Feasibility of MRI Quantification of Myelin Water Fraction in the Fetal Guinea Pig Brain

Abstract

Background Fetal myelination assessment is important for understanding neurodevelopment and neurodegeneration. Myelin water imaging (MWI) quantifies myelin water fraction (MWF), a validated marker for myelin content, and has been used to assess brain myelin in children and neonates. Purpose To demonstrate that MWI can quantify MWF in fetal guinea pigs (GPs). Study Type Animal model. Animal Model Nine pregnant, Dunkin‐Hartley GPs with 31 fetuses (mean ± standard deviation = 60 ± 1.5 days gestation). Field Strength/Sequence 3D spoiled gradient echo and balanced steady‐state free precession sequences at 3.0 T. Assessment MWF maps were reconstructed for maternal and fetal GP brains using the multicomponent driven equilibrium single pulse observation of T1 and T2 (mcDESPOT) approach. Myelin basic protein (MBP) stain provided histological validation of the MWF. Regions of interest were placed in the maternal corpus callosum (CC), maternal fornix (FOR), fetal CC, and fetal FOR in MWF maps and MBP stains. Statistical Tests Linear regression between MWF and MBP stain intensity (SI) of all four regions (coefficient of determination, R2). A paired t‐test compared the MWF of maternal and mean fetal CC, MBP SI of maternal and mean fetal CC, MWF of maternal and mean fetal FOR, MBP SI of maternal and mean fetal FOR. A paired t‐test with a linear mixed model compared the MWF of fetal CC and fetal FOR, and MBP SI of fetal CC and fetal FOR. A P value < 0.0083 was considered statistically significant. Results The mean MWF of the analyzed regions are as follows (mean ± standard deviation): 0.338 + 0.016 (maternal CC), 0.340 ± 0.017 (maternal FOR), 0.214 ± 0.016 (fetal CC), and 0.305 ± 0.025 (fetal FOR). MWF correlated with MBP SI in all regions (R2 = 0.81). Significant differences were found between MWF and MBP SI of maternal and fetal CC, and MWF and MBP SI of fetal CC and fetal FOR. Data Conclusion This study demonstrated the feasibility of MWI in assessing fetal brain myelin content. Evidence Level: 2 Technical Efficacy: Stage 1

Quantifying Myelin Water Fraction in a Guinea Pig Model of Spontaneous Intrauterine Growth Restriction

“…Although weight markers are commonly used in animal studies for IUGR determination, this study employed each weight marker's corresponding volume marker instead for human translational purposes. Furthermore, the strong correlation between weight and volume demonstrated in previous work further supported the use of volume markers (11). Hence, fetal body, brain, liver, and placental volumes were quantified using the T2-weighted images.…”

“…The feasibility of MWI has been successfully demonstrated in numerous animal models (10) and the fetal environment by quantifying MWF in a fetal guinea pig model (11). Preliminary results from the guinea pig work suggested that the MWF in the fetal corpus callosum and the fornix was lower in the fetuses with IUGR than in control fetuses (11). This current study builds on the pilot study by quantifying the difference in MWF in various brain regions.…”

“…Like the feasibility study, this study employed mcDESPOT as the technique for MWI. Hence, this study's imaging protocol was based on the protocol in the feasibility study, with the main difference being a decrease in voxel size to 0.6 mm 3 from 0.7 mm 2 (11). Since this study looked at only fetal brains as opposed to both fetal and maternal brains, the decrease in the field of view to only the uterus allowed increased resolution and improved identification of fetal brain structures.…”

“…The ROIs were placed on the T2-weighted images and then transferred to the MWF maps to quantity the regions' MWF values. Images from Sethi et al and Gareau et al were used for reference to identify the CC with the FOR and PSW located below and above the CC, respectively (11,23). The ROI placements were done blinded and before IUGR determination.…”

“…MWF is the ratio of the signal from myelin water to the signal from both myelin and intra-/extra-cellular water and is validated as a strong marker for myelin lipid (9). The feasibility of MWI has been successfully demonstrated in numerous animal models (10) and the fetal environment by quantifying MWF in a fetal guinea pig model (11). Preliminary results from the guinea pig work suggested that the MWF in the fetal corpus callosum and the fornix was lower in the fetuses with IUGR than in control fetuses (11).…”