Ronald H. Silverman

Design of efficient, broadband single-element (20-80 MHz) ultrasonic transducers for medical imaging applications

This paper discusses the design, fabrication, and testing of sensitive broadband lithium niobate (LiNbO/sub 3/) single-element ultrasonic transducers in the 20-80 MHz frequency range. Transducers of varying dimensions were built for an f# range of 2.0-3.1. The desired focal depths were achieved by either casting an acoustic lens on the transducer face or press-focusing the piezoelectric into a spherical curvature. For designs that required electrical impedance matching, a low impedance transmission line coaxial cable was used. All transducers were tested in a pulse-echo arrangement, whereby the center frequency, bandwidth, insertion loss, and focal depth were measured. Several transducers were fabricated with center frequencies in the 20-80 MHz range with the measured -6 dB bandwidths and two-way insertion loss values ranging from 57 to 74% and 9.6 to 21.3 dB, respectively. Both transducer focusing techniques proved successful in producing highly sensitive, high-frequency, single-element, ultrasonic-imaging transducers. In vivo and in vitro ultrasonic backscatter microscope (UBM) images of human eyes were obtained with the 50 MHz transducers. The high sensitivity of these devices could possibly allow for an increase in depth of penetration, higher image signal-to-noise ratio (SNR), and improved image contrast at high frequencies when compared to previously reported results.

ULTRASONIC SPECTRUM ANALYSIS FOR TISSUE ASSAYS AND THERAPY EVALUATION

Ultrasonic spectrum analysis procedures have been developed to measure tissue morphologic features that are not well depicted with conventional ultrasonography. This article reviews some of the applications of spectral techniques and provides an expanded theoretical framework showing how measured spectral features are related to the spatial autocorrelation function descriptive of tissue microstructure. Explicit relationships are obtained that describe how linear‐regression spectral parameters are related to the effective mean sizes, concentrations, and relative mechanical properties of scattering centers in tissue. In vitro, in vivo, and clinical results are presented illustrating how these techniques can be used to evaluate tissue alterations induced by ultrasonic hyperthermia and ablative treatments of tumors. These results show that ultrasonic spectrum analysis can provide quantitative information regarding changes in microstructure attributes. Spectral parameter images in two and three dimensions demonstrate how such procedures can map the spatial extent and severity of these changes, thereby providing a quantitative basis for assessing the results of tumor therapy.

Arc-scanning Very High-frequency Digital Ultrasound for 3D Pachymetric Mapping of the Corneal Epithelium and Stroma in Laser in situ Keratomileusis

PURPOSE To test and demonstrate measurement precision, imaging resolution, 3D thickness mapping, and clinical utility of a new prototype 3D very high-frequency (VHF) (50 MHz) digital ultrasound scanning system for corneal epithelium, flap, and residual stromal thickness after laser in situ keratomileusis (LASIK). METHODS VHF ultrasonic 3D data was acquired by arc-motion, meridional scanning within a 10-mm zone. Digital signal processing techniques provided high-resolution B-scan imaging, and I-scan traces for high-precision pachymetry in 4 eyes. Thickness maps of individual corneal layers were constructed. Reproducibility of epithelial, flap, and full corneal pachymetry was assessed for single-point and 3D thickness mapping by repeated measures. Thickness mapping of the epithelium, stroma, flap, and full cornea were determined before and after LASIK. Preoperative to postoperative difference maps for epithelium, flap, and stroma were produced to demonstrate anatomical changes in the thickness profile of each layer. RESULTS Surface localization precision was 0.87 microm. Central reproducibility for single-point pachymetry of epithelium was 0.61 microm; flap, 1.14 microm; and full cornea, 0.74 microm. Reproducibility for central pachymetry on 3D thickness mapping was 0.5 microm for epithelium and 1.5-microm for full cornea. B-scans and 3D thickness maps after LASIK demonstrated resolution of epithelial, stromal component of the flap, and residual stromal layers. Large epithelial profile changes were demonstrated after LASIK. Topographic variability of flap thickness and residual stromal thickness were significant. CONCLUSIONS VHF digital ultrasound arc-B scanning provides high-resolution imaging and high-precision three-dimensional thickness mapping of corneal layers, enabling accurate anatomical evaluation of the changes induced in the cornea by LASIK.

Stromal Thickness in the Normal Cornea: Three-Dimensional Display with Artemis Very High-Frequency Digital Ultrasound

