CT-guided Irreversible Electroporation Research Articles

Irreversible Electroporation in Treating Colorectal Liver Metastases in Proximity to Critical Structures

PurposeTo evaluate the safety, efficacy, and oncological outcomes of irreversible electroporation (IRE) of unresectable colorectal liver metastases (CRLMs) close to critical structures. Materials and MethodsThis is a single-center, institutional review board (IRB)–approved, retrospective analysis of patients who underwent percutaneous computed tomography (CT)–guided IRE of CRLM. Between August 2018 and October 2023, 26 patients had 46 tumors treated with percutaneous IRE in 30 ablation sessions. Primary end points were tumor response and local progression-free survival analyzed using Kaplan-Meier survival curves. Secondary end points were overall survival (OS), distant progression-free survival (DPFS) analyzed using Kaplan-Meier survival curves, adverse events rated according to the Common Terminology Criteria for Adverse Events (CTCAE), and length of hospital stay. ResultsAll tumors were close to critical structures, including the portal and hepatic veins, inferior vena cava, bile ducts, and gallbladder. All patients received preprocedural systemic therapy (median 10 cycles). Median length of hospital stay was 1 night. Adverse events occurred in 7 (23%) of 30 procedures, with four Grade 1 and two Grade 2 adverse events, including pleural effusions (n = 2), ileus (n = 1), small hematoma (n = 1), and pneumothorax (n = 2) requiring chest tube placements. Following IRE, the 1- and 2-year local tumor progression-free survival rates were 55.0% and 51.3%. The median DPFS was 3.5 months, with 1- and 2-year DPFS rates of 23.3% and 9.7%. Six patients (23.1%) died during follow-up, with a median OS of 40.4 months. The 1- and 2-year OS rates were 90.9% and 83.9%. ConclusionsIRE is a safe and viable option in the treatment of unresectable CRLMs in locations close to critical structures, but carries a risk of local recurrence.

Simultaneous Gemcitabine and Percutaneous CT-Guided Irreversible Electroporation for Locally Advanced Pancreatic Cancer.

Background Irreversible electroporation (IRE) is a new local ablation technique for pancreatic cancer. The aim of this study is to analyse the safety and effectiveness of simultaneous gemcitabine and percutaneous CT-guided IRE for locally advanced pancreatic cancer (LAPC). Materials and Methods From October 2016 to January 2018, 61 patients with LAPC who received simultaneous gemcitabine and IRE therapy (GEM-IRE group, n = 31) or IRE alone therapy (IRE group, n = 30). Routine intravenous gemcitabine chemotherapy was performed 2 weeks after IRE in both groups. Results Technical success rates were 90.0% (27/30) and 93.3% (28/30) in the GEM-IRE and IRE groups. Compared with the IRE group, the GEM-IRE group exhibited longer overall survival (OS), local tumor progression free survival (LTPFS), and distant disease free survival (DDFS) from IRE (OS, 17.1 vs. 14.2 months, p=0.031; LTPFS, 14.6 vs. 10.2 months, p=0.045; DDFS, 15.4 vs. 11.7 months, p=0.071). Multivariate Cox regression analysis results suggested that tumor volume ≤37 cm3 and simultaneous gemcitabine with IRE were significant independent prognostic factors of OS, LTPFS, and DDFS. Four major adverse reactions occurred; all of them were resolved after symptomatic treatment. Conclusions Simultaneous gemcitabine and percutaneous CT-guided IRE therapy model was effective and well-tolerated therapeutic strategy in LAPC patients.

Recurrent Colorectal Liver Metastases in the Liver Remnant After Major Liver Surgery\u2014IRE as a Salvage Local Treatment When Resection and Thermal Ablation are Unsuitable

