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Biomedical subjects

W D O'Brien

Publications and source records attributed to W D O'Brien.

At least 19 recordsLinked to original sources
PubMed1996

Behavioral effects of prenatal exposure to pulsed-wave ultrasound in unanesthetized rats.

The present experiment examined the developmental neurotoxicity of pulsed-wave (pw) ultrasound in rats, using an exposure system designed to eliminate restraint or anesthesia from the exposure conditions. Pregnant Sprague-Dawley CD rats trained to remain immobile in a water-filled ultrasound exposure tank were scanned with 3-MHz pw ultrasound at spatial peak temporal average intensities (ISPTA) of 0, 2, 20, or 30 W/cm2 on embryonic days 4-20 for approximately 10 min/day. The data showed that such insonation produced no adverse effects on maternal weight gain or reproductive outcome, nor on the postnatal growth or survival of the offspring. No exposure-related alterations in behavioral development were observed in the offspring of rats scanned with pw ultrasound during gestation. In addition, there was no consistent evidence of an ultrasound-associated change in the adult offspring behaviors tested; i.e., no treatment effects were found on measures of locomotor activity, water maze learning, and acoustic startle reactivity. An effect on tactile startle was observed on some trials in the low exposure group male offspring, but this effect was neither dose dependent nor consistent with any other finding. Overall, these results indicate that the neurobehavioral development of rats was not altered by prenatal exposure to pw ultrasound at ISPTA levels of up to 30 W/cm2.

Animals↗
PubMed1996

Rabbit and pig lung damage comparison from exposure to continuous wave 30-kHz ultrasound.

Previous comparative studies of ultrasound-induced pulmonary hemorrhage in mice and rabbits suggested that sensitivity to damage was species dependent (O'Brien and Zachary 1994b). In order to understand better these differences in species more analogous to the human, 74 pigs and 75 rabbits were each exposed for 10 min at 1 of 6 acoustic pressure levels (0, 145, 290, 340 [rabbits only], 460 and 490 [pigs only] kPa) at an ultrasonic frequency of CW 30 kHz. Eighteen mice were used as positive controls (10-min duration at 145 kPa). Because pig lung has numerous physiological and anatomical similarities to human lung, it was selected as the appropriate animal model for these studies. Pig lung data were compared to rabbit lung data; rabbit lung data have already been compared with mouse lung data (O'Brien and Zachary 1994a). Comparative analyses and extrapolation of these experimental data are intended to provide a better scientific basis for understanding the potential biological effects of ultrasound on human lungs since such studies will probably never be conducted with humans. Under the same exposure conditions and lung assessment criteria, mouse lung was determined to be more sensitive to ultrasound-induced damage than that of the rabbit by a factor of 3.9, the rabbit lung was more sensitive to ultrasound-induced damage than that of the pig by a factor of 3.7, and the mouse lung was more sensitive to ultrasound-induced damage than that of the pig by a factor of 14.4.

Analysis of Variance↗
PubMed1995

Acoustic propagation properties of normal, stunned, and infarcted myocardium. Morphological and biochemical determinants.

