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L A Frizzell

Publications and source records attributed to L A Frizzell.

At least 19 recordsLinked to original sources

Superthreshold behavior of ultrasound-induced lung hemorrhage in adult mice and rats: role of pulse repetition frequency and exposure duration.

Superthreshold behavior for ultrasound-induced lung hemorrhage was investigated in adult mice and rats at an ultrasound center frequency of 2.8 MHz to assess the role of pulse repetition frequency and exposure duration. One hundred fifty, 6-7-week-old female ICR mice and 150 10-11-week-old female Sprague-Dawley rats were each divided into 15 exposure groups (10 animals per group) for a 3 x 5 factorial design (3 exposure durations of 5, 10, and 20 s and 5 pulse repetition frequencies of 25, 50, 100, 250, and 500 Hz). The in situ (at the pleural surface) peak rarefactional pressure of 12.3 MPa and the pulse duration of 1.42 micros were the same for all ultrasonically-exposed animals. In addition, 15 sham exposed mice and 15 sham exposed rats were included into both studies. In each study of 165 animals, the exposure conditions were randomized. The lesion depth and surface area were measured for each animal, as well as the percentage of animals with lesions per group. The characteristics of the lesions produced in mice and rats were similar to those described in studies by our research group and others, suggesting a common pathogenesis for the initiation and propagation of the lesions at the gross and microscopic levels. The proportion of lesions in both species was related statistically to pulse repetition frequency (PRF) and exposure duration (ED), with the exception that PRF in rats was not quite significant; the PRF x ED interaction (number of pulses) for lesion production was not significant for either species. The PRF, but not ED, significantly affected lesion depth in both species; the PRF x ED interaction for depth was not significant for either species. Both PRF and ED significantly affected lesion surface area in mice, while neither affected area in rats; the PRF x ED interaction for surface area was not significant for either species.

Analysis of Variance↗

Temporal and spatial evaluation of lesion reparative responses following superthreshold exposure of rat lung to pulsed ultrasound.

This study characterized the reparative responses in rat lung. Forty-five adult female rats were exposed at two sites over the left lung to 3.1-MHz superthreshold pulsed ultrasound. The repair of lung lesions was evaluated from 0 through 44 days postexposure. Macroscopic lesions at 0 days postexposure were large bright red ellipses of hemorrhage. By 1 and 3 days postexposure, lesions were the same size and dark red to red-black, but, by 3 days postexposure, lesions had a raised surface appearance. From 5 to 10 days postexposure, lesions grew smaller in size, progressed from red-gray to yellow-brown, and retained a raised surface appearance. From 13 through 44 days postexposure, lesions gradually decreased in size, had a faint yellow-brown discoloration, and gradually lost the raised surface appearance. By 37 and 44 days postexposure, lung returned to near normal morphology, but had small areas of light yellow-brown discoloration in the areas where lung was exposed. Microscopic lesions at 0 and 1 days postexposure were areas of acute alveolar hemorrhage. By 3 days postexposure, lesions had loss of alveolar erythrocytes and the formation of hemoglobin crystals. From 5 through 44 days postexposure, iron in degraded erythrocytes was processed to hemosiderin and was negligible in quantity at 44 days postexposure. The proliferation of resident cells (likely alveolar epithelial cells, fibroblasts and endothelial cells) and the infiltration of inflammatory cells in lesions declined in intensity as the lesions aged and was minimal by 44 days postexposure. Under the superthreshold exposure conditions described, lesions induced by ultrasound do not seem to have long-term residual effects in lung.

Animals↗

Superthreshold behavior and threshold estimation of ultrasound-induced lung hemorrhage in adult mice and rats.

