GPU-accelerated iterative method for FD-OCT image reconstruction with an image-level cross-domain regularizer.

The image reconstruction for Fourier-domain optical coherence tomography (FD-OCT) could be achieved by iterative methods, which offer a more accurate estimation than the traditional inverse discrete Fourier transform (IDFT) reconstruction. However, the existing iterative methods are mostly A-line-based and are developed on CPU, which causes slow reconstruction. Besides, A-line-based reconstruction makes the iterative methods incompatible with most existing image-level image processing techniques. In this paper, we proposed an iterative method that enables B-scan-based OCT image reconstruction, which has three major advantages: (1) Large-scale parallelism of the OCT dataset is achieved by using GPU acceleration. (2) A novel image-level cross-domain regularizer was developed, such that the image processing could be performed simultaneously during the image reconstruction; an enhanced image could be directly generated from the OCT interferogram. (3) The scalability of the proposed method was demonstrated for 3D OCT image reconstruction. Compared with the state-of-the-art (SOTA) iterative approaches, the proposed method achieves higher image quality with reduced computational time by orders of magnitude. To further show the image enhancement ability, a comparison was conducted between the proposed method and the conventional workflow, in which an IDFT reconstructed OCT image is later processed by a total variation-regularized denoising algorithm. The proposed method can achieve a better performance evaluated by metrics such as signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR), while the speed is improved by more than 30 times. Real-time image reconstruction at more than 20 B-scans per second was realized with a frame size of 4096 (axial) × 1000 (lateral), which showcases the great potential of the proposed method in real-world applications.

Effect of spectral leakage on the image formation of Fourier-domain optical coherence tomography.

We report on the investigation of spectral leakage's impact on the reconstruction of Fourier-domain optical coherence tomography (FD-OCT). We discuss the shift-variant nature introduced by the spectral leakage and develop a novel spatial-domain FD-OCT image formation model. A proof-of-concept phantom experiment is conducted to validate our model. Compared with previous models, the proposed framework could better describe the image formation process, especially when the fineness of the axial structure approaches the theoretical resolution limit.

Evaluation of Retinal Pigment Epithelium and Choroidal Neovascularization in Rats Using Laser-Scanning Optical-Resolution Photoacoustic Microscopy.

PURPOSE: To demonstrate the value of the laser-scanning optical-resolution (LSOR)-photoacoustic (PA) microscopy (PAM) system and the conventional multimodal imaging techniques in the evaluation of laser-induced retinal injury and choroidal neovascularization (CNV) in rats. METHODS: Different degrees of retinal injury were induced using laser photocoagulation. We compared the LSOR-PAM system with conventional imaging techniques in evaluating retinal injury with or without CNV. Six additional rats, treated with an anti-VEGF antibody or immunoglobulin G immediately after photocoagulation, were imaged 7 and 14 days after injection, and CNV lesion areas were compared. RESULTS: In the retinal injury model, fundus autofluorescence showed well-defined hyperreflection, while the lesion displayed abundant PA signals demonstrating nonuniform melanin distribution in retinal pigment epithelium (RPE). RPE was detected with higher contrast in the PAM B-scan image than optical coherence tomography (OCT). Additionally, the CNV lesion was present with multiple PA signal intensities which distinctly characterized the location and area of CNV as found in fundus fluorescein angiography. Furthermore, the decreased PA signals extending from the CNV lesion were similar to those of the vascular bud in ex vivo imaging, which was invisible in other in vivo images. When treated with anti-VEGF agents, statistically significant differences can be demonstrated by PAM similar to other modalities. CONCLUSIONS: LSOR-PAM can detect the melanin distribution of RPE in laser-induced retinal injury and CNV in rats. PAM imaging provides a potential new tool to evaluate the vitality and functionality of RPE in vivo as well as to monitor the development and treatment of CNV.

[Research progress of visual prosthesis].

Vision is one of the most important human sensations about the surrounding world. Visual deprivation not only markedly affects the life of blind people, but also gives a heavy burden to their family and the society. A visual prosthesis is an electronic device that helps the blinds to regain visual perception by directly stimulating the visual pathway using the microelectrodes implanted into the body. In recent years, visual prostheses have been developed rapidly and some devices have already become clinically available. In this paper, we reviewed the history of visual prosthesis, introduced different visual prostheses classified according to the location of the implanted stimulating electrodes. Clinical study results as well as the functional status of the currently available visual prosthesis devices were also summarized.

