title: Quantitative assessment of central nervous system disorder induced by prenatal X-ray exposure using diffusion and manganese-enhanced MRI.
abstract: Prenatal radiation exposure induces various central nervous system (CNS) disorders depending on the dose, affected region and gestation period. The goal of this study was to assess noninvasively 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 (T(2)) maps in comparison with immunohistological staining. The changes in ΔR(1) (increase in the longitudinal relaxation rate (R(1)) from before and after MnCl(2) administration.) induced by the Mn(2+) contrast agent were evaluated in the CNS of normal and prenatally irradiated rats. ADC and T(2) were also compared with the histological results obtained using hematoxylin and eosin (to estimate cell density), activated caspase-3 (apoptotic cells) and glial fibrillary acidic protein (proliferation of astrocytes/astroglia). We found the following: (i) the decreased Mn(2+) uptake (indicated by a smaller ΔR(1)) for radiation-exposed rats was predominantly correlated with a decrease in cell viability (apoptotic cytopathogenicity) and CNS cell density after prenatal radiation exposure; (ii) the longer T(2) and ADC were associated with a decrease in CNS cell density and apoptotic alteration after radiation exposure. In addition to the slight proliferation of astroglia (+58%), there was a substantial decrease in cell density (-78%) and an excessive increase in apoptotic cells (+613%) 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/T(2) mapping provides objective information for the in vivo assessment of cellular level alterations by prenatal radiation exposure, and has the potential to be used as a standard approach for the evaluation of the cellular damage of radiotherapy.
authors.affiliation: Department of Molecular and Neuroimaging, Graduate School of Medicine, Tohoku University, Sendai, Japan.
authors.forename: Shigeyoshi
authors.initials: S
authors.lastname: Saito
authors.forename: Ichio
authors.initials: I
authors.lastname: Aoki
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Sawada
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Suhara
mesh_terms: D000818:Animals; D001921:Brain / Q000201:enzymology / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D002493:Central Nervous System Diseases / Q000175:diagnosis*; D004058:Diffusion; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D004789:Enzyme Activation; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D008345:Manganese / Q000008:administration & dosage; D009929:Organ Size; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000175:diagnosis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014965:X-Rays
chemical_list: D005904:Glial Fibrillary Acidic Protein; D008345:Manganese; D053148:Caspase 3