Irreversible Electroporation Ablation Zone Research Articles

Abstract No. 51 Differentiation of Irreversible Electroporation Regions in Normal and Tumor Tissues Using MRI Textures

Irreversible electroporation (IRE) is a promising tissue ablation technique for liver cancer patients unsuitable for surgical resection or liver transplantation. The main clinical challenge in IRE ablation is differentiating IRE ablation zones for immediate assessment. Here, we investigated the reproducibility of radiomic analysis of conventional T1w MRI data acquired from liver tumors and normal liver tissues for assessment of IRE outcomes. IRE ablation was performed on twenty-six rabbits' normal liver or tumors. Anatomical and perfusion MRI data were acquired immediately after the completion of the procedure. IRE and RE zones were outlined on perfusion MRI data with histology validation and mask images were translated to T1w images. T1w MRI data were normalized using three levels to examine the effects of different image specificity (8, 16, and 32) while determining the characteristic patterns related to IRE ablation. At each specificity level, quantitative imaging features were computed by analyzing intensity distribution and textural patterns. The relevant variables were identified by following a multi-step feature selection framework that integrates pairwise likelihood, analysis, and LASSO. Multiple classification models were generated using logistic regression, nonlinear support vector machines, and random forest (RF) with a five-fold cross-validation approach. The accuracy, sensitivity, specificity, and receiver operating characteristic (ROC) curves were employed for the evaluation of the developed classification methods. Random forest classification models outperformed logistic regression and support vector machine models. In terms of image specificity levels, the images sampled with sixteen intensity levels facilitated the most accurate and robust performance compared with images with lower and higher details. The random forest classifier equipped with features computed from images with sixteen levels obtained a training accuracy of 90.86% and a validation accuracy of 81.09% for T1w images. The model sensitivity was 92.33% and 81.33%, and specificity was 89.33% and 80.67% for training and validation sets, respectively. Moreover, we recorded the area under the ROC curve as 97.86% for training and 89.47% for the validation cohort. T1w MRI radiomic features reveal IRE ablation-related effects performed on normal liver and tumor tissues, which demonstrates the potential benefit of quantitative analysis of conventional MRI data for immediate assessment of IRE ablation zones in other solid cancers.

MP15-04 SAFETY AND FEASIBILITY OF SALVAGE RADICAL PROSTATECTOMY FOLLOWING PRIMARY IRE TREATMENT FOR RECURRENT LOCALIZED PROSTATE CANCER: AN INTERNATIONAL AND MULTICENTER ANALYSIS

