Spatially confined quantification of bilirubin concentrations by spectroscopic visible-light optical coherence tomography.

Spatially confined measurements of bilirubin in tissue can be of great value for noninvasive bilirubin estimations during neonatal jaundice, as well as our understanding of the physiology behind bilirubin extravasation. This work shows the potential of spectroscopic visible-light optical coherence tomography (sOCT) for this purpose. At the bilirubin absorption peak around 460 nm, sOCT suffers from a strong signal decay with depth, which we overcome by optimizing our system sensitivity through a combination of zero-delay acquisition and focus tracking. In a phantom study, we demonstrate the quantification of bilirubin concentrations between 0 and 650 µM with only a 10% difference to the expected value, thereby covering the entire clinical pathophysiological range.

Phase-stable Doppler OCT at 19 MHz using a stretched-pulse mode-locked laser.

We present a swept-wavelength optical coherence tomography (OCT) system with a 19 MHz laser source and electronic phase-locking of the source, acquisition clock, and beam scanning mirrors. The laser is based on stretched-pulse active mode-locking using an electro-optic modulator. Beam scanning in the fast axis uses a resonant micro-electromechanical systems (MEMS) -based mirror at ~23.8 kHz. Acquisition is performed at 1.78 Gigasamples per second using an external fixed clock. Phase sensitive imaging without need for k-clocking, A-line triggers, or phase-calibration methods is demonstrated. The system was used to demonstrate inter-frame and inter-volume Doppler imaging in the mouse ear and brain at 4D acquisition rates of 1, 30, 60 and 100 volumes/sec (V-scans/s). Angiography based on inter-frame and inter-volume methods are presented. The platform offers extremely fast and phase-stable measurements that can be used in preclinical angiographic and Doppler investigations of perfusion dynamics.

Clinical prototype of pigment and flow imaging optical coherence tomography for posterior eye investigation.

Measurements of the randomness of polarization (RP) obtained using polarization-sensitive optical coherence tomography (PS-OCT) are applied in several applications, and RP is attractive for posterior eye imaging. The addition of RP without retardation requires a minimal extension to standard OCT; therefore, we developed a prototype OCT system with a simplified scheme for RP measurement. A compact polarization-diversity receiver module is the only required hardware extension to a standard OCT system. All components were packed into the retinal scanning head. The degree-of-polarization uniformity and complex-decorrelation based OCT angiography were calculated using noise-corrected algorithms that accounted for the depth-dependent noise power. The structure, melanin, and blood flow distribution imaging of in vivo human eyes were demonstrated. Pathological eye imaging shows potential applications for combinations of these contrasts.

Shared-hole graph search with adaptive constraints for 3D optic nerve head optical coherence tomography image segmentation.

Optic nerve head (ONH) is a crucial region for glaucoma detection and tracking based on spectral domain optical coherence tomography (SD-OCT) images. In this region, the existence of a "hole" structure makes retinal layer segmentation and analysis very challenging. To improve retinal layer segmentation, we propose a 3D method for ONH centered SD-OCT image segmentation, which is based on a modified graph search algorithm with a shared-hole and locally adaptive constraints. With the proposed method, both the optic disc boundary and nine retinal surfaces can be accurately segmented in SD-OCT images. An overall mean unsigned border positioning error of 7.27 ± 5.40 µm was achieved for layer segmentation, and a mean Dice coefficient of 0.925 ± 0.03 was achieved for optic disc region detection.

Eye-motion-corrected optical coherence tomography angiography using Lissajous scanning.

To correct eye motion artifacts in en face optical coherence tomography angiography (OCT-A) images, a Lissajous scanning method with subsequent software-based motion correction is proposed. The standard Lissajous scanning pattern is modified to be compatible with OCT-A and a corresponding motion correction algorithm is designed. The effectiveness of our method was demonstrated by comparing en face OCT-A images with and without motion correction. The method was further validated by comparing motion-corrected images with scanning laser ophthalmoscopy images, and the repeatability of the method was evaluated using a checkerboard image. A motion-corrected en face OCT-A image from a blinking case is presented to demonstrate the ability of the method to deal with eye blinking. Results show that the method can produce accurate motion-free en face OCT-A images of the posterior segment of the eye in vivo.

Design and implementation of a low-cost, portable OCT system.

Optical coherence tomography (OCT) is a widely used biomedical imaging tool, primarily in ophthalmology to diagnose and stage retinal diseases. In order to increase access for a wider range of applications and in low resource settings, we developed a portable, low-cost OCT system that has comparable imaging performance to commercially available systems. Here, we present the system design and characterization and compare the system performance to other commercially available OCT systems. In addition, future cost reductions and potential additional applications of the low-cost OCT system are discussed.

