High-resolution ultrasonic imaging and characterization of the ciliary body.

PURPOSE: To develop a means for noninvasive in vivo visualization of the ciliary processes using very-high-frequency (50 MHz) ultrasound and to develop quantitative morphologic descriptors that may relate to physiologic function. METHODS: The region of the ciliary body was scanned with very-high-frequency ultrasound, both in rabbits and in normal human subjects. Data were acquired in a series of planes so that the spacing between them was less than the beam width of the transducer in its focal plane. Three-dimensional perspective images were constructed, representing the anatomy of the angle region, including the ciliary processes. The automatically detected boundaries of the ciliary processes were analyzed to compute their periphery, area, shape factor, and fractal dimension. These measures were compared between the human and the rabbit eye and analyzed for periodicities related to the spacing of successive processes. RESULTS: Three-dimensional images allowed visualization of the radial arrangement of the processes. All biometric descriptors were significantly different between the rabbit and human eye and showed periodicities consistent with spacing between processes. CONCLUSIONS: The methods described in this report are sensitive descriptors of the state of the ciliary processes. These techniques may be of value in measurement of changes in the ciliary body associated with disease, medical therapy, and aging.

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.

Three-dimensional ultrasound imaging. Clinical applications.

OBJECTIVE: The aim of this report is to describe the technology of three-dimensional (3-D) ultrasonic imaging and its impact on improved diagnosis and monitoring of ocular disease. DESIGN: The authors reviewed techniques for acquiring and displaying 3-D ultrasound data of the eye. PARTICIPANTS: The authors applied these techniques to representative individual cases, including a choroidal hemorrhage, a ciliary body melanoma, a ciliary body detachment, a displaced posterior chamber intraocular lens, and topographic analysis of a normal cornea. INTERVENTION: A computer-controlled motion system was used to perform very high-frequency (VHF) (50-MHz) and conventional (10-MHz) digital 3-D ultrasound data collection. The scanning system allowed digitization of ultrasound data from a series of parallel planes. The 3-D data could be manipulated interactively to obtain two-dimensional images in any plane through the scan volume. The 3-D images were constructed by volume rendering and could be positioned for viewing from a variety of perspectives. The 3-D ultrasound parameter images representing acoustic scatterer properties were generated by spectrum analysis of digitized echo data. Color maps representing the contour and thickness of the epithelium and stroma of the central corneal were generated by digital signal processing of 3-D echo data. RESULTS: Quantitative volume measurement and biometric techniques enhanced the diagnostic and treatment planning information content in 3-D ultrasound images. The location and extent of hemorrhage and clots within the suprachoroidal space were shown with solid modeling. Volume changes in ciliary body melanoma over time were documented and 3-D ultrasound parameter image changes associated with radiation therapy observed. In ciliary body detachment, the extent of the detachment was shown. Solid modeling of a posterior chamber intraocular lens showed misplacement of the haptic in relation to the lens capsule remnants. Keratopachymetric maps showed the range and variance of thickness and local radius of curvature measurements in the cornea. CONCLUSIONS: Quantitative volume measurement and biometric tools combined with segmentation of 3-D ultrasound images improve diagnostic and treatment planning informational content of 3-D ultrasound images through improved localization of tissue structures.

Advances in ophthalmic ultrasound.

New ultrasound technologies, including three-dimensional imaging, tissue characterization, and very high frequency (50 MHz) ultrasound, have become available recently. We demonstrate how these technologies can be used alone and together to improve the use of ultrasound for diagnosis of ocular pathology.

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.

Ultrasonically induced hyperthermia for adjunctive treatment of intraocular malignant melanoma.

PURPOSE: This report describes results of a prospective pilot trial to evaluate the safety and efficacy of hyperthermia as an adjunct to enucleation or brachytherapy in the treatment of patients with intraocular malignant melanoma. METHODS: Twenty-five patients with intraocular malignant melanomas were treated with ultrasonically induced hyperthermia. In 14 patients, hyperthermia was administered before enucleation (median follow-up period, 44 months), and in 11 patients, hyperthermia was used as an adjunct to brachytherapy (median follow-up period, 79 months). RESULTS: Patient survival in each group was compared with that of a control group treated with enucleation or brachytherapy alone, using Kaplan-Meier and Cox analysis. Taking into account the simultaneous effects of tumor size and location, the relative risk ratios and 95% confidence bounds associated with adjunctive hyperthermia were 1.68 (range, 0.60-4.72) and 0.68 (range, 0.16-2.89) for the enucleation and brachytherapy groups, respectively. CONCLUSIONS: Patients receiving adjunctive hyperthermia with brachytherapy showed increased survival, whereas those receiving hyperthermia before enucleation showed decreased survival. Neither trend was statistically significant in this small series. The synergism of hyperthermia with radiation may offer the possibility of improved tumor management.

High frequency ultrasound imaging in pupillary block glaucoma.

