Nicholas Hawrylak, Pratik Ghosh, Julie Broadus, Carol Schlueter, William T. Greenough, Paul C. Lauterbur

Nuclear magnetic resonance (NMR) imaging in vivo of adult rat brains was used to observe the fate of iron oxide-labeled intracerebral neural grafts. The host animals received grafts of fetal (E17-E18) rat tissue prepared as cell suspensions and labeled by incubation with reconstituted Sendai viral envelopes containing iron oxide particles. Control studies were performed in animals following surgical trauma alone or transplantation of unlabeled cell suspensions. In vivo NMR imaging (either two-dimensional Fourier transform or three-dimensional Fourier transform) was performed once on each animal between 5 and 60 days postsurgery. The NMR images of the host brains containing the labeled cells showed sufficient anatomical detail for the identification of the major brain structures. The graft sites were seen in the T2-weighted NMR images as dark regions (low-intensity signal) in the cortex. Histochemical staining for ferric iron (prussian blue stain) demonstrated the presence of numerous prussian blue-positive cells in tissue sections corresponding to the dark regions in the NMR images. Surviving prussian blue-positive cells with neuron-like morphology were relatively more numerous 10 days after transplantation than at 1-2 months postgrafting. The NMR images and immunohistochemical and histochemical staining of hosts containing labeled cells suggest cell migration of astrocytes and macrophages up to 2 mm away from the graft sites. The migrating cells were primarily along fiber tracts in the host white matter. Prussian blue deposits were also present within the brains of the control animals, but the NMR images from the same animals did not contain distinct dark regions like those in the images of brains which had received labeled cell transplants. These results demonstrate that NMR imaging can be used to study cell survival and migration following neural grafting procedures.