You have accessJournal of UrologyCME1 May 2022MP15-04 SAFETY AND FEASIBILITY OF SALVAGE RADICAL PROSTATECTOMY FOLLOWING PRIMARY IRE TREATMENT FOR RECURRENT LOCALIZED PROSTATE CANCER: AN INTERNATIONAL AND MULTICENTER ANALYSIS Luigi A.M.J.G. van Riel, Alexander Blazevski, Ertunc Kabaktepe, Bart Geboers, Daan Reesink, Pascal Stijns, Philip D. Stricker, Juan Casanova, Jose Luis Dominguez-Escrig, Theo M. de Reijke, Matthijs J. Scheltema, and Jorg R. Oddens Luigi A.M.J.G. van RielLuigi A.M.J.G. van Riel More articles by this author , Alexander BlazevskiAlexander Blazevski More articles by this author , Ertunc KabaktepeErtunc Kabaktepe More articles by this author , Bart GeboersBart Geboers More articles by this author , Daan ReesinkDaan Reesink More articles by this author , Pascal StijnsPascal Stijns More articles by this author , Philip D. StrickerPhilip D. Stricker More articles by this author , Juan CasanovaJuan Casanova More articles by this author , Jose Luis Dominguez-EscrigJose Luis Dominguez-Escrig More articles by this author , Theo M. de ReijkeTheo M. de Reijke More articles by this author , Matthijs J. ScheltemaMatthijs J. Scheltema More articles by this author , and Jorg R. OddensJorg R. Oddens More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002544.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Irreversible electroporation (IRE) is among the available ablative techniques in carefully selected prostate cancer (PCa) patients. Yet, there is a risk of recurrence leading to the need for salvage therapy. It is unknown whether initial IRE treatment jeopardizes functional and oncological outcomes following salvage radical prostatectomy (sRP) for recurrent localized PCa. The aim of this study is to evaluate safety, feasibility, functional and short-term oncological outcomes of sRP for recurrent localized PCa after initial primary IRE treatment. METHODS: An international, multicenter and retrospective analysis of prospectively collected data of patients that underwent sRP for recurrent localized PCa after initial primary IRE treatment. Data were reported on functional outcomes (urinary continence and erectile function), quality of life and oncological outcomes (time interval between IRE and sRP, pathology, overall survival) and safety (surgical complications) and feasibility of sRP (as reported by surgeons). RESULTS: In four participating centers a total of 39 patients with a median (IQR) age of 64 (7.0) years were identified that underwent sRP following initial IRE treatment. Median (IQR) time to recurrence after IRE was 14.3 (29.8) months. sRP was feasible without dissection difficulties and serious adverse events. Location of recurrence was observed in-field the initial IRE ablation zone in 23 patients (59%), see Figure 1. Significant positive surgical margin (PSM) rate was 15.4%. A persistent detectable PSA was found in one case post-sRP (2.6%), caused by metastatic disease. One patient (2.6%) had a biochemical recurrence 6 months following sRP. These two cases, together with a PSM case, required additional therapy following sRP. Overall survival was 100% with a median (IQR) follow-up duration of 6.9 (12.2) months. At last follow-up urinary continence and erectile function were preserved in 26 patients (76.5%) and 14 patients (41.2%), respectively, while quality of life remained stable. CONCLUSIONS: sRP is safe and feasible for PCa patients with recurrent localized disease following initial IRE treatment. Functional outcomes following sRP seem comparable to primary RP. Source of Funding: Cure for Cancer foundation © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e242 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Luigi A.M.J.G. van Riel More articles by this author Alexander Blazevski More articles by this author Ertunc Kabaktepe More articles by this author Bart Geboers More articles by this author Daan Reesink More articles by this author Pascal Stijns More articles by this author Philip D. Stricker More articles by this author Juan Casanova More articles by this author Jose Luis Dominguez-Escrig More articles by this author Theo M. de Reijke More articles by this author Matthijs J. Scheltema More articles by this author Jorg R. Oddens More articles by this author Expand All Advertisement PDF DownloadLoading ...

Early Differentiation of Irreversible Electroporation Ablation Regions With Radiomics Features of Conventional MRI

Irreversible electroporation (IRE) is a promising non-thermal ablation technique for the treatment of patients with hepatocellular carcinoma. Early differentiation of the IRE zone from surrounding reversibly electroporated (RE) penumbra is vital for the evaluation of treatment response. In this study, an advanced statistical learning framework was developed by evaluating standard MRI data to differentiate IRE ablation zones, and to correlate with histological tumor biomarkers. Fourteen rabbits with VX2 liver tumors were scanned following IRE ablation and forty-six features were extracted from T1w and T2w MRI. Following identification of key imaging variables through two-step feature analysis, multivariable classification and regression models were generated for differentiation of IRE ablation zones, and correlation with histological markers reflecting viable tumor cells, microvessel density, and apoptosis rate. The performance of the multivariable models was assessed by measuring accuracy, receiver operating characteristics curve analysis, and Spearman correlation coefficients. The classifiers integrating four radiomics features of T1w, T2w, and T1w+T2w MRI data distinguished IRE from RE zones with an accuracy of 97%, 80%, and 97%, respectively. Also, pixelwise classification models of T1w, T2w, and T1w+T2w MRI labeled each voxel with an accuracy of 82.8%, 66.5%, and 82.9%, respectively. Regression models obtained a strong correlation with behavior of viable tumor cells (0.62 ≤ r2 ≤ 0.85, p < 0.01), apoptosis (0.40 ≤ r2 ≤ 0.82, p < 0.01), and microvessel density (0.48 ≤ r2 ≤ 0.58, p < 0.01). MRI radiomics features provide descriptive power for early differentiation of IRE and RE zones while observing strong correlations among multivariable MRI regression models and histological tumor biomarkers.

