Brain Topography

, Volume 25, Issue 4, pp 374–388 | Cite as

Imaging Brain Neuronal Activity Using Functionalized Magnetonanoparticles and MRI

  • Massoud Akhtari
  • Anatol Bragin
  • Rex Moats
  • Andrew Frew
  • Mark Mandelkern
Original Paper

Abstract

This study explored the use of non-radioactive 2-deoxy glucose (2DG)-labeled magnetonanoparticles (MNP) and magnetic resonance imaging (MRI) to detect functional activity during rest, peripheral stimulation, and epileptic seizures, in animal models. Non-radioactive 2DG was covalently attached to magnetonanoparticles composed of iron oxide and dextran and intravenous (tail) injections were performed. 2DG-MNP was injected in resting and stimulated naïve rodents and the subsequent MRI was compared to published 14C-2DG autoradiography data. Reproducibility and statistical significance was established in one studied model. Negative contrast enhancement (NCE) in acute seizures and chronic models of epilepsy were investigated. MRI NCE due to 2DG-MNP particles was compared to that of plain (unconjugated) MNP in one animal. NCE due to 2DG-MNP particles at 3 T, which is approved for human use, was also investigated. Histology showed presence of MNP (following intravenous injection) in the brain tissues of resting naïve animal. 2DG-MNP intraparenchymal uptake was visible on MRI and histology. The locations of NCE agreed with published results of 2DG autoradiography in resting and stimulated animals and epileptic rats. Localization of epileptogenicity was confirmed by subsequent depth-electrode EEG (iEEG). Non-radioactive 2DG-MNP can cross the blood–brain barrier (BBB) and may accurately localize areas of increased activity. Although, this proof-of-principle study involves only a limited number of animals, and much more research and quantification are necessary to demonstrate that 2DG-MNP, or MNPs conjugated with other ligands, could eventually be used to image localized cerebral function with MRI in humans, this MNP-MRI approach is potentially applicable to the use of many bioactive molecules as ligands for imaging normal and abnormal localized cerebral functions.

Keywords

Magnetonanoparticles Targeted Brain Function 2-deoxy glucose MRI Contrast 

Notes

Acknowledgement

The authors are greatly indebted to Drs Gevorg Karapetian, and Ira Harutyunyan for their invaluable help and input with acquisition of the MR images. The authors are also indebted Dr Leonard Rome of UCLA School of Medicine Dean’s Office for his foresight and support of this project. This Work was supported by generous grants from Stein/Oppenheimer Award, Jane & Terry Semel Institute for Neuroscience & Human Behavior Chairman’s and Opportunity funds, as well as, Office of the Dean, David Geffen School of Medicine, Davis Fund. This technology is owned by the University of California, and Dr. Akhtari has received royalty payments from the University of California during the past 3 years. None of the other authors has any conflict of interest. We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Massoud Akhtari
    • 1
    • 5
  • Anatol Bragin
    • 2
  • Rex Moats
    • 3
  • Andrew Frew
    • 2
  • Mark Mandelkern
    • 4
  1. 1.Jane & Terry Semel Institute for Neuroscience & Human BehaviorDavid Geffen School of Medicine, University of CaliforniaLos AngelesUSA
  2. 2.Department of NeurologyDavid Geffen School of Medicine, University of CaliforniaLos AngelesUSA
  3. 3.Department of RadiologyChildren’s Hospital of Los Angeles, University of Southern CaliforniaLos AngelesUSA
  4. 4.Department of PhysicsUniversity of CaliforniaIrvineUSA
  5. 5.Los AngelesUSA

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