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

Subechhya Pradhan; Kushal Kapse; Marni Jacobs; Nickie Niforatos-Andescavage; Jessica Lynn Quistorff; Catherine Lopez; Kathryn Lee Bannantine; Nicole Reinholdt Andersen; Gilbert Vezina; Catherine Limperopoulos

doi:10.1016/j.neuroimage.2020.117016

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.

Affiliations

¹ Center for the Developing Brain, Children's National Hospital, Washington, DC, 20010, USA; Department of Diagnostic Imaging and Radiology, Children's National Hospital, Washington, DC, 20010, USA; Department of Radiology, The George Washington University School of Medicine, Washington, DC, 20052, USA; Department of Pediatrics, The George Washington University School of Medicine, Washington, DC, 20052, USA.
² Center for the Developing Brain, Children's National Hospital, Washington, DC, 20010, USA.
³ Department of Biostatistics and Study Methodology, Children's Research Institute, Children's National Hospital, Washington, DC, 20010, USA; Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Diego, CA, 92093, USA.
⁴ Center for the Developing Brain, Children's National Hospital, Washington, DC, 20010, USA; Department of Pediatrics, The George Washington University School of Medicine, Washington, DC, 20052, USA; Division of Neonatology, Children's National Hospital, Washington, DC, 20010, USA.
⁵ Department of Diagnostic Imaging and Radiology, Children's National Hospital, Washington, DC, 20010, USA.
⁶ Center for the Developing Brain, Children's National Hospital, Washington, DC, 20010, USA; Department of Diagnostic Imaging and Radiology, Children's National Hospital, Washington, DC, 20010, USA; Department of Radiology, The George Washington University School of Medicine, Washington, DC, 20052, USA; Department of Pediatrics, The George Washington University School of Medicine, Washington, DC, 20052, USA. Electronic address: climpero@childrensnational.org.

Abstract

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

Substances

Aspartic Acid
Creatine
Choline

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

Authors

Affiliations

Abstract

Publication types

MeSH terms

Substances

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