Evaluation of Alterations to Bile Ducts and Laboratory Values During the First 3 Months After Irreversible Electroporation of Malignant Hepatic Tumors.

PurposeTo assess the incidence and evolution of biliary alterations adjacent to the ablation area in patients with hepatic malignancies during the first 3 months after percutaneous irreversible electroporation (IRE) and to investigate associated changes in laboratory values.Material and MethodsBile ducts located within a ≤1.0 cm radius of the ablation zone were analyzed in 45 patients by preinterventional and postinterventional MRI (1–3 days, 6 weeks, and 3 months after IRE). Moreover, levels of alkaline phosphatase (AP) and serum bilirubin (SB) were examined for evidence of bile duct injury. Biliary alterations and the presence of postinterventional-elevated laboratory levels were correlated with features of the lesions, patients, ablation procedures, and laboratory values.ResultsA total of 80 bile ducts were located within a 1.0 cm radius of the ablation zone: 59 were encased, 16 were abutting and 5 were located within a radius of 0.1–1.0 cm of the ablation area. In total, 38 biliary injuries (narrowing, n=22; dilatation, n=14; biloma, n=2) were detected, 3 cases of narrowing occurred for the first time 6 weeks and 3 months after IRE, 21 alterations (dilatation: n=9; narrowing; n=10; biloma: n=2) had resolved during the first 6 weeks, 1 alteration (dilatation: n=1) had resolved by the last follow-up control. Three months after IRE, 19 patients showed elevated levels of AP, whereas SB levels were increased in 10 cases. No significant association between biliary alterations or postinterventional-elevated laboratory values and the investigated characteristics of lesions, patients, ablation procedures or laboratory values could be proven.ConclusionDifferent alterations of bile ducts adjacent to an IRE ablation zone are common, of which dilatation and especially narrowing commonly represent a long-term complication after IRE. Moreover, a definite correlation between the frequently observed prolonged post-ablative elevation of AP- and SB-levels and the postinterventional biliary alterations could not be proven.

Histological analysis of human pancreatic carcinoma following irreversible electroporation in a nude mouse model.

AIMTo determine changes in the morphology and function of pancreatic cancer cells after irreversible electroporation (IRE) treatment, and to explore the clinical significance of IRE treatment for pancreatic cancer providing an experimental basis for the clinical application of IRE treatment.METHODSIRE was carried out in an athymic nude mouse model of pancreatic carcinoma generated with human pancreatic cancer cells 1. In therapy groups, IRE electrodes were inserted with 90 pulses per second at 800 V/cm applied to ablate the targeted tumor tissues. Histological assessment of the affected tissue was performed by hematoxylin and eosin staining (HE). Quantification of cell proliferation and apoptosis was performed by evaluating Ki67 and caspase-3 levels, respectively. Flow cytometry was used to assess cell apoptosis. Ultrasound imaging was carried out to evaluate IRE treatment results. Pathological correlation studies showed IRE is effective for the targeted ablation of pancreatic tumors in an orthotopic mouse model.RESULTSIRE was efficacious in removing tumors in the orthotopic mouse model. The IRE-ablated zone displays characteristics of nude mouse models at different time-points as assessed by hematoxylin and eosin staining. Immunohistochemical analysis of samples from the pancreatic cancer models showed significantly enhanced caspase-3 cleavage and Ki67. Flow cytometry data corroborated the above findings that apoptosis in tumor cells was observed immediately on the first postoperative day, and with time the middle and late stages of apoptosis were observed. For ultrasound imaging studies, the IRE ablation zone became a hyperechoic area due to increasing inflammatory and immunologic cellular contents.CONCLUSIONIRE is a promising new approach for pancreatic cancer, with many potential advantages over conventional ablation techniques.