Full ocular biometry through dual-depth whole-eye optical coherence tomography.

We propose a new method of determining the optical axis (OA), pupillary axis (PA), and visual axis (VA) of the human eye by using dual-depth whole-eye optical coherence tomography (OCT). These axes, as well as the angles "α" between the OA and VA and "κ" between PA and VA, are important in many ophthalmologic applications, especially in refractive surgery. Whole-eye images are reconstructed based on simultaneously acquired images of the anterior segment and retina. The light from a light source is split into two orthogonal polarization components for imaging the anterior segment and retina, respectively. The OA and PA are identified based on their geometric definitions by using the anterior segment image only, while the VA is detected through accurate correlation between the two images. The feasibility of our approach was tested using a model eye and human subjects.

Deep learning for the segmentation of preserved photoreceptors on en face optical coherence tomography in two inherited retinal diseases.

The objective quantification of photoreceptor loss in inherited retinal degenerations (IRD) is essential for measuring disease progression, and is now especially important with the growing number of clinical trials. Optical coherence tomography (OCT) is a non-invasive imaging technology widely used to recognize and quantify such anomalies. Here, we implement a versatile method based on a convolutional neural network to segment the regions of preserved photoreceptors in two different IRDs (choroideremia and retinitis pigmentosa) from OCT images. An excellent segmentation accuracy (~90%) was achieved for both IRDs. Due to the flexibility of this technique, it has potential to be extended to additional IRDs in the future.

Selective retina therapy enhanced with optical coherence tomography for dosimetry control and monitoring: a proof of concept study.

Selective treatment of the retinal pigment epithelium (RPE) by using short-pulse lasers leads to a less destructive treatment for certain retinal diseases in contrast to conventional photocoagulation. The introduction of selective retina therapy (SRT) to clinical routine is still precluded by the challenges to reliably monitor treatment success and to automatically adjust dose within the locally varying therapeutic window. Combining micrometer-scale depth resolving capabilities of optical coherence tomography (OCT) with SRT can yield real-time information on the laser-induced changes within the RPE after a laser pulse or even during treatment with a laser pulse train. In the present study, SRT and OCT were combined to treat ex-vivo porcine eyes demonstrating closed-loop dose-control. We found a reliable correlation of specific signal changes in time resolved OCT images and physiological lesions in the RPE. First experiments, including 23 porcine eyes, prove the feasibility of the novel treatment concept.

Temporally and spatially adaptive Doppler analysis for robust handheld optical coherence elastography.

Optical coherence elastography (OCE), a functional extension of optical coherence tomography (OCT), can be used to characterize the mechanical properties of biological tissue. A handheld fiber-optic OCE instrument will allow the clinician to conveniently interrogate the localized mechanical properties of in vivo tissue, leading to better informed clinical decision making. During handheld OCE characterization, the handheld probe is used to compress the sample and the displacement of the sample is quantified by analyzing the OCT signals acquired. However, the motion within the sample inevitably varies in time due to varying hand motion. Moreover, the motion speed depends on spatial location due to the sample deformation. Hence, there is a need for a robust motion tracking method for manual OCE measurement. In this study, we investigate a temporally and spatially adaptive Doppler analysis method. The method described here strategically chooses the time interval (δt) between signals involved in Doppler analysis to track the motion speed v(z,t) that varies temporally and spatially in a deformed sample volume under manual compression. Enabled by temporally and spatially adaptive Doppler analysis, we report the first demonstration of real-time manual OCE characterization of in vivo tissue to the best of our knowledge.

The value of ultrahigh resolution OCT in dermatology - delineating the dermo-epidermal junction, capillaries in the dermal papillae and vellus hairs.

