Irreversible electroporation adjacent to the rectum: evaluation of pathological effects in a pig model.

PURPOSE: To evaluate the effects of irreversible electroporation (IRE) on the rectum wall after IRE applied adjacent to the rectum. MATERIAL AND METHODS: CT-guided IRE adjacent to the rectum wall was performed in 11 pigs; a total of 44 lesions were created. In five pigs, ablations were performed without a water-filled endorectal coil (group A); in six pigs, ablation was performed with the coil to avoid displacement of the rectum wall (group B). The pigs were killed after 7-15 days and the rectums were harvested for pathological evaluation. RESULTS: There was no evidence of perforation on gross postmortem examination. Perirectal muscle lesions were observed in 18 of 20 ablations in group A and in 21 of 24 ablations in group B. Inflammation and fibrosis of the muscularis propria was observed in ten of 18 lesions in group A and in ten of 21 lesions in group B. In group A, findings were limited to the external layer of the muscularis propria except for one lesion; in group B, findings were transmural in all cases. Transmural necrosis with marked suppurative mucosal inflammation was observed in seven of 21 lesions in group B and in no lesion in group A. CONCLUSION: IRE-ablation adjacent to the rectum may be uneventful if the rectum wall is mobile and able to contract. IRE-ablation of the rectum may be harmful if the rectum wall is fixed adjacent to the IRE-probe.

The delayed effects of irreversible electroporation ablation on nerves.

OBJECTIVE: To evaluate the delayed effects of irreversible electroporation (IRE) ablation on nerves. METHODS: The study was approved by the institutional animal care and use committee. CT-guided IRE-ablation (electric field per distance, 1,500 V/cm; pulse length, 70 µs; number of pulses, 90) of 6 sciatic nerves was performed in 6 pigs that were euthanized 2 months after ablation. The sciatic nerves were harvested immediately after euthanasia for histopathological evaluation. Sections from selected specimens were stained with haematoxylin and eosin (H&E), Masson's trichrome (MT) method for collagen, and immunohistochemistry was performed for S100 and neurofilaments (markers for Schwann cells and axons, respectively). RESULTS: All nerves showed a preserved endoneural architecture and presence of numerous small calibre axons associated with Schwann cell hyperplasia, consistent with axonal regeneration. A fibrous scar was observed in the adjacent muscle tissue, confirming ablation at the site examined. CONCLUSION: After IRE-ablation of nerves, the preservation of the architecture of the endoneurium and the proliferation of Schwann cells may enable axonal regeneration as demonstrated after 2 months in this study.

Acute and subacute effects of irreversible electroporation on nerves: experimental study in a pig model.

PURPOSE: To evaluate whether irreversible electroporation (IRE) has the potential to damage nerves in a porcine model and to compare histopathologic findings after IRE with histopathologic findings after radiofrequency ablation (RFA). MATERIALS AND METHODS: This study was approved by the institutional animal care and use committee. Computed tomography (CT)-guided IRE of 11 porcine sciatic nerves was performed in nine pigs, and histopathologic analysis was performed on the day of ablation or 3, 6, or 14 days after ablation. In addition, acute RFA of six porcine sciatic nerves was performed in six pigs that were harvested on the day of ablation. All nerves and associated muscles and tissues were assessed for histopathologic findings consistent with athermal or thermal injury, respectively, such as axonal swelling, axonal fragmentation and loss, Wallerian degeneration, inflammatory infiltrates, Schwann cell proliferation, and coagulative necrosis. The percentage of fascicles affected was recorded. RESULTS: All nerves had an axonal injury. The percentage of affected nerve fascicles after IRE was 50%-100%. Axonal swelling and perineural inflammatory infiltrates were detectable at every time point after ablation. Axonal fragmentation and loss, macrophage infiltration, and Schwann cell proliferation were found 6 and 14 days after ablation. Distal Wallerian axonal degeneration was observed 14 days after ablation. The endoneurium and perineurium architecture remained intact in all cases. RFA specimens at the day of ablation revealed acute coagulative necrosis associated with intense basophilic staining of extracellular matrix, including collagen of the perineurium and epineurium consistent with thermal injury. CONCLUSION: IRE has the potential to damage nerves and may result in axonal swelling, fragmentation, and distal Wallerian degeneration. However, preservation of endoneurium architecture and proliferation of Schwann cells may suggest the potential for axonal regeneration. In contrast, RFA leads to thermal nerve damage, causing protein denaturation, and suggests a much lower potential for regeneration.

Percutaneous irreversible electroporation lung ablation: preliminary results in a porcine model.

