Irreversible Electroporation in the Liver: Contrast-enhanced Inversion-Recovery MR Imaging Approaches to Differentiate Reversibly Electroporated Penumbra from Irreversibly Electroporated Ablation Zon (2024)

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Radiology. 2011 Feb; 258(2): 461–468.

Published online 2011 Feb. doi:10.1148/radiol.10100645

PMCID: PMC3029885

PMID: 21131581

Yang Guo, MD, Yue Zhang, BS, Grace M. Nijm, PhD, Alan V. Sahakian, PhD, Guang-Yu Yang, MD, PhD, Reed A. Omary, MD, MS, and Andrew C. Larson, PhD

Author information Copyright and License information PMC Disclaimer

Associated Data

Supplementary Materials

Contrast-enhanced MR imaging permits accurate depiction of ablated tissue zones in the liver after irreversible electroporation ablation procedures.

Abstract

Purpose:

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.

Materials and Methods:

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.

Results:

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.

Conclusion:

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.

Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.10100645/-/DC1

Introduction

Minimally invasive locoregional ablation therapies have been widely advocated for the treatment of a variety of solid tumors (eg, breast, lung, liver, and prostate tumors) (1–4). One such strategy, irreversible electroporation (IRE), has been introduced as a new modality for locoregional tissue ablation (5).

Electroporation involves targeted delivery of electrical pulses to make the cell membrane permeable, either temporarily (reversible electroporation) or permanently (with IRE). Whether the effect is temporary or permanent is determined by the electric field magnitude, pulse duration, and number of pulses applied (6). IRE causes tissue necrosis through the formation of nanometer-scale defects in the cell membrane (7). Preclinical studies in human hepatocellular carcinoma (HepG2) (8) and cancerous mammary epithelial cells (MDA-MB-231 cells) (9), normal liver (10) and prostate tissues (11,12), and cutaneous tumor and liver hepatoma models (13,14) have each demonstrated the feasibility of using IRE as a new tissue ablation option with negligible thermal side effects (15). However, during these IRE ablation procedures, the application of strong pulses to the IRE electrodes actually produces both a central ablation zone (wherein electric field levels exceed a lethal threshold, irreversibly electroporating tissues within this zone) and a surrounding region that experiences sublethal electric field potentials. The tissues in the latter region, located immediately adjacent to the ablation zone, will be reversibly electroporated but remain viable. This “reversibly electroporated penumbra” should not be considered part of the treated tissue volume. To accurately quantify the size of the IRE ablation zones, follow-up imaging methods should ideally permit differentiation of the central treated tissue zone from the reversibly electroporated penumbra. IRE is a promising new ablation modality; however, similar to prior ablation methods, accurate follow-up imaging approaches will remain critical for properly evaluating treatment outcomes (16).

Magnetic resonance (MR) imaging methods may be ideal for the assessment of IRE response in liver tissues. MR imaging is generally considered to be a more accurate imaging method for the detection of liver tumors of both primary and metastatic origin, particularly smaller lesions (17–19), and MR imaging guidance methods have already been widely advocated for intraprocedural monitoring (20–22) and follow-up imaging after liver tumor ablation (23). T1-weighted contrast material–enhanced MR imaging methods can be particularly effective for differentiating treated from untreated tissue regions after ablation therapies given that contrast agent pharmaco*kinetics are greatly altered within the targeted treatment zones (24,25). Contrast-enhanced MR imaging methods have been used to assess the efficacy of electrotransfer procedures during gene therapy (26,27). These previous studies demonstrated that a small-molecular-weight contrast agent (eg, gadopentetate dimeglumine) injected into muscle tissue prior to electric field application can be trapped within reversibly permeabilized cells, thereby serving as a surrogate imaging marker of gene delivery. Similarly, we would anticipate substantially altered contrast agent pharmaco*kinetics within treated and untreated tissues during IRE procedures; contrast-enhanced MR imaging should permit accurate quantification of IRE ablated tissue volumes.

The purpose of our study was to evaluate the use of contrast-enhanced MR imaging with conventional T1-weighted gradient-recalled echo (GRE) and inversion-recovery (IR)-prepared GRE methods to quantitatively measure the size of IRE ablation zones in the liver in a rat model.

Materials and Methods

Animal Model

All studies were approved by the institutional animal care and use committee of Northwestern University and were performed in accordance with institutional guidelines. Seventeen adult male Sprague-Dawley rats (Charles River Laboratories, Wilmington, Mass) initially weighing 301–325 g were used for these experiments.

