Cooling Effects Occur in Hepatic Microwave Ablation At Low Vascular Flow Rates and in Close Proximity to Liver Vessels - Ex Vivo.

Background. The impact of vascular cooling effects in hepatic microwave ablation (MWA) is controversially discussed. The objective of this study was a systematic assessment of vascular cooling effects in hepatic MWA ex vivo. Methods. Microwave ablations were performed in fresh porcine liver ex vivo with a temperature-controlled MWA generator (902-928 MHz) and a non-cooled 14-G-antenna. Energy input was set to 9.0 kJ. Hepatic vessels were simulated by glass tubes. Three different vessel diameters (3.0, 5.0, 8.0 mm) and vessel to antenna distances (5, 10, 20 mm) were examined. Vessels were perfused with saline solution at nine different flow rates (0-500 mL/min). Vascular cooling effects were assessed at the largest cross-sectional ablation area. A quantitative and semi-quantitative/morphologic analysis was carried out. Results. 228 ablations were performed. Vascular cooling effects were observed at close (5 mm) and medium (10 mm) antenna to vessel distances (P < .05). Vascular cooling effects occurred around vessels with flow rates ≥1.0 mL/min (P < .05) and a vessel diameter ≥3 mm (P < .05). Higher flow rates did not result in more distinct cooling effects (P > .05). No cooling effects were measured at large (20 mm) antenna to vessel distances (P > .05). Conclusion. Vascular cooling effects occur in hepatic MWA and should be considered in treatment planning. The vascular cooling effect was mainly affected by antenna to vessel distance. Vessel diameter and vascular flow rate played a minor role in vascular cooling effects.

Establishing and Maintaining an Etruscan Shrew Colony.

The Etruscan shrew (Suncus etruscus) is one of the smallest mammals on earth and is used in many fields of research, including physiology, behavioral science and neuroscience. However, establishing and maintaining a breeding colony of this species in the laboratory can be challenging, as it requires specific husbandry conditions that greatly differ from those of more common laboratory species such as mice or rats. Over the past 15 y, we have successfully established a long-term thriving colony of 150 to 200 animals originating from 36 founders. The colony shows longer life expectancy and larger litter sizes than wild conspecifics. Breeding occurs year-round, independent of seasons, and a breeding pair can regularly produce 2 to 6 offspring with an average life expectancy of more than 3 y. The shrews are housed in glass or plastic enclosures on a specific soil-sand-mixture bedding and are provided with hideouts and nesting material consisting of moss, wood, or bark. Due to their high basal metabolic rate, the shrews require food intake greater than their body weight per day, can hunt arthropods as large as themselves, and cannot survive more than a few hours without food. Live feed such as crickets or mealworms is crucial and must be provided daily or, at the very least, every 2 d. Although our husbandry practices have constantly been adapted and refined, shrew husbandry remains challenging, and great care is necessary to meet the specific needs of this species. Here, we describe the establishment of a long-term stable colony of Etruscan shrews in a research animal facility and the specific husbandry requirements for animal wellbeing.

Periportal fields cause stronger cooling effects than veins in hepatic microwave ablation: an in vivo porcine study.

BACKGROUND: Vascular cooling effects are a well-known source for tumor recurrence in thermal in situ ablation techniques for hepatic malignancies. Microwave ablation (MWA) is an ablation technique to be considered in the treatment of malignant liver tumors. The impact of vascular cooling in MWA is still controversial. PURPOSE: To evaluate the influence of different intrahepatic vessel types, vessel sizes, and vessel-to-antenna-distances on MWA geometry in vivo. MATERIAL AND METHODS: Five MWAs (902-928 MHz) were performed with an energy input of 24.0 kJ in three porcine livers in vivo. MWA lesions were cut into 2-mm slices. The minimum and maximum radius of the ablation area was measured for each slice. Distances were measured from ablation center toward all adjacent hepatic vessels with a diameter of ≥1 mm and within a perimeter of 20 mm around the antenna. The respective vascular cooling effect relative to the maximum ablation radius was calculated. RESULTS: In total, 707 vessels (489 veins, 218 portal fields) were detected; 370 (76%) hepatic veins and 185 (85%) portal fields caused a cooling effect. Portal fields resulted in higher cooling effects (37%) than hepatic veins (26%, P < 0.01). No cooling effect could be observed in close proximity of vessels within the central ablation zone. CONCLUSION: Hepatic vessels influenced MWA zones and caused a distinct cooling effect. Portal fields resulted in more pronounced cooling effect than hepatic veins. No cooling effect was observed around vessels situated within the central white zone.

CT-based quantification of short-term tissue shrinkage following hepatic microwave ablation in an in vivo porcine liver model.

