µm for oblique trefoil, - 0.33 to 0.25 µm for vertical coma, - 0.20 to 0.22 µm for horizontal coma, - 0.22 to 0.20 µm for horizontal trefoil, - 0.11 to 0.08 µm for spherical aberration, and - 0.22 to 0.28 µm for RMS HOA. Vector analysis revealed no statistically significant mean differences for anterior, total, and posterior corneal astigmatism in dioptric vector space. CONCLUSION: In eyes undergoing cataract surgery with a regular elderly cornea, corneal wavefront analysis from the SS-OCT device showed functional equivalency to the reference device. Nevertheless, clinically relevant higher order aberration parameters should be interpreted with caution for surgical decision-making.

30 Years of Optical Coherence Tomography: introduction to the feature issue.

The guest editors introduce a feature issue commemorating the 30th anniversary of Optical Coherence Tomography.

Surgical microscope integrated MHz SS-OCT with live volumetric visualization.

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.

Live 4D-OCT denoising with self-supervised deep learning.

By providing three-dimensional visualization of tissues and instruments at high resolution, live volumetric optical coherence tomography (4D-OCT) has the potential to revolutionize ophthalmic surgery. However, the necessary imaging speed is accompanied by increased noise levels. A high data rate and the requirement for minimal latency impose major limitations for real-time noise reduction. In this work, we propose a low complexity neural network for denoising, directly incorporated into the image reconstruction pipeline of a microscope-integrated 4D-OCT prototype with an A-scan rate of 1.2 MHz. For this purpose, we trained a blind-spot network on unpaired OCT images using a self-supervised learning approach. With an optimized U-Net, only a few milliseconds of additional latency were introduced. Simultaneously, these architectural adaptations improved the numerical denoising performance compared to the basic setup, outperforming non-local filtering algorithms. Layers and edges of anatomical structures in B-scans were better preserved than with Gaussian filtering despite comparable processing time. By comparing scenes with and without denoising employed, we show that neural networks can be used to improve visual appearance of volumetric renderings in real time. Enhancing the rendering quality is an important step for the clinical acceptance and translation of 4D-OCT as an intra-surgical guidance tool.

Multiple instance learning based classification of diabetic retinopathy in weakly-labeled widefield OCTA en face images.

Diabetic retinopathy (DR), a pathologic change of the human retinal vasculature, is the leading cause of blindness in working-age adults with diabetes mellitus. Optical coherence tomography angiography (OCTA), a functional extension of optical coherence tomography, has shown potential as a tool for early diagnosis of DR through its ability to visualize the retinal vasculature in all spatial dimensions. Previously introduced deep learning-based classifiers were able to support the detection of DR in OCTA images, but require expert labeling at the pixel level, a labor-intensive and expensive process. We present a multiple instance learning-based network, MIL-ResNet,14 that is capable of detecting biomarkers in an OCTA dataset with high accuracy, without the need for annotations other than the information whether a scan is from a diabetic patient or not. The dataset we used for this study was acquired with a diagnostic ultra-widefield swept-source OCT device with a MHz A-scan rate. We were able to show that our proposed method outperforms previous state-of-the-art networks for this classification task, ResNet14 and VGG16. In addition, our network pays special attention to clinically relevant biomarkers and is robust against adversarial attacks. Therefore, we believe that it could serve as a powerful diagnostic decision support tool for clinical ophthalmic screening.