Experimental Overview

A total of 17 adult male Sprague-Dawley rats were divided into four separate treatment groups. The first three groups received an intramuscular hind limb injection of 8 uL gadopentetate dimeglumine (Magnevist; Berlex, Montville, NJ) per gram of body weight. This was immediately followed by IRE performed with parameters that varied between the three groups. Group 1 (with three rats and two separate ablation regions per rat, for a total of six regions) underwent IRE with 1000 V and 10-mm electrode spacing, group 2 (with six rats and one ablation region per rat, for a total of six regions) underwent IRE with 500 V and 5-mm electrode spacing, and group 3 (with six rats and one ablation region per rat, for a total of six regions) underwent IRE with 1000 V and 5-mm electrode spacing. The final group, group 4 (with two rats and one ablation region per rat, for a total of two regions), was a control group treated with IRE performed with 1000 V and 5-mm electrode spacing without gadopentetate dimeglumine injection. IRE procedures were performed in a small-animal procedure room adjacent to the MR imaging facility. MR imaging was performed 2 hours after treatment, and animals were sacrificed 24 hours after treatment for histopathologic analysis. Figure 1 shows a summary description of the experimental overview.

IRE Procedures

IRE apparatus and dosing plan.—A BTX Electroporator (ECM830; Harvard Apparatus, Holliston, Mass) function generator and a parallel two-electrode array were used for all rat IRE procedures. The electrode array (each electrode was 35 mm long, with a diameter of 0.4 mm) was inserted through a plastic block to maintain 5- or 10-mm spacing between the two parallel needles. Before the in vivo IRE procedures, we used a commercial finite-element modeling software package (Multi-Physics, version 3.3; Comsol, Burlington, Mass) to simulate the anticipated electroporation pattern on the basis of the selected IRE parameters (Fig 2) (28). On the basis of results of prior electroporation studies in hepatic tissues (29), we assumed that the thresholds for reversible and IRE field potentials were 362 V/cm and 637 V/cm, respectively. Our finite-element simulation closely followed that described in a previous study with IRE (5) in solving the Laplace equation to calculate induced electrical field potentials based on anticipated tissue and electrode conductivities.

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Figure 2a:

(a–d) Images in experimental groups 1 (top), 2 (middle), and 3 (bottom). (a) Finite-element modeling software simulation results show the anticipated IRE zone (with the white zone encompassed within the penumbra) and the reversible electroporation penumbra (colored zones represent the electric field between 362 V/cm [blue] and 637 V/cm [red]). The length of the arrows represents the electrode spacing of 10 mm. (b) T1-weighted GRE MR images obtained 2 hours after IRE show uniformly hyperintense lesions. (c) IR fast low-angle shot (FLASH) MR images adjusted to null signal intensity (SI) from within the anticipated region of reversible electroporation (with hyperintense central ablation regions) were obtained 2 hours after IRE. (d) Histologic slices show the corresponding IRE ablation zones. (Hematoxylin-eosin stain.)

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Figure 2b:

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Figure 2c:

IRE procedures.—Before the IRE procedures, rats were anesthetized with a hind limb injection of ketamine (75–100 mg/kg, Ketaset; Fort Dodge Animal Health, Fort Dodge, Iowa) and xylazine (2–6 mg/kg, Isothesia; Abbott Laboratories, North Chicago, Ill). After anesthesia and immediately prior to the IRE procedure, rats in groups 1–3 were given an intramuscular injection of 8 μL/g gadopentetate dimeglumine (Magnevist) solution. Next, each rat was fixed in a supine position within a restraining apparatus. A mini-laparotomy incision was performed to expose the left medial hepatic lobe. This lobe was gently pulled out with two cotton applicators and placed on sterile gauze. The parallel two-electrode array was inserted into this lobe (avoiding major vessels and bile ducts) to a depth of 4–5 mm (Y.G. and Y.Z., both with 2 years of experience). The following IRE parameters were identical for groups 1–4: total number of pulses, eight; each pulse length, 100 μsec; and interval between two pulses, 100 msec. The parameters that were varied among the groups (to produce different IRE ablation zone sizes) included the applied electrode voltage and the spacing between the two electrodes (1000 V and 10-mm electrode spacing for group 1, 500 V and 5-mm spacing for group 2, and 1000 V and 5-mm spacing for groups 3 and 4). After the IRE procedure, the abdominal incisions were closed with a two-layer technique; this was followed by topical application of antibiotic ointment and subcutaneous injection of meloxicam (1–2 mg/kg, Metacam; Boehringer Ingelheim Vetmedica, St Joseph, Mo).

