Grace M. Nijm

Irreversible Electroporation Therapy in the Liver: Longitudinal Efficacy Studies in a Rat Model of Hepatocellular Carcinoma

Irreversible electroporation (IRE) is an innovative local-regional therapy that involves delivery of intense electrical pulses to tissue to induce nanoscale cell membrane defects for tissue ablation. The purpose of this study was to investigate the feasibility of using IRE as a liver-directed ablation technique for the treatment of hepatocellular carcinoma (HCC). In the N1-S1 rodent model, hepatomas were grown in 30 Sprague-Dawley rats that were divided into treatment and control groups. For treatment groups, IRE electrodes were inserted and eight 100-mus 2,500-V pulses were applied to ablate the targeted tumor tissues. For both groups, magnetic resonance imaging scans were performed at baseline and 15-day follow-up intervals to determine tumor sizes (one-dimensional maximum diameter, D(max); estimated two-dimensional cross-sectional area, C(max)) as a tactic to assess longitudinal outcomes. Additional groups of treated animals were sacrificed at 1-, 3-, and 7-day intervals posttherapy for pathology assessment of treatment response. Magnetic resonance images showed significant tumor size reductions within 15 days posttherapy (32 +/- 31% D(max) and 52 +/- 39% C(max) decreases compared with 110 +/- 35% D(max) and 286 +/- 125% C(max) increases for untreated tumors). Pathology correlation studies documented progression from poorly differentiated viable HCC tissues before treatment to extensive tumor necrosis and full regression in 9 of 10 treated rats 7 to 15 days after treatment. Our findings suggest that IRE can be an effective strategy for targeted ablation of liver tumors, prompting its further evaluation for HCC therapy.

Atrial fibrillation and waveform characterization

The surface electrocardiogram (ECG) is a convenient, cost effective, and noninvasive tool for the study of atrial fibrillation (AF). It can be used to examine the hypothesized mechanisms of AF as well as to quantify and assess the effect of electrophysiological remodeling and the effectiveness of treatment on different types of AF. Time domain methods can be used to characterize the signal in the surface ECG. The authors described observations that can be obtained directly from the signal, such as the general characteristics of AF in the surface ECG and the ventricular response to AF. A discussion on commonly used methods to characterize atrial activity is also presented. These methods include cancellation techniques, vector analysis, and autocorrelation. Observations show that combining time and frequency domain methods provides a more thorough understanding of the characteristics of the atrial activity in the surface ECG. Whether the study of atrial activity in the surface ECG can be used to distinctively distinguish between different mechanisms of AF is not yet known, but further investigation can improve our understanding of these mechanisms and help with the management of this common arrhythmia

MR imaging to assess immediate response to irreversible electroporation for targeted ablation of liver tissues: preclinical feasibility studies in a rodent model.

PURPOSE 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. MATERIALS AND METHODS 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. RESULTS 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). CONCLUSION 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.

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

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.

Extraction of the magnetohydrodynamic blood flow potential from the surface electrocardiogram in magnetic resonance imaging

The magnetohydrodynamic effect generates voltages related to blood flow, which are superimposed on the electrocardiogram (ECG) used for gating during cardiac magnetic resonance imaging (MRI). A method is presented for extracting the magnetohydrodynamic signal from the ECG. The extracted magnetohydrodynamic blood flow potential may be physiologically meaningful due to its relationship to blood flow. Removal of the magnetohydrodynamic voltages from the ECG can potentially lead to improved gating and diagnostically useful ECGs.

Comparison of self-gated cine MRI retrospective cardiac synchronization algorithms

To determine whether improved self‐gating (SG) algorithms can provide superior synchronization accuracy for retrospectively gated cine MRI.

Comparison of signal peak detection algorithms for self-gated cardiac cine MRI

Self-gating (SG) is a cardiac MRI technique to synchronize data acquisition to the cardiac cycle based upon MR signal triggers as opposed to conventional ECG triggers. Fourteen healthy subjects underwent cardiac MRI scans in four different orientations: two chamber, three chamber, four chamber, and short axis. SG trigger times were computed using two methods, first difference and template matching, and ECG trigger times were also recorded for comparison. The root-mean-square (RMS) error was used to evaluate performance, defined as the variability relative to the mean difference between SG trigger times and ECG trigger times. The mean RMS error was lower for template matching than first difference approach for all scan orientations; the improvement in RMS error was statistically significant for all orientations except short axis. In conclusion, compared to the first difference approach, template matching improved the accuracy of trigger detection for two, three, and four chamber SG cardiac MRI scans.

A 3D model of magnetohydrodynamic voltages: Comparison with voltages observed on the surface ECG during cardiac MRI

The magnetohydrodynamic (MHD) effect generates voltages which distort the ECG obtained during cardiac MRI. Consequently, MHD voltages result in triggering problems for MR image acquisition. In addition, since the MHD effect is related to blood flow, analysis of it not only as interference, but also as a signal may provide useful blood flow information. Comsol Multiphysics modeling software was used to compute and model the MHD voltages in 3D. These voltages were compared with MHD voltages obtained experimentally from the subtraction of ECGs taken outside the MRI magnet from ECGs taken inside the magnet. The maximum MHD voltage magnitude for the experimental data was 0.2 mV and was 3.04 mV for the modeled data when calculated on the surface of the uniform volume conductor. By modeling MHD voltages in 3D, we can learn about their effect on the ECG during cardiac MRI.

Inhomogeneous human torso model of magnetohydrodynamic blood flow potentials generated in the MR environment

Magnetohydrodynamic (MHD) voltages resulting from blood flow in a magnetic field contribute to the ECG acquired in the MR environment. These MHD voltages may result in triggering problems for MR image acquisition, since the ECG is typically used for gating. Comsol Multiphysics software was used to model blood flow through the aorta in an inhomogeneous 3D human torso model in a 3.0 Tesla static magnetic field. These voltages were compared with experimentally acquired MHD voltages as well as MHD voltages computed using a simplified torso model. The maximum MHD voltage magnitude was 0.2 mV for the experimental data, 3.04 mV for the simplified model and 0.285 mV for the inhomogeneous torso model. Modeling MHD voltages using an inhomogeneous torso model may aid in optimizing ECG electrode placement for cardiac MRI. In addition, analysis of MHD not only as interference, but also as a physiological signal, may provide blood flow information.

Estimation of T-wave alternans from multi-lead ECG signals using a modified moving average method

T-wave alternans (TWA) manifests on the surface ECG as a pattern of alternating amplitude T-waves, typically in the microvolt range. Consequently, TWA is usually invisible at standard ECG display scales and must be detected using signal processing methods. There is a predictive relationship between TWA and sudden cardiac death, so proper detection and estimation may contribute to clinical decision-making. The objective of the 2008 Physionet/Computers in Cardiology Challenge was to estimate the magnitude of TWA in a dataset of 100 multi-lead ECGs. We used a modified moving average method (MMA) to detect and estimate TWA. We found that the TWA magnitude ranged from to 1.3 to 256.9 muV (43.9 plusmn 49.7 muV). The Kendall rank correlation coefficient obtained for the challenge was 0.451. In conclusion, the MMA method can be used for detection and estimation of TWA, though additional work could further improve the method.