Lack of bioeffects of ultrasound energy after intravenous administration of FS069 (Optison) in the anesthetized rabbit.

Killam, Anne L.; Greener, Yigal; McFerran, Britta A.; Maniquis, Jack; Bloom, A E; Widder, Kenneth J.; Dittrich, Howard C.

doi:10.7863/jum.1998.17.6.349

Cited by 24 publications

(14 citation statements)

References 18 publications

(15 reference statements)

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“…Hemorrhage in the vascular beds of the intestine and skin (Miller and Quddus, 2000b;Miller and Gies, 2000) and damage to cells in the heart (Skyba et al, 1998) were also demonstrated in mice and dogs, respectively, following intravenous injection of contrast agent and exposure to pulsed ultrasound. In vivo studies have reported induction of petechiae and hemolysis (Killam et al, 1998;Skyba et al, 1998;Miller and Quddus, 2000b;Wible et al, 2002;Hwang et al 2005), damage to the intestinal wall Gies, 1998a,b,2000;Kobayashi et al, 2002Kobayashi et al, ,2003, and alteration to the blood-brain barrier (Schlachetzki et al, 2002;Hynynen et al, 2003).…”

Section: Cavitation With Injected Microbubblesmentioning

confidence: 99%

Ultrasound–biophysics mechanisms

O’Brien

2007

Progress in Biophysics and Molecular Biology

593

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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Section: Cavitation With Injected Microbubblesmentioning

confidence: 99%

Ultrasound–biophysics mechanisms

O’Brien

2007

Progress in Biophysics and Molecular Biology

593

416

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“…Pulsed ultrasound with contrast agent has been shown to cause hemolysis in vivo at levels near those used for diagnostic instruments (24), but other tests for induction of hemolysis with an actual diagnostic scanner were negative (25). During intravital microscopy, microvessel rupture has been observed to occur within the rat spinotrapezius muscle with Optison gas bodies sonicated with a diagnostic ultrasound scanner (26,27).…”

mentioning

confidence: 99%

Diagnostic ultrasound activation of contrast agent gas bodies induces capillary rupture in mice

Miller

Quddus

2000

Proc. Natl. Acad. Sci. U.S.A.

213

137

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Interaction of diagnostic ultrasound with gas bodies produces a useful contrast effect in medical images, but the same interaction also represents a mechanism for bioeffects. Anesthetized hairless mice were scanned by using a 2.5-MHz transducer (610-ns pulses with 3.6-kHz repetition frequency and 61-Hz frame rate) after injection of Optison and Evans blue dye. Petechial hemorrhages (PHs) in intestine and abdominal muscle were counted 15 min after exposure to characterize capillary rupture, and Evans blue extravasation was evaluated in samples of muscle tissue. For 5 ml⅐kg -1 contrast agent and exposure to 10 alternating 10-s on and off periods, PH counts in muscle were approximately proportional to the square of peak negative pressure amplitude and were statistically significant above 0.64 MPa. PH counts in intestine and Evans blue extravasation into muscle tissue were significant above 1.0 MPa. The PH effect in muscle was proportional to contrast dose and was statistically significant for the lowest dose of 0.05 ml⅐kg -1 . The effects decreased nearly to sham levels if the exposure was delayed 5 min. The PH effect in abdominal muscle was significant and statistically indistinguishable for uninterrupted 100-s exposure, 10-s exposure, 100 scans repeated at 1 Hz, and even for a single scan. The results confirms a previous report of PH induction by diagnostic ultrasound with contrast agent in mammalian skeletal muscle [Skyba, D. M., Price, R.

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“…The percent of reported hemolysis for mice exposed at the highest amplitude in the absence of exogenous microbubbles was comparable to that of sham-exposed animals, indicates that the presence of nuclei in normal blood in vivo is rare [20]. Experimental study from Kilam et al provides further evidence of the relatively low likelihood of significant ultrasound-induced hemolysis in vivo for clinical diagnostic procedures [21].…”

Section: Technical Considerations-biological Ef-fectsmentioning

confidence: 82%

Ultrasound Contrast Agents: Updated Data on Safety Profile

Aggeli

Felekos²,

Siasos³

et al. 2012

CPD

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Contrast echocardiography represents a major technological advancement in the constantly evolving field of cardiovascular imaging. Over the last twenty years numerous studies have been published, illustrating the incremental value of contrast implementation into a variety of clinical scenarios. However, serious concerns have been raised about contrast safety profile, mainly based on postmarketing observational data and several animal studies. The latter have investigated contrast bio effects under experimental conditions that are not consistent with daily clinical practice. On the other hand, numerous clinical trials with large registries have proven otherwise. Not only contrast agents are efficient, but they also demonstrate a remarkable safety profile. So the question is: should we fear contrast utilization or should we consider them as an adjunctive and indispensable clinical tool for daily bedside practice?

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Lack of bioeffects of ultrasound energy after intravenous administration of FS069 (Optison) in the anesthetized rabbit.

Cited by 24 publications

References 18 publications

Ultrasound–biophysics mechanisms

Ultrasound–biophysics mechanisms

Diagnostic ultrasound activation of contrast agent gas bodies induces capillary rupture in mice

Ultrasound Contrast Agents: Updated Data on Safety Profile

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