Pediatric Radiology

, Volume 49, Issue 7, pp 941–950 | Cite as

Early proton magnetic resonance spectroscopy during and after therapeutic hypothermia in perinatal hypoxic–ischemic encephalopathy

  • Ashley M. LuckeEmail author
  • Anil N. Shetty
  • Joseph L. Hagan
  • Allison Walton
  • Tiffany D. Stafford
  • Zili D. Chu
  • Christopher J. Rhee
  • Jeffrey R. Kaiser
  • Magdalena Sanz Cortes
Original Article



Hypoxic–ischemic encephalopathy (HIE) remains a significant cause of mortality and neurodevelopmental impairment despite treatment with therapeutic hypothermia. Magnetic resonance H1-spectroscopy measures concentrations of cerebral metabolites to detect derangements in aerobic metabolism.


We assessed MR spectroscopy in neonates with HIE within 18–24 h of initiating therapeutic hypothermia and at 5–6 days post therapeutic hypothermia.

Materials and methods

Eleven neonates with HIE underwent MR spectroscopy of the basal ganglia and white matter. We compared metabolite concentrations during therapeutic hypothermia and post-therapeutic hypothermia and between moderate and severe HIE.


During therapeutic hypothermia, neonates with severe HIE had decreased basal ganglia N-acetylaspartate (NAA; 0.62±0.08 vs. 0.72±0.05; P=0.02), NAA + N-acetylaspartylglutamate (NAAG; 0.66±0.11 vs. 0.77±0.06; P=0.05), glycerophosphorylcholine + phosphatidylcholine (GPC+PCh; 0.28±0.05 vs. 0.38±0.06; P=0.02) and decreased white matter GPC+PCh (0.35±0.13 vs. 0.48±0.04; P=0.02) compared to neonates with moderate HIE. For all subjects, basal ganglia NAA decreased (−0.08±0.07; P=0.01), whereas white matter GPC+PCh increased (0.03±0.04; P=0.04) from therapeutic hypothermia MRI to post-therapeutic-hypothermia MRI. All metabolite values are expressed in mmol/L.


Decreased NAA and GPC+PCh were associated with greater HIE severity and could distinguish neonates who might benefit most from targeted additional neuroprotective therapies.


Brain Hypoxic–ischemic encephalopathy Magnetic resonance imaging Neonates Spectroscopy 


Compliance with ethical standards

Conflicts of interest

This research was supported by the Evangelina Whitlock Foundation Grant for fellows in Neonatal-Perinatal Medicine at the Baylor College of Medicine. Dr. Lucke wrote the first draft of the manuscript. There was no honorarium, grant or other form of payment given to anyone to produce the manuscript.


