Resolution Optical Coherence Tomography Imaging Research Articles

Volume electron microscopy reveals human retinal mitochondria that align with reflective bands in optical coherence tomography [Invited

Mitochondria are candidate reflectivity signal sources in optical coherence tomography (OCT) retinal imaging. Here, we use deep-learning-assisted volume electron microscopy of human retina and in vivo imaging to map mitochondria networks in the outer plexiform layer (OPL), where photoreceptors synapse with second-order interneurons. We observed alternating layers of high and low mitochondrial abundance in the anatomical OPL and adjacent inner nuclear layer (INL). Subcellular resolution OCT imaging of human eyes revealed multiple reflective bands that matched the corresponding INL and combined OPL sublayers. Data linking specific mitochondria to defined bands in OCT may help improve clinical diagnosis and the evaluation of mitochondria-targeting therapies.

Self super-resolution of optical coherence tomography images based on deep learning.

As a medical imaging modality, many researches have been devoted to improving the resolution of optical coherence tomography (OCT). We developed a deep-learning based OCT self super-resolution (OCT-SSR) pipeline to improve the axial resolution of OCT images based on the high-resolution and low-resolution spectral data collected by the OCT system. In this pipeline, the enhanced super-resolution asymmetric generative adversarial networks were built to improve the network outputs without increasing the complexity. The feasibility and effectiveness of the approach were demonstrated by experimental results on the images of the biological samples collected by the home-made spectral-domain OCT and swept-source OCT systems. More importantly, we found the sidelobes in the original images can be obviously suppressed while improving the resolution based on the OCT-SSR method, which can help to reduce pseudo-signal in OCT imaging when non-Gaussian spectra light source is used. We believe that the OCT-SSR method has broad prospects in breaking the limitation of the source bandwidth on the axial resolution of the OCT system.

Efficacy and safety of cysteamine-isobionicamide complex in postinflammatory hyperpigmentation: A 16-week, randomized, double-blinded, vehicle-controlled trial

Abstract Background: Postinflammatory hyperpigmentation (PIH) is a prevalent acquired hyperpigmentation disorder with significant psychosocial implications. Cysteamine has demonstrated notable efficacy and safety in treating hyperpigmentation disorders. This study conducted a double-blinded, randomized clinical trial to evaluate the efficacy and safety of the cysteamine-isobionicamide complex in managing PIH. Objectives: The objective was to assess the cysteamine-isobionicamide complex’s efficacy for PIH treatment through comprehensive clinical and imaging evaluations. Methods: Forty patients with PIH were recruited at a tertiary medical center from 2021 to 2022 and randomized into the cysteamine-isobionicamide complex treatment group and placebo-vehicle control group. Dermatological assessments, investigator and patient global assessments, and quality of life scores were collected at baseline, week 4, week 8, and week 16. Quantitative evaluation of skin type and lesion pigmentation was performed with the Mexameter®, VISIA skin analyzer, and cellular resolution optical coherence tomography (OCT). Results: At week 8, the cysteamine-isobionicamide complex treatment group exhibited marked advancement in dermatological assessments, melasma area and severity index (MASI), total postacne hyperpigmentation index, and life quality score compared with the placebo-vehicle control group. Furthermore, melanin index and erythema index scores from Mexameter® and VISIA analysis exhibited significant improvement for brown spots at week 16. Cellular resolution OCT imaging revealed decreased melanosome capping and fewer hyperreflective melanophages. Conclusion: This study demonstrated the clinical effectiveness and safety of the cysteamine-isobionicamide complex through comprehensive dermatological assessments, imaging techniques, and patient-reported outcomes. The complex emerges as a promising therapeutic option for PIH, offering potential relief to individuals affected by this hyperpigmentation disorder.

Riehl's Melanosis: A Multimodality, In Vivo, Real-Time Skin Imaging Study with Cellular Resolution Optical Coherence Tomography and Advanced Skin Diagnosis System in a Tertiary Medical Center.

