Non-invasive measurement of biochemical profiles in the healthy fetal brain

Neuroimage. 2020 Oct 1:219:117016. doi: 10.1016/j.neuroimage.2020.117016. Epub 2020 Jun 8.


Proton magnetic resonance spectroscopy (1H-MRS) of the fetal brain can be used to study emerging metabolite profiles in the developing brain. Identifying early deviations in brain metabolic profiles in high-risk fetuses may offer important adjunct clinical information to improve surveillance and management during pregnancy.

Objective: To investigate the normative trajectory of the fetal brain metabolites during the second half of gestation, and to determine the impact of using different Cramer-Rao Lower Bounds (CRLB) threshold on metabolite measurements using magnetic resonance spectroscopy.

Study design: We prospectively enrolled 219 pregnant women with normal fetal ultrasound and biometric measures. We performed a total of 331 fetal 1H-MRS studies with gestational age in the rage of 18-39 weeks with 112 of the enrolled participants scanned twice. All the spectra in this study were acquired on a GE 1.5 T scanner using long echo-time of 144 ​ms and analyzed in LCModel.

Results: We successfully acquired and analyzed fetal 1H-MRS with a success rate of 93%. We observed increases in total NAA, total creatine, total choline, scyllo inositol and total NAA-to-total choline ratio with advancing GA. Our results also showed faster increases in total NAA and total NAA-to-total choline ratio during the third trimester compared to the second trimester. We also observed faster increases in total choline and total NAA in female fetuses. Increasing the Cramer-Rao lower bounds threshold progressively from 100% to 40%-20% increased the mean metabolite concentrations and decreased the number of observations available for analysis.

Conclusion: We report serial fetal brain biochemical profiles in a large cohort of health fetuses studied twice in gestation with a high success rate in the second and third trimester of pregnancy. We present normative in-vivo fetal brain metabolite trajectories over a 21-week gestational period which can be used to non-invasively measure and monitor brain biochemistry in the healthy and high-risk fetus.

Keywords: CRLB; Fetal brain; Magnetic resonance spectroscopy; Metabolite trajectory; Metabolites; Normative.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aspartic Acid / metabolism
  • Brain / metabolism*
  • Choline / metabolism
  • Creatine / metabolism
  • Female
  • Fetal Development / physiology*
  • Gestational Age
  • Humans
  • Magnetic Resonance Imaging
  • Pregnancy
  • Pregnancy Trimester, Second / metabolism*
  • Pregnancy Trimester, Third / metabolism*
  • Prospective Studies
  • Proton Magnetic Resonance Spectroscopy / methods
  • Reference Values


  • Aspartic Acid
  • Creatine
  • Choline