Irreversible Electroporation: Defining the MRI Appearance of the Ablation Zone With Histopathologic Correlation in a Porcine Liver Model.

The purpose of this study is to evaluate the MRI appearance of the irreversible electroporation zone in porcine liver, with histopathologic correlation. Nine irreversible electroporation ablations were percutaneously created in two Yorkshire pigs. Irreversible electroporation was performed with a bipolar 16-gauge electrode with 3-cm exposure tip and fixed 8-mm interpolar distance. Gadoxetate disodium-enhanced 3-T MRI was performed 50 hours after irreversible electroporation. Livers were harvested immediately after MRI for histopathologic analysis. Ablation zone size was measured on each pulse sequence and correlated with pathologic ablation zone size. Qualitative MRI features of the ablation zone were assessed, and contrast-to-noise ratios (CNRs) were calculated. Statistical analysis included Pearson correlation and t tests. Histopathologically, three distinct layers were present in the irreversible electroporation ablation zone: an inner layer of coagulative necrosis (hyperintense at T1- and T2-weighted imaging and nonenhancing), a middle layer of congestion and hemorrhage (hypointense at T1-weighted imaging, hyperintense at T2-weighted imaging and DWI, and progressively enhancing but hypointense at the hepatobiliary phase), and a peripheral layer of inflammation (hyperintense at the arterial phase but isointense at all other sequences). The hepatobiliary phase ablation zone size showed the highest correlation with the pathologic ablation zone size (r = 0.973). This correlation was significant (p < 0.001). T2-weighted imaging had the highest lesion-to-normal tissue CNR. The irreversible electroporation ablation zone contains three distinct histopathologic zones, each with unique MRI features. T2-weighted imaging had the highest CNR, and the hepatobiliary phase had the strongest correlation with ablation zone size.

Characterization of Irreversible Electroporation Ablation with a Validated Perfused Organ Model

PurposeTo develop and validate a perfused organ model for characterizing ablations for irreversible electroporation (IRE)–based therapies. Materials and MethodsEight excised porcine livers were mechanically perfused with a modified phosphate-buffered saline solution to maintain viability during IRE ablation. IRE pulses were delivered using 2 monopolar electrodes over a range of parameters, including voltage (1,875–3,000 V), pulse length (70–100 µsec), number of pulses (50–600), electrode exposure (1.0–2.0 cm), and electrode spacing (1.5–2.0 cm). Organs were dissected, and treatment zones were stained with triphenyl tetrazolium chloride to demonstrate viability and highlight the area of ablation. Results were compared with 17 in vivo ablations performed in canine livers and 35 previously published ablations performed in porcine livers. ResultsAblation dimensions in the perfused model correlated well with corresponding in vivo ablations (R2 = 0.9098) with a 95% confidence interval of < 2.2 mm. Additionally, the validated perfused model showed that the IRE ablation zone grew logarithmically with increasing pulse numbers, showing small difference in ablation size over 200–600 pulses (3.2 mm ± 3.8 width and 5.2 mm ± 3.9 height). ConclusionsThe perfused organ model provides an alternative to animal trials for investigation of IRE treatments. It may have an important role in the future development of new devices, algorithms, and techniques for this therapy.