Optical coherence tomography (OCT) imaging of the skin is gaining recognition and is increasingly applied to dermatological research. A key dermatological parameter inferred from an OCT image is the epidermal (Ep) thickness as a thickened Ep can be an indicator of a skin disease. Agreement in the literature on the signal characters of Ep and the subjacent skin layer, the dermis (D), is evident. Ambiguities of the OCT signal interpretation in the literature is however seen for the transition region between the Ep and D, which from histology is known as the dermo-epidermal junction (DEJ); a distinct junction comprised of the lower surface of a single cell layer in epidermis (the stratum basale) connected to an even thinner membrane (the basement membrane). The basement membrane is attached to the underlying dermis. In this work we investigate the impact of an improved axial and lateral resolution on the applicability of OCT for imaging of the skin. To this goal, OCT images are compared produced by a commercial OCT system (Vivosight from Michaelson Diagnostics) and by an in-house built ultrahigh resolution (UHR-) OCT system for dermatology. In 11 healthy volunteers, we investigate the DEJ signal characteristics. We perform a detailed analysis of the dark (low) signal band clearly seen for UHR-OCT in the DEJ region where we, by using a transition function, find the signal transition of axial sub-resolution character, which can be directly attributed to the exact location of DEJ, both in normal (thin/hairy) and glabrous (thick) skin. To our knowledge no detailed delineating of the DEJ in the UHR-OCT image has previously been reported, despite many publications within this field. For selected healthy volunteers, we investigate the dermal papillae and the vellus hairs and identify distinct features that only UHR-OCT can resolve. Differences are seen in tracing hairs of diameter below 20 µm, and in imaging the dermal papillae where, when utilising the UHR-OCT, capillary structures are identified in the hand palm, not previously reported in OCT studies and specifically for glabrous skin not reported in any other in vivo optical imaging studies.

Effective bidirectional scanning pattern for optical coherence tomography angiography.

We demonstrate the utility of a novel scanning method for optical coherence tomography angiography (OCTA). Although raster scanning is commonly used for OCTA imaging, a bidirectional approach would lessen the distortion caused by galvanometer-based scanners as sources continue to increase sweep rates. As shown, a unidirectional raster scan approach has a lower effective scanning time than bidirectional approaches; however, a strictly bidirectional approach causes contrast variation along the B-scan direction due to the non-uniform time interval between B-scans. Therefore, a stepped bidirectional approach is introduced and successfully applied to retinal imaging in normal controls and in a pathological subject with diabetic retinopathy.

Automatic analysis of bioresorbable vascular scaffolds in intravascular optical coherence tomography images.

The bioresorbable vascular scaffold (BVS) is a new generation of bioresorbable scaffold (BRS) for the treatment of coronary artery disease. A potential challenge of BVS is malapposition, which may possibly lead to late stent thrombosis. It is therefore important to conduct malapposition analysis right after stenting. Since an intravascular optical coherence tomography (IVOCT) image sequence contains thousands of BVS struts, manual analysis is labor intensive and time consuming. Computer-based automatic analysis is an alternative, but faces some difficulties due to the interference of blood artifacts and the uncertainty of the struts number, position and size. In this paper, we propose a novel framework for a struts malapposition analysis that breaks down the problem into two steps. Firstly, struts are detected by a cascade classifier trained by AdaBoost and a region of interest (ROI) is determined for each strut to completely contain it. Then, strut boundaries are segmented within ROIs through dynamic programming. Based on the segmentation result, malapposition analysis is conducted automatically. Tested on 7 pullbacks labeled by an expert, our method correctly detected 91.5% of 5821 BVS struts with 12.1% false positives. The average segmentation Dice coefficient for correctly detected struts was 0.81. The time consumption for a pullback is 15 sec on average. We conclude that our method is accurate and efficient for BVS strut detection and segmentation, and enables automatic BVS malapposition analysis in IVOCT images.

Real-time visualization and interaction with static and live optical coherence tomography volumes in immersive virtual reality.

Virtual reality (VR) head-mounted displays are an attractive technology for viewing intrasurgical optical coherence tomography (OCT) volumes because they liberate surgeons from microscope oculars. We demonstrate real-time, interactive viewing of OCT volumes in a commercial HTC Vive immersive VR system using previously reported ray casting techniques. Furthermore, we show interactive manipulation and sectioning of volumes using handheld controllers and guidance of mock surgical procedures in porcine eyes exclusively within VR. To the best of our knowledge, we report the first immersive VR-OCT viewer with stereo ray casting volumetric renders, arbitrary sectioning planes, and live acquisition support. We believe VR-OCT volume displays will advance ophthalmic surgery towards VR-integrated surgery.

Visible-light optical coherence tomography oximetry based on circumpapillary scan and graph-search segmentation.

Visible-light optical coherence tomography (vis-OCT) enables retinal oximetry by measuring the oxygen saturation of hemoglobin (sO2) from within individual retinal blood vessels. The sO2 calculation requires reliable estimation of the true spectrum of backscattered light from the posterior vessel wall. Unfortunately, subject motion and image noise make averaging from multiple A-lines at the same depth position challenging, and lead to inaccurate sO2 estimation. In this study, we developed an algorithm to reliably extract the backscattered light's spectrum. We used circumpapillary scanning to sample the vessels repeatedly at the same location. A combination of cross-correlation and graph-search based segmentation extracted the posterior wall locations. Using measurements from 100 B-scans as a gold standard, we demonstrated that our method achieved highly accurate measures of sO2 with minimal bias. In addition, we also investigated how the number of repeated measurements affects the accuracy of sO2 measurement. Our method sets the stage for large-scale studies of retinal oxygenation in animals and humans.