MR Imaging Technique

MR imaging was performed by using a 3.0-T clinical MR imaging unit (Magnetom Trio; Siemens Medical Solutions, Erlangen, Germany). Rats were imaged in the supine position with a custom-built rodent receiver coil (Chenguang Med Tech, Shanghai, China). The MR imaging examination was performed 2 hours after the IRE procedure (preliminary experiments allowed the optimization of timing for gadopentetate dimeglumine accumulation in hom*ogeneous hyperintense lesions on conventional T1-weighted GRE images).

After the acquisition of initial localization images, contrast-enhanced images were obtained by using a T1-weighted GRE sequence and a segmented IR turbo FLASH sequence at identical coronal section positions that provided complete coverage of the electroporation zone. The parameters for the T1-weighted GRE sequence were as follows: repetition time/echo time msec, 200/2.7; flip angle, 90°; section thickness, 2 mm; number of signals acquired, three; field of view, 70 × 150 mm²; matrix, 90 × 192 (0.8 × 0.8 × 2 mm); and bandwidth, 500 Hz/pixel. The parameters of the IR turbo FLASH sequence were as follows: 200/2.7; flip angle, 20°; section thickness, 2 mm; number of signals acquired, three; field of view, 70 × 150 mm²; matrix, 90 × 192 (0.8 × 0.8 × 2 mm); and bandwidth, 500 Hz/pixel. Images were acquired at multiple inversion times (100, 120, 150, 180, 200, and 250 msec) to separately null SI from regions that included either the anticipated IRE zone, the reversibly electroporated penumbra (producing images corresponding to the finite-element model simulation electric field patterns), or normal unaffected liver parenchyma.

Histologic Evaluation

Each rat was euthanized by means of intravenous injection of pentobarbital sodium and phenytoin sodium solution (Euthasol; Delmarva Laboratories, Midlothian, Va) at a dose of 150 mg/kg and underwent bilateral thoracotomy 24 hours after the IRE procedure. Two or three tissue slices sampled along an orientation perpendicular to the IRE electrodes (and including the ablation region) were removed and were fixed in 10% formaldehyde solution; these tissue slices were then embedded in paraffin for hematoxylin-eosin staining. Histologic slides were digitized with optical magnification (×100) by using a multichannel automated imaging system (TissueGnostics, Vienna, Austria). ImageJ software (http://rsb.info.nih.gov/ij/) was used to draw regions of interest (ROIs) that encompassed all areas of coagulative necrosis within the exported pathology slides (regions were drawn on the basis of observed changes in cell morphology within regions of necrosis) on all the slides sectioned to average the IRE ablated zone (Y.G. and another physician with more than 20 years of experience). Y.G. performed the measurements twice for calculation of interobserver agreement.

Image Analysis

Image postprocessing was performed offline by using software (Matlab; MathWorks, Natick, Mass). On T1-weighted GRE images, ROIs were manually drawn to encompass the enhancing hyperintense regions (in groups 1–3). For IR image series, we first selected images for which the inversion time had been adjusted to null SI from the normal unaffected liver parenchyma; then, similar to our approach with the T1-weighted images, these images were used to draw ROIs that encompassed hyperintense regions that were anticipated to be the IRE zone. Next, we selected images with IR times that nulled SI within the peripheral zones anticipated to be representative of the reversibly electroporated penumbra (essentially using those images in a way that was qualitatively concordant with our corresponding finite-element model simulation for the specific IRE protocol); within these images, ROIs were manually drawn to include only those hyperintense zones encompassed within the nulled penumbra. MR imaging–based IRE ablation zone measurements (in square millimeters) from T1-weighted GRE images and the selected IR-FLASH images were compared with the corresponding histology-based ablation zone measurements (in square millimeters) (Y.G. [who performed the measurements twice] and the other physician).