Ultrasound and Contrast-Enhanced Ultrasound for Evaluation of Irreversible Electroporation Ablation: In Vivo Proof of Concept in Normal Porcine Liver

The objective of this study was to describe the performance of ultrasound (US) and contrast-enhanced ultrasound (CEUS) within 2 h after irreversible electroporation (IRE) ablation of porcine liver. Six IRE ablations were performed on porcine liver in vivo; ultrasound assessments were performed within 2 h after IRE ablation. On US images, the ablation zone appeared as a hypo-echoic area within 10 min after the ablation, and then the echo of the ablation zone gradually increased. On CEUS images, the ablation zone appeared as a non-enhanced area within 10 min after ablation and then was gradually centripetally filled by microbubbles. A hyper-echoic rim on US images and a hyper-enhanced rim on CEUS images appeared in the periphery of the ablation zone 60 min after the ablation. Characteristic and dynamic ultrasound images of the IRE ablation zone were obtained within 2 h after IRE ablation of in vivo porcine liver.

Optimizing Irreversible Electroporation Ablation with a Bipolar Electrode

PurposeTo optimize single-insertion bipolar irreversible electroporation (IRE) by characterizing effects of electric parameters and controlling tissue electric properties in a porcine model. Materials and MethodsSingle-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. ResultsDelivering 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). ConclusionsBipolar 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.

Histopathological Outcomes after Irreversible Electroporation for Prostate Cancer: Results of an Ablate and Resect Study

Irreversible electroporation is a tissue ablation modality that uses high voltage electric energy to induce an increase in cell membrane permeability. This causes destabilization of the existing cellular transmembrane potential leading to cell death, due to the inability to maintain cellular homeostasis. This phase I-II study was designed to evaluate the histopathological outcomes of irreversible electroporation to prostate and surrounding tissue in radical prostatectomy specimens. Sixteen patients with prostate cancer underwent an irreversible electroporation ablation without curative intent, followed by radical prostatectomy scheduled 4 weeks later. For histopathological examination of the prostate, whole mounted tissue slices were examined by dedicated genitourinary pathologists. The borders of the ablation zone and residual tumor were outlined on the slides. The irreversible electroporation ablation zones were characterized as areas of fibrosis, necrosis and loss of epithelial tissue in terms of denudation in the glandular structures. The ablation zone was well demarcated, showing trenchant delineations between viable and nonviable tissue. The ablated tissue showed mild to moderate inflammation, with atrophic cells in 1 case. The area was surrounded by hemorrhage at the location of the electrodes. No skip lesions or viable tissue was seen in the ablation zone. Fibrinoid necrosis of the neurovascular bundle was observed in 13 patients and denudation of the urothelium of the prostatic urethra was seen in 9. Histopathological assessment of the prostate 4 weeks after irreversible electroporation ablation showed sharply demarcated fibrotic and necrotic tissue in the ablation zone. No viable tissue was observed in the irreversible electroporation ablation zone.

Irreversible Electroporation of Malignant Hepatic Tumors--Alterations in Venous Structures at Subacute Follow-Up and Evolution at Mid-Term Follow-Up.

PurposeTo evaluate risk factors associated with alterations in venous structures adjacent to an ablation zone after percutaneous irreversible electroporation (IRE) of hepatic malignancies at subacute follow-up (1 to 3 days after IRE) and to describe evolution of these alterations at mid-term follow-up.Materials and Methods43 patients (men/women, 32/11; mean age, 60.3 years) were identified in whom venous structures were located within a perimeter of 1.0 cm of the ablation zone at subacute follow-up after IRE of 84 hepatic lesions (primary/secondary hepatic tumors, 31/53). These vessels were retrospectively evaluated by means of pre-interventional and post-interventional contrast-enhanced magnetic resonance imaging or computed tomography or both. Any vascular changes in flow, patency, and diameter were documented. Correlations between vascular change (yes/no) and characteristics of patients, lesions, and ablation procedures were assessed by generalized linear models.Results191 venous structures were located within a perimeter of 1.0 cm of the ablation zone: 55 (29%) were encased by the ablation zone, 78 (41%) abutted the ablation zone, and 58 (30%) were located between 0.1 and 1.0 cm from the border of the ablation zone. At subacute follow-up, vascular changes were found in 19 of the 191 vessels (9.9%), with partial portal vein thrombosis in 2, complete portal vein thrombosis in 3, and lumen narrowing in 14 of 19. At follow-up of patients with subacute vessel alterations (mean, 5.7 months; range, 0 to 14 months) thrombosis had resolved in 2 of 5 cases; vessel narrowing had completely resolved in 8 of 14 cases, and partly resolved in 1 of 14 cases. The encasement of a vessel by ablation zone (OR = 6.36, p<0.001), ablation zone being adjacent to a portal vein (OR = 8.94, p<0.001), and the usage of more than 3 IRE probes (OR = 3.60, p = 0.035) were independently associated with post-IRE vessel alterations.ConclusionVenous structures located in close proximity to an IRE ablation zone remain largely unaffected by this procedure, and thrombosis is rare.

