Computational modeling of microwave ablation with thermal accelerants.

PURPOSE: To develop a computational model of microwave ablation (MWA) with a thermal accelerant gel and apply the model toward interpreting experimental observations in ex vivo bovine and in vivo porcine liver. METHODS: A 3D coupled electromagnetic-heat transfer model was implemented to characterize thermal profiles within ex vivo bovine and in vivo porcine liver tissue during MWA with the HeatSYNC thermal accelerant. Measured temperature dependent dielectric and thermal properties of the HeatSYNC gel were applied within the model. Simulated extents of MWA zones and transient temperature profiles were compared against experimental measurements in ex vivo bovine liver. Model predictions of thermal profiles under in vivo conditions in porcine liver were used to analyze thermal ablations observed in prior experiments in porcine liver in vivo. RESULTS: Measured electrical conductivity of the HeatSYNC gel was ∼83% higher compared to liver at room temperature, with positive linear temperature dependency, indicating increased microwave absorption within HeatSYNC gel compared to tissue. In ex vivo bovine liver, model predicted ablation zone extents of (31.5 × 36) mm with the HeatSYNC, compared to (32.9 ± 2.6 × 40.2 ± 2.3) mm in experiments (volume differences 4 ± 4.1 cm3). Computational models under in vivo conditions in porcine liver suggest approximating the HeatSYNC gel spreading within liver tissue during ablations as a plausible explanation for larger ablation zones observed in prior in vivo studies. CONCLUSION: Computational models of MWA with thermal accelerants provide insight into the impact of accelerant on MWA, and with further development, could predict ablations with a variety of gel injection sites.

Adjuvant Thermal Accelerant Gel Use Increases Microwave Ablation Zone Temperature in Porcine Liver as Measured by MR Thermometry.

PURPOSE: To determine the effects of a thermal accelerant gel on temperature parameters during microwave liver ablation. MATERIALS AND METHODS: Sixteen consecutive liver ablations were performed in 5 domestic swine under general anesthesia with (n = 8) and without (n = 8) administration of thermal accelerant gel. Ablation zone temperature was assessed by real-time MR thermometry, measured as maximum temperature (Tmax) and the volume of tissue ≥ 60°C (V60). Tissue heating rate, ablation zone shape, and thermal energy deposition using the temperature degree-minutes at 43°C (TDM43) index were also measured. Differences between groups were analyzed using generalized mixed modeling with significance set at P = .05. RESULTS: Mean peak ablation zone temperature was significantly greater with thermal accelerant use (mean Tmax, thermal accelerant: 120.0°C, 95% confidence interval [CI] 113.0°C-126.9°C; mean Tmax, control: 80.3°C, 95% CI 72.7°C-88.0°C; P < .001), and a significantly larger volume of liver tissue achieved or exceeded 60°C when thermal accelerant was administered (mean V60, thermal accelerant: 22.2 cm3; mean V60, control: 15.9 cm3; P < .001). Significantly greater thermal energy deposition was observed during ablations performed with accelerant (mean TDM43, thermal accelerant: 198.4 min, 95% CI 170.7-230.6 min; mean TDM43, control: 82.8 min, 95% CI 80.5-85.1 min; P < .0001). The rate of tissue heating was significantly greater with thermal accelerant use (thermal accelerant: 5.8 min ± 0.4; control: 10.0 min; P < .001), and accelerant gel ablations demonstrated a more spherical temperature distribution (P = .002). CONCLUSIONS: Thermal accelerant use is associated with higher microwave ablation zone temperatures, greater thermal energy deposition, and faster and more spherical tissue heating compared with control ablations.

Effects of a Thermal Accelerant Gel on Microwave Ablation Zone Volumes in Lung: A Porcine Study.

Background Thermal ablation of cancers may be associated with high rates of local tumor progression. A thermal accelerant gel has been developed to improve the transmission of microwave energy in biologic tissues with the aim of enlarging the thermal ablation zone. Purpose To determine the effects of a thermal accelerant gel on microwave ablation zone volumes in porcine lung and to compare percutaneous and endobronchial delivery methods. Materials and Methods Thirty-two consecutive microwave lung ablations were performed in nine 12-week-old domestic male swine under general anesthesia by using fluoroscopic guidance between September 2017 and April 2018. Experimental ablations were performed following percutaneous injection of thermal accelerant into the lung (n = 16) or after endobronchial injection by using a flexible bronchoscope (n = 8). Control ablations were performed without accelerant gel (n = 8). Lung tissue was explanted after the animals were killed, and ablation zone volumes were calculated as the primary outcome measure by using triphenyltetrazolium chloride vital staining. Differences in treatment volumes were analyzed by generalized mixed modeling. Results Thermal accelerant ablation zone volumes were larger than control ablations (accelerant vs control ablation, 4.3 cm3 [95% confidence interval: 3.4, 5.5] vs 2.1 cm3 [95% confidence interval: 1.4, 2.9], respectively; P < .001). Among ablations with the thermal accelerant, those performed following percutaneous injection had a larger average ablation zone volume than those performed following endobronchial injection (percutaneous vs endobronchial, 4.8 cm3 [95% confidence interval: 3.6, 6.4] vs 3.3 cm3 [95% confidence interval: 2.9, 3.8], respectively; P = .03). Ablation zones created after endobronchial gel injection were more uniform in size distribution (standard error, percutaneous vs endobronchial: 0.13 vs 0.07, respectively; P = .03). Conclusion Use of thermal accelerant results in larger microwave ablation zone volumes in normal porcine lung tissue. Percutaneous thermal accelerant injection leads to a larger ablation zone volume compared with endobronchial injection, whereas a more homogeneous and precise ablation zone size is observed by using the endobronchial approach. © RSNA, 2019 See also the editorial by Goldberg in this issue.

Hepatoselectivity of statins: design and synthesis of 4-sulfamoyl pyrroles as HMG-CoA reductase inhibitors.

4-Sulfamoyl pyrroles were designed as novel hepatoselective HMG-CoA reductase inhibitors (statins) to reduce myalgia, a statin-induced adverse effect. The compounds were prepared via a [3+2] cycloaddition of a Münchnone with a sulfonamide-substituted alkyne. We identified compounds with greater selectivity for hepatocytes compared to L6-myocytes than rosuvastatin and atorvastatin. There was an inverse correlation of myocyte potencies and ClogP values. A number of analogs were effective at reducing cholesterol in acute and chronic in vivo models but they lacked sufficient chronic in vivo activity to warrant further development.