BACKGROUND: Identification of viable but stunned myocardium remains a major problem. Since stunned myocardium results in impairment of myocardial function without any structural damage and infarcted myocardium causes major structural disruption, we postulated that acoustic properties could distinguish between the two insults. METHODS AND RESULTS: Anesthetized open-chest dogs underwent a total occlusion of the left anterior descending coronary artery for 15 minutes (stunned, n = 7) and 90 minutes (infarcted, n = 8), followed by reperfusion for 3 hours. Circumflex coronary artery perfusion territory (n = 15) served as normal control tissue. Regions of myocardium were quantitatively evaluated with a scanning laser acoustic microscope operating at 100 MHz and a research ultrasound system operating at 4 to 7 MHz. Four ultrasonic parameters were determined: attenuation coefficient (an index of loss per unit distance), speed of propagation, a spatial variation of propagation speed called the heterogeneity index (HI), and ultrasonic backscatter at 5 MHz (IBR5). Myocardial water, lipid, and protein contents of normal, stunned, and infarcted myocardium were also determined. The attenuation coefficient of normal myocardium (179 +/- 20 dB/cm) was significantly greater than that of stunned (136 +/- 7 dB/cm, P < .001) and infarcted (130 +/- 8 dB/cm, P < .001) myocardium. The propagation speed of normal myocardium (1597 +/- 6 m/s) was similar to that of stunned (1600 +/- 6 m/s) and significantly higher than that of infarcted (1575 +/- 7 m/s, P < .001) myocardium. The HI for specimen thicknesses of 75 to 100 microns showed an increase of 33% between normal (5.0 +/- 0.8 m/s) and stunned (7.5 +/- 2.3 m/s, P < .05) myocardium. However, for the infarcted myocardium (5.8 +/- 2.0 m/s), the HI was essentially the same as that of the normal myocardium (5.0 +/- 0.8 m/s). The IBR5 of normal (-47.1 +/- 1.0 dB) was not significantly different from that of stunned myocardium (-46.8 +/- 0.9 dB). The IBR5 of infarcted myocardium (-42.4 +/- 1.0 dB) was significantly greater than that of normal myocardium. Myocardial water and protein contents were similar in the normal and stunned myocardium. Water content in the infarcted myocardium (80.8 +/- 2%) was significantly greater (P < .05) than in the normal (72.7 +/- 1.3%), and protein content of 18.5 +/- 0.7% was significantly lower (P < .05) than the normal (21.4 +/- 0.8%). Lipid content was increased in the stunned (8.5 +/- 0.5%) and virtually absent in the infarcted myocardium (0.8 +/- 0.3%) compared with normal (5.5 +/- 0.6%). CONCLUSIONS: We conclude that acoustic propagation properties can identify stunned and infarcted myocardium and may be related to biochemical/morphological differences.

Animals↗
PubMed1995

Relation of ultrasonic backscatter and acoustic propagation properties to myofibrillar length and myocardial thickness.

BACKGROUND: Ultrasonic backscatter demonstrates a cardiac cycle-dependent modulation. The exact mechanism of the modulation is under debate. The objective of the present study was to test the hypothesis that a change in size and configuration of myofilaments from systole to diastole alters acoustic propagation properties and backscatter. METHODS AND RESULTS: In vivo measurements were made of integrated backscatter at 5 MHz (IBR5), followed by in vitro measurements of ultrasonic attenuation, speed, and heterogeneity index using a scanning laser acoustic microscope at 100 MHz. Studies were performed in canine hearts (16) arrested in systole (8) with calcium chloride or arrested in diastole (8) with potassium chloride. Sarcomere length was measured with a calibrated eyepiece on a Ziess microscope. Wall thickness was measured with calipers. The attenuation coefficient of 220 +/- 34 dB/cm during systole was significantly higher than the coefficient of 189 +/- 24 dB/cm during diastole (P < .01); the IBR5 of -44.7 +/- 1.2 dB during systole was significantly greater than the IBR5 of -47.0 +/- 1.0 dB during diastole (P < .01); the ultrasonic speed of 1591 +/- 11 m/s during systole was higher than the speed of 1575 +/- 4.2 m/s during diastole (P < .01); and the heterogeneity index of 7.4 +/- 1.8 m/s during systole was significantly lower than the index of 9.0 +/- 2.0 m/s during diastole (P < .02). The sarcomere length of 1.804 +/- 0.142 microns during diastole was significantly higher than the length of 1.075 +/- 0.177 micron during systole (P < .01). Wall thickness was significantly greater during systole than during diastole (20 +/- 3 versus 9 +/- 3 mm, P < .01). CONCLUSIONS: Ultrasonic backscatter and propagation properties are directly related to sarcomere length and myocardial thickness and may be responsible for cardiac cycle-dependent variation in backscatter.

