Ocular blood flow in preterm neonates Silverman, Ronald H; Urs, Raksha; Horowitz, Jason D ...
Scientific reports,
04/2024, Letnik:
14, Številka:
1
Journal Article
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Retinopathy of prematurity (ROP) is a disorder affecting low birthweight, preterm neonates. In the preterm eye, the retina is not fully developed and neovascularization may occur at the margin ...between the developed vascular retina and undeveloped avascular retina. Without timely treatment by laser or intravitreal anti-vascular endothelial growth factor (VEGF) therapy, this can lead to tractional retinal detachment and blindness. Visualization of the retina in regular examinations by indirect ophthalmoscopy is hence the current standard of care, but the exams are stressful and interpretation of images is subjective. The upregulation of VEGF in ROP would suggest an increase in ocular blood flow. In this report, we evaluate the potential of ultrafast plane-wave Doppler ultrasound (PWU) to detect increased flow velocities in the orbital vessels supplying the eye in a gentle exam with objective findings. We imaged both eyes of 50 low-birthweight preterm neonates using 18 MHz PWU. Flow velocity in the central retinal artery (CRA) and vein (CRV), and the short posterior ciliary arteries were determined and values at each ROP Stage compared. We found significantly increased velocities in the CRA and CRV in Stage 3 ROP eyes, where intervention would be considered. We compared multivariate models for identifying Stage 3 eyes comprised solely of clinical factors, solely of Doppler parameters, and clinical plus Doppler parameters. The respective models provided areas under their respective ROC curves of 0.760, 0.812, and 0.904. PWU Doppler represents a gentle, objective means for identifying neonates at risk for ROP that could complement ophthalmoscopy.
Elevated intraocular pressure (IOP) is the most prevalent risk factor for initiation and progression of neurodegeneration in glaucoma. Ocular hypertension results from increased resistance to aqueous ...fluid outflow caused by reduced porosity and increased stiffness of tissues of the outflow pathway. Acoustic activation and resulting bioeffects of the perfluorocarbon (PFC) nanodroplets (NDs) introduced into the anterior chamber (AC) of the eye could potentially represent a treatment for glaucoma by increasing permeability in the aqueous outflow track. To evaluate the potential of NDs to enter the outflow track, 100-nm diameter perfluoropentane (PFP) NDs with a lipid shell were injected into the AC of ex vivo pig eyes and in vivo rat eyes. The NDs were activated and imaged with 18- and 28-MHz linear arrays to assess their location and diffusion. NDs in the AC could also be visualized using optical coherence tomography (OCT). Because of their higher density with respect to aqueous humor, some NDs settled into the iridocorneal angle where they entered the outflow pathway. After acoustic activation of the NDs at the highest acoustic pressure, small gas bubbles were observed in the AC. After two days, no acoustic activation events were visible in the AC of the rats and their eyes showed no evidence of inflammation.
To assess the effectiveness of a keratoconus-detection algorithm derived from Artemis very high-frequency (VHF) digital ultrasound (ArcScan Inc., Morrison, CO) epithelial thickness maps in the fellow ...eye from a series of patients with unilateral keratoconus.
The study included 10 patients with moderate to advanced keratoconus in one eye but a clinically and algorithmically topographically normal fellow eye. VHF digital ultrasound epithelial thickness data were acquired and a previously developed classification model was applied for identification of keratoconus to the clinically normal fellow eyes. Pentacam (Oculus Optikgeräte, Wetzlar, Germany) Belin-Ambrósio Enhanced Ectasia Display "D" score (BAD-D) data (5 of 10 eyes), and Orbscan (Bausch & Lomb, Rochester, NY) SCORE data (9 of 10 eyes) were also evaluated.
Five of the 10 fellow eyes were classified as keratoconic by the VHF digital ultrasound epithelium model. Five of 9 fellow eyes were classified as keratoconic by the SCORE model. For the 5 fellow eyes with Pentacam and VHF digital ultrasound data, one was classified as keratoconic by the VHF digital ultrasound model, one (different) eye by a combined VHF digital ultrasound and Pentacam model, and none by BAD-D alone.