Fast subcellular optical coherence photoacoustic microscopy for pigment cell imaging.

We developed a fast ultrahigh resolution optical coherence photoacoustic microscopy (FU-OCPAM) system by combining two complementary imaging modes of optical coherence microscopy (OCM) and photoacoustic microscopy (PAM) for cellular/subcellular imaging. The system used optical scanning to realize fast imaging speed and provided ultrahigh resolution of 1.24 and 0.59 µm for OCM and PAM, respectively. We imaged the retinal pigment epithelium (RPE) to demonstrate the subcellular imaging capability of the FU-OCPAM system. The OCM and PAM images clearly showed the RPE cell morphology and reflected the complementary optical properties of scattering and absorption. A quantitative analysis of the RPE cells was made based on photoacoustic (PA) signals. The cell area mainly ranged from 80 to 300 µm2, and had a linear relationship with the sum intensity of PA signals which mainly reflected the melanin content of the cells. The morphology and the PA signal could be used to identify qualitatively and quantitatively the aging and healthy states of the RPE cells. The results show the potential applications in studying the real-time cellular response to external stimulations and the progress of aging and diseases at the cellular level with FU-OCPAM.

Photo-thermal effect enhances the efficiency of radiotherapy using Arg-Gly-Asp peptides-conjugated gold nanorods that target αvß3 in melanoma cancer cells.

BACKGROUND: Thermotherapy has been known to be one of the most effective adjuvants to radiotherapy (RT) in cancer treatment, but it is not widely implemented clinically due to some limitations, such as, inadequate temperature concentrations to the tumor tissue, nonspecific and non-uniform distribution of heat. So we constructed arginine-glycine-aspartate peptides-conjugated gold nanorods (RGD-GNRs) that target the alpha(v) beta(3) Integrin (αvß3) and investigate whether the photo-thermal effect of RGD-GNRs by near infrared radiation (NIR) could enhance the efficiency of RT in melanoma cancer cells. RESULTS: RGD-GNRs could be seen both on the surface of the cell membranes and cytoplasm of A375 cells with high expression of αvß3. After exposed to 808 nm NIR, RGD-GNRs with various concentrations could be rapidly heated up. Compared to other treatments, flow cytometric analysis indicated that RT + NIR + RGD-GNRs increased apoptosis (p < 0.001) and decreased the proportion of cells in the more radioresistant S phase (p = 0.014). Treated with NIR + RGD-GNRs, the radiosensitivity was also significantly enhanced (DMFSF2: 1.41). CONCLUSION: Results of the current study showed the feasibility of using RGD-GNRs for synergetic RT with photo-thermal therapy. And it would greatly benefit the therapeutic effects of refractory or recurrent malignant cancers.

Air puff induced corneal vibrations: theoretical simulations and clinical observations.

PURPOSE: To investigate air puff induced corneal vibrations and their relationship to the intraocular pressure (IOP), viscoelasticity, mass, and elasticity of the cornea based on theoretical simulations and preliminary clinical observations. METHODS: To simulate the corneal movement during air puff deformation, a kinematic viscoelastic corneal model was developed involving the factors of corneal mass, damping coefficient, elasticity, and IOP. Different parameter values were taken to investigate how factors would affect the corneal movements. Two clinical ocular instruments, CorVis ST (Oculus Optikgeräte GmbH, Wetzlar, Germany) and the Ocular Response Analyzer (ORA; Reichert, Inc., Buffalo, NY), were employed to observe the corneal dynamical behaviors. RESULTS: Numerical results showed that during the air puff deformation, there would be vibrations along with the corneal deformation, and the damping viscoelastic response of the cornea had the potential to reduce the vibration amplitude. With consistent IOP, the overall vibration amplitude and inward motion depths were smaller with a stiffer cornea. CONCLUSIONS: A kinematic viscoelastic model of the cornea is presented to illustrate how the vibrations are associated with factors such as corneal mass, viscoelasticity, and IOP. Also, the predicted corneal vibrations during air puff deformation were confirmed by clinical observation.

