Very High-frequency Ultrasound Research Articles

Corneal Epithelial Thickness Mapping: A Major Review.

The corneal epithelium (CE) is the outermost layer of the cornea with constant turnover, relative stability, remarkable plasticity, and compensatory properties to mask alterations in the underlying stroma. The advent of quantitative imaging modalities capable of producing epithelial thickness mapping (ETM) has made it possible to characterize better the different patterns of epithelial remodeling. In this comprehensive synthesis, we reviewed all available data on ETM with different methods, including very high-frequency ultrasound (VHF-US) and spectral-domain optical coherence tomography (SD-OCT) in normal individuals, corneal or systemic diseases, and corneal surgical scenarios. We excluded OCT studies that manually measured the corneal epithelial thickness (CET) (e.g., by digital calipers) or the CE (e.g., by confocal scanning or handheld pachymeters). A comparison of different CET measuring technologies and devices capable of producing thickness maps is provided. Normative data on CET and the possible effects of gender, aging, diurnal changes, refraction, and intraocular pressure are discussed. We also reviewed ETM data in several corneal disorders, including keratoconus, corneal dystrophies, recurrent epithelial erosion, herpes keratitis, keratoplasty, bullous keratopathy, carcinoma in situ, pterygium, and limbal stem cell deficiency. The available data on the potential role of ETM in indicating refractive surgeries, planning the procedure, and assessing postoperative changes are reviewed. Alterations in ETM in systemic and ocular conditions such as eyelid abnormalities and dry eye disease and the effects of contact lenses, topical medications, and cataract surgery on the ETM profile are discussed.

Enhanced Diagnostics for Corneal Ectatic Diseases: The Whats, the Whys, and the Hows.

There are different fundamental diagnostic strategies for patients with ectatic corneal diseases (ECDs): screening, confirmation of the diagnosis, classification of the type of ECD, severity staging, prognostic assessment, and clinical follow-up. The conscious application of such strategies enables individualized treatments. The need for improved diagnostics of ECD is related to the advent of therapeutic refractive procedures that are considered prior to keratoplasty. Among such less invasive procedures, we include corneal crosslinking, customized ablations, and intracorneal ring segment implantation. Besides the paradigm shift in managing patients with ECD, enhancing the sensitivity to detect very mild forms of disease, and characterizing the inherent susceptibility for ectasia progression, became relevant for identifying patients at higher risk for progressive iatrogenic ectasia after laser vision correction (LVC). Moreover, the hypothesis that mild keratoconus is a risk factor for delivering a baby with Down's syndrome potentially augments the relevance of the diagnostics of ECD. Multimodal refractive imaging involves different technologies, including Placido-disk corneal topography, Scheimpflug 3-D tomography, segmental or layered tomography with layered epithelial thickness using OCT (optical coherence tomography), and digital very high-frequency ultrasound (VHF-US), and ocular wavefront. Corneal biomechanical assessments and genetic and molecular biology tests have translated to clinical measurements. Artificial intelligence allows for the integration of a plethora of clinical data and has proven its relevance in facilitating clinical decisions, allowing personalized or individualized treatments.

Abstract P509: Identification of Radial Vascular Wall Abnormalities by Very-high Frequency Ultrasound in Patients With Fibromuscular Dysplasia: The Fuchsia Study

Aim: This case-control study is aimed at identifying radial vascular wall abnormalities in patients with fibromuscular dysplasia (FMD). Methods: High-frequency ultrasound scans of the radial arteries and of FMD patients and healthy controls were obtained by Vevo MD (70 MHz probe, FUJIFILM, VisualSonics, Toronto, Canada). Radial wall showed in all individuals two echogenic interfaces: the 1 st ( lumen-media) and the 2 nd (media-adventitia). Intima-media (IMT), adventitia (AT), and global thickness (IMAT) were measured and wall cross-sectional area (WCSA) calculated. The disarray level of the two echogenic interfaces was assessed calculating the root mean square error (RMSE) between 20 gray-level profiles crossing the two interfaces and the profile obtained averaging them. For each echogenic interface, the RMSE was normalized for the maximum value of the corresponding mean profile (RMSE/mean). Results: 11 treated hypertensive female FMD patients and 8 healthy control women (C) were enrolled (age 52±5 vs 45±13 years, p=0.51; BMI 26±3 vs 23±3, p=0.12; mean BP 97±7 vs 85±10, p=0.01). Radial internal diameter was similar (1.938±0.432 vs 1.701±0.532 mm, p=0.21). IMT (0.166±0.037 vs 0.128±0.022 mm, p=0.03), AT (0.114±0.029 vs 0.083±0.019 mm, p=0.008) and IMAT (0.281±0.042 vs 0.211±0.027 mm, p=0.003) were higher in FMD. Wall/lumen ratio was similar and WCSA increased in FMD, calculated with either IMT or IMAT. The maximum values of 1 st (121±43 vs 157±22, p=0.09) and 2 nd interface 109 ±44 vs133±18, p=0.09) tended to be lower, whereas RMSE/mean was higher in FMD (1 st 1.31±0.24 vs 0.83±0.32, p=0.006; 2 nd 1.37±0.38 vs 0.94±0.32, p=0.03). The difference was attenuated for the 1 st but not for the 2 nd interface when considering age and mean BP as covariates (p=0.054 and p=0.016 respectively). Conclusions: Wall ultrastructure of radial arteries of hypertensive FMD patients showed eutrophic remodeling. Furthermore, a peculiar “blurred” pattern occurred, characterized of loss of echogenicity and inhomogeneity of the two echogenic layers, independent of age and mean BP.

