Abstract

Therapeutic angiogenesis is pertinent to the acute survival of distal ischemic tissue and a relevant treatment for critical limb ischemia (CLI). Therapeutic arteriogeneis is pertinent to the restoration of function, via collateral vessel formation in proximal tissue that is not typically ischemic, and a relevant treatment for preventing intermittent claudication from advancing to CLI. In preclinical models of peripheral artery disease (PAD), laser perfusion imaging methods are applicable to the former. However, recently published results indicate they underestimate recovery and their limited penetration depth restrict their application to the latter. Our objective was to evaluate whether phase contrast magnetic resonance imaging (PC-MRI) could be used as a complementary method in murine models of PAD. C57BL/6 male mice underwent femoral artery ligation (n=5). Mice were imaged prior to and day 3 after surgery. PC-MRI uses the phase of the MRI signal to calculate velocity of blood flow within a voxel. Integrating velocity across the vessel lumen results in flow measurements. Maximum velocity and mean volumetric flow were compared at the infrarenal aorta and ipsilateral (Ip) and contralateral (Con) iliac arteries. Maximum velocities did not change in the aorta or Con (pre vs. day 3: aorta, 55.4±7.2 vs. 48.9±9.4 cm/sec; Con, 45.7±7.5 vs. 40.7±8.0 cm/sec). Mean volumetric flows also did not change in the aorta or Con (pre vs. day 3: aorta, 2.0±0.7 vs. 1.53±0.4 mL/min; Con, 1.1±0.4 vs. 0.92±0.3 mL/min). In the ipsilateral iliac artery, maximum velocity was reduced by ~35% (pre vs. day 3: 43.6±5.7 vs. 28.4±5.5 cm/sec, p=0.002), leading to a reduction in mean flow of ~41% (1.1±0.4 vs. 0.63±0.3 mL/min, p=0.04). Ip/Con ratios for both metrics were: 0.98±0.2 vs. 0.74±0.2 cm/sec, p=0.03; and, 1.0±0.1 vs. 0.72±0.3 mL/min, p=0.03. Our previous work demonstrated the ability to promote proximal-arteriogenesis by inducing distal-angiogenesis via application of a slow-release growth factor. Having developed a non-invasive method to directly quantify velocity and flow in large proximal vessels, we will have the opportunity to explore the biomechanical mechanisms coupling angio- and arterio-genesis even though they occur temporally and spatially separated.

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