on June 13, 2005
Published online before print June 13, 2005, doi: 10.1161/CIRCULATIONAHA.104.481515
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Submitted on June 4, 2004
From the Cardiovascular Imaging Center and Cardiovascular Division, University of Virginia School of Medicine, Charlottesville. * To whom correspondence should be addressed. E-mail: jlindner{at}virginia.edu.
Background--We hypothesized that molecular imaging with contrast-enhanced ultrasound (CEU) and microbubbles targeted to endothelial integrins could be used to noninvasively assess early angiogenic responses to ischemia and growth factor therapy. Methods and Results--Hindlimb ischemia was produced in 48 rats by ligation of an iliac artery. Half of the animals received intramuscular sustained-release fibroblast growth factor-2 (FGF-2). Immediately after ligation and at subsequent intervals from 4 to 28 days, blood flow and oxygen tension in the proximal adductor muscles were measured by CEU perfusion imaging and phosphor quenching, respectively. Targeted CEU imaging of Conclusions--Targeted CEU can be used to assess endogenous and therapeutic arteriogenesis before recovery of tissue perfusion. These results suggest that molecular imaging of integrin expression may be useful for evaluating proangiogenic therapies.
Revised on December 29, 2004
Accepted on February 7, 2005
Assessment of Endogenous and Therapeutic Arteriogenesis by Contrast Ultrasound Molecular Imaging of Integrin Expression
Howard Leong-Poi MD,
v- and 5
1-integrin expression was performed with microbubbles bearing the disintegrin echistatin. Iliac artery ligation produced a 65% to 70% reduction in blood flow and oxygen tension. In untreated ischemic muscle, muscle flow and oxygen tension partially recovered by days 14 to 28. In these animals, signal from integrin-targeted microbubbles was intense and peaked before flow increase (days 4 to 7). In comparison to untreated animals, FGF-2-treated muscle had a greater rate and extent of blood flow recovery and greater signal intensity from integrin-targeted microbubbles, which peaked before maximal recovery of flow. On immunohistology, arteriolar but not capillary density increased in the ischemic limb after ligation, the rate and degree of which were greater in FGF-2-treated rats. Immunofluorescence demonstrated intense staining for v in arterioles, the temporal course of which correlated with targeted imaging.
Key words: angiogenesis • echocardiography • ischemia • peripheral vascular diseases • ultrasonics
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Circulation 2005 111: 3188-3191.
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