Under the assumption that keratoconus is a bilateral but asymmetric disease, half of the 'normal' fellow eyes could be found to have keratoconus using epithelial thickness maps. The Orbscan SCORE or the combination of topographic BAD-D criteria with epithelial maps did not perform better.
Purpose To compare corneal thickness and epithelial thickness measurements in maps obtained using the RTVue spectral domain optical coherence tomography (SD-OCT) system and the Artemis 2 immersion ...arc-scanning very-high-frequency ultrasound (VHF-US) system. Setting Department of Ophthalmology, Columbia University Medical Center, New York, New York, USA. Design Comparative study. Methods Eyes of normal volunteers were scanned with the SD-OCT system followed by the VHF-US system and then again by the SD-OCT system. On each map, the minimum corneal thickness and mean values of corneal thickness and epithelial thickness in the 3.0 mm radius zone and in 0.5 mm wide concentric annuli of up to a 3.0 mm radius around the corneal vertex were determined. Results Both eyes of 12 normal volunteers were scanned. The corneal thickness values from both devices were highly correlated ( R > 0.96); in the 3.0 mm radius zone, they were not statistically significantly different. There was no statistically significant change in epithelial thickness or corneal thickness in SD-OCT measurements taken before versus after immersion US. Although highly correlated ( R > 0.76), the SD-OCT epithelial thickness values were systematically thinner (1.7 ± 2.1 μm) than the VHF-US measurements in the 3.0 mm radius zone ( P < .01). Conclusions The corneal thickness measurements in the 3.0 mm radius zone in normal eyes were equivalent between the 2 systems. Although correlated, the VHF-US epithelial thickness measurements were systemically thicker than the SD-OCT values. Financial Disclosures Drs. Silverman and Reinstein have a commercial interest in Arcscan, Inc. Dr. Reinstein is a consultant to Carl Zeiss Meditec. None of the other authors has a financial or proprietary interest in any material or method presented.
Mapping of epithelial thickness (ET) is useful for detection of keratoconus, a disease characterized by corneal thinning and bulging in which epithelial thinning occurs over the apex. In prior ...clinical studies, optical coherence tomography (OCT) measurements of ET were systematically thinner than those obtained by 40-MHz high-frequency ultrasound (HFU) where a constant speed of sound (
) of 1636 m/s was used for all corneal layers. The purpose of this work was to study the acoustic properties, that is,
, acoustic impedance (
), and attenuation (
) of the corneal epithelium and stroma independently using a scanning acoustic microscope (SAM) to investigate the discrepancy between OCT and HFU estimates of ET.
Twelve unfixed pig corneas were snap-frozen and 6-μm sections were scanned using a custom-built SAM with an F-1.08, 500-MHz transducer and a 264-MHz bandwidth. Two-dimensional maps of
,
, and
with a spatial resolution of 4 μm were derived.
SAM showed that the value of
in the epithelium (i.e., 1548 ± 18 m/s) is substantially lower than the value of
in the stroma (i.e., 1686 ± 33 m/s).
SAM results demonstrated that the assumption of a constant value of
for all corneal layers is incorrect and explains the prior discrepancy between OCT and HFU ET determinations.
The findings of this study have important implications for HFU-based ET measurements and will improve future keratoconus diagnosis by providing more-accurate ET estimates.
Ophthalmic ultrasound imaging is currently performed with mechanically scanned single-element probes. These probes have limited capabilities overall and lack the ability to image blood flow. ...Linear-array systems are able to detect blood flow, but these systems exceed ophthalmic acoustic intensity safety guidelines. Our aim was to implement and evaluate a new linear-array-based technology, compound coherent plane-wave ultrasound, which offers ultrafast imaging and depiction of blood flow at safe acoustic intensity levels.