  1. 1.
    Douglas-Escobar M, Weiss MD (2015) Hypoxic-ischemic encephalopathy: a review for the clinician. JAMA Pediatr 169:397–403CrossRefPubMedGoogle Scholar
  2. 2.
    Shah PS (2010) Hypothermia: a systematic review and meta-analysis of clinical trials. Semin Fetal Neonatal Med 15:238–246CrossRefPubMedGoogle Scholar
  3. 3.
    Volpe JJ, Inder TE, du Plessis AJ et al (2018) Volpe’s neurology of the newborn, 6th edn. Elsevier, PhiladelphiaGoogle Scholar
  4. 4.
    Gunn AJ, Gunn TR, de Haan HH et al (1997) Dramatic neuronal rescue with prolonged selective head cooling after ischemia in fetal lambs. J Clin Invest 99:248–256CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Gluckman PD, Wyatt JS, Azzopardi D et al (2005) Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial. Lancet 365:663–670CrossRefPubMedGoogle Scholar
  6. 6.
    Shankaran S, Laptook AR, Ehrenkranz RA et al (2005) Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med 353:1574–1584CrossRefPubMedGoogle Scholar
  7. 7.
    Azzopardi DV, Strohm B, Edwards AD et al (2009) Moderate hypothermia to treat perinatal asphyxial encephalopathy. N Engl J Med 361:1349–1358CrossRefPubMedGoogle Scholar
  8. 8.
    Rollins N, Booth T, Morriss MC et al (2014) Predictive value of neonatal MRI showing no or minor degrees of brain injury after hypothermia. Pediatr Neurol 50:447–451CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Cady EB, Dawson MJ, Hope PL et al (1983) Non-invasive investigation of cerebral metabolism in newborn infants by phosphorus nuclear magnetic resonance spectroscopy. Lancet 1:1059–1062CrossRefPubMedGoogle Scholar
  10. 10.
    Amess PN, Penrice J, Wylezinska M et al (1999) Early brain proton magnetic resonance spectroscopy and neonatal neurology related to neurodevelopmental outcome at 1 year in term infants after presumed hypoxic-ischaemic brain injury. Dev Med Child Neurol 41:436–445PubMedGoogle Scholar
  11. 11.
    Zhu W, Zhong W, Qi J et al (2008) Proton magnetic resonance spectroscopy in neonates with hypoxic-ischemic injury and its prognostic value. Trans Res 152:225–232CrossRefGoogle Scholar
  12. 12.
    Bonifacio SL, Saporta A, Glass HC et al (2012) Therapeutic hypothermia for neonatal encephalopathy results in improved microstructure and metabolism in the deep gray nuclei. AJNR Am J Neuroradiol 33:2050–2055CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Wyatt JS, Edwards AD, Azzopardi D et al (1989) Magnetic resonance and near infrared spectroscopy for investigation of perinatal hypoxic-ischaemic brain injury. Arch Dis Child 64:953–963CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Lucke AM, Kaiser JR (2017) Encephalopathy. In: Fernandes CJ, Pammi M, Katakam L (eds) Guidelines for acute care of the neonate, 25th edn. Baylor College of Medicine, Houston, pp 122–124Google Scholar
  15. 15.
    Sarnat HB, Sarnat MS (1976) Neonatal encephalopathy following fetal distress a clinical and electroencephalographic study. Arch Neurol 33:696–705CrossRefPubMedGoogle Scholar
  16. 16.
    Bhakoo KK, Pearce D (2001) In vitro expression of N-acetyl aspartate by oligodendrocytes: implications for proton magnetic resonance spectroscopy signal in vivo. J Neurochem 74:254–262CrossRefGoogle Scholar
  17. 17.
    Wisnowski JL, Wu T, Reitman AJ et al (2016) The effects of therapeutic hypothermia on cerebral metabolism in neonates with hypoxic-ischemic encephalopathy: an in vivo 1H-MR spectroscopy study. J Cereb Blood Flow 36:1075–1086CrossRefGoogle Scholar
  18. 18.
    Boichot C, Walker PM, Durand C et al (2006) Term neonate prognoses after perinatal asphyxia: contributions of MR imaging, MR spectroscopy, relaxation times, and apparent diffusion coefficients. Radiology 239:839–848CrossRefPubMedGoogle Scholar
  19. 19.
    Kadri M, Shu S, Holshouser B et al (2003) Proton magnetic resonance spectroscopy improves outcome prediction in perinatal CNS insults. J Perinatol 23:181–185CrossRefPubMedGoogle Scholar
