On The Physical And Chemical Enhancement Of Radiofrequency Ablation Of Tumors

Radiofrequency ablation(RFA)is an energy-based tumor ablation modality,and it uses the so-called "resistive heat" to destroy tumors.An RFA system consists of an RF power generator,one or more RF applicators,and one or more ground pads,and these components form a closed electric circuit by the inclusion of patient's body.With the help of an image-guided device,such as ultrasound,CT,or MRI,the RF applicator is inserted into targeted tissues to deliver the RF energy to them.In the RFA procedure,the heat is generated due to the interaction between the ions of the biological tissues and the electrons of the alternating current at the frequency of 460-500 kHz;in particular,the highest heat flux occurs at the active tip of the applicator,where the current density is highest.Heat induces temperatre rises to the lethal temperature to burn the tissues(including tumor tissue).RFA has been widely used in the treatment of various unresectable tumors due to favorable outcome,minimal invasiveness,and few complications.It is noteworthy that the survival rate of RFA in the treatment of small tumors(<3 cm in diameter)is competitive to that of surgical resection.RFA has been taken as the first-line treatment of small tumors in clinic especially liver tumors.Unfortunately,RFA often fails to achieve a complete ablation of large tumors(?3 cm in diameter)with the monopolar RF applicator or in a single session of RFA treatment.It is well-accepted that this incomplete ablation is the main reason leading to the local recurrence and failure of further treatments.Meanwhile,it causes a lower survival ratio and a higher recurrence ratio in the clinical treatment.This thesis study was motivated to address this problem and further improve the efficacy of RFA.The overall objective of this study was to advance the RFA technique in terms of ablation zone and completeness of ablation by both physical and chemical means.Three specific objectives were defined for this study.Objective 1:to prove that there is a significant difference in outcome between the small tumor and large tumor.Objective 2:to optimize the design of the RF applicator based on the idea of active tip by employing the axiomatic design theory(ADT),well-known in the design community,aiming to maximize the ablation zone.Objective 3:to develop a chemical approach to modulate the tissue so that more RF energy can be delivered to the tumor tissue and thus the ablaztion zone can be increased.Regaring Objective 1,a survey-based statisitical analysis was performed.In particular,145 cases in a hospital in Shanghai were tracked for the overall survival and recurrence-free survival rates.The factors such as the age,gender,liver function level,tumor diameter,tumor number,and tumor location were considered.The finding was such that the overall survival rate for patients with large liver tumors is significantly lower than those with small liver tumors.Regarding Objective 2,ADT was employed to conduct the concept design of the RF applicator,which led to a new structure of the applicator.After that,the finite element method was employed to assist in the embodiment design of this novel applicator.Finally,the vitro experiment was carried out to validate the novel design.Two conclusions were drawn from the study:(1)the electric field and temperature distribution in tissues can be affected significantly by the active tip of RF applicator,and 2)an ablation zone of 3.5 cm can be achieved with the new the RF applicator.Regarding Objective 3,the cationic polymers were chosen to pre-treat tumor tissues,namely chitooligosaccharides(COS)and carboxymethyl chitosan(CMC),because of their non-cytotoxicity and bio-compatibility.The other important advantage of them,in comparison to the saline solution(commonly used to enhance the efficacy of RFA),is that they can be easily controlled to distribute into a desired pattern and thus precisely to cover the tumor zone.Both in vivo experiment and computer simulation were performed to prove the efficacy of the two polymers.Two conclusions were drawn from the study:(1)pre-treatment of liver tumor tissues with COS and CMC can significant increase the electrical conductivity of the tissues,and(2)RFA with the pre-treatment with COS and CMC can increase the ablation zone and improve the regularity of the ablation shape.The main contribution of this thesis study in the field of RFA includes:(1)the provision of a new design of RF applicator with an active tip,which can increase the size and roundness of ablation zone.Meanwhile,the egg white experiments and simulations were performed to verify the effectiveness of the new design of RF applicator;(2)the finding of two cationic polymers,COS and CMC,that can be used to pre-treat tumor tissues in the RFA procedure to increase the ablation zone with a regular ablation shape;and(3)the in vivo experimental validation of a solution diffusion RFA model,which provide an experimental basis for this newly proposed model.