ABSTRACT NASA IS CONCERNED ABOUT THE FUNCTIONAL CONSEQUENCES OF INFLIGHT ACUTE EXPOSURE TO SPACE RADIATION AND THE PROBABILITY OF RADIATION EXPOSURE ENHANCING OR ACCELERATING LATE NEURODEGENERATIVE CONDITIONS POST-MISSION. THIS PROPOSED RESEARCH AIMS TO ACQUIRE DATA ON NEUROCOGNITIVE/BEHAVIORAL IMPAIRMENTS AND ASSOCIATED BIOMARKERS OBSERVED IN PATIENTS WHO ARE UNDERGOING CRANIAL EXPOSURE TO IONIZING RADIATION WITH AN EMPHASIS ON NON-INVASIVE IMAGING MODALITIES AND SERUM BIOMARKERS TO QUANTIFY PREDICTIVE CHANGES LINKED TO ACUTE AND LATE NEUROCOGNITIVE IMPAIRMENT AND RADIATION DOSE. THIS WORK WILL PROVIDE BENCHMARK DATA ON STRUCTURAL AND FUNCTIONAL CHANGES IN PATIENTS RESULTING FROM PHOTON (X-RAY) AND PROTON EXPOSURES DURING RADIOTHERAPY OF HEAD AND NECK AND INTRACRANIAL NEOPLASMS. EXISTING RESEARCH DATA SUGGEST THAT ANIMALS AND HUMANS MAY BE SHARE SIMILAR PATHOPHYSIOLOGICAL MECHANISMS FOLLOWING BRAIN RADIATION EXPOSURE THAT LEAD TO ADVERSE COGNITIVE OR BEHAVIORAL CONDITIONS OR THE EXACERBATION OR ACCELERATION OF LATE DEGENERATIVE CONDITIONS. TO ESTABLISH THRESHOLDS OF PERMISSIBLE EXPOSURE FOR EFFECTS ON THE CENTRAL NERVOUS SYSTEM IT IS CRUCIAL TO UNDERSTAND SCALING RELATIONSHIPS BETWEEN HUMANS AND ANIMALS. IN THE PROPOSED RESEARCH THE BROADER RANGE IN RADIATION DOSE EXPOSURE IN A MORE NEUROCOGNITIVELY VULNERABLE POPULATION WILL FACILITATE MORE RAPID SIGNAL FINDING INVESTIGATIONS OF THESE BIOMARKERS THAT CAN BE FURTHER REFINED FOR SUBSEQUENT INVESTIGATION IN ASTRONAUTS. THERE IS COMPLEMENTARY OVERLAP BETWEEN THIS WORK AND PROPOSED DIRECTED WORK AT MD ANDERSON INVOLVING RADIATION-INDUCED CARDIOTOXICITIES THAT WILL TIE IN COMMON PATHWAYS BETWEEN CVD AND CNS DECREMENTS THROUGH THE INVESTIGATION OF COMMON BIOMARKERS. THE GAPS DEGEN-2 AND -3 AND CNS-1 -2 AND -6 INVOLVE IDENTIFICATION OF ADVERSE OUTCOME PATHWAYS PROGRESSION RATES AND LATENCY PERIODS AND EARLY SURROGATE MARKERS FOR RADIATION-INDUCED CARDIOVASCULAR/CEREBROVASCULAR DISEASE AND EARLY AND LATE CNS DECREMENTS. RESEARCH DELIVERABLES FROM THIS WORK WILL HELP CLOSE THE ABOVE GAPS AND SERVE AS QUANTIFIABLE MEASURES OF RESPONSE TO GUIDE COUNTERMEASURE DEVELOPMENT AND VALIDATION IN ANIMAL STUDIES WITH HZE EXPOSURES. RESULTS WILL ALSO DRIVE PREDICTIVE MODEL DEVELOPMENT (DEGEN-5 AND CNS-5).