Project Grant R41HL170898

PRECISION MRI WITH A NOVEL PROTEIN CONTRAST AGENT FOR EARLY DETECTION AND STAGING OF LUNG FIBROSIS - SUMMARY LUNG DISEASES, SUCH AS INTERSTITIAL LUNG DISEASES INCLUDING IDIOPATHIC PULMONARY FIBROSIS (IPF), CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD), AND ACUTE VIRAL INFECTION ARE MAJOR LEADING CAUSES OF DEATH WORLDWIDE. THE RECENT INCREASE DUE TO AIR POLLUTION, TOBACCO SMOKING IS AND USE OF E-CIGARETTES HAS GROWN RAPIDLY IN THE US CONTRIBUTING TO A SHARP INCREASE IN CHRONIC LUNG DISEASES. IPF IS CHARACTERIZED BY INCREASED EXTRACELLULAR MATRIX (ECM), INCLUDING COLLAGEN, WITHIN THE LUNG, CAUSING IRREVERSIBLE LUNG DAMAGE. WHILE HIGH-RESOLUTION COMPUTED TOMOGRAPHY (HRCT) IS COMMONLY USED TO DIAGNOSE IPF. THIS METHOD CAN PRODUCE LARGE VARIATION AND ERROR (UP TO 50%) AND IS UNABLE TO DETECT EARLY-STAGE LUNG FIBROSIS. AS THE PRESENCE OF SYMPTOMS DOES NOT ALWAYS INDICATE DISEASE TYPE, DIAGNOSIS IS USUALLY OBTAINED AT A MUCH LATER STAGE. DESPITE THE ADVANTAGES OF MRI, WHICH INCLUDES DEPOSITION DEPTH PENETRATION, LACK OF IONIZING RADIATION, AND HIGH RESOLUTION, THE APPLICATION OF MRI TO LUNG IMAGING HAS BEEN VERY CHALLENGING DUE TO REDUCED (10X LOWER) DENSITY OF THE LUNGS COMPARED TO OTHER TISSUES AND LIMITATIONS FROM EXTENSIVE DIPOLAR INTERACTIONS WITH MOLECULAR OXYGEN IN THE LUNGS. THEREFORE, THERE IS A PRESSING UNMET MEDICAL NEED TO DEVELOP NONINVASIVE IMAGING METHODOLOGIES AND CONTRAST AGENTS TO DETECT EARLY STAGES OF LUNG FIBROSIS, AND STAGE FIBROSIS SEVERITY BASED ON PROGRESSION OF IPF.