Biomedical subjects
Publications and source records attributed to F L Lizzi.
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.
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.
Thirty-five rabbit eyes were implanted subchoroidally with Greene's hamster melanoma. When the tumours reached a base diameter of 5 mm, they were treated with ultrasonically induced hyperthermia with a range of temperatures and exposure durations (43-67 degrees C and 75 s to 60 min). Of the 23 treated eyes examined two months after treatment eight showed complete regression of the tumour. Seven showed initial tumour regression, but there was subsequent regrowth of tumour round the margins of the original mass. In eight eyes the tumour continued to grow, though in some cases the rate of growth appeared to be slower than in the controls. In contrast, in all untreated animals the tumour grew to fill the vitreous cavity. These preliminary findings indicate that ultrasonically induced hyperthermia can be an effective local treatment of this intraocular tumour model.
High-intensity focused ultrasound was employed to seal lens capsular tears in a rabbit model. Ultrasound therapy was applied either contiguously, thereby completely covering the tear, or in a discrete exposure pattern around the tear. Both methods prevented the formation of a generalised cataract. This was in contrast to results observed in a group of control (untreated) animals which all developed generalised lens opacities. Each control animal also developed a local lens opacity at the site of the capsular tear, as did half the animals treated with the discrete pattern. No animal treated with contiguous exposures developed any local or generalised traumatic-type cataract other than the small lens opacity immediately produced by the treatment. These treatment cataracts would not constitute a significant impediment to vision so long as they did not fall on the visual axis.
Quantitative microstructural sonography differs from conventional sonography in several ways. The frequency as well as the amplitude of echoes is recorded and assessed using spectral analysis techniques. The effects of diffraction of the ultrasound beam are calibrated, as are the transfer characteristics of the system. Studies of patients with alcoholic liver disease revealed significantly increased attenuation, heterogeneity of scatterers, and local scattering strength in those with severe disease; in contrast, patients with mild cirrhosis exhibited decreased local scattering strength compared to normal individuals. Using retrospective three-parameter discriminant analysis, 23 out of 24 patients were successfully categorized, suggesting that the parameters used were capable of measuring microstructural changes associated with these disease states. Parameters varied widely among 6 types of hepatic tumors, suggesting that this method may offer promise in distinguishing tumors from normal cases and alcoholic liver disease as well as from each other. Further applications and evaluation of this method appear justified.
Human intraocular tumors and tumors derived from human tumor cell lines grown subcutaneously in the athymic nude mouse were scanned by diagnostic ultrasound. Radiofrequency scan data were converted to digital form and analyzed in the frequency domain. Characteristics of normalized power spectra were found to be significantly different among human spindle cell malignant melanomas, mixed/epithelioid malignant melanomas, metastatic carcinomas, and hemangiomas. Significant differences, as well, were found between implanted primary skin malignant melanomas and adenocarcinomas of the lung, colon, and stomach. Comparison of spectral properties of human intraocular and implanted tumors revealed that human spindle cell malignant melanomas and implanted melanomas exhibit similar characteristics. Human intraocular metastatic tumors from the lung were found to exhibit characteristics similar to those of implanted lung tumors. These results indicate that the implantation of human tumor cell lines in the nude mouse may provide a very useful model for application of diagnostic and therapeutic ultrasound modalities to human intraocular tumors.
Mathematical evaluation techniques to derive the calibrated power spectrum of reflected ultrasonic echoes from ocular tumors can be used with a clinical computer system to objectively classify malignant melanoma and metastatic carcinoma of the eye. Sets of spectral data provide a reproducible standard for classification that closely approximates the Callender system used in histologic classification. We used spectral data with a computer data library to separate spindle B malignant melanomas (20 tests in 17 patients) from mixed-epithelioid melanomas (17 tests in 13 patients) and to identify metastatic carcinoma (20 tests in 17 patients) with approximately 98% reliability. Tissue structures can be acoustically stained in B-mode images to define the specific anatomic and structural properties that provide the acoustic differentiation. These data are obtained under in vivo conditions and allow a noninvasive classification of tumors in a way not previously possible, aiding in the definitive diagnosis of ocular tumors, as well as in the planning and monitoring of treatment.
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.
