Ten-Fold Resolution Boost for Magnetic Particle Imaging with Applications to Rapid, Non-Invasive Imaging of CAR-T Cell Therapies, Stroke, GI Bleeds and Pulmonary Embolisms

摘要

Abstract Magnetic Particle Imaging (MPI) is a new tracer imaging technology that could soon allow MDs to tell whether a CAR-T cell immunotherapy is actually targeting a tumor— with zero radiation, and in just 3 days. This is much safer and much faster than today’s practice of a followup PET/CT, which is too slow to allow for personalized immunotherapy care. MPI uses no radiation and yet it matches even the sensitivity of advanced nuclear medicine scans. MPI could soon revolutionize the early diagnosis of life-threatening Strokes, Traumatic Brain Injuries, Cardiovascular disease, Pulmonary Embolisms (PE), Gastrointestinal (GI) Bleeds and Cancer. In essence, MPI offers the the sensitivity of Nuclear Medicine with the safety of MRI. MPI is quantitative and robust everywhere in the body and it uses no radiation. MPI also is ideal for emergency diagnoses because MPI tracers can be bound to a targeting agent in the factory and then injected directly from the refrigerator. Hence, emergency MPI scans can be done in just 5 minutes with MPI, much faster than the 2 hours typical for nuclear medicine scans. We aim to remove the only technical weakness holding back MPI from clinical adoption, its weak spatial resolution. Our key innovation is to improve the spatial resolution of MPI by 10-fold in each di- mension. Our innovations span hardware, pulse sequences, reconstruction algorithms and the nanoscale physics and chemistry of innovative high-resolution MPI tracers. Our preliminary experiments show 10- fold (routinely) and 30-fold (occasionally) boost in resolution and SNR compared to the MPI standard, VivoTrax. Once our new tracers are made biocompatible they will pave the way for unprecedented 10- cell sensitivity at 2mm resolution in humans with a safe and affordable human MPI scanner, at roughly $100,000 hardware costs—a truly enabling advance. Our Specific Aims are to (1) Develop high-resolution MPI tracers shared between Industry and Academia; (2) Develop Engineering Tools for High Resolution MPI shared between academia and industry; and (3) In vivo scanning to prove the efficacy of high-resolution MPI. This Bioengineering Partnership with Industry is the ideal mechanism to foster this breakthrough in MPI resolution by a collaboration between three labs at UC Berkeley and a startup out of the PI’s lab (Magnetic Insight).