Optimization and characterization of a novel internally-cooled radiofrequency ablation system with optimized pulsing algorithm in an ex-vivo bovine liver.

Purpose: To prospectively characterize and optimize radiofrequency energy deposition to determine ideal parameters for achieving large ablation zones. Materials and methods: An internally-cooled RF system was used to perform 214 ablations in 72 ex-vivo bovine livers. Tip exposure (1-5 cm), electrode current (400-2500 mA), and application duration (3-15 min) were systematically varied. A pulsing algorithm optimized efficiency of RF deposition, including initial automatic ramping followed by adjustment in current, in response to changes in tissue impedance. Following the procedure ablation diameter and length were measured, sphericity calculated, and correlated with parameters of energy deposition and tissue temperatures. Results: Increasing electrode exposure from 1-5 cm produced linear increases in ablation diameter from 1.4 ± 0.1 to 5.3 ± 0.1 cm (y = 1.1x-0.5; R2 = 0.93), and length (y = 1.18x + 0.34; R2 = 0.92). A sphericity index >0.85 was noted at optimal energy setting for electrode exposures of 1-4 cm. Maximum temperatures post-ablation increased with active tip length from 68.5 ± 4.9 °C to 91.3 ± 1.5 °C in a logarithmic (y = 0.94ln(x)-2.75; R2 = 0.90) or power relationship between temperature and the resultant ablation diameter (y = 0.27e0.0295x; R2 = 0.76). A tight exponential relationship (y = 0.28x0.38; R2 = 0.97) was also observed between total energy deposition and ablation diameter. Finally, a multifactor relationship of the diameter of ablation to electrode tip exposure and the time to first impedance rise was successfully modeled, with a root mean squared error of 1.9 mm and R2 = 0.95. Conclusion: Large, reproducible, and spherical ablation areas can be achieved with the novel system described, with efficient delivery of RF energy deposited into tissue. These findings may have important clinical relevance in regards to the clinical utility of RF ablation compared to other competitive forms of thermal tumor ablation.

Evaluation of a CT-Guided Robotic System for Precise Percutaneous Needle Insertion.

PURPOSE: To assess overall targeting accuracy for CT-guided needle insertion using prototype robotic system for common target sites. MATERIALS AND METHODS: Using CT guidance, metallic (2 × 1 mm) targets were embedded in retroperitoneum (n = 8), kidneys (n = 8), and liver (n = 14) of 8 Yorkshire pigs (55-65 kg). Bronchial bifurcations were targeted in the lung (n = 13). CT datasets were obtained for planning and controlled needle placement of commercially available 17- to 19-gauge needles (length 15-20 cm) using a small, patient-mounted, CT-guided robotic system with 5° of motion. Mean distance to target was 92.9 mm ± 19.7 (range, 64-146 mm). Planning included selection of target, skin entry point, and 4.6 ± 1.3 predetermined checkpoints (range, 2-9) where additional CT imaging was performed to permit stepwise correction of needle trajectory path as needed. Scanning and needle advancement were coordinated with breath motion using respiratory gating. Accuracy was assessed as distance from needle tip to predefined target. RESULTS: Of 45 needle insertions performed, 2 were unsuccessful owing to technical issues. Accuracy of targeting was 1.2-1.4 mm ± 0.6 for kidney, retroperitoneum, and lung (P = .51), with 2.9 mm ± 1.9 accuracy for liver (P = .0003). This was achieved in 39 cases (91%) using a single insertion. Intraprocedural target movement was detected (3.5 mm ± 2.1 in retroperitoneum and 6.4 mm ± 3.9 in liver); the system compensated for 52.9% ± 30.3 of this movement. One pneumothorax was the only complication (8%). CONCLUSIONS: Accurate needle insertion (< 3 mm error) can be achieved in common target sites when using a CT-guided robotic system. Stepwise checks with corrective angulation can potentially overcome issues of target movement during a procedure from organ deformity and other causes.

Optimizing Irreversible Electroporation Ablation with a Bipolar Electrode.