PurposeTo examine the safety and short-term oncologic outcomes of computer-tomography-guided (CT-guided) irreversible electroporation (IRE) of recurrent, irresectable colorectal liver metastases (CRLM) after major hepatectomy deemed unsuitable for thermal ablation.Patients and MethodsTwenty-three patients undergoing CT-guided IRE of recurrent CRLM after major hepatectomy were included in this study. All tumors were located adjacent to sole remaining intrahepatic blood vessels and bile ducts, precluding thermal ablation. Patients underwent systematic clinical and imaging follow-up, including magnetic resonance imaging of the liver at 1-month and 3-month intervals thereafter. Time to local and intrahepatic tumor progression within 12 and 36 months and associated risk factors were assessed using Kaplan Meier and Cox regression analysis, respectively.ResultsComplete ablation with a safety margin of at least 0.5 cm was achieved in 22/23 (95.6%) patients. No vessel injury or thrombosis occurred. Five patients developed moderate biliary stenosis after a median of 4 weeks, without requiring treatment. Local tumor-progression-free rates within 12/36 months were 64%/57.4%, respectively. Intrahepatic-progression-free rate within 12/36 months was 36.4%/19.5%, respectively. Five (23%) patients were tumor-free at the end of follow-up. Multivariate Cox regression analysis did not show any association between local tumor-progression-free rates and patient age, target tumor size, primary tumor side or synchronicity of liver metastases.ConclusionIn this highly selected patient population with local recurrences of CRLM after major surgery, IRE was shown to be a safe salvage treatment option when thermal ablation is unsuitable.

Percutaneous Irreversible Electroporation for Treatment of Small Hepatocellular Carcinoma Invisible on Unenhanced CT: A Novel Combined Strategy with Prior Transarterial Tumor Marking.

Simple SummaryIrreversible electroporation (IRE) is an effective alternative for the ablation of small hepatocellular carcinoma (HCC) less than 2 cm, which is often poorly visible under unenhanced computed tomography (CT) and/or an ultrasound resulting in the difficulties of complete ablation. In this study, to achieve successful ablation on these small target HCCs with poor invisibility, the combination of transarterial ethiodized oil tumor marking with sequential computed tomography (CT)-guided IRE was performed. After marking, all 11 target-HCCs demonstrated complete visualization in post-marking CT, which were invisible in pre-marking CT. Technically successful ablation was achieved in all sequential IRE procedures. In the follow-up, no residual unablated tumor was observed and the two-year local tumor progression was 27.3%. Thus, ethiodized oil tumor marking with sequential CT-guided IRE is a safe and feasible combination to treat small HCC which was invisible in unenhanced CT.Introduction. To explore the feasibility, safety, and efficiency of ethiodized oil tumor marking combined with irreversible electroporation (IRE) for small hepatocellular carcinomas (HCCs) that were invisible on unenhanced computed tomography (CT). Methods. A retrospective analysis of the institutional database was performed from January 2018 to September 2018. Patients undergoing ethiodized oil tumor marking to improve target-HCC visualization in subsequent CT-guided IRE were retrieved. Target-HCC visualization after marking was assessed, and the signal-to-noise ratios (SNRs) and contrast-to-noise ratios (CNR) were compared between pre-marking and post-marking CT images using the paired t-test. Standard IRE reports, adverse events, therapeutic endpoints, and survival were summarized and assessed. Results. Nine patients with 11 target-HCCs (11.1–18.8 mm) were included. After marking, all target-HCCs demonstrated complete visualization in post-marking CT, which were invisible in pre-marking CT. Quantitatively, the SNR of the target-HCCs significantly increased after marking (11.07 ± 4.23 vs. 3.36 ± 1.79, p = 0.006), as did the CNR (4.32 ± 3.31 vs. 0.43 ± 0.28, p = 0.023). In sequential IRE procedures, the average current was 30.1 ± 5.3 A, and both the delta ampere and percentage were positive with the mean values of 5.8 ± 2.1 A and 23.8 ± 6.3%, respectively. All procedures were technically successful without any adverse events. In the follow-up, no residual unablated tumor (endpoint-1) was observed. The half-year, one-year, and two-year local tumor progression (endpoint-2) rate was 0%, 9.1%, and 27.3%. The two-year overall survival rate was 100%. Conclusions. Ethiodized oil tumor marking enables to demarcate small HCCs that were invisible on unenhanced CT. It potentially allows a safe and complete ablation in subsequent CT-guided IRE.

