Biomedical subjects

E L Carstensen

Publications and source records attributed to E L Carstensen.

At least 19 recordsLinked to original sources

PubMed1999

Nonlinear propagation and the output indices.

By ignoring the effects of nonlinear propagation, current exposimetry protocols may yield significant underestimates of the acoustic pressure in situ. This problem can be avoided simply by (1) extrapolating pressures linearly from low amplitude measurements in water and (2) linearly derating these values to obtain estimates of fields in situ. The mechanical index was designed to provide an indication of temporal peak acoustic fields for use in prediction of nonthermal biological effects in tissues. At low outputs, the mechanical index, together with the frequency, gives the peak negative pressure near the focus of the field. As currently formulated, however, the pressure used in the mechanical index may be far from the focus at high output levels. Recommendations of the World Federation of Ultrasound in Medicine and Biology avoid the underestimate associated with nonlinear propagation as well as other problems with the mechanical index and may be preferable in dealing with non-thermal bioeffects. The thermal indices that are implemented currently in the Output Display Standard (American Institute of Ultrasound in Medicine/National Electrical Manufacturers' Association) are affected less seriously by nonlinear propagation.

Acoustics↗

PubMed1998

Enhancement of fibrinolysis with 40-kHz ultrasound.

BACKGROUND: Ultrasound at frequencies of 0.5 to 1 MHz and intensities of > or =0.5 W/cm2 accelerates enzymatic fibrinolysis in vitro and in some animal models, but unacceptable tissue heating can occur, and limited penetration would restrict application to superficial vessels. Tissue heating is less and penetration better at lower frequencies, but little information is available regarding the effect of lower-frequency ultrasound on enzymatic fibrinolysis. We therefore examined the effect of 40-kHz ultrasound on fibrinolysis, tissue penetration, and heating. METHODS AND RESULTS: 125I-fibrin-radiolabeled plasma clots in thin-walled tubes were overlaid with plasma containing tissue plasminogen activator (tPA) and exposed to ultrasound. Enzymatic fibrinolysis was measured as solubilization of radiolabel. Tissue attenuation and heating were examined in samples of porcine rib cage. Fibrinolysis was increased significantly in the presence of 40-kHz ultrasound at 0.25 W/cm2, reaching 39+/-7% and 93+/-11% at 60 minutes and 120 minutes, compared with 13+/-8% and 37+/-4% in the absence of ultrasound (P<0.0001). The acceleration of fibrinolysis increased at higher intensities. Attenuation of the ultrasound field was only 1.7+/-0.5 dB/cm through the intercostal space and 3.4+/-0.9 dB/cm through rib. Temperature increments in rib were <1 C/(W/cm2). CONCLUSIONS: These findings indicate that 40-kHz ultrasound significantly accelerates enzymatic fibrinolysis at intensities of > or =0.25 W/cm2 with excellent tissue penetration and minimal heating. Externally applied 40-kHz ultrasound at low intensities is a potentially useful therapeutic adjunct to enzymatic fibrinolysis with sufficient tissue penetration for both peripheral vascular and coronary applications.

Animals↗

PubMed1998

Lack of lung hemorrhage in humans after intraoperative transesophageal echocardiography with ultrasound exposure conditions similar to those causing lung hemorrhage in laboratory animals.

This study investigated the phenomenon of ultrasonically induced lung hemorrhage in humans. Multiple experimental laboratories have shown that diagnostic ultrasound exposure can cause hemorrhage in the lungs of laboratory animals. The left lung of 50 patients (6 women, 44 men, mean age 61 years) was observed directly by the surgeon after routine intraoperative transesophageal echocardiography was performed. From manufacturer specifications the maximum derated intensity in the sound field of the system used was 186 W/cm2, the maximum derated rarefactional acoustic pressure was 2.4 MPa, and the maximum mechanical index was 1.3. The lowest frequency used was 3.5 MHz. This exposure exceeds the threshold found for surface lung hemorrhage seen on gross observation of laboratory animals. No hemorrhage was noted on any lung surface by the surgeon on gross observation. We conclude that clinical transesophageal echocardiography, even at field levels a little greater than the reported thresholds for lung hemorrhage in laboratory animals, did not cause surface lung hemorrhage apparent on gross observation. These negative results support the conclusion that the human lung is not markedly more sensitive to ultrasound exposure than that of other mammals.

