PubMed HealthSearch

Biomedical subjects

F L Lizzi

Publications and source records attributed to F L Lizzi.

At least 19 recordsLinked to original sources

Computer model of ultrasonic hyperthermia and ablation for ocular tumors using B-mode data.

Computer simulations have been conducted to examine hyperthermia and ablation for treating ocular tumors. An interactive software package has been implemented that permits relevant tissue dimensions to be determined from B-mode data. This package also permits interactive beam positioning, and it provides image displays depicting computed absorbed doses and temperature rises. Results are presented showing how hyperthermia temperature patterns are influenced by beam position, beam geometry and frequency. Images showing ablative temperature rises at various time intervals are also presented. For hyperthermia, geometric models of beam profiles showed that a non-uniform beam pattern (with a central low-intensity region) can produce more uniform heating of small ocular tumors than a beam with a uniform intensity profile. For a given tumor, the uniformity of hyperthermia temperatures was found to be a function of frequency, with 4.75 MHz providing reasonably uniform results for typical tumor heights (near 7 mm). For ablation, diffraction computations were employed to calculate beam intensity profiles; results show an initially rapid rise in temperature levels with subsequent, slower heating beyond the -3-dB limits of the focal volume. The model is now being refined, and additional phenomena, including nonlinear propagation, will be incorporated.

Body Temperature

Computer simulations of ultrasonic heating for ocular therapy.

Computer simulations are being performed to model the temperature patterns produced during ultrasonically induced hyperthermia of ocular tumours. The software package for these simulations incorporates operator interaction and uses tissue geometry obtained from B-mode data. Previous studies used geometric approximations for the incident beams used for hyperthermia. In the current study, these beams were computed using diffraction analysis to obtain more realistic simulations of clinical exposures.

Body Temperature

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.

Brachytherapy

A new philosophy of medical imaging.

In general, the traditional approach to medical imaging is based on the solution of the inverse problem of deducing the characteristics of tissues within the body from the received field resulting from probing radiation. Ambiguities and lack of complete data, and physical limitations such as diffraction, field non-uniformity and so on, prevent the image from being an exact representation of what would be seen if the imaged part of the patient were to be exposed to direct vision or drawn by an artist. Much more exact representation could be produced, however, if the philosophy of imaging were to be changed to involve the solution of the forward problem in which the received field is iteratively compared with that calculated to be produced by a computer-simulated model of the object from a knowledge base of anatomy, pathology, histology, physical properties of tissues etc. As a result of this converging process of comparison and iterative minimisation of the difference signal, a model of the object would be simulated consistent with the received field resulting from probing radiation as well as with all the relevant information form a knowledge base containing general knowledge and also including the personal records of the particular patient. Using such a model, any required cross-section or three-dimensional pictorial representation of the region of interest in the investigated object could be displayed in the form of a pictorial image. Thus the proposed philosophy would make medical imaging much less subjective and increase its information value, because inherently it includes all relevant biomedical data in the displayed image.

Diagnostic Imaging

Histologic effects of contact ultrasound for the treatment of glaucoma.

The histologic effects of a contact ultrasound applicator were compared with those of the immersion applicator that is currently used clinically for the treatment of glaucoma. The applicator coupling cone uses a distensible rubber membrane that can be inflated to control stand-off distance relative to the surface of the eye. This feature allows the focal point of the therapeutic beam to be placed at selective depths. Histologic comparisons of lesions in rabbit and pig eyes showed lesions in the sclera and ciliary body that were similar to those produced by the immersion transducer when the same focal position was used. Moving the focal point to a greater depth resulted in less superficial damage, yet still produced ciliodestruction. Damage to the blood supply of the ciliary body, as found in human cadaver eyes, may be an additional mechanism of action of therapeutic ultrasound, and perhaps of other transscleral high-energy modalities.

Animals

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.

Eye Enucleation

Ultrasonic tissue characterization of blood clots.

Ultrasonic tissue characterization based on an analysis of the power spectrum of backscattered signals obtained with ultrasound was used to distinguish morphologic components of blood clots. The three morphologic features for which discrimination was attempted were loose fibrin, red-cell, and dense fibrin clots. The UTC was able to distinguish the morphologic blood components tested. This in vitro work was based on the analysis of parameters related to ultrasound-tissue interaction and on inferences related to the physical properties of scatterer properties (scatterer size, scatterer concentration, and ratio of scatterer to medium acoustic impedances). The ability to distinguish these blood-clot components suggests that UTC may be able to distinguish red from white thrombi and to assess the structures and changes within thrombi associated with the age of the thrombus, their mechanical properties, and treatment monitoring.

Blood Coagulation

Production of corneal lesions using high-intensity focused ultrasound.

