SUBJECT: Ph.D. Dissertation Defense
   
BY: Yidong Yang
   
TIME: Monday, June 21, 2010, 3:00 p.m.
   
PLACE: Boggs, 3-47
   
TITLE: Monitor Cell Infiltration into the Myocardial Infarction Site Using Micrometer-Sized Iron Oxide Particles-Enhanced MRI
   
COMMITTEE: Dr. Tom Hu, Co-Chair (MCG)
Dr. Sang Cho, Co-Chair (NRE/MP)
Dr. Chris Wang (NRE/MP)
Dr. John Oshinski (BME)
Dr. Nathan Yanasak (MCG)
Dr. Autumn Schumacher (MCG)
 

SUMMARY

The cell infiltration into the myocardial infarction (MI) site was studied using MRI with micrometer-sized iron oxide particles (MPIO) as cell labeling probes. MI is the leading cause of global death and disability. However, the roles of inflammatory cells and stem cells during the post-MI remodeling and repair processes are still yet to know. This study was to develop a noninvasive MRI technique to monitor and quantify the cellular infiltration into the MI site. MPIO can produce pronounced signal attenuation at the region of interest in MRI. Therefore cells labeled with these particles could be detected after they were activated and homed to the myocardial infarction site. In the first project, MPIO of various doses were injected into the mouse blood stream 7 days before the MI surgery. Serial MRI was performed at various time points post-MI to monitor the inflammatory cellular infiltration to the MI site. Significant signal attenuation caused by labeled cells in particular macrophages was observed at the MI site. The study suggests an optimal imaging window between 7 and 14 days post-MI, during which the MR signal was negatively proportional to the MPIO dose. The study also suggests an optimal MPIO dose between 9.1 and 14.5 g Fe/g body weight. In the second project, mesenchymal stem cells labeled with MPIO were transplanted into the mouse bone marrow 14 days before the myocardial infarction surgery. MRI was performed at various time points post-MI to monitor the labeled cells, which mobilized from the bone marrow and homed to the MI site. All the MRI findings were further confirmed by histology. In addition to revealing the characteristics of cellular infiltration in the MI, this study also provides a noninvasive MRI technique to monitor and potentially quantify labeled cells at the pathological site. The technique can also be used to investigate the function of cells engaged in the MI and to test the effect on cellular infiltration caused by any treatment strategies.