Background: Riehl’s melanosis is a psychologically devastating hyperpigmentary disorder that typically occurs on the face and neck. The study of Riehl’s melanosis is limited due to its rarity, variable morphology, and lack of noninvasive diagnostic tools. Recent advances in skin imaging analysis and diagnostic systems improve diagnostic accuracy and enable the noninvasive, real-time evaluation of pigmentary disease. A comprehensive study of Riehl’s melanosis clinical morphology with multimodality and in vivo skin imaging systems has yet to be reported. Objectives: To investigate the clinical features and in vivo advanced skin imaging findings of Riehl’s melanosis. Methods: We retrospectively investigated the clinical characteristics, dermoscopic, and histopathological features of Riehl’s melanosis. We further utilized multimodality skin imaging analysis systems, including a cellular resolution optical coherence tomography (OCT) and new skin diagnosis system, to investigate the features of Riehl’s melanosis. In addition, we compared OCT findings with histopathological features and clinical assessment. Results: We evaluated 30 patients with Riehl’s melanosis at a tertiary medical center from 2010 to 2022. The average age was 47.7 ± 12.3 (mean ± SD) years, predominantly female patients (female: n = 23; male: n = 7). Cellular resolution OCT imaging from lesion skin shows increased melanocyte capping, disrupted basement membrane, telangiectatic blood vessels, and melanophages in the dermis. The advanced skin diagnosis system captured subclinical erythema of the skin, highlighting the inflammatory nature of the disease. The results correlated well with histopathological findings. Limitations: This is a single-center, cross-sectional study. Conclusions: We highlight the features of Riehl’s melanosis through a novel cellular resolution OCT and photographic skin diagnosis system. A multimodality skin diagnosis system can serve as a real-time, in vivo, noninvasive method for evaluating pigmentary disorders.

Dynamic microscopic optical coherence tomography to visualize the morphological and functional micro-anatomy of the airways.

In the imaging of airway tissue, optical coherence tomography (OCT) provides cross-sectional images of tissue structures, shows cilia movement and mucus secretion, but does not provide sufficient contrast to differentiate individual cells. By using fast sequences of microscopic resolution OCT (mOCT) images, OCT can use small signal fluctuations to overcome lack in contrast and speckle noise. In this way, OCT visualizes airway morphology on a cellular level and allows the tracking of the dynamic behavior of immune cells, as well as mucus transport and secretion. Here, we demonstrate that mOCT, by using temporal tissue fluctuation as contrast (dynamic mOCT), provides the possibility to study physiological and pathological tissue processes in vivo.

Lateral image reconstruction of optical coherence tomography using one-dimensional deep deconvolution network.

Optical coherence tomography (OCT) is a cross-sectional imaging method utilizing a low coherence interferometry. The lateral resolution of the OCT is limited by the numerical aperture (NA) of the imaging lens. Using a high NA lens improves the lateral resolution but reduces the depth of focus (DOF). In this study, we propose a method to improve the lateral resolution of OCT images by end-to-end training of a deep 1-D deconvolution network without use of high-resolution images. To improve the lateral resolution of the OCT, we trained the 1-D deconvolution network using lateral profiles of OCT images and the beam spot size. We used our image-guided laparoscopic surgical tool (IGLaST) to acquire OCT images of nonbiological and biological samples ex vivo. The OCT images were then blurred by applying Gaussian functions with various full width half maximums ranging from 40to 160 µm. The network was trained using the blurred OCT images as input and the non-blurred original OCT images as output. We quantitatively evaluated the developed network in terms of similarity and signal-to-ratio (SNR), using in-vivo images of mesenteric tissue from a porcine model that was not used for training. In addition, we performed knife-edge tests and qualitative evaluation of the network to show the lateral resolution improvement of ex-vivo and in-vivo OCT images. The proposed method showed an improvement of image quality on both blurred images and non-blurred images. When the proposed deconvolution network was applied, the similarity to the non-blurred image was improved by 1.29 times, and the SNR was improved by 1.76 dB compared to the artificially blurred images, which was superior to the conventional deconvolution method. The knife-edge tests at distances at 200 to 1000 µm from the imaging probe showed an approximately 1.2 times improvement in lateral resolution. In addition, through qualitative evaluation, it was found that the image quality of both ex-vivo and in-vivo tissue images was improved with clear structure and less noise. This study showed the ability of the 1-D deconvolution network to improve the image quality of OCT images with variable lateral resolution. We were able to train the network with a small amount of data by constraining the network in 1-D. The quantitative evaluation showed better results than conventional deconvolution methods for various amount of blurring. Qualitative evaluation showed analogous results with quantitative results. This simple yet powerful image restoration method provides improved lateral resolution and suppresses background noise, making it applicable to a variety of OCT imaging applications.

