Conversion of the bronchial tree into a conforming electrode to ablate the lung nodule in a porcine model

Figures

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  Fig. 1. Basic concept of CAROL ablation. a, b Typical illustration of centrifugal ablation that requires tumor center orientation of the ablative electrode. c Typical illustration of centripetal ablation with multiple ablative electrodes. d, e Egg white experiment shows that the bronchial structure-shaped electrode has a larger ablation volume than the straight electrode under the same ablation conditions. f Computer simulation of a bronchus filled with E-GaIn (bronchial electrode) without side branches and g with side branches. h–j Computer simulation of CAROL ablation showing the ablation spread pattern according to ablation time. Note that the temperature rise first occurs at sharp tips and then spreads to the proximal parts in CAROL.

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  Fig. 2. CAROL ablation system and the relationship between CAROL ablation and the bronchial diameter and length. a Denotes the CAROL ablation catheter and the bronchial electrode (E-GaIn) during CAROL ablation. The bronchial electrode is injected through the CAROL catheter to turn the bronchial structure around a mass into the RF electrodes. b reveals that the CAROL catheter and the bronchial electrode (E-GaIn) are retrieved from the bronchoscopy(black) after ablation. c The CAROL ablation catheter with a balloon at its distal tip & RF generator used in this experiment. d E-GaIn was used in this experiment for the bronchial electrode. e Computer simulation shows that a bronchus with a smaller diameter, a higher temperature of ablation, and a bronchial length longer than 6 cm leads to an inadequate rise in temperature compared with one that is 3 cm in length. f Computer simulation of a real CAROL ablation case shows a similar outcome to the actual data seen on the 1-week follow-up CT image. g The hypo-enhanced area (yellow dot circle, g) was similar to the area heated by CAROL in the computer simulation (red circle in f). The red dot circle of g denotes ground glass opacity (GGO). h A…

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  Fig. 3. CAROL ablation in ex vivo and in vivo porcine lungs. CAROL ablation in an ex vivo porcine lung segment under a temperature-controlled mode set at 80 °C and gross findings of CAROL ablation. a The X-ray fluoroscopic image of a piece of ex vivo porcine lung filled with the bronchial electrode (black tree-like structure) in its bronchus. Multiple temperature sensors (A–C) are placed in the piece of the lung. b The rise in temperature begins at the distal area (C) and then spreads to the proximal area. The site where the temperature of the bronchial electrode (central bronchial electrode temperature) is measured is shown by (a). c The brown color of coagulation necrosis of the ex vivo lung is evident with a part of the bronchus filled with the bronchial electrode (in the silver-colored dot). b In vivo lung with CAROL ablation. d Denotes the bronchoscopically guided bronchial electrode injection through the CAROL catheter. e Denotes the ablated bronchus seen by bronchoscopy after CAROL ablation. The bronchial electrode in silver is seen in the lumen. f Shows the cone-beam CT finding right after CAROL ablation. The lung segment of the corresponding bronchial territory shows ablation…

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  Fig. 4. Comparison of CAROL ablation with saline-assisted ablation with a linear RF electrode. a Linear RF coil catheter (TIRA ablation catheter, 15 mm length, internal cooling at a rate of 2 ml/min) ablation for 27 min (temperature control set at 80 °C, total of 9419 W) was performed in the saline-wet lung at the target site. b Contrast CT finding at 1 week: the red box denotes the zone of CAROL ablation. The central hypo-enhancement area (dark area) contains the white bright signal of residual E-GaIn in the lung. The hypo-enhancement area is surrounded by peripheral ground glass opacity (GGO). The saline-assisted ablation area (blue box) resulted in irregular ablations. c CAROL ablation with 0.5 ml of the bronchial electrode (temperature control set at 80 °C for 7 min, total of 33,636 W). d Small scattered irregular foci of ablative injury are seen in the almost normal lung area harvested at 12 weeks follow-up. e CT finding at 12 weeks follow-up. f Discrete areas of necrosis are surrounded by a well-organized outer fibrotic layer. Scattered residual bronchial electrode particles (black dots indicated by green arrows) are seen within the fibrotic encapsulated area, especially on the…