Animals↗
PubMed1995

In situ human obstetrical ultrasound exposimetry: estimates of derating factors for each of three different tissue models.

A specialized in vivo exposimetry system was developed to acquire transabdominal in situ ultrasound exposure quantities in obstetric patients. Under surgical conditions, the sterilized 7-element calibrated linear array hydrophone was introduced into the uterus under direct ultrasound guidance and placed in direct contact with the products of conception, usually in the saggital midplane of the uterine cavity. Twenty-five patients with empty bladders and 10 patients with full bladders were studied at gestational ages between 7 and 20 weeks. In the empty bladder condition, the sound beam traversed the anterior abdominal wall, uterus, amniotic fluid and fetal parts and in the full bladder condition, the sound beam also traversed the fluid-filled bladder. Each study was conducted with a 3 MHz, mechanical sector transducer in combination with an ATL Ultramark 4 diagnostic ultrasound imaging system. Calibration data were recorded after completion of each in vivo patient study. The acquired exposimetry data from the 35 obstetric patients were used to evaluate the appropriateness of three tissue attenuation models, viz., fixed path, homogeneous and overlying. All three tissue models yield a mean attenuation coefficient value of about a factor of 3 to 4 greater than their respective minimum values. In the case of the overlying and homogeneous tissue models, there was a statistically significant correlation between their calculated attenuation coefficients and total distance for the combined data set whereas there was no such dependency for the calculated fixed-path tissue model. In summary, any one of the three tissue models may be used to estimate in utero acoustic quantities during the first and second trimesters of human pregnancy based on this study.

Adult↗
PubMed1995

Hematologic and growth-related effects of frequent prenatal ultrasound exposure in the long-tailed macaque (Macaca fascicularis).

Prior investigations have shown that reduced birth weights and transient neutropenias result from frequent exposure of monkey fetuses to ultrasound. To further explore these findings, 26 animals were studied (16 exposed, 10 controls; "triple mode"; ATL Ultramark 9 with HDI; ISPTAd approximately 645 to 714 mW/cm2). Exposures were performed daily for 5 days each week from gestational days (GD) 21 to 35 (5 min), three times weekly from GD 36 to 60 (5 min), then weekly from GD 61 to 153 +/- 1 (10 min). Fetal blood samples (FBS) were collected for complete blood counts (CBCs), hematopoietic progenitor assay, circulating insulin-like growth factors (IGF-I, IGF-II) and binding proteins (IGFBP-3) (GD 120, 140, 153 +/- 1). Animals were delivered by Cesarean section at term (GD 153 +/- 1), and body weights, morphometrics, CBCs, and bone marrow aspirates assessed at delivery and postnatally for 3 months. Fetal neutropenias were noted in exposed animals in addition to reduced circulating progenitors (colony forming unit-granulocyte-macrophage [CFU-GM]). Growth of CFU-GM from bone marrow was exuberant at term, whereas circulating levels were diminished comparable to prenatal samples. Exposed animals were smaller at birth; marked reductions in IGFBP-3 were noted prenatally. These data suggest that frequent prenatal ultrasound exposure can transiently alter the neutrophil lineage, although these findings may be the result of enhanced margination and organ sequestration. Data also suggest that transient, altered growth patterns may be due to perturbations of the IGF axis.

Animals↗
PubMed1995

Ultrasound tissue displacement imaging with application to breast cancer.

A method for quantitative imaging of internal tissue motion based on speckle tracking is described. Tissue displacement images from eight patients with sonographically apparent breast masses are used to illustrate the technique. The local displacement response of tissues surrounding malignant and benign breast masses is compared, testing the hypothesis that altered mechanical properties may result in motion signatures for many soft tissue tumors relative to their host tissue. In addition, the potential or anticipated influence of various biological and physical factors on tissue motion response is discussed.