Irreversible electroporation (IRE) in renal cell carcinoma (RCC): a mid-term clinical experience

ObjectivesTo evaluate the safety and efficacy of CT-guided IRE of clinical T1a (cT1a) renal tumours close to vital structures and to assess factors that may influence the technical success and early oncological durability.MethodsCT-guided IRE (2015–2020) was prospectively evaluated. Patients’ demographics, technical details/success, Clavien-Dindo (CD) classification of complications (I–V) and oncological outcome were collated. Statistical analysis was performed to determine variables associated with complications. The overall 2- and 3-year cancer-specific (CS), local recurrence-free (LRF) and metastasis-free (MF) survival rates are presented using the Kaplan-Meier curves.ResultsThirty cT1a RCCs (biopsy-proven/known VHL disease) in 26 patients (age 32–81 years) were treated with IRE. The mean tumour size was 2.5 cm and the median follow-up was 37 months. The primary technical success rate was 73.3%, where 22 RCCs were completely IRE ablated. Seven residual diseases were successfully ablated with cryoablation, achieving an overall technical success rate of 97%. One patient did not have repeat treatment as he died from unexpected stroke at 4-month post-IRE. One patient had CD-III complication with a proximal ureteric injury. Five patients developed > 25% reduction of eGFR immediately post-IRE. All patients have preservation of renal function without the requirement for renal dialysis. The overall 2- and 3-year CS, LRF and MF survival rates are 89%, 96%, 91% and 87%.ConclusionCT-guided IRE in cT1a RCC is safe with acceptable complications. The primary technical success rate was suboptimal due to the early operator’s learning curve, and long-term follow-up is required to validate the IRE oncological durability.Key Points• Irreversible electroporation should only be considered when surgery or image-guided thermal ablation is not an option for small renal cancer.• This non-thermal technique is safe in the treatment of small renal cancer and the primary technical success rate was 73.3%.• This can be used when renal cancer is close to important structure.

A retrospective study of CT-guided percutaneous irreversible electroporation (IRE) ablation: clinical efficacy and safety

BackgroundTo evaluate the clinical efficacy and safety of ablating renal cell carcinoma (RCC) by irreversible electroporation (IRE).MethodsFifteen patients (19 lesions) with RCC who underwent IRE were retrospectively reviewed. Seven patients had solitary kidneys. Two lesions were located in the renal hilus. One patient had chronic renal insufficiency. Percutaneous biopsy for histopathology was performed. The best puncture path plan was evaluated before CT-guided IRE. The estimated glomerular filtration rate (eGFR) was compared vs baseline at 1–2 months after the ablation. Contrast-enhanced computed tomography imaging changes were evaluated immediately after IRE. Contrast-enhanced computed tomography/magnetic resonance was performed 1 month, 3 months, 6 months, 12 months and every year thereafter. The complications after treatment were also reviewed.ResultsThe success rate of the procedure was 100%. The median tumor size was 2.4 (IQR 1.3–2.9) cm, with an median score of 6 (IQR 5.5–8) per R.E.N.A.L. criteria (radius, exophytic/endophytic, nearness to collecting system or sinus, anterior/posterior, and location relative to polar lines). Two cases (3 lesions) were punctured through the liver. In other cases, puncture was performed through the perirenal space. There were no severecomplications in interventional therapy. Transient gross hematuria occurred in 2 patients (centrally located). Self-limiting perinephric hematomas occurred in 1 patient. Needle puncture path metastasis was found in 1 patient 2.5 years after IRE. The subcutaneous metastasis was surgically removed, and there was no evidence of recurrence. There was no significant change in eGFR levels in terms of short- term clinical outcomes (t = 0.348, P = 0.733). At 6 months, all 15 patients with imaging studies available had no evidence of recurrence. At 1 year, 1 patient (1 of 15) was noted to have experienced needle tract metastasis and accepted salvage radiofrequency ablation (RFA) therapy.ConclusionsIRE appears to be a safe and effective treatment for RCC that may offer a tissue-sparing method and complete ablation as an alternative therapy for RCC.

Predictors of Occlusion of Hepatic Blood Vessels after Irreversible Electroporation of Liver Tumors

PurposeTo examine predictors of midterm occlusion in portal and hepatic veins within or adjacent to the ablation zone after irreversible electroporation (IRE) of liver tumors. Materials and MethodsThis retrospective cohort analysis included 39 patients who underwent CT-guided IRE of liver tumors. Vessels within or adjacent to the ablation zone were identified on CT images acquired immediately after the procedure, and the positional relationships with the ablation zone (within/adjacent), locations (proximal/distal), and diameters (< 4 mm or ≥ 4 mm) were evaluated. Using contrast-enhanced follow-up scans, each vessel was classified as patent, stenosed, or occluded. Associations between vessel occlusion and each variable were investigated. ResultsOverall, 33 portal veins and 64 hepatic veins were analyzed. Follow-up scans showed occlusion in 12/33 (36.7%) portal veins and 17/64 (26.6%) hepatic veins. Vessels within the ablation zone were occluded significantly more frequently than vessels adjacent to the ablation zone (portal: 55.6% [10/18] vs 13.3% [2/15], P = .04; hepatic: 45.4% [15/33] vs 6.4% [2/31], P = .011). Vessels with a diameter < 4 mm were also occluded significantly more frequently than vessels with a diameter ≥ 4 mm (portal: 72.7% [8/11] vs 18.1% [4/22], P = .011; hepatic: 54.8% [17/31] vs 0% [0/33], P < .001). The respective positive and negative predictive values for occlusion of vessels categorized as both within and < 4 mm were 88% (7/8) and 82% (20/25) for portal veins and 79% (15/19) and 96% (43/45) for hepatic veins. ConclusionsMidterm vessel occlusion after liver IRE could be predicted with relatively high accuracy by assessing ablation location and vessel diameter.

