SUMMARY/ABSTRACT In this SBIR grant proposal, “Ultra-low distortion and noise electronics to enable a clinical MPI imaging platform,” we will develop the RF subsystem for a clinical magnetic particle imaging (MPI) platform to enable three classes of MPI applications: cell tracking, functional imaging, and endogenous contrast imaging. Our overall approach is to improve sensitivity and resolution by minimizing distortion, adding transmit/receive channels, decoupling, improving preamplifiers, and developing new pulse sequences. MPI is an emerging molecular and tracer imaging technology that directly detects magnetic nanoparticles (MNPs) with high sensitivity at mm-scale resolutions. MPI images are direct views of tracer distribution with no signal arising from tissue, no perturbations from materials such as air, and image intensity directly linear with tracer concentration. This “hot-spot” contrast provides spatial localization and quantification without ambiguity. MPI’s contrast is similar to nuclear medicine but without the workflow, safety, and half-life limitations of a radioactive tracer. MPI has many applications in the brain and body, as demonstrated by our customers in small animals. Despite significant efforts by multiple institutions, the lack of a clinical MPI scanner remains a significant limitation for the technique. In this Direct to Phase II SBIR proposal, we will advance the medical imaging field by building the world’s first general-purpose clinical MPI scanner to serve the myriad applications our customers are testing on our preclinical instrument. We will design and implement a new transmit/receive subsystem and install it in our prototype scanner to achieve the performance necessary for clinical imaging applications. This new transmit/receive subsystem includes the following innovations that push our sensitivity from our current rough prototype to near the physics limit through the following specific aims: Aim 1. Drive transmit distortion and the noise floor to the physics limit for a one-channel Tx/Rx coil Aim 2. Design a clinical multi-channel transmit and receive subsystem Aim 3. Develop new acquisition pulse sequences to improve sensitivity, resolution, and speed