Publications by authors named "Yukun Guo"

23 Publications

  • Page 1 of 1

Chimeric virus-like particles of universal antigen epitopes of coronavirus and phage Qβ coat protein trigger the production of neutralizing antibodies.

Curr Top Med Chem 2021 Jun 18. Epub 2021 Jun 18.

College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, China; b Key Laboratory of Animal Biochemistry and Nutrition, Ministry of Agriculture and Rural Affairs, Henan Agricultural University, Zhengzhou 450046, China.

Background: Virus-like particles (VLPs) are non-genetic multimeric nanoparticles synthesized through in vitro or in vivo self-assembly of one or more viral structural proteins. Immunogenicity and safety of VLPs make them ideal candidates for vaccine development and efficient nanocarriers for foreign antigens or adjuvants to activate the immune system.

Aims: The present study aimed to design and synthesize a chimeric VLP vaccine of the phage Qbeta (Qβ) coat protein presenting the universal epitope of the coronavirus.

Methods: The RNA phage Qβ coat protein was designed and synthesized, denoted as Qbeta. The CoV epitope, a universal epitope of coronavirus, was inserted into the C-terminal of Qbeta using genetic recombination, which was designated as Qbeta-CoV. The N-terminal of Qbeta-CoV was successively inserted into the TEV restriction site using mCherry red fluorescent label and modified affinity-purified histidine label 6xHE, which was denoted as HE-Qbeta-CoV. Isopropyl β-D-1-thiogalactopyranoside (IPTG) assessment revealed the expression of Qbeta, Qbeta-CoV, and HE-Qbeta-CoV in the BL21 (DE3) cells. The fusion protein was purified by salting out using ammonium sulfate and affinity chromatography. The morphology of particles was observed using electron microscopy. The female BALB/C mice were immunized intraperitoneally with the Qbeta-CoV and HE-Qbeta-CoV chimeric VLPs vaccines. Their sera were collected for the detection of antibody level and antibody titer using ELISA. The serum is used for the neutralization test of the three viruses of MHV, PEDV, and PDCoV.

Results: The results revealed that the fusion proteins Qbeta, Qbeta-CoV, and HE-Qbeta-CoV could all obtain successful expression. Particles with high purity were obtained after purification; the chimeric particles of Qbeta-CoV and HE-Qbeta-CoV were found to be similar to Qbeta particles in morphology and formed chimeric VLPs. In addition, two chimeric VLP vaccines induced specific antibody responses in mice, and the antibodies showed certain neutralizing activity.

Conclusion: The successful construction of the chimeric VLPs of the phage Qβ coat protein presenting the universal epitope of coronavirus provides a vaccine form with potential clinical applications for the treatment of coronavirus disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1568026621666210618145411DOI Listing
June 2021

Comparison of Central Macular Fluid Volume With Central Subfield Thickness in Patients With Diabetic Macular Edema Using Optical Coherence Tomography Angiography.

JAMA Ophthalmol 2021 Jul;139(7):734-741

Casey Eye Institute, Oregon Health & Science University, Portland.

Importance: Diabetic macular edema (DME) is the predominant cause of visual impairment in patients with type 1 or 2 diabetes. Automated fluid volume measurements using optical coherence tomography (OCT) may improve the diagnostic accuracy of DME screening.

Objective: To assess the diagnostic accuracy of an automated central macular fluid volume (CMFV) quantification using OCT for DME.

Design, Setting, And Participants: A cross-sectional observational study was conducted at a tertiary academic center among 215 patients with diabetes (1 eye each) enrolled from January 26, 2015, to December 23, 2019. All participants underwent comprehensive examinations, 6 × 6-mm macular structural OCT horizontal raster scans, and 6 × 6-mm macular OCT angiography volumetric scans. From January 1 to March 30, 2020, 2 retinal specialists reviewed the structural OCT scans independently and diagnosed DME if intraretinal or subretinal fluid was present. Diabetic macular edema was considered center involved if fluid was present within the central fovea (central 1-mm circle). A third retinal specialist arbitrated any discrepancy. The mean central subfield thickness (CST) within the central fovea was measured on structural OCT horizontal raster scans. A deep learning algorithm automatically quantified fluid volumes on 6 × 6-mm OCT angiography volumetric scans and within the central foveas (CMFV).

