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Showing papers by "Ruikang K. Wang published in 2019"


Journal ArticleDOI
TL;DR: Perfusable constructs of human embryonic stem cell-derived endothelial cells seeded in collagen matrix in patterned microchannels that form anastomosed vessels in vitro and have increased coronary vascular perfusion on transplantation in rats are engineer.
Abstract: Vascularization and efficient perfusion are long-standing challenges in cardiac tissue engineering. Here we report engineered perfusable microvascular constructs, wherein human embryonic stem cell-derived endothelial cells (hESC-ECs) are seeded both into patterned microchannels and the surrounding collagen matrix. In vitro, the hESC-ECs lining the luminal walls readily sprout and anastomose with de novo-formed endothelial tubes in the matrix under flow. When implanted on infarcted rat hearts, the perfusable microvessel grafts integrate with coronary vasculature to a greater degree than non-perfusable self-assembled constructs at 5 days post-implantation. Optical microangiography imaging reveal that perfusable grafts have 6-fold greater vascular density, 2.5-fold higher vascular velocities and >20-fold higher volumetric perfusion rates. Implantation of perfusable grafts containing additional hESC-derived cardiomyocytes show higher cardiomyocyte and vascular density. Thus, pre-patterned vascular networks enhance vascular remodeling and accelerate coronary perfusion, potentially supporting cardiac tissues after implantation. These findings should facilitate the next generation of cardiac tissue engineering design.

100 citations


Journal ArticleDOI
TL;DR: In normal aging, the FD% increased with age across the central 5 mm of the macula, but the greatest increase was found in the central 1-mm region of theMacula, and the smallest increases in the peripheral macula R2.5 regions.

100 citations


Journal ArticleDOI
TL;DR: Contrary to expectations, the global CC FD measurements had a better correlation with the ERs of GA than those in the regions immediately around the GA, and may reflect FD alterations related to AMD severity.

81 citations


Journal ArticleDOI
TL;DR: Quantitative CC analysis with commercially available OCTA is complicated and researchers need to pay close attention to how they conduct such analyses.

67 citations


Journal ArticleDOI
TL;DR: In this paper, the authors used images from optical coherence tomography angiography (OCTA), a relatively new imaging modality that measures retinal blood flow, to train an AI algorithm to generate flow maps from standard OCT images.
Abstract: Despite advances in artificial intelligence (AI), its application in medical imaging has been burdened and limited by expert-generated labels. We used images from optical coherence tomography angiography (OCTA), a relatively new imaging modality that measures retinal blood flow, to train an AI algorithm to generate flow maps from standard optical coherence tomography (OCT) images, exceeding the ability and bypassing the need for expert labeling. Deep learning was able to infer flow from single structural OCT images with similar fidelity to OCTA and significantly better than expert clinicians (P < 0.00001). Our model allows generating flow maps from large volumes of previously collected OCT data in existing clinical trials and clinical practice. This finding demonstrates a novel application of AI to medical imaging, whereby subtle regularities between different modalities are used to image the same body part and AI is used to generate detailed inferences of tissue function from structure imaging.

59 citations


Journal ArticleDOI
TL;DR: In this review article, a number of imaging techniques are summarized that have been utilized to investigate the microvasculature of skin, along with their advantages, disadvantages and future perspectives in preclinical and clinical settings.
Abstract: Despite our understanding that the microvasculature plays a multifaceted role in the development and progression of various conditions, we know little about the extent of this involvement. A need exists for non-invasive, clinically meaningful imaging modalities capable of elucidating microvascular information to aid in our understanding of disease, and to aid in the diagnosis/monitoring of disease for more patient-specific care. In this review article, a number of imaging techniques are summarized that have been utilized to investigate the microvasculature of skin, along with their advantages, disadvantages and future perspectives in preclinical and clinical settings. These techniques include dermoscopy, capillaroscopy, Doppler sonography, laser Doppler flowmetry (LDF) and perfusion imaging, laser speckle contrast imaging (LSCI), optical coherence tomography (OCT), including its Doppler and dynamic variant and the more recently developed OCT angiography (OCTA), photoacoustic imaging, and spatial frequency domain imaging (SFDI). Attention is largely, but not exclusively, placed on optical imaging modalities that use intrinsic optical signals to contrast the microvasculature. We conclude that whilst each imaging modality has been successful in filling a particular niche, there is no one, all-encompassing modality without inherent flaws. Therefore, the future of cutaneous microvascular imaging may lie in utilizing a multi-modal approach that will counter the disadvantages of individual systems to synergistically augment our imaging capabilities.

