Project Summary I am currently an Instructor in the Department of Radiology at Massachusetts General Hospital and Harvard Medical School. My long-term career goal is to become an independent investigator in biomarker imaging development and translation to better understand and diagnose inflammation in cardiopulmonary diseases. I will perform the proposed study at the Center for Systems Biology at the Simches Research Center (CSB) and MGH?s Navy Yard campus under the mentorship of Drs. John Chen, Umar Mahmood and Mikael Pittet, who have complementary expertise in imaging agent development, cardiovascular imaging development and innate immunology. Drs. Filip Swirski and Guangbin Dong will join on the advisory committee to provide advice and guidance. In addition to the mentorship and advisory meetings, I plan to deepen and broaden my knowledge and training in biomedical imaging, immunology and cardiopulmonary pathophysiology through attending formal courses, workshops and seminars at Harvard Medical School and the Harvard community as well as attending relevant conferences in the fields. This K25 grant will provide me with the training and experience necessary to grow into an independent investigator in biomedical imaging research. Research Summary Two major activated macrophage phenotypes, classically activated macrophages (M1), which are pro- inflammatory and bactericidal, and alternatively activated macrophages (M2) which, are anti-inflammatory and reparative, play critical roles in various diseases including wound healing, myocardial infarction and cancer. The importance of macrophage phenotypes and function make them an attractive diagnostic and therapeutic target. However, in vivo detection of these cells remains challenging due to the heterogeneity and complexity of the macrophage phenotypes. Efficacious and specific in vivo tools are greatly needed. Few imaging methods have been developed to tackle this issue. Mannose receptors are a well-established marker for M2- like macrophages, which recognize and bind to terminal mannose, fucose or N-acetylglucosamine on the surface of pathogenic viruses, bacteria or fungi. We hypothesize that by screening and optimizing mannose- based ligands targeting the mannose receptor we will identify a highly efficacious magnetic resonance imaging (MRI) probe that can differentiate M2-like macrophages from M1-like macrophages. Therefore, the goals of this proposal are 1) to develop an MRI probe targeting mannose receptors to detect M2-like macrophages and validate it in a mouse model of wound healing, and 2) to apply the optimal probe to longitudinally track M2-like macrophages in mouse models of myocardial infarction and lung carcinoma, with the ultimate goal of translating this technology for human use in a future study. !