Magnetic resonance (MR) tracking of magnetically labeled stem and progenitor cells is an emerging technology, leading to an urgent need for magnetic probes that can make cells highly magnetic during their normal expansion in culture. We have developed magnetodendrimers as a versatile class of magnetic tags that can efficiently label mammalian cells, including human neural stem cells (NSCs) and mesenchymal stem cells (MSCs), through a nonspecific membrane adsorption process with subsequent intracellular (non-nuclear) localization in endosomes. The superparamagnetic iron oxide nanocomposites have been optimized to exhibit superior magnetic properties and to induce sufficient MR cell contrast at incubated doses as low as 1 microg iron/ml culture medium. When containing between 9 and 14 pg iron/cell, labeled cells exhibit an ex vivo nuclear magnetic resonance (NMR) relaxation rate (1/T2) as high as 24-39 s-1/mM iron. Labeled cells are unaffected in their viability and proliferating capacity, and labeled human NSCs differentiate normally into neurons. Furthermore, we show here that NSC-derived (and LacZ-transfected), magnetically labeled oligodendroglial progenitors can be readily detected in vivo at least as long as six weeks after transplantation, with an excellent correlation between the obtained MR contrast and staining for beta-galactosidase expression. The availability of magnetodendrimers opens up the possibility of MR tracking of a wide variety of (stem) cell transplants.

Myelin-specific T lymphocytes are considered essential in the pathogenesis of multiple sclerosis. The myelin basic protein peptide (a.a. 83-99) represents one candidate antigen; therefore, it was chosen to design an altered peptide ligand, CGP77116, for specific immunotherapy of multiple sclerosis. A magnetic resonance imaging-controlled phase II clinical trial with this altered peptide ligand documented that it was poorly tolerated at the dose tested, and the trial had therefore to be halted. Improvement or worsening of clinical or magnetic resonance imaging parameters could not be demonstrated in this small group of individuals because of the short treatment duration. Three patients developed exacerbations of multiple sclerosis, and in two this could be linked to altered peptide ligand treatment by immunological studies demonstrating the encephalitogenic potential of the myelin basic protein peptide (a.a. 83-99) in a subgroup of patients. These data raise important considerations for the use of specific immunotherapies in general.

A fundamental characteristic of working memory is that its capacity to handle information is limited. While there have been many brain mapping studies of working memory, the physiological basis of its capacity limitation has not been explained. We identified characteristics of working memory capacity using functional magnetic resonance imaging (fMRI) in healthy subjects. Working memory capacity was studied using a parametric 'n-back' working memory task involving increasing cognitive load and ultimately decreasing task performance. Loci within dorsolateral prefrontal cortex (DLPFC) evinced exclusively an 'inverted-U' shaped neurophysiological response from lowest to highest load, consistent with a capacity-constrained response. Regions outside of DLPFC, in contrast, were more heterogeneous in response and often showed early plateau or continuously increasing responses, which did not reflect capacity constraints. However, sporadic loci, including in the premotor cortex, thalamus and superior parietal lobule, also demonstrated putative capacity-constrained responses, perhaps arising as an upstream effect of DLPFC limitations or as part of a broader network-wide capacity limitation. These results demonstrate that regionally specific nodes within the working memory network are capacity-constrained in the physiological domain, providing a missing link in current explorations of the capacity characteristics of working memory.

Magnetic labeling of mammalian cells with use of ferumoxides and TAs is possible and may enable cellular MR imaging and tracking in experimental and clinical settings.

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