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Micro-engineered local field control for high-sensitivity multispectral MRI


In recent years, biotechnology and biomedical research have benefited from the introduction of a variety of specialized nanoparticles whose well-defined, optically distinguishable signatures enable simultaneous tracking of numerous biological indicators. Unfortunately, equivalent multiplexing capabilities are largely absent in the field of magnetic resonance imaging (MRI). Comparable magnetic-resonance labels have generally been limited to relatively simple chemically synthesized superparamagnetic microparticles that are, to a large extent, indistinguishable from one another. Here we show how it is instead possible to use a top-down microfabrication approach to effectively encode distinguishable spectral signatures into the geometry of magnetic microstructures. Although based on different physical principles from those of optically probed nanoparticles, these geometrically defined magnetic microstructures permit a multiplexing functionality in the magnetic resonance radio-frequency spectrum that is in many ways analogous to that permitted by quantum dots in the optical spectrum. Additionally, in situ modification of particle geometries may facilitate radio-frequency probing of various local physiological variables.

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Figure 1: Magnetic structure and field diagrams.
Figure 2: Microfabricated magnetic structures.
Figure 3: Multi-spectral MRI.
Figure 4: Engineered spectral shifting.
Figure 5: Controlling diffusion to turn tags on or off.


  1. Lauterbur, P. C. Image formation by induced local interactions: Examples employing nuclear magnetic resonance. Nature 242, 190–191 (1973)

    ADS  CAS  Article  Google Scholar 

  2. Mansfield, P. & Grannell, P. K. NMR ‘diffraction’ in solids? J. Phys. C 6, L422–L426 (1973)

    ADS  CAS  Article  Google Scholar 

  3. Callaghan, P. T. Principles of Nuclear Magnetic Resonance Microscopy (Oxford Univ. Press, New York, 1991)

    Google Scholar 

  4. Nelson, K. L. & Runge, V. M. Basic principles of MR contrast. Top. Magn. Reson. Imag. 7, 124–136 (1995)

    CAS  Article  Google Scholar 

  5. Runge, V. M. & Wells, J. W. Update: Safety, new applications, new MR agents. Top. Magn. Reson. Imag. 7, 181–195 (1995)

    CAS  Google Scholar 

  6. Weissleder, R. et al. Ultrasmall superparamagnetic iron oxide: Characterization of a new class of contrast agents for MR imaging. Radiology 175, 489–493 (1990)

    CAS  Article  Google Scholar 

  7. Woods, M., Woessner, D. E. & Sherry, A. D. Paramagnetic lanthanide complexes as PARACEST agents for medical imaging. Chem. Soc. Rev. 35, 500–511 (2006)

    CAS  Article  Google Scholar 

  8. Lanza, G. M. et al. 1H/19F magnetic resonance molecular imaging with perfluorocarbon nanoparticles. Curr. Top. Dev. Bio. 70, 57–76 (2005)

    CAS  Article  Google Scholar 

  9. Mason, W. T. (ed.) Fluorescent and Luminescent Probes for Biological Activity (Academic, London, 1999)

    Google Scholar 

  10. Bruchez, M., Moronne, M., Gin, P., Weiss, S. & Alivisatos, A. P. Semiconductor nanocrystals as fluorescent biological labels. Science 281, 2013–2016 (1998)

    ADS  CAS  Article  Google Scholar 

  11. Chan, W. C. W. & Nie, S. Quantum dot bioconjugates for ultrasensitive nonisotopic detection. Science 281, 2016–2018 (1998)

    ADS  CAS  Article  Google Scholar 

  12. Alivisatos, P. The use of nanocrystals in biological detection. Nature Biotechnol. 22, 47–52 (2004)

    CAS  Article  Google Scholar 

  13. Elghanian, R., Storhoff, J. J., Mucic, R. C., Letsinger, R. L. & Mirkin, C. A. Selective colorimetric detection of polynucleotides based on the distance-dependent optical properties of gold nanoparticles. Science 277, 1078–1081 (1997)

    CAS  Article  Google Scholar 

  14. Haes, A. J. & Van Duyne, R. P. A nanoscale optical biosensor: Sensitivity and selectivity of an approach based on the localized surface plasmon resonance spectroscopy of triangular silver nanoparticles. J. Am. Chem. Soc. 124, 10596–10604 (2002)

