Longitudinal Evaluation Using Preclinical 7T-Magnetic Resonance Imaging/Spectroscopy on Prenatally Dose-Dependent Alcohol-Exposed Rats

Abstract

Prenatal alcohol exposure causes many detrimental alcohol-induced defects in children, collectively known as fetal alcohol spectrum disorders (FASD). This study aimed to evaluate a rat model of FASD, in which alcohol was administered at progressively increasing doses during late pregnancy, using preclinical magnetic resonance (MR) imaging (MRI) and MR spectroscopy (MRS). Wistar rats were orally administered 2.5 mL/day of ethanol (25% concentration) on gestational day 15, and postnatal fetuses were used as FASD models. Four groups were used: a control group (non-treatment group) and three groups of FASD model rats that received one, two, or four doses of ethanol, respectively, during the embryonic period. Body weight was measured every other week until eight weeks of age. MRI and MRS were performed at 4 and 8 weeks of age. The volume of each brain region was measured using acquired T2-weighted images. At 4 weeks of age, body weight and cortex volume were significantly lower in the three FASD model groups (2.5 × 1: 304 ± 6 mm3, p < 0.05; 2.5 × 2: 302 ± 8 mm3, p < 0.01; 2.5 × 4: 305 ± 6 mm3, p < 0.05) than they were in the non-treatment group (non-treatment: 313 ± 6 mm3). The FASD model group that received four doses of alcohol (2.5 × 4: 0.72 ± 0.09, p < 0.05) had lower Taurine/Cr values than the non-treatment group did (non-treatment: 0.91 ± 0.15), an effect that continued at 8 weeks of age (non-treatment: 0.63 ± 0.09; 2.5 × 4: 0.52 ± 0.09, p < 0.05). This study is the first to assess brain metabolites and volume over time using MRI and MRS. Decreases in brain volume and taurine levels were observed at 4 and 8 weeks of age, suggesting that the effects of alcohol persisted beyond adulthood.