Project Grant F32EB038811

BEDSIDE OXIMETRY SYSTEM FOR MINIMALLY INVASIVE QUANTITATIVE MEASUREMENT AND MONITORING OF TISSUE OXYGENATION. - PROJECT SUMMARY SEVERAL OF THE MOST DEVASTATING DISEASES WE FACE TODAY, INCLUDING CANCER, CARDIOVASCULAR DISEASES, STROKE, TRAUMA AND PERIPHERAL ARTERY DISEASE FEATURE CHANGES IN TISSUE OXYGENATION, WHICH CAN BE USED AS A CRUCIAL PREDICTOR OF DISEASE SEVERITY AND TREATMENT OUTCOME. CANCEROUS TUMORS, FOR EXAMPLE, OFTEN CONTAIN REGIONS OF LOW OXYGEN AND HYPOXIA, WHICH ARE MORE CHALLENGING TO TREAT THAN TUMOR AREAS WITH NORMAL OXYGEN. HIGHER AMOUNTS OF HYPOXIA IN CANCERS ARE ASSOCIATED WITH HIGHER AGGRESSION, METASTASIS, FAST PROGRESSION, AND WORSE PATIENT OUTCOME. CLINICIANS NEED THE ABILITY TO QUANTITATIVELY MEASURE OXYGEN (OXIMETRY) DIRECTLY IN PATIENT TUMORS, ESPECIALLY AT THE BEDSIDE AND IN THE PROCEDURE ROOM TO AID DIAGNOSIS, TREATMENT PLANNING, AND TREATMENT SUCCESS. THIS KNOWLEDGE WOULD PROVIDE TARGETED TREATMENT TO THE HYPOXIC REGIONS WITH OXIMETRY-GUIDED TREATMENT. VARIOUS METHODS EXIST TO MEASURE RELATIVE OXYGEN AND RELATED ATTRIBUTES LIKE BLOOD OXYGEN SATURATION, BUT ELECTRON PARAMAGNETIC RESONANCE (EPR) WITH OXYCHIP IS CURRENTLY THE ONLY OXIMETRY METHOD THAT HAS CLEARANCE FOR CLINICAL TRIALS. OUR LAB HAS DEVELOPED OXYCHIP AND AN OXYCHIP-BASED NEEDLE SENSOR FOR OXIMETRY IN DEEP TISSUE. TO MAKE THE SENSOR MORE ACCESSIBLE TO CLINICIANS, WE PROPOSE TO BUILD, VALIDATE, AND TEST A STANDALONE SENSOR BUILT AS A REUSABLE SYRINGE PLUNGER (OXYSYRINGE SENSOR), INTEGRATED INTO A COMPACT BEDSIDE SYSTEM. THIS REUSABLE SENSOR ALLOWS THE USE OF DISPOSABLE SYRINGES WITH VERY SMALL NEEDLES FOR MINIMALLY INVASIVE OXYGEN MEASUREMENT AND MONITORING. WE WILL DO THIS THROUGH THE FOLLOWING SPECIFIC AIMS: 1) DESIGN, CONSTRUCT AND TEST THE OXYSYRINGE SENSOR. 2) DEVELOP HARDWARE AND SOFTWARE FOR BEDSIDE PULSE BRIDGE, INTERFACE, AND PERIPHERALS. 3) TEST, EVALUATE, AND VALIDATE THE OXYSYRINGE USING PHANTOMS AND PRECLINICAL MODELS OF CANCER AND HEALTHY TISSUES IN VIVO. WE WILL UTILIZE A TISSUE EMULATING PHANTOM, A MURINE SQUAMOUS CELL CARCINOMA MODEL (SCC7), AND DOG CANCER PATIENTS TO INFORM DESIGN AND VALIDATE THE OXYSYRINGE. THIS PROJECT INCLUDES SIGNIFICANT TRAINING IN INDEPENDENT RESEARCH, MEDICAL DEVICE DEVELOPMENT, EPR OXIMETRY, AND CANCER BIOLOGY AND WILL BE OVERSEEN BY A COMMITTEE OF NATIONALLY-RECOGNIZED SCHOLARS TO PREPARE THE PI FOR A CAREER AS AN INDEPENDENT RESEARCHER. TAKEN AS A WHOLE, THE GOAL OF THIS PROJECT IS TO DEVELOP AND VALIDATE A NEW TOOL FOR MEASURING QUANTITATIVE OXYGEN IN PRECLINICAL AND, LATER, CLINICAL SETTINGS WHILE TRAINING THE PI TO BECOME AN INDEPENDENT RESEARCHER IN THE FIELDS OF MEDICAL DEVICE DEVELOPMENT, EPR OXIMETRY, AND CANCER BIOLOGY.