PURPOSE To characterize the stromal thickness profile in a population of normal eyes. METHODS Stromal thickness profile was measured in vivo by Artemis very high-frequency digital ultrasound scanning (ArcScan, Morrison, Colo) across the central 10-mm corneal diameter on 110 normal eyes. Maps of the average, standard deviation, minimum, maximum, and range of stromal thickness were plotted. The average location of the thinnest stroma was found. The cross-sectional hemi-meridional stromal thickness profile was calculated using annular averaging. The absolute stromal thickness progression relative to the thinnest point was calculated using annular averaging as well as for 8 hemi-meridians individually. RESULTS The mean stromal thickness at the corneal vertex and at the thinnest point were 465.4+/-36.9 mum and 461.8+/-37.3 mum, respectively. The thinnest stroma was displaced on average 0.17+/-0.31 mm inferiorly and 0.33+/-0.40 mm temporally from the corneal vertex. The average absolute stromal thickness progression from the thinnest point could be described by the quadratic equation: stromal thickness = 6.411 x radius(2) + 2.444 x radius (R(2) = 0.999). Absolute stromal thickness progression was independent of stromal thickness at the thinnest point. The increase in hemi-meridional absolute stromal thickness progression was greatest superiorly and lowest temporally. CONCLUSIONS Three-dimensional thickness mapping of the corneal stroma and stromal thickness progression in a population of normal eyes represent a normative data set, which may help in early diagnosis of corneal abnormalities such as keratoconus and pellucid marginal degeneration. Absolute stromal thickness progression was found to be independent of stromal thickness.

Epithelial and corneal thickness measurements by high-frequency ultrasound digital signal processing

PURPOSE The authors determine the mean central corneal and epithelial thickness in a group of normal human subjects using a new high-frequency ultrasound technique, incorporating digital signal processing. METHOD Both eyes of ten volunteers (age range, 23-44 years) were scanned through a normal saline standoff. Digitized ultrasonic echo data were mathematically transformed to produce a plot, the I-scan, which optimally localizes acoustic interfaces to provide improved measurement precision. System precision was determined by analysis of variance of repeated measures. Central epithelial thickness was obtained by averaging multiple measurements. Central corneal thickness was determined by fitting measurements of apparent corneal thickness in consecutive parallel B-scans to a mathematically modeled cornea. A speed of sound of 1640 m/second was used. RESULTS Epithelial pachymetric precision using A-scan and I-scan was 4.8 and 2.0 microns (standard deviation), respectively. The mean epithelial thicknesses for the right and left eyes were 50.7 +/- 3.7 microns and 50.3 +/- 3.4 microns, respectively. The mean corneal thicknesses in the right and left eyes were 514.6 +/- 38.4 microns and 516.2 +/- 37.8 microns, respectively. The root mean-square differences in epithelial and corneal thickness between the left and right eyes of each subject were 1.3 and 7.7 microns, respectively (neither was statistically significant). CONCLUSION This system provides a pachymetric precision superior to current optical and ultrasound methods. Epithelial and corneal pachymetry is obtained noninvasively by a method that is not limited to optically clear media.

Therapeutic Ultrasound in the Treatment of Glaucoma: II. Clinical Applications

Focused, high-intensity therapeutic ultrasound was used to treat 69 selected patients with uncontrollably elevated intraocular pressure (IOP). This new technique selectively thins scleral collagen, and produces focal damage to the ciliary epithelium. These tissue modifications provide a reduction in IOP pressure to 25 mmHg or less in 83% of patients with a minimum three-month follow-up period.

Very high-frequency ultrasound corneal analysis identifies anatomic correlates of optical complications of lamellar refractive surgery: anatomic diagnosis in lamellar surgery.

OBJECTIVE To examine the utility of very high-frequency (VHF) ultrasound scanning in determining the anatomic changes and correlates of optical complications in lamellar refractive surgery. STUDY DESIGN Case series. PARTICIPANTS Cases analyzed included marked asymmetric astigmatism postautomated lamellar keratoplasty (ALK), image ghosting despite normal videokeratography post-ALK, uncomplicated myopic laser in situ keratomileusis (LASIK), and hyperopic LASIK with regression. METHODS A prototype VHF ultrasound scanner (50 MHz) was used to obtain sequences of parallel B-scans of the cornea. Digital signal processing techniques were used to measure epithelial, stromal, and flap thickness values in a grid encompassing the central 4 to 5 mm of the cornea, enabling pachymetric mapping of each layer with 2-micron precision. MAIN OUTCOME MEASURE The appearance of the corneas in VHF ultrasound images and thickness values of individual corneal layers determined from VHF ultrasound data. RESULTS VHF ultrasound resolved the epithelial, stromal cap, or flap and residual stromal layers 1 year after lamellar surgery. Asymmetric stromal tissue removal was differentiated from stromal cap irregularity. Epithelium acted to compensate for asymmetry of the stromal surface about the visual axis and for localized surface irregularities. Irregularities in the epithelial-stromal interface accounted for image ghosting present despite apparently normal videokeratography. Epithelial thickening was shown after uncomplicated myopic LASIK. Hyperopic LASIK demonstrated relative epithelial thickening localized to the region of ablation accounting for refractive regression. CONCLUSIONS VHF ultrasound shows promise as a sensitive method of determining the anatomic correlates of optical complications in lamellar refractive surgery.

