摘要：

Introduction: Mouse models of hindlimb ischemia (HLI) are used to explore therapies for peripheral artery disease (PAD). Degrees of ischemia can be induced by selection of ligation sites during surgery. Laser Doppler perfusion imaging (LDPI) is often used to measure perfusion recovery, but contrast-enhanced ultrasound (CEUS) may offer advantages like muscle-specific perfusion.Hypothesis: CEUS is a more sensitive indicator of muscle ischemia, since LDPI is biased towards skin perfusion. Mice with severe HLI show a greater initial perfusion deficit than mice with mild HLI.Methods: C57BL/6 mice were studied: 17 mild and 18 severe HLI. Mild and severe HLI were induced by a unilateral single or double femoral artery ligation, respectively. Perfusion was measured in the feet by LDPI and the calves by CEUS before surgery and 1, 4, 7, 14, 28, 60 and 90 days after. A standard LDPI protocol was used and data analyzed with PimSoft software. A Sequoia 512 was used for CEUS with IV infusion of contrast. Intensity over time was fit to a standard equation y=A*(1-exp(-β*t)) where A~blood volume and β~blood flow rate.Results: Results are reported as a ratio of ischemic to control limb. By both measures the severe group was less perfused than the mild group through day 7. LDPI showed full recovery at day 4 for mild HLI and day 7 for severe HLI. In contrast, CEUS shows only a 60% (mild) and 39% (severe) recovery plateau was reached at the same time points. These plateaus remained until the end of the study. CEUS also detected the variation in spatial perfusion patterns due to anatomic variability in HLI mice.Conclusions: LDPI results are similar to previous reports using that technique, however LDPI and CEUS show different perfusion recoveries. MRI studies are ongoing to validate findings. CEUS has several advantages over LDPI including muscle-specific perfusion. These results suggest a novel, more physiologically relevant model of PAD where therapies are tested during the plateau of reduced perfusion.

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