Adult↗

PubMed1997

Hemolysis in vivo from exposure to pulsed ultrasound.

Ultrasonically induced hemolysis in vivo when a commercial ultrasound contrast agent, Albunex, was present in the blood. Murine hearts were exposed for 5 min at either 1.15 or 2.35 MHz with a pulse length of 10 microseconds and pulse repetition frequency of 100 Hz. During the exposure period, four boluses of Albunex were injected into a tail vein for a total of approximately 0.1 mL of Albunex. Following exposure, blood was collected by heart puncture and centrifuged, and the plasma was analyzed for hemoglobin concentration. With Albunex present in the blood, the threshold for hemolysis at 1.15 MHz was 3.0 +/- 0.8 MPa (mean +/- SD) peak positive pressure (approximately 1.9 MPa negative pressure, approximately 180 W cm-2 pulse average intensity). For the highest exposure levels (10 MPa peak positive pressure at the surface of the animal), the mean value for hemolysis was approximately 4% at 1.15 MHz and 0.46% at 2.35 MHz, i.e., the threshold at 2.35 MHz is > 10 MPa peak positive pressure. In contrast, hemolysis in control mice receiving saline injections at 10 MPa or sham-exposed (0 MPa) mice receiving Albunex was approximately 0.4%.

Albumins↗

PubMed1997

Effects of pulsed ultrasound on the frog heart: III. The radiation force mechanism.

Earlier studies have shown that a single, millisecond duration pulse of ultrasound delivered to the frog heart in vivo during systole can produce a reduction in the developed aortic pressure, while a pulse delivered during diastole can produce a premature ventricular contraction. The threshold for these effects is 5-10 MPa with a 5-ms pulse. Since cardiac tissues respond to mechanical stimulation, the objective of this study was to investigate acoustic radiation force as a possible mechanism for the observed effects of ultrasound on the frog heart. In two experiments, the radiation force exerted on the heart was varied by varying the ultrasonic frequency and the acoustic beam width. Results of these studies indicated that the rate of occurrence of the reduced aortic pressure effect was directly correlated with the magnitude of the radiation force exerted on the heart. A third experiment tested the radiation force mechanism directly by placing an acoustic reflector on the frog heart. The acoustic reflector maximized the radiation force delivered to the heart, but eliminated direct interaction of the ultrasound with the heart and experimentally eliminated heating and cavitation as mechanisms of action. The reduced aortic pressure effect was observed with the reflector on the heart, indicating that radiation force is capable of producing this effect. No premature ventricular contractions were observed with the acoustic reflector over the heart, suggesting that another property of the exposure may be responsible for this bioeffect.

Animals↗

PubMed1997

Thresholds for fetal hemorrhages produced by a piezoelectric lithotripter.

Hemorrhage to fetal tissues occurred when late-term pregnant mice were exposed to lithotripter fields of relatively low amplitude. These hemorrhages were always observed in tissues near developing bone or cartilaginous structures such as the head, limbs and ribs, while soft tissues distant from bone were relatively free of hemorrhage. Thresholds for hemorrhage in the fetus were determined for exposures of pregnant mice on the 18th day of gestation to 200 pulses from a piezoelectric lithotripter. Animals were exposed to axial peak positive pressures of either 0 (sham), 1, 2, 3, 5 or 10 MPa. Thresholds for hemorrhage to the head, limbs, ribs and lung were all < 1 MPa.