51 citations


Journal ArticleDOI
TL;DR: In this paper, the authors investigated the prevalence, incidence, and natural history of subclinical macular neovascularization (MNV) in eyes with unilateral nonexudative age-related macular degeneration.

50 citations


Journal ArticleDOI
TL;DR: The use of multi-parametric OCT imaging may aid in the comprehensive evaluation of ischemic lesions during the early stages of stroke, thereby providing essential knowledge for guiding treatment decisions.
Abstract: Cerebral ischemic stroke causes injury to brain tissue characterized by a complex cascade of neuronal and vascular events. Imaging during the early stages of its development allows prediction of tissue infarction and penumbra so that optimal intervention can be determined in order to salvage brain function impairment. Therefore, there is a critical need for novel imaging techniques that can characterize brain injury in the earliest phases of the ischemic stroke. This paper examined optical coherence tomography (OCT) for imaging acute injury in experimental ischemic stroke in vivo . Based on endogenous optical scattering signals provided by OCT imaging, we have developed a single, integrated imaging platform enabling the measurement of changes in blood perfusion, blood flow, erythrocyte velocity, and light attenuation within a cortical tissue, during focal cerebral ischemia in a mouse model. During the acute phase (from 5 min to the first few hours following the blood occlusion), the multi-parametric OCT imaging revealed multiple hemodynamic and tissue scattering responses in vivo , including cerebral blood flow deficits, capillary non-perfusion, displacement of penetrating vessels, and increased light attenuation in the cortical tissue at risk that are spatially correlated with the infarct core, as determined by postmortem staining with triphenyltetrazolium chloride. The use of multi-parametric OCT imaging may aid in the comprehensive evaluation of ischemic lesions during the early stages of stroke, thereby providing essential knowledge for guiding treatment decisions.

36 citations


Journal ArticleDOI
TL;DR: It is shown that propagating mechanical waves are mode converted at interfaces, creating a finite region on the order of an acoustic wavelength where there is not a simple one-to-one correspondence between wave speed and elastic modulus.
Abstract: Dynamic optical coherence elastography (OCE) tracks elastic wave propagation speed within tissue, enabling quantitative three-dimensional imaging of the elastic modulus. We show that propagating mechanical waves are mode converted at interfaces, creating a finite region on the order of an acoustic wavelength where there is not a simple one-to-one correspondence between wave speed and elastic modulus. Depending on the details of a boundary’s geometry and elasticity contrast, highly complex propagating fields produced near the boundary can substantially affect both the spatial resolution and contrast of the elasticity image. We demonstrate boundary effects on Rayleigh waves incident on a vertical boundary between media of different shear moduli. Lateral resolution is defined by the width of the transition zone between two media and is the limit at which a physical inclusion can be detected with full contrast. We experimentally demonstrate results using a spectral-domain OCT system on tissue-mimicking phantoms, which are replicated using numerical simulations. It is shown that the spatial resolution in dynamic OCE is determined by the temporal and spatial characteristics (i.e., bandwidth and spatial pulse width) of the propagating mechanical wave. Thus, mechanical resolution in dynamic OCE inherently differs from the optical resolution of the OCT imaging system.

34 citations


Journal ArticleDOI
TL;DR: Compared to conventional OCT systems, the high-speed hand-held OCT system significantly improves the operator's experience and scanning efficiency, which is important for imaging infants, as well as the image quality of OCT angiography.
Abstract: We report a novel design and operation of a highly integrated miniature handheld OCT probe, with high-speed angiography function that can be used in clinical settings for young children and infants, providing rapid, non-invasive structural and angiographic imaging of the retina and choroid. The imaging system is operated at 200 kHz, with 3D OCT and OCTA scan time of 0.8 and 3.2 seconds, respectively, and the scanning angle on the pupil is ± 36°, covering the full perifoveal region. Operator assisting features of the direct-view iris camera and on-probe display are integrated into the hand-held probe, and the fixation target can display animations to attract the attention of young subjects. Compared to conventional OCT systems, the high-speed hand-held OCT system significantly improves the operator’s experience and scanning efficiency, which is important for imaging infants. Imaging results indicate a significant reduction in total time consumption in pediatric ophthalmic imaging sessions, as well as the image quality of OCT angiography.

32 citations


Journal ArticleDOI
TL;DR: Age, sex, and systemic influences, such as diabetes duration, need to be considered when assessing changes in RPC VD in glaucoma and other ocular diseases.