Threshold estimates and superthreshold behaviors for ultrasound-induced lung hemorrhage were investigated as a function of species (adult mice and rats) and ultrasound frequency (2.8 and 5.6 MHz). A total of 151 6-to-7-week-old female ICR mice and 160 10-to-11-week-old female Sprague-Dawley rats were randomly divided into two ultrasonic frequency groups, and further randomly divided into seven or eight ultrasonic peak rarefactional pressure groups. Each group consisted of about 10 animals. Animals were exposed to pulsed ultrasound at either 2.8-MHz center frequency (1-kHz PRF, 1.42-microsecond pulse duration) or 5.6-MHz center frequency (1-kHz PRF, 1.17-microsecond pulse duration) for a duration of 10 seconds. The in situ (at the pleural surface) peak rarefactional pressure levels ranged between 2.5 and 10.5 MPa for mice and between 2.3 and 11.3 MPa for rats. The mechanical index (MI) ranged between 1.4 and 6.3 at 2.8 MHz for mice and between 1.1 and 3.1 at 5.6 MHz for rats. The lesion surface area and depth were measured for each animal as well as the percentage of animals with lesions per group. The characteristics of the lesions produced in mice and rats were similar to those described in previous studies by our research group and others, suggesting a common pathogenesis in the initiation and propagation of the lesions at the gross and microscopic levels. The percentage of animals with lesions showed no statistical differences between species or between ultrasound frequencies. These findings suggest that mice and rats are similar in sensitivity to ultrasound-induced lung damage and that the occurrence of lung damage is independent of frequency. Lesion depth and surface area also showed no statistically significant differences between ultrasound frequencies for mice and rats. However, there was a significant difference between species for lesion area and a suggestive difference between species for lesion depth. The superthreshold behavior of lesion area and depth showed that rat lung had more damage than mouse lung, and the threshold estimates showed a weak, or lack of, frequency dependency, suggesting that the MI is not consistent with the observed findings.

Animals↗

Attenuation coefficient estimates of mouse and rat chest wall.

Attenuation coefficients of intercostal tissues were estimated from chest walls removed postmortem (pm) from 41 6-to-7-week-old female ICR mice and 27 10-to-11-week-old female Sprague-Dawley rats. These values were determined from measurements through the intercostal tissues, from the surface of the skin to the parietal pleura. Mouse chest walls were sealed in plastic wrap and stored at 4 degrees C until evaluated, and rat chest walls were sealed in Glad-Lock Zipper sandwich bags, and stored at -15 degrees C. When evaluated, chest wall storage time ranged between 1 and 2 days pm for mice and between 41 and 110 days pm for rats. All chest walls were allowed to equilibrate to 22 degrees C in a water bath prior to evaluation. For both mouse and rat intercostal tissues, the estimated frequency normalized attenuation coefficient was 1.1 dB/cm-MHz. In order to determine if there was an effect of storage time on estimates of attenuation coefficient, an independent experiment was conducted. The intercostal tissues from six mouse chest walls were evaluated at three time points (1, 22, and 144 days pm), and from six rat chest walls were evaluated at four time points (1, 22, 50, and 125 days pm). There was no difference in the estimated intercostal tissue attenuation coefficient as a function of time postmortem.

Animals↗

Superthreshold behavior and threshold estimates of ultrasound-induced lung hemorrhage in adult rats: role of beamwidth.

It is well documented that ultrasound-induced lung hemorrhage can occur in mice, rats, rabbits, pigs, and monkeys. The objective of this study was to assess the role of the ultrasound beamwidth (beam diameter incident on the lung surface) on lesion threshold and size. A total of 144 rats were randomly exposed to pulsed ultrasound at three exposure levels and four beamwidths (12 rats per group). The three in situ peak rarefactional pressures were about 5, 7.5, and 10 MPa. The four 19-mm-diameter focused transducers had measured pulse-echo -6-dB focal beamwidths of 470 microm (2.8 MHz; f/1), 930 microm (2.8 MHz; f/2), 310 microm (5.6 MHz; f/1), and 510 microm (5.6 MHz; f/2). Exposure durations were 10 s, pulse repetition frequencies were 1 kHz, and pulse durations were 1.3 micros (2.8 MHz; f/1), 1.2 micros (2.8 MHz; f/2), 0.8 micros (5.6 MHz; f/1) and 1.1 micros (5.6 MHz; f/2). The lesion surface area and depth were measured for each rat as well as the percentage of rats with lesions per group. Logistic regression analysis and Gaussian-Tobit analysis methods were used to analyze the data. The effects of in situ peak rarefactional pressure and beamwidth were highly significant, but ultrasonic frequency was not significant. In addition, the estimated interaction between in situ peak rarefactional pressure and beamwidth was positive and highly significant. The ultrasound beamwidth incident on the lung surface was shown to strongly affect the percentage and size of ultrasound-induced lung hemorrhage lesions. Even though ultrasonic frequency was an experimental variable, it was not shown to affect the lesion percentage or size.