Optimization of X-ray Investigations in Dentistry Using Optical Coherence Tomography

The most common imaging technique for dental diagnoses and treatment monitoring is X-ray imaging, which evolved from the first intraoral radiographs to high-quality three-dimensional (3D) Cone Beam Computed Tomography (CBCT). Other imaging techniques have shown potential, such as Optical Coherence Tomography (OCT). We have recently reported on the boundaries of these two types of techniques, regarding. the dental fields where each one is more appropriate or where they should be both used. The aim of the present study is to explore the unique capabilities of the OCT technique to optimize X-ray units imaging (i.e., in terms of image resolution, radiation dose, or contrast). Two types of commercially available and widely used X-ray units are considered. To adjust their parameters, a protocol is developed to employ OCT images of dental conditions that are documented on high (i.e., less than 10 μm) resolution OCT images (both B-scans/cross sections and 3D reconstructions) but are hardly identified on the 200 to 75 μm resolution panoramic or CBCT radiographs. The optimized calibration of the X-ray unit includes choosing appropriate values for the anode voltage and current intensity of the X-ray tube, as well as the patient’s positioning, in order to reach the highest possible X-rays resolution at a radiation dose that is safe for the patient. The optimization protocol is developed in vitro on OCT images of extracted teeth and is further applied in vivo for each type of dental investigation. Optimized radiographic results are compared with un-optimized previously performed radiographs. Also, we show that OCT can permit a rigorous comparison between two (types of) X-ray units. In conclusion, high-quality dental images are possible using low radiation doses if an optimized protocol, developed using OCT, is applied for each type of dental investigation. Also, there are situations when the X-ray technology has drawbacks for dental diagnosis or treatment assessment. In such situations, OCT proves capable to provide qualitative images.

Optical coherence microangiography of the mouse kidney for diagnosis of circulatory disorders

Optical coherence tomography (OCT) has become widespread in clinical applications in which precise three-dimensional functional imaging of living organs is required. Nevertheless, the kidney is inaccessible for the high resolution OCT imaging due to a high light attenuation coefficient of skin and soft tissues that significantly limits the penetration depth of the probing laser beam. Here, we introduce a surgical protocol and fixation scheme that enables functional visualization of kidney's peritubular capillaries via OCT microangiography. The model of reversible/irreversible glomerulus embolization using drug microcarriers confirms the ability of OCT to detect circulatory disorders. This approach can be used for choosing optimal carriers, their dosages and diagnosis of other blood flow pathologies.

Automatic evaluation of stratum basale and dermal papillae using ultrahigh resolution optical coherence tomography

Diagnosis of many skin conditions requires evaluation of dermal papillae and stratum basale, such as vitiligo. In clinical practice, imaging dermal papillae structures relies on excisional biopsy followed by histological processing and analysis. As biopsy is invasive and associated with complications, a noninvasive imaging method such as optical coherence tomography (OCT) can complement the existing method by enabling large area scanning. However, because OCT image analysis requires training and it takes time to review OCT images from large skin areas, an automatic evaluation method is preferred to reduce the workload and avoid ‘sampling errors’ during image analysis. Here we report an automatic method to enhance and detect dermal papillae and stratum basale in ultrahigh resolution OCT images. A high detection accuracy is achieved by rejecting image artifacts using a surface flattening algorithm and an artifact recognition algorithm. We further demonstrated the efficacy of this automatic method in detecting vitiligo in human subjects.

Cellular resolution corneal imaging with extended imaging range.

Current optical coherence tomography (OCT) technology, which is used for imaging the eye's anterior segment, has been established as a clinical gold standard for the diagnosis of corneal diseases. However, the cellular resolution level information that is critical for many clinical applications is still not available. The major technical challenges toward cellular resolution OCT imaging are the limited ranging depth and depth of focus (DOF). In this work, we present a novel ultrahigh resolution OCT system that achieves an isotropic spatial resolution of <2 µm in tissue. The proposed system could approximately double the ranging depth and extend the DOF using the dual-spectrometer design and the forward-model based digital refocusing method, respectively. We demonstrate that the novel system is capable of visualizing the full thickness of the pig cornea over the ranging depth of 3.5 mm and the border of the corneal endothelial cells 8 times Rayleigh range away from the focal plane. This technology has the potential to realize cellular resolution corneal imaging in vivo.