BACKGROUND: Microwave ablation (MWA) is a minimally invasive treatment option for solid tumors and belongs to the local ablative therapeutic techniques, based on thermal tissue coagulation. So far there are mainly ex vivo studies that describe tissue shrinkage during MWA. PURPOSE: To characterize short-term volume changes of the ablated zone following hepatic MWA in an in vivo porcine liver model using contrast-enhanced computer tomography (CECT). MATERIAL AND METHODS: We performed multiple hepatic MWA with constant energy parameters in healthy, narcotized and laparotomized domestic pigs. The volumes of the ablated areas were calculated from venous phase CT scans, immediately after the ablation and in short-term courses of up to 2 h after MWA. RESULTS: In total, 19 thermally ablated areas in 10 porcine livers could be analyzed (n = 6 with two volume measurements during the measurement period and n = 13 with three measurements). Both groups showed a statistically significant but heterogeneous volume reduction of up to 12% (median 6%) of the ablated zones in CECT scans during the measurement period (P < 0.001 [n = 13] and P = 0.042 [n = 6]). However, the dimension and dynamics of volume changes were heterogenous both absolutely and relatively. CONCLUSION: We observed a significant short-term volume reduction of ablated liver tissue in vivo. This volume shrinkage must be considered in clinical practice for technically successful tumor treatment by MWA and therefore it should be further investigated in in vivo studies.

Immediate post-interventional contrast-enhanced computed tomography overestimates hepatic microwave ablation - an in vivo animal study.

Objectives: Contrast-enhanced computed tomography (CECT) is used to monitor technical success immediately after hepatic microwave ablation (MWA). However, it remains unclear, if CECT shows the exact extend of the thermal destruction zone, or if tissue changes such as peri-lesionary edema are depicted as well. The objective of this study was to correlate immediate post-interventional CECT with histological and macroscopic findings in hepatic MWA in porcine liver in vivo.Methods: Eleven MWA were performed in porcine liver in vivo with a microwave generator (928 MHz; energy input 24 kJ). CECT was performed post-interventionally. Livers were explanted and ablations were bisected immediately after ablation. Samples were histologically analyzed after vital staining (NADH-diaphorase). Ablation zones were histologically and macroscopically outlined. We correlated histologic findings, macroscopic images and CECT.Results: Three ablation zones were identified in histological and macroscopic findings. Only one ablation zone could be depicted in CECT. Close conformity was observed between histological and macroscopic findings. The ablation zone depicted in CECT overestimated the histological avital central zone and inner red zone (p < = .01). No differences were found between CECT and the histological outer red zone (p > .05).Conclusions: Immediate post-interventional CECT overestimated the clinically relevant zone of complete cell ablation after MWA in porcine liver in vivo. This entails the risk of incomplete tumor ablation and could lead to tumor recurrence.

Exploring Patterns of Dynamic Size Changes of Lesions after Hepatic Microwave Ablation in an In Vivo Porcine Model.

Microwave ablation (MWA) is a type of minimally invasive cancer therapy that uses heat to induce necrosis in solid tumours. Inter- and post-ablational size changes can influence the accuracy of control imaging, posing a risk of incomplete ablation. The present study aims to explore post-ablation 3D size dynamics in vivo using computed tomography (CT). Ten MWA datasets obtained in nine healthy pigs were used. Lesions were subdivided along the z-axis with an additional planar subdivision into eight subsections. The volume of the subsections was analysed over different time points, subsequently colour-coded and three-dimensionally visualized. A locally weighted polynomial regression model (LOESS) was applied to describe overall size changes, and Student's t-tests were used to assess statistical significance of size changes. The 3D analysis showed heterogeneous volume changes with multiple small changes at the lesion margins over all time points. The changes were pronounced at the upper and lower lesion edges and characterized by initially eccentric, opposite swelling, followed by shrinkage. In the middle parts of the lesion, we observed less dimensional variations over the different time points. LOESS revealed a hyperbolic pattern for the volumetric changes with an initially significant volume increase of 11.6% (111.6% of the original volume) over the first 32 minutes, followed by a continuous decrease to 96% of the original volume (p < 0.05).

Improved Visualization of the Necrotic Zone after Microwave Ablation Using Computed Tomography Volume Perfusion in an In Vivo Porcine Model.

After hepatic microwave ablation, the differentiation between fully necrotic and persistent vital tissue through contrast enhanced CT remains a clinical challenge. Therefore, there is a need to evaluate new imaging modalities, such as CT perfusion (CTP) to improve the visualization of coagulation necrosis. MWA and CTP were prospectively performed in five healthy pigs. After the procedure, the pigs were euthanized, and the livers explanted. Orthogonal histological slices of the ablations were stained with a vital stain, digitalized and the necrotic core was segmented. CTP maps were calculated using a dual-input deconvolution algorithm. The segmented necrotic zones were overlaid on the DICOM images to calculate the accuracy of depiction by CECT/CTP compared to the histological reference standard. A receiver operating characteristic analysis was performed to determine the agreement/true positive rate and disagreement/false discovery rate between CECT/CTP and histology. Standard CECT showed a true positive rate of 81% and a false discovery rate of 52% for display of the coagulation necrosis. Using CTP, delineation of the coagulation necrosis could be improved significantly through the display of hepatic blood volume and hepatic arterial blood flow (p < 0.001). The ratios of true positive rate/false discovery rate were 89%/25% and 90%/50% respectively. Other parameter maps showed an inferior performance compared to CECT.