Main Outcomes And Measures: The area under the receiver operating characteristic curve (AUROC) and the sensitivity and specificity of CST and CMFV for DME diagnosis.

Results: We enrolled 1 eye each of 215 patients with diabetes (117 women [54.4%]; mean [SD] age, 59.6 [12.4] years). Diabetic macular edema was present in 136 eyes; 93 cases of DME were center involved. The AUROC of CMFV for diagnosis of center-involved DME (0.907 [95% CI, 0.861-0.954]) was greater than the AUROC of CST (0.832 [95% CI, 0.775-0.889]; P = .02). With the specificity set at 95%, the sensitivity of CMFV for detection of center-involved DME (78.5% [95% CI, 68.8%-86.3%]) was higher than that of CST (53.8% [95% CI, 43.1%-64.2%]; P = .002). Center-involved DME cases not detected by CST but detected by CMFV were associated with a thinner CST (290.8 μm [95% CI, 282.3-299.3 μm] vs 369.4 μm [95% CI, 347.1-391.7 μm]; P < .001), higher proportion of previous macular laser treatment (11 of 28 [39.3%; 95% CI, 21.5%-59.4%] vs 12 of 65 [18.5%; 95% CI, 9.9%-30.0%]; P = .03), and female sex (20 of 28 [71.4%; 95% CI, 51.3%-86.8%] vs 31 of 65 [47.7%; 95% CI, 35.1%-60.5%]; P = .04).

Conclusions And Relevance: These findings suggest that an automated CMFV is a more accurate diagnostic biomarker than CST for DME and may improve screening for DME.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamaophthalmol.2021.1275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120439PMC
July 2021

Plexus-specific retinal capillary avascular area in exudative age-related macular degeneration with projection-resolved OCT angiography.

Br J Ophthalmol 2020 Dec 22. Epub 2020 Dec 22.

Ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, USA

Objective: To detect the plexus-specific retinal capillary avascular area in exudative age-related macular degeneration (EAMD) with projection-resolved optical coherence tomography angiography (PR-OCTA).

Methods And Analysis: In this prospective cross-sectional single centre study, eyes with treatment-naïve EAMD underwent macular 3×3 mm OCTA with AngioVue system. OCTA scans were analysed and processed including three-dimensional projection artefact removal, retinal layer semi-automated segmentation and en face angiogram generation. Automated quantification of extrafoveal (excluding the central 1 mm circle) avascular area (EAA) were calculated on projection-resolved superficial vascular complex (SVC), intermediate capillary plexus (ICP) and deep capillary plexus (DCP), respectively.

Results: Nineteen eyes with EAMD and 19 age-matched healthy control eyes were included. There was no significant difference between the EAMD and control eyes in terms of age, sex, axial length and mean ocular perfusion pressure (all p>0.05). Compared with control eyes, EAMD eyes had significantly larger EAA in SVC (median 0.125 vs 0.059 mm, p=0.006), ICP (0.016 vs 0.000 mm, p=0.004) and DCP (0.033 vs 0.000 mm, p<0.001).

Conclusion: PR-OCTA showed that EAMD is associated with focal avascular area in all the three retinal vascular plexuses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bjophthalmol-2020-317562DOI Listing
December 2020

Automated Segmentation of Retinal Fluid Volumes From Structural and Angiographic Optical Coherence Tomography Using Deep Learning.

Transl Vis Sci Technol 2020 10 8;9(2):54. Epub 2020 Oct 8.

Casey Eye Institute, Oregon Health & Science University, Portland, OR, USA.

Purpose: We proposed a deep convolutional neural network (CNN), named Retinal Fluid Segmentation Network (ReF-Net), to segment retinal fluid in diabetic macular edema (DME) in optical coherence tomography (OCT) volumes.