We compared acoustic intensity generated by a 128-element, 18-MHz linear array operated in conventionally focused and plane-wave modes and characterized signal-to-noise ratio (SNR) and lateral resolution. We developed plane-wave B-mode, real-time color-flow, and high-resolution depiction of slow flow in postprocessed data collected continuously at a rate of 20,000 frames/s. We acquired in vivo images of the posterior pole of the eye by compounding plane-wave images acquired over ±10° and produced images depicting orbital and choroidal blood flow.
With the array operated conventionally, Doppler modes exceeded Food and Drug Administration safety guidelines, but plane-wave modalities were well within guidelines. Plane-wave data allowed generation of high-quality compound B-mode images, with SNR increasing with the number of compounded frames. Real-time color-flow Doppler readily visualized orbital blood flow. Postprocessing of continuously acquired data blocks of 1.6-second duration allowed high-resolution depiction of orbital and choroidal flow over the cardiac cycle.
Newly developed high-frequency linear arrays in combination with plane-wave techniques present opportunities for the evaluation of ocular anatomy and blood flow, as well as visualization and analysis of other transient phenomena such as vessel wall motion over the cardiac cycle and saccade-induced vitreous motion.
To develop and evaluate automated computerized algorithms for differentiation of normal and keratoconus corneas based solely on epithelial and stromal thickness data.
Maps of the corneal epithelial ...and stromal thickness were generated from Artemis-1 very high-frequency ultrasound arc-scans of 130 normal and 74 keratoconic subjects diagnosed by combined topography and tomography examination. Keratoconus severity was graded based on anterior curvature, minimum corneal thickness, and refractive error. Computer analysis of maps produced 161 features for one randomly selected eye per subject. Stepwise linear discriminant analysis (LDA) and neural network (NN) analysis were then performed to develop multivariate models based on combinations of selected features to correctly classify cases. The sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were determined for each classifier.
Stepwise LDA resulted in a six-variable model that provided an AUC of 100%, indicative of complete separation of keratoconic from normal corneas. Leave-one-out analysis resulted in 99.2% specificity and 94.6% sensitivity. Neural network analysis using the same six variables resulted in an AUC of 100% for the training set. Test set performance averaged over 10 trials gave a specificity of 99.5 ± 1.5% and sensitivity of 98.9 ± 1.9%. The LDA function values correlated with keratoconus severity grade.
The results demonstrate that epithelial remodeling in keratoconus represents an independent means for differentiation of normal from advanced keratoconus corneas.
Preclinical imaging, especially of rodent models, plays a major role in experimental ophthalmology. Our aim was to determine if ultrasound can be used to visualize and measure flow dynamics in the ...retrobulbar vessels supplying and draining the eye and the potential of contrast microbubbles to provide image and measurement enhancement. To accomplish this, we used a 128-element, 18 MHz linear array ultrasound probe and performed plane-wave imaging of the eyes of Sprague Dawley rats. Compound images were acquired by emitting unfocused wavefronts at multiple angles and combining echo data from all angles to form individual B-scans. Multiple imaging sequences were utilized, compounding up to six angles, with imaging rate of up to 3000 compound B-scans per second and sequence durations from 1.5 to 180 s. Data were acquired before and after intravenous introduction of contrast microbubbles. We found the total power of the Doppler signal in the image plane to increase approximately 20 fold after injection of contrast, followed by an exponential decay to baseline in about 90 s, The best-fit time constant of the decay averaged 41 s. While major vessels and the retinal/choroidal complex were evident pre-contrast, they were dramatically enhanced with contrast present, with details such as choroidal arterioles seen only with contrast. Ocular arteriovenous transit time determined from comparative enhancement curves in arteries and veins was approximately 0.2 s. In conclusion, plane wave ultrasound, especially with enhancement by contrast microbubbles, offers a means for the study of ocular hemodynamics using the rat eye as a model.
•Blood-flow in the retrobulbar vessels of the rat eye was visualized using plane-wave ultrasound.•Spectrograms allowed determination of arterial and venous velocities over the cardiac cycle.•Intravenous contrast microbubbles enhanced visualization of blood-flow.•After initial peak, contrast enhancement declined exponentially.•Tail-vein to eye and arteriovenous ocular transit time were measured.