Journal ArticleDOI
TL;DR: To find the potential relation between changes in retinal large vessels and terminal vessels using colour Doppler flow imaging (CDFI) and optical coherence tomography angiography (OCTA) and to compare the respective advantages of CDFI and OCTA in evaluating vascular changes in Retinitis pigmentosa (RP) patients.
Abstract: PURPOSE To find the potential relation between changes in retinal large vessels and terminal vessels using colour Doppler flow imaging (CDFI) and optical coherence tomography angiography (OCTA) and to compare the respective advantages of CDFI and OCTA in evaluating vascular changes in retinitis pigmentosa (RP) patients. METHODS A prospective series of case study was conducted to enrol RP patients and age-matched controls, who were, respectively, imaged by CDFI and OCTA. Repeatability and reproducibility of both CDFI and OCTA were performed among healthy volunteers. The central retinal artery (CRA) was detected by CDFI analysis to provide parameters of peak systolic velocity (PSV), end-diastolic velocity (EDV) and time-averaged maximum velocity (TAMV). Retinal parameters were evaluated from OCTA images, including vascular area density (VAD) of the superficial vascular layer, the fovea avascular zone (FAZ) area and retinal thickness. RP patients were separated into a high-vision group and a low-vision group, according to median vision (0.3, LogMAR 0.5). Multiple comparisons were used to analyse the data between groups. A correlation analysis was used to determine the correlation between CDFI and OCTA parameters. RESULTS Twenty RP patients (40 eyes) and thirteen normal volunteers (26 eyes) were enrolled in this study. Repeatability and reproducibility of the measurements by CDFI had higher CVs, from 4.5% to 15.4%, than those measurements by OCTA (<5%). All the CDFI and OCTA parameters examined had significant reductions in RP patients compared to those in the controls (p < 0.01). Compared to the high-vision group, the low-vision group exhibited a statistically significant decrease in vascular parameters of the FAZ area, fovea VAD and parafovea nasal side VAD (p < 0.05); as well as in the parameters of the fovea thickness, and the parafovea nasal, superior and inferior side thickness (p < 0.05). From the correlation analysis, a significant association was found between the vision and CDFI parameters (PSV and time-averaged maximum velocity (TAMX), p < 0.05), and the vision and OCTA parameters (FAZ area, fovea and nasal side VAD, retinal thickness in all sides, p < 0.05). PSV and TAMX of the CRA were closely related to the OCTA superficial VAD in all sides, whereas the CDFI parameters showed poor correlation with retinal thickness. CONCLUSIONS Colour Doppler flow imaging (CDFI) and OCTA parameters revealed a significant reduction in RP patients when compared to the controls. OCTA can detect vision-related microvascular and thickness changes around the macula between high- and low-vision groups, which happen earlier than the changes in large vessels. In addition to good repeatability and reproducibility, OCTA may have significant utility in the diagnosis and monitoring of disease progression in RP patients.

Journal ArticleDOI
TL;DR: The OCE community is urged to be careful in using the group velocity to evaluate tissue elasticity and to focus on developing robust reconstruction methods to accurately reconstruct images of the shear elastic modulus in bounded media.
Abstract: Dynamic elastography is an attractive method to evaluate tissue biomechanical properties. Recently, it was extended from US- and MR-based modalities to optical ones, such as optical coherence tomography for three-dimensional (3-D) imaging of propagating mechanical waves in subsurface regions of soft tissues, such as the eye. The measured group velocity is often used to convert wave speed maps into 3-D images of the elastic modulus distribution based on the assumption of bulk shear waves. However, the specific geometry of OCE measurements in bounded materials such as the cornea and skin calls into question elasticity reconstruction assuming a simple relationship between group velocity and shear modulus. We show that in layered media the bulk shear wave assumption results in highly underestimated shear modulus reconstructions and significant structural artifacts in modulus images. We urge the OCE community to be careful in using the group velocity to evaluate tissue elasticity and to focus on developing robust reconstruction methods to accurately reconstruct images of the shear elastic modulus in bounded media.

