Abstract
OBJECTIVE: We are aimed at analyzing the correlation between contrast-enhanced ultrasound (CEUS) quantitative perfusion parameters and serum levels of vascular endothelial growth factor (VEGF) and C-X-C motif chemokine ligand 12 (CXCL-12) in a rabbit model of diabetic foot, and exploring the value of CEUS in evaluating microcirculatory lesions of diabetic foot. METHODS: Ten New Zealand white rabbits were intravenously injected with alloxan to induce diabetes (fasting blood glucose > 16 mmol/L, accompanied by symptoms of polydipsia, polyphagia, and polyuria). Diabetic foot ulcer (DFU) was then induced by magnetic disk compression. Serum VEGF and CXCL-12 levels were measured by enzyme-linked immunosorbent assay (ELISA) at three stages (normal stage, diabetes mellitus [DM] stage, and DFU stage). CEUS was performed on the gastrocnemius muscle to quantify three perfusion-related parameters derived from time-intensity curves: time to peak (TTP), peak intensity (PI), and area under the curve (AUC). RESULTS: Serum VEGF and CXCL-12 levels in diabetic rabbits were significantly higher than those in normal rabbits (p < 0.01); in DFU rabbits, these levels remained elevated but were slightly lower than those in diabetic rabbits (p > 0.1). CEUS-derived perfusion parameters (TTP, PI, and AUC) showed an increasing trend across disease stages, with the highest values observed in the DFU group. All three parameters were significantly positively correlated with serum VEGF and CXCL-12 levels (r = 0.509-0.649, p < 0.01). CONCLUSION: Serum VEGF and CXCL-12 levels increase in diabetes but slightly decrease when DFU develops, indicating microcirculatory decompensation. CEUS-derived perfusion parameters, especially TTP, can sensitively reflect microcirculatory impairment and are positively correlated with angiogenic factor levels. This study suggests that CEUS provides a novel noninvasive tool for evaluating microcirculatory lesions in diabetic foot, with potential clinical translational value.