    CAS  Article  Google Scholar 

  15. Nicewarner-Peña, S. R. et al. Submicrometer metallic barcodes. Science 294, 137–141 (2001)

    ADS  Article  Google Scholar 

  16. Dodd, S. J. et al. Detection of single mammalian cells by high-resolution magnetic resonance imaging. Biophys. J. 76, 103–109 (1999)

    ADS  CAS  Article  Google Scholar 

  17. Cunningham, C. H. et al. Positive contrast magnetic resonance imaging of cells labeled with magnetic nanoparticles. Magn. Reson. Med. 53, 999–1005 (2005)

    CAS  Article  Google Scholar 

  18. Bulte, J. W. M. et al. Magnetodendrimers allow endosomal magnetic labeling and in vivo tracking of stem cells. Nature Biotechnol. 19, 1141–1147 (2001)

    CAS  Article  Google Scholar 

  19. Hinds, K. A. et al. Highly efficient endosomal labeling of progenitor and stem cells with large magnetic particles allows magnetic resonance imaging of single cells. Blood 102, 867–872 (2003)

    CAS  Article  Google Scholar 

  20. Shapiro, E. M., Skrtic, S. & Koretsky, A. P. Sizing it up: Cellular MRI using micron-sized iron oxide particles. Magn. Reson. Med. 53, 329–338 (2005)

    Article  Google Scholar 

  21. Wu, Y. L. et al. In situ labeling of immune cells with iron oxide particles: An approach to detect organ rejection by cellular MRI. Proc. Natl Acad. Sci. USA 103, 1852–1857 (2006)

    ADS  CAS  Article  Google Scholar 

  22. Kotzar, G. et al. Evaluation of MEMS materials of construction for implantable medical devices. Biomaterials 23, 2737–2750 (2002)

    CAS  Article  Google Scholar 

  23. Voskerician, G. et al. Biocompatibility and biofouling of MEMS drug delivery devices. Biomaterials 24, 1959–1967 (2003)

    CAS  Article  Google Scholar 

  24. Chikazumi, S. Physics of Ferromagnetism (Oxford Univ. Press, New York, 1997)

    Google Scholar 

  25. Bozorth, R. M. Ferromagnetism (Van Nostrand, New York, 1951)

    Google Scholar 

  26. Sato, M., Wond, T. Z. & Allen, R. D. Rheological properties of living cytoplasm: Endoplasm of Physarum plasmodium. J. Cell Biol. 97, 1089–1097 (1983)

    CAS  Article  Google Scholar 

  27. Ashkin, A. & Dziedzic, J. M. Internal cell manipulation using infrared laser traps. Proc. Natl Acad. Sci. USA 86, 7914–7918 (1989)

    ADS  CAS  Article  Google Scholar 

  28. Henkelman, R. M., Stanisz, G. J. & Graham, S. J. Magnetization transfer in MRI: A review. NMR Biomed. 14, 57–64 (2001)

    CAS  Article  Google Scholar 

  29. Zurkiya, O. & Hu, X. Off-resonance saturation as a means of generating contrast with superparamagnetic nanoparticles. Magn. Reson. Med. 56, 726–732 (2006)

    Article  Google Scholar 

  30. Grad, J. & Bryant, R. G. Nuclear magnetic cross-relaxation spectroscopy. J. Magn. Reson. 90, 1–8 (1990)

    ADS  CAS  Google Scholar 

  31. Olson, D. L., Peck, T. L., Webb, A. G., Magin, R. L. & Sweedler, J. V. High-resolution microcoil 1H-NMR for mass-limited nanoliter-volume samples. Science 270, 1967–1970 (1995)

    ADS  CAS  Article  Google Scholar 

  32. Shellock, F. G. & Kanal, E. Safety of magnetic resonance imaging contrast agents. J. Magn. Reson. Imag. 10, 477–484 (1999)

    CAS  Article  Google Scholar 

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We thank the Mouse Imaging Facility at the NIH for use of the 4.7T magnet, and A. Silva for use of the 7T magnet. This work was supported in part by the NINDS NIH Intramural Research Program. G.Z. also acknowledges support from a National Research Council fellowship award.

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Correspondence to Gary Zabow.

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Zabow, G., Dodd, S., Moreland, J. et al. Micro-engineered local field control for high-sensitivity multispectral MRI. Nature 453, 1058–1063 (2008).

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