Animals↗

Ultrasound phased arrays for prostate treatment.

The effect of array geometry on the steering performance of ultrasound phased arrays is examined theoretically, in order to maximize array performance under the given anatomical constraints. This paper evaluates the performance of arrays with spherical and cylindrical geometry, determined by using computer simulations of the pressure fields produced at various extremes of steering. The spherical segment arrays were truncated for insertion into the rectum, and contained either annular or linear elements. The cylindrical arrays were either flat or had a variable curvature applied along their length. Fields were computed by dividing the array elements into many point sources. The effectiveness of an array configuration when steered to a particular focal location was assessed by defining a parameter, G, as the ratio of the intensity at the desired focus to the maximum intensity of any unwanted lobes. The performance of truncated spherical arrays with annular elements was evaluated for focal steering along the array axis (in depth, in the z direction). When steered 15 mm toward the source, these truncated spherical annular arrays exhibited excellent performance, with G>5.7 for arrays containing more than 10 elements. Similarly, the spherical arrays with linear elements performed well when steered along the array axis to the same degree, with G>7 (for element widths up to 3 lambda), though many more array elements were required. However, when these arrays were steered 15 mm laterally, along the length of the prostate (the y direction), the value for G fell below 1 for element widths greater than about 1.6 lambda. It was found that the cylindrical arrays performed much better for y-direction steering (G>4, for 60 mm arrays with an element width of 1.75 lambda), but their performance was poorer when steered in the z direction (G approximately 4 for an element width of 1.5 lambda). In order to find a compromise between these extremes, a curved cylindrical array was examined, which was a cylindrical array with additional curvature along its length. These curved cylindrical arrays yielded performance between that of spherical linear arrays and cylindrical arrays, with better steering along the y direction than the spherical arrays and better z-direction steering than the cylindrical arrays.

Humans↗

Cardiopulmonary function in rats with lung hemorrhage induced by pulsed ultrasound exposure.

OBJECTIVE: To assess cardiopulmonary function in rats exposed to pulsed ultrasound using superthreshold exposure conditions known to produce significant lung hemorrhage. METHODS: In 1 group of 9 anesthetized Sprague-Dawley rats, 5 foci of ultrasound-induced hemorrhage were produced in the left lung of each rat. In a second group of 6 rats, 5 foci of ultrasound-induced hemorrhage were produced in the left and right lungs of each rat. Each lesion was induced using superthreshold pulsed ultrasound exposure conditions (3.1-MHz center frequency, 1.7-kHz pulse repetition frequency, 1.3-micro-second pulse duration, 60-second exposure duration, 39-MPa in situ peak compressional pressure, and 17-MPa in situ peak rarefactional pressure). After exposure, the lungs were fixed in formalin and assessed histologically. The total lesion volume was calculated for each lesion in each lung lobe. Measurements of cardiopulmonary function included assessment of pulsatile arterial pressure, heart rate, end-tidal carbon dioxide, respiratory rate, and arterial blood gases (PCO2 and PO2). Functional data were quantified before (baseline) and 30 minutes after exposure to ultrasound. RESULTS: In the 9 rats that had lesions in only the left lung, the mean (SEM) lesion volume was 97 (13) mm3 and represented about 3.4% of the total lung volume. In the 6 rats that had lesions in both the left and right lungs, the left, right, and total mean lesion volumes, respectively, were 102 (16), 114 (11), and 216 (18) mm3 and represented about 3.7%, 4.2%, and 7.9% of the total lung volume. There were no statistically significant differences in cardiopulmonary measurements between baseline values and values obtained after exposure to ultrasound in the 9 rats exposed on the left lung only. The 6 rats exposed bilaterally had statistically significant differences in arterial pressure (134 +/- 4 versus 113 +/- 9 mm Hg; P= .047) and arterial PO2 (70 +/- 5 versus 58 +/- 4 mm Hg; P = .024) between baseline values and values obtained after exposure to ultrasound. CONCLUSIONS: The severity of ultrasound-induced lesions produced in 1 lung did not affect measurements of cardiopulmonary function because of the functional respiratory reserve in the unexposed lung. However, when both the left and right lungs had ultrasound-induced lesions, the functional respiratory reserve was decreased to a point at which rats were unable to maintain systemic arterial pressure or resting levels of arterial PO2.

