Abstract 12789: Assessment of the Microvascular Response to Stem Cell Therapy with Contrast Ultrasound Perfusion Imaging and Maximum Intensity Projection Angiography
Background: Pro-angiogenic stem cell therapy is a promising option for patients with coronary and peripheral artery disease who cannot undergo mechanical revascularization. Adequate methods for directly assessing vascular responses to cell therapy are lacking. We hypothesized that contrast-enhanced ultrasound (CEU) could be used to quantify vascular remodeling and changes in perfusion after stem cell therapy.
Methods: Unilateral hindlimb ischemia was produced in 42 C57/Bl6 mice by iliac artery ligation. One day after ligation, the proximal hindlimb received either: (1) 1×106 multipotent adult progenitor cells (MAPC) by IM injection, (2) sham injection of saline, or (3) no therapy. CEU perfusion imaging in the proximal adductor muscles was performed at rest at days 1, 3, 7 and 21; and during contractile exercise at day 21. Time-intensity data after microbubble destruction was used to quantify microvascular blood flow (MBF) and blood volume (MBV). Microvascular angiography was performed with maximum intensity projection (MIP) processing of CEU data to assess arterial distribution and was compared to post-mortem fluorescent microangiography.
Results: Iliac ligation resulted in a ≈70% reduction in MBF to 0.20±0.06 ml/min/g. Although resting MBF in the ischemic limb gradually improved in all groups, MAPC therapy resulted in a more rapid and complete recovery of MBF (0.61±0.06 ml/min/g at day 21, 25% higher than controls, p<0.05). At day 21, the MAPC group also had a 70% higher hyperemic MBF compared to controls, p<0.05). MBV was greater (p<0.05) than controls at days 3, 7, and 21. On MIP angiography treatment with MAPC resulted in a proliferation of distal (3rd to 4th branch order) vessels, which was corroborated with fluorescent microangiography data, and a greater spatial distribution of perfusion. Interestingly, there was a 15–20% reduction in the normal leg at days 1 and 3.
Conclusions: Measurement of MBF, MBF reserve, and arteriolar proliferation by CEU can be used to quantify response to pro-angiogenic stem cell therapy. In ischemic hindlimb models, changes in MBF can occur in the contralateral ischemic limb, underscoring the importance for measuring absolute MBF rather than relative flow.
- © 2010 by American Heart Association, Inc.