Assessment of Various Types of US Findings after Irreversible Electroporation in Porcine Liver: Comparison with Radiofrequency Ablation

PurposeTo assess various ultrasound (US) findings, including B-mode, shear-wave elastography (SWE), and contrast-enhanced US, in accurately assessing ablation margins after irreversible electroporation (IRE) based on radiologic–pathologic correlation, and to compare these findings between IRE and radiofrequency (RF) ablation. Materials and MethodsIRE (n = 9) and RF ablation (n = 3) were performed in vivo in three pig livers. Each ablation zone was imaged by each method immediately after the procedure and 90 minutes later. Ablation zones were evaluated based on gross pathologic and histopathologic findings in samples from animals euthanized 2 hours after the last ablation. The characteristics and dimensions of the histologic ablation zones were qualitatively and quantitatively compared against each US finding. ResultsIn B-mode US at 90 minutes after IRE, the ablation zones appeared as hyperechoic areas with a peripheral hyperechoic rim, showing excellent correlation (r2 = 0.905, P < .0001) with gross pathologic findings. SWE showed that tissue stiffness in the IRE ablation zones increased over time. Contrast-enhanced US depicted the IRE ablation zones as hypovascular areas in the portal phase, and showed the highest correlation (r2 = 0.923, P < .0001) with gross pathologic findings. The RF ablation zones were clearly visualized by B-mode US. SWE showed that tissue stiffness after RF ablation was higher than after IRE. Contrast-enhanced US depicted the RF ablation zones as avascular areas. ConclusionsIRE and RF ablation zones can be most accurately predicted by portal-phase contrast-enhanced US measurements obtained immediately after ablation.

Abstract No. 270 - Multimodality imaging to assess immediate response to irreversible electroporation in a rat liver tumor model

Purpose The purpose was to compare induced changes within US, CT, and MRI images shortly after irreversible electroporation (IRE) ablation of normal liver parenchyma and hepatic tumors. Materials and Methods All procedures were approved by IACUC. 48 rats were divided into 8 groups, 24 were implanted with N1-S1 tumors. US, CT, and MRI measurements were performed in both normal and tumor tissues pre/post-IRE. MRI was also performed in one group pre/post-IRE after hepatic vessel ligation. Pre/post-IRE US images were graded by 3 radiologists to determine echogenicity changes (0: no change; 1: slight change; 2: clear change; 3: dramatic change). Hounsfield units (HU) were measured based on CT and signal to noise ratio (SNR) measured within T2W MR images pre/post-IRE. Results The average grade was 2.0 for echogenicity change in ablated normal liver and 1.3 for ablated tumor. HU of ablated normal liver (62.53±2.24) was significantly different (p=0.0001) from unablated parenchyma (46.99±5.259); while small, HU difference between ablated tumor (42.11±2.11) and control tumor (45.14±2.64) did trend toward significance (p=0.0524). SNR in ablated normal liver was significantly increased post-IRE (PRE: 47.37±18.31, POST: 90.88±37.15, p=0.0227). SNR difference between tumors pre/post-IRE was not significant (PRE: 102.13±31.36, POST: 101.09±21.66, p=0.9401). No post-IRE signal changes were observed for rats that underwent portal vein and hepatic artery ligation prior to MRI-monitored IRE. IRE ablation zones were confirmed with HandE and micro-structural changes observed with transmission electron microscopy. Conclusion IRE induces rapid changes within US, CT, and MRI images. However, these imaging methods characterized IRE-induced signal changes more effectively in normal parenchyma than in tumors. MRI findings following hepatic ligation indicate that early signal changes are likely the result of local fluid accumulation in the treated zones. Future studies are necessary to develop superior imaging methods to better characterize electroporation-induced changes in tumors.

