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 #
5R37EB002641-16
Application #
8442274
Study Section
Biomedical Imaging Technology Study Section (BMIT)
Program Officer
Lopez, Hector
Project Start
1997-12-10
Project End
2016-03-31
Budget Start
2013-04-01
Budget End
2014-03-31
Support Year
16
Fiscal Year
2013
Total Cost
$586,031
Indirect Cost
$206,675
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
Han, Aiguo (2018) A Method for Stereological Determination of the Structure Function From Histological Sections of Isotropic Scattering Media. IEEE Trans Ultrason Ferroelectr Freq Control 65:1007-1016
Muleki-Seya, Pauline; Han, Aiguo; Andre, Michael P et al. (2018) Analysis of Two Quantitative Ultrasound Approaches. Ultrason Imaging 40:84-96
Paige, Jeremy S; Bernstein, Gregory S; Heba, Elhamy et al. (2017) A Pilot Comparative Study of Quantitative Ultrasound, Conventional Ultrasound, and MRI for Predicting Histology-Determined Steatosis Grade in Adult Nonalcoholic Fatty Liver Disease. AJR Am J Roentgenol 208:W168-W177
Bravo Cruz, Ariana G; Han, Aiguo; Roy, Edward J et al. (2017) Deletion of the K1L Gene Results in a Vaccinia Virus That Is Less Pathogenic Due to Muted Innate Immune Responses, yet Still Elicits Protective Immunity. J Virol 91:
Han, Aiguo; Andre, Michael P; Erdman, John W et al. (2017) Repeatability and Reproducibility of a Clinically Based QUS Phantom Study and Methodologies. IEEE Trans Ultrason Ferroelectr Freq Control 64:218-231
Coiado, Olivia C; O'Brien Jr, William D (2017) The Negative Chronotropic Effect in Rat Heart Stimulated by Ultrasonic Pulses: Role of Sex and Age. J Ultrasound Med 36:799-808
Zhu, Yang; Han, Aiguo; O'Brien Jr, William D et al. (2017) Limitations on estimation of effective scatterer diameters. J Acoust Soc Am 142:3677
Koenig, Mary Dawn; McFarlin, Barbara L; Steffen, Alana D et al. (2017) Decreased Nutrient Intake Is Associated With Premature Cervical Remodeling. J Obstet Gynecol Neonatal Nurs 46:123-134
Han, Aiguo; O'Brien, William D (2016) Structure Function Estimated From Histological Tissue Sections. IEEE Trans Ultrason Ferroelectr Freq Control 63:1296-305
Rosado-Mendez, Ivan M; Drehfal, Lindsey C; Zagzebski, James A et al. (2016) Analysis of Coherent and Diffuse Scattering Using a Reference Phantom. IEEE Trans Ultrason Ferroelectr Freq Control 63:1306-20

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