Journal ArticleDOI
TL;DR: The SS-OCTA handheld device can capture important vitreoretinal characteristics such as peripapillary and foveal microvasculature, as well as hyperreflective punctate vitreous opacities and tractional vitreOUS bands, which may predict ROP severity.
Abstract: Background Retinopathy of prematurity (ROP) can lead to retinal detachment and severe vision loss and is a common cause of childhood blindness. Optical coherence tomography angiography (OCTA) is a non-invasive imaging modality that can be used to detect potential abnormalities in the microvasculature in this population. The objective of this study is to assess the feasibility of a newly developed handheld swept source OCT (SS-OCT) device to successfully acquire structural vitreoretinal and retinal microvascular images in awake premature infants. Methods OCT and OCTA images were acquired at the time of routine ROP examinations from awake, unsedated preterm infants in the Neonatal Intensive Care Unit using a clinical research prototype handheld probe integrated with an SS-OCT system working at 1,060 nm wavelength and an imaging speed of 200,000 A-scans per second (200 kHz), enabling volume OCT and OCTA scans. Each volume was acquired with approximately 36˚ field of view (~6.3×6.3 mm in infants) in 4.8 s. Quality of acquired OCT and OCTA volume images, microvascular information, and vitreoretinal features were determined by 3-masked grader consensus. Results Twelve infants (5 females, mean gestational age 28.3 weeks, median birth weight 901 g, stages 0 to 3 ROP) underwent a total of 73 individual eye imaging sessions. High-quality OCT images of the fovea and the optic nerve were present in 69/73 (94.5%) and 56/73 (76.7%) scans, respectively. Vitreous bands were observed in 10/73 (13.7%); punctate hyperreflective vitreous opacities in 47/73 (64.4%); epiretinal membrane (ERM) in 6/73 (8.2%); and cystoid macular edema (CME) in 12/73 (16.4%) scans. Mild vessel elevation was noted in 3/73 (4.1%) images, and severe vessel elevation in 4/73 (5.5%) scans. OCTA images obtained in 8 awake infants revealed good quality images of the foveal microvasculature in 11/19 (58%) eye imaging sessions for 6/8 (75%) infants; and peripapillary microvasculature in 14/19 (74%) eye imaging sessions for 5/8 (63%) infants. Conclusions The SS-OCTA handheld device can capture important vitreoretinal characteristics such as peripapillary and foveal microvasculature, as well as hyperreflective punctate vitreous opacities and tractional vitreous bands, which may predict ROP severity. These images were captured in awake, premature infants without the use of direct ocular contact, an eyelid speculum, or sedation.

Journal ArticleDOI
TL;DR: The retinal capillaries, assessed with SS-OCTA, in subjects with DR preferentially reacted to hyperoxia but not hypercapnia, while the healthy controls reacted to both; the difference in the vascular reactivity may be indicative of the underlying pathophysiology of DR.
Abstract: Purpose To assess retinal vascular reactivity in healthy controls and subjects with diabetic retinopathy (DR). Methods A total of 22 healthy control eyes and 16 eyes with DR were enrolled. Images were acquired using a commercially available swept-source optical coherence tomography angiography (SS-OCTA) system. Three conditions were tested for each patient (hyperoxia, hypercapnia, and room-air) by employing a non-rebreathing apparatus that delivered appropriate gas mixtures (100% O2, 5% CO2, room air). Vessel skeleton density (VSD) and vessel diameter index (VDI) were compared between the conditions using mixed-model ANOVA adjusting for age and hypertension. Significant gas or interaction effects were followed by a Bonferroni adjusted pairwise post hoc analysis. Statistical significance was defined at P < 0.05. Results The mixed-model ANOVA of the VSD found a significant intraindividual gas effect (F[2, 70] = 20.3, P < 0.001) and intergroup effect (F[1, 35] = 6.9, P = 0.001), and interaction effects (F[2, 70] = 4.6, P = 0.03). The post hoc pairwise comparison found significant differences among all three gas conditions in the healthy controls. In the subjects with DR, there were significant differences in VSD between hyperoxic and room air, and between hyperoxic and hypercapnic conditions, but not between hypercapnic and room-air conditions. Similar results were found for VDI. Conclusions The retinal capillaries, assessed with SS-OCTA, in subjects with DR preferentially reacted to hyperoxia but not hypercapnia, while the healthy controls reacted to both. The difference in the vascular reactivity may be indicative of the underlying pathophysiology of DR.

Journal ArticleDOI
TL;DR: Thinner RNFL and longer AL were the most influential ocular determinants of lower peripapillary perfusion in healthy AA eyes, and additional research is needed to clarify whether longer AL increases risk of glaucoma by affecting capillary perfusions.
Abstract: Purpose The African American (AA) population has unique ocular anatomic characteristics and a disproportionately high incidence of glaucoma, which is associated with lower peripapillary vessel density (VD). This study aimed to identify ocular determinants of peripapillary VD in healthy AAs. Methods This was a cross-sectional, population-based study of 1029 AAs, ages 40 and older. Participants underwent examination to obtain axial length (AL), IOP, central corneal thickness (CCT), mean retinal nerve fiber layer (RNFL) thickness, visual field mean deviation (MD), and 6 × 6-mm optical coherence tomography angiography scans of the optic nerve. Participants with glaucoma, vision-threatening diabetic retinopathy, or other relevant ocular disease were excluded. Prototype software was used to quantify VD. A multivariable regression model, controlling for age and signal strength, identified the ocular variables that predicted peripapillary VD. The contribution of each variable was assessed with the magnitude of standardized regression coefficients (SRC). Results Based on univariate regressions, AL, RNFL thickness, and MD had significant associations with peripapillary VD (all P < 0.001). In the final multivariate model, lower mean RNFL thickness (β = 0.0022, P < 0.001, SRC = 0.542) and longer AL (β = -0.0055, P < 0.001, SRC = -0.118) were associated with lower peripapillary VD, controlling for age and signal strength, with model R2 of 0.69. Conclusions Thinner RNFL and longer AL were the most influential ocular determinants of lower peripapillary perfusion in healthy AA eyes. Additional research is needed to clarify whether longer AL increases risk of glaucoma by affecting capillary perfusion.

