MRI scans were performed in myelin deficient animals in which magnetically labeled rat progenitor oligodendrocytes were implanted into lateral ventricles of the brain. MR imaging at clinically relevant magnetic field strengths was performed in vivo on brains and showed extensive migration of magnetically labeled grafted cells along the ventricles and into the olfactory lobe of these animals. Similar migration patterns were observed in the mono-phasic experimental allergic encephalomyelitis (EAE) rat model where iron oxide labeled embryonic stem cells were injected into the lateral ventricles and differentiated labeled neural cells were found in the surrounding parenchyma. MR images were correlated with histopathologic staining for iron, myelin, oligodendrocytes, astrocytes, and microglia. Both the Prussian blue and myelin staining closely matched the area of contrast enhancement seen on the MR images. Magnetically labeled encephalotigenic lymphocytes were intravenously infused as part of an adoptive transfer model of EAE in the mouse. Infiltration of labeled cells into the spinal cord and nerve roots of neurologically impaired mice was detected using in vivo magnetic resonance microscopy at 7T. This is the first demonstration of being able to track activated lymphocytes into the central nervous system in an autoimmune disease model and opens the possibility of monitoring the trafficking of pharmaceutically or genetically engineered cells into the brain to further the understanding of the pathophysiology of EAE and the pre-clinical evaluation of new cell-based therapies. Serial MRI studies performed in the marmoset model experimental autoimmune encephalomyelitis (EAE) are used for pre-clinical evaluation of heparin for multiple sclerosis (MS). Recently it has been recognized that there is an ischemic component associated with acute inflammatory EAE and MS lesions with fibrin deposition along activated endothelial cells. Subcutaneous heparin is used to prevent fibrin deposition within vessels as well as being an anti-inflammatory agent and having direct effects on T-cell and macrophage migration. Preliminary results comparing low and high dose heparin to placebo in the EAE marmoset model using clinical, pathologic and MRI evaluations as outcome measures revealed no therapeutic advantage in the heparin treated versus placebo treated animals. There was no difference in the between the high dose and placebo arms of the study in the incidence of hemorrhage into the spinal cords. Future studies are planned of using the EAE marmoset model as basis for harvesting stem cells and transplantation to determine if these cells will stimulate remyelination in EAE lesions.
