SUMMARY

Cardiovascular disease remains the leading cause of death in the developed countries. Experimental evidences strongly support the conclusion that inflammatory responses, accompanied by elevated levels of cytokines, are a common immunopathological feature following myocardial infarction (MI). Triggers of cytokine release post-MI lead to inflammatory-cell infiltration into the injured site, which produces a positive feedback of damaging responses. In spite of the established importance of inflammatory cell infiltration following MI, non-invasive monitoring strategies to assess localized inflammation and to monitor the characteristics of cell infiltration process are currently extremely limited. Consequently, improvements in imaging techniques to visualize cellular infiltration would greatly advance monitoring of therapeutic effects to both prevention and treatment of cardiovascular diseases. Our preliminary study demonstrated that inflammatory-cell infiltration post-MI can be temporally and non-invasively monitored using the micrometer-sized iron oxide particles (MPIO)-enhanced magnetic resonance imaging (MRI) technique at a dose level of 0.040 mg Fe/g body weight. As the continuation of the study, the dose level used to introvenously label the inflammatory cells warrants optimization. Therefore two lower doses, 0.010 and 0.025 mg Fe/g body weight respectively, are being investigated. The optimized dose should maitain the capability of the MPIO-enhanced MRI technique to monitor the cell infiltration while minimizing the dose received by the animal, thereby reducing the potential side effect or risk regarding to safty. Furthermore, the spatial information of localized inflmmation will be investigated and temporal characteristics of inflammatory-cell infiltration will be simulated. The optimization of this MPIO-enhanced MRI technique will provide a noval method to assist investigation of the inflammation process following MI.