Finite-difference time-domain analysis of increased penetration depth in optical coherence tomography by wavefront shaping.

Multiple scattering in turbid media inhibits optimal light focusing and thus limits the penetration depth in optical coherence tomography (OCT). However, the effects of multiple scattering in a turbid medium can be systematically controlled by shaping the incident wavefront. The authors utilize the reciprocity of Maxwell's equations and finite-difference time-domain numerical analysis to investigate the ultimate performance bounds of wavefront shaping-OCT under ideal and realistic configurations and compare them with the conventional method. The results reveal that the optimized impinging wavefront significantly enhances the penetration depth of OCT.

Robust layer segmentation of esophageal OCT images based on graph search using edge-enhanced weights.

Automatic segmentation of esophageal layers in OCT images is crucial for studying esophageal diseases and computer-assisted diagnosis. This work aims to improve the current techniques to increase the accuracy and robustness for esophageal OCT image segmentation. A two-step edge-enhanced graph search (EEGS) framework is proposed in this study. Firstly, a preprocessing scheme is applied to suppress speckle noise and remove the disturbance in the esophageal structure. Secondly, the image is formulated into a graph and layer boundaries are located by graph search. In this process, we propose an edge-enhanced weight matrix for the graph by combining the vertical gradients with a Canny edge map. Experiments on esophageal OCT images from guinea pigs demonstrate that the EEGS framework is more robust and more accurate than the current segmentation method. It can be potentially useful for the early detection of esophageal diseases.

In vivo detection of UV-induced acute skin effects using optical coherence tomography.

Ultraviolet (UV) rays have been identified as a carcinogen with long-term irradiation and are an important risk factor for skin cancer. Here, we report the use of optical coherence tomography/optical coherence tomography angiography (OCT/OCTA) to study acute UV-induced effects on skin in vivo. To understand the relationship between the acute effects and irradiated UV power density, three groups were irradiated with different power densities in our experiments. Furthermore, the same skin area was repeatedly scanned with OCT during UV irradiation to investigate the progress of the induced acute effects and after irradiation for observation of skin recovery. Subsequently, the OCT/OCTA results were quantitatively analyzed to acquire skin thickness and blood-vessel density for comparison. UV-induced acute effects on morphology and microcirculation can be identified from OCT/OCTA results, which showed the increases in the skin thickness and blood-vessel density and even severe damage types such as blisters. The results of quantitative analyses also illustrated that the severity of damage induced by UV irradiation can be distinguished and the skin recovery can be monitored with OCT. Our results indicate that OCT can be a promising tool for early detection of UV-induced acute skin damage.

Automated segmentation of retinal layer boundaries and capillary plexuses in wide-field optical coherence tomographic angiography.

Advances in the retinal layer segmentation of structural optical coherence tomography (OCT) images have allowed the separation of capillary plexuses in OCT angiography (OCTA). With the increased scanning speeds of OCT devices and wider field images (≥10 mm on fast-axis), greater retinal curvature and anatomic variations have introduced new challenges. In this study, we developed a novel automated method to segment seven retinal layer boundaries and two retinal plexuses in wide-field OCTA images. The algorithm was initialized by a series of points forming a guidance point array that estimates the location of retinal layer boundaries. A guided bidirectional graph search method consisting of an improvement of our previous segmentation algorithm was used to search for the precise boundaries. We validated the method on normal and diseased eyes, demonstrating subpixel accuracy for all groups. By allowing independent visualization of the superficial and deep plexuses, this method shows potential for the detection of plexus-specific peripheral vascular abnormalities.

Frequency of the resonance of the human sweat duct in a normal mode of operation.

The applications of terahertz (THz) waves have been increasing rapidly in different fields such as information and communication technology, homeland security and biomedical engineering. However, study on the possible health implications due to various biological effects induced by THz waves is relatively scarce. Previously, it has been reported that the human sweat ducts play a significant role in the interaction of the THz wave with human skin due to its coiled structure. This structure imposes on them the electromagnetic character of a helical antenna. To further understand these phenomena, we investigated the morphological features of human sweat ducts and the dielectric properties of their surrounding medium. Based upon these parameters, we estimated the frequency of the resonance of the human sweat duct in a normal mode of operation and our estimation showed that there is a broad resonance around 228 GHz. This result indicates that careful consideration should be given while designing electronic and photonic devices operating in the sub-terahertz frequency region in order to avoid various effects on human health due to these waves.