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  Fig. 5. Retrievability of the bronchial electrode (E-GaIn). a A total of 0.75 ml of the bronchial electrode was injected into the target site for CAROL ablation. b Bronchoscopic suction immediately after CAROL ablation. c Week 12 follow-up shows further removal of the bronchial electrode by self-expectoration. d–f A total of 5 ml of the bronchial electrode was injected into the bronchus to examine the efficacy of self-expectoration. Most electrodes were removed by self-expectoration. g, h The dose (injected volume) dependent expansion of the bronchial electrode ranging from the optimal amount of the bronchial electrode (1st and 2nd shot) up to a forceful high-pressure injection of a total 3 ml of the bronchial electrode performed into the target site. h, i The alveolar space was filled with bronchial electrodes by this forceful injection, and bronchial electrodes in this small airway zone tended to be trapped. j, k CT findings show that this excessive residual bronchial electrode material was well confined in its zone without causing any other lung problems.

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  Fig. 6. Pseudotumor model in CAROL ablation. a A pseudotumor was made from porcine muscle to be injected through the seldinger needle. b, c Ex vivo lung experiment with the pseudotumor shows that the tumors had temperatures that were higher than that of the target normal lung tissue during CAROL ablation. b The fluoroscopic image of the reverse Y-shaped black tree denotes the bronchial electrode in the piece of ex vivo lung. The round dotted circle is a pseudotumor injected into the piece of ex vivo lung. c The temperature of the pseudotumor I is higher than those of B (distal target tissue) and C (proximal target tissue). d Gross finding after CAROL ablation. The whitish pseudotumor is well ablated showing similar findings to the right panel of (a). e, f, i, j CAROL ablation in vivo porcine lung with the pseudotumor injected through the chest wall. e, i The pseudotumor (round dark one) is surrounded by a black tree with multiple branches (the bronchial electrode). f, j Harvested lung after CAROL ablation. The whitish pseudotumor is well ablated with surrounding brownish discolored lung tissue. g, h CAROL ablation of a pseudotumor lying in the margin of the target ablation zone showing…

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  Fig. 7. Vulnerable area (red oval area) versus tolerable area (blue area) for CAROL. a, b In vulnerable areas, the example of left lung CAROL ablation is more likely to result in collateral damage than in the example of right lung CAROL ablation due to insufficient distancing between the bronchial electrode and the pleura. c Computer simulation shows that a distance of at least 5–10 mm from the tip of the bronchial electrode could prevent thermal injury to non-target tissue. d–f Collateral damage to the pleura and diaphragm in the case of prolonged CAROL ablation (15 min) and its findings at 1 week (d), 6 weeks (e), and 12 weeks (f). g Pleural adhesion is observed during dissection at the 12-week follow-up. h CAROL ablation reached the left heart boundary which resulted in a burn injury on the surface of the heart (i). j, k In CAROL ablation directed only to the diaphragm surface, without the chest wall, the injected liquid metal reaches the pleural surface (red dotted line), and a diaphragmatic hernia through the defect was observed at the 3-week follow-up, which corresponds to the example of left lung CAROL in (b).

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  Fig. 8. Histological and biochemical analysis. a An excessive amount of the bronchial electrode (5 ml) was injected intentionally into the lung. b Almost no residual bronchial electrode was noted on the fluoroscopic findings at the 12-week follow-up. c After harvesting the lung at the 12-week follow-up, histology findings show only mild inflammation in situ along the residual bronchial electrode particle.H&E staining was used in histopathologic features. d Conducted an experiment with 8 pigs from baseline to 4 weeks and 6 pigs from baseline to 12 weeks. Serial blood test results showed no significant change in liver function (AST, ALT, LDH), blood components (Hb: hemoglobin, WBC: white blood cells, Platelets), and electrolytes (Na+, K+, Ca: calcium). Most serum creatinine values were within the normal range of porcine serum creatinine (0.75–2.12 mg/dl)25 except for one case of high serum creatinine (2.2 mg/dl) at baseline. e, f, g, h Negligible gallium and indium concentrations were observed in the subjects’ blood samples. (5 ml of E-GaIn each in subject #13, 14, 3 ml in subject #15, 3 ml with intentional pressurized injection of E-Gain into alveolar space in subject #16, and 1 ml in…