Medical practice involves a significant and growing application of ultrasonic energy both for diagnostic purposes, which should not incur bioeffects, and for therapeutic purposes, which should efficaciously induce desired effects. Ultrasound causes biological change in mammalian tissue primarily through heating, but can also produce bioeffects via ultrasonic cavitation. Due to uncertainties about cavitation, there is a lack of definitive information on appropriate dosimetric parameters, exposure criteria or guidance with regard to the use of ultrasound relative to alternative modalities. If bodies of gas are initially present in a biological medium, then a subtle form of cavitation called gas body activation can occur at all levels of exposure and produce effects even at levels relevant to medical diagnostic methods. We propose a thorough, basic study of the physics of gas body activation, and the etiology of its bioeffects.
Specific aims are: 1) to study ATP release from erythrocytes exposed to ultrasonically activated gas-filled micropores as a function of various physical and biophysical parameters, 2) to analyze these experimental data through application of physical theory for the oscillation of the micropore gas bodies and for nonthermal mechanisms which act on cells near the micropores, 3) to consider the existence and behavior of new forms of gas bodies, such as the stabilized microbubbles employed as ultrasonic contrast agents in echocardiography, and 4) to investigate the possibility of sublytic effects of the micropore gas bodies, such as functional, morphological and surface effects on phagocytic cells. Our hypothesis-testing approach leads to insights with predictive value beyond the limited conditions of specific experiments. Such results reduce the uncertainties about cavitation bioeffects, and progress toward the elucidation of the role of gas body activation in the medical physics of ultrasound.

National Institute of Health (NIH)
National Cancer Institute (NCI)
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Diagnostic Radiology Study Section (RNM)
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University of Vermont & St Agric College
Schools of Arts and Sciences
United States
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Miller, Douglas L; Quddus, Jawaid (2002) Diagnostic ultrasound-induced membrane damage in phagocytic cells loaded with contrast agent and its relation to Doppler-mode images. IEEE Trans Ultrason Ferroelectr Freq Control 49:1094-102
Miller, D L; Quddus, J (2001) Lysis and sonoporation of epidermoid and phagocytic monolayer cells by diagnostic ultrasound activation of contrast agent gas bodies. Ultrasound Med Biol 27:1107-13
Miller, D L; Spooner, G J; Williams, A R (2001) Photodisruptive laser nucleation of ultrasonic cavitation for biomedical applications. J Biomed Opt 6:351-8
Miller, D L; Quddus, J (2000) Sonoporation of monolayer cells by diagnostic ultrasound activation of contrast-agent gas bodies. Ultrasound Med Biol 26:661-7
Miller, D L; Quddus, J (2000) Diagnostic ultrasound activation of contrast agent gas bodies induces capillary rupture in mice. Proc Natl Acad Sci U S A 97:10179-84
Miller, D L; Gies, R A (2000) The influence of ultrasound frequency and gas-body composition on the contrast agent-mediated enhancement of vascular bioeffects in mouse intestine. Ultrasound Med Biol 26:307-13
Miller, D L; Bao, S; Gies, R A et al. (1999) Ultrasonic enhancement of gene transfection in murine melanoma tumors. Ultrasound Med Biol 25:1425-30
Miller, D L; Bao, S; Morris, J E (1999) Sonoporation of cultured cells in the rotating tube exposure system. Ultrasound Med Biol 25:143-9
Miller, D L; Gies, R A (1999) Consequences of lithotripter shockwave interaction with gas body contrast agent in mouse intestine. J Urol 162:606-9
Williams, A R; Bao, S; Miller, D L (1999) Filtroporation: A simple, reliable technique for transfection and macromolecular loading of cells in suspension. Biotechnol Bioeng 65:341-6

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