Statistical Analysis

All statistical analyses were performed by using a statistical software package (SPSS, version 17; SPSS, Chicago, Ill). MR imaging–measured IRE ablation zones (measured on T1-weighted images, IR-FLASH images adjusted to null the SI of the reversible penumbra, and IR images adjusted to null the SI of the normal unaffected liver tissue) were compared by using the Wilcoxon test. The relationship between MR imaging–measured IRE ablation zones (measured on T1-weighted images and on both sets of the IR-FLASH images) and the ablated necrosis areas measured on histologic slides was assessed by using the Spearman correlation coefficient. Interobserver variance (between Y.G and the other physician) and intraobserver variance (Y.G.) in measuring the IRE ablation zones on both MR images and histologic slides were assessed with intraclass correlation coefficients. Bland-Altman plots were generated to further investigate the agreement between MR imaging–measured IRE ablation zones and the reference standard histologic measurements of corresponding ablation zones (30). P < .05 was considered to indicate a significant difference.

Results

MR Imaging

Representative T1-weighted GRE images and IR-prepared images (with IR adjusted to null the SI of the reversibly electroporated penumbra) in groups 1–3 are shown in Figure 2. These lesions were consistently uniformly hyperintense on both T1-weighted GRE images and the IR images selected to null SI from normal unaffected liver parenchyma. However, there were consistently two different zones of SI on the IR images adjusted to null the penumbra: the hyperintense central lesion and the peripheral hypointense nulled signal zone. We found no significant difference between measurements on the T1-weighted GRE images and those on the normal-tissue-nulled IR images (P = .727), but both sets of measurements were significantly different from the measurements on the original IR images (with inversion time selected to null the peripheral penumbra) (P < .001).

IR images with inversion times adjusted to null the SI of the IRE ablation zone (TI_ire), those with inversion times adjusted to null the SI of the reversible penumbra (TI_re), and those with inversion times adjusted to null the SI of the normal liver parenchyma (TI_nor) are shown in Figure E1 (online). The relationship between these tissue-specific inversion times for each study was consistently TI_ire > TI_re > TI_nor. This relationship was clearly depicted by the representative IR curves for separate ROIs drawn within the normal liver parenchyma, the reversibly electroporated penumbra, and IRE zones (Figure 3). No penumbra was observed in the control animals that did not undergo contrast agent infusion.

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Figure 3:

IR curves show the different T1 relaxation characteristics for (red) normal liver parenchyma, (black) reversibly electroporated penumbra, and (blue) IRE zones after contrast agent injection and IRE. Figure E1 (online) shows corresponding IR images obtained at inversion times that were selected to null signal from different tissue regions.

Histologic Findings

Histologic slides prepared from the corresponding hematoxylin-eosin–stained liver specimens showed an ablation region of coagulative necrosis and a well-delineated margin between treated and untreated liver tissues 1 day after IRE (Fig 2d). The necrosis areas (in square millimeters) measured on the ×100 magnification histologic images were well correlated with the hyperintense regions measured on the T1-weighted GRE images (r = 0.891, P < .001), the normal-tissue-nulled IR-FLASH images (r = 0.874, P < .001), and the IR images adjusted to null the SI of the penumbra (r = 0.939, P < .001) for groups 1–3 (Fig 4a). Intraclass correlation coefficients, which ranged from 0.948 to 0.991, indicated interobserver and intraobserver reproducibility between MR imaging and histologic ablation zone measurements (Table). Bland-Altman plots indicated a bias for the conventional contrast-enhanced T1-weighted GRE method tending to overestimate the IRE ablation zone compared with histologic measurements (Fig 4b). The larger lesion size predicted with the T1-weighted GRE approach as compared with that predicted with the penumbra-nulled IR approach is shown in Figure 4a. The mean difference was 0.711 mm² (95% confidence interval [CI]: −1.542, 2.963 mm²) for penumbra-nulled IR-FLASH measurements; this was much smaller than the mean difference for T1-weighted GRE measurements (mean difference, 10.387 mm² [95% CI: −6.403, 14.391 mm²]). The limits of agreement (−8.846 to 10.267 mm²) for penumbra-nulled IR-FLASH were smaller than those for T1-weighted GRE (−6.517 to 27.291 mm²). MR imaging–measured IRE ablation zones were more accurately measured by using the IR images adjusted to null the SI of the reversible penumbra (Fig 4c). Bland-Altman plots for corresponding normal-tissue-nulled IR measurements were consistent with T1-weighted GRE measurements in tending to overestimate the IRE ablation zones compared with histologic measurements (Figure E3 [online]).

