In vivo imaging of the nanoparticle-tissue interaction reveals processes which aid in the improvement of disease-specific markers. Magnetomotive optical coherence tomography (MM-OCT) may fill this role by imaging magnetic nanoparticles (Fe3O4, 20-30nm diameter) similar to those currently used for MRI contrast. This is performed by modulating a small (<20mm) electromagnet during conventional OCT imaging and detecting the induced displacement (magnetomotion) of the nanoparticles. In a recent advance, increased specificity was achieved using a 3-pulse sequence to measure the intrinsic background fluctuation to normalize the magnetomotive signal. In this way ghosting due to physiological and Brownian motion are eliminated. Silicone tissue phantoms which are both optically and mechanically similar to soft human tissue were used to measure the scaling of the magnetomotive signal with magnetic field strength, local optical scattering efficiency, and magnetic nanoparticle concentration. MM-OCT is sensitive to magnetite nanoparticles at a concentration of 220μg/g (P>.975), with the possibility of detecting even lower concentrations (63μg/g) with minor improvements. The MM-OCT signal exhibits a gentler falloff in depth (~4dB over 0.5mm) than conventional OCT imaging, limited ultimately by shot noise. The performance of MM-OCT was evaluated in vivo in a Xenopus laevis tadpole exposed to magnetic nanoparticles for 24 hours prior to imaging. Corresponding histology demonstrates the ability to correctly identify regions of high nanoparticle concentration with in vivo MM-OCT.© (2006) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.