Animals↗

Ultrasound-induced lung hemorrhage is not caused by inertial cavitation.

In animal experiments, the pathogenesis of lung hemorrhage due to exposure to clinical diagnostic levels of ultrasound has been attributed to an inertial cavitation mechanism. The purpose of this article is to report the results of two experiments that directly contradict the hypothesis that ultrasound-induced lung hemorrhage is caused by inertial cavitation. Elevated hydrostatic pressure was used to suppress the involvement of inertial cavitation. In experiment one, 160 adult mice were equally divided into two hydrostatic pressure groups (0.1 or 1.1 MPa), and were randomly exposed to pulsed ultrasound (2.8-MHz center frequency, 1-kHz PRF, 1.42-micros pulse duration, 10-s exposure duration). For the two hydrostatic pressure groups (80 mice each), 8 in situ peak rarefactional pressure levels were used that ranged between 2.82 and 11.8 MPa (10 mice/group). No effect of hydrostatic pressure on the probability of hemorrhage was observed. These data lead to the conclusion that lung hemorrhage is not caused by inertial cavitation. Also, the higher hydrostatic pressure enhanced rather than inhibited the impact of ultrasonic pressure on the severity (hemorrhage area, depth, and volume) of lesions. These counterintuitive findings were confirmed in a second experiment using a 2 x 5 factorial design that consisted of two ultrasonic pressure levels and five hydrostatic pressure levels (100 mice, 10 mice/group). If inertial cavitation were the mechanism responsible for lung hemorrhage, then elevated hydrostatic pressures should have resulted in less rather than more tissue damage at each ultrasonic pressure level. This further supports the conclusion that the pathogenesis of ultrasound-induced lung hemorrhage is not caused by inertial cavitation.

Animals↗

Effects of pulsed ultrasound on the mouse neonate: hind limb paralysis and lung hemorrhage.

Exposure conditions were determined for hind limb paralysis and lung hemorrhage of neonatal mice due to pulsed exposure (10 microsecond pulse duration) to 1 MHz focused ultrasound. Spatial peak pulse average intensity and peak rarefactional pressure levels for paralysis in 50% of specimens sonicated were determined for pulse repetition frequencies of 1, 5 and 50 kHz at 10 degrees C and 2.4 s exposure duration. The results suggest that cavitation was involved in the paralysis at a pulse repetition frequency (PRF) of 50 kHz, but that cavitation took place in the coupling medium and probably not within the specimen during exposures at a PRF of 5 kHz. The results show an inverse relation between spatial peak pulse average intensity, or peak rarefactional pressure and sound on-time. Exposure conditions for lung hemorrhage were determined for a pulse duration of 10 microseconds at 10 degrees C and exposure durations of 2.4 and 180 s. The results show that the threshold exposure conditions for lung hemorrhage are much less than the conditions for cavitational or other effects reported for tissues that do not contain well defined gas bodies. In addition, the results show an inverse relation between exposure level and either exposure duration or sound on-time, suggesting that time is an important parameter associated with bubble effects.

Animals↗

Effect of mode conversion on ultrasonic heating at tissue interfaces.

A number of investigators have observed localized heating by ultrasound beams near impedance discontinuities within tissues. It has been suggested that mode conversion to shear waves at impedance discontinuities and subsequent absorption of these waves in a very small distance was the explanation for this heating. A mathematical model for mode conversion at a plane interface between two viscoelastic media is presented. Longitudinal and shear properties are used to calculate the amount of mode conversion that occurs at muscle-air and muscle-bone interfaces. Shear waves in bone are found to be an important source of heating, but shear waves in the muscle provide a negligible effect on heating at the interface.

