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

O’Brien, William D.; Simpson, Douglas G.; Frizzell, Leon A.; Zachary, James F.

doi:10.1109/58.971723

Cited by 34 publications

(49 citation statements)

References 29 publications

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“…Ultrasound-induced lung lesions were similar in all species, under all exposure conditions. Ultrasound exposure conditions and transducer calibration procedures used in these studies were described previously (Sempsrott and O'Brien 1999;Sempsrott 2000;O'Brien et al 2001aO'Brien et al ,2001bZachary et al 2001aZachary et al ,2001b) and based on established standards (AIUM/NEMA 1998;ODS 1998).…”

Section: Ultrasoundmentioning

confidence: 99%

Lesions of ultrasound-induced lung hemorrhage are not consistent with thermal injury

Zachary

Blue

Miller

et al. 2006

Ultrasound in Medicine & Biology

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Thermal injury, a potential mechanism of ultrasound-induced lung hemorrhage, was studied by comparing lesions induced by an infrared laser (a tissue-heating source) with those induced by pulsed ultrasound. A 600-mW continuous-wave CO 2 laser (wavelength ∼10.6 μm) was focused (680-μm beamwidth) on the surface of the lungs of rats for a duration between 10 to 40 s; ultrasound beamwidths were between 310 and 930 μm. After exposure, lungs were examined grossly and then processed for microscopic evaluation. Grossly, lesions induced by laser were somewhat similar to those induced by ultrasound; however, microscopically, they were dissimilar. Grossly, lesions were oval, red to dark red and extended into subjacent tissue to form a cone. The surface was elevated, but the center of the laser-induced lesions was often depressed. Microscopically, the laser-induced injury consisted of coagulation of tissue, cells and fluids, whereas injury induced by ultrasound consisted solely of alveolar hemorrhage. These results suggest that ultrasound-induced lung injury is most likely not caused by a thermal mechanism.

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Section: Ultrasoundmentioning

confidence: 99%

Lesions of ultrasound-induced lung hemorrhage are not consistent with thermal injury

Zachary

Blue

Miller

et al. 2006

Ultrasound in Medicine & Biology

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“…Fig. 21 shows all of occurrence threshold findings across four species using the same methodology [mouse (Zachary et al, 2001a), rat (Zachary et al, 2001a;O'Brien et al, 2001O'Brien et al, , 2003b, rabbit , and pig (O'Brien et al, 2003a)]. Pre-2000 occurrence threshold findings (Fig.…”

Section: Ultrasound-induced Lung Hemorrhagementioning

confidence: 99%

“…Error bars are SEMs. These data, by groupings from left to right, are derived, respectively, from Zachary et al (2001a) and O'Brien et al (2001O'Brien et al ( ,2003aO'Brien et al ( ,b,2006. Summary of lesion occurrence thresholds in terms of p r(in situ) (MPa) (bars; left axis) and MI (lines, right axis) from studies not using our experimental techniques and statistical approach.…”

Section: Fig 19mentioning

confidence: 99%

Ultrasound–biophysics mechanisms

O’Brien

2007

Progress in Biophysics and Molecular Biology

609

416

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Ultrasonic biophysics is the study of mechanisms responsible for how ultrasound and biological materials interact. Ultrasound-induced bioeffect or risk studies focus on issues related to the effects of ultrasound on biological materials. On the other hand, when biological materials affect the ultrasonic wave, this can be viewed as the basis for diagnostic ultrasound. Thus, an understanding of the interaction of ultrasound with tissue provides the scientific basis for image production and risk assessment. Relative to the bioeffect or risk studies, that is, the biophysical mechanisms by which ultrasound affects biological materials, ultrasound-induced bioeffects are generally separated into thermal and nonthermal mechanisms. Ultrasonic dosimetry is concerned with the quantitative determination of ultrasonic energy interaction with biological materials. Whenever ultrasonic energy is propagated into an attenuating material such as tissue, the amplitude of the wave decreases with distance. This attenuation is due to either absorption or scattering. Absorption is a mechanism that represents that portion of ultrasonic wave that is converted into heat, and scattering can be thought of as that portion of the wave, which changes direction. Because the medium can absorb energy to produce heat, a temperature rise may occur as long as the rate of heat production is greater than the rate of heat removal. Current interest with thermally mediated ultrasound-induced bioeffects has focused on the thermal isoeffect concept. The non-thermal mechanism that has received the most attention is acoustically generated cavitation wherein ultrasonic energy by cavitation bubbles is concentrated. Acoustic cavitation, in a broad sense, refers to ultrasonically induced bubble activity occurring in a biological material that contains pre-existing gaseous inclusions. Cavitation-related mechanisms include radiation force, microstreaming, shock waves, free radicals, microjets and strain. It is more challenging to deduce the causes of mechanical effects in tissues that do not contain gas bodies. These ultrasonic biophysics mechanisms will be discussed in the context of diagnostic ultrasound exposure risk concerns.

