| Currently,surgical treatments of arrhythmias are mainly based on large ring isolation to block erratic action potential conduction.The main drawback of this operation method is that lots of normal tissue will be damaged,which may cause serious postoperative complication,such as pulmonary veins stenosis.Based on the development progress and prospect of electrophysiological diagnosis technology,this dissertation assumed that the foci or the origins of arrhythmias can be positioning via optical imaging technologies as the advances of voltage sensitive dye and then the foci tissue can be destroyed via focused laser beam in the future,which contributes to reducing the damage of healthy tissues in principle.In this dissertation,we selected the arrhythmias caused by mitochondrial dysfunction as the research object and focused on the key issues involved in the new type of operation method at cellular,tissue and organs levels respectively.The main research contents and innovative results obtained in this dissertation are as follows:One of the important issues for finding origins of arrhythmias is knowing the characteristics of electrophysiological signal in the diseased and healthy heart tissue.Although the detailed mechanistic pathways remain incompletely understood,works from others suggest that the proarrhythmic effect of mitochondria dysfunction is at least partially attributed to the mitochondria-derived reactive oxygen species(md ROS).In addition,oxidative stress–mediated Ca MKII phosphorylation of cardiac ion channels has emerged as a critical contributor to arrhythmogenesis in cardiac pathology.However,the link between md ROS and increased Ca MKII activity in the context of cardiac arrhythmias has not been fully elucidated and is difficult to establish experimentally.In order to understand the characteristics of electrical activity of arrhythmias induced by md ROS at the cellular level,we hypothesized that pathological md ROS can cause erratic action potentials through oxidation dependent Ca MKII activation pathway and then validate the proposed hypothesis via modeling and simulation method,and finally analysis the characteristics of electrical activity of diseased heart tissue.In order to verify whether it is necessary to eliminate the influence of cardiac motion during laser ablation,a laser-tissue interaction model was constructed based on the radiation transfer equation(RTE)and heat conduction equation.Then,taking a twodimensional myocardial tissue with size of 5 8)8)× 5 8)8)as the research object,the irreversible thermal damage caused by laser irradiation under different conditions(e.g.,power,spot diameter,the motion of tissue,etc.)was analyzed.The research results showed that reducing tissue movement during ablation and precise positioning of instrument were very important for the quality of ablation.In order to reduce the relative motion between the end of surgical tool and tissue via active motion compensation(AMC)strategy,this dissertation proposed an imagebased method measuring the movement of living tissue,which was simple in structure and easy to integrate with minimally invasive instruments.The effectiveness of the proposed method was verified through theoretical analysis and a series of experiments.The experimental results showed that the motion curve of living animal tissue obtained by the prototype was similar to the results measured by the state-of-the art commercialized laser displacement sensor.Based on the proposed image-based displacement sensing method,this dissertation finally proposed a design method for diagnostic-therapeutic surgical tool based on active motion compensation,and developed the corresponding experimental prototypes.The feasibility and effectiveness of the proposed design method were validated by various experiments in vitro and in vivo.Experiments results reveal that the laboratory-built prototype could effectively reduce the influence of tissue movement during fluorescent imaging and individualized ablation. |
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