Quantitative assessment of central nervous system disorder induced by prenatal X-ray exposure using diffusion and manganese-enhanced MRI

Prenatal radiation-exposure induces various central nervous system (CNS) disorders depending on the dose, affected region and gestation-period. The goal of this study is to non-invasively assess a CNS development disorder induced by prenatal X-ray exposure using quantitative manganese-enhanced MRI (MEMRI) as well as apparent diffusion coefficient (ADC) and transverse relaxation time (T2) maps in comparison to immunohistological stainings. Changes in delta R1 (increment of the relaxation rate before and after MnCl2 administration) induced by Mn2+ contrast agent were evaluated in the CNS of normal and prenatally irradiated rats. The ADC and T2 were also compared to histological results obtained using Hematoxylin-Eosin (HE; to estimate cell density), Activated Caspase-3 (apoptotic cells), and Glial fibrillary acidic protein (GFAP; proliferation of astrocytes/astroglia). We found that: 1) a decreased Mn2+ uptake (as indicated by smaller delta R1) for radiation-exposed rats were predominantly correlated with a decrease of cell viability (apoptotic cytopathogenicity) and CNS cell density after prenatal radiation exposure; 2) longer T2 and ADC were associated with a decrease in CNS cell density and apoptotic alteration after radiation exposure. In addition to a slight proliferation of astroglia (+58%), a substantial decrease in cell density (-78%) and an excessive increase of apoptotic cells (+613%) observed in our prenatal radiation-exposure model. The results suggest that MEMRI in the prenatal X-ray exposure model predominantly reflected the decrease in cell density and viability rather than the proliferation of astroglia. In conclusion, quantitative MEMRI with ADC/T2 mapping provide objective information for in vivo assessment of cellular-level alterations by prenatal radiation-exposure, and potentially becoming a standard approach for evaluating cellular-damage of radiotherapy