Quantitative "Hot Spot" Imaging of Transplanted Stem Cells using Superparamagnetic Tracers and Magnetic Particle Imaging (MPI)

J W M Bulte; P Walczak; M Janowski; K M Krishnan; H Arami; A Halkola; B Gleich; J Rahmer

doi:10.18383/j.tom.2015.00172

Quantitative "Hot Spot" Imaging of Transplanted Stem Cells using Superparamagnetic Tracers and Magnetic Particle Imaging (MPI)

Tomography. 2015 Dec;1(2):91-97. doi: 10.18383/j.tom.2015.00172.

Authors

J W M Bulte¹, P Walczak², M Janowski², K M Krishnan³, H Arami³, A Halkola⁴, B Gleich⁵, J Rahmer⁵

Affiliations

¹ Russell H. Morgan Dept. of Radiology and Radiological Science, Division of MR Research and Cellular Imaging Section, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Dept. of Chemical & Biomolecular Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Dept. of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Dept. of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
² Russell H. Morgan Dept. of Radiology and Radiological Science, Division of MR Research and Cellular Imaging Section, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
³ University of Washington, Dept. of Materials Science and Dept. of Physics, Seattle, WA 98195, USA.
⁴ Philips Healthcare, Finland;
⁵ Philips GmbH Innovative Technologies, Research Laboratories Hamburg, Germany.

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.

Keywords: Magnetic particle imaging (MPI); cell tracking; stem cells; superparamagnetic iron oxide (SPIO).

Grants and funding

R01 DA026299/DA/NIDA NIH HHS/United States