WITHIN THE RISK OF CARDIOVASCULAR DISEASE AND OTHER DEGENERATIVE TISSUE EFFECTS FROM RADIATION EXPOSURE AND SECONDARY SPACEFLIGHT STRESSORS THE GAPS DEGEN-2 AND -3 INVOLVE IDENTIFICATION OF ADVERSE OUTCOME PATHWAYS PROGRESSION RATES AND LATENCY PERIODS AND EARLY SURROGATE MARKERS FOR RADIATION-INDUCED CARDIOVASCULAR DISEASE. TO DATE NO TASKS HAVE INCLUDED HUMAN RADIOTHERAPY COHORTS TO ASSESS THOSE PARAMETERS AND IDENTIFY BIOMARKERS. THE PROPOSED WORK WILL ACQUIRE DATA ON CARDIOVASCULAR IMPAIRMENTS AND ASSOCIATED BIOMARKERS OBSERVED IN PATIENTS UNDERGOING CARDIAC EXPOSURE TO IONIZING RADIATION WITH EMPHASIS ON NON-INVASIVE IMAGING MODALITIES TO QUANTIFY PREDICTIVE CHANGES LINKED TO LATE IMPAIRMENT. PROMPT IDENTIFICATION OF DAMAGE MAY ENABLE INTERVENTIONS TO PREVENT PROGRESSION TO CARDIAC DYSFUNCTION. FURTHERMORE STUDY OF CARDIAC CHANGES THAT OCCUR DURING AND SOON AFTER RADIOTHERAPY WOULD GRANT INSIGHT INTO THE PATHOPHYSIOLOGY WHICH MAY LEAD TO NOVEL THERAPEUTIC INTERVENTIONS. THE RESULTS MAY THEN BE CORRELATED WITH OTHER STUDIES PERFORMED IN ANIMALS OR IN HUMAN COHORTS WITH DIFFERENT TYPES OF RADIATION EXPOSURE SUCH AS ASTRONAUTS. RESEARCH DELIVERABLES FROM THIS WORK WILL HELP CLOSE GAPS DEGEN-2 AND -3 AS WELL AS FEED INTO COUNTERMEASURE DEVELOPMENT AND VALIDATION IN ANIMAL STUDIES WITH SPACE RADIATION EXPOSURES. RESULTS WILL ALSO DRIVE PREDICTIVE MODEL DEVELOPMENT (DEGEN-5).