Development of a commercial Magnetic Particle Imaging platform for the detection and quantification of localized inflammation in cancer

Magnetic Insight has developed a Magnetic Particle ImagingMPIproduct based on new pulse sequences and image reconstruction approachesMPI is an emerging tracer imaging technology that is well suited for ultrasensitive imaging of localized inflammationusing safelow frequency magnetic fields to directly detect the spatial distribution of superparamagnetic iron oxideSPIOtracerLocalized inflammation is an attractive diagnostic imaging target for a variety of diseases and conditionsFor examplethe local accumulation of tumor associated macrophagesTAMsis a potential biomarker of metastatic aggressivenessNearly all medical imaging techniques have been used in some way to image localized inflammationmost notably MRInuclear medicineand bioluminescenceHoweverno current diagnostic approach is ideal for imaging local inflammationand current techniques suffer from limitationsNew techniques are needed before localized inflammation imaging can be routinely used to diagnosestageand follow pathologies such as cancerIn our MPI platformsignal is only generated when the magnetic moments of the SPIOs rotate in response to the applied fieldsthere is no signal from tissueThis imbues MPI with a positivehot spotcontrast that provides spatial localization and quantification without ambiguityAs a tracer techniqueMPI images resemble those taken with nuclear medicine and are often co registered with an anatomic modality such as MRI or CTThe properties of the MPI signal are ideal for cell tracking applicationssince MPI signal does not change with tissue depthenabling linear quantification and longitudinal tracking for days to weeksMPI is sensitivewith our early commercial systems already achieving a andltlabeled cell in vivo detection limits using optimized nanoparticle and sub millimeter resolutionWith further developmentsignificant improvements to the sensitivity and resolution limits are possibleSPIO tracers are biologically compatiblelong lastingnon radioactiveand have been used safely for decades in clinical MRIThe current grant application proposes to develop the technologies necessary for reliablehigh dynamic range MPI imaging of immune cells trafficking to a tumorOur Specific Aims areAimDevelopment of MPI pulse sequences and reconstruction approaches optimized for high dynamic rangequantitative detection of immune cells in vicinity of the liverMilestonesDetection limit of andltng Fe using FerucarbotranImprovement of dynamic range of a small signalcm away from a large signal by an order of magnitude while introducing minimal ringingAimIn vivo imaging of immune cell density in murine breast cancer modelvalidated by MRI and histologyMilestonesMPI detection of immune cells trafficking to a tumorCo registration of MPI andampMRI imagesAbsolute quantitation of immune cell density through MPI calibrated with histology Magnetic Insight has developed a Magnetic Particle ImagingMPIproduct based on new pulse sequences and image reconstruction approachesLocalized inflammation is an attractive diagnostic imaging target for a variety of diseases and conditionsWe will develop reliablehigh dynamic range MPI imaging of immune cells trafficking to a tumorby integrating pulse sequences and Fourier equalization techniques with optimized FISTA reconstruction