Direct comparison between apparent diffusion coefficient and macromolecular proton fraction as quantitative biomarkers of the human fetal brain maturation

Background Apparent diffusion coefficient (ADC) is known as a quantitative biomarker of prenatal brain maturation. Fast macromolecular proton fraction (MPF) mapping is an emerging method for quantitative assessment of myelination that was recently adapted to fetal MRI. Purpose To compare the capability of ADC and MPF to quantify the normal fetal brain development. Study Type Prospective. Population Forty-two human fetuses in utero (gestational age [GA] = 27.7 +/- 6.0, range 20-38 weeks). Field Strength/Sequence 1.5 T; diffusion-weighted single-shot echo-planar spin-echo with five b-values for ADC mapping; spoiled multishot echo-planar gradient-echo with T-1, proton density, and magnetization transfer contrast weightings for single-point MPF mapping. Assessment Two operators measured ADC and MPF in the medulla, pons, cerebellum, thalamus, and frontal, occipital, and temporal cerebral white matter (WM). Statistical Tests Mixed repeated-measures analysis of variance (ANOVA) with the factors of pregnancy trimester and brain structure; Pearson correlation coefficient (r); Hotelling-Williams test to compare strengths of correlations. Results From the 2(nd) to 3(rd) trimester, ADC significantly decreased in the thalamus and cerebellum (P < 0.005). MPF significantly increased in the medulla, pons, thalamus, and cerebellum (P < 0.005). Cerebral WM had significantly higher ADC and lower MPF compared with the medulla and pons in both trimesters. MPF (r range 0.83, 0.89, P < 0.001) and ADC (r range -0.43, -0.75, P <= 0.004) significantly correlated with GA and each other (r range -0.32, -0.60, P <= 0.04) in the medulla, pons, thalamus, and cerebellum. No significant correlations or distinctions between regions and trimesters were observed for cerebral WM (P range 0.1-0.75). Correlations with GA were significantly stronger for MPF compared with ADC in the medulla, pons, and cerebellum (Hotelling-Williams test, P < 0.003) and similar in the thalamus. Structure-averaged MPF and ADC values strongly correlated (r = 0.95, P < 0.001). Data Conclusion MPF and ADC demonstrated qualitatively similar but quantitatively different spatiotemporal patterns. MPF appeared more sensitive to changes in the brain structures with prenatal onset of myelination. Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2019;50:52-61.