BACKGROUND: The diagnosis of pupillary block glaucoma requires sufficient clarity of the ocular media. This is particularly important for assessment of both the presence and patency of an iridotomy, and the determination of central anterior chamber depth. METHODS: High frequency ultrasonography was used in three patients with suspected pupillary block to determine iris configuration, posterior chamber volume, and ciliary body conformation. RESULTS: All patients demonstrated high frequency ultrasonographic findings consistent with pupillary block: iris bombé, a formed posterior chamber, and a lack of anterior rotation of the ciliary processes. CONCLUSION: High frequency ultrasound imaging appears to be a valuable adjunct in making or corroborating the diagnosis of pupillary block glaucoma.

High-frequency ultrasound spectral parameter imaging of anterior corneal scars.

High frequency (50-MHz) ultrasound allows greater resolution (approximately 30 microns) and improved tissue differentiation of the anterior ocular structures than conventional (8-10 MHz) ultrasonic techniques. Spectral analysis of tissue acoustic backscatter is sensitive to both the concentration and size of tissue inhomogeneities. We studied the healing process of experimentally induced corneal scars using high frequency ultrasound spectral analysis. Scatterer size and concentration parameter images of scarred corneas showed distinctive patterns that were correlated with histology over time. This quantitative technique offers a new, noninvasive, in vivo method for the assessment of the internal microarchitecture of surgically altered corneal tissue and its healing dynamics.

Three-dimensional high-frequency 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.

Correlation of microcirculation architecture with ultrasound backscatter parameters of uveal melanoma.

Ultrasound tissue characterization parameters of size and acoustic concentration can be used to sub-classify uveal melanoma and estimate the patient's risk of death. Histologically determined microcirculation patterns have also been found to sub-classify uveal melanoma and predict patient's risk of death. This study examines the spatial relationship between tumor features detected by the two techniques. Three dimensional ultrasound images that depict the size and relative concentration of scattering elements in uveal melanoma within a range of approximately 50-120 microns were compared with PAS (without hematoxylin) stained histological sections graded and localized according to tumor microvascular patterns. Both ultrasound parameter imaging and histopathology were accomplished by workers masked to the other procedure. In three of five patients vascular networks were identified histopathologically. The predominant ultrasound feature seen in the regions of the histologically identified networks were clusters of scatterers in the range of approximately 50-80 microns. In the two cases without a network vascular pattern, lower range scatterers dominated the tumor volume. All the cases could be distinguished by the size and distribution of contiguous spatial clusters of acoustic scatterers. Scatterer size features detected in three dimensional ultrasound parameter images can identify tumor regions containing a specific microvascular pattern. Ultrasound tissue characterization features used to sub-classify uveal melanoma may have a biophysical basis related to patterns of tumor microcirculation.

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.

Measurement of ocular tumor volumes from serial, cross-sectional ultrasound scans.

A system has been developed to determine intraocular tumor volume, a characteristic that has been estimated in previous studies from linear dimensions using a variety of models. Volume was determined by tracing tumor boundaries in sequential, parallel ultrasound scans, adding the areas and multiplying by the interslice interval. The in vitro accuracy of the technique was within +/- 2%. The mean difference between volumes determined from replicate in vivo scans of intraocular tumors was 4.3%. Serial scan volumes were, on average, 19% smaller than volumes computed from an ellipsoidal model and 13% smaller than area-rotational volumes. Differences of as much as 50% were observed between serial scan volumes and volumes computed with these models. The results indicate that methods based on either linear measurements or the tumor area in a single cross-section will tend to both systematically overestimate tumor volume and suffer from unpredictable, nonsystematic errors.

Ophthalmic ultrasonography.

Definition and differentiation of ocular structures and abnormalities necessitates the use of high-frequency, high-resolution, and high-definition ultrasound. Frequencies of 10 to 100 MHz are being employed. Color Doppler imaging, tissue characterization, parameter image staining, and three-dimensional volume rendering are new and useful adjuncts to ocular diagnosis.

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.

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%).

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.

Histopathologic effects of ultrasonically induced hyperthermia in intraocular malignant melanoma.

Four cases of human intraocular malignant melanoma were treated with ultrasonically induced hyperthermia immediately before enucleation. Tumors were treated in two regimens: 30 minutes at 43 degrees to 45 degrees C and 5 minutes at greater than 50 degrees C. Temperatures were estimated from applied power levels, based on empirical data and mathematical models. Histopathologic changes observed in human tumors were compared with changes seen in malignant melanoma xenografts in athymic nude mice which were treated with ultrasonically induced hyperthermia for 30 minutes at 42 degrees to 46 degrees C. The effects of treatment were similar to changes seen in the animal model treated under analogous conditions: increased intercellular spacing, cytoplasmic vacuole formation, clumping of chromatin, breaks in cell membranes, and swelling and collapse of cells. Perivascular and peripheral zones sometimes showed decreased damage levels. The high temperature (greater than 50 degrees C) technique is presently being used as a means of "sterilizing" tumors before planned enucleation. The moderate temperature (43 degrees-45 degrees C) technique has been used in combination with radiotherapy to treat tumors when vision can be salvaged.

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.