Adult↗
PubMed1995

Performance of ultrasonic speckle tracking in various tissues.

The purpose of this study was to investigate the accuracy of ultrasound speckle tracking in various tissues. Results from two-dimensional tissue speckle tracking in liver, muscle, fat, and sponge samples are presented, while keeping other speckle tracking parameters constant. Speckle tracking performance was characterized both in terms of the magnitude of tracking errors and in terms of the percentage of correctly tracked displacement vectors. Speckle tracking in muscle tissue, which contains myofibrils and significant tissue microstructure, produced the highest percentage of correctly tracked vectors and smallest tracking errors relative to other tissues.

Adipose Tissue↗
PubMed1995

Lung lesions induced by continuous- and pulsed-wave (diagnostic) ultrasound in mice, rabbits, and pigs.

These studies documented the presence or absence of macroscopic and microscopic intraparenchymal hemorrhage in individual lung lobes of mice, rabbits, and pigs exposed to continuous- and pulsed-wave (diagnostic) ultrasound; we described the character of and lesions associated with the hemorrhage and compared differences in the lesions among species and exposure conditions to investigate the pathogenic mechanisms and species differences associated with ultrasound-induced lung hemorrhage. In a series of three sequential interdependent studies, 312 mice, 91 rabbits, and 74 pigs were divided at random into experimental groups and exposed to continuous-wave ultrasound (3 kHz modulated at 120 Hz) of acoustic pressure levels ranging from 0 to 490 kPa for 5, 10, or 20 minutes. In a fourth study, three mice, 43 rabbits, and six pigs were divided at random into experimental groups and exposed to pulsed-wave ultrasound (3- and 6-MHz center frequency) of peak rarefactional acoustic pressure levels ranging from 0 to 5.6 MPa for 5 minutes. Macroscopic lesions induced by continuous- and pulsed-wave ultrasound consisted of dark red to black areas of hemorrhage that extended from visceral pleural surfaces into lung parenchyma. Hemorrhage appeared spatially related to the edges of lung lobes where pleura of dorsal and ventral surfaces met, occurred in specific lung lobes in all three species, and appeared anatomically related to lung that was closest to and in contiguous alignment with the ultrasound transducer and thus the path of the sound beam. Macroscopic lesions were similar in all species under all exposure conditions for both continuous- and pulsed-wave ultrasound; however, hemorrhage was not induced in pig lung exposed to pulsed-wave ultrasound at any peak rarefactional acoustic pressure level. Eighteen mice (145 kPa exposure pressure), 60 rabbits (145-460 kPa exposure pressure), and 58 pigs (145-490 kPa exposure pressure) from study 3 were used for microscopic evaluation of lung exposed to continuous-wave ultrasound; three mice (6 MHz; 2.9 and 5.4 MPa), 39 rabbits (3 and 6 MHz; 2.3-5.4 MPa), and six pigs (3 and 6 MHz; 3.3, 5.4, and 5.6 MPa) from study 4 were used for microscopic evaluation of lung exposed to pulsed-wave ultrasound. Microscopic lesions and the character of hemorrhage induced by continuous-wave ultrasound were different from those induced by pulsed-wave ultrasound. Lesions induced by continuous-wave ultrasound under all exposure conditions were similar in all three species. Lesions induced by pulsed-wave ultrasound under all exposure conditions were similar in all three species.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1995

Guided tissue regeneration using a biodegradable barrier membrane for new attachment: a clinical, histologic, and histometric study in dogs.

Although nonbiodegradable barrier membranes have proven partially successful in achieving regeneration of lost periodontium through the principles of guided tissue regeneration, their use requires a second surgical procedure for their removal. The results of a study, in which a biodegradable collagen membrane was used to treat dehiscence defects in dogs, are presented. The membrane was an effective barrier to the downgrowth of gingival epithelium during the early stages of healing and tended to increase the regeneration of new cementum and connective tissue attachment. It was also biocompatible and biodegradable.