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A noninvasive procedure was used to treat membranes within the vitreous with controlled exposure to focused high-intensity ultrasound in rabbit eyes. Membranes were created by injecting small quantities of platelet-rich plasma into the vitreous of the intact globe of anesthetized rabbits. The average time for untreated membranes (controls and shams) to be resorbed was 34 days, whereas the average time to total resorption of membranes treated with ultrasound was 21 days. This comparison showed that high-intensity ultrasound was effective in accelerating the resorption of this type of vitreous membrane. This ultrasound technique is totally noninvasive and can be used without damage to other ocular tissues. Although this animal model departs in some respects from human vitreous membranes, eventual clinical applications are indicated in selected cases where vitrectomy must be delayed or is contraindicated. Noninvasive disruption of vitreous membranes by therapeutic ultrasound offers great promise for reducing the visual limitations produced by such membranes, and eliminating the sequence of disease leading to permanent visual loss.
We developed a system that permits exceptionally accurate measurements of human choroidal thickness in vivo by means of ultrasound. With minicomputer techniques, the complementary functions of the time and spectral domains of reflected sound can be used to permit measurements accurate to less than 20 mu at 10 MHz center frequency. Even more accuracy can be obtained with higher center frequencies. Choroidal thickness has been found to exceed that previously reported, with typical values of 420 mu found at the posterior pole. Even greater values are seen in regions outside the macula.
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After testing high intensity focused ultrasound on ocular tissues in animals, to obtain damage threshold equations, we used ultrasound for ocular therapy in experimental animals. We developed a therapeutic system for use in conjunction with a low=energy diagnostic ultrasound visualization technique. Our system included a spherical focused transducer operated at a frequency of 9.8 MHz to produce a focal spot 9 cm from the transducer surface. This technique produced controlled ocular tissue damage similar to that produced by laser and xenon are photocoagulation. It can be used to treat any level of tissue, ocular or orbital, and does not require media clarity. Specific tissue absorption properties necessary for laser damage were not required to produce the desired damage.
Lesions of the retina, choroid, and sclera were created in the proptosed eye of the rabbit with the use of focused ultrasound at 9.8 MHz. Exposure levels greatly exceeding those encountered in diagnostic systems were required. Histological examination of selected tissue samples, analysis of lesion-producing exposures, and lesion size variations suggest that thermal mechanisms are the principal cause of permanent tissue alterations. Subthreshold lesions, which consist of transitory effects, were observed. 'Threshold" lesions first manifested tansitory effects followed by permanent alterations which appeared within 24 hr. Suprathreshold lesions were evidenced by the immediate appearance of a highly blanched area with an overlying edema and occasional hemorrhage, appearing within 24 hr. The edema in these cases was resorbed within a few days, leaving behind a permanently blanched region. The threshold curve developed from these data is similar in shape to the threshold curve for light-induced lesions created with a commensurate focal spot.
In vivo animal experiments were performed to study the cataractogenic effects of high-frequency, high-intensity ultrasound. A series of anesthetized rabbits was insonified with quantified exposures of ultrasound using a 9.8 MHz focused ultrasonic beam. Ophthalmoscopic and slit lamp examinations revealed small haze cataracts as the first stage of lenticular damage. Larger exposures produced totally opaque cataracts. These first appeared as fine white threads surrounded by haze cataracts. The intensity-exposure time conjugates required to produce haze cataracts were determined over times ranging from 35 msec to 5 sec. At short times (under 100 msec) a relatively constant amount of energy was needed for cataract production. At longer times, the requried energy progressively increased. This observation, together with the physical appearance of these cataracts, suggests that those lesions are the result of thermal phenomena.
This report describes a system that allows amplitude information to be used as a third dimension or aspect of display on B-scan ultrasonograms. The relative strength of reflected echoes can be shown on B-scan by means of gray scale, color coding, or on A-scan with amplitude deflection. With this new technique, called isometric display, superimposition of the A-scan trace on the B-scan allows preservation of these amplitude characteristics. The three-dimensional presentation can be rotated around any azimuth to provide isometric viewing of the ultrasonogram. Tissue may then be characterized on a more reliable basis than is permitted by independent analysis of outline and amplitude features.
The velocity of sound determinations made in this study are the result of measurements accurate to 0.5 m/sec. The velocity of sound in a series of 50 cataractous lenses was found to be an average of 1,629 m/sec, 11 m/sec slower than that of normal adult lenses. The velocity of sound found in a smaller series of child lenses was 1,659 m/sec, 30 m/sec faster than the cataractous adult lens. It is postulated that this represents a trend of decreasing velocity of sound in the lens with increasing age.
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