PURPOSE: To optimize single-insertion bipolar irreversible electroporation (IRE) by characterizing effects of electric parameters and controlling tissue electric properties in a porcine model. MATERIALS AND METHODS: Single-insertion electrode bipolar IRE was performed in 28 in vivo pig livers (78 ablations). First, effects of voltage (2,700-3,000 V), number of pulses, repeated cycles (1-6 cycles), and pulse width (70-100 µs) were studied. Next, electric conductivity was altered by instillation of hypertonic and hypotonic fluids. Finally, effects of thermal stabilization were assessed using internal electrode cooling. Treatment effect was evaluated 2-3 hours after IRE. Dimensions were compared and subjected to statistical analysis. RESULTS: Delivering 3,000 V at 70 µs for a single 90-pulse cycle yielded 3.8 cm ± 0.4 × 2.0 cm ± 0.3 of ablation. Applying 6 cycles of energy increased ablation to 4.5 cm ± 0.4 × 2.6 cm ± 0.3 (P < .001). Further increasing pulse lengths to 100 µs (6 cycles) increased ablation to 5.0 cm ± 0.4 × 2.9 cm ± 0.3 (P < .001) but resulted in electric spikes and system crashes in 40%-50% of cases. Increasing tissue electric conductivity via hypertonic solution instillation in surrounding tissues increased frequency of generator crashes, whereas continuous instillation of distilled water eliminated this arcing phenomenon but reduced ablation to 2.3 cm ± 0.1. Controlled instillation of distilled water when electric arcing was suspected from audible popping produced ablations of 5.3 cm ± 0.6 × 3.1 cm ±0.3 without crashes. Finally, 3.1 cm ± 0.1 short-axis ablation was achieved without system crashes with internal electrode perfusion at 37°C versus 2.3 cm ± 0.1 with 4°C-10°C perfusion (P < .001). CONCLUSIONS: Bipolar IRE ablation zones can be increased with repetitive high voltage and greater pulse widths accompanied by either judicious instillation of hypotonic fluids or internal electrode perfusion to minimize unwanted electric arcing.

Irreversible electroporation: treatment effect is susceptible to local environment and tissue properties.

PURPOSE: To study the effects of the surrounding electrical microenvironment and local tissue parameters on the electrical parameters and outcome of irreversible electroporation (IRE) ablation in porcine muscle, kidney, and liver tissue. MATERIALS AND METHODS: Animal Care and Use Committee approval was obtained, and National Institutes of Health guidelines were followed. IRE ablation (n = 90) was applied in muscle (n = 44), kidney (n = 28), and liver (n = 18) tissue in 18 pigs. Two electrodes with tip exposure of 1.5-2 cm were used at varying voltages (1500-3000 V), pulse repetitions (n = 70-100), pulse length (70-100 µsec), and electrode spacing (1.5-2 cm). In muscle tissue, electrodes were placed exactly parallel, in plane, or perpendicular to paraspinal muscle fibers; in kidney tissue, in the cortex or adjacent to the renal medulla; and in liver tissue, with and without metallic or plastic plates placed 1-2 cm from electrodes. Ablation zones were determined at gross pathologic (90-120 minutes after IRE) and immunohistopathologic examination (6 hours after) for apoptosis and heat-shock protein markers. Multivariate analysis of variance with multiple comparisons and/or paired t tests and regression analysis were used for analysis. RESULTS: Mean (± standard deviation) ablation zones in muscle were 6.2 cm ± 0.3 × 4.2 cm ± 0.3 for parallel electrodes and 4.2 cm ± 0.8 × 3.0 cm ± 0.5 for in-plane application. Perpendicular orientation resulted in a cross-shaped zone. Orientation significantly affected IRE current applied (28.5-31.7A for parallel, 29.5-39.7A for perpendicular; P = .003). For kidney cortex, ovoid zones of 1.5 cm ± 0.1 × 0.5 cm ± 0.0 to 2.5 cm ± 0.1 × 1.3 cm ± 0.1 were seen. Placement of electrodes less than 5 mm from the medullary pyramids resulted in treatment effect arcing into the collecting system. For liver tissue, symmetric 2.7 cm ± 0.2 × 1.4 cm ± 0.3 coagulation areas were seen without the metallic plate but asymmetric coagulation was seen with the metallic plate. CONCLUSION: IRE treatment zones are sensitive to varying electrical conductivity in tissues. Electrode location, orientation, and heterogeneities in local environment must be considered in planning ablation treatment. Online supplemental material is available for this article.

Irreversible electroporation ablation: is all the damage nonthermal?

