The proposed research program is a basic science (non-clinical) investigation of a potentially significant ultrasound (US)-induced biological effect, that is, whether the application of ultrasound contrast agents (UCAs) in humans adversely affects the vasculature. The medical profession benefits from these studies if it is shown that diagnostic US is a significant medical risk to the patient by advising clinicians about this risk, and by suggesting how the clinician can monitor the degree of risk. Likewise, the medical profession benefits from these studies if it is shown that diagnostic US is not a significant medical risk to the patient by eliminating vascular injury as a clinical concern. In either case, there is clear medical significance. The data necessary to decide this issue are not currently available. Today, we are faced with a significant challenge about the use of UCAs in humans, that is, the lack of knowledge as to whether the interaction of US with UCAs is a significant medical problem in humans. The FDA is also uncertain about UCAs'safety and/or effectiveness and is waiting until more is known about the risk of these agents before approving new UCAs, thus denying their well-known benefits to the patient. Studies have been designed to address directly this "safe-use" issue by an interdisciplinary group of investigators who have considerable experience with US-induced tissue damage studies, as well as considerable experimental and theoretical experience with US biophysics and related physics areas. Using our continued proactive approach, we propose to utilize our extensive US bioeffects/biophysics expertise, along with our pathological, nutritional, biostatistical modeling and animal model expertise, to determine whether the interaction of US with UCAs is a significant medical problem in humans. The experimental (animal-based) and theoretical (mechanism-development) research program has four specific aims, viz., 1) to determine the US thresholds for arterial damage in normal, healthy New Zealand white (NZW) rabbits when US interacts with UCAs in vivo;2) to determine the US thresholds for arterial damage in post-exposure atherogenic diet-fed NZW rabbits when US interacts with UCAs in vivo;3) to determine the US thresholds for arterial damage in pre-exposure atherogenic diet-fed NZW rabbits when US interacts with UCAs in vivo;and 4) to determine UCA thresholds in vitro. We are proposing 7 in vivo studies and a set of in vitro studies to accomplish our experimental and theoretical objectives.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
3R37EB002641-16S1
Application #
8723339
Study Section
Biomedical Imaging Technology Study Section (BMIT)
Program Officer
Lopez, Hector
Project Start
1997-12-10
Project End
2016-03-31
Budget Start
2013-09-01
Budget End
2014-03-31
Support Year
16
Fiscal Year
2013
Total Cost
$99,190
Indirect Cost
$36,649
Name
University of Illinois Urbana-Champaign
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
041544081
City
Champaign
State
IL
Country
United States
Zip Code
61820
King, Daniel A; O'Brien Jr, William D (2014) Quantitative analysis of ultrasound contrast agent postexcitation collapse. IEEE Trans Ultrason Ferroelectr Freq Control 61:1237-41
Coiado, Olivia C; O'Brien Jr, William D (2014) The role of the duty factor in ultrasound-mediated cardiac stimulation. J Acoust Soc Am 136:EL231
Gauthier, Marianne; King, Daniel A; O'Brien Jr, William D (2013) Evaluation of the temporal stability of Definity using double passive cavitation detection. J Ultrasound Med 32:1535-7
Gauthier, Marianne; King, Daniel; O'Brien, William (2013) Influence of microbubble size on postexcitation collapse thresholds for single ultrasound contrast agents using double passive cavitation detection. IEEE Trans Ultrason Ferroelectr Freq Control 60:877-9
Borrelli, Michael J; O'Brien Jr, William D; Bernock, Laura J et al. (2012) Production of uniformly sized serum albumin and dextrose microbubbles. Ultrason Sonochem 19:198-208
Smith, Brendon W; Simpson, Douglas G; Sarwate, Sandhya et al. (2012) Contrast ultrasound imaging of the aorta alters vascular morphology and circulating von Willebrand factor in hypercholesterolemic rabbits. J Ultrasound Med 31:711-20
Forbes, Monica M; O'Brien Jr, William D (2012) Development of a theoretical model describing sonoporation activity of cells exposed to ultrasound in the presence of contrast agents. J Acoust Soc Am 131:2723-9
Leithem, Scott M; Lavarello, Roberto J; O'Brien Jr, William D et al. (2012) Estimating concentration of ultrasound contrast agents with backscatter coefficients: experimental and theoretical aspects. J Acoust Soc Am 131:2295-305
Johnson, Chenara A; Miller, Rita J; O'Brien Jr, William D (2011) Ultrasound contrast agents affect the angiogenic response. J Ultrasound Med 30:933-41
Forbes, Monica M; Steinberg, Ryan L; O'Brien Jr, William D (2011) Frequency-dependent evaluation of the role of definity in producing sonoporation of Chinese hamster ovary cells. J Ultrasound Med 30:61-9

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