title: Imaging brain neuronal activity using functionalized magnetonanoparticles and MRI.
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 (14)C-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.
authors.affiliation: Jane & Terry Semel Institute for Neuroscience & Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, CA, USA. akhtarim@ucla.edu
authors.forename: Massoud
authors.initials: M
authors.lastname: Akhtari
authors.forename: Anatol
authors.initials: A
authors.lastname: Bragin
authors.forename: Rex
authors.initials: R
authors.lastname: Moats
authors.forename: Andrew
authors.initials: A
authors.lastname: Frew
authors.forename: Mark
authors.initials: M
authors.lastname: Mandelkern
mesh_terms: D000344:Afferent Pathways / Q000502:physiology; D000818:Animals; D001921:Brain / Q000033:anatomy & histology* / Q000000981:diagnostic imaging; D001931:Brain Mapping; D003292:Convulsants / Q000633:toxicity; D003911:Dextrans / Q000378:metabolism*; D004195:Disease Models, Animal; D004558:Electric Stimulation; D004569:Electroencephalography; D005290:Ferric Compounds / Q000378:metabolism*; D007294:Inositol / Q000031:analogs & derivatives; D008279:Magnetic Resonance Imaging; D051379:Mice; D009474:Neurons / Q000378:metabolism*; D010433:Pentylenetetrazole / Q000633:toxicity; D010862:Pilocarpine / Q000633:toxicity; D011877:Radionuclide Imaging; D051381:Rats; D017207:Rats, Sprague-Dawley; D012146:Rest; D012640:Seizures / Q000139:chemically induced / Q000473:pathology; D014738:Vibrissae / Q000294:innervation
chemical_list: D003292:Convulsants; D003911:Dextrans; D005290:Ferric Compounds; D010862:Pilocarpine; C000499:ferric oxide; D007294:Inositol; C075548:2-deoxyinosose; D010433:Pentylenetetrazole