Methods: The 3- × 3-mm OCT scans were acquired on one eye by a 70-kHz OCT commercial AngioVue system (RTVue-XR; Optovue, Inc., Fremont, CA, USA) from 51 participants in a clinical diabetic retinopathy (DR) study (45 with retinal edema and six healthy controls, age 61.3 ± 10.1 (mean ± SD), 33% female, and all DR cases were diagnosed as severe NPDR or PDR). A CNN with U-Net-like architecture was constructed to detect and segment the retinal fluid. Cross-sectional OCT and angiography (OCTA) scans were used for training and testing ReF-Net. The effect of including OCTA data for retinal fluid segmentation was investigated in this study. Volumetric retinal fluid can be constructed using the output of ReF-Net. Area-under-receiver-operating-characteristic-curve, intersection-over-union (IoU), and F1-score were calculated to evaluate the performance of ReF-Net.

Results: ReF-Net shows high accuracy (F1 = 0.864 ± 0.084) in retinal fluid segmentation. The performance can be further improved (F1 = 0.892 ± 0.038) by including information from both OCTA and structural OCT. ReF-Net also shows strong robustness to shadow artifacts. Volumetric retinal fluid can provide more comprehensive information than the two-dimensional (2D) area, whether cross-sectional or en face projections.

Conclusions: A deep-learning-based method can accurately segment retinal fluid volumetrically on OCT/OCTA scans with strong robustness to shadow artifacts. OCTA data can improve retinal fluid segmentation. Volumetric representations of retinal fluid are superior to 2D projections.

Translational Relevance: Using a deep learning method to segment retinal fluid volumetrically has the potential to improve the diagnostic accuracy of diabetic macular edema by OCT systems.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1167/tvst.9.2.54DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7552937PMC
October 2020

Reconstruction of high-resolution 6×6-mm OCT angiograms using deep learning.

Biomed Opt Express 2020 Jul 8;11(7):3585-3600. Epub 2020 Jun 8.

Casey Eye Institute, Oregon Health & Science University, Portland, OR 97239, USA.

Typical optical coherence tomographic angiography (OCTA) acquisition areas on commercial devices are 3×3- or 6×6-mm. Compared to 3×3-mm angiograms with proper sampling density, 6×6-mm angiograms have significantly lower scan quality, with reduced signal-to-noise ratio and worse shadow artifacts due to undersampling. Here, we propose a deep-learning-based high-resolution angiogram reconstruction network (HARNet) to generate enhanced 6×6-mm superficial vascular complex (SVC) angiograms. The network was trained on data from 3×3-mm and 6×6-mm angiograms from the same eyes. The reconstructed 6×6-mm angiograms have significantly lower noise intensity, stronger contrast and better vascular connectivity than the original images. The algorithm did not generate false flow signal at the noise level presented by the original angiograms. The image enhancement produced by our algorithm may improve biomarker measurements and qualitative clinical assessment of 6×6-mm OCTA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1364/BOE.394301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7510902PMC
July 2020

High-resolution wide-field OCT angiography with a self-navigation method to correct microsaccades and blinks.

Biomed Opt Express 2020 Jun 21;11(6):3234-3245. Epub 2020 May 21.

Casey Eye Institute, Oregon Health and Science University, Portland, Oregon 97239, USA.

In this study, we demonstrate a novel self-navigated motion correction method that suppresses eye motion and blinking artifacts on wide-field optical coherence tomographic angiography (OCTA) without requiring any hardware modification. Highly efficient GPU-based, real-time OCTA image acquisition and processing software was developed to detect eye motion artifacts. The algorithm includes an instantaneous motion index that evaluates the strength of motion artifact on OCTA images. Areas with suprathreshold motion and eye blinking artifacts are automatically rescanned in real-time. Both healthy eyes and eyes with diabetic retinopathy were imaged, and the self-navigated motion correction performance was demonstrated.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1364/BOE.390430DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7316026PMC
June 2020

Optical Coherence Tomography Angiography Avascular Area Association With 1-Year Treatment Requirement and Disease Progression in Diabetic Retinopathy.

Am J Ophthalmol 2020 09 29;217:268-277. Epub 2020 Apr 29.

Casey Eye Institute, Oregon Health and Science University, Portland, Oregon, USA. Electronic address:

Purpose: To assess the association between optical coherence tomography angiography (OCTA)-quantified avascular areas (AAs) and diabetic retinopathy (DR) severity, progression, and treatment requirement in the following year.

