Collateral vessel growth was visualized in a rabbit femoral artery ligation model by serial contrast-enhanced magnetic resonance angiography (MRA) at 1.5 T in comparison with X-ray angiography (XRA). XRA and MRA were performed directly after femoral artery ligation (day 0+) and after 7 and 21 days. XRA (in-plane resolution, 0.3x0.3 mm) was performed with arterial catheterization for fast injection of iodinated contrast agent just proximal to the aortic bifurcation. MRA (in-plane, 0.6x0.6 mm) was performed at 1.5 T with a five-element phased-array coil and slow injection of gadolinium-based MR contrast agent into an ear vein. Collateral vessel scores on two-dimensional XRA projections and on three-dimensional digitally subtracted rotational MRA maximum intensity projections were obtained by two observers and compared. Collateral vessel counts and minimal detectable vessel diameters for MRA and XRA were combined in a computational flow model to interpret differences in spatial detection limits between imaging modalities in terms of flow. Collateral vessel scores were significantly higher in the ligated limb at day 7 (P < 0.05) and more so at day 21 (P < 0.001), in comparison with day 0+ or in the non-ligated control limb on both XRA and MRA. Significantly more (smaller) vessels were visualized with XRA than with MRA, particularly on day 21 (P < 0.05). Inter-observer agreement was high for both XRA (kappa = 0.82) and MRA (kappa = 0.78). The flow model showed that collateral vessels with diameters > 0.3 mm scored by XRA as well as MRA represent nearly 100% of the total blood flow, whereas smaller (0.1-0.3 mm diameter) vessels that can only be detected with XRA contribute little to the blood flow. Serial contrast-enhanced MRA can non-invasively visualize sub-millimeter collateral vessels that represent nearly 100% of the restored blood flow, in a femoral artery ligation model.

To assess the use of MRI for evaluating changes in muscle blood flow and number of collateral arteries, serial dynamic contrast-enhanced MRI (DCE-MRI) was combined with high-spatial-resolution contrast-enhanced MR angiography (MRA) in a peripheral ischemia model. The combined MRI (DCE-MRI and MRA) protocol was performed serially in 15 male rabbits at 2 h (day 0(+)), 7 days, and 21 days after femoral artery ligation. In the anterior tibial and soleus muscle, changes in resting muscle blood flow determined as the endothelial transfer coefficient (K(trans)) and arterial inflow delay from DCE-MRI and changes in the number of sub-millimeter sized collateral arteries as scored with MRA were measured. Directly after ligation, K(trans) in the anterior tibial muscle was reduced to 23% of that in the control limb, then recovered to 81% on day 7, and to 85 % on day 21. K(trans) in the soleus muscle recovered from a reduction to 63% on day 0(+), to 85% on day 7, and to 90% on day 21. The number of collaterals around the ligated femoral artery increased from 1.1 on day 0(+) to 4.2 on day 7, and 6.0 on day 21 in the ligated limb only. Combined DCE-MRI and MRA allows non-invasive serial monitoring of changes in muscle blood flow and growth of sub-millimeter sized collateral arteries in a rabbit femoral artery ligation model.