ENHANCING THE CUTTING EDGE ABLATIVE THERAPIES BY CONTROLLING THE BEHAVIOUS OF TISSUES AND CELLS USING ELECTROMAGNETIC FIELDS

THE SEARCH FOR THE OPTIMAL PROCEDURE TO APPLY ELECTROMAGNETIC (EM) FIELDS TO TREAT CANCER, CARDIAC ARRHYTHMIAS AND BRAIN DISORDERS IS OF PARAMOUNT IMPORTANCE. THE CERAPI PROJECT WILL EXPLORE HOW SOME SPECIFIC ELECTROMAGNETIC (EM) ENERGIES CAN CONTROL THE TISSUE AND CELL BEHAVIOR IN ORDER TO IMPROVE THE SAFETY AND PERFORMANCE OF ABLATIVE THERAPIES INTENDED TO CURE HIGH-PREVALENCE AND INCIDENCE DISEASES IN A MINIMALLY INVASIVE WAY, REDUCES THE NUMBER OF COMPLICATIONS AND THE RISK OF INFECTION, AS WELL AS SHORTENS THE HOSPITAL STAY AND RECOVERY. IN PARTICULAR, THE PROJECT FOCUSES ON ABLATIVE TECHNIQUES BASED ON THE FOLLOWING EM ENERGIES: RADIOFREQUENCY (RF), MICROWAVE (MW), LASER AND PULSE ELECTRIC FIELD (PEF). CERAPI IS A COORDINATED PROJECT SINCE REQUIRES COMPLEMENTARY METHODOLOGIES AND KNOWLEDGE WHICH WILL BE SYNERGISTICALLY BROUGHT TOGETHER, SPECIFICALLY FROM ELECTRONIC ENGINEERING, MATHEMATICAL MODELING AND EXPERIMENTAL SURGERY (PRE-CLINICAL MODELS). OUR MOTIVATION IS FOCUSED ON EXPANDING THE CURRENT KNOWLEDGE ABOUT THE INTERACTION OF EM ENERGY WITH BIOLOGICAL TISSUES, FROM THE CELLULAR TO THE PHYSIOLOGICAL LEVEL. SPECIFICALLY THE SUBPROJECT WILL CONTRIBUTE TO IMPROVING THE TREATMENT OF THE FOLLOWING DISEASES: 1) TREATMENT OF CARDIAC ARRHYTHMIAS BY MEANS OF MINIMALLY INVASIVE ABLATIVE THERAPIES BASED ON RF AND PEF; 2) ABLATION OF TUMORS IN LIVER WITH THERMAL (RF, MW, LASER) AND NON-THERMAL ENERGIES (PEF); 3) REDUCTION OF THE RISK OF POST-OPERATIVE PANCREATIC FISTULA AFTER THE RESECTION; AND 4) NON-THERMAL ABLATION OF GASTROINTESTINAL (GI) CANCERS USING PEF. THE GENERAL OBJECTIVE IS TO OBTAIN A FULL DESCRIPTION OF THE BIOPHYSICS INVOLVED IN CUTTING EDGE ENERGY-BASED ABLATIVE THERAPIES, INCLUDING SHORT AND LONG-TERM TISSUE AND CELL RESPONSE. THE SPECIFIC OBJECTIVES ARE: 1) TO CHARACTERIZE IN VIVO BIOLOGICAL TISSUES IN TERMS OF THERMAL AND ELECTRICAL PROPERTIES RELEVANT IN THE CONTEXT OF ABLATIVE TECHNIQUES; 2) TO ASSESS THE PROGRESSIVE PHYSIOLOGICAL, HISTOLOGICAL AND BIOCHEMICAL CHANGES RESULTING FROM EM ENERGY-BASED ABLATIVE TECHNIQUES, BOTH DURING THE ACUTE PHASE AND AT CHRONIC STAGE; 3) TO UNDERSTAND THE CAUSES AND CONDITIONS OF OVERHEATING INDUCED BY EM ENERGY-BASED ABLATIVE TECHNIQUES, IN PARTICULAR TO CHARACTERIZE THE TISSUE VAPORIZATION (AND RESULTING DESICCATION), DYNAMICS OF INTRATISSUE GAS DISPLACEMENT, AND POSSIBLE RISK OF POPPING (DISRUPTION OF TISSUE SURFACE); 4) TO DEVELOP PERSONALIZED MODELS BASED ON PATIENT-SPECIFIC DATA THAT REPRESENT A QUALITATIVE LEAP WITH RESPECT TO THE STATE OF THE ART AND BECOME A DEFINITIVE STEP TOWARDS THE DEVELOPMENT OF FUTURE PERSONALIZED PREDICTIVE TOOLS; AND 5) TO APPLY MATHEMATICAL OPTIMIZATION TECHNIQUES TO IMPROVE SPECIFIC ABLATIVE PROCEDURES IN TERMS OF ENERGY APPLICATOR DESIGN (HARDWARE), WAY OF DELIVERING THE ENERGY (E.G. IN CASE OF APPLICATORS ARRAY) AND SPATIAL MATCHING BETWEEN THE CREATED ABLATION ZONE AND THE TARGET TO BE ABLATED (E.G. TUMOR, ORIGIN OF THE ARRHYTHMIA, EPILEPSY FOCUS, ETC.).