Abstract

A diagnostic technique capable of accurately assessing pathologic changes of the peripheral microcirculation in patients with diabetes could be used to detect early microvascular complications, to assess response to new and established therapies, and possibly to detect large-vessel vascular disease. The overall purpose of this proposal is to apply the recently developed non-invasive perfusion imaging technique of contrast-enhanced ultrasound, which is able to assess skeletal muscle perfusion at the capillary level, for the evaluation of microvascular alterations associated with diabetes and insulin-resistance.
The first aim of this proposal is to determine whether contrast ultrasound can be used to detect abnormalities in the skeletal muscle capillary responses to increased muscle oxygen demand (exercise) and to insulin in patients and animal models of insulin-resistance and diabetes. Any association between abnormal capillary responses and diabetic microvascular complications will be characterized.
The second aim i s to develop a method for detecting peripheral vascular disease and for assessing its physiologic significance on limb perfusion using contrast ultrasound in a canine model and in patients with peripheral vascular disease. Data from these studies will be clinically important since information will be provided on the total impact of combined large-vessel and microvascular disease on distal perfusion.
The final aim will be to use contrast ultrasound with novel site-targeted ultrasound contrast agents that bind to activated leukocytes in regions of injury/inflammation to assess tissue inflammatory responses that occur in response to peripheral vascular disease and demand ischemia. Data from these studies will be used to determine whether inflammatory responses are enhanced in animal models of diabetes. Successful completion of these studies will represent the first step in developing a reliable, widely available, and inexpensive method for ultrasound detection and characterization of diabetic vascular disease and microvascular complications.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK063508-02
Application #
6666957
Study Section
Special Emphasis Panel (ZRG1-SRB (08))
Program Officer
Laughlin, Maren R
Project Start
2002-09-30
Project End
2006-08-31
Budget Start
2003-09-01
Budget End
2004-08-31
Support Year
2
Fiscal Year
2003
Total Cost
$333,000
Indirect Cost

  Institution

Name
University of Virginia
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
065391526
City
Charlottesville
State
VA
Country
United States
Zip Code
22904

  Publications

Lindner, Jonathan R (2018) Cause or Effect? Microvascular Dysfunction in Insulin-Resistant States. Circ Cardiovasc Imaging 11:e007725
Belcik, J Todd; Davidson, Brian P; Xie, Aris et al. (2017) Augmentation of Muscle Blood Flow by Ultrasound Cavitation Is Mediated by ATP and Purinergic Signaling. Circulation 135:1240-1252
Lindner, Jonathan R (2016) Phase-Conversion Nanoparticle Contrast Agents: Do Good Things Come in Small Packages? Circ Cardiovasc Imaging 9:
Seol, Sang-Hoon; Davidson, Brian P; Belcik, J Todd et al. (2015) Real-time contrast ultrasound muscle perfusion imaging with intermediate-power imaging coupled with acoustically durable microbubbles. J Am Soc Echocardiogr 28:718-26.e2
Belcik, J Todd; Davidson, Brian P; Foster, Ted et al. (2015) Contrast-enhanced ultrasound assessment of impaired adipose tissue and muscle perfusion in insulin-resistant mice. Circ Cardiovasc Imaging 8:
Inaba, Yoichi; Davidson, Brian P; Kim, Sajeevani et al. (2014) Echocardiographic evaluation of the effects of stem cell therapy on perfusion and function in ischemic cardiomyopathy. J Am Soc Echocardiogr 27:192-9
Chadderdon, Scott M; Belcik, J Todd; Bader, Lindsay et al. (2014) Proinflammatory endothelial activation detected by molecular imaging in obese nonhuman primates coincides with onset of insulin resistance and progressively increases with duration of insulin resistance. Circulation 129:471-8
Davidson, Brian P; Chadderdon, Scott M; Belcik, J Todd et al. (2014) Ischemic memory imaging in nonhuman primates with echocardiographic molecular imaging of selectin expression. J Am Soc Echocardiogr 27:786-793.e2
Shim, Chi Young; Kim, Sajeevani; Chadderdon, Scott et al. (2014) Epoxyeicosatrienoic acids mediate insulin-mediated augmentation in skeletal muscle perfusion and blood volume. Am J Physiol Endocrinol Metab 307:E1097-104
Liu, Yani; Davidson, Brian P; Yue, Qi et al. (2013) Molecular imaging of inflammation and platelet adhesion in advanced atherosclerosis effects of antioxidant therapy with NADPH oxidase inhibition. Circ Cardiovasc Imaging 6:74-82

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