3:00 PM Abstract No. 127 Computed tomography–guided IrReversible Electroporation of hepatocellular carcinoma smaller than 2 cm: the value of transarterial Pre-MARKing with iodized oil for improved guidance during electrode positioning

To report our experience with CT-guided irreversible electroporation (IRE) of hepatocellular carcinoma (HCC) <2 cm performed after transarterial Pre-MARKing with iodized oil (Pre-MARK) for improved guidance during electrode positioning. A systematic review of the institutional prospective database was performed according to the following search strategy: (I) non-enhanced CT-guided IRE as treatment modality, (II) de novo HCC <2 cm as target tumor, (III) Pre-MARK performed for improved guidance during electrode positioning, and (IV) May 2014 to September 2018 as treatment period. Different technical and clinical endpoints were defined. Nine consecutive patients with 11 HCCs (11.1-18.8 mm) were identified. After Pre-MARK with iodized oil (volume of 1.9 ± 1.1 mL), all HCCs demonstrated direct iodized oil uptake when applying non-enhanced CT (signal-to-noise ratio of target HCC vs. non-tumorous liver were 11.1 ± 4.1 vs. 3.1 ± 1.0, respectively [P <0.001]). Subsequent CT-guided IRE was technically successful in all HCCs without complications. Number of electrodes, active electrode tip exposure, distance between pairs of electrodes, preset for electric field intensity and resulting current during pulse application were 3 ± 1, 2.0 ± 0.2 mm, 1.4 ± 0.3 mm, 1957.6 ± 259.8 V/cm, and 29.8 ± 5.4A, respectively. Residual unablated tumor and local tumor progression were noted in zero and three HCCs, respectively. During a follow-up of 517 ± 335 days, overall treatment failure, extrahepatic metastasis and overall survival rates were 27.3%, 0% and 100%, respectively. CT-guided IRE of HCC <2 cm after Pre-MARK for improved guidance during electrode positioning is feasible, safe and effective. Randomized controlled trials are warranted to compare the oncological long-term outcome between this concept and CT-guided IRE of small HCC without Pre-MARK.

Does Drug-Eluting Bead TACE Enhance the Local Effect of IRE? Imaging and Histopathological Evaluation in a Porcine Model.

We conducted an in vivo trial on swine to compare the ablation volumes of irreversible electroporation (IRE) followed by drug-eluting beads transarterial chemoembolization (DEB-TACE) versus IRE only. Nine swine underwent CT-guided IRE in one liver lobe and IRE immediately followed by DEB-TACE in a different liver lobe. For DEB-TACE, 100-300µm beads (DC-Beads®) were loaded with 50mg doxorubicin. For IRE, the NanoKnife® was used employing two electrodes according to the vendor's protocol. Imaging follow-up was performed including CT-based lesion volume assessment using contrast-enhanced CT (venous phase) on days 1, 3, and 7 after the procedure. Three animals were killed for histopathological analysis after each follow-up. Ablation volumes in CT in the IRE + DEB-TACE group were 15.4 ± 10.5ml on day 1, 8.7 ± 5.6ml on day 3, and 1.6 ± 0.7ml on day 7. In the IRE group, the corresponding values were 5.2 ± 5.2ml on day 1, 1.0 ± 1.2ml on day 3, and 0.1 ± 0.1ml on day 7. On day 1 and day 3, ablation volumes of IRE + TACE group were significantly larger than in the IRE group (p < 0.05). 96% of beads were depicted in or around ablative lesions. 69% of these beads were found in the surrounding hemorrhagic infiltration and 31% within the ablative lesion itself. Combination of IRE immediately followed by DEB-TACE resulted in larger ablation volumes compared to IRE alone, suggesting that local efficacy of IRE can be enhanced by post-IRE DEB-TACE.

