Detection threshold of single SPIO‐labeled cells with FIESTA

MRI of superparamagnetic iron oxide (SPIO)‐labeled cells has become a valuable tool for studying the in vivo trafficking of transplanted cells. Cellular detection with MRI is generally considered to be orders of magnitude less sensitive than other techniques, such as positron emission tomography (PET), single photon emission‐computed tomography (SPECT), or optical fluorescence microscopy. However, an analytic description of the detection threshold for single SPIO‐labeled cells and the parameters that govern detection has not been adequately provided. In the present work, the detection threshold for single SPIO‐labeled cells and the effect of resolution and SNR were studied for a balanced steady‐state free precession (SSFP) sequence (3D‐FIESTA). Based on the results from both theoretical and experimental analyses, an expression that predicts the minimum detectable mass of SPIO (mc) required to detect a single cell against a uniform signal background was derived: mc = 5v/(Kfsl · SNR), where v is the voxel volume, SNR is the image signal‐to‐noise ratio, and Kfsl is an empirical constant measured to be 6.2 ± 0.5 × 10−5 μl/pgFe. Using this expression, it was shown that the sensitivity of MRI is not very different from that of PET, requiring femtomole quantities of SPIO iron for detection under typical micro‐imaging conditions (100 μm isotropic resolution, SNR = 60). The results of this work will aid in the design of cellular imaging experiments by defining the lower limit of SPIO labeling required for single cell detection at any given resolution and SNR. Magn Reson Med 53:312–320, 2005. © 2005 Wiley‐Liss, Inc.

[1]  S. Canevari,et al.  Comparison of three different methods for radiolabelling human activated T lymphocytes , 1997, European Journal of Nuclear Medicine.

[2]  H. Mao,et al.  Magnetic Resonance Imaging of Activated Proliferating Rhesus Macaque T Cells Labeled With Superparamagnetic Monocrystalline Iron Oxide Nanoparticles , 2004, Journal of acquired immune deficiency syndromes.

[3]  Michael E. Phelps,et al.  PET: A biological imaging technique , 1991, Neurochemical Research.

[4]  Heather Kalish,et al.  Characterization of biophysical and metabolic properties of cells labeled with superparamagnetic iron oxide nanoparticles and transfection agent for cellular MR imaging. , 2003, Radiology.

[5]  Jeff W M Bulte,et al.  Intracytoplasmic tagging of cells with ferumoxides and transfection agent for cellular magnetic resonance imaging after cell transplantation: methods and techniques , 2003, Transplantation.

[6]  R. Weissleder,et al.  In vivo high resolution three-dimensional imaging of antigen-specific cytotoxic T-lymphocyte trafficking to tumors. , 2003, Cancer research.

[7]  Alan P Koretsky,et al.  Highly efficient endosomal labeling of progenitor and stem cells with large magnetic particles allows magnetic resonance imaging of single cells. , 2003, Blood.

[8]  E T Ahrens,et al.  Receptor‐mediated endocytosis of iron‐oxide particles provides efficient labeling of dendritic cells for in vivo MR imaging , 2003, Magnetic resonance in medicine.

[9]  Brian K Rutt,et al.  Imaging single mammalian cells with a 1.5 T clinical MRI scanner , 2003, Magnetic resonance in medicine.

[10]  S. Gambhir,et al.  Molecular imaging in living subjects: seeing fundamental biological processes in a new light. , 2003, Genes & development.

[11]  K. Scheffler,et al.  Is TrueFISP a gradient‐echo or a spin‐echo sequence? , 2003, Magnetic resonance in medicine.

[12]  Mathias Hoehn,et al.  Monitoring of implanted stem cell migration in vivo: A highly resolved in vivo magnetic resonance imaging investigation of experimental stroke in rat , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[13]  Scott E. Fraser,et al.  Tracking Transplanted Stem Cell Migration Using Bifunctional, Contrast Agent-Enhanced, Magnetic Resonance Imaging , 2002, NeuroImage.

