Hemolysis in vivo from exposure to pulsed ultrasound

Dalecki, Diane; Raeman, Carol H.; Child, Sally Z.; Cox, Christopher; Francis, Charles W.; Meltzer, Richard S.; Carstensen, Edwin L.

doi:10.1016/s0301-5629(96)00203-7

Cited by 112 publications

(53 citation statements)

References 9 publications

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“…In vitro studies with laboratory exposure systems indicate that cavitation thresholds are low relative to DUS upper limits and that thresholds for cellular bioeffects with UCAs increase with ultrasonic frequency more rapidly than f ½ (Miller et al, 1997;Dalecki et al 1997;Miller and Dou, 2004a,b). These insights are important but cannot be related directly to in vivo DUS conditions with circulating contrast agent.…”

Section: Introduction and Literaturementioning

confidence: 99%

Frequency Dependence of Kidney Injury Induced by Contrast-Aided Diagnostic Ultrasound in Rats

Miller¹,

Dou²,

Wiggins³

2008

Ultrasound in Medicine & Biology

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This study was performed to examine the frequency dependence of glomerular capillary hemorrhage (GCH) induced by contrast aided diagnostic ultrasound in rats. Diagnostic ultrasound (DUS) scanners were utilized for exposure at 3.2, 5.0 and 7.4 MHz, and previously published data at 1.5 and 2.5 MHz also was included. A laboratory exposure system was used to simulate DUS exposure at 1.0, 1.5, 2.25, 3.5, 5.0 and 7.5 MHz with higher peak rarefactional pressure amplitudes (PRPAs) than were available from our DUS systems. The right kidneys of rats mounted in a water bath were exposed to intermittent image pulse sequences at 1 s intervals during infusion of diluted ultrasound contrast agent. The percentage of GCH was zero for low PRPAs, and then rapidly increased with increasing PRPAs above an apparent threshold, p t . The values of p t were approximately proportional to the ultrasound frequency, f, such that p t /f was approximately 0.5 MPa/MHz for DUS and 0.6 MPa/MHz for laboratory-system exposures. The increasing thresholds with increasing frequency limited the GCH effect for contrast aided DUS, and no GCH was seen for DUS at 5.0 or 7.4 MHz for the highest available PRPAs.

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Section: Introduction and Literaturementioning

confidence: 99%

Frequency Dependence of Kidney Injury Induced by Contrast-Aided Diagnostic Ultrasound in Rats

Miller¹,

Dou²,

Wiggins³

2008

Ultrasound in Medicine & Biology

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“…These concerns were raised by studies documenting hemolysis of erythrocytes in vitro in cell suspensions that contained contrast agent and in vivo in mice injected with intravenous contrast agent that were exposed to pulsed ultrasound (Williams et al, 1991;Dalecki et al, 1997b;Miller et al, 1997;Miller and Gies, 1998a,b;Poliachik et al, 1999;Brayman and Miller, 1999). In vitro studies have reported damage to monolayers of cultured cells whose culture media contained contrast agent and were exposed to pulsed ultrasound (Brayman et al, 1999a;Ward et al, 1999;Miller and Bao, 1998;Miller and Quddus, 2000a).…”

Section: Cavitation With Injected Microbubblesmentioning

confidence: 99%

Ultrasound–biophysics mechanisms

O’Brien

2007

Progress in Biophysics and Molecular Biology

605

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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“…7 Concerns have been raised about the interaction of ultrasound with microbubble contrast agents in studies documenting in vitro and in vivo bioeffects. [8][9][10][11][12][13][14][15][16][17][18][19][20] These concerns have been addressed by the Bioeffects Committee of the American Institute of Ultrasound in Medicine. 21,22 It was advised that contrast agent exposure conditions that minimize the potential for bioeffect occurrence should be used.…”

mentioning

confidence: 99%

Arrhythmias in Rat Hearts Exposed to Pulsed Ultrasound After Intravenous Injection of a Contrast Agent

Zachary

Hartleben

Frizzell

et al. 2002

Journal of Ultrasound in Medicine

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Objective.To develop an animal model suitable for characterizing electrocardiographic arrhythmias in hearts exposed to ultrasound after injection of a microbubble contrast agent. Methods. Conduction complex and heart lesion data were recorded from 20 rats that received intravenous injections of 0.25 mL of a contrast agent and were exposed to pulsed ultrasound (frequency, 3.1 MHz; pulse duration, 1.3 microseconds; pulse repetition frequency, 1700 Hz; and in situ peak rarefactional pressure, 15.9 MPa). The volume of the contrast agent based on body weight and the mechanical index (ultrasonic pressure) exceeded those used in echocardiography by 14 to 345 and 3 to 29 times, respectively. Results. Premature atrial complexes, premature ventricular complexes, or polymorphic ventricular tachycardia occurred in 10 rats. When ultrasound exposure was halted, arrhythmias ceased but reoccurred in 4 of the 10 rats when exposure resumed. Myocardial degeneration identified by histochemical staining (hematoxylin-basic fuchsinpicric acid) was observed in 16 rats; however, only 10 rats had arrhythmias. There was no significant difference in the amount of histochemical staining in hearts from rats with arrhythmias when compared with rats without arrhythmias. Conclusions. An animal model suitable for characterizing electrocardiographic arrhythmias in rat hearts exposed to ultrasound after injection of a microbubble contrast agent was developed. Because arrhythmias were induced principally when the contrast agent interacted with ultrasound during exposure, the presence of myocardial degeneration alone was not a sufficient explanation for ectopic electrical activity. Under these extreme exposure conditions, the data suggest that pulsed ultrasound through its biomechanical interactions with contrast agents has the potential to induce arrhythmias.

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Hemolysis in vivo from exposure to pulsed ultrasound

Cited by 112 publications

References 9 publications

Frequency Dependence of Kidney Injury Induced by Contrast-Aided Diagnostic Ultrasound in Rats

Frequency Dependence of Kidney Injury Induced by Contrast-Aided Diagnostic Ultrasound in Rats

Ultrasound–biophysics mechanisms

Arrhythmias in Rat Hearts Exposed to Pulsed Ultrasound After Intravenous Injection of a Contrast Agent

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