Design: Prospective cohort study.

Methods: We recruited patients with diabetes from a tertiary academic retina practice and obtained 3-mm × 3-mm macular OCTA scans with the AngioVue system and standard 7-field color photographs at baseline and at a 1-year follow-up visit. A masked grader determined the severity of DR from the color photographs using the Early Treatment of Diabetic Retinopathy scale. A custom algorithm detected extrafoveal AA (EAA) excluding the central 1-mm circle in projection-resolved superficial vascular complex (SVC), intermediate capillary plexus (ICP), and deep capillary plexus (DCP).

Results: Of 138 patients, 92 (41 men, ranging in age from 26-84 years [mean 59.4 years]) completed 1 year of follow-up. At baseline, EAAs for SVC, ICP, and DCP were all significantly correlated with retinopathy severity (P < .0001). DCP EAA was significantly associated with worse visual acuity (r = -0.24, P = .02), but SVC and ICP EAA were not. At 1 year, 11 eyes progressed in severity by at least 1 step. Multivariate logistic regression analysis demonstrated the progression was significantly associated with baseline SVC EAA (odds ratio = 8.73, P = .04). During the follow-up period, 33 eyes underwent treatment. Multivariate analysis showed that treatment requirement was significantly associated with baseline DCP EAA (odds ratio = 3.39, P = .002). No baseline metric was associated with vision loss at 1 year.

Conclusions: EAAs detected by OCTA in diabetic eyes are significantly associated with baseline DR severity, disease progression, and treatment requirement over 1 year.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ajo.2020.04.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7492451PMC
September 2020

Depth-resolved optimization of a real-time sensorless adaptive optics optical coherence tomography.

Opt Lett 2020 May;45(9):2612-2615

Sensorless adaptive optics optical coherence tomography (AO-OCT) is a technology to image retinal tissue with high resolution by compensating ocular aberrations without wavefront sensors. In this Letter, a fast and robust hill-climbing algorithm is developed to optimize five Zernike modes in AO-OCT with a numerical aperture between that of conventional AO and commercial OCT systems. The merit function is generated in real time using graphics processing unit while axially tracking the retinal layer of interest. A new method is proposed to estimate the largest achievable field of view for which aberrations are corrected uniformly in sensorless AO-OCT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1364/OL.390134DOI Listing
May 2020

Automated diagnosis and segmentation of choroidal neovascularization in OCT angiography using deep learning.

Biomed Opt Express 2020 Feb 14;11(2):927-944. Epub 2020 Jan 14.

Casey Eye Institute, Oregon Health & Science University, Portland, OR 97239, USA.

Accurate identification and segmentation of choroidal neovascularization (CNV) is essential for the diagnosis and management of exudative age-related macular degeneration (AMD). Projection-resolved optical coherence tomographic angiography (PR-OCTA) enables both cross-sectional and visualization of CNV. However, CNV identification and segmentation remains difficult even with PR-OCTA due to the presence of residual artifacts. In this paper, a fully automated CNV diagnosis and segmentation algorithm using convolutional neural networks (CNNs) is described. This study used a clinical dataset, including both scans with and without CNV, and scans of eyes with different pathologies. Furthermore, no scans were excluded due to image quality. In testing, all CNV cases were diagnosed from non-CNV controls with 100% sensitivity and 95% specificity. The mean intersection over union of CNV membrane segmentation was as high as 0.88. By enabling fully automated categorization and segmentation, the proposed algorithm should offer benefits for CNV diagnosis, visualization monitoring.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1364/BOE.379977DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7041469PMC
February 2020

Robust non-perfusion area detection in three retinal plexuses using convolutional neural network in OCT angiography.

Biomed Opt Express 2020 Jan 18;11(1):330-345. Epub 2019 Dec 18.

Casey Eye Institute, Oregon Health & Science University, Portland, OR 97239, USA.