Super-Resolution in Optical Coherence Tomography.

Optical coherence tomography (OCT) is an essential medical imaging tool for retinal disease diagnosis. Nevertheless, as with all optical imaging techniques, image degradation is a very common phenomenon, affecting the quality of the images. In this paper, we address issues related to the resolution of OCT images and propose solutions based on solving inverse problems. A cost function for deconvolution and super-resolution is formulated and the alternating direction method of multiplier (ADMM) and forward-backward splitting (FBS) algorithms are then employed for its minimisation. On the one hand, the standard Ll norm regularisation with soft thresholding is compared with a total variation (TV) regularisation within an ADMM scheme. On the other hand, nonconvex regularisation is also considered via a multivariate generalisation of the minimax-concave scheme in FBS. In the latter case, the regularisation function is judiciously chosen in order to preserve the overall convexity of the cost function. To be able to evaluate our algorithms qualitatively, a number of standard images are initially used. Then, we also assess our algorithms subjectively by applying them to real OCT images of the human eye. Given that the point spread function (PSF) of OCT images is generally unknown, we also propose ways of estimating it in the deconvolution component of our methods. Our results show that the ADMM scheme with soft thresholding achieves the best performance in terms of enhancing the overall quality of OCT images.

Assessment of Corneal Biomechanical Properties with Inflation Test Using Optical Coherence Tomography.

Biomechanical properties are important for the cornea to maintain its normal shape and function. There is still a need to develop better methods for accurate measurement of corneal mechanical properties. In this study, we propose to introduce the optical coherence tomography (OCT) in inflation test for the imaging of corneal deformation in order to measure its biomechanical properties. Ten cornea-mimicking silicone phantoms with different stiffness and five fresh porcine corneas were tested using the proposed method. Intra-ocular pressure was changed from 10 to 90mmHg using two different loading rates to observe the pressure-apex displacement relationship and calculate the apparent stiffness of the corneas. Stiffness of the corneal phantoms obtained by the inflation test ranged from 0.2 to 1MPa, which was highly consistent with the results from the mechanical tensile test (y=0.70x, p<0.001). The porcine corneas showed highly viscoelastic behavior with obvious hysteresis in inflation. The apparent stiffness of the porcine corneas was 0.63±0.07 and 1.05±0.08MPa with loading rates of 3.3 and 33mmHg/min, respectively. Mapping of corneal surface displacement was also generated for both the phantom and porcine corneas. This study showed that it is feasible to incorporate the high resolution OCT imaging in inflation test to measure the biomechanical properties of the cornea.

Automated in vivo 3D high-definition optical coherence tomography skin analysis system.

The in vivo assessment and visualization of skin structures can be performed through the use of high resolution optical coherence tomography imaging, also known as HD-OCT. However, the manual assessment of such images can be exhaustive and time consuming. In this paper, we present an analysis system to automatically identify and quantify the skin characteristics such as the topography of the surface of the skin and thickness of the epidermis in HD-OCT images. Comparison of this system with manual clinical measurements demonstrated its potential for automatic objective skin analysis and diseases diagnosis. To our knowledge, this is the first report of an automated system to process and analyse HD-OCT skin images.

Light-Induced Thickening of Photoreceptor Outer Segment Layer Detected by Ultra-High Resolution OCT Imaging.

