Research Project
9775721
Magnetic Insight has developed a Magnetic Particle Imaging (MPI) product based on new pulse sequences and image reconstruction approaches. MPI is an emerging tracer imaging technology that is well suited for ultra- sensitive imaging of localized inflammation, using safe, low frequency magnetic fields to directly detect the spatial distribution of superparamagnetic iron oxide (SPIO) tracer. Localized inflammation is an attractive diagnostic imaging target for a variety of diseases and conditions. For example, the local accumulation of tumor-associated macrophages (TAMs) is a potential biomarker of metastatic aggressiveness. Nearly all medical imaging techniques have been used in some way to image localized inflammation, most notably MRI, nuclear medicine, and bioluminescence. However, no current diagnostic approach is ideal for imaging local inflammation, and current techniques suffer from limitations. New techniques are needed before localized inflammation imaging can be routinely used to diagnose, stage, and follow pathologies such as cancer. In our MPI platform, signal is only generated when the magnetic moments of the SPIOs rotate in response to the applied fields ? there is no signal from tissue. This imbues MPI with a positive ?hot-spot? contrast that provides spatial localization and quantification without ambiguity. As a tracer technique, MPI images resemble those taken with nuclear medicine and are often co-registered with an anatomic modality such as MRI or CT. The properties of the MPI signal are ideal for cell tracking applications, since MPI signal does not change with tissue depth, enabling linear quantification and longitudinal tracking for days to weeks. MPI is sensitive, with our early commercial systems already achieving a <250 labeled cell in vivo detection limits using optimized nanoparticle and sub-millimeter resolution [7]. With further development, significant improvements to the sensitivity and resolution limits are possible. SPIO tracers are biologically compatible, long lasting, non-radioactive, and have been used safely for decades in clinical MRI. The current grant application proposes to develop the technologies necessary for reliable, high-dynamic range MPI imaging of immune cells trafficking to a tumor. Our Specific Aims are: Aim 1: Development of MPI pulse sequences and reconstruction approaches optimized for high dynamic range, quantitative detection of immune cells in vicinity of the liver. Milestones: Detection limit of <10 ng Fe using Ferucarbotran. Improvement of dynamic range of a small signal 1 cm away from a large signal by an order of magnitude while introducing minimal ringing. Aim 2: In vivo imaging of immune cell density in murine breast cancer model, validated by MRI and histology. Milestones: MPI detection of immune cells trafficking to a tumor. Co-registration of MPI & MRI images. Absolute quantitation of immune cell density through MPI calibrated with histology.