CT-guided percutaneous irreversible electroporation of locally advanced pancreatic cancer: a complications analysis

Objective To investigate the CT-guided percutaneous irreversible electroporation (IRE) in treating locally advanced pancreatic cancer (LAPC) and providing guidance for its prevention and treatment. Methods We retrospectively analyzed the clinical and imaging data of 17 patients (17 lesions) of LAPC treated with CT-guided IRE in our hospital from July 2015 to June 2016. Complications were documented and reviewed at day 7, 30 and 90 follow up as well as during the procedure. The Clavien-Dindo was used for classification. The reasons that induced complications were summarized and to further discuss the prevention and treatment approaches. Results Of 17 patients, 2 patients suffered a transient tachycardia during the procedure. Eleven patients (65%) showed complications at day 7, of which grade Ⅰ complications occurred in 6 cases, including abdominal pain, nausea, vomiting, or a few of inflammatory exudations around the pancreas; four patients have grade Ⅱ complications, along with portal vein thrombosis;one patient showed grade Ⅲa complications for retroperitoneal infection. With 30 days follow up, the grade Ⅰ complications disappeared, grade Ⅱ complications have not getting better, while grade Ⅲa complications have been improved. With 90 days follow up, patients with grade Ⅲ a complications getting better;two patients with grade Ⅱ complications didn't show any changes; 2 cases progressed to grade Ⅴ, and died of digestive tract bleeding at 82 days and 98 days after procedure. Conclusion CT-guided irreversible electroporation for treating LAPC is a safe ablation approach. Strict patient selection before procedure and make a reasonable prevention and treatment measures can reduce the complications. Key words: Pancreatic neoplasms; Ablation techniques; Irreversible electroporation; Radiology, interventional

Irreversible Electroporation in the Epidural Space of the Porcine Spine: Effects on Adjacent Structures.

Purpose To determine the effects of irreversible electroporation (IRE) on the neural tissues after ablation in the epidural space of the porcine spine. Materials and Methods The institutional animal care and use committee approved this study. With the IRE electrode positioned in the right lateral recess of the spinal epidural space, 20 IRE ablations were performed with computed tomographic (CT) guidance by using different applied voltages in four animals that were euthanized immediately after magnetic resonance (MR) imaging of the spine, performed 6 hours after IRE (terminal group). Histopathologic characteristics of the neural tissues were assessed and used to select a voltage for a survival study. Sixteen CT-guided IRE ablations in the epidural space were performed by using 667 V in four animals that were survived for 7 days (survival group). Clinical characteristics, MR imaging findings (obtained 6 hours after IRE and before euthanasia), histopathologic characteristics, and simulated electric field strengths were assessed. A one-way analysis of variance was used to compare the simulated electric field strength to histologic findings. Results The mean distance between the IRE electrode and the spinal cord and nerve root was 1.71 mm ± 0.90 and 8.47 mm + 3.44, respectively. There was no clinical evidence of paraplegia after IRE ablation. MR imaging and histopathologic examination showed no neural tissue lesions within the spinal cord; however, five of 16 nerve roots (31.2%) demonstrated moderate wallerian degeneration in the survival group. The severity of histopathologic injury in the survival group was not significantly related to either the simulated electric field strength or the distance between the IRE electrode and the neural structure (P > .05). Conclusion Although the spinal cord appears resistant to the toxic effects of IRE, injury to the nerve roots may be a limiting factor for the use of IRE ablation in the epidural space. © RSNA, 2016 Online supplemental material is available for this article.

Minimally Invasive Percutaneous Treatment of Small Renal Tumors with Irreversible Electroporation: A Single-Center Experience