Analysis of Variance↗
PubMed1994

Teratologic evaluation of rats prenatally exposed to pulsed-wave ultrasound.

While there are no known risks associated with diagnostic ultrasound, uncertainty about the safety of prenatal ultrasound exposure remains. The purpose of the present experiment was to evaluate the teratogenic potential of pulsed-wave (pw) ultrasound in rats, in the absence of maternal anesthesia or restraint. Pregnant CD rats, trained to remain immobile in a water-filled ultrasound exposure tank, were scanned with 3-MHz pw ultrasound at levels of 0, 2, 20 or 30 W/cm2 ISPTA (spatial peak, temporal average intensity) on gestational days 4-19 for approximately 10 min/day. Examination of fetuses on E20 revealed no increase in skeletal or visceral malformations in groups exposed to pw ultrasound in utero. The number of implantations/dam was significantly increased in all pw ultrasound exposure groups compared to sham-exposed animals and, in a possibly related finding, resorptions were increased in the two highest exposure groups. Although significantly increased compared to controls, resorption frequencies in these groups were low (< 10%). No exposure-related changes in fetal weights were observed in offspring of rats scanned with pw ultrasound during gestation. The results indicate that, under the conditions described, no overt embryotoxicity is associated with gestational exposure to pw ultrasound intensities of up to 30 W/cm2.

Animals↗
PubMed1994

Behavioral teratologic effects of prenatal exposure to continuous-wave ultrasound in unanesthetized rats.

While there are no known risks associated with diagnostic ultrasound, uncertainty about the safety of prenatal ultrasound exposure remains. The purpose of the present experiment was to evaluate the behavioral teratogenic potential of continuous-wave (cw) ultrasound in rats, in the absence of maternal anesthesia or restraint. Pregnant CD rats, trained to remain immobile in a water-filled ultrasound exposure tank, were scanned with 3 MHz cw ultrasound at levels of 0, 2, 10, 20, or 30 W/cm2 ISPTA (spatial peak, temporal average intensity) on gestational days 4-20 for approximately 10 min/day. Offspring were examined postnatally for survival, growth, physical landmarks of development, behavioral development, and the adult functions of locomotor activity, learning and memory, and startle reactivity. No effects of prenatal ultrasound were found on maternal characteristics, offspring survival or growth, physical or behavioral landmarks of development, or adult tests of passive avoidance or startle. Effects at the highest intensity were obtained on corner and side locomotor activity and in a multiple-T water maze on measures of errors of commission and time spent finding the goal. The results showed that prenatal cw ultrasound in rats can induce effects on some postnatal neurobehavioral functions at high exposure intensities (30 W/cm2), but at lower intensities (2-20 W/cm2) no consistent evidence of neurobehavioral effects was observed.

Animals↗
PubMed1994

Mouse lung damage from exposure to 30 kHz ultrasound.

Two hundred and seventy mice were evaluated at three exposure durations (5, 10 and 20 min) and at six peak acoustic pressure levels (0, 65, 80, 87, 100 and 145 kPa) with 15 mice per exposure condition, at an ultrasonic frequency of 30 kHz modulated at 120 Hz. Threshold acoustic pressure levels for hemorrhage in mouse lung exposed for the three exposure durations appear to be in the range of 100 kPa. There did not appear to be a strong dependency on exposure duration. When compared to a study with mice in the megahertz frequency range (Child et al. 1990), it appeared that the threshold values followed a square root of frequency dependency, suggesting that the concept of the Mechanical Index (AIUM/NEMA, 1992), although developed for pulsed ultrasound conditions, may be extended to frequencies well below the diagnostic ultrasound frequency range.

Acoustics↗
PubMed1994

Comparison of mouse and rabbit lung damage exposure to 30 kHz ultrasound.