[14]  B. Rutt,et al.  Application of the static dephasing regime theory to superparamagnetic iron‐oxide loaded cells , 2002, Magnetic resonance in medicine.

[15]  Michael E. Phelps,et al.  Ex vivo cell labeling with 64Cu–pyruvaldehyde-bis(N4-methylthiosemicarbazone) for imaging cell trafficking in mice with positron-emission tomography , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[16]  J. Bulte,et al.  Magnetic intracellular labeling of mammalian cells by combining (FDA-approved) superparamagnetic iron oxide MR contrast agents and commonly used transfection agents. , 2002, Academic radiology.

[17]  Peter van Gelderen,et al.  Magnetodendrimers allow endosomal magnetic labeling and in vivo tracking of stem cells , 2001, Nature Biotechnology.

[18]  R Weissleder,et al.  Normal T-cell response and in vivo magnetic resonance imaging of T cells loaded with HIV transactivator-peptide-derived superparamagnetic nanoparticles. , 2001, Journal of immunological methods.

[19]  S A Wickline,et al.  Novel MRI Contrast Agent for Molecular Imaging of Fibrin: Implications for Detecting Vulnerable Plaques , 2001, Circulation.

[20]  C Zimmer,et al.  Magnetic labeling of activated microglia in experimental gliomas. , 2001, Neoplasia.

[21]  Ralph Weissleder,et al.  Tat peptide-derivatized magnetic nanoparticles allow in vivo tracking and recovery of progenitor cells , 2000, Nature Biotechnology.

[22]  J A Frank,et al.  Neurotransplantation of magnetically labeled oligodendrocyte progenitors: magnetic resonance tracking of cell migration and myelination. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[23]  G A Johnson,et al.  Detection of neuritic plaques in Alzheimer's disease by magnetic resonance microscopy. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[24]  R. Brooks,et al.  Relaxometry and magnetometry of the MR contrast agent MION‐46L , 1999, Magnetic resonance in medicine.

[25]  Donald S. Williams,et al.  Detection of single mammalian cells by high-resolution magnetic resonance imaging. , 1999, Biophysical journal.

[26]  H. Benveniste,et al.  Nervous System Defects of AnkyrinB (−/−) Mice Suggest Functional Overlap between the Cell Adhesion Molecule L1 and 440-kD AnkyrinB in Premyelinated Axons , 1998, The Journal of cell biology.

[27]  T. Irimura,et al.  Tumor cells with organ-specific metastatic ability show distinctive trafficking in vivo: analyses by positron emission tomography and bioimaging. , 1997, Cancer research.

[28]  J. Hamers,et al.  [Methods and techniques]. , 1997, Verpleegkunde.

[29]  C Zimmer,et al.  MR imaging of phagocytosis in experimental gliomas. , 1995, Radiology.

[30]  T. Irimura,et al.  Real-time PET analysis of metastatic tumor cell trafficking in vivo and its relation to adhesion properties. , 1995, Biochimica et biophysica acta.

[31]  R K Jain,et al.  A method for labeling cells for positron emission tomography (PET) studies. , 1994, Journal of immunological methods.

[32]  T Irimura,et al.  Positron emission tomography analysis of metastatic tumor cell trafficking. , 1994, Cancer research.

[33]  C. Springer,et al.  Bulk magnetic susceptibility shifts in nmr studies of compartmentalized samples: use of paramagnetic reagents , 1990, Magnetic resonance in medicine.

[34]  R. Kavet,et al.  Phagocytosis: quantification of rates and intercellular heterogeneity. , 1977, Journal of applied physiology: respiratory, environmental and exercise physiology.

[35]  R. Freeman,et al.  Phase and intensity anomalies in fourier transform NMR , 1971 .

[36]  A. Rose The sensitivity performance of the human eye on an absolute scale. , 1948, Journal of the Optical Society of America.