PurposeTo evaluate whether irreversible electroporation (IRE) can be used as an ablation technique for small renal tumors (T1a cancers or small benign tumors) and to describe features after ablation on computed tomography (CT) or magnetic resonance (MR) imaging. Materials and MethodsIn this retrospective study, 20 patients (mean age, 65 y ± 12.8 y) underwent CT-guided IRE of T1a renal carcinoma (n = 13) or small benign or indeterminate renal masses < 4 cm in size (n = 7). Mean tumor size was 2.2 cm ± 0.7. The ablation area was verified with contrast-enhanced imaging performed immediately after the procedure to determine technical success. Imaging was performed 6 weeks (20 of 20 patients), 6 months (15 of 20), and 12 months (6 of 20) after ablation. Medical records and CT/MR imaging features of all patients were reviewed for recurrence, symptoms, and complications after treatment. ResultsTechnical success was achieved in all patients (100%); there were no major procedure-related complications. Minor complications occurred in 7 patients, including self-limiting perinephric hematomas, pain difficult to control, and urinary retention. Mean procedure time was 2.0 hours ± 0.7. At 6 weeks, 2 patients required salvage therapy because of incomplete ablation. At 6 months, all 15 patients with imaging studies available had no evidence of recurrence. At 1 year, 1 patient (1 of 6) was noted to have experienced recurrence. CT/MR imaging after IRE ablation demonstrated an area of nonenhancement in the treatment zone that involuted over ~6 months. ConclusionsRenal IRE appears to be a safe treatment for small renal tumors. Tumors treated with IRE demonstrated nonenhancement in the treatment zone with involution on follow-up CT/MR imaging.

CT-guided irreversible electroporation in an acute porcine liver model: effect of previous transarterial iodized oil tissue marking on technical parameters, 3D computed tomographic rendering of the electroporation zone, and histopathology.

To evaluate the effect of previous transarterial iodized oil tissue marking (ITM) on technical parameters, three-dimensional (3D) computed tomographic (CT) rendering of the electroporation zone, and histopathology after CT-guided irreversible electroporation (IRE) in an acute porcine liver model as a potential strategy to improve IRE performance. After Ethics Committee approval was obtained, in five landrace pigs, two IREs of the right and left liver (RL and LL) were performed under CT guidance with identical electroporation parameters. Before IRE, transarterial marking of the LL was performed with iodized oil. Nonenhanced and contrast-enhanced CT examinations followed. One hour after IRE, animals were killed and livers collected. Mean resulting voltage and amperage during IRE were assessed. For 3D CT rendering of the electroporation zone, parameters for size and shape were analyzed. Quantitative data were compared by the Mann-Whitney test. Histopathological differences were assessed. Mean resulting voltage and amperage were 2,545.3 ± 66.0 V and 26.1 ± 1.8 A for RL, and 2,537.3 ± 69.0 V and 27.7 ± 1.8 A for LL without significant differences. Short axis, volume, and sphericity index were 16.5 ± 4.4 mm, 8.6 ± 3.2 cm(3), and 1.7 ± 0.3 for RL, and 18.2 ± 3.4 mm, 9.8 ± 3.8 cm(3), and 1.7 ± 0.3 for LL without significant differences. For RL and LL, the electroporation zone consisted of severely widened hepatic sinusoids containing erythrocytes and showed homogeneous apoptosis. For LL, iodized oil could be detected in the center and at the rim of the electroporation zone. There is no adverse effect of previous ITM on technical parameters, 3D CT rendering of the electroporation zone, and histopathology after CT-guided IRE of the liver.

Planning irreversible electroporation in the porcine kidney: are numerical simulations reliable for predicting empiric ablation outcomes?

Numerical simulations are used for treatment planning in clinical applications of irreversible electroporation (IRE) to determine ablation size and shape. To assess the reliability of simulations for treatment planning, we compared simulation results with empiric outcomes of renal IRE using computed tomography (CT) and histology in an animal model. The ablation size and shape for six different IRE parameter sets (70-90 pulses, 2,000-2,700 V, 70-100 µs) for monopolar and bipolar electrodes was simulated using a numerical model. Employing these treatment parameters, 35 CT-guided IRE ablations were created in both kidneys of six pigs and followed up with CT immediately and after 24 h. Histopathology was analyzed from postablation day 1. Ablation zones on CT measured 81 ± 18 % (day 0, p ≤ 0.05) and 115 ± 18 % (day 1, p ≤ 0.09) of the simulated size for monopolar electrodes, and 190 ± 33 % (day 0, p ≤ 0.001) and 234 ± 12 % (day 1, p ≤ 0.0001) for bipolar electrodes. Histopathology indicated smaller ablation zones than simulated (71 ± 41 %, p ≤ 0.047) and measured on CT (47 ± 16 %, p ≤ 0.005) with complete ablation of kidney parenchyma within the central zone and incomplete ablation in the periphery. Both numerical simulations for planning renal IRE and CT measurements may overestimate the size of ablation compared to histology, and ablation effects may be incomplete in the periphery.

