Multimodality Imaging Approach for Serial Assessment of Regional Changes in Lower Extremity Arteriogenesis and Tissue Perfusion in a Porcine Model of Peripheral Arterial Disease

Background A standard quantitative imaging approach to evaluate peripheral arterial disease does not exist. Quantitative tools for evaluating arteriogenesis in vivo are not readily available, and the feasibility of monitoring serial regional changes in lower extremity perfusion has not been examined. Methods and Results Serial changes in lower extremity arteriogenesis and muscle perfusion were evaluated after femoral artery occlusion in a porcine model using single photon emission tomography (SPECT)/CT imaging with postmortem validation of in vivo findings using gamma counting, postmortem imaging, and histological analysis. Hybrid Tl-201 SPECT/CT imaging was performed in pigs (n=8) at baseline, immediately postocclusion, and at 1 and 4 weeks postocclusion. CT imaging was used to identify muscle regions of interest in the ischemic and nonischemic hindlimbs for quantification of regional changes in CT-defined arteriogenesis and quantification of Tl-201 perfusion. Four weeks postocclusion, postmortem tissue Tl-201 activity was measured by gamma counting, and immunohistochemistry was performed to assess capillary density. Relative Tl-201 retention (ischemic/nonischemic) was reduced immediately postocclusion in distal and proximal muscles and remained lower in calf and gluteus muscles 4 weeks later. Analysis of CT angiography revealed collateralization at 4 weeks within proximal muscles (P<0.05). SPECT perfusion correlated with tissue gamma counting at 4 weeks (P=0.01). Increased capillary density was seen within the ischemic calf at 4 weeks (P=0.004). Conclusions Tl-201 SPECT/CT imaging permits serial, regional quantification of arteriogenesis and resting tissue perfusion after limb ischemia. This approach may be effective for detection of disease and monitoring therapy in peripheral arterial disease.