OBJECTIVE: Irreversible electroporation (IRE) uses direct electrical pulses to create permanent "pores" in cell membranes to cause cell death. In contrast to conventional modalities, IRE has a nonthermal mechanism of action. Our objective was to study the histopathological and imaging features of IRE in normal swine lung. MATERIALS AND METHODS: Eleven female swine were studied for hyperacute (8 h), acute (24 h), subacute (96 h), and chronic (3 week) effects of IRE ablation in lung. Paired unipolar IRE applicators were placed under computed tomography (CT) guidance. Some applicators were deliberately positioned near bronchovascular structures. IRE pulse delivery was synchronized with the cardiac rhythm only when ablation was performed within 2 cm of the heart. Contrast-enhanced CT scan was performed immediately before and after IRE and at 1 and 3 weeks after IRE ablation. Representative tissue was stained with hematoxylin and eosin for histopathology. RESULTS: Twenty-five ablations were created: ten hyperacute, four acute, and three subacute ablations showed alveolar edema and necrosis with necrosis of bronchial, bronchiolar, and vascular epithelium. Bronchovascular architecture was maintained. Chronic ablations showed bronchiolitis obliterans and alveolar interstitial fibrosis. Immediate post-procedure CT images showed linear or patchy density along the applicator tract. At 1 week, there was consolidation that resolved partially or completely by 3 weeks. Pneumothorax requiring chest tube developed in two animals; no significant cardiac arrhythmias were noted. CONCLUSION: Our preliminary porcine study demonstrates the nonthermal and extracellular matrix sparing mechanism of action of IRE. IRE is a potential alternative to thermal ablative modalities.

Irreversible electroporation near the heart: ventricular arrhythmias can be prevented with ECG synchronization.

OBJECTIVE: Irreversible electroporation is a nonthermal ablative tool that uses direct electrical pulses to create irreversible membrane pores and cell death. The ablation zone is surrounded by a zone of reversibly increased permeability; either zone can cause cardiac arrhythmias. Our purpose was to establish a safety profile for the use of irreversible electroporation close to the heart. MATERIALS AND METHODS: The effect of unsynchronized and synchronized (with the R wave on ECG) irreversible electroporation in swine lung and myocardium was studied in 11 pigs. Twelve lead ECG recordings were analyzed by an electrophysiologist for the presence of arrhythmia. Ventricular arrhythmias were categorized as major events. Minor events included all other dysrhythmias or ECG changes. Cardiac and lung tissue was submitted for histopathologic analysis. Electrical field modeling was performed to predict the distance from the applicators over which cells show electroporation-induced increased permeability. RESULTS: At less than or equal to 1.7 cm from the heart, fatal (major) events occurred with all unsynchronized irreversible electroporation. No major and three minor events were seen with synchronized irreversible electroporation. At more than 1.7 cm from the heart, two minor events occurred with only unsynchronized irreversible electroporation. Electrical field modeling correlates well with the clinical results, revealing increased cell membrane permeability up to 1.7 cm away from the applicators. Complete lung ablation without intervening live cells was seen. No myocardial injury was seen. CONCLUSION: Unsynchronized irreversible electroporation close to the heart can cause fatal ventricular arrhythmias. Synchronizing irreversible electroporation pulse delivery with absolute refractory period avoids significant cardiac arrhythmias.

Renal tissue ablation with irreversible electroporation: preliminary results in a porcine model.

OBJECTIVES: To evaluate the histopathologic and computed tomography imaging features associated with irreversible electroporation (IRE) ablation performed in normal porcine kidneys. IRE is a nonthermal ablative tool that uses direct electrical pulses to create permanent "pores" in cell membranes and cell death. It does not affect the extracellular matrix. METHODS: Fifteen female swine were treated with IRE using acute (<24 hours), subacute (36 hours), and chronic (3 weeks) treatment settings. Unipolar IRE applicators were placed under CT guidance. The renal pelvis/calyx was included in 18 ablations. Imaging and histopathologic follow-up were performed. RESULTS: A total of 29 ablations (19 acute, 4 subacute, and 6 chronic) were created. Acute/subacute ablations showed complete cortical necrosis without intervening live cells. The pelvic epithelium was necrotic with urothelial sloughing; pelvic extracellular matrix was intact. Chronic ablations showed cortical fibrosis, regenerating renal pelvic epithelium and intact pelvic extracellular matrix. No thermal injury, renal pelvic, or blood vessel injury was seen. Immediate postprocedure CT imaging demonstrated a hypodense nonenhancing lesion that persisted at 1 week. Of the 6 chronic lesions, 4 showed complete resolution at 3 weeks on imaging. No collecting system damage was seen. CONCLUSIONS: This preliminary porcine study demonstrates the nonthermal and connective tissue sparing mechanism of action of IRE. These features may protect against collecting system damage after IRE ablation of renal tissue. IRE could therefore play an important role in ablation of centrally located renal tumors.