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
Affiliations
Subechhya Pradhan
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
Kushal Kapse
Center for the Developing Brain, Children’s National Hospital, Washington, DC, 20010, USA
Marni Jacobs
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
Nickie Niforatos-Andescavage
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
Jessica Lynn Quistorff
Center for the Developing Brain, Children’s National Hospital, Washington, DC, 20010, USA
Catherine Lopez
Center for the Developing Brain, Children’s National Hospital, Washington, DC, 20010, USA
Kathryn Lee Bannantine
Center for the Developing Brain, Children’s National Hospital, Washington, DC, 20010, USA
Nicole Reinholdt Andersen
Center for the Developing Brain, Children’s National Hospital, Washington, DC, 20010, USA
Gilbert Vezina
Department of Diagnostic Imaging and Radiology, Children’s National Hospital, Washington, DC, 20010, USA
Catherine Limperopoulos
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; Corresponding author. 111 Michigan Ave NW, Washington, DC, 20010, USA.
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.
