Quantitative “Hot-Spot” Imaging of Transplanted Stem Cells Using Superparamagnetic Tracers and Magnetic Particle Imaging

TLDR

Magnetic labeling of stem cells permits non‑invasive MRI detection, yet MRI is limited to local engraftment visualization, confounded by endogenous hypointense contrast, and remains inherently non‑quantitative. The study aims to assess magnetic particle imaging (MPI) as a novel tomographic method for hot‑spot imaging and quantitative tracking of transplanted stem cells using superparamagnetic iron oxide tracers. Neural and mesenchymal stem cells were labeled with three SPIO formulations—including Feridex® and Resovist®—and imaged by MPI to evaluate signal response. MPI signal correlated linearly with iron content, allowing detection of as few as 5 × 10⁴ labeled cells in mouse brain, with signal ratios matching cell numbers and excellent agreement with MRI hypointense areas, underscoring MPI’s quantitative imaging potential.

Abstract

Magnetic labeling of stem cells enables their non-invasive detection by magnetic resonance imaging (MRI). Practically, most MRI studies have been limited to visualization of local engraftment as other sources of endogenous hypointense contrast complicate the interpretation of systemic (whole body) cell distribution. In addition, MRI cell tracking is inherently non-quantitative in nature. We report here on the potential of magnetic particle imaging (MPI) as a novel tomographic technique for non-invasive hot spot imaging and quantification of stem cells using superparamagnetic iron oxide (SPIO) tracers. Neural and mesenchymal stem cells, representing small and larger cell bodies, were labeled with three different SPIO tracer formulations, including two preparations that have previously been used in clinical MRI cell tracking studies (Feridex® and Resovist®). Magnetic particle spectroscopy (MPS) measurements demonstrated a linear correlation between MPI signal and iron content, for both homogeneous solutions of free particles in solution and for internalized and aggregated particles in labeled cells over a wide range of concentrations. The overall MP signal ranged from 1×10-3 - 3×10-4 Am2/g Fe, which was equivalent to 2×10-14 - 1×10-15 Am2 per cell, indicating that cell numbers can be quantified with MPI analogous to the use of radiotracers in nuclear medicine or fluorine tracers in 19F MRI. When SPIO-labeled cells were transplanted in mouse brain, they could be readily detected by MPI at a detection threshold of about 5×104 cells, with MPI/MRI overlays showing an excellent agreement between the hypointense MRI areas and MPI hot spots. The calculated tissue MPI signal ratio for 100,000 vs. 50,000 implanted cells was 2.08. Hence, MPI has potential to be further developed for quantitative and easy-to-interpret, tracer-based non-invasive imaging of cells, preferably with MRI as an adjunct anatomical imaging modality.