Journal ArticleDOI
TL;DR: New multimodal imaging features that enhance the authors' understanding of the inflammatory and ischemic nature of acute idiopathic maculopathy (AIM) and to correlate structural and functional changes due to a reversible initial choroidal ischemia over a clinical course of 3.5 months are reported.
Abstract: Purpose To report new multimodal imaging features that enhance our understanding of the inflammatory and ischemic nature of acute idiopathic maculopathy (AIM) and to correlate structural and functional changes due to a reversible initial choroidal ischemia over a clinical course of 3.5 months. Methods A 31-year-old man presented with acute central vision loss in his right eye due to coxsackievirus-associated AIM. Serial multimodal retinal imaging including confocal true color fundus photography, blue-light fundus autofluorescence (BAF), near-infrared reflectance (NIR), spectral domain optical coherence tomography and swept-source optical coherence tomography (SD-OCT + SS-OCT), and en face SS-OCT angiography (SS-OCTA) were performed over a 3.5-month follow-up. Eidon true color confocal scanner camera (Centervue, Padova, Italy) was used for color and BAF imaging. Near-infrared reflectance and SD-OCT images were obtained with the Heidelberg Spectralis OCT (HRA2 + OCT; Heidelberg Engineering, Heidelberg, Germany). For SS-OCT and en face SS-OCT and SS-OCTA images, the PLEX Elite 9,000 (Carl Zeiss Meditec, Inc, Dublin, CA) was used. Central alterations in choriocapillaris flow were analyzed with SS-OCTA using the University of Washington choriocapillaris (CC) flow deficit quantification algorithm available through the ARI Network. Flow deficit area and density values were analyzed and compared between the first and last examinations. Corresponding en face OCT imaging was used to distinguish true flow defects from artifacts secondary to shadowing. Results In the acute stage of AIM, a bacillary layer detachment appearing as a yellow-grayish foveal elevation surrounded by a hypopigmented parafoveal ring was evident in a Bull's eye configuration, corresponding to a hyperreflective ring upon NIR and a hyperautofluorescent ring with BAF. SD + SS-OCT showed mostly intraretinal fluid consistent with a bacillary layer detachment in conjunction with a thickened inner choroid. At presentation, SS-OCTA demonstrated a marked reduction of choriocapillaris flow signal. At 1 week, early resolution of retinal fluid was followed by restoration of the ellipsoid zone at 5 weeks, while restoration of the interdigitation zone and reduction in retinal pigment epithelium/Bruch membrane complex thickening occurred more slowly. Swept-source OCT angiography showed a gradual, but incomplete, recovery of inner choroidal flow signal at 3.5-month follow-up. Conclusion Acutely, AIM may present with a photoreceptor splitting foveal bacillary layer detachment associated with a marked reduction in inner choroidal flow signal on SS-OCTA. Thereafter, restoration of the outer retinal layers and gradual normalization of choroidal flow signal appear to support the often-benign nature of the disease.

Journal ArticleDOI
TL;DR: The proposed hyperspectral imaging system improves the device simplicity and is immune to motion artifacts, and promises a robust skin assessment tool with abilities for qualitative visualization and potentially quantitative analysis of skin features, useful in the applications of cosmetics and clinical dermatology.
Abstract: We propose a snapshot hyperspectral imaging system and methods for skin morphological feature analysis and real-time monitoring of skin activities. The analysis method includes a strategy using weighted subtractions between sub-channel images to extract absorption information due to specific chromophores within skin tissue, for example hemoglobin and melanin. Based on morphological analysis results, we carry out real-time monitoring of the skin features to verify the ability of this method to provide temporal responses of the skin tissue activities, which is experimentally shown to be useful in the measurement of heartrate, monitoring of the tissue recovery after a body exercise, and studying of the tissue response due to a vascular occlusion. Compared to conventional multispectral imaging system, the proposed system improves the device simplicity and is immune to motion artifacts. Coupled with the extraction algorithms, the hyperspectral imaging promises a robust skin assessment tool with abilities for qualitative visualization and potentially quantitative analysis of skin features, useful in the applications of cosmetics and clinical dermatology.