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Figure 2d:

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Figure 4a:

(a–c) Graphs show results of comparison between IRE ablation zones on T1-weighted GRE MR images and IR-FLASH MR images (with the IR time adjusted to null the reversibly electroporated penumbra) and areas of necrosis on hematoxylin-eosin (H&E)–stained slides. (a) Both T1-weighted GRE– and IR-FLASH–measured IRE zones were well correlated with histologically measured tissue necrosis areas (r = 0.891, P < .001 and r = 0.939, P < .001, respectively). Bland-Altman plots were used to compare (b) T1-weighted (T1-w) GRE–measured IRE zones with the area of tissue necrosis measured on histologic slides and (c) IR-FLASH–measured IRE zones with these same histologically confirmed areas of tissue necrosis. See Figure E2 (online) for supporting images.

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Figure 4b:

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Figure 4c:

Summary Description of Experimental Results

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Note.—Data are intraclass correlation coefficients; P < .001 for all.

Discussion

Our study results demonstrated that contrast-enhanced MR imaging measurements of IRE ablation zones are well correlated with corresponding necrosis zones measured at histologic examination. IR-prepared FLASH images were able to better delineate the central IRE ablation zone when IR times specifically selected to null SI within a peripheral zone surrounding the ablation lesion were used. While both T1-weighted GRE and IR-FLASH measurements were each well correlated with necrosis areas measured at histologic examination, penumbra-nulled IR-prepared images provided more accurate predictions of the IRE ablation zone; T1-weighted GRE measurements tended to overestimate the absolute size of the ablation zones.

We observed that the IR-prepared images were able to differentiate two separate zones: a central zone of IRE and a peripheral zone assumed to be representative of the reversibly electroporated penumbra. Using these nulled peripheral zones as margins for drawing ROIs during our MR imaging–based measurements, we were able to perform more accurate quantification of the IRE ablation zones. T1-weighted GRE images were not able to permit us to differentiate these two zones. For the IR-prepared method, optimal inversion time selection was important to permit visualization of the treated tissue margin. In our study, we observed that the order of inversion times adjusted to null the SI from the IRE ablation zone (TI_ire), reversible penumbra (TI_re), and normal liver parenchyma (TI_nor), was consistently TI_nor > TI_re > TI_ire. The reason for these different null inversion times is likely the different contrast agent concentration levels within these tissues after the 2-hour interval between the ablation procedure and the subsequent MR imaging examination (leading to different T1 recovery rates within these tissues). While further studies are clearly necessary to elucidate the exact mechanisms for these differences in contrast agent concentrations, one can reasonably speculate that (a) initial contrast agent accumulation was much greater within IRE zones because of the formation of nanometer-scale pores in tissue cell membranes that allowed internalization of the agent (essentially producing an artificially larger contrast agent accumulation volume than simply the extracellular space) and (b) unlike in normal liver parenchyma with more rapid contrast agent washout kinetics, in reversibly electroporated tissues, contrast agent is expected to be retained with temporary intracellular uptake similar to that demonstrated in prior electro-transfer studies (26). Within electroporated regions, increased contrast agent uptake may also result from acute cell injury leading to hyperemia.

On the T1-weighted GRE images, we consistently observed hyperintense lesions in all IRE-treated animals in groups 1–3. These MR imaging–based measurements of the IRE ablation zones were well correlated with the histologic measurements, but Bland-Altman plots indicated a bias for these T1-weighted measurements that tended to overestimate ablation zone sizes. These T1-weighted measurements likely included both irreversible and reversibly electroporated tissue regions given the lack of sufficient image contrast to differentiate these two zones. These results suggest that increased image contrast may be necessary to readily discriminate between these zones. IR-prepared methods provided the requisite contrast with the inversion time optimized to null the peripheral region, which presumably represents penumbra (thus differentiating these two zones). This approach bears much similarity to the use of IR-prepared MR imaging methods to optimize T1-weighted image contrast during delayed hyperenhancement imaging of myocardial infarction (31,32). MR imaging guidance methods have already been widely advocated for intraprocedural monitoring of percutaneous tissue ablation procedures. For hyperthermic ablation approaches, rapid T2-weighted images and T1-weighted short inversion time inversion-recovery (STIR) methods have been used to monitor thermal lesion formation, typically visualized as hypointensity on T2-weighted images or STIR images and nonenhancement on T1-weighted contrast-enhanced images (33,34). Quantitative intraprocedural MR thermometry measurements can also serve to optimize these thermal ablation techniques. However, our study was the first, to our knowledge, to use a contrast-enhanced IR approach to differentiate the reversible and IRE zones in liver ablation treatments.