3:54 PM Abstract No. 55 - Irreversible electroporation (IRE) ablation of the lumbar vertebrae in a porcine model: a correlation of clinical, radiologic and pathologic findings

Purpose To evaluate the effects of IRE ablation of the lumbar vertebrae in pigs. Materials and Methods Sixteen CT-guided IRE ablations [transpedicular location, (n=8 vertebrae) and directly over the posterior cortex (n=8 vertebrae)] were performed in the lumbar vertebrae of 8 pigs. Magnetic resonance imaging (MRI) was obtained immediately prior to euthanasia at 2 or 7-days postablation. Clinical, imaging and histopathological data were analyzed. The maximum length and width of the ablation zone was measured on the T2 and T1 + contrast MRI sequences and compared with histopatholgic measurements. Miller’s low-bias back-transformation was used to construct 95% confidence intervals for the mean absolute percent difference using square root transformed data. Results IRE probe placement and ablation was successful in all cases. The mean distances from the IRE probe to the posterior wall of vertebral body or the exiting nerve root were 2.93 ± 0.77 mm and 7.87 ± 1.99 mm respectively. None of the animals had neurologic deficits or MRI findings of focal myelopathy or radiculopathy. Well delineated areas of necrosis of bone marrow and bone tissues, and acute degeneration and necrosis of skeletal muscle adjacent to the vertebral body were present. These lesions were associated with tissue repair changes in the 7-day postablation animals. Four of 8 ablations in the transpedicular group and 3 of 8 ablations in the posterior cortex group had minimal to moderate acute degenerative lesions of adjacent nerve roots that were not clinically significant. The absolute percent difference of ablation measurements between MRI sequences and histopathological lesions showed an average error range of 24.2-28.8% [95% CI: (12.2%, 47.3%)] on T2 and 26.1-33.3% [95% CI: (15.1%, 52.6%)] on T1+contrast sequences. Conclusion IRE ablation of the lumbar vertebrae in pigs is feasible, safe, and produces localized necrosis of the bone, bone marrow and muscle tissues. No neurological clinical symptoms were associated with this procedure. MRI signal changes are not accurate indicators of the ablation zone when compared with histopathologic findings.

Abstract No. 320 - New device and technique for application of irreversible electroporation for focal rectal ablation

Purpose Irreversible electroporation (IRE) is a non thermal ablation technique whose working mechanism allows the sparing of extracellular matrix and lumen structures within the ablated region. This makes IRE a potentially valuable tool for the debulking, palliation or for the treatment of rectal tumors while providing quality of life benefits over surgical resection and anastomosis. However, there is a lack of devices and knowledge as to how this therapy can be delivered for focal ablation in the rectum. Materials and Methods CT-guided IRE ablations were performed using a specially designed endorectal electrode probe. A monopolar probe with a grounding pad was used to create 10 ablations in 5 pigs, and a bipolar probe was used to create 2 ablations in a single pig. Numerical simulations were used to identify two treatment settings, one that would result in the ablation of just the mucosal layers and a second setting that would cause transmural ablation of the rectal wall. Each treatment setting was attempted once in each animal. The pigs were sacrificed acutely and the rectum was removed for pathological analysis. Results Treatment proceeded normally with minimal rectal bleeding, no treatment related complications or perforation of the rectum. 9 of the 10 monopolar lesions and both bipolar lesions were successfully located and extracted. All lesions evidenced uniform coagulative necrosis with mild inflammation and hyperemia. There was a sharp demarcation between ablated and adjacent normal tissue. The lesions corresponded in shape and the depth of penetration to the values predicted using numerical simulation. Lesions created with the lower treatment setting resulted in complete ablation of the mucosal layers with superficial or no injury to muscularis propia. Lesions created with the higher treatment setting resulted in uniform ablation with transmural necrosis of the rectal wall. Conclusion An endorectal probe can be used to safely deliver IRE treatment and create controlled focal lesions in the rectal wall. Treatment parameters can be determined through numerical modeling to control the depth of penetration of the lesion and an endorectal electrode probe be used to deliver the treatment.