Dual-channel spectral-domain optical-coherence tomography system based on 3 × 3 fiber coupler for extended imaging range.

We have demonstrated a dual-channel multiplexing spectral-domain optical-coherence tomography (SD-OCT) system based on a 3×3 fiber coupler for extended imaging range of whole human eye depth, with a single light source and spectrometer. OCT images of anterior segments of a human eye were sequentially performed and constructed to demonstrate an extended depth range as large as 15 mm in air. A good quality OCT image of the whole anterior segment of an eye was present. Furthermore, whole eye segmental imaging was performed and ocular distances were calculated to show the validation of the system for whole eye morphological measurement.

The role of transforming growth factor ß1 in fractional laser resurfacing with a carbon dioxide laser.

The aim of this study was to investigate the role of transforming growth factor ß1 in mechanisms of cutaneous remodeling induced by fractional carbon dioxide laser treatment. The dorsal skin of Kunming mice was exposed to a single-pass fractional CO2 laser treatment. Biopsies were taken at 1 h and at 1, 3, 7, 14, 21, 28, and 56 days after treatment. Transforming growth factor (TGF) ß1 expression in skin samples was evaluated by ELISA, dermal thickness by hematoxylin-eosin staining, collagen and elastic fibers by Ponceau S and Victoria blue double staining, and types I and III collagens by ELISA. The level of TGF ß1 in the laser-treated areas of skin was significantly increased compared with that in the control areas on days 1 (p < 0.05), 3 (p < 0.01), and 7 (p < 0.05) and then decreased by day 14 after treatment, at which time it had returned to the baseline level. Dermal thickness and the amount of type I collagen of the skin of the laser-treated areas had increased significantly (p < 0.05) compared with that in control areas on days 28 and 56. Fibroblast proliferation showed a positive correlation with TGF ß1 expression during the early stages (r = 0.789, p < 0.01), and there was a negative correlation between the level of TGF ß1 and type I collagen in the late stages, after laser treatment (r = -0.546, p < 0.05). TGF ß1 appears to be an important factor in fractional laser resurfacing.

The retinal oxygen metabolism and hemodynamics as a substitute for biochemical tests to predict nonproliferative diabetic retinopathy.

Predicting the occurrence of nonproliferative diabetic retinopathy (NPDR) using biochemical parameters is invasive, which limits large-scale clinical application. Noninvasive retinal oxygen metabolism and hemodynamics of 215 eyes from 73 age-matched healthy subjects, 90 diabetic patients without DR, 40 NPDR, and 12 DR with postpanretinal photocoagulation were measured with a custom-built multimodal retinal imaging device. Diabetic patients underwent biochemical examinations. Two logistic regression models were developed to predict NPDR using retinal and biochemical metrics, respectively. The predictive model 1 using retinal metrics incorporated male gender, insulin treatment condition, diastolic duration, resistance index, and oxygen extraction fraction presented a similar predictive power with model 2 using biochemical metrics incorporated diabetic duration, diastolic blood pressure, and glycated hemoglobin A1c (area under curve: 0.73 vs. 0.70; sensitivity: 76% vs. 68%; specificity: 64% vs. 62%). These results suggest that retinal oxygen metabolic and hemodynamic biomarkers may replace biochemical parameters to predict the occurrence of NPDR .

Predicting the cognitive impairment with multimodal ophthalmic imaging and artificial neural network for community screening.

BACKGROUND/AIMS: To investigate the comprehensive prediction ability for cognitive impairment in a general elder population using the combination of the multimodal ophthalmic imaging and artificial neural networks. METHODS: Patients with cognitive impairment and cognitively healthy individuals were recruited. All subjects underwent medical history, blood pressure measurement, the Montreal Cognitive Assessment, medical optometry, intraocular pressure and custom-built multimodal ophthalmic imaging, which integrated pupillary light reaction, multispectral imaging, laser speckle contrast imaging and retinal oximetry. Multidimensional parameters were analysed by Student's t-test. Logistic regression analysis and back-propagation neural network (BPNN) were used to identify the predictive capability for cognitive impairment. RESULTS: This study included 104 cognitive impairment patients (61.5% female; mean (SD) age, 68.3 (9.4) years), and 94 cognitively healthy age-matched and sex-matched subjects (56.4% female; mean (SD) age, 65.9 (7.6) years). The variation of most parameters including decreased pupil constriction amplitude (CA), relative CA, average constriction velocity, venous diameter, venous blood flow and increased centred retinal reflectance in 548 nm (RC548) in cognitive impairment was consistent with previous studies while the reduced flow acceleration index and oxygen metabolism were reported for the first time. Compared with the logistic regression model, BPNN had better predictive performance (accuracy: 0.91 vs 0.69; sensitivity: 93.3% vs 61.70%; specificity: 90.0% vs 68.66%). CONCLUSIONS: This study demonstrates retinal spectral signature alteration, neurodegeneration and angiopathy occur concurrently in cognitive impairment. The combination of multimodal ophthalmic imaging and BPNN can be a useful tool for predicting cognitive impairment with high performance for community screening.