Non-perfusion area (NPA) is a quantitative biomarker useful for characterizing ischemia in diabetic retinopathy (DR). Projection-resolved optical coherence tomographic angiography (PR-OCTA) allows visualization of retinal capillaries and quantify NPA in individual plexuses. However, poor scan quality can make current NPA detection algorithms unreliable and inaccurate. In this work, we present a robust NPA detection algorithm using convolutional neural network (CNN). By merging information from OCT angiograms and OCT reflectance images, the CNN could exclude signal reduction and motion artifacts and detect the avascular features from local to global with the resolution preserved. Across a wide range of signal strength indices, and on both healthy and DR eyes, the algorithm achieved high accuracy and repeatability.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1364/BOE.11.000330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6968759PMC
January 2020

75-degree non-mydriatic single-volume optical coherence tomographic angiography.

Biomed Opt Express 2019 Dec 15;10(12):6286-6295. Epub 2019 Nov 15.

Casey Eye Institute, Oregon Health & Science University, Portland, OR 97239, USA.

Optical coherence tomography (OCT) and OCT angiography (OCTA) enable three-dimensional, high-resolution imaging of the eye. Yet, while they provide unprecedented structural and angiographic imaging detail, both have only limited fields of view in comparison to other imaging modalities like fundus photography. In this paper, we present a high-speed, high-sensitivity, swept source laser-based system that can acquire non-mydriatic 75-degree field of view OCT and OCTA images in a single complete scan without resorting to montaging techniques. The system uses an optimized scanning protocol and achieves capillary-level image quality. Such data may improve early detection of pathology and provide valuable information during disease monitoring.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1364/BOE.10.006286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6913399PMC
December 2019

Detecting and measuring areas of choriocapillaris low perfusion in intermediate, non-neovascular age-related macular degeneration.

Neurophotonics 2019 Oct 12;6(4):041108. Epub 2019 Sep 12.

Oregon Health and Science University, Casey Eye Institute, Portland, Oregon, United States.

Age-related macular degeneration (AMD) is a vision-threatening disease that affects the outer retina and choroid of elderly adults. Because photoreceptors are found in the outer retina and rely primarily on the trophic support of the underlying choriocapillaris, imaging of flow or lack thereof in choriocapillaris by optical coherence tomography angiography (OCTA) has great clinical potential in AMD assessment. We introduce a metric using OCTA, named "focal perfusion loss" (FPL) to describe the effects of age and non-neovascular AMD on choriocapillaris flow. Because OCTA imaging of choriocapillaris is vulnerable to artifacts-namely motion, projections, segmentation errors, and shadows-they are removed by postprocessing software. The shadow detection software is a machine learning algorithm recently developed for the evaluation of the retinal circulation and here adapted for choriocapillaris analysis. It aims to exclude areas with unreliable flow signal due to blocking of the OCT beam by objects anterior to the choriocapillaris (e.g., drusen, retinal vessels, vitreous floaters, and iris). We found that both the FPL and the capillary density were able to detect changes in the choriocapillaris of AMD and healthy age-matched subjects with respect to young controls. The dominant cause of shadowing in AMD is drusen, and the shadow exclusion algorithm helps determine which areas under drusen retain sufficient signal for perfusion evaluation and which areas must be excluded. Such analysis allowed us to determine unambiguously that choriocapillaris density under drusen is indeed reduced.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1117/1.NPh.6.4.041108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6739623PMC
October 2019

Detection of Reduced Retinal Vessel Density in Eyes with Geographic Atrophy Secondary to Age-Related Macular Degeneration Using Projection-Resolved Optical Coherence Tomography Angiography.

Am J Ophthalmol 2020 01 14;209:206-212. Epub 2019 Sep 14.

Casey Eye Institute, Oregon Health and Science University, Portland, Oregon, USA. Electronic address:

Purpose: To compare retinal vessel density in eyes with geographic atrophy (GA) secondary to age-related macular degeneration (AMD) to age-matched healthy eyes by using projection-resolved optical coherence tomography angiography (PR-OCTA).

Design: Prospective cross-sectional study.

Methods: Study participants underwent macular 3- × 3-mm OCTA scans with spectral domain OCTA. Reflectance-compensated retinal vessel densities were calculated on projection-resolved superficial vascular complex (SVC), intermediate capillary plexus (ICP), and deep capillary plexus (DCP). Quantitative analysis using normalized deviation compared the retinal vessel density in GA regions, 500-μm GA rim regions, and non-GA regions to similar macular locations in control eyes.