Journal ArticleDOI
TL;DR: In this article, the changes in optic nerve head perfusion following intravitreal antivascular endothelial growth factor injections were evaluated using OCTA angiography images of both the injected and uninjected fellow eyes.
Abstract: PURPOSE To use optical coherence tomography angiography (OCTA) to evaluate the changes in optic nerve head perfusion following intravitreal antivascular endothelial growth factor injections. METHODS Preinjection and postinjection intraocular pressure (IOP) and OCTA images were taken of both the injected and uninjected fellow eyes. RESULTS Mean preinjection IOP was 16.6±4.7 mm Hg, which increased to a mean of 40.3±13.0 mm Hg (P<0.0001) during the first postinjection image and remained elevated at 36.1±11.5 mm Hg (P<0.0001) during the second postinjection image. Although no significant change was observed in flux, vessel area density, or normalized flux when comparing the OCTA preinjection and first postinjection images, a significant decrease at the second postinjection image was observed (P=0.03, 0.02, and 0.03, respectively). No significant change was observed in the uninjected fellow eye during the same time period (P=0.47, 0.37, and 0.38, respectively). CONCLUSIONS Following an antivascular endothelial growth factor injection, mean IOP increased significantly and OCTA imaging of the optic nerve demonstrated a mild but significant decrease in optic nerve head perfusion parameters. Clinicians performing these injections should be aware of these findings and monitor the status of the optic nerve in patients undergoing injections.

Journal ArticleDOI
TL;DR: These results provide for the first time direct visualization of hyperemia-induced capillary de-recruitment distal to arterial stenosis and demonstrate that pericyte constriction underlies this phenomenon in vivo.
Abstract: In the setting of coronary arterial stenosis, hyperemia produces a reversible perfusion defect resulting from capillary derecruitment that is believed to underlie cardiac ischemia under hyperemic c...

Journal ArticleDOI
TL;DR: Parameters from 4.5 scans generally outperformed those from 6.0 scans in the global and quadrant regions, suggesting greater digital resolution in 4.
Abstract: Precis When comparing 4.5×4.5 mm to 6.0×6.0 mm optical coherence tomography angiography scans of the radial peripapillary capillaries (RPCs) for glaucoma diagnostic capability, there was a trend of 4.5 scans outperforming 6.0 scans, especially for inferior, nasal, and superior quadrants. Objectives The main purpose of this study was to compare diagnostic ability of peripapillary vessel parameters from 4.5×4.5 mm (4.5) and 6.0×6.0 mm (6.0) spectral-domain optical coherence tomography angiography scans of the RPC in detecting primary open-angle glaucoma from nonglaucoma eyes. Methods Consecutive patients from an academic glaucoma clinic underwent 4.5 and 6.0 scans (CIRRUS HD-OCT 5000 with AngioPlex OCT Angiography; ZEISS, Dublin, CA). Automatic segmentation created en face RPC images. Vessel area density, vessel skeleton density, and flux were calculated using custom quantification software, and perfusion density and flux index (FI) using automated quantification software. Area under the curve statistics included age and hypertension in the analysis. Results Of 173 eyes from 123 patients who underwent both 4.5 and 6.0 imaging, 32 primary open-angle glaucoma eyes from 32 patients and 95 nonglaucoma eyes from 95 patients were studied. For the global region of 4.5 versus 6.0 scans, area under the curve was 0.940 and 0.916 for vessel area density (P=0.286); 0.941 and 0.921 for vessel skeleton density (P=0.385); 0.942 and 0.916 for flux (P=0.239); 0.912 and 0.884 for perfusion density (P=0.103); and 0.913 and 0.865 for FI (P=0.159), respectively. For the quadrant regions, 4.5 images significantly outperformed 6.0 images for the superior and inferior quadrants for flux and superior and nasal quadrants for FI (P-values=0.007, 0.047, 0.011, 0.007, respectively); other quadrant differences were not significant. Conclusions Parameters from 4.5 scans generally outperformed those from 6.0 scans in the global and quadrant regions, suggesting greater digital resolution in 4.5 scans of the immediate peripapillary RPC is important in detecting glaucomatous changes.

