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Atherosclerosis is a significant contributor to cardiovascular disease, which is a leading cause of death in the United States. Optical imaging is emerging as a promising molecular imaging tool to detect the biomarkers of vascular disease and plaque vulnerability. We describe a Monte Carlo method of investigating the use of targeted fluorescent nanoparticles as a reporter agent for optical molecular imaging. In particular, we used the model to provide insight into the optimum excitation and emission wavelengths for in vivo imaging in the presence of blood and auto fluorescence.