Whole-Genome Resequencing of Ujimqin Sheep Identifies Genes Associated with Vertebral Number.

The number of vertebrae is a crucial economic trait that can significantly impact the carcass length and meat production in animals. However, our understanding of the quantitative trait loci (QTLs) and candidate genes associated with the vertebral number in sheep (Ovis aries) remains limited. To identify these candidate genes and QTLs, we collected 73 Ujimqin sheep with increased numbers of vertebrae (T13L7, T14L6, and T14L7) and 23 sheep with normal numbers of vertebrae (T13L6). Through high-throughput genome resequencing, we obtained a total of 24,130,801 effective single-nucleotide polymorphisms (SNPs). By conducting a selective-sweep analysis, we discovered that the most significantly selective region was located on chromosome 7. Within this region, we identified several genes, including VRTN, SYNDIG1L, LTBP2, and ABCD4, known to regulate the spinal development and morphology. Further, a genome-wide association study (GWAS) performed on sheep with increased and normal vertebral numbers confirmed that ABCD4 is a candidate gene for determining the number of vertebrae in sheep. Additionally, the most significant SNP on chromosome 7 was identified as a candidate QTL. Moreover, we detected two missense mutations in the ABCD4 gene; one of these mutations (Chr7: 89393414, C > T) at position 22 leads to the conversion of arginine (Arg) to glutamine (Gln), which is expected to negatively affect the protein's function. Notably, a transcriptome expression profile in mouse embryonic development revealed that ABCD4 is highly expressed during the critical period of vertebral formation (4.5-7.5 days). Our study highlights ABCD4 as a potential major gene influencing the number of vertebrae in Ujimqin sheep, with promising prospects for future genome-assisted breeding improvements in sheep.

Biomechanical and refractive behaviors of keratoconic cornea based on three-dimensional anisotropic hyperelastic models.

PURPOSE: To investigate the biomechanical and refractive behaviors of normal and keratoconic corneas based on three-dimensional anisotropic hyperelastic corneal models with two layers. METHODS: Based on an anisotropic hyperelastic formula, the finite element method was employed to develop normal and keratoconic corneal models in which the fiber orientations and the biomechanical differences between corneal layers were taken into account. The displacements for normal and keratoconic corneal models were studied, as well as changes in corneal refractive power with intraocular pressure (IOP). RESULTS: There were different displacements for keratoconic and normal corneas. Positive correlations were found in the keratoconic cornea between IOP and apical displacement, as well as between IOP and corneal refractive power. Under normal IOP, both the corneal shape and refractive power map were affected by the stiffness distributions of the corneal layers. CONCLUSIONS: Finite element analysis can be used to demonstrate the biomechanical and refractive behavior of a cornea with keratoconus. From a biomechanical viewpoint, the displacement changes seen under normal IOP were due to the decreased stiffness in the keratoconic corneal tissue and local thinning disorders. Thus, the curvature and corneal refractive power map will be abnormal in keratoconus.

Corneal hysteresis with intraocular pressure of a wide range: a test on porcine eyes.