Animals↗

PubMed1997

Ultrasonically induced lung hemorrhage in young swine.

Ten-day old swine were used in the final step of a study of the age dependence of the threshold for lung hemorrhage resulting from exposure to diagnostically relevant levels of pulsed ultrasound. A 2.3-MHz focused transducer (pulse length of 10 microseconds, 100-Hz pulse repetition frequency) was incremented vertically at several sites for a distance of 2 or 2.5 cm over the chest of the subject for a total exposure period of 16 or 20 min. The procedure was repeated at a total of four sites per animal. Animals were euthanized and lungs were scored by visual inspection for numbers and areas of gross hemorrhages. The threshold level for hemorrhage was approximately 1.3-MPa peak positive pressure in water and the surface of the animal or, at the surface of the lung, 0.8-MPa peak positive pressure, 0.8-MPa fundamental pressure, 0.7-MPa maximum negative pressure and 20 Wcm-2 pulse average intensity. These values are essentially the same as those reported previously for neonatal swine, and neonatal, juvenile and adult mice.

Animals↗

PubMed1997

Age dependence of ultrasonically induced lung hemorrhage in mice.

Thresholds for ultrasonically induced lung hemorrhage were determined in neonatal mice (24-36 h old), juvenile mice (14 d old) and adult mice (8-10 weeks old) to assess whether or not the threshold for lung hemorrhage is dependent upon age. Ultrasonic exposures were at 1.15 MHz with a pulse length of 10 microseconds, pulse repetition frequency of 100 Hz and a total exposure duration of 3 min. The threshold for lung hemorrhage occurred at a peak positive acoustic pressure of approximately 1 MPa for mice in all three age groups. Although the thresholds were similar for neonatal, juvenile and adult mice, the sizes of the suprathreshold hemorrhages were significantly larger in adult mice than in neonatal or juvenile mice.

Aging↗

PubMed1997

Remnants of Albunex nucleate acoustic cavitation.

Mice were injected with 0.1 mL Albunex and exposed to 200 pulses from a piezoelectric lithotripter at times ranging from 5 min to 24 h following injection. Each pulse was approximately 1.5 sinusoidal oscillations at a fundamental frequency of approximately 0.1 MHz with pressure amplitude of approximately 2 MPa. Although the contrast agent ceases to be an effective scatterer of diagnostic ultrasound after a few minutes in the circulation, the modest lithotripter exposures caused significant hemorrhaging in bladder, mesentery and intestine for periods of up to 4 h after injection. The results demonstrate either that highly stable bubbles much smaller than resonance size or air-containing fragments of the shells of Albunex serve as effective nuclei for acoustic cavitation.

Albumins↗

PubMed1997

The influence of contrast agents on hemorrhage produced by lithotripter fields.

Ultrasonic contrast agents greatly increase the side effects of low-amplitude lithotripter fields in mice. Using a piezoelectric lithotripter, adult mice were exposed to 200 lithotripter pulses with a peak positive pressure amplitude of 2 MPa. During the exposure period, mice were injected with approximately 0.1 mL of the ultrasonic contrast agent Albunex. For comparison, another group of mice experienced the same lithotripter exposures, but were not injected with contrast agent. Following exposures, animals were sacrificed and observed for hemorrhage in various organs and tissues. Mice exposed to the lithotripter field alone had minimal hemorrhage only in the intestine and lung. In comparison, mice injected with Albunex during exposure exhibited extensive hemorrhage in the intestine, kidney, muscle, mesentery, stomach, bladder, seminal vesicle and fat.

Albumins↗

PubMed1996

A test of the hypothesis that ELF magnetic fields affect calcium uptake in rat thymocytes in vitro.

