Magnetic Particle Imaging: A Novel in Vivo Imaging Platform for Cancer Detection

Abstract

Cancer remains one of the leading causes of death worldwide. Biomedical imaging plays a crucial role in all phases of cancer management. Physicians often need to choose the ideal diagnostic imaging modality for each clinical presentation based on complex trade-offs among spatial resolution, sensitivity, contrast, access, cost, and safety. Magnetic particle imaging (MPI) is an emerging tracer imaging modality that detects superparamagnetic iron oxide (SPIO) nanoparticle tracer with high image contrast (zero tissue background signal), high sensitivity (200 nM Fe) with linear quantitation, and zero signal depth attenuation. MPI is also safe in that it uses safe, in some cases even clinically approved, tracers and no ionizing radiation. The superb contrast, sensitivity, safety, and ability to image anywhere in the body lends MPI great promise for cancer imaging. In this study, we show for the first time the use of MPI for in vivo cancer imaging with systemic tracer administration. Here, long circulating MPI-tailored SPIOs were created and administered intravenously in tumor bearing rats. The tumor was highlighted with tumor-to-background ratio of up to 50. The nanoparticle dynamics in the tumor was also well-appreciated, with initial wash-in on the tumor rim, peak uptake at 6 h, and eventual clearance beyond 48 h. Lastly, we demonstrate the quantitative nature of MPI through compartmental fitting in vivo.

Keywords: Magnetic particle imaging; cancer imaging; medical imaging; nanoparticles.

Figure 1

(a) Illustration of Field Free Point (FFP) Magnetic Particle Imaging. A magnetic field gradient is created with NdFeB permanent magnets (green) and the FFP is shifted in x and y directions with electromagnets (yellow and red, respectively), and the animal bed is translated via a motor in the z direction. The FFP follows the specified trajectory through the sample in the FOV as shown, and a 3D MPI image is acquired. A maximum intensity projection of the 3D MPI image is shown. (b) Photograph of our custom-built FFP MPI scanner. (c) Plot of MPI signal from six samples of LS-008 particles from Lodespin Labs with concentrations ranging from 36 μg Fe/mL to 1.2 mg Fe/mL. SPIO signal in MPI is linear with SPIO concentration (R²= 0.99). (d) Representative bioluminescence image of the MDA-MD-231-luc xenograft tumor. (e) Corresponding maximum intensity projection of the 3D MPI image (shown FOV for lower abdomen: 4 × 4 × 5.8 cm) acquired 6 hours after injection of long circulating LS-008 particles from Lodespin Labs with CT overlay.

Figure 2

(a) Bright field TEM image of uncoated iron oxide cores of LS-008 and (inset) Selected Area Diffraction pattern showing crystal morphology and characteristic spinel diffraction rings. (b) MPS signal intensity vs. time of blood samples taken from female CD-1 mice following tail vein injection of 5 mg Fe/kg. (c) Hydrodynamic size measured by DLS. (d) Magnetization curves measured by VSM at room temperature.

Figure 3

Tracer Dynamics in Group A rats. Cropped FOV: 4 × 4 × 5.8 cm. Slices through the MPI volume over time are coregistered to corresponding CT slices and shown here. The exquisite contrast of MPI allows clear visualization of the dynamics: initial rim enhancement, followed by accumulation and then clearance.

Figure 4

Tracer Dynamics in Group B rats. Maximum intensity projection of 3D MPI volumes coregistered with a CT skeletal reference. The whole body tracer dynamics along with the tumor are clearly visualized.

Figure 5

(a) Group A two-compartment model fitting and biodistribution through time, n = 3. (b) Group B two-compartment model fitting and biodistribution through time, n = 3. (c) ex vivo MPI scan (right) and corresponding photograph (left) 2 days post SPIO injection.