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“…However, concerns for its safety continue to be raised and addressed by members of the bioeffects research community (WFUMB 1998;AIUM 2000). These concerns are the result of numerous US-induced lung hemorrhage studies in mice, rats, rabbits, monkeys and pigs at exposure conditions similar to those used for scanning in humans Hartman et al 1990;Penney et al 1993;Raeman et al ,1996Frizzell et al 1994Frizzell et al ,2003Tarental and Canfield 1994;Zachary and O'Brien 1995;Harrison et al 1995;Baggs et al 1996;Holland et al 1996;O'Brien and Zachary 1997;Dalecki et al 1997aDalecki et al ,1997bWFUMB 1998;AIUM 2000;O'Brien et al 2000O'Brien et al ,2001aO'Brien et al , 2001bO'Brien et al ,2003aO'Brien et al ,2003bO'Brien et al ,2005Kramer et al 2001;Zachary et al 2001aZachary et al ,2001b.…”

Section: Introductionmentioning

confidence: 99%

“…Further, because there have been other threshold studies conducted using the same experimental and analysis protocols, but with different species, the rabbit threshold findings are compared against adult mouse ) and adult rat O'Brien et al 2001b), as well as pig threshold findings (O'Brien et al 2003a). These threshold findings represent a unique species-dependent dataset that is not available for any other in vivo US-induced biologic effect.…”

Section: Introductionmentioning

confidence: 99%

Threshold estimation of ultrasound-induced lung hemorrhage in adult rabbits and comparison of thresholds in mice, rats, rabbits and pigs

O’Brien

Yang

Simpson

et al. 2006

Ultrasound in Medicine & Biology

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The objective of this study was to assess the threshold and superthreshold behavior of ultrasound (US)-induced lung hemorrhage in adult rabbits to gain greater understanding about species dependency. A total of 99 76 ± 7.6-d-old 2.4 ± 0.14-kg New Zealand White rabbits were used. Exposure conditions were 5.6-MHz, 10-s exposure duration, 1-kHz PRF and 1.1-μs pulse duration. The in situ (at the pleural surface) peak rarefactional pressure, p r(in situ) , ranged between 1.5 and 8.4 MPa, with nine acoustic US exposure groups plus a sham exposure group. Rabbits were assigned randomly to the 10 groups, each with 10 rabbits, except for one group that had nine rabbits. Rabbits were exposed bilaterally with the order of exposure (left then right lung, or right then left lung) and acoustic pressure both randomized. Individuals involved in animal handling, exposure and lesion scoring were blinded to the exposure condition. Probit regression analysis was used to examine the dependence of the lesion occurrence on in situ peak rarefactional pressure and order of exposure (first vs. second). Likewise, lesion depth and lesion root surface area were analyzed using Gaussian tobit regression analysis. Neither probability of a lesion nor lesion size measurements was found to be statistically dependent on the order of exposure after the effect of p r(in situ) was considered. Also, a significant correlation was not detected between the two exposed lung sides on the same rabbit in either lesion occurrence or size measures. The p r(in situ) threshold estimates (in MPa) were similar to each other across occurrence (3.54 ± 0.78), depth (3.36 ± 0.73 and surface area (3.43 ± 0.77) of lesions. Using the same experimental techniques and statistical approach, great consistency of thresholds was demonstrated across three species (mouse, rat and rabbit). Further, there were no differences in the biologic mechanism of injury induced by US and US-induced lesions were similar in morphology in all species and age groups studied. The extent of US-induced lung damage and the ability of the lung to heal led to the conclusion that, although US can produce lung damage at clinical levels, the degree of damage does not appear to be a significant medical problem.

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

Cited by 34 publications

References 29 publications

Lesions of ultrasound-induced lung hemorrhage are not consistent with thermal injury

Lesions of ultrasound-induced lung hemorrhage are not consistent with thermal injury

Ultrasound–biophysics mechanisms

Threshold estimation of ultrasound-induced lung hemorrhage in adult rabbits and comparison of thresholds in mice, rats, rabbits and pigs

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