Irreversible Electroporation in Porcine Liver

The objective of this study was to define acute computed tomography (CT) characteristics of ablation zone created by irreversible electroporation (IRE) in porcine liver, with histopathologic correlation. Twenty-three IRE ablation zones were created in 4 Yorkshire pig livers percutaneously under image guidance. A prototype generator was used (Ethicon Endo-surgery, Cincinnati, Ohio). Variable spacing of paired electrodes between 1 and 2.0 cm was used. Contrast-enhanced multiphasic CT scans were obtained. Pigs were killed after 5 to 6 hours for gross pathology sectioning with routine and vital histological stains. Computed tomography images were analyzed using 3-dimensional software, and ablation zone size measured on CT was correlated with pathologically determined size. Nineteen of 19 ablation zones created with up to 1.5-cm spacing showed fusion between individual ablation zones generated by each electrode. Ablation zones were isodense precontrast and hypodense to liver postcontrast, with best delineation in the portal phase. Nine of these had nondistorted circumferential margins on both CT and gross pathology suitable for correlation, and among these, size measurements on CT were closely correlated with pathologically determined ablation zone size. Most importantly, on the delayed venous phase, there is internal enhancement within the ablation zone itself, except for small perielectrode zones that remained hypodense. On histopathology, IRE ablation zones showed preserved microvasculature with congestion of sinusoids, except for small perielectrode zones where coagulative changes were suggested. Portal phase contrast-enhanced CT scans correlate well with liver IRE ablation size and shape on histopathology.

Abstract No. 146: MRI and 3D finite element modeling for prediction of irreversible electroporation ablation zones: Feasibility studies in a rat liver tumor model

Abstract No. 146: MRI and 3D finite element modeling for prediction of irreversible electroporation ablation zones: Feasibility studies in a rat liver tumor model

Irreversible Electroporation in the Liver: Contrast-enhanced Inversion-Recovery MR Imaging Approaches to Differentiate Reversibly Electroporated Penumbra from Irreversibly Electroporated Ablation Zones

To evaluate the use of contrast material-enhanced magnetic resonance (MR) imaging with conventional T1-weighted gradient-recalled echo (GRE) and inversion-recovery (IR)-prepared GRE methods to quantitatively measure the size of irreversible electroporation (IRE) ablation zones in the liver in a rat model. All studies were approved by the institutional animal care and use committee and were performed in accordance with institutional guidelines. Seventeen adult male Sprague-Dawley rats were divided into four groups. Rats in groups 1-3 (n = 15 total) underwent IRE performed by using different IRE parameters after gadopentetate dimeglumine administration. Rats in group 4 (n = 2) underwent IRE ablation without prior gadopentetate dimeglumine injection to serve as control animals. MR imaging measurements (with conventional T1-weighted GRE and IR-prepared GRE methods) were performed 2 hours after IRE to predict the IRE ablation zones, which were correlated with pathology-confirmed necrosis areas 24 hours after IRE by using the Spearman correlation coefficient. Bland-Altman plots were also generated to investigate the agreement between MR imaging-measured ablation zones and reference standard histologic measurements of corresponding ablation zones. The necrotic areas measured on the pathology images were well correlated with the hyperintense regions measured on T1-weighted GRE images (r = 0.891, P < .001) and normal tissue-nulled IR images (r = 0.874, P < .001); pathology measurements were also well correlated with the smaller hyperintense regions measured on those IR images with inversion times specifically selected to null signal from the peripheral penumbra surrounding the ablation zone (r = 0.939, P < .001). Bland-Altman plots indicated that these penumbra-nulled IR images provided more accurate predictions of IRE ablation zones, with T1-weighted GRE measurements tending to overestimate ablation zone sizes. Contrast-enhanced MR imaging permits accurate depiction of ablated tissue zones after IRE procedures. IR-prepared contrast-enhanced MR imaging can be used to quantitatively measure IRE ablation zones in the liver. http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.10100645/-/DC1.