PurposeWe examined if light induces changes in the retinal structure that can be observed using optical coherence tomography (OCT).MethodsNormal C57BL/6J mice (age 3–6 months) adapted to either room light (15 minutes to ∼5 hours, 50–500 lux) or darkness (overnight) were imaged using a Bioptigen UHR-OCT system. Confocal histologic images were obtained from mice killed under light- or dark-adapted conditions.ResultsThe OCT image of eyes adapted to room light exhibited significant increases (6.1 ± 0.8 μm, n = 13) in total retina thickness compared to the same eyes after overnight dark adaptation. These light-adapted retinal thickness changes occurred mainly in the outer retina, with the development of a hyporeflective band between the RPE and photoreceptor-tip layers. Histologic analysis revealed a light-evoked elongation between the outer limiting membrane and Bruch's membrane from 45.8 ± 1.7 μm in the dark (n = 5) to 52.1 ± 3.7 μm (n = 5) in the light. Light-adapted retinas showed an increase of actin staining in RPE apical microvilli at the same location as the hyporeflective band observed in OCT images. Elongation of the outer retina could be detected even with brief light exposures, increasing 2.1 ± 0.3 μm after 15 minutes (n = 9), and 4.1 ± 1.0 μm after 2 hours (n = 6). Conversely, dark-adaptation caused outer retinal shortening of 1.4 ± 0.4 μm (n = 7) and 3.0 ± 0.5 μm (n = 8) after 15 minutes and 2 hours, respectively.ConclusionsLight-adaption induces an increase in the thickness of the outer retina and the appearance of a hyporeflective band in the OCT image. This is consistent with previous reports of light-induced fluid accumulation in the subretinal space.

Tunable Emission Wavelength Stacked InAs/GaAs Quantum Dots by Chemical Beam Epitaxy for Optical Coherence Tomography.

We report on Chemical Beam Epitaxy (CBE) growth of wavelength tunable InAs/GaAs quantum dots (QD) based superluminescent diode’s active layer suitable for Optical Coherence Tomography (OCT). The In-flush technique has been employed to fabricate QD with controllable heights, from 5 nm down to 2 nm, allowing a tunable emission band over 160 nm. The emission wavelength blueshift has been ensured by reducing both dots’ height and composition. A structure containing four vertically stacked height-engineered QDs have been fabricated, showing a room temperature broad emission band centered at 1.1 µm. The buried QD layers remain insensitive to the In-flush process of the subsequent layers, testifying the reliability of the process for broadband light sources required for high axial resolution OCT imaging.

Heidelberg Spectralis Optical Coherence Tomography Angiography: Technical Aspects.

Optical coherence tomography angiography (OCT-A) is a promising new method for visualizing the retinal vasculature and choroidal vascular layers in the macular area and provides depth-resolved functional information on blood flow in these vessels. OCT-A is based on the concept that in a static eye the only moving structure in the fundus of the eye is blood flowing through the vessels. Contrast is generated based on the difference between moving cells in the vasculature and the static surrounding tissue. Artifacts can arise due to scan positioning errors caused by normal ocular microsaccades. In order to avoid artifacts, a sequence of OCT B-scans in the exact same retinal location must be taken to detect flow. Active eye-tracking (TruTrack™) using the simultaneous acquisition of fundus and optical coherence tomography (OCT) images presents a very reliable method of acquiring OCT volume scans without motion artifacts and helps significantly improve signal-to-noise ratio. This system also allows the use of a full spectrum amplitude decorrelation algorithm that produces clear differentiation between blood flow and static tissue without sacrificing the axial resolution of OCT images. Accuracy in layer segmentation, which requires high-resolution OCT B-scans, is crucial for producing reliable OCT-A images. This can be achieved through automated or manual layer segmentation. During OCT scan acquisition, the effect of axial motion (e.g. a patient moving towards the camera) is compensated for by geometric alignment of successive B-scans before analyzing temporal changes.

Iterative re-weighted approach to high-resolution optical coherence tomography with narrow-band sources

Optical coherence tomography (OCT) is a non-invasive optical imaging modality capable of high resolution imaging of internal tissue structures. It is widely believed that the high axial resolution in OCT systems requires a wide-bandwidth light source. As a result, often the potential advantages of narrow-bandwidth sources (in terms of cost and/or imaging speed) are understood to come at the cost of significant reduction in imaging resolution. In this paper, we argue that this trade-off between resolution and speed is a shortcoming imposed by the-state-of-the-art A-scan reconstruction algorithm, Fast Fourier Transform, and can be circumvented through use of alternative processing methods. In particular, we investigate the shortcomings of the FFT as well as previously proposed alternatives and demonstrate the first application of an iterative regularized re-weighted l(2) norm method to improve the axial resolution of fast scan rate OCT systems in the narrow-bandwidth imaging conditions. We validate our claims via experimental results generated from a home-built OCT system used to image layered phantom and in vivo data. Our results rely on new, sophisticated signal processing algorithms to generate higher precision (i.e., higher resolution) OCT images at correspondingly fast scan rates. In other words, our work demonstrates the feasibility of simultaneously more reliable and more comfortable medical imaging systems for patients by reducing the overall scan time, without sacrificing image quality.