Our study had limitations. First, a small-rodent model was used for these IRE procedures; owing to the animal’s relatively small liver volume, this limited the size of the IRE ablation zone that could be completely contained within the liver (while continuing to allow a clear depiction of the ablation zone margin on both in vivo images and histologic slides). A second limitation of this study was that no reference standard evidence was provided to definitively demonstrate intracellular and/or extracellular accumulation of gadopentetate dimeglumine. Inductively coupled plasma mass spectroscopy methods will be necessary to validate the presence of gadolinium-based contrast agent within these tissues, and x-ray fluorescence methods would be necessary to validate the presence of gadolinium inside the cells within representative penumbra tissues (35). Furthermore, studies using scanning electron microscopy would be valuable for rigorously differentiating tissue regions that were reversibly electroporated from those that were irreversibly electroporated; our study provided no reference standard to definitively validate that the nulled penumbra within IR-prepared images was due to the presence of reversibly electroporated tissues. However, our indirect evidence is suggestive of the validity of this assumption; these nulled penumbra zones were remarkably well correlated with the peripheral regions predicted to experience electric field levels necessary for reversible electroporation (on the basis of finite-element modeling simulations; more importantly, the results of our in vivo studies that used these nulled penumbrae as margins for IRE ablation zone measurements produced more accurate results than corresponding T1-weighted MR imaging measurements that included these peripheral zones as part of the ablation lesion). The regions surrounding lethal IRE treatment zones will inherently contain a gradient of electric field potentials, starting at the lethal electric field threshold at the immediate border then reducing with increasing distance from the electrode, thus inherently passing through a range of potentials sufficient for reversible electroporation. An additional consideration is that we chose an intramuscular route for gadopentetate dimeglumine administration to simplify procedures. Intravenous (tail vein) or intraperitoneal routes should also be effective; however, given that intravenous injection is most commonly used for the administration of contrast agents in clinical settings, it will be important to validate the continued efficacy of these methods with the intravenous injection route prior to translation. Finally, for these initial preclinical feasibility studies, imaging was performed at only a single time point after therapy. Future studies at delayed intervals could also be quite valuable. While this 2-hour posttherapy time interval suggests that the proposed method could be quite valuable for relatively early detection of therapy response, further translational studies in liver tumor models and in patients are needed to fully characterize contrast agent pharmaco*kinetics in the setting of IRE therapies.

Practical application: We have demonstrated that IR-prepared contrast-enhanced MR imaging can be used to quantitatively measure IRE ablation zones in the liver. These noninvasive follow-up imaging measurements could be used to rapidly assess patient-specific treatment responses to prompt appropriate adjustments to therapy as needed.

Advance in Knowledge

Contrast-enhanced MR imaging with inversion-recovery preparation can be used to accurately depict ablation regions after targeted irreversible electroporation (IRE) procedures in liver tissues.

Implication for Patient Care

Accurate depiction of treated tissue regions early after IRE procedures may permit rapid adjustments to a patient’s therapeutic regimen as needed to improve clinical outcomes.

Disclosures of Potential Conflicts of Interest: Y.G. No potential conflicts of interest to disclose. Y.Z. No potential conflicts of interest to disclose. G.M.N. No potential conflicts of interest to disclose. A.V.S. No potential conflicts of interest to disclose. G.Y.Y. No potential conflicts of interest to disclose. R.A.O. No potential conflicts of interest to disclose. A.C.L. No potential conflicts of interest to disclose.

Supplementary Material

Supplemental Figures:

Click here to view.

Acknowledgments

We thank Zhuoli Zhang, MD, PhD, for helping us with all of the MR and histologic image measurements.

Received April 9, 2010; revision requested June 8; revision received July 28; accepted September 1; final version accepted September 8.

Funding: This research was supported by the National Cancer Institute and the National Center for Research Resources, National Institutes of Health and National Institutes of Health Roadmap for Medical Research (grants CA134719; and UL1 RR025741).

Abbreviations:

FLASH: fast low-angle shot
GRE: gradient-recalled echo
IR: inversion recovery
IRE: irreversible electroporation
ROI: region of interest
SI: signal intensity

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