PURPOSE: To investigate the relationship between corneal hysteresis (CH) and intraocular pressure (IOP) using porcine eyes in the low to high IOP ranges. METHODS: In vitro porcine eyes were used to investigate the relationship of CH and IOP. IOP was altered by changing the height of a drip stand within the dynamic range of 60 mm Hg. CH and IOP were measured with the Ocular Response Analyzer (ORA; Reichert Ophthalmic Instruments, Depew, NY) at different heights. Second-order polynomial regression method was employed to assess the nonlinear correlation of CH and IOP. RESULTS: CH demonstrated an initial plateau stage with low IOP, which then decreased as IOP increased to higher values up to 60 mm Hg. The maximum CH value of approximately 6 to 8 mm Hg was achieved when IOP ranged from 11 to 25 mm Hg. The nonlinear regression lines of Goldmann correlated IOP (IOPg) and CH can be described as CH = − 0.0029 × IOPg2 + 0.1005 × IOPg + 5.2824, R2 = 0.3676, P < .05. CONCLUSIONS: CH was relatively constant for lower values of IOP and showed a decreasing relationship at higher values of IOP. This nonlinear relationship provides insight into understanding the viscoelastic nature of CH over a wider range of IOP values. The experimental data on porcine eyes may indicate that IOP should be taken into account when analyzing the deformation response of the cornea to an applied air puff.

In vitro and in vivo evaluation of a photosensitive polyimide thin-film microelectrode array suitable for epiretinal stimulation.

BACKGROUND: Epiretinal implants based on microelectro-mechanical system (MEMS) technology with a polyimide (PI) material are being proposed for application. Many kinds of non-photosensitive PIs have good biocompatibility and stability as typical MEMS materials for implantable electrodes. However, the effects of MEMS microfabrication, sterilization and implantation using a photosensitive polyimide (PSPI) microelectrode array for epiretinal electrical stimulation has not been extensively examined. METHODS: A novel PSPI (Durimide 7510) microelectrode array for epiretinal electrical stimulation was designed, fabricated based on MEMS processing and microfabrication techniques. The biocompatibility of our new microelectrode was tested in vitro using an MTT assay and direct contact tests between the microelectrode surface and cells. Electrochemical impedance characteristics were tested based on a three-electrode testing method. The reliability and stability was evaluated by a chronic implantation of a non-functional array within the rabbit eye. Histological examination and SEM were performed to monitor possible damage of the retina and microelectrodes. Electrically evoked potentials (EEPs) were recorded during the acute stimulation of the retina. RESULTS: The substrate was made of PSPI and the electrode material was platinum (Pt). The PSPI microelectrode array showed good biocompatibility and appropriate impedance characteristics for epiretinal stimulation. After a 6-month epiretinal implantation in the eyes of rabbits, we found no local retinal toxicity and no mechanical compression caused by the array. The Pt electrodes adhesion to the PSPI remained stable. A response to electrical stimuli was with recording electrodes lying on the visual cortex. CONCLUSION: We provide a relevant design and fundamental characteristics of a PSPI microelectrode array. Strong evidences on testing indicate that implantation is safe in terms of mechanical pressure and biocompatibility of PSPI microelectrode arrays on the retina. The dual-layer process we used proffers considerable advantages over the more traditional single-layer approach and can accommodate much many electrode sites. This lays the groundwork for a future, high-resolution retinal prosthesis with many more electrode sites based on the flexible PSPI thin film substrate.

[The design of all solid-state tunable pulsed Ti:sapphire laser system].

This paper presented a design of broadly all solid-state tunable pulsed Ti:sapphire laser with high power and stable performance. The laser was pumped by custom-made Nd:YAG laser which had water cooling system and amplified by two stage amplifier. The method accomplished tunable output of all solid-state tunable pulsed Ti:sapphire laser by modifying the reflection angle of the back mirror. We investigated the relationship between the power of the pumping laser and the all solid-state tunable pulsed Ti: sapphire laser by changing the power of the pumping source.

URNet: System for recommending referrals for community screening of diabetic retinopathy based on deep learning.