2:26 PM Abstract No. 88 - Irreversible electroporation (IRE) in cirrhotic liver: preliminary experience in a large animal model

Purpose To compare the efficacy of tissue ablation using IRE in cirrhotic versus normal liver parenchyma in a porcine model. Materials and Methods Eight pigs received a mixture containing iodized oil and ethanol into the hepatic artery to induce liver injury. Cirrhosis was allowed to develop over 4 weeks. Four control animals received a sham hepatic arterial injection of normal saline. CT-guided IRE lesions were created using paired electrodes (18g, 2 cm tip) and a Nanoknife generator (Angiodynamics, Fremont, CA) in cirrhotic (n=14 lesions) and normal liver (n=8 lesions) with the aid of cardiac gating. All animals were euthanized within three hours of the ablation procedure. IRE parameters and pathological data were recorded and analyzed. Immunohistochemical analysis of cleaved caspase-3 was used to assess for apoptosis. These data were compared and subject to statistical analysis using the Satterthwaite t-test. Results Cirrhosis was successfully induced in all experimental animals with histological analysis revealing a median METAVIR score of 3.38. The median calculated electrical resistance of the liver parenchyma during pulse application was greater in the cirrhotic parenchyma 113.9 ohm [95% CI: (92.2,134.7)] than normal liver 90.2 ohm [95% CI: (53.4,126.9)], but it failed to reach statistical significance (p=0.05). The mean ablation volume in the cirrhotic and normal livers at gross pathology was 17.2 cm3 [95% CI: (14.3,20)] and 11.8 cm3 [95% CI: (9.7,13.8)], respectively. Difference in ablation volumes was also not statistically significant (p=0.48). Histological analysis of ablation lesions was similar in both groups and characterized by hepatocellular dissociation often associated with hemorrhage and sinusoidal dilatation with minimal surrounding inflammation. Hepatocytes did not show any substantial evidence of apoptosis at the time of necropsy. Conclusion IRE tissue destruction appears equally effective in cirrhotic and normal liver parenchyma in a porcine model. Although, a trend toward greater electrical resistance was observed in the cirrhotic liver, it did not impact the overall volume of ablation.

Abstract No. 377 - CT findings after irreversible electroporation ablation in a porcine model: Radiologic-pathologic correlation

Purpose To characterize computed tomography (CT) findings after irreversible electroporation (IRE) in a porcine model Materials and Methods Twenty two CT-guided IRE lesions were created in livers of 12 pigs. Energy was delivered at 2250-3000 V (pulse length, 90-100 μsec; pulse repetition, 70-90) by using two 18-gauge electrodes with 2-2.5 cm active tip, 1.5-2.0 cm distance between electrodes and a Nanoknife generator (Angiodynamics, Fremont, CA). Triple-phase multi-detector CT imaging was performed prior to IRE application and immediately before euthanasia (2 hours after ablation). Multiple CT imaging features were studied, including: dimensions; coagulation zone attenuation; and presence, as well as characteristics of post ablation enhancement. Zones of ablation were evaluated at gross and histopathologic examination, correlated with CT findings, and subjected to statistical analysis. Results The mean ablation volume measured by CT imaging and gross pathology was 31.8 cm 3 [95% CI: (14.3, 49.4)] and 15.2 cm 3 [95% CI: (12.8,17.6)]. Using a mixed-effects regression model, the two volume means are significantly different (p=0.04) with the size of the ablation zone on the CT appearing larger than the gross size (p=0.0416). Two hours after IRE energy application, the ablation zone appeared as a well demarcated hypoattenuating area. Mean pre, arterial and portal HU for the zone of ablation was 79.6 [95% CI: (73.1, 87.2), 64.3 [95% CI: (57.3, 72.0)], and 73.9 [95% CI: (61.8, 86.1). An incomplete rim of enhancement was observed surrounding the zone of ablation in both the arterial and portal phase with a median thickness of 2.5 mm. Histologic examination revealed a clear demarcation between the ablated liver and adjacent unaffected parenchyma. Coagulation zone was characterized by hepatocellular dissociation often associated with hemorrhage and sinusoidal dilatation. Conclusion CT imaging in the acute period after IRE depicts the ablation zone as a hypoattenuating lesion with a surrounding rim of enhancement. However, it appears to overestimate the dimensions of the ablative injury.

Irreversible Electroporation Adjacent to the Rectum: Evaluation of Pathological Effects in a Pig Model

To evaluate the effects of irreversible electroporation (IRE) on the rectum wall after IRE applied adjacent to the rectum. 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 7-15days and the rectums were harvested for pathological evaluation. 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. 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.