Ultra-High Resolution Optical Coherence Tomography Imaging of Unilateral Drusen in a 31 Year Old Woman.

We report a case of widespread unilateral drusen in a healthy 31 year old Caucasian woman using multi-modal imaging including ultra-high resolution optical coherence tomography (UHR-OCT). Dilated fundus exam showed multiple drusen-like lesions in the posterior pole without heme or fluid. Fundus auto fluorescence demonstrated hyperautofluorescent at the deposits. Fluorescein angiography revealed mild hyperfluorescence and staining of the lesions. Spectral-domain optical coherence tomography (SD-OCT) OS showed accumulations in the temporal macula at Bruch's membrane. UHR-OCT provided improved axial resolution compared to the standard 5 μm on the commercial SD-OCT and confirmed the presence of deposits in Bruch's membrane, consistent with drusen. The retinal layers were draped over the excrescences but did not show any disruption.

Depth-encoded synthetic aperture optical coherence tomography of biological tissues with extended focal depth.

Optical coherence tomography (OCT) has proven to be able to provide three-dimensional (3D) volumetric images of scattering biological tissues for in vivo medical diagnostics. Unlike conventional optical microscopy, its depth-resolving ability (axial resolution) is exclusively determined by the laser source and therefore invariant over the full imaging depth. In contrast, its transverse resolution is determined by the objective's numerical aperture and the wavelength which is only approximately maintained over twice the Rayleigh range. However, the prevailing laser sources for OCT allow image depths of more than 5 mm which is considerably longer than the Rayleigh range. This limits high transverse resolution imaging with OCT. Previously, we reported a novel method to extend the depth-of-focus (DOF) of OCT imaging in Mo et al.Opt. Express 21, 10048 (2013)]. The approach is to create three different optical apertures via pupil segmentation with an annular phase plate. These three optical apertures produce three OCT images from the same sample, which are encoded to different depth positions in a single OCT B-scan. This allows for correcting the defocus-induced curvature of wave front in the pupil so as to improve the focus. As a consequence, the three images originating from those three optical apertures can be used to reconstruct a new image with an extended DOF. In this study, we successfully applied this method for the first time to both an artificial phantom and biological tissues over a four times larger depth range. The results demonstrate a significant DOF improvement, paving the way for 3D high resolution OCT imaging beyond the conventional Rayleigh range.

Noise-compensated homotopic non-local regularized reconstruction for rapid retinal optical coherence tomography image acquisitions.

BackgroundOptical coherence tomography (OCT) is a minimally invasive imaging technique, which utilizes the spatial and temporal coherence properties of optical waves backscattered from biological material. Recent advances in tunable lasers and infrared camera technologies have enabled an increase in the OCT imaging speed by a factor of more than 100, which is important for retinal imaging where we wish to study fast physiological processes in the biological tissue. However, the high scanning rate causes proportional decrease of the detector exposure time, resulting in a reduction of the system signal-to-noise ratio (SNR). One approach to improving the image quality of OCT tomograms acquired at high speed is to compensate for the noise component in the images without compromising the sharpness of the image details.MethodsIn this study, we propose a novel reconstruction method for rapid OCT image acquisitions, based on a noise-compensated homotopic modified James-Stein non-local regularized optimization strategy. The performance of the algorithm was tested on a series of high resolution OCT images of the human retina acquired at different imaging rates.ResultsQuantitative analysis was used to evaluate the performance of the algorithm using two state-of-art denoising strategies. Results demonstrate significant SNR improvements when using our proposed approach when compared to other approaches.ConclusionsA new reconstruction method based on a noise-compensated homotopic modified James-Stein non-local regularized optimization strategy was developed for the purpose of improving the quality of rapid OCT image acquisitions. Preliminary results show the proposed method shows considerable promise as a tool to improve the visualization and analysis of biological material using OCT.