Diabetic retinopathy (DR) will cause blindness if the detection and treatment are not carried out in the early stages. To create an effective treatment strategy, the severity of the disease must first be divided into referral-warranted diabetic retinopathy (RWDR) and non-referral diabetic retinopathy (NRDR). However, there are usually no sufficient fundus examinations due to lack of professional service in the communities, particularly in the developing countries. In this study, we introduce UGAN_Resnet_CBAM (URNet; UGAN is a generative adversarial network that uses Unet for feature extraction), a two-stage end-to-end deep learning technique for the automatic detection of diabetic retinopathy. The characteristics of DDR fundus data set were used to design an adaptive image preprocessing module in the first stage. Gradient-weighted Class Activation Mapping (Grad-CAM) and t-distribution and stochastic neighbor embedding (t-SNE) were used as the evaluation indices to analyze the preprocessing results. In the second stage, we enhanced the performance of the Resnet50 network by integrating the convolutional block attention module (CBAM). The outcomes demonstrate that our proposed solution outperformed other current structures, achieving 94.5% and 94.4% precisions, and 96.2% and 91.9% recall for NRDR and RWDR, respectively.

SGLSA: Sphygmus gated laser speckle angiography for microcirculation hemodynamics imaging.

Hemodynamics imaging of the retinal microcirculation has been demonstrated to be potential access to evaluating ophthalmic diseases, cardio-cerebrovascular diseases, and metabolic diseases. However, existing structural and functional imaging techniques are insufficient in spatial or temporal resolution. The sphygmus gated laser speckle angiography (SGLSA) is proposed for structural and functional imaging with high spatiotemporal resolution. Compared with classic LSCI algorithms, SGLSA presents a much clearer perfusion image and higher signal-to-noise ratio pulsatility. The SGLSA algorithm also shows better performance on patients than traditional LSCI methods. The high spatiotemporal resolution provided by the SGLSA algorithm greatly enhances the ability of retinal microcirculation analysis, which makes up for the deficiency of the LSCI technology, and attaches great significance to retinal hemodynamic imaging, biomarker research, and clinical diagnosis.

Optical coherence tomography for whole eye segment imaging.

We proposed a dual focus dual channel spectral domain optical coherence tomography (SD-OCT) for simultaneous imaging of the whole eye segments from cornea to the retina. By using dual channels the system solved the problem of limited imaging depth of SD-OCT. By using dual focus the system solved the problem of simultaneous light focusing on the anterior segment of the eye and the retina. Dual focusing was achieved by adjusting the collimating lenses so the divergence of the two probing beams was tuned to make them focused at different depth in the eye. We further achieved full range complex (FRC) SD-OCT in one channel to increase the depth range for anterior segment imaging. The system was successfully tested by imaging a human eye in vivo.

The role of vascular endothelial growth factor in fractional laser resurfacing with the carbon dioxide laser.

The aim of this study was to analyze the role of vascular endothelial growth factor (VEGF) in mechanisms of cutaneous remodeling induced by fractional CO(2) laser treatment. The dorsal skin of Kunming mice was exposed to a single-pass fractional CO(2) laser treatment. Biopsies were taken 1 h, and 1, 3, 7, 14, 28 and 56 days after treatment. Skin samples VEGF expression was evaluated by immunohistochemistry and ELISA, fibroblasts by hematoxylin-eosin staining, and types I and III collagen by ELISA. Staining for VEGF was found in many types of cell including fibroblasts. The amount of VEGF in the skin of laser-treated areas had increased significantly compared to that in the control areas on days 1 and 3 (P < 0.05, P < 0.01, respectively), then decreased by day 7 after treatment and returned to the baseline level. The number of fibroblasts in the skin of the laser-treated areas had increased significantly compared to that in control areas on days 3, 7, 14, 28 and 56 after irradiation (P < 0.05, P < 0.01, P < 0.01, P < 0.01, P < 0.01, respectively). The amount of type I collagen was significantly higher in the skin of the laser-treated areas compared to that in control areas from day 28 to day 56 (P < 0.05, respectively), and type III collagen was significantly higher from day 3 to day 56 (P < 0.05, P < 0.05, P < 0.05, P < 0.05, P < 0.01, respectively). There was a positive correlation between the level of VEGF and fibroblast proliferation early stage after laser treatment (r = 0.853, P < 0.01), but there was no correlation after the first week (r = -0.124, P > 0.05). The amounts of type I and III collagen showed no significant correlations with the expression of VEGF in the late stages after laser treatment (r = 0.417, P > 0.05 and r = 0.340, P > 0.05, respectively). The results suggest that VEGF might be mainly involved in the early stages of wound healing, including the stages of acute inflammation, fibroblast proliferation and vessel formation induced by fractional CO(2) laser resurfacing.