PURPOSE: To determine whether high-dose irreversible electroporation (IRE) ablation induces thermal effects in normal liver tissue. MATERIALS AND METHODS: Animal care and use committee approval was obtained prior to the experiments. IRE ablation (n = 78) was performed by a single four-person team in vivo in 22 porcine livers by applying electric current to two 1.3-cm-diameter circular flat-plate electrodes spaced 1 cm apart. Cardiac-gated IRE pulses (n = 40-360) were systematically applied at varying voltages (1500-2900 V). End temperatures at the ablation zone center were measured and were correlated with ablation time, energy parameters, and resultant treatment effect as determined at gross pathologic and histopathologic examination. Temperatures were then monitored at the center and periphery of four ablations created by using a four-electrode IRE array (3000 V, 90 pulses per electrode pair). Data were analyzed by using multivariate analysis of variance with multiple comparisons and/or paired t tests and regression analysis, as appropriate. RESULTS: Temperature rose above the 34°C baseline after IRE in all flat-plate experiments and correlated linearly (R(2) = 0.39) with IRE "energy dose" (product of voltage and number of pulses) and more tightly in univariate analysis with both voltage and number of pulses. Thus, mean temperatures as high as 86°C ± 3 (standard deviation) were seen for 2500 V and 270 pulses. Ablations of 90 pulses or more at 2500 V produced temperatures of 50°C or greater and classic gross and histopathologic findings of thermal coagulation (pyknotic nuclei and streaming cytoplasm). For lower IRE doses (ie, 2100 V, 90 pulses), temperatures remained below 45°C, and only IRE-associated pathologic findings (ie, swollen sinusoids, dehydrated cells, and hemorrhagic infiltrate) were seen. For the four-electrode arrays, temperatures measured 54.2°C ± 6.1 at the electrode surfaces and 38.6°C ± 3.2 at the ablation zone margin. CONCLUSION: In some conditions of high intensity, IRE can produce sufficient heating to induce "white zone" thermal coagulation. While this can be useful in some settings to increase tumor destruction, further characterization of the thermal profile created with clinical electrodes and energy parameters is therefore needed to better understand the best ways to avoid unintended damage when ablating near thermally sensitive critical structures.

Characterization of irreversible electroporation ablation in in vivo porcine liver.

OBJECTIVE: The purpose of this study was to prospectively characterize and optimize irreversible electroporation ablation to determine the best parameters to achieve the largest target zones of coagulation for two electrodes. MATERIALS AND METHODS: Ultrasound-guided irreversible electroporation ablation (n=110) was performed in vivo in 25 pig livers using two 18-gauge electroporation electrodes and an irreversible electroporation generator. Five variables for energy deposition and electrode configuration were sequentially studied: number of electrical pulses (n=20-90), length of pulses (20-100 microseconds), generator voltage (2250-3000 V), interelectrode spacing (1.5-2.5 cm), and length of active electrode exposure (1.0-3.0 cm). Zones of ablation were determined at gross pathology and histopathology 2-3 hours after irreversible electroporation. Dimensions were compared and subjected to statistical analysis. RESULTS: For 1.5-cm spacing and 2-cm electrode exposure at 2250 V, there was no statistical difference in the size of coagulation when varying the number or length of pulses from 50 to 90 repetitions or 50-100 microseconds, respectively, with each parameter combination yielding 3.0±0.4×1.7±0.4×3.0±0.6 cm (width, depth, and height, respectively). Yet, increasing the pulse width or number over 70 caused increased hyperechogenic or gas and coagulation around the electrode. Increasing the voltage from 2250-3000 V for 70 pulses of 70 microseconds increased coagulation to 3.1±0.4×2.0±0.2 cm (p<0.01 for depth). Greater coagulation width of 3.9±0.5 cm (p<0.01) was achieved at 2-cm interelectrode spacing (with similar depth of 1.9±0.4 cm). However, consistent results required 90 repetitions and a 100-microsecond pulse width; 2.5-cm spacing resulted in two separate zones of ablation. Although electrode exposure did not influence width or depth, a linear correlation (r2=0.77) was noted for height, which ranged from 2.0±0.2-5.0±0.8 cm (for 1- and 3-cm exposures, respectively). CONCLUSION: Predictable zones of tissue destruction can be achieved for irreversible electroporation. Ablation dimensions are sensitive to multiple parameters, suggesting that precise technique and attention to detail will be particularly important when using this modality.