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Experimental Studies |
1 From the Department of Medicine, Cardiovascular Angiogenesis Research Center, Beth Israel Deaconess Medical Center-East, 330 Brookline Ave, DA 827, Boston, MA 02215. Received October 12, 1998; revision requested December 17; final revision received June 20, 1999; accepted July 19. J.D.P. supported in part by National Institutes of Health (NIH) grant HL55354, R.J.L. supported in part by NIH grant HL MO1 RR01032, and M.S. supported in part by NIH grants HL53793 and HL56993. Address reprint requests to J.D.P. (e-mail: jdp@shogi.bidmc.harvard.edu).
PURPOSE: To assess the ability to track neovascularization over time with a magnetic resonance (MR) imaging technique sensitized to new intramyocardial collateral development as a means of evaluating therapeutic angiogenesis.
MATERIALS AND METHODS: Magnetization preparation plus spatial frequency reordering was applied to distinguish new intramyocardial collateral vessels from normal circulation on the basis of geometric differences. A vascular occluder was inserted in 34 pigs, and they were assigned randomly to treatment groups with either placebo or angiogenic growth factor. Collateral extent determined with collateral-sensitive MR imaging was correlated with direct measurements by means of three-dimensional (3D) computed tomography (CT), coronary blood flow distribution determined with microspheres, and findings at histologic examination. Changes in the signal at collateral-sensitive MR imaging before and after treatment were assessed by two observers blinded to treatment.
RESULTS: The collateral extent determined with collateral-sensitive MR imaging correlated well with findings at 3D CT (r = 0.95) and with microspheres (r = 0.86). Furthermore, the collateral extent determined with collateral-sensitive MR imaging increased significantly (P < .001) in response to the administration of an angiogenic growth factor but not to placebo. The correspondence of findings at collateral-sensitive MR imaging to collateral neovascularization was confirmed at histologic examination.
CONCLUSION: The presence of intramyocardial collateral microvessels was accurately determined with collateral-sensitive MR imaging. The technique may be useful in clinical studies of therapeutic angiogenesis.
Index terms: Animals • Coronary angiography, technology, 54.121417, 54.121419 • Coronary vessels, flow dynamics, 54.121417, 54.121419 • Coronary vessels, MR, 54.121417, 54.121419 • Heart, CT, 51.12116, 51.12117 • Myocardium, infarction, 51.121419, 511.121417
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