Epithelial, Stromal, and Total Corneal Thickness in Keratoconus: Three-dimensional Display With Artemis Very-high Frequency Digital Ultrasound

PURPOSE To characterize the epithelial, stromal, and total corneal thickness profile in a population of eyes with keratoconus. METHODS Epithelial, stromal, and total corneal thickness profiles were measured in vivo by Artemis very high-frequency (VHF) digital ultrasound scanning (ArcScan) across the central 6- to 10-mm diameter of the cornea on 54 keratoconic eyes. Maps of the average, standard deviation, minimum, maximum, and range of epithelial, stromal, and total corneal thickness were plotted. The average location of the thinnest epithelium, stroma, and total cornea were found. The cross-sectional semi-meridional stromal and total corneal thickness profiles were calculated using annular averaging. The absolute stromal and total corneal thickness progressions relative to the thinnest point were calculated using annular averaging as well as for 8 semi-meridians individually. RESULTS The mean corneal vertex epithelial, stromal, and total corneal thicknesses were 45.7+/-5.9 microm, 426.4+/-38.5 microm, and 472.2+/-41.4 microm, respectively. The average epithelial thickness profile showed an epithelial doughnut pattern characterized by localized central thinning surrounded by an annulus of thick epithelium. The thinnest epithelium, stroma, and total cornea were displaced on average by 0.48+/-0.66 mm temporally and 0.32+/-0.67 mm inferiorly, 0.31+/-0.45 mm temporally and 0.54+/-0.37 mm inferiorly, and 0.31+/-0.43 mm temporally and 0.50+/-0.35 mm inferiorly, respectively, with reference to the corneal vertex. The increase in semi-meridional absolute stromal and total corneal thickness progressions was greatest inferiorly and lowest temporally. CONCLUSIONS Three-dimensional thickness mapping of the epithelial, stromal, and total corneal thickness profiles characterized thickness changes associated with keratoconus and may help in early diagnosis of keratoconus.

Corneal Pachymetric Topography

PURPOSE The authors developed a system for producing topographic pachymetric maps of the corneal epithelium and anterior scar tissue. METHOD The system uses high-frequency ultrasound scanning enhanced by digital signal processing. Ultrasonic echo data from consecutive parallel B-scans of the cornea spaced at 250-microns intervals are digitized and stored. Using the I-scan (obtained by computing the analytic signal magnitude of the deconvolved ultrasound signal), layer thickness measurements are made with a precision of 2 microns (standard deviation) at 120-microns intervals along each scan plane. The data are stored as an array, z(x,y), mapping thickness, z, onto horizontal and vertical (x,y) spatial coordinates. Pachymetric maps are then constructed by plotting local thickness, represented by a color scale, against measurement point position. RESULTS Examples of a normal cornea, a contact lens-wearing cornea, Reis-Bückler dystrophy, and postphotorefractive keratectomy are presented. Areas with significant subepithelial scarring and general epithelial thickening in a subject with Reis-Bückler dystrophy are mapped. Unevenness in the epithelial thickness profile of the cornea in a subject after photorefractive keratectomy is shown, relative to the fellow (untreated) cornea. CONCLUSION This technique provides the corneal surgeon with a new tool for the topographic evaluation of the thickness of anterior corneal layers in normal and pathologic corneas with high precision. In addition, the technique is not limited to optically transparent tissue.

Determination of size of aortic emboli and embolic load during coronary artery bypass grafting

BACKGROUND Embolic signals have been detected within both the aortic lumen and the intracranial vasculature during coronary artery bypass grafting. Total numbers of these emboli have been reported. The present study examined the size of individual emboli and the total volume of embolization. METHODS Using transesophageal echocardiography, we continuously monitored the aortic lumen of 10 patients undergoing isolated coronary artery bypass grafting. We manually analyzed 720,000 individual echo frames over a 4-minute period after the release of aortic clamps to track and to calculate the volume of 657 individual particles. The embolic load for the entire procedure was calculated from mean volume based on analysis of 1,508 particles. We simultaneously monitored the middle cerebral artery using transcranial Doppler ultrasonography and compared numbers of emboli detected by the two techniques. RESULTS Particle diameter ranged from 0.3 to 2.9 mm (mean, 0.8 mm), and particle volume from 0.01 to 12.5 mm3 (mean, 0.8 mm3). Twenty-eight percent of particles measured 1 mm or more, 44% measured 0.6 to 1.0 mm, and only 27% measured 0.6 mm or less in diameter. Aortic embolic load for the procedure ranged from 0.6 cm3 to 11.2 cm3 (mean, 3.7 cm3). Estimated cerebral embolic load for the procedure ranged from 60 to 510 mm3 (mean, 276 mm3). The fraction of aortic emboli entering the cerebral circulation was very variable (3.9% to 18.1%). Seventy-six percent of the embolic volume after the release of clamps occurred over a 20-second period. Only 1 patient was encephalopathic perioperatively. This patient had the largest estimated cerebral embolic load (510 mm3) and the second largest aortic embolic load (8.4 cm3). CONCLUSIONS We determined the size of individual intraaortic embolic particles and the total volume of embolization during coronary artery bypass grafting, and found the proportion entering the cerebral circulation to be very variable. The constitution of these particles and the neurologic impairment resulting from such embolization remains to be determined.