Summary/Abstract: Title: Development of a 3D multi-modal perfusion-thermal electrode system Advances in image-guided interventional technologies have greatly improved the management of malignancies in patients. Among different interventional oncologic techniques, thermal ablations, such as radiofrequency ablation (RFA) and microwave ablation (MWA), have become the principal tools for treatment of unresectable primary and metastatic malignancies. However, tumor recurrence post- thermal ablation of medium (3-5 cm) to large (5-7 cm) lesions often occurs due to incomplete ablation of tumor margins. To date, there is no an ideal image-guided interventional method for effective management of medium-to-large solid organ malignancies. This project is specifically designed to conquer the critical clinical problem ─ persistence or recurrence of medium-to-large malignancies post-thermal ablation, by development of a novel three- dimensional (3D) multi-modal perfusion-thermal electrode system. To this end, we have proposed two specific goals: (1) Aim I: to design and develop the novel 3D multi-modal perfusion-thermal electrode system that is specifically built for using RFA-induced peri-tumoral RF hyperthermia (RFH) to enhance direct chemotherapeutic destruction of tumor margins; and (2) Aim II: to validate the technical feasibility of the new multi-modal electrode system with optimizing the technical protocols via serial preclinical studies in living animal models with orthotopic liver tumors. As the first step of the new technique development, we will primarily focus on the treatment of hepatic tumors by using first- line chemotherapeutics. If successful, we will extend its application in treating malignancies to other organs with more advanced therapies, such as gene therapy and immunotherapy. The success of this project will revolutionize current thermal ablation technology, leading to significant advancement in eradicating medium-to-large malignant lesions, not only in the liver but also in other solid organs. This will, in turn, greatly improve survival and quality of life of patients suffering from medium-to-large malignancies.