Of Molecules and Magnets: Designer Contrast Agents for Better Looking MRI

Organizers: Joseph Helpern and Jens Jensen, New York University School of Medicine; James Canary, Chemistry Department, New York University

The Imaging Discussion Group meets periodically to explore the state of imaging as applied to the most important scientific questions of the day. Meetings focus on particular themes as they relate to a biological problem and will aim to put the use of imaging technologies (MR spectroscopy, fMRI, MRI, PET, optical imaging, magnetoencephalography, and image processing) into the context of these biological questions. This group is part of the Frontiers of Science Program.

Program

Erik Shapiro, National Institutes of Health, National Institutes of Health, New York University School of Medicine, "Sizing Up Cellular Magnetic Resonance Imaging."

Daniel Turnbull, New York University: "Contrast-Enhanced micro-MRI of Mouse Brain Development."

Youssef Zaim Wadghiri, New York University School of Medicine, "Mapping Molecular Signatures of Diseases with Magnetic Resonance Imaging: Towards an Early Diagnosis in Alzheimer's and Prion Diseases."

Ivan Dmochowski, University of Pennsylvania, "¹²⁹Xe MRI Biosensors: Sensitive Probes for Cancer Biomarker Detection."

Abstract

"Sizing Up Cellular Magnetic Resonance Imaging"
Erik Shapiro
The usefulness of micron sized iron oxide particles (MPIOs) for magnetic labeling of cells for cellular MRI has recently been established. A variety of cell types can be labeled in culture by simple incubation of cells with particles, allowing for the MRI detection of single cells in vitro harboring even just single 1.63 micron diameter MPIOs. Indeed, single 0.96 micron MPIOs have been detected in single cells in 11.5 day old mouse embryos following injection of the fertilized single cell and subsequent re-implantation. This talk will focus on in vivo cell labeling of neural stem cells and MRI detection of neural precursor migration from the subventricular zone (SVZ) to the olfactory bulb (OB). The SVZ is a neurogenic center in the rodent brain. Here, neural stem cells lining the lateral cerebral ventricles produce neural progenitors which migrate within the rostral migratory stream exclusively to the OB. This migration was observed by directly labeling the stem cells in the SVZ by injection of MPIOs into the ventricle. Once particles are endocytosed by the neural stem cells, through asymmetric cell division, the particles are transferred to the daughter neural progenitors and carried along during their migration. This is the first demonstration of in vivo cell labeling of any cell other than blood born cells and the first observation of endogenous stem cell migration by MRI.

"Contrast-Enhanced micro-MRI of Mouse Brain Development"
Daniel Turnbull
Extensive genetic information and the expanding number of techniques available to manipulate the genome of the mouse have led to its widespread use in studies of brain development and to model human neurological diseases. Motivated by the this revolution in developmental genetics, we have developed a number of magnetic resonance micro-imaging (micro-MRI) approaches to allow in vivo analysis of brain development in normal and genetically-engineered mice. In this area, paramagnetic contrast agents are providing critical new information at the cellular and molecular levels. Topics to be discussed will include a novel manganese-enhanced MRI method for mapping neural activity in the mouse auditory system, and the transgenic expression of proteins involved in uptake and storage of iron as a genetic approach for controlling cellular MRI contrast.