In vivo evaluation of retinal and callosal projections in early postnatal development and plasticity using manganese-enhanced MRI and diffusion tensor imaging

The rodents are an excellent model for understanding the development and plasticity of the visual system. In this study, we explored the feasibility of Mn-enhanced MRI (MEMRI) and diffusion tensor imaging (DTI) at 7 T for in vivo and longitudinal assessments of the retinal and callosal pathways in normal neonatal rodent brains and after early postnatal visual impairments. Along the retinal pathways, unilateral intravitreal Mn2+ injection resulted in Mn2+ uptake and transport in normal neonatal visual brains at postnatal days (P) 1, 5 and 10 with faster Mn2+ clearance than the adult brains at P60. The reorganization of retinocollicular projections was also detected by significant Mn2+ enhancement by 2%-10% in the ipsilateral superior colliculus (SC) of normal neonatal rats, normal adult mice and adult rats after neonatal monocular enucleation (ME) but not in normal adult rats or adult rats after monocular deprivation (MD). DTI showed a significantly higher fractional anisotropy (FA) by 21% in the optic nerve projected from the remaining eye of ME rats compared to normal rats at 6 weeks old, likely as a result of the retention of axons from the ipsilaterally uncrossed retinal ganglion cells, whereas the anterior and posterior retinal pathways projected from the enucleated or deprived eyes possessed lower FA after neonatal binocular enucleation (BE), ME and MD by 22%-56%, 18%-46% and 11%-15% respectively compared to normal rats, indicative of neurodegeneration or immaturity of white matter tracts. Along the visual callosal pathways, intracortical Mn2+ injection to the visual cortex of BE rats enhanced a larger projection volume by about 74% in the V1/V2 transition zone of the contralateral hemisphere compared to normal rats, without apparent DTI parametric changes in the splenium of corpus callosum. This suggested an adaptive change in interhemispheric connections and spatial specificity in the visual cortex upon early blindness. The results of this study may help determine the mechanisms of axonal uptake and transport, microstructural reorganization and functional activities in the living visual brains during development, diseases, plasticity and early interventions in a global and longitudinal setting.