Journal ArticleDOI
TL;DR: It is demonstrated that a clearer CC lobular capillary network is resolved in the angiograms provided by a larger beam size, concluding that the beam size is a key parameter for CC angiography if the purpose of the investigation is to visualize the individual CC capillaries.
Abstract: Imaging choriocapillaris (CC) is a long-term challenge for commercial OCT angiography (OCTA) systems due to limited transverse resolution. Effects of transverse resolution on the visualization of a CC microvascular network are explored and demonstrated in this paper. We use three probe beams with sizes of ~1.12 mm, ~2.51 mm and ~3.50 mm at the pupil plane, which deliver an estimated transverse resolution at the retina of 17.5 µm, 8.8 µm and 7.0 µm, respectively, to investigate the ability of OCTA to resolve the CC capillary vessels. The complex optical microangiography algorithm is applied to extract blood flow in the CC slab. Mean retinal pigment epithelium (RPE) to CC (RPE-CC) distance, mean CC inter-vascular spacing and the magnitude in the radially-averaged power spectrum are quantified. We demonstrate that a clearer CC lobular capillary network is resolved in the angiograms provided by a larger beam size. The image contrast of the CC angiogram with a large beam size of 3.50 mm is 114% higher than that with a small beam size of 1.12 mm. While the measurements of the mean RPE-CC distance and CC inter-vascular spacing are almost consistent regardless of the beam sizes, they are more reliable and stable with the larger beam size of 3.50 mm. We conclude that the beam size is a key parameter for CC angiography if the purpose of the investigation is to visualize the individual CC capillaries.

Journal ArticleDOI
TL;DR: The macular microvascular parameters on OCTA may serve as biomarkers of changes in the retinal periphery on WFA, and patients with FEVR demonstrated abnormalities in the macularmicrovasculature and capillary network, in addition to the peripheral retina.

Journal ArticleDOI
TL;DR: The results indicate that reduction in perfusion of the choroid in response to elevated IOP is delayed compared to that seen in the retina, and the superior image quality offered by SS-OCT may allow more comprehensive investigation of IOP-related ocular perfusion changes and their pathological roles in glaucomatous optic nerve damage.

Journal ArticleDOI
TL;DR: Choriocapillaris flow deficits were significantly greater in wet AMD subjects than age-similar normal subjects, suggesting that choroidal hypo-perfusion likely plays a role in the pathogenesis of neovascular AMD.
Abstract: Author(s): Keiner, Cathrine M; Zhou, Hao; Zhang, Qinqin; Wang, Ruikang K; Rinella, Nicholas T; Oldenburg, Catherine E; Duncan, Jacque L; Schwartz, Daniel M | Abstract: Purpose:To compare choriocapillaris flow voids (FV) in patients with neovascular age-related macular degeneration (AMD) with age-matched normal controls using swept-source optical coherence tomography angiography (SS-OCTA). Patients and methods:Eleven eyes of 11 subjects with neovascular AMD and 11 eyes of 11 age-similar normal subjects were imaged using SS-OCTA with a 6x6mm scanning pattern. Choriocapillaris FV, defined as a percentage of regions determined to have flow deficits divided by the total scanned region, was measured using a one standard deviation thresholding algorithm developed from a database of age-similar normal subjects. Results:Choriocapillaris FV was more extensive in patients with choroidal neovascularization (CNV) compared to age-similar normal subjects (FV: 20.56±4.95, 95% CI: 17.64-23.49 vs FV: 10.95±2.08, 95% CI: 9.73-12.18, respectively; P=0.0001). FV within a two-degree margin surrounding CNV in wet AMD subjects (FV: 35.04±9.34; 95% CI: 29.52-40.56) was increased compared to normal subjects (Pl0.001). FV of the region outside the two-degree margin surrounding CNV (FV: 19.61±6.08, 95% CI: 16.02-23.20) was increased compared to age-similar controls (P=0.0002). In neovascular AMD eyes, FV was greater within two degrees of the margin of CNV than in the remainder of the macula (margin: 35.04±9.34; outside: 19.61±6.08; P=0.002), and CNV lesion area was positively correlated with FV (correlation coefficient =0.84; 95% CI: 0.49-0.96; P=0.001). Conclusion:Choriocapillaris flow deficits were significantly greater in wet AMD subjects than age-similar normal subjects, suggesting that choroidal hypo-perfusion likely plays a role in the pathogenesis of neovascular AMD. Recognition of choriocapillaris flow deficits in patients with AMD may facilitate earlier diagnosis and identify alternative therapeutic targets for this multifactorial disease.

Journal ArticleDOI
TL;DR: In this article, a swept-source optical coherence tomography angiography (SS-OCTA) was used to quantify vessel tortuosity in patients with familial retinal arteriolar tortusosity.

Journal ArticleDOI
TL;DR: An overview of OCT as used in the otological research is provided, describing advances and different techniques in vibrometry, angiography, and structural imaging.
Abstract: Optical coherence tomography (OCT) has revolutionized physiological studies of the hearing organ, the vibration and morphology of which can now be measured without opening the surrounding bone. In this review, we provide an overview of OCT as used in the otological research, describing advances and different techniques in vibrometry, angiography, and structural imaging.