MR Imaging to Assess Immediate Response to Irreversible Electroporation for Targeted Ablation of Liver Tissues: Preclinical Feasibility Studies in a Rodent Model

To test the hypothesis that magnetic resonance (MR) imaging measurements can be used to immediately detect treated tissue regions after irreversible electroporation (IRE) ablation procedures in rodent liver tissues. All experiments received institutional animal care and use committee approval. In four rats for preliminary studies and 18 rats for formal assessment, MR imaging-compatible electrodes were inserted into the liver and MR imaging-monitored IRE procedures were performed at one of three electrode voltages (1000, 1500, or 2500 V), with T1- and T2-weighted images acquired before and immediately after application of the IRE pulses. MR imaging measurements were compared with both finite element modeling (FEM)-anticipated ablation zones and histologically confirmed ablation zones at necropsy. Intraclass and Spearman correlation coefficients were calculated for statistical comparisons. MR imaging measurements permitted immediate depiction of IRE ablation zones that were hypointense on T1-weighted images and hyperintense on T2-weighted images. MR imaging-based measurements demonstrated excellent consistency with FEM-anticipated ablation zones (r > 0.90 and P < .001 for both T1- and T2-weighted images). MR imaging measurements were also highly correlated with histologically confirmed ablation zone measurements (rho > 0.90 and P < .001 for both T1- and T2-weighted images). MR imaging permits immediate depiction of ablated tissue zones for monitoring of IRE ablation procedures. These measurements could potentially be used during treatment to elicit repeat application of IRE pulses or adjustments to electrode positions to ensure complete treatment of targeted lesions.

Advanced Hepatic Ablation Technique for Creating Complete Cell Death: Irreversible Electroporation

To evaluate the effectiveness of irreversible electroporation (IRE) in hepatic tissue ablation and the radiologic-pathologic correlation of IRE-induced cell death. On approval of the animal research committee, 16 Yorkshire pigs underwent ultrasonography (US)-guided IRE of normal liver. A total of 55 ablation zones were created, which were imaged with US, magnetic resonance (MR) imaging, and computed tomography (CT) and evaluated with immunohistochemical analysis, including hematoxylin-eosin (H-E), Von Kossa, and von Willibrand factor (vWF) staining and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. At gross section examination, the mean diameter of the ablation zones was 33.5 mm + or - 3.0 (standard deviation) and was achieved in 6.9 minutes (mean total procedure time per ablation), with a mean difference of 2.5 mm + or - 3.6 between US and gross section measurements (r = 0.804). No complications were seen in any of the 16 animals. IRE ablation zones were well characterized with US, CT, and MR imaging, and real-time monitoring was feasible with US. H-E, Von Kossa, and vWF staining showed complete cell death, with a sharply demarcated treatment area. Bile ducts and vessels were completely preserved. Areas of complete cell death were stained positive for apoptotic markers (TUNEL, BCL-2 oncoprotein), suggesting involvement of the apoptotic process in the pathophysiology of cell death caused by IRE. In an animal model, IRE proved to be a fast, safe, and potent ablative method, causing complete tissue death by means of apoptosis. Cell death is seen with full preservation of periablative zone structures, including blood vessels, bile ducts, and neighboring nonablated tissues.