Results: Ten eyes with GA and 10 control eyes were studied. Eyes with GA had significantly lower vessel density in the SVC (54.8 ± 2.4% vs. 60.8 ± 3.1%; P < 0.001), ICP (34.0 ± 1.5% vs. 37.3 ± 1.7%; P = 0.003) and DCP (24.4 ± 2.3% vs. 28.0 ± 2.3%; P < 0.001) than control eyes. Retinal vessel density within the GA region decreased significantly in SVC, ICP, and DCP. Retinal vessel density in the GA rim region decreased in SVC and ICP but not in DCP. The non-GA region did not significantly deviate from normal controls. Eyes with GA had significantly reduced photoreceptor layer thickness; but similar nerve fiber layer, ganglion cell complex, inner nuclear layer, and outer plexiform layer thickness.

Conclusions: Eyes with GA have reduced retinal vessel density in SVC, ICP, and DCP compared to those in controls. Loss is greatest within regions of GA. Vessel density may be more sensitive than retinal layer thickness measurement in the detection of inner retinal change in eyes with GA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ajo.2019.09.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6911625PMC
January 2020

High dynamic range optical coherence tomography angiography (HDR-OCTA).

Biomed Opt Express 2019 Jul 24;10(7):3560-3571. Epub 2019 Jun 24.

Casey Eye Institute, Oregon Health & Science University, Portland, OR, 97239, USA.

The dynamic range of current optical coherence tomography (OCT) angiography (OCTA) images is limited by the fixed scanning intervals. High speed OCT devices introduce the possibility of extending the flow signal dynamic range. In this study, we created a novel scanning pattern for achieving high dynamic range (HDR)-OCTA with a superior scanning efficiency. We implemented a bidirectional, interleaved scanning pattern that is sensitive to different flow speeds by adjustable adjacent inter-scan time intervals. We found that an improved flow dynamic range can be achieved by generating 3 different B-scan time intervals using 3 repetitions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1364/BOE.10.003560DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6640830PMC
July 2019

Three-dimensional structural and angiographic evaluation of foveal ischemia in diabetic retinopathy: method and validation.

Biomed Opt Express 2019 Jul 24;10(7):3522-3532. Epub 2019 Jun 24.

Casey Eye Institute, Oregon Health & Science University, Portland, OR, 97239, USA.

Optical coherence tomography angiography (OCTA) allows us to noninvasively investigate foveal ischemia, a key feature of diabetic retinopathy (DR). However, the sizes of the foveal avascular zone (FAZ) have a significant variation in normal population, preventing the objective assessment of pathological enlargement of FAZ due to capillary dropout. Based on the relationship between FAZ and ganglion cell complex (GCC) thickness in normal eyes, we defined a theoretical baseline FAZ (tbFAZ) on structural OCT and measured 2D and 3D vessel density in its vicinity on the simultaneously acquired OCTA in normal and diabetic eyes. We found that the structure-based tbFAZ was a reliable reference to identify foveal ischemia and that the 3D vessel density demonstrated ischemia more effectively than the 2D method. The proposed 3D para-FAZ vessel density correlates well with DR severity and potentially is a useful diagnostic biomarker, especially in the early stages of DR.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1364/BOE.10.003522DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6640826PMC
July 2019

Development and validation of a deep learning algorithm for distinguishing the nonperfusion area from signal reduction artifacts on OCT angiography.

Biomed Opt Express 2019 Jul 12;10(7):3257-3268. Epub 2019 Jun 12.

Casey Eye Institute, Oregon Health & Science University, Portland, OR 97239, USA.

The capillary nonperfusion area (NPA) is a key quantifiable biomarker in the evaluation of diabetic retinopathy (DR) using optical coherence tomography angiography (OCTA). However, signal reduction artifacts caused by vitreous floaters, pupil vignetting, or defocus present significant obstacles to accurate quantification. We have developed a convolutional neural network, MEDnet-V2, to distinguish NPA from signal reduction artifacts in 6×6 mm OCTA. The network achieves strong specificity and sensitivity for NPA detection across a wide range of DR severity and scan quality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1364/BOE.10.003257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6640834PMC
July 2019

Monitoring retinal responses to acute intraocular pressure elevation in rats with visible light optical coherence tomography.

