Novel MRI Contrast Agent for Monitoring Thermal Ablation

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DESCRIPTION (provided by applicant): Surgical resection has been shown to be an effective treatment for secondary liver tumors, with five-year survival rates between 20-30%. Unfortunately, only select patients are candidates for resection, and it has a relatively high complication rate. About 35% of patients suffer minor complications, 15% have more serious complications, and the mortality rate is 2-5%. In addition, the average hospital stay is about two weeks, even without complications. Minimally invasive methods to thermally coagulate liver tumors have eliminated some of these disadvantages and have been shown to be an effective alternative treatment. The number of patients who receive such thermal ablation treatments is growing rapidly, and this technology is poised to enter widespread use. A way to substantially improve the safety and effectiveness of these treatments would be to have a method to easily and reliably quantify the tissue online that has reached a sufficient thermal exposure to induce thermal coagulation. Our hypothesis is that a novel magnetic resonance imaging (MRI) contrast agent that is activated at a threshold temperature level can be used to reliably successfully monitor thermal ablation of liver tumors. This agent consists of paramagnetic material encapsulated in a liposome shell. When encapsulated, the material has a minimal effect on the MR signal intensity. The liposome shell undergoes a phase transition at a temperature (Tc) that can be precisely chosen, and MR signal enhancement occurs which can be easily detected with standard imaging methods. With a Tc of 57¿C, which is the approximate threshold for thermal coagulation for heating of at least a few seconds, the signal intensity enhancement thus indicates the regions that are thermally ablated. Since perfusion is halted after thermal coagulation, any released paramagnetic agent will remain in the tissue for an extended period of time, clearly marking the ablation progression. Our preliminary tests of this agent in vivo have demonstrated its basic functionally. Here, we propose in vivo animal experiments to extensively characterize its performance and to test its effectiveness in monitoring thermal ablation of liver tumors. This research will lead to more effective and safer thermal ablation treatments in liver, and perhaps allow more difficult cases to be feasibly treated with thermal ablation methods, since it would provide straightforward and reliable online feedback of the treatment progression.