Recent advances in nanotechnology have allowed for the effective use of iron oxide nanoparticles (IONPs) for cancer imaging and therapy. When activated by an alternating magnetic field (AMF), intra-tumoral IONPs have been effective at controlling tumor growth in rodent models. To accurately plan and assess IONP-based therapies in clinical patients, noninvasive and quantitative imaging technique for the assessment of IONP uptake and biodistribution will be necessary. Proven techniques such as confocal, light and electron microscopy, histochemical iron staining, ICP-MS, fluorescent labeled mNPs and magnetic spectroscopy of Brownian motion (MSB), are being used to assess and quantify IONPs in vitro and in ex vivo tissues. However, a proven noninvasive in vivo IONP imaging technique has not yet been developed. In this study we have demonstrated the shortcomings of computed tomography (CT) and magnetic resonance imaging (MRI) for effectively observing and quantifying iron/IONP concentrations in the clinical setting. Despite the poor outcomes of CT and standard MR sequences in the therapeutic concentration range, ultra-short T2 MRI methods such as, Sweep Imaging With Fourier Transformation (SWIFT), provide a positive iron contrast enhancement and a reduced signal to noise ratio. Ongoing software development and phantom and in vivo studies, will further optimize this technique, providing accurate, clinically-relevant IONP biodistribution information.