Most studies of the effect of acute elevation of intraocular pressure (IOP) on ocular blood-flow have utilized optical coherence tomography (OCT) to characterize retinal and choroidal flow and ...vascular density. This study investigates the effect of acute IOP elevation on blood flow velocity in the retrobulbar arteries and veins supplying and draining the eye, which, unlike the retinal and choroidal vasculature, are not directly compressed as IOP is increased. By cannulation of the anterior chamber of 20 Sprague-Dawley rats, we increased IOP in 10 mmHg steps from 10 to 60 mmHg and returned to 10 mmHg. After 1 min at each IOP (and 3 min after return to 10 mmHg), we acquired 18 MHz plane-wave ultrasound data at 3000 compound images/sec for 1.5 s. We produced color-flow Doppler images by digital signal processing of the ultrasound data, identified retrobulbar arteries and veins, generated spectrograms depicting flow velocity over the cardiac cycle and characterized changes of vascular density and perfusion in the orbit overall. Systolic, diastolic and mean velocities and resistive and pulsatile indices were determined from arterial spectrograms at each IOP level. Baseline mean arterial and mean venous velocities averaged 30.9 ± 10.8 and 8.5 ± 3.3 mm/s, respectively. Arterial velocity progressively decreased and resistance indices increased at and above an IOP of 30 mmHg. Mean arterial velocity at 60 mmHg dropped by 55% with respect to baseline, while venous velocity decreased by 20%. Arterial and venous velocities and resistance returned to near baseline after IOP was restored to 10 mmHg. Both vascular density and orbital perfusion decreased with IOP, but while perfusion returned to near normal when IOP returned to 10 mmHg, density remained reduced. Our findings are consistent with OCT-based studies showing reduced perfusion of the retina at levels comparable to retrobulbar arterial flow velocity change with increased IOP. The lesser effect on venous flow is possibly attributable to partial collapse of the venous lumen as volumetric venous outflow decreased at high IOP. The continued reduction in orbital vascular density 3 min after restoration of IOP to 10 mmHg might be attributable to persisting narrowing of capillaries, but this needs to be verified in future studies.
•Retrobulbar blood flow of the rat eye was measured by ultrasound at intraocular pressures (IOP) from 10 to 60 mmHg.•The retrobulbar vasculature was not directly compressed by elevated IOP.•Arterial velocities decreased markedly at and above an IOP of 30 mmHg, dropping by over 50% at 60 mmHg.•Arterial pulsatility increased with increasing IOP.•Orbital perfusion (total Doppler power) decreased with increasing IOP.
Preeclampsia (PE) is a severe complication of pregnancy characterized by hypertension, proteinuria and compromised fetal blood supply. The eye, like other end organs, is affected by this systemic ...condition, but unlike in other organs, ocular media transparency allows high-resolution optical visualization of the vascular structure of the retina. Our aim was to assess how ultrasound-determined ocular blood-flow correlates with vascular structure of the retina and choriocapillaris determined by optical coherence tomography angiography (OCTA).
Plane-wave ultrasound and OCTA were performed on both eyes of 40 consecutive subjects consisting of normal controls (n = 11), mild PE (n = 5), severe PE (n = 17) and chronic or gestational hypertension (n = 7) within 72 hours following delivery. From ultrasound, we measured pulsatile flow velocity and resistance indices in the central retinal artery (CRA) and vein, the short posterior ciliary arteries (SPCAs) and choroid. From OCTA, we measured vascular density (VD) in the superficial, deep retina and choriocapillaris. We determined differences in Doppler and OCTA parameters among groups and correlations between ultrasound and OCTA.
In severe PE, flow resistance was reduced with respect to controls. Flow velocity and resistance in the and SPCA were moderately correlated with VD in the choriocapillaris and peripapillary retina, but VD in PE did not differ significantly from controls.
Although OCTA parameters were moderately correlated with Doppler ultrasound, OCTA did not demonstrate significant differences between PE and controls postpartum.
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