Hypericin as a marker for determination of tissue viability after radiofrequency ablation in a murine liver tumor model

AbstractHepatic radiofrequency ablation (RFA) induces a drastic alteration of the biomechanical environment in the peritumoral liver tissue. The resulting increase in matrix stiffness has been shown to significantly influence carcinogenesis and cancer progression after focal RF ablation. To investigate the potential of an elastin-specific MR agent (ESMA) for the assessment of extracellular matrix (ECM) remodeling in the periablational rim following RFA in a VX2 rabbit liver tumor-model, twelve New-Zealand-White-rabbits were implanted in the left liver lobe with VX2 tumor chunks from donor animals. RFA of tumors was performed using a perfused RF needle-applicator with a mean tip temperature of 70 °C. Animals were randomized into four groups for MR imaging and scanned at four different time points following RFA (week 0 [baseline], week 1, week 2 and week 3 after RFA), followed by sacrifice and histopathological analysis. ESMA-enhanced MR imaging was used to assess ECM remodeling. Gadobutrol was used as a third-space control agent. Molecular MR imaging using an elastin-specific probe demonstrated a progressive increase in contrast-to-noise ratio (CNR) (week 3: ESMA: 28.1 ± 6.0; gadobutrol: 3.5 ± 2.0), enabling non-invasive imaging of the peritumoral zone with high spatial-resolution, and accurate assessment of elastin deposition in the periablational rim. In vivo CNR correlated with ex vivo histomorphometry (ElasticaVanGiesson-stain, y = 1.2x − 1.8, R2 = 0.89, p < 0.05) and gadolinium concentrations at inductively coupled mass spectroscopy (ICP-MS, y = 0.04x + 1.2, R2 = 0.95, p < 0.05). Laser-ICP-MS confirmed colocalization of elastin-specific probe with elastic fibers. Following thermal ablation, molecular imaging using an elastin-specific MR probe is feasible and provides a quantifiable biomarker for the assessment of the ablation-induced remodeling of the ECM in the periablational rim.

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Design of a Novel Electrode of Radiofrequency Ablation for Large Tumors: In Vitro Validation and Evaluation

Journal of Biomechanical Engineering ◽

10.1115/1.4042179 ◽

2019 ◽

Vol 141 (3) ◽

Cited By ~ 2

Author(s):

Zheng Fang ◽

Micheal A. J. Moser ◽

Edwin Zhang ◽

Wenjun Zhang ◽

Bing Zhang

Keyword(s):

Computer Simulation ◽

Radiofrequency Ablation ◽

Liver Tumor ◽

Tumor Model ◽

Egg White ◽

Large Tumor ◽

Ablation Volume ◽

Conventional Electrode

In a prior study, we proposed a novel monopolar expandable electrode (MEE) for use in radiofrequency ablation (RFA). The purpose of our work was to now validate and evaluate this electrode using on in vitro experimental model and computer simulation. Two commercially available RF electrodes (conventional electrode (CE) and umbrella electrode (UE)) were used to compare the ablation results with the novel MEE using an in vitro egg white model and in vivo liver tumor model to verify the efficacy of MEE in the large tumor ablation, respectively. The sharp increase in impedance during RFA procedures was taken as the termination of RFA protocols. In the in vitro egg white experiment, the ablation volume of MEE, CE, and UE was 75.3 ± 1.6 cm3, 2.7 ± 0.4 cm3, and 12.4±1.8 cm3 (P < 0.001), respectively. Correspondingly, the sphericity was 88.1±0.9%, 12.9±1.3%, and 62.0 ± 3.0% (P < 0.001), respectively. A similar result was obtained in the in vitro egg white computer simulation. In the liver tumor computer simulation, the volume and sphericity of ablation zone generated by MEE, CE, and UE were 36.6 cm3 and 93.6%, 3.82 cm3 and 16.9%, and 13.5 cm3 and 56.7%, respectively. In summary, MEE has the potential to achieve complete ablation in the treatment of large tumors (>3 cm in diameter) compared to CE and UE due to the larger electrode–tissue interface and more round shape of hooks.

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