Air↗

A perfused tissue phantom, for ultrasound hyperthermia.

A perfused tissue phantom, developed as a tool for analyzing the performance of ultrasound hyperthermia applicators, was investigated. The phantom, consisting of a fixed porcine kidney with thermocouples placed throughout the tissue, was perfused with degassed water by a variable flow rate pump. The phantom was insonated by an unfocused multielement ultrasound applicator and the temperatures in the phantom were recorded. The results indicate that for testing protocols where tissue phantoms are needed, the fixed kidney preparation offers an opportunity to use a more realistic phantom than has previously been available to assess the heating performance of ultrasound hyperthermia applicators.

Animals↗

Thresholds for cavitation produced in water by pulsed ultrasound.

The threshold for transient cavitation produced in water by pulsed ultrasound was measured as a function of pulse duration and pulse repetition frequency at both 0.98 and 2.30 MHz. The cavitation events were detected with a passive acoustic technique which relies upon the scattering of the irradiation field by the bubble clouds associated with the events. The results indicate that the threshold is independent of pulse duration and acoustic frequency for pulses longer than approximately 10 acoustic cycles. The threshold increases for shorter pulses. The cavitation events are likely to be associated with bubble clouds rather than single bubbles.

Acoustics↗

Exposure levels for ultrasonic cavitation in the mouse neonate.

The levels for hind limb paralysis from 1 MHz, continuous wave, unfocused ultrasound in the neonatal mouse were determined at 1 and 16 bars hydrostatic pressure and at 10 and 37 degrees C. Above a specific intensity level at each temperature, the exposure duration for paralysis of 50% of specimens exposed (t50) was found to be greater at 16 bars than at 1 bar suggesting a threshold for cavitational involvement. Using these results, the intensity thresholds for cavitation were found to be in the ranges of 120-150 W/cm2 and 53-74 W/cm2 at 10 degrees C and 37 degrees C, respectively. This temperature dependence is consistent with a cavitation mechanism. In addition, the t50 at 289 W/cm2 and 10 degrees C was measured as a function of hydrostatic pressure and showed that cavitation was suppressed at hydrostatic pressures above approximately 10 bars. This result and the intensity threshold for cavitation at 1 bar and 10 degrees C yielded similar values for the threshold negative total pressure for cavitation in the neonatal mouse.

Animals↗

Ultrasonically induced intravascular streaming and thrombus formation adjacent to a micropipette.

Ultrasonically induced microstreaming around bubbles of gas have been shown to cause damage to biological materials in vitro at clinical exposure levels. The potential for ultrasonically induced cavitation and microstreaming in mammalian systems is of interest with respect to the safe application of clinical ultrasound. Ultrasonically induced intravascular microstreaming and formation of thrombi at 1 MHz is demonstrated adjacent the tip of a micropipette in contact with a mesenteric vessel of the mouse. These effects occur at or above therapeutic levels.

Animals↗

Ultrasonically induced morphological changes in the mammalian neonatal spinal cord.

Light and electron microscopy were employed to examine ultrasonically irradiated murine neonate spinal cords. Spinal cord damage was always associated with functional changes, i.e. hind limb paralysis, and was never apparent in initially paralyzed specimens which had recovered function. Damage occurred preferentially at the periphery of the spinal cord and on the ventral side, though the ultrasound was incident on the dorsal side. The distribution of the damage suggests spinal column involvement and nonthermal effects that are enhanced by temperature elevation.

Animals↗

Interlaboratory comparison of ultrasonic attenuation and speed measurements.

A set of test samples, all containing ultrasonically equivalent tissue-mimicking material, was produced and measurements of ultrasonic speed and ultrasonic attenuation coefficients were made at seven laboratories using various techniques. The ultrasonic speed values agree well with one another, having a spread of about 0.3 per cent; thus, speed values for tissue parenchyma appearing in the literature are likely to be accurate. Values of ultrasonic attenuation coefficients agree fairly well with one another, with differences between individual values and the group mean of generally less than 20 per cent of the group mean.

Humans↗