Magnetic Particle Imaging (MPI) is an emerging non-invasive tomographic imaging modality; like CT or MRI, it could be applied in clinical and research settings as a safe diagnostic technique, but without ionizing radiation or toxic tracers. One of the major MPI challenges toward clinical translation has been the ability to scale up the coils to surround a human body while being able to generate and drive the sufficiently strong magnetic field gradient required for high spatial resolution. These requirements, however, demand prohibitively high power consumption in a device with cylindrical geometry; therefore, alternative topologies, such as an open geometry scanner, would be highly desirable. The goal of this proposal is to develop a novel single-sided MPI imager and demonstrate in vivo cancer imaging in rodents. The single-sided device has all the hardware on one side of the imaging volume; therefore, such a device can be used equally well on small animals and humans for multidimensional diagnostic imaging and as an MPI spectrometer (MPS). In our unique approach, we will develop a single-sided MPI imager with much more promising field topology, namely, field-free line (FFL) as opposed to the more common and relatively easier to implement field-free point (FFP) geometry, for a potential 10-fold increase of SNR, more robust image reconstruction, and larger field of view. To date, we have built a first prototype of a single-sided coils assembly with the FFL geometry that consists of all the required coils in a unilateral configuration. The measured magnetic field showed perfect agreement with the simulations. We further validated our device by demonstrating magnetic particle signal detection using a point-source phantom. Developing a fully capable multidimensional scanner based on single-sided geometry has direct clinical relevance in breast cancer imaging. We pursue two specific aims: 1) Develop a multidimensional imaging technique, which can be implemented in our single-sided device. The main objectives of this aim are to drastically increase the sensitivity of the device and identify an imaging sequence that combines both selection and excitation coils and works in tandem with our unique surface-coil receive approach. We will implement the required hardware modification and signal automation. 2) Validate the imaging method by obtaining the MPI images. The performance of the MPI scanner will be analyzed using phantoms with iron oxide nanoparticles. Finally, we will validate the scanner performance in in vivo imaging of breast tumor-bearing mice. The overall strength of the proposed research lies in developing the first ever MPI scanner that could potentially be translated to clinical settings. Specifically, we hope to deliver a more sensitive and non-invasive tool for breast cancer screening that has a direct impact on women health.