Comparison of very-high-frequency ultrasound and spectral-domain optical coherence tomography corneal and epithelial thickness maps

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. Department of Ophthalmology, Columbia University Medical Center, New York, New York, USA. Comparative study. 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. 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). 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. 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.

Very high frequency ultrasound: New therapeutic method in aesthetic medicine and dermatology

Very high frequency ultrasound (VHF-US) is new therapy method with a broad application spectrum in dermatology and aesthetic medicine. In this method, ultrasound waves with frequencies over 10 MHz, which were for a long time only used in ultrasound diagnostics, are applied for therapeutic purposes. Such US waves demonstrate specific biophysical efficiencies which warrant their application for the treatment of the skin efflorescences, chronic wounds and hypertrophic scars as well as in anti-aging and skin improvement procedures in aesthetic medicine. VHF-US can be applied not only for stand-alone treatments, but also as a supportive pre- and posttreatment method in combination with laser, radiofrequency currents, injection lipolysis, etc. as well as in aesthetic plastic surgery.

Very High-frequency Ultrasound Analysis of Non-contact Holmium Laser Thermal Keratoplasty Treatment Spots

To objectively measure the corneal treatment spots in vivo using very high-frequency ultrasound (VHFU) after non-contact laser thermal keratoplasty (LTK) to better understand the variability and regression of refractive outcomes. In an institutional setting, VHFU was performed on 128 spots (8 eyes of 4 patients) using an immersion scanning technique 1 to 2 years after LTK with a single element focused transducer (50 MHz arc scanning ultrasound). Biometric techniques were used to evaluate the treatment spot depth, corresponding corneal thickness, and spot profile between patients, eyes (left/right), and by location on the cornea. The identical technique was used in a rabbit immediately after LTK to compare ultrasound versus histologic findings. The mean treatment spot penetration depth ranged between 0.373 and 0.533 mm, representing 64% to 78% of the corneal thickness compared to previous reports of 80% to 90%. Treatment spot depth, the corresponding corneal thickness, and percentage of overall cornea penetrated differed significantly across patients. Treatment spot depth was not significantly related to the level of applied laser energy (230 to 258 mJ) (0.082 Pearson sign). Spot profiles were not uniformly cone-shaped; W- and wedge-shaped were also identified. Ultrasound findings in the rabbit were similar to histology results and confirmed evidence of epithelial remodeling. Very high-frequency ultrasound of 128 treatment spots after non-contact LTK demonstrates epithelial remodeling and inconsistencies in penetration depth and profile.

Design and testing of an annular array for very-high-frequency imaging

Very-high-frequency ultrasound (VHFU) transducer technology is currently experiencing a great deal of interest. Traditionally, researchers have used single-element transducers which achieve exceptional lateral image resolution although at a very limited depth of field. A 5-ring focused annular array, a transducer geometry that permits an increased depth of field via electronic focusing, has been constructed. The transducer is fabricated with a PVDF membrane and a copper-clad Kapton film with an annular array pattern. The PVDF is bonded to the Kapton film and pressed into a spherically curved shape. The back side of the transducer is then filled with epoxy. One side of the PVDF is metallized with gold, forming the ground plane of the transducer. The array elements are accessed electrically via copper traces formed on the Kapton film. The annular array consists of 5 equal-area rings with an outer diameter of 1 cm and a radius of curvature of 9 mm. A wire reflector target was used to test the imaging capability of the transducer by acquiring B-scan data for each transmit/receive pair. A synthetic aperture approach was then used to reconstruct the image and demonstrate the enhanced depth of field capabilities of the transducer.

Imaging and Spectrum Analysis of Contrast Agents in the In Vivo Rabbit Eye Using Very-High–Frequency Ultrasound

We have conducted initial studies that demonstrated the feasibility of employing ultrasonic contrast agents with very-high–frequency ultrasound (VHFU), using wideband transducers with center frequencies near 40 MHz. These studies were undertaken with an ultimate objective of quantifying perfusion in vessels in the eye and other organs. We expanded the model developed by Lizzi et al (1983) to incorporate the scattering characteristics from encapsulated bubbles, such as contrast agents. Our analysis shows how the spectral slopes and intercepts measured from contrast agents are related to factors that include the radii and concentration of contrast-agent particles. We conducted in vitro experiments to validate the theoretical predictions and obtained excellent agreement. We obtained in vivo VHFU data from the eyes of anesthetized rabbits before and after injection of Albunex® and Aerosomes ™. Digitally computed B-mode images demonstrated echo enhancement within the ciliary body and its processes. The magnitudes of these enhancements were quantified using calibrated spectrum-analysis techniques.