This application proposes to develop an ultrasound technique that uses microbubble-based contrast agents to measure blood flow in mouse tumors. Towards this goal, the investigators have developed a multigating pulse sequence that allows acquisition of ultrasound images at a variable frame rate during bolus injection of the contrast agent. The rate at which the microbubbles are destroyed as a function of image acquisition is used to measure contrast flow. The overall goal is to validate this approach and to develop it to a form that can be used to measure flow on a routine basis. The proposed research has five specific aims involving (i) further refinement of the technique, (ii) its validation by comparison with true flow in phantoms and mouse tumors, (iii) establishing the influence of various imaging and contrast agent properties on the measurements, (iv) establishing the limits imposed by inter- and intra- subject variability in the measurements and (v) demonstrating the feasibility of the technique for measuring change in blood flow in response to physiological and therapeutic interventions. At the completion of this project the investigators anticipate having a thoroughly evaluated method for the assessment of blood flow using ultrasound contrast agents. With the approval of various contrast agents for use in clinics by the regulatory agencies impending, this technology is timely and is likely to useful in the diagnosis and treatment of many cancers and cardiovascular diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB001713-03
Application #
6923591
Study Section
Special Emphasis Panel (ZRG1-EB (52))
Program Officer
Zhang, Yantian
Project Start
2003-09-20
Project End
2007-07-31
Budget Start
2005-08-01
Budget End
2006-07-31
Support Year
3
Fiscal Year
2005
Total Cost
$336,813
Indirect Cost
Name
University of Pennsylvania
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Wood, Andrew K W; Sehgal, Chandra M (2015) A review of low-intensity ultrasound for cancer therapy. Ultrasound Med Biol 41:905-28
Wood, Andrew K W; Bunte, Ralph M; Schultz, Susan M et al. (2009) Acute increases in murine tumor echogenicity after antivascular ultrasound therapy: a pilot preclinical study. J Ultrasound Med 28:795-800
Sehgal, Chandra M; Cary, Theodore W; Arger, Peter H et al. (2009) Delta-projection imaging on contrast-enhanced ultrasound to quantify tumor microvasculature and perfusion. Acad Radiol 16:71-8
Wood, Andrew K W; Bunte, Ralph M; Price, Heather E et al. (2008) The disruption of murine tumor neovasculature by low-intensity ultrasound-comparison between 1- and 3-MHz sonication frequencies. Acad Radiol 15:1133-41
Seiler, Gabriela S; Ziemer, Lisa S; Schultz, Susan et al. (2007) Dose-response relationship of ultrasound contrast agent in an in vivo murine melanoma model. Cancer Imaging 7:216-23
Wood, Andrew K W; Bunte, Ralph M; Cohen, Jennie D et al. (2007) The antivascular action of physiotherapy ultrasound on a murine tumor: role of a microbubble contrast agent. Ultrasound Med Biol 33:1901-10
Bunte, Ralph M; Ansaloni, Sara; Sehgal, Chandra M et al. (2006) Histopathological observations of the antivascular effects of physiotherapy ultrasound on a murine neoplasm. Ultrasound Med Biol 32:453-61
Ziemer, Lisa S; Lee, William M F; Vinogradov, Sergei A et al. (2005) Oxygen distribution in murine tumors: characterization using oxygen-dependent quenching of phosphorescence. J Appl Physiol 98:1503-10
Wood, Andrew K W; Ansaloni, Sara; Ziemer, Lisa S et al. (2005) The antivascular action of physiotherapy ultrasound on murine tumors. Ultrasound Med Biol 31:1403-10
Tsai, Jeff H; Makonnen, Sosina; Feldman, Michael et al. (2005) Ionizing radiation inhibits tumor neovascularization by inducing ineffective angiogenesis. Cancer Biol Ther 4:1395-1400