The experiment's objective was to test the statistical hypothesis that a 60-min exposure of rat thymocytes in vitro to a unique combination of static and a.c. magnetic fields results in suppression of calcium influx triggered by concanavalin A (Con A). Con A (10 micrograms/ml) induced about a 50% increase in 45Ca2+ uptake relative to no Con A (control). Magnetic field exposures had no statistically significant effect on Con A-stimulated calcium uptake. The data did not support the hypothesis.

Animals↗

PubMed1996

Thresholds for ultrasonically induced lung hemorrhage in neonatal swine.

The threshold for generation of lung hemorrhage in adult mice by pulsed ultrasound has been shown to be approximately 1 MPa at the surface of the lung (10-microseconds pulse and a carrier frequency of 2 MHz). This investigation used neonatal swine to determine if the findings for mice can be generalized to other species. After exploratory observations, the inverse sampling method was used in a primary study (22 animals, 88 exposure sites) to determine the threshold for lung hemorrhage in neonatal swine. The primary study was followed by a separate confirmation study (13 animals, 48 exposure sites), testing the conclusions of the first study and comparing damage at subthreshold levels with sham-exposed animals. A separate investigation explored the histological nature of tissue damage at suprathreshold levels. A 2.3-MHz focused transducer (10 microseconds at 100-Hz pulse-repetition frequency) was incremented vertically for a distance of 2 cm over the chest of the subject for a total exposure period of 16 min. Animals were euthanized and lungs were scored by visual inspection for numbers and areas of gross hemorrhages. The threshold level for hemorrhage was approximately 1.5 MPa peak positive pressure in water at the surface of the animal or, at the surface of the lung, 1.1 MPa peak positive pressure, 1 MPa fundamental pressure, 0.9 MPa maximum negative pressure, 25 W cm-2 pulse average intensity or a mechanical index of 0.6. These values are essentially the same as those reported for adult mice.

Animals↗

PubMed1996

Exposure-time dependence of the threshold for ultrasonically induced murine lung hemorrhage.

Although the extent of suprathreshold damage to murine lung that results from exposure to pulsed ultrasound increases with time, the threshold level for lung hemorrhage is relatively insensitive to total exposure time. Adult mice were exposed for 20 s and 3 min to 2.3-MHz ultrasound (10-microseconds pulses, 100-Hz pulse repetition frequency) at peak positive pressures ranging up to 3 MPa. Threshold pressures for the two exposure times, 1.6 MPa and 1.4 MPa, respectively, are the same within the statistical significance of the measurements.

Animals↗

PubMed1996

A test for cavitation as a mechanism for intestinal hemorrhage in mice exposed to a piezoelectric lithotripter.

This study tested the hypothesis that intestinal hemorrhage produced by exposure to lithotripter fields depends upon the presence of gas in the intestine. The extent of hemorrhage in the gas-containing intestines of pregnant mice was compared to the amount of hemorrhage in the bubble-free intestines of their fetuses. On day 18 of gestation, the abdominal regions of pregnant C3H mice (n = 6) were exposed to 200 pulses from a piezoelectric lithotripter. Acoustic pulses had a peak pressure amplitude of 10 MPa and were administered at a rate of approximately 1 Hz. All maternal intestines showed hemorrhagic regions extending several centimeters in length. In contrast, only 1 of 43 exposed fetuses showed an intestinal hemorrhage and this one lesion was less than 1 mm in diameter. These results support the hypothesis of the study and are consistent with a cavitation-related mechanism for the production of intestinal hemorrhage by exposure to acoustic fields.

Animals↗

PubMed1996

Finite amplitude distortion and its relationship to linear derating formulae for diagnostic ultrasound systems.