Neurophotonics 2019 Oct 12;6(4):041104. Epub 2019 Jul 12.

Oregon Health and Science University, Casey Eye Institute, Portland, Oregon, United States.

Elevated intraocular pressure (IOP) is an important risk factor for glaucoma. However, the role of IOP in glaucoma progression, as well as retinal physiology in general, remains incompletely understood. We demonstrate the use of visible light optical coherence tomography to measure retinal responses to acute IOP elevation in Brown Norway rats. We monitored retinal responses in reflectivity, angiography, blood flow, oxygen saturation ( ), and oxygen metabolism over a range of IOP from 10 to 100 mmHg. As IOP was elevated, nerve fiber layer reflectivity was found to decrease. Vascular perfusion in the three retinal capillary plexuses remained steady until IOP exceeded 70 mmHg and arterial flow was noted to reverse periodically at high IOPs. However, a significant drop in total retinal blood flow was observed first at 40 mmHg. As IOP increased, the venous demonstrated a gradual decrease despite steady arterial , which is consistent with increased arterial-venous oxygen extraction across the retinal capillary beds. Calculated total retinal oxygen metabolism was steady, reflecting balanced responses of blood flow and oxygen extraction, until IOP exceeded 40 mmHg, and fell to 0 at 70 and 80 mmHg. Above this, measurements were unattainable. All measurements reverted to baseline when the IOP was returned to 10 mmHg, indicating good recovery following acute pressure challenge. These results demonstrate the ability of this system to monitor retinal oxygen metabolism noninvasively and how it can help us understand retinal responses to elevated IOP.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1117/1.NPh.6.4.041104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6624745PMC
October 2019

DETECTION OF CLINICALLY UNSUSPECTED RETINAL NEOVASCULARIZATION WITH WIDE-FIELD OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

Retina 2020 May;40(5):891-897

Department of Ophthalmology, Casey Eye Institute, Oregon Health and Science University, Portland, Oregon; and.

Purpose: To evaluate wide-field optical coherence tomography angiography (OCTA) for detection of clinically unsuspected neovascularization (NV) in diabetic retinopathy (DR).

Methods: This prospective observational single-center study included adult patients with a clinical diagnosis of nonproliferative DR. Participants underwent a clinical examination, standard 7-field color photography, and OCTA with commercial and prototype swept-source devices. The wide-field OCTA was achieved by montaging five 6 × 10-mm scans from a prototype device into a 25 × 10-mm image and three 6 × 6-mm scans from a commercial device into a 15 × 6-mm image. A masked grader determined the retinopathy severity from color photographs. Two trained readers examined conventional and wide-field OCTA images for the presence of NV.

Results: Of 27 participants, photographic grading found 13 mild, 7 moderate, and 7 severe nonproliferative DR. Conventional 6 × 6-mm OCTA detected NV in 2 eyes (7%) and none with 3 × 3-mm scans. Both prototype and commercial wide-field OCTA detected NV in two additional eyes. The mean area of NV was 0.38 mm (range 0.17-0.54 mm). All eyes with OCTA-detected NV were photographically graded as severe nonproliferative DR.

Conclusion: Wide-field OCTA can detect small NV not seen on clinical examination or color photographs and may improve the clinical evaluation of DR.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/IAE.0000000000002487DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6722037PMC
May 2020

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

Biomed Opt Express 2018 Sep 24;9(9):4429-4442. Epub 2018 Aug 24.

Casey Eye Institute, Oregon Health & Science University, Portland, OR 97239, USA.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1364/BOE.9.004429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6157796PMC
September 2018

Rapid Synthesis of -Tosylhydrazones under Solvent-Free Conditions and Their Potential Application Against Human Triple-Negative Breast Cancer.

ChemistryOpen 2018 Dec 21;7(12):977-983. Epub 2018 Nov 21.

College of Basic Medicine Jining Medical University Jining 272067 China.

