Imaging neuronal development with magnetic resonance imaging (NMR) microscopy

An ideal technique for following the development of the vertebrate nervous system would allow cells to be followed at the resolution of light microscopy at depths of several millimeters into the tissue. This would permit critical events to be followed at cellular or sub-cellular resolution even deep within the developing organism. To date, no technique has emerged with all of the needed properties. Light microscopy can follow a cell and its descendants after they have been labeled by either the infection of embryonic cells with a recombinant retrovirus or the microinjection of individual precursor cells with enzymes or fluorescent dyes. However, light microscopy cannot image events deeper than a few hundred micrometers within an embryo due to light scattering and aberrations in the objective lenses and other optics. Magnetic resonance imaging (MRI) does not suffer from these limitations, routinely being used to image in 3 dimensions through specimens as large as adult humans. However, it is relatively slow and, as implemented to date, it cannot routinely achieve cellular resolution. Here, we present our attempts to meet the technical challenges posed by in vivo MRI microscopy. As an example of both the progress and the future challenges, we present images of cells within the developing frog embryo over a several day time course.