Mark J. Rondeau

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.

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.

Management of Intraocular Foreign Bodies

Thirty-five consecutive cases of perforating ocular injuries with retained intraocular foreign body (IOFB) are examined in this retrospective study. Of the 35 cases with injuries, 30 (86%) were due to metallic foreign bodies. Of these, 25 (83%) involved foreign bodies of ferromagnetic origin. Magnetic extraction in combination with pars plana vitrectomy (or when possible, magnetic extraction alone) was successfully used to remove these foreign bodies. Even in cases where posterior vitrectomy is indicated, magnetic extraction allows good control of the foreign body during removal minimizing surgical trauma and the subsequent postoperative inflammatory response.

Correlations of Acoustic Tissue Typing of Malignant Melanoma and Histopathologic Features as a Predictor of Death

Forty-six eyes with uveal melanoma were scanned with a computerized diagnostic ultrasound system before enucleation, and light microscope sections were obtained. Tumors were characterized by ultrasonically measured dimensions and power spectrum analysis, which provided information not available in conventional A- or B-scan ultrasonography. Histopathologic features, including cell clustering pattern, cell type, pigmentation, vascularity, and necrosis, were quantified. Statistically significant correlations were found between parameters derived from the power spectrum and histologic characteristics. Patients were followed up for up to ten years with 14 deaths occurring because of metastases. Using a Cox relative risk model with histopathologic data, a risk model comprising pigmentation and cell type (P less than .0001) was obtained. Using ultrasonic characteristics, a model comprising tumor volume and scatterer concentration (P = .0062) was obtained. The results suggest that ultrasonic tissue characterization and three-dimensional biometry may provide improved in vivo prognostic indicators for uveal melanoma.

Measurement of choroidal perfusion and thickness following systemic sildenafil (Viagra

Purpose:  To demonstrate anatomic and physiologic changes in the human choroid following systemic sildenafil citrate (Viagra®) using enhanced depth imaging spectral domain–optical coherence tomography (EDI‐OCT) and swept‐scan high‐frequency digital ultrasound.

Three-dimensional Highfrequency Ultrasonic Parameter Imaging of Anterior Segment Pathology

PURPOSE High-frequency ultrasound allows high-resolution imaging of anterior segment anatomy and pathology. Acoustic echo data, however, contain information relating to the microanatomic structure of the interrogated tissue which is not evident in B-mode images. The aim of this study is to develop imaging techniques to demonstrate and quantify the distribution of acoustic scattering properties in ocular tissues in three dimensions. METHODS A tumor of the iris and a hyphema were scanned using a 50-MHz ultrasound probe mounted on a computer-controlled two-axis positioning system. Scan data from sequential parallel planes were used to make three-dimensional reconstructions. Digital signal processing and a mathematical model of acoustic backscatter then were used to represent the effective size and acoustic concentration of scattering elements using a false color representation superimposed on B-mode images. RESULTS Three-dimensional reconstructions improved appreciation of the size and extent of pathology and allowed computation of tissue volumes. Parameter images demonstrated distinctive differences between diffuse and organized blood and allowed quantification of tumor scattering properties. CONCLUSIONS Three-dimensional imaging of the anterior segment with high-frequency ultrasound allows construction of perspective images, which adds to the already significant clinical use of individual high-resolution B-mode images. Acoustic backscatter properties determined by tissue microstructure can be computed from echo data and represented in false color in three-dimensional reconstructions.

Therapeutic Ultrasound for the Treatment of Glaucoma

A multicenter clinical trial of therapeutic ultrasound for the treatment of glaucoma included 20 centers in the United States in which 1,117 treatments were performed on 880 eyes. The study was limited to patients with refractory glaucoma who had not benefited from conventional medical and surgical techniques. Approximately 782 of 1,117 treatments (70%) showed an initial decrease in intraocular pressure from a pretreatment mean of 38.1 mm Hg to 22 mm Hg or less. By Kaplan-Meier survival analysis, the single treatment success rate (intraocular pressure between 6 and 22 mm Hg) was 48.7% at six months posttreatment. When retreatment was used subsequent to failure, the one-year multitreatment success rate was 79.3%. The most common complications were an immediate posttreatment intraocular pressure increase lasting a few hours and mild iritis. Other complications included scleral thinning in 28 of 1,117 treatments (2.5%) and phthisis bulbi in 12 of 1,117 treatments (1.1%).

Ultrasonic tissue characterization of uveal melanoma and prediction of patient survival after enucleation and brachytherapy

We performed survival studies on 136 patients with uveal malignant melanoma who were examined with ultrasonic tissue characterization before treatment with cobalt-60 brachytherapy (74 patients) or enucleation (62 patients). Mean follow-up time was 58.7 months for the brachytherapy group and 59.0 months for the enucleated group. The maximal follow-up time was nearly ten years. Univariate survival analysis showed that patients with small tumors (less than 250 mm3, 49 patients) had a higher five-year survival when treated with brachytherapy than when treated with enucleation. No patients in this study with tumor volumes greater than 1,500 mm3 (13 patients) were treated with brachytherapy. For tumors of intermediate size (74 patients), survival analysis did not indicate appreciable differences between the treatment options. However, multivariate models including two ultrasonic tissue characterization variables, scatterer size and concentration, showed appreciable intergroup differences in the dependence of survival on these factors. Results suggest that tissue properties detectable with ultrasonic techniques are related to differences in patient survival and may be used for treatment planning for tumors of intermediate size.

Correlation of ultrasound parameter imaging with microcirculatory patterns in uveal melanomas

Previous studies demonstrated a correlation between acoustic backscatter parameters and survival in ocular melanoma. The histologic presence of microvascular networks in ocular melanoma is also associated with death from metastases. This study tests the hypothesis that melanomas grouped on the basis of these microvascular patterns are separable by ultrasound spectrum analysis. We scanned 40 melanomas using a 10-MHz ultrasound unit equipped for digitization of radio frequency data. After enucleation, tumors were sectioned in planes corresponding to the ultrasonographic examination and stained to demonstrate microcirculation. Acoustic spectral parameters were compared between 14 melanomas with a nevuslike microcirculation and 26 with foci of high-risk microvascular structures. Smaller scatterer size, lower acoustic concentration and greater spatial variability were found to correlate with high-risk microvascular patterns and areas of cystic degeneration. We suggest that nonvascular extracellular matrix components associated with microvessels may be responsible for the correlation of acoustic parameters with microvascular pattern and distribution.