Comparison of different 4D CT-Perfusion algorithms to visualize lesions after microwave ablation in an in vivo porcine model.

Background: Accurate lesion visualization after microwave ablation (MWA) remains a challenge. Computed tomography perfusion (CTP) has been proposed to improve visualization, but it was shown that different perfusion-models delivered different results on the same data set.Purpose: Comparison of different perfusion algorithms and identification of the algorithm enables for the best imaging of lesion after hepatic MWA.Materials and methods: 10 MWA with consecutive CTP were performed in healthy pigs. Parameter-maps were generated using a single-input-dual-compartment-model with Patlak's algorithm (PM), a dual-input-maximum-slope-model (DIMS), a dual-input-one-compartment-model (DIOC), a single-(SIDC) and dual-input-deconvolution-model (DIDC). Parameter-maps for hepatic arterial (AF) and portal venous blood flow (PF), mean transit time, hepatic blood volume (HBV) and capillary permeability were compared regarding the values of the normal liver tissue (NLT), lesion, contrast- and signal-to-noise ratios (SNR, CNR) and inter- and intrarater-reliability using the intraclass correlation coefficient, Bland-Altman plots and linear regression.Results: Perfusion values differed between algorithms with especially large fluctuations for the DIOC. A reliable differentiation of lesion margin appears feasible with parameter-maps of PF and HBV for most algorithms, except for the DIOC due to large fluctuations in PF. All algorithms allowed for a demarcation of the central necrotic zone based on hepatic AF and HBV. The DIDC showed the highest CNR and the best inter- and intrarater reliability.Conclusion: The DIDC appears to be the most feasible model to visualize margins and necrosis zones after microwave ablation, but due to high computational demand, a single input deconvolution algorithm might be preferable in clinical practice.

Microwave ablation zones are larger than they macroscopically appear - Reevaluation based on NADH vitality staining ex vivo.

BACKGROUND: Animal liver is established as an ex vivo model for studies on hepatic microwave ablation (MWA). Macroscopically visible color changes in the ablation zone are used to assess cell destruction and confirm successful ablation ex vivo. OBJECTIVE: Macroscopy and histology of MWA zones regarding cell viability in ex vivo porcine livers were compared in this study. METHODS: Six MWA were performed in porcine livers post mortem. A 14-G antenna and microwave generator (928 MHz; 9.0 kJ) were used. MWA were cut at the maximum cross section in vertical alignment to the antenna. NADH-diaphorase staining determined cell vitality. Macroscopic and microscopic ablation zones were statistically analyzed. RESULTS: Histology showed two distinct ablation zones: central white zone (WZH) with no cell viability and peripheral red zone (RZH) with partial cell viability. However, the macroscopically visible WZM was significantly smaller than the microscopic WZH with an area difference of 43.1% (p < 0.05) and a radius difference of 21.2% (1.6 mm; p < 0.05). Macroscopy and histology showed a very high correlation for the complete lesion area (WZH/M+RZH/M; r = 0.9; p = 0.001). CONCLUSIONS: The avital central zone is significantly larger as the macroscopically visible WZ which is commonly used to assess successful ablation in MWA ex vivo studies. Irreversible cell destruction can be underestimated in macroscopic evaluation.

Intermittent Pringle maneuver may be beneficial for radiofrequency ablations in situations with tumor-vessel proximity.

BACKGROUND: Radiofrequency ablation (RFA) represents a treatment option for non-resectable liver malignancies. Larger ablations can be achieved with a temporary hepatic inflow occlusion (Pringle maneuver - PM). However, a PM can induce dehydration and carbonization of the target tissue. The objective of this study was to evaluate the impact of an intermittent PM on the ablation size. METHODS: Twenty-five multipolar RFAs were performed in porcine livers ex vivo. A perfused glass tube was used to simulate a natural vessel. The following five test series (each n=5) were conducted: (1) continuous PM, (2-4) intermittent PM, and (5) no PM. Ablations were cut into half. Ablation area, minimal radius, and maximal radius were compared. RESULTS: No change in complete ablation size could be measured between the test series (p>0.05). A small rim of native liver tissue was observed around the glass tube in the test series without PM. A significant increase of ablation area could be measured on the margin of the ablations with an intermittent PM, starting without hepatic inflow occlusion (p<0.05). CONCLUSION: An intermittent PM did not lead to smaller ablations compared to a continuous or no PM ex vivo. Furthermore, an intermittent PM can increase the ablation area when initial hepatic inflow is succeeded by a PM.