In order to study the potential use of ultrasound as a noninvasive system for altering corneal curvature, we used high-density focused ultrasound at a frequency of 4.8 MHz and 7.9 MHz to produce corneal lesions in the rabbit eye. Intensity and duration threshold exposure conditions were determined for the production of minimally visible lesions. Threshold lesions were initially apparent as discrete white opacities resulting from stromal edema and disruption. Light and scanning electron microscopy of higher-energy, suprathreshold lesions revealed more extensive disruption, including the formation of a superficial stromal depression and a larger zone of edema and disorganization surrounding each lesion. Posterior stromal lamellae, endothelium, and Descemet's membrane were intact. Healing and reepithelialization resulted in a smooth corneal surface with no residual opacification. Threshold determinations predict safe exposure levels to the cornea during insonification of other ocular structures. Selective heating of the peripheral cornea using focused ultrasound may be a useful technique for correcting astigmatism.

Animals

In vivo thickness of the human detached retina by ultrasonic signal processing.

Fourier operations on digitized radio-frequency (rf) data can provide the most sensitive measure of the thickness of thin, deterministic structures such as membranes. After deconvolution against the system transfer function, the cepstrum and the analytic signal magnitude can provide measures of membrane thickness on the order of a half-wavelength. A total of 19 patients with rhegmatogenous retinal detachments were scanned using a diagnostic ultrasound system adapted for analog to digital conversion of rf data. Data were analyzed using the signal processing techniques described above to measure retinal thickness. Recent retinal detachments tended to be significantly thicker than normal attached retinas, and thickness decreased with the age of detachment. A statistically significant correlation was found to exist between retinal thickness and the duration of detachment.

Adolescent

Ultrasonically induced disruption and hemolysis of vitreous hemorrhages.

High-intensity focused ultrasound was used to insonify simulated vitreous hemorrhages in two in vitro models and one in vivo animal model. Histopathologic evaluation of the treatment effect was performed with light and electron microscopy. Ultrasonic parameters resulting in histopathologically proven disruption and hemolysis of intravitreal blood were investigated. Most important in obtaining this effect were the temporal average acoustic power and pulse repetition rate of the applied ultrasonic beam. Accurate positioning of the therapeutic beam and visualization of internal spatio-temporal response patterns in the blood during insonification were monitored via simultaneous diagnostic B-mode imaging. Results suggested that high-intensity focused ultrasound might facilitate the two major mechanisms involved in the natural resorption process of vitreous hemorrhages namely hemolysis and surface-dependent phagocytosis.

Animals

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.

Humans

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.

Animals

Analytical modelling of ultrasonically induced tissue heating.

Ultrasonically induced heating in biological tissues has been studied for decades because of its implications for the safety of diagnostic systems and for possible therapeutic applications. Analytical models have been developed to study heating for short-term, ablative exposures and for long-term hyperthermia exposures. These models account for many of the acoustic and thermal phenomena implicated in heating but several factors remain to be fully included. Excellent agreement has been found between model results and experimental lesions in the brain and eye. Future developments may provide new capabilities for computer simulations related to safety and therapy.

Animals

Histologic changes in porcine eyes treated with high-intensity focused ultrasound.

High-intensity focused ultrasound (HIFU) has recently been described in the treatment of patients with glaucoma. However, despite previous studies in animal and mathematical models, the mechanisms of action are not completely understood. We therefore undertook a histologic study of 15 porcine eyes to evaluate the effect of HIFU and, in particular, the changes seen after sequential insonification on previously treated areas of sclera. We demonstrated initial scleral swelling that was followed by scleral thinning. The scleral thinning could be maximized by a second superimposed course of HIFU. The most consistent change in the ciliary body was necrosis of the pars plana. Some treated animals developed a hemorrhagic retinal detachment that we believe to be due to the presence of a circumferential blood vessel, which runs in the ora serrata of the pig but which is not present in humans. Based on our observations, possible mechanisms of action of this treatment are discussed.

Animals

Ultrasonic hyperthermia and radiation in the management of intraocular malignant melanoma.

Hyperthermia and radiation were used in combination to treat four patients with choroidal malignant melanoma. This technique uses ultrasonically induced hyperthermia synergistically with radiation to destroy tumor cells. The lower levels of radiation used should avoid the late vascular and inflammatory complications seen in conventional radiation therapy. Tumors were scanned by a computerized diagnostic ultrasound system before treatment and assigned an acoustic tissue type on the basis of a statistical comparison of their ultrasound backscatter spectrum with spectra of tumors of known pathologic status. During the follow-up period, the longest of which was 15 months, all tumors demonstrated regression patterns consistent with choroidal tumors of the same acoustic tissue types treated with conventional radiation therapy.

Aged