Journal ArticleDOI
TL;DR: Results suggest that SEW measurements may be a robust method to quantify elasticity in soft media, particularly in complex, bounded materials where dispersive Rayleigh-Lamb modes complicate measurements.
Abstract: We describe surface wave propagation in soft elastic media at speeds exceeding the bulk shear wave speed. By linking these waves to the elastodynamic Green's function, we derive a simple relationship to quantify the elasticity of a soft medium from the speed of this supershear evanescent wave (SEW). We experimentally probe SEW propagation in tissue-mimicking phantoms, human cornea ex vivo, and skin in vivo using a high-speed optical coherence elastography system. Measurements confirm the predicted relationship between SEW and bulk shear wave speeds, agreeing well with both theoretical and numerical models. These results suggest that SEW measurements may be a robust method to quantify elasticity in soft media, particularly in complex, bounded materials where dispersive Rayleigh-Lamb modes complicate measurements.

Proceedings ArticleDOI
01 Jul 2019
TL;DR: The photothrombotic stroke model in NHPs has the potential to enhance the understanding of perilesional neural dynamics and can be used to develop reliable neurorehabilitative therapeutic strategies to treat stroke.
Abstract: Ischemic stroke is a major cause of disability among adults worldwide. Despite its prevalence, few effective treatment options exist to alleviate sensory and motor dysfunctions that result from stroke. In the past, rodent models of stroke have been the primary experimental models used to develop stroke therapies. However, positive results in these studies have failed to replicate in human clinical trials, highlighting the importance of nonhuman primate (NHP) models as a preclinical step. Although there are a few NHP models of stroke, the extent of tissue damage is highly variable and dependent on surgical skill. In this study, we employed the photothrombotic stroke model in NHPs to generate controlled, reproducible ischemic lesions. Originally developed in rodents, the photothrombotic technique consists of intravenous injection of a photosensitive dye such as Rose Bengal followed by illumination of an area of interest to induce endothelial damage resulting in the formation of thrombi in the illuminated vasculature. We developed a quantitative model to predict the extent of tissue damage based on the light scattering profile of light in the cortex of NHPs. We then employed this technique in the sensorimotor cortex of two adult male Rhesus Macaques. In vivo optical coherence tomography imaging of the cortical microvasculature and subsequent histology confirmed the formation of focal cortical infarcts and demonstrated its reproducibility and ability to control the sizes and locations of light-induced ischemic lesions in the cortex of NHPs. This model has the potential to enhance our understanding of perilesional neural dynamics and can be used to develop reliable neurorehabilitative therapeutic strategies to treat stroke.

Journal ArticleDOI
TL;DR: The results suggest that neural activation evokes the spatial transit time homogenization within the capillary bed, which is regulated via both the heterogeneous acceleration of RBC flow and theheterogeneous increase of temporal RBC fluctuation, ensuring sufficient oxygenation during functional hyperemia.
Abstract: The cerebral vascular system provides a means to meet the constant metabolic needs of neuronal activities in the brain. Within the cerebral capillary bed, the interactions of spatial and temporal hemodynamics play a deterministic role in oxygen diffusion, however, the progression of which remains unclear. Taking the advantages of high-spatiotemporal resolution of optical coherence tomography capillary velocimetry designed with the eigen-decomposition statistical analysis, we investigated intrinsic red blood cell (RBC) velocities and their spatiotemporal adjustment within the capillaries permeating mouse cerebral cortex during electrical stimulation of contralateral hind paw. We found that the mean capillary transit velocity (mCTV) is increased and its temporal fluctuation bandwidth (TFB) is broadened within hind-paw somatosensory cortex. In addition, the degree to which the mCTV is increased negatively correlates with resting state mCTV, and the degree to which the TFB is increased negatively correlates with both the resting state mCTV and the TFB. In order to confirm the changes are due to hemodynamic regulation, we performed angiographic analyses and found that the vessel density remains almost constant, suggesting the observed functional activation does not involve recruitment of reserved capillaries. To further differentiate the contributions of the mCTV and the TFB to the spatiotemporally coupled hemodynamics, changes in the mCTV and TBF of the capillary flow were modeled and investigated through a Monte Carlo simulation. The results suggest that neural activation evokes the spatial transit time homogenization within the capillary bed, which is regulated via both the heterogeneous acceleration of RBC flow and the heterogeneous increase of temporal RBC fluctuation, ensuring sufficient oxygenation during functional hyperemia.