Some -tosylhydrazone derivatives were effectively synthesized under solvent-free conditions by using a grinding method at room temperature. The short reaction time, clean and mild process with simple workup and easy purification of the target compounds were salient features of the present protocol, which enables straightforward access to -tosylhydrazones. Among the tosylhydrazone derivatives evaluated, compound exhibits excellent apoptosis-promoting and anticancer potential against triple-negative breast cancer (TNBC) cell lines. This research shows that our synthesized compound may be a desirable and effective therapeutic drug against TNBC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/open.201800206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6276103PMC
December 2018

MEDnet, a neural network for automated detection of avascular area in OCT angiography.

Biomed Opt Express 2018 Nov 2;9(11):5147-5158. Epub 2018 Oct 2.

Casey Eye Institute, Oregon Health & Science University, Portland, OR 97239, USA.

Screening and assessing diabetic retinopathy (DR) are essential for reducing morbidity associated with diabetes. Macular ischemia is known to correlate with the severity of retinopathy. Recent studies have shown that optical coherence tomography angiography (OCTA), with intrinsic contrast from blood flow motion, is well suited for quantified analysis of the avascular area, which is potentially a useful biomarker in DR. In this study, we propose the first deep learning solution to segment the avascular area in OCTA of DR. The network design consists of a multi-scaled encoder-decoder neural network (MEDnet) to detect the non-perfusion area in 6 × 6 mm and in ultra-wide field retinal angiograms. Avascular areas were effectively detected in DR subjects of various disease stages as well as in the foveal avascular zone of healthy subjects.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1364/BOE.9.005147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6238913PMC
November 2018

AFM Nanoindentation Experiments on Protein Shells: A Protocol.

Methods Mol Biol 2019 ;1886:243-257

Moleculaire Biofysica, Zernike Instituut, Rijksuniversiteit Groningen, Groningen, The Netherlands.

Proteinaceous assemblies are ubiquitous in nature. One important form of these assemblies are protein nanoshells such as viruses; however, a variety of other protein shells exist. To deepen our knowledge on the structure and function of protein shells, a profound insight into their mechanical properties is required. Nanoindentation measurements with an atomic force microscope (AFM) are increasingly being performed to probe such material properties. This single particle approach allows us to determine the spring constant, the Young's modulus, as well as the force and deformation at which failure occurs of the nanoshells. The experimental procedures for these mechanical measurements are described here in detail, focusing on surface preparation, AFM imaging and nanoindentation, and the subsequent data analysis of the force-distance curves. Whereas AFM can be operated in air and in liquid, the described methods are for probing single particles in liquid to enable studies in close to physiological environments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/978-1-4939-8894-5_14DOI Listing
June 2019

Low-Temperature Copper Bonding Strategy with Graphene Interlayer.

ACS Nano 2018 03 6;12(3):2395-2402. Epub 2018 Feb 6.

Department of Electrical Engineering and Computer Science , Massachusetts Institute of Technology , Cambridge , Massachusetts 02139 , United States.

The reliability of lead-free Cu bonding technology is often limited by high bonding temperature and perpetual growth of intermetallic compounds between Sn solder and Cu substrate. Here, we report a low-bonding-temperature and highly reliable Cu bonding strategy with the use of graphene as an interlayer. By integrating a nanoscale graphene/Cu composite on the Cu substrate prior to thermocompression bonding, we observe a macroscale phenomenon where reliable Sn-Cu joints can be fabricated at a bonding temperature as low as 150 °C. During the bonding process, nanoscale features are replicated in the Sn solder by the Cu nanocone array morphology. Compared to microscale Sn, nanoscale Sn is mechanically weaker and thus can distribute on the Cu substrate at a much lower temperature. Furthermore, insertion of a graphene interlayer, which is one atom thick, can successfully retard the intermetallic compounds' growth and preserve a high bonding yield, following 96 h of aging, as confirmed through SEM and shear strength analyses. Our graphene-based Cu bonding strategy demonstrated in this work is highly reliable, cost-effective, and environmentally friendly, representing a much closer step toward industrial applications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsnano.7b07739DOI Listing
March 2018
-->