Twenty-four mice and sixteen rabbits were evaluated at one exposure duration (10 min) and at three exposure acoustic pressure levels (0, 100 and 145 kPa) at an ultrasonic frequency of 30 kHz, continuous wave for the purpose of testing whether there was a species difference in the degree of sensitivity to ultrasound-induced lung damage. This study was undertaken because it was hypothesized that the mouse may not be an acceptable or suitable animal model for studies that examine the effects of ultrasound on lung tissue for purposes of extrapolating or estimating the degree of potential damage in other species. The rabbit was selected for comparison to the mouse because the rabbit exhibited sufficient physiological and morphological differences from those of the mouse to test this hypothesis. Using exactly the same exposure conditions and lung assessment criteria, it appeared that the mouse lung was more sensitive to ultrasound-induced damage than that of the rabbit by a factor of between 2.8 and 3.6. Lung lesions in mice and rabbits were similar in character, but were much more severe and extensive in mice. Lesions in both species consisted of intraalveolar hemorrhage that appeared as dark red to red-black areas that were visible on the pleural surfaces and that extend within the lung parenchyma.

Acoustics↗
PubMed1993

Evaluation of the bioeffects of prenatal ultrasound exposure in the cynomolgus macaque (Macaca fascicularis): III. Developmental and hematologic studies.

The multiple applications of diagnostic ultrasound in obstetrics have resulted in a continued rise in the prenatal population exposed each year. Although human epidemiologic and experimental studies with various animal models have not consistently documented any significant, reproducible findings related to clinically relevant exposures, technologic changes in scanning equipment and gaps in our knowledge regarding the interaction(s) of ultrasound with tissues emphasize the need to pursue safety issues. Studies with nonhuman primates have provided information on the potential for pre and postnatal effects on offspring exposed repeatedly during gestation (ATL MK 600, 7.5 MHz, ISPTA = 27 mW/cm2; ISPPA = 85 W/cm2; Estimated power = 12 mW--scanned for 10 min 5 times weekly gestational day [GD] 20-35; 3 times weekly GD 36-60; once weekly for 20 min GD 60-150). These studies have indicated transient effects on body weight, white blood cell counts (WBCs), and muscle tone postnatally. In an effort to confirm these findings and focus on hematologic changes, a second series of studies was initiated using the same exposure conditions (N = 22; 11 exposed, 11 sham controls). Data derived from both studies were combined and confirmed transient reductions in body weights for infants up through 4 months of age (P < or = 0.03); no statistically significant differences in muscle tone were noted. Similar to the original findings, WBCs were transiently reduced on days 3 (P < or = 0.02) and 21 (P < or = 0.05); prenatal sampling indicated a significant difference between the groups on GD 140 (P < or = 0.04). No direct effects were evident in bone marrow aspirates collected on postnatal days 3, 9, and 21 +/- 1. Although animals were able to compensate for these observed changes and remained unaffected by their occurrence, additional studies will be required to further our understanding of this phenomenon.

Animals↗
PubMed1993

Sonographic heat generation in vivo in the gravid long-tailed macaque (Macaca fascicularis).

Temperature elevations that occur during diagnostic ultrasonic exposure were assessed in vivo in gravid macaques after 10, 20, or 30 min (scan mode; N = 30) or 5, 10, or 15 min (pulsed Doppler; N = 32). Five time points were assessed during the second and third trimesters (gestational days 70 to 150 +/- 2; term, approximately 165 days) using a transient thermocouple technique. Measurements were obtained intracranially or at the muscle-bone interface using a commercial sector scanner (ATL MK 600, 7.5 MHz scanhead; scan mode, ISPTA) = 27 mW/cm2, ISPPA = 85 W/cm2, pulse repetition frequency (PRF) = 1 kHz; pulsed Doppler - ISPTA = 54 mW/cm2, ISPPA = 1.5 W/cm2, PRF = 18.5 kHz). Overall, the greatest temperature elevation achieved with either modality or location was 0.6 degrees C.

Animals↗