Formulation of indices that can be used as predictors of biological effects of ultrasound involves a process called derating, in which measurements of the sound field made in water are extrapolated to estimates of the magnitude of the sound fields in the tissues of the body. All indices that have been formulated up to the present time assume that the propagation of ultrasound is linear. In fact, under most exposure conditions for which biological effects may be a concern, sound propagation is highly nonlinear. A nonlinear propagation model has been used in this study to evaluate the nature of the effects that occur under realistic exposure conditions encountered in diagnostic procedures. Because of the way that the thermal index is defined, it turns out that ignoring nonlinear propagation leads to underestimates of tissue temperature increments that typically are less than 40%. As currently implemented, the mechanical index may be underestimated by more than a factor of two because it ignores the saturation of the sound fields that result from nonlinear propagation. For large propagation distances in soft tissues (e.g., 10 cm at 3 MHz in liver); however, it is physically difficult to exceed tissue pressures corresponding to MI > 2 because of these same saturation phenomena.

Adipose Tissue↗

PubMed1996

Bioeffects of positive and negative acoustic pressures in vivo.

In water, the inertial collapse of a bubble is more violent after expansion by a negative acoustic pressure pulse than when directly compressed by a positive pulse of equal amplitude and duration. In tissues, gas bodies may be limited in their ability to expand and, therefore, the relatively strong effectiveness of negative pressure excursions may be tempered. To determine the relative effectiveness of positive and negative pressure pulses in vivo, the mortality rate of Drosophila larvae was determined as a function of exposure to microsecond length, nearly unipolar, positive and negative pressure pulses. Air-filled tracheae in the larvae serve as biological models of small, constrained bubbles. Death from exposure to ultrasound has previously been correlated with the presence of air in the respiratory system. The degree of hemorrhage in murine lung was also compared using positive and negative pulses. The high sensitivity of lung to exposure to ultrasound also depends on its gas content. The mammalian lung is much more complex than the respiratory system of insect larvae and, at the present time, it is not clear that acoustic cavitation is the physical mechanism for hemorrhage. A spark from an electrohydraulic lithotripter was used to produce a spherically diverging positive pulse. An isolated negative pulse was generated by reflection of the lithotripter pulse from a pressure release interface. Pulse amplitudes ranging from 1 to 5 MPa were obtained by changing the proximity of the source to the biological target. For both biological effects, the positive pulse was found to be at least as damaging as the negative pulse at comparable temporal peak pressure levels. These observations may be relevant to an evaluation of the mechanical index (MI) as an exposure parameter for tissues including lung since MI currently is defined in terms of the magnitude of the negative pressure in the ultrasound field.

Acoustics↗

PubMed1995

A test of the hypothesis that a 60-Hz magnetic field affects ornithine decarboxylase activity in mouse L929 cells in vitro.

Four replicate experiments were performed to test the hypothesis that a 4-hr exposure of L929 cells in vitro to a 60 Hz, 10 microT magnetic field results in a large increase in ornithine decarboxylase (ODC) enzyme activity (1-2). A positive control yielded a highly statistically significant increase in ODC activity. However, magnetic field exposure had no statistically significant effect on extractable ODC activity of L929 cells relative to that of sham-exposed cells.

Analysis of Variance↗

PubMed1995

Intestinal hemorrhage from exposure to pulsed ultrasound.

Threshold exposures for producing intestinal hemorrhage in mice were determined using focused sources operating at 0.7, 1.1, 2.4 and 3.6 MHz. The choice of pulse length (10 microseconds) and pulse repetition frequency (100 Hz) made the exposures diagnostically relevant, while at the same time, minimized possible thermal contributions to the mechanism of action of the ultrasound. Each animal was irradiated at four to five abdominal sites for 5 min per site. Suprathreshold lesions ranged from small petechiae to hemorrhagic regions extending 4 mm or more along the intestine, depending upon the exposure levels. Higher frequencies were less effective in producing intestinal hemorrhage than lower frequencies. Thermocouple measurements of temperature rise in the intestine during ultrasound exposure revealed temperature increments between 1 degrees and 2 degrees C at the highest exposure levels. The frequency dependence of the production of intestinal hemorrhage together with the observed limited heating is consistent with a cavitation-related mechanism of action of pulsed ultrasound.

Abdominal Muscles↗