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 T₁ , 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.

Level of evidence: 2 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2019;50:52-61.