Frederic L. Lizzi

Theoretical framework for spectrum analysis in ultrasonic tissue characterization.

An analytic model is described for application in ultrasonic tissue characterization. The model is applicable to clinical broadband pulse echo systems. It treats spectra derived from received echo signals and relates them to physical tissue properties. The model can be applied to deterministic tissue structures (e.g., retinal detachments, larger blood vessels, and surface layers of the kidney) and to stochastic tissue structures (e.g., various tumors). The beam patterns included in the model are those generated by focused transducers typically used in high-resolution clinical ultrasound. Appropriate calibration procedures are also treated; these are needed for interpretation of absolute spectral parameters. The results obtained with the analytic model have been used to design a digital processing system and the associated techniques which are now being applied during examinations of the eye and abdominal organs. The results have proven useful in interpreting data from various types of tissues. To illustrate the application of these results, representative clinical data, obtained from the digital system, are presented for two types of tissue architectures. The first case is a detached retina representing a deterministic structure characterized by well-defined thickness and reflection coefficients. The second case is asteroid hyalosis and represents a stochastic entity in which the positions of small scattering particles are best described in statistical terms, and characterization is accompanied by means of normalized power spectra.

Relationship of Ultrasonic Spectral Parameters to Features of Tissue Microstructure

Absfract-&mlytical studies have been conducted to investigate the importance of specific tissue features in determining ultrasonic spectral “signatures” that have proven to be diagnostically useful. Three models of tissue microstructure were considered, and calibrated power spectra were computed for a series of scatterer sizes, concentrations, and acoustic impedances. General results were obtained, then specific parameters were employed to simulate studies of the eye and liver. These results were compared to clinical data-base information, and excellent correspondence was found. Studies using acoustic microscopy, test objects, and clinical data are continuing to refine the analytical model. I. INTRODUCTION U

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.

Radiation-force technique to monitor lesions during ultrasonic therapy.

This report describes a monitoring technique for high-intensity focused ultrasound (US), or HIFU, lesions, including protein-denaturing lesions (PDLs) and those made for noninvasive cardiac therapy and tumor treatment in the eye, liver and other organs. Designed to sense the increased stiffness of a HIFU lesion, this technique uniquely utilizes the radiation force of the therapeutic US beam as an elastographic push to detect relative stiffness changes. Feasibility was demonstrated with computer simulations (treating acoustically induced displacements, concomitant heating, and US displacement-estimation algorithms) and pilot in vitro experimental studies, which agree qualitatively in differentiating HIFU lesions from normal tissue. Detectable motion can be induced by a single 5 ms push with temperatures well below those needed to form a lesion. Conversely, because the characteristic heat diffusion time is much longer than the characteristic relaxation time following a push, properly timed multiple therapy pulses will form lesions while providing precise control during therapy.

Design and fabrication of a 40-MHz annular array transducer

This paper investigates the feasibility of fabricating a five-ring, focused annular array transducer operating at 40 MHz. The active piezoelectric material of the transducer was a 9-/spl mu/m thick polyvinylidene fluoride (PVDF) film. One side of the PVDF was metallized with gold and forms the ground plane of the transducer. The array pattern of the transducer and electrical traces to each annulus were formed on a copper-clad polyimide film. The PVDF and polyimide were bonded with a thin layer of epoxy, pressed into a spherically curved shape, then back filled with epoxy. A five-ring transducer with equal area elements and 100 /spl mu/m kerfs between annuli was fabricated and tested. The transducer had a total aperture of 6 mm and a geometric focus of 12 mm. The pulse/echo response from a quartz plate located at the geometric focus, two-way insertion loss (IL), complex impedance, electrical crosstalk, and lateral beamwidth all were measured for each annulus. The complex impedance data from each element were used to perform electrical matching, and the measurements were repeated. After impedance matching, f/sub c/ /spl sim/ 36 MHz and -6-dB bandwidths ranged from 31 to 39%. The ILs for the matched annuli ranged from -28 to -38 dB.

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.

Statistical framework for ultrasonic spectral parameter imaging

This study examines the statistics of ultrasonic spectral parameter images that are being used to evaluate tissue microstructure in several organs. The parameters are derived from sliding-window spectrum analysis of radiofrequency echo signals. Calibrated spectra are expressed in dB and analyzed with linear regression procedures to compute spectral slope, intercept and midband fit, which is directly related to integrated backscatter. Local values of each parameter are quantitatively depicted in gray-scale cross-sectional images to determine tissue type, response to therapy and physical scatterer properties. In this report, we treat the statistics of each type of parameter image for statistically homogeneous scatterers. Probability density functions are derived for each parameter, and theoretical results are compared with corresponding histograms clinically measured in homogeneous tissue segments in the liver and prostate. Excellent agreement was found between theoretical density functions and data histograms for homogeneous tissue segments. Departures from theory are observed in heterogeneous tissue segments. The results demonstrate how the statistics of each spectral parameter and integrated backscatter are related to system and analysis parameters. These results are now being used to guide the design of system and analysis parameters, to improve assays of tissue heterogeneity and to evaluate the precision of estimating features associated with effective scatterer sizes and concentrations.

Comparison of theoretical scattering results and ultrasonic data from clinical liver examinations

A theoretical analysis of soft-tissue ultrasonic scattering has been used to formulate specific results describing spectral parameters for tissue characterization. Results are applicable to clinical liver examinations. Three spectral parameters are mathematically expressed in terms of acoustic attenuation and the effective sizes, concentrations, and relative acoustic impedances of tissue scatters. Results from a clinical data base are shown to agree well with analytical results for each spectral parameter. Agreement is found for: spectral shapes; effects of attenuation; and correlations between parameters. Images of three spectral parameters are presented and their gray-scale features are evaluated with reference to analytical results.

Ultrasonic spectrum analysis for tissue evaluation

Spectrum analysis procedures have been developed to improve upon the diagnostic capabilities afforded by conventional ultrasonic images. These procedures analyze the frequency content of broadband, coherent echo signals returned from the body. They include calibration procedures to remove system artifacts and thereby provide quantitative measurements of tissue backscatter. Several independent spectral parameters have been used to establish databases for various organs; several investigations have shown that these parameters can be used with statistical classifiers to identify tissue type. Locally computed spectra have been used to generate sets of images displaying independent spectral parameters. Stained images have been derived by analyzing these parameter images with statistical classifiers and using color to denote tissue type (e.g., cancer). This report describes spectrum analysis procedures, discusses how measured parameters are related to physical tissue properties, and summarizes results describing estimator precision. It also presents illustrative clinical results showing how such procedures are being adapted to address specific clinical problems for a number of organs. This report indicates where further developments are needed and suggests how these techniques may improve image segmentation for three-dimensional displays and volumetric assays.

Therapeutic Ultrasound in the Treatment of Glaucoma: I. Experimental Model

Controlled ultrasonic energy was used to treat a series of laboratory animals in which glaucoma had been induced experimentally. Insonification successfully reduced elevated intraocular pressure in the majority (86%) of test animals. Histopathologic review of globes examined at varying time intervals following treatment showed localized thinning of the sclera with intact conjunctiva, allowing filtration and focal disruption of ciliary epithelium. This technique of treating elevated intraocular pressure in a noninvasive manner offers potential for clinical application in humans.