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

Abstract

Background A standard quantitative imaging approach to evaluate peripheral arterial disease (PAD) 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 following femoral artery occlusion in a porcine model using SPECT/CT imaging with post-mortem validation of in vivo findings using gamma counting, post-mortem imaging, and histological analysis. Hybrid thallium-201 (201Tl) SPECT/CT imaging was performed in pigs (n=8) at baseline, immediately post-occlusion, and at 1 and 4 weeks post-occlusion. CT imaging was used to identify muscle regions of interest in the ischemic (I) and non-ischemic (NI) hindlimbs for quantification of regional changes in CT defined arteriogenesis and quantification of 201Tl perfusion. Four weeks post-occlusion, post-mortem tissue 201Tl activity was measured by gamma counting and immunohistochemistry was performed to assess capillary density. Relative 201Tl retention (I/NI) was reduced immediately post-occlusion 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 201Tl SPECT/CT imaging permits serial, regional quantification of arteriogenesis and resting tissue perfusion following limb ischemia. This approach may be effective for detection of disease and monitoring therapy in PAD.

SPECT and PET imaging of angiogenesis and arteriogenesis in pre-clinical models of myocardial ischemia and peripheral vascular disease

“…Stacy et al investigated serial changes in lower extremity arteriogenesis and muscle perfusion in a pig model for PVD [162]. Significant increases in collateral artery formation in the biceps femoris and semimembranosus muscle area were shown using CT angiography 4 weeks after ligation.…”

Application of BOLD Magnetic Resonance Imaging for Evaluating Regional Volumetric Foot Tissue Oxygenation: A Feasibility Study in Healthy Volunteers

“…Our research team has previously developed image segmentation tools that have been applied for serial analysis of lower extremity tissue perfusion 10 and angiogenesis. 11 In the present study, we sought to expand on these tools by developing a segmental three-dimensional (3D) model of the foot to quantify volumetric tissue oxygenation within specific territories.…”

State-of-the-Art Methods for Evaluation of Angiogenesis and Tissue Vascularization

“…Radiotracer imaging, including hybrid single-photon emission tomography/CT approaches, has been applied to evaluate angiogenesis and arteriogenesis in rodent models of hind-limb ischemia 218 and myocardial ischemia, 187 as well as in larger canine and porcine models of ischemia-induced angiogenesis. 185,186 Figure 8 illustrates the integration of physiological perfusion imaging and targeted molecular imaging of angiogenesis using hybrid singlephoton emission tomography/CT imaging in a murine model of hind-limb ischemia and the application of serial perfusion imaging for the evaluation of angiogenesis in a porcine model of hind-limb ischemia.…”

“…I indicates ischemic; and NI, nonischemic. Modified with permission from Stacy et al 185 Copyright © 2014, American Heart Association, Inc. inflammation, angiogenesis, apoptosis, oxidative stress, and calcification.…”