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Purpose The purpose of this study was to evaluate potential biological and thermal mechanisms for the observed differences in thrombosis rates between hepatic vessels during microwave ablation procedures. Materials and Methods Microwave ablation antennas were placed in single liver lobes of two in-vivo porcine (n=3 in each animal; n =6 total) liver models in the proximity of a large (>5mm) portal vein and hepatic veins. Each ablation was performed with 100 W for 5 minutes. Conventional ultrasound imaging and intravascular temperature probes were used to evaluate vessel patency and temperature changes during the ablation procedure. Vascular endothelium was harvested 1 hour after ablation and used to characterize genes and proteins associated with thrombosis in portal and hepatic veins. Results Targeted portal veins and hepatic veins did not show a significant difference between average vessel size (8.7 ± 2.4 mm vs 9.7 ± 3.4 mm; p=0.44). Portal veins within the microwave ablation zone thrombosed at a significantly higher rate compared to hepatic veins (54.5% vs 0.0%, p=0.0046). There was a negligible change in intravascular temperature in both portal and hepatic veins during the ablation procedure (0.2 ± 0.4 vs 0.6 ± 0.9 °C, p=0.46). Portal veins demonstrated significantly higher gene expression compared to hepatic veins in terms of fold-differences in thrombomodulin (2.9 ± 2.0; p=0.0001), von Willebrand Factor (7.6 ± 1.5; p=0.0001), endothelial protein C receptor (3.50 ± 0.49; p=0.0011) and plasminogen activator inhibitor (SERPINE1: 1.46 ± 0.05; p=0.0014). Western blot analysis showed significantly higher expression of von Willebrand Factor (2.32 ± 0.92; p=0.031) in portal veins compared to hepatic veins. Conclusions Large portal veins thrombose more frequently than hepatic veins during microwave ablation procedures. Biological differences in thrombogenicity, rather than heat transfer, between portal veins and hepatic veins may contribute to their different rates of thrombosis.

Tumor acute hypoxia has a dynamic component that is also, at least partially, coherent. Using blood oxygen level dependent (BOLD) magnetic resonance imaging (MRI), we observed coherent oscillations in hemoglobin saturation dynamics in cell line xenograft models of head and neck squamous cell carcinoma. We posit a well-established biochemical nonlinear oscillatory mechanism called the glycolytic oscillator as a potential cause of the coherent oscillations in tumors. These data suggest that metabolic changes within individual tumor cells may affect the local tumor microenvironment including oxygen availability and therefore radiosensitivity. These individual cells can synchronize the oscillations in patches of similar intermediate glucose levels. These alterations have potentially important implications for radiation therapy and are a potential target for optimizing the cancer response to radiation.

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