Rachel Klein

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.

Electroporation-mediated transcatheter arterial chemoembolization in the rabbit VX2 liver tumor model.

Rationale and Objectives:Electropermeabilization involves the application of electrical pulses to increase cell membrane permeability. The purpose of our study was to demonstrate the potential to use electroporation-mediated transcatheter arterial chemoembolization (E-TACE) approaches to increase liver tumor drug uptake while using magnetic resonance imaging (MRI) for intraprocedural optimization of these procedures. Methods:Fourteen VX2 tumors were grown in the left hepatic lobes of 8 rabbits. Two tumors were grown in each of 6 rabbits (1 tumor serving as E-TACE-treated tumor and the other as nonelectroporated control), and solitary larger tumors were grown in 2 rabbits (half of the tumor treated with E-TACE, remaining half serving as control). Each rabbit was selectively catheterized under digital subtraction angiography guidance. Baseline MRI was performed to generate tumor contrast enhancement curves following catheter-directed infusion of gadopentetate dimeglumine to estimate the proper time delay between subsequent bolus infusion of cisplatin and application of electrical pulses (electrodes were used to deliver 8, 100-&mgr;s, 1300-V pulses at the selected delay interval postinfusion). Three hours after E-TACE, rabbits were euthanized, and tumors were sectioned for inductively coupled plasma mass spectroscopy measurements of platinum concentration (serving as reference standard of cisplatin uptake levels). Results:Inductively coupled plasma mass spectroscopy results demonstrated significantly increased cisplatin uptake in E-TACE-treated tumor tissues, increases of 6.0 ± 3.3-fold compared with transcatheter infusion alone (P = 0.017). Conclusions:Our findings suggest that our E-TACE approach may significantly increase liver tumor drug uptake after targeted transcatheter infusion. MRI measurements permitted intraprocedural guidance during these catheter-directed E-TACE procedures.

Artifact‐reduced two‐dimensional cine steady state free precession for myocardial blood‐ oxygen‐level‐dependent imaging

To minimize image artifacts in long TR cardiac phase‐resolved steady state free precession (SSFP) based blood‐oxygen‐level‐dependent (BOLD) imaging.

Gas challenge-blood oxygen level-dependent (GC-BOLD) MRI in the rat Novikoff hepatoma model.

PURPOSE The purpose of the study was to investigate the relationship between gas challenge-blood oxygen level-dependent (GC-BOLD) response angiogenesis and tumor size in rat Novikoff hepatoma model. MATERIALS AND METHODS Twenty adult male Sprague-Dawley rats (weighting 301-325 g) were used for our Animal Care and Use Committee-approved experiments. N1-S1 Novikoff hepatomas were grown in 14 rats with sizes ranging from 0.42 to 2.81 cm. All experiments were performed at 3.0 T using a custom-built rodent receiver coil. A multiple gradient-echo sequence was used for R2* measurements, first during room air (78% N(2)/20% O(2)) breathing and then after 10 min of carbogen (95% O(2)/5% CO(2)) breathing. After image acquisition, rats were euthanized, and the tumors were harvested for histological evaluation. RESULTS The R2* change between air and carbogen breathing for small hepatomas was positive; R2* changes changed to negative values for larger hepatomas. We found a significant positive correlation between tumor R2* change and tumor microvessel density (MVD) (r=0.798, P=.001) and a significant inverse correlation between tumor R2* change and tumor size (r=-0.840, P<.0001). CONCLUSIONS GC-BOLD magnetic resonance imaging measurements are well correlated to MVD levels and tumor size in the N1-S1 Novikoff hepatoma model; GC-BOLD measurements may serve as noninvasive biomarkers for evaluating angiogenesis and disease progression and/or therapy response.

Four-dimensional transcatheter intraarterial perfusion MRI monitoring of radiofrequency ablation of rabbit VX2 liver tumors.

To investigate the hypothesis that four‐dimensional (4D) transcatheter intraarterial perfusion (TRIP) magnetic resonance imaging (MRI) can quantify immediate perfusion changes after radiofrequency (RF) ablation in rabbit VX2 liver tumors.

T2-weighted STIR imaging of myocardial edema associated with ischemia-reperfusion injury: The influence of proton density effect on image contrast

To investigate the contribution of proton density (PD) in T2‐STIR based edema imaging in the setting of acute myocardial infarction (AMI).

Parametric dependence of myocardial blood oxygen level dependent, balanced steady-state free-precession imaging at 1.5 T: theory and experiments.

Myocardial blood oxygen level dependent, balanced steady‐state free precession (bSSFP) imaging is a relatively new technique for evaluating myocardial oxygenation changes in the presence of coronary artery stenosis. However, the dependence of myocardial bSSFP blood oxygen level dependent signal on imaging parameters has not been well studied. In this work, modeling capillaries as cylinders that act as magnetic perturbers, the Monte Carlo method was used to simulate spin relaxation via diffusion in a field variation inside and outside blood vessels. bSSFP signal changes at various levels of capillary blood oxygen saturation, for a range of pulse repetition times, flip angle, capillary blood volume fraction, vessel wall permeability, water diffusion coefficient, vessel angle to static magnetic field, and the impact of bulk frequency shifts were studied. The theoretical dependence of bSSFP blood oxygen level dependent contrast on pulse repetition times and flip angle was confirmed by experiments in an animal model with controllable coronary stenosis. Results showed that, with the standard bSSFP acquisition, optimum bSSFP blood oxygen level dependent contrast could be obtained at pulse repetition times = 6.0 ms and flip angle = 70°. Additional technical improvements that preserve the image quality may be necessary to further increase the myocardial bSSFP blood oxygen level dependent sensitivity at 1.5 T through even longer pulse repetition times. Magn Reson Med, 2010.

Myocardial edema contrast in acute myocardial infarction: a comparative study of the sensitivity of different CMR Methods

Introduction A number of CMR imaging approaches have been proposed for detecting myocardial edema accompanying acute myocardial infarctions (AMI). Besides the most commonly employed T2-weighted STIR (T2-STIR), T2prepared SSFP (T2-prep SSFP) and cine SSFP (bSSFP) methods have also been proposed. To quantitatively assess myocardial edema, the utility of T1 and T2 maps has been described. However, the relative sensitivities of the various approaches in relation to the routinely used, T2-STIR, method is not fully known.

On the mechanism of myocardial edema contrast in T2-STIR images

Acute myocardial infarcts (AMI) are typically discriminated with T2-STIR imaging [1], albeit with limited specificity [2]. Guided by the association that T2-STIR images identify AMI territories on the basis of edema-related T2 changes, even some of the recently proposed improvements [2,3] have relied on preferential sensitization of magnetization to T2-weighting. However, whether T2-STIR imaging itself may also be sensitive to other sources of contrast have not been fully investigated.

Detecting reperfusion myocardial hemorrhage with T2 and T2* maps at 1.5T

Reperfusion into severely ischemic myocardium can lead to myocardial hemorrhage (MH). Recent studies have employed T2- and T2*-weighted imaging to assess MH. However, a direct comparison of myocardial T2 and T2* changes in the setting of MH is not available.