During the first 3 days after MR-HIFU ablation, the ablation region increases in size, after which it gradually decreases in size. The NPA on CE-T1-w imaging underestimates the extent of tissue necrosis on histology in the initial few days, but after 1 week, the NPA is reliable in delineating the necrotic tissue area. The 240-EM thermal dose limit underestimates the necrotic tissue area immediately after MR-HIFU ablation. Reliable treatment evaluation techniques are particularly important for noninvasive, image-guided tumor ablation. Our results indicate that CE-T1-w imaging is reliable for MR-HIFU treatment evaluation after 1 week.
Our results demonstrate the feasibility and safety of MR-HIFU ablation of liver tissue volumes. The imaging data and cell viability histology show, for the first time, that confluent ablation volumes can be achieved with motion-gated ablation and MR guidance. These results were obtained using a readily available MR-HIFU system with only minor modifications, within a clinically acceptable time frame, and with only minor adverse events. This shows that this technique is sufficiently reliable and safe to initiate a clinical trial.
Purpose
The aim of this study was to characterize tumor growth of N1S1 cells implanted into the liver of Sprague Dawley rats in order to determine if this model could be used for survival studies. These results were compared with tumor growth after implantation with McA-RH77777 cells.
Materials and Methods
N1S1 cells or McA-RH77777 cells were implanted into the liver of Sprague Dawley rats (n=20 and n=12, respectively) using ultrasound (US) and tumor growth was followed using US. Additionally, we compared the serum profile of 19 cytokines in naïve rats to tumor bearing rats.
Results
Both types of tumors were visible on US imaging 1 week after tumor implantation, but the mean tumor volume of N1S1 tumors was larger compared to McA-RH7777 tumors (231 mm3 versus 82.3 mm3, respectively). Tumor volumes in both groups continued to increase reaching a mean tumor volume of 289 mm3 and 160 mm3 in the N1S1 and McA-RH7777 group, respectively, 2 weeks post tumor implant. By week 3, tumor volumes had declined considerably, and 6 (50%) tumors in the McA-RH7777 had spontaneously regressed, versus 2 (10%) tumors in the N1S1 group. Tumor volumes continued to decrease over the following 3 weeks, and complete tumor regression of all tumors was seen 5 weeks and 6 weeks after tumor implantation in the McA-RH7777 and N1S1 group, respectively. In an N1S1 implanted rat, multiple cytokines that have been shown to correlate with the ability of the tumor to survive in a hostile environment were increased by up to 50%, whereas the average increase in cytokine levels was 90%. These findings suggest that the net cytokine environment favors an anti-tumor immune response. A similar trend was observed in a rat with a McA-RH77777 tumor, and the increase in cytokine levels was considerably more pronounced with an average increase of 320%.
Conclusion
We therefore conclude that this model cannot be used for survival studies, and should only be used with great caution in short-term studies that involve cancer therapies.
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