Elliot J Stein1, Nicholas R Perkons1, Joseph C Wildenberg2, Srikant K Iyer2, Stephen J Hunt2, Gregory J Nadolski2, Walter R Witschey2, Terence P Gade3. 1. Department of Radiology, Penn Image-Guided Interventions Laboratory, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. 2. Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. 3. Department of Radiology, Penn Image-Guided Interventions Laboratory, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Department of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address: gadet@pennmedicine.upenn.edu.
Abstract
PURPOSE: To evaluate the capability of T2-weighted magnetic resonance (MR) imaging to monitor electrolytic ablation-induced cell death in real time. MATERIALS AND METHODS: Agarose phantoms arranged as an electrolytic cell were exposed to varying quantities of electric charge under constant current to create a pH series. The pH phantoms were subjected to T2-weighted imaging with region of interest quantitation of the acquired signal intensity. Subsequently, hepatocellular carcinoma (HCC) cells encapsulated in an agarose gel matrix were subjected to 10 V of electrolytic ablation for variable lengths of time with and without concurrent T2-weighted MR imaging. Cellular death was confirmed by a fluorescent reporter. Finally, to confirm that real-time MR images corresponded to ablation zones, 10 V electrolytic ablations were performed followed by the addition of pH-neutralizing 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) buffer. RESULTS: Analysis of MR imaging from agarose gel pH phantoms demonstrated a relationship between signal intensity and pH at the anodes and cathodes. The steep negative phase of the anode model (pH < 3.55) and global minimum of the cathode model (pH ≈ 11.62) closely approximated established cytotoxic pH levels. T2-weighted MR imaging demonstrated a strong correlation of ablation zones with regions of HCC cell death (r = 0.986; R2 = 0.916; P < .0001). The addition of HEPES buffer to the hydrogel resulted in complete obliteration of MR imaging-observed ablation zones, confirming that change in pH directly caused the observed signal intensity attenuation of the ablation zone. CONCLUSIONS: T2-weighted MR imaging enabled the real-time detection of electrolytic ablation zones, demonstrating a strong correlation with histologic cell death.
PURPOSE: To evaluate the capability of T2-weighted magnetic resonance (MR) imaging to monitor electrolytic ablation-induced cell death in real time. MATERIALS AND METHODS:Agarose phantoms arranged as an electrolytic cell were exposed to varying quantities of electric charge under constant current to create a pH series. The pH phantoms were subjected to T2-weighted imaging with region of interest quantitation of the acquired signal intensity. Subsequently, hepatocellular carcinoma (HCC) cells encapsulated in an agarose gel matrix were subjected to 10 V of electrolytic ablation for variable lengths of time with and without concurrent T2-weighted MR imaging. Cellular death was confirmed by a fluorescent reporter. Finally, to confirm that real-time MR images corresponded to ablation zones, 10 V electrolytic ablations were performed followed by the addition of pH-neutralizing 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) buffer. RESULTS: Analysis of MR imaging from agarose gel pH phantoms demonstrated a relationship between signal intensity and pH at the anodes and cathodes. The steep negative phase of the anode model (pH < 3.55) and global minimum of the cathode model (pH ≈ 11.62) closely approximated established cytotoxic pH levels. T2-weighted MR imaging demonstrated a strong correlation of ablation zones with regions of HCC cell death (r = 0.986; R2 = 0.916; P < .0001). The addition of HEPES buffer to the hydrogel resulted in complete obliteration of MR imaging-observed ablation zones, confirming that change in pH directly caused the observed signal intensity attenuation of the ablation zone. CONCLUSIONS: T2-weighted MR imaging enabled the real-time detection of electrolytic ablation zones, demonstrating a strong correlation with histologic cell death.