Abstract

Electrolytic ablation (EA) causes cell death by creating an inhospitably alkaline or acidic microenvironmental pH (1). We hypothesized that MRI may enable the monitoring of the ablation zone created by electrolytic ablation (EA) in vitro in real time. First, a series of phantoms containing Corgel™ (tyramine-substituted hyaluronate) (Lifecore Biomedical) were created and titrated to pHs ranging from 2 to 12. T1 and T2 mapping studies using the TSE and SE sequences, respectively, were performed in a 1.5 T scanner (Siemens). Second, agarose gels containing encapsulated human hepatocellular carcinoma (HCC) Huh-7 cells were treated with 10 V EA for 120, 240, 360, 480, and 600 sec. The LIVE/DEAD® Viability/Cytotoxicity Kit (ThermoFisher Scientific) was used to assess cell death. This experiment was repeated under MRI guidance, and a correlation between the MRI ablation zone and the histologic ablation zone was performed. T2 mapping studies of the Corgel™ phantoms revealed that acidic and basic pH consistently elongated the T2 relaxation time of the phantoms, suggesting that pH change may be visible on conventional T2-weighted imaging without contrast. In the in vitro ablation experiment, increasing ablation duration produced larger zones of cellular death, with a peak reached at 360 seconds. Furthermore, when EA was observed on T2-weighted MRI, zones of hypointensity closely approximated the region of cell death as confirmed by the fluorescent live / dead reporter. Correlational analysis revealed r = 0.985, R2 = 0.916, and p < 0.0001, suggesting that real-time T2-weighted MRI may be an accurate predictor of cell death induced by EA. T2-weighted MRI reliably detects alkaline and acidic pHs as relative signal hypointensity. This T2 prolongation enables the real-time visualization of the ablation zone created by EA, which has a strong correlation to the zone of histologic cell death in vitro.

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