We have developed a new high-frequency ultrasound scanning system that provides the opportunity to obtain a two-dimensional map of blood flow in the anterior segment of the eye in one second, with spatial resolution on the order of 40 microns and velocity resolution on the order of 0.2 mm/s. This represents approximately an order of magnitude improvement in resolution over existing techniques, and provides the first non-invasive opportunity to evaluate blood flow in arterioles and venules in opaque tissues. In addition, a new strategy to estimate capillary volume and flow rate has been developed by combining a theoretical model and a system to interrogate individual contrast microbubbles. This new suite of tools can be applied to improve the understanding of the mechanisms of ophthalmic diseases including glaucoma and age-related macular degeneration as well as the mechanisms and effectiveness of treatment options. Here, we specifically address glaucoma. The clinical significance of an improvement in the management of ophthalmic diseases is enormous since 3 million people in the US alone suffer from glaucoma, 100,000 per year suffer some form of ocular trauma, and over 6 million people in the US suffer from degenerative retinal diseases. Most experts agree that glaucoma is a series of conditions characterized by a particular form of optic nerve damage that is often associated with elevated intra-ocular pressure, although the mechanisms responsible for damage and successful therapy are not understood. Many drug therapies for glaucoma are assumed to decrease intra-ocular pressure through the constriction of arterioles in the ciliary body, however, it has been impossible to measure these changes in ciliary body blood flow, or to measure optic nerve head perfusion. Our new technique to estimate arteriolar diameter and flow rate will be evaluated in a human study of glaucoma therapies. Contrast-assisted methods for the estimation of capillary volume and flow rate will be developed for the high resolution requirements of ophthalmology. This requires the further development of our experimental system, the evaluation of new contrast agents with higher resonant frequencies, and the validation of our new strategies for the estimation of capillary density. These new techniques will be used to evaluate perfusion in the ciliary body and in the optic nerve head in an animal model study of drug therapies, and compared with the output of a scanning laser Doppler flowmeter. In conjunction with this study, mechanical damage to the vessel wall will be directly assessed through the use of fluorescent markers.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY011468-05
Application #
6179912
Study Section
Special Emphasis Panel (ZRG1-DMG (06))
Program Officer
Liberman, Ellen S
Project Start
1996-05-01
Project End
2004-08-31
Budget Start
2000-09-01
Budget End
2001-08-31
Support Year
5
Fiscal Year
2000
Total Cost
$200,955
Indirect Cost
Name
University of California Davis
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
094878337
City
Davis
State
CA
Country
United States
Zip Code
95618
Kruse, Dustin E; Ferrara, Katherine W (2005) A new imaging strategy using wideband transient response of ultrasound contrast agents. IEEE Trans Ultrason Ferroelectr Freq Control 52:1320-9
Sun, Yang; Kruse, Dustin E; Dayton, Paul A et al. (2005) High-frequency dynamics of ultrasound contrast agents. IEEE Trans Ultrason Ferroelectr Freq Control 52:1981-91
Kruse, Dustin E; Ferrara, Katherine W (2002) A new high resolution color flow system using an eigendecomposition-based adaptive filter for clutter rejection. IEEE Trans Ultrason Ferroelectr Freq Control 49:1739-54
Silverman, Ronald H; Ursea, Roxana; Kruse, Dustin et al. (2002) Ultrasound measurement of the effect of temperature on microperfusion in the eye. Ultrasound Med Biol 28:1413-9
Kruse, Dustin E; Ferrara, Katherine W (2002) A new high resolution color flow system using an eigendecomposition-based adaptive filter for clutter rejection. IEEE Trans Ultrason Ferroelectr Freq Control 49:1384-99
Allen, J S; Kruse, D E; Ferrara, K W (2001) Shell waves and acoustic scattering from ultrasound contrast agents. IEEE Trans Ultrason Ferroelectr Freq Control 48:409-18
Silverman, R H; Kruse, D E; Coleman, D J et al. (1999) High-resolution ultrasonic imaging of blood flow in the anterior segment of the eye. Invest Ophthalmol Vis Sci 40:1373-81
Zagar, B G; Fornaris, R J; Ferrara, K W (1998) Ultrasonic mapping of the microvasculature: signal alignment. Ultrasound Med Biol 24:809-24