Coronary Angiogenesis: Detection in Vivo with MR Imaging Sensitive to Collateral Neocirculation—Preliminary Study in Pigs
Abstract
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.
References
- 1 Schaper W, Ito W. Molecular mechanisms of collateral vessel growth. Circ Res 1996; 79:911-919. Crossref, Medline, Google Scholar
- 2 Betriu A, Castaner A, Sanz G, et al. Angiographic findings 1 month after myocardial infarction: a prospective study of 259 survivors. Circulation 1982; 65:1099-1105. Crossref, Medline, Google Scholar
- 3 Freedman S, Dunn R, Bernstein L, Morris J, Kelly D. Influence of coronary collateral blood flow on the development of exertional ischemia and Q wave infarction in patients with severe single-vessel disease. Circulation 1985; 71:681-686. Crossref, Medline, Google Scholar
- 4 Fujita M, Sasayama S, Ohno A, Nakajima H, Asanoi H. Importance of angina for development of collateral circulation. Br Heart J 1987; 57:139-143. Crossref, Medline, Google Scholar
- 5 Sasayama S, Fujita M. Recent insights into coronary collateral circulation. Circulation 1992; 85:1197-1204. Crossref, Medline, Google Scholar
- 6 Kolibash A, Bush C, Wepsic R, et al. Coronary collateral vessels: spectrum of physiological capabilities with respect to providing rest and stress myocardial perfusion, maintenance of left ventricular function and protection against infarction. Am J Cardiol 1982; 50:230-238. Crossref, Medline, Google Scholar
- 7 Ware JA, Simons M. Angiogenesis in ischemic heart disease. Nat Med 1997; 3:158-164. Crossref, Medline, Google Scholar
- 8 Oshio K, Singh M. A computer simulation of T2 decay effects in echo planar imaging. Magn Reson Med 1989; 11(suppl 1):389-397. Crossref, Medline, Google Scholar
- 9 Mathur-De Vre R, Grimee R, Parmentier F, Binet J. The use of agar gel as a basic reference material for calibrating relaxation times and imaging parameters. Magn Reson Med 1985; 2:176-179. Crossref, Medline, Google Scholar
- 10 Pearlman JD, Hibberd MG, Chuang ML, et al. Magnetic resonance mapping demonstrates benefits of VEGF-induced myocardial angiogenesis. Nat Med 1995; 1:1085-1089. Crossref, Medline, Google Scholar
- 11 Harada K, Grossman W, Friedman M, et al. Basic fibroblast growth factor improves myocardial function in chronically ischemic porcine hearts. J Clin Invest 1994; 94:623-630. Crossref, Medline, Google Scholar
- 12 Lopez JJ, Edelman ER, Stamler A, et al. Basic fibroblast growth factor in a porcine model of chronic ischemia: a comparison of angiographic, echocardiographic and coronary flow parameters. J Pharmacol Exp Ther 1997; 282:385-390. Medline, Google Scholar
- 13 Pearlman J, Laham R, Simons M, Gladstone S, Raptopoulos V. 3D elastic subtraction spiral CT definition of myocardial collateralization extent. Acad Radiol 1997; 4:680-686. Crossref, Medline, Google Scholar
- 14 Imaging apparatus and method with compensation for object motion; Pearlman JD, inventor. Beth Israel Deaconess Medical Center, assignee. US patent 5,602,891. 1997 Feb 11.. Google Scholar
- 15 Roth DM, Maruoka Y, Rogers J, et al. Development of coronary collateral circulation in left circumflex Ameroid-occluded swine myocardium. Am J Physiol 1987; 253:H1279-H1288. Medline, Google Scholar
- 16 Harada K, Friedman M, Lopez JJ, et al. Vascular endothelial growth factor administration in chronic myocardial ischemia. Am J Physiol 1996; 270:H1791-H1802. Medline, Google Scholar
- 17 Unger E, Banai S, Shou M, et al. Basic fibroblast growth factor enhances myocardial collateral flow in a canine model. Am J Physiol 1994; 266:H1588-H1595. Medline, Google Scholar
- 18 Banai S, Jaklitsch M, Shou M, et al. Angiogenic-induced enhancement of collateral blood flow to ischemic myocardium by vascular endothelial growth factor in dogs. Circulation 1994; 89:2183-2189. Crossref, Medline, Google Scholar
- 19 Sellke FW, Wang SY, Stamler A, et al. Enhanced microvascular relaxations to VEGF and bFGF in chronically ischemic porcine myocardium. Am J Physiol 1996; 271:H713-H720. Medline, Google Scholar
- 20 Boxerman J, Bandettini P, Kwong K, et al. The intravascular contribution to fMRI signal change: Monte Carlo modeling and diffusion-weighted studies in vivo. Magn Reson Med 1995; 34:4-10. Crossref, Medline, Google Scholar