  20. 20.
    Gideon P, Henriksen O, Sperling B et al (1992) Early time course of N-acetylaspartate, creatine and phosphocreatine, and compounds containing choline in the brain after acute stroke. Stroke 23:1566–1572CrossRefPubMedGoogle Scholar
  21. 21.
    Li Y-K, Liu G-R, Zhou X et al (2010) Experimental hypoxic-ischemic encephalopathy: comparison of apparent diffusion coefficients and proton magnetic resonance spectroscopy. Magn Reson Imaging 28:487–494CrossRefPubMedGoogle Scholar
  22. 22.
    Miller SP, Newton N, Ferriero DM et al (2002) Predictors of 30-month outcome after perinatal depression: role of proton MRS and socioeconomic factors. Pediatr Res 52:71–77CrossRefPubMedGoogle Scholar
  23. 23.
    Barta H, Jermendy A, Kolossvary M et al (2018) Prognostic value of early, conventional proton magnetic resonance spectroscopy in cooled asphyxiated infants. BMC Pediatr 18:302CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Shibasaki J, Aida N, Morisaki N et al (2018) Changes in brain metabolite concentrations after neonatal hypoxic-ischemic encephalopathy. Radiology 288:840–848CrossRefPubMedGoogle Scholar
  25. 25.
    Cheong JL, Cady EB, Penrice J et al (2006) Proton MR spectroscopy in neonates with perinatal cerebral hypoxic-ischemic injury: metabolite peak-area ratios, relaxation times, and absolute concentrations. AJNR Am J Neuroradiol 27:1546–1554PubMedGoogle Scholar
  26. 26.
    Guo L, Wang D, Bo G et al (2016) Early identification of hypoxic-ischemic encephalopathy by combination of magnetic resonance (MR) imaging and proton MR spectroscopy. Exp Ther Med 12:2835–2842CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Fan G, Wu Z, Chen L et al (2003) Hypoxia-ischemic encephalopathy in full-term neonate: correlation proton MR spectroscopy with MR imaging. Eur J Radiol 45:91–98CrossRefPubMedGoogle Scholar
  28. 28.
    Holshouser BA, Ashwal S, Shu S et al (2000) Proton MR spectroscopy in children with acute brain injury: comparison of short and long echo time acquisitions. J Magn Reson Imaging 11:9–19CrossRefPubMedGoogle Scholar
  29. 29.
    Shu SK, Ashwal S, Holshouser BA et al (1997) Prognostic value of 1H-MRS in perinatal CNS insults. Pediatr Neurol 17:309–318CrossRefPubMedGoogle Scholar
  30. 30.
    Robertson NJ, Lewis RH, Cowan FM et al (2001) Early increases in brain myo-inositol measured by proton magnetic resonance spectroscopy in term infants with neonatal encephalopathy. Pediatr Res 50:692–700CrossRefPubMedGoogle Scholar
  31. 31.
    Ancora G, Soffritti S, Lodi R et al (2010) A combined a-EEG and MR spectroscopy study in term newborns with hypoxic-ischemic encephalopathy. Brain Dev 32:835–842CrossRefPubMedGoogle Scholar
  32. 32.
    Barkovich AJ, Westmark KD, Harvinder SB et al (2001) Proton spectroscopy and diffusion imaging on the first day of life after perinatal asphyxia: preliminary report. AJNR Am J Neuroradiol 22:1786–1794PubMedGoogle Scholar
  33. 33.
    Barkovich AJ, Miller SP, Bartha A et al (2006) MR imaging, MR spectroscopy, and diffusion tensor imaging of sequential studies in neonates with encephalopathy. AJNR Am J Neuroradiol 27:533–547PubMedGoogle Scholar
  34. 34.
    Garcias da Silva LF, Filho JRH, Anes M et al (2006) Prognostic value of 1H-MRS in neonatal encephalopathy. Pediatr Neurol 34:360–366CrossRefGoogle Scholar
  35. 35.
    Brissaud O, Chateil J-F, Bordessoules M et al (2005) Chemical shift imaging and localized magnetic resonance spectroscopy in full-term asphyxiated neonates. Pediatr Radiol 35:998–1005CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Ashley M. Lucke
    • 1
    • 2
    Email author
  • Anil N. Shetty
    • 3
  • Joseph L. Hagan
    • 2
  • Allison Walton
    • 2
  • Tiffany D. Stafford
    • 2
  • Zili D. Chu
    • 4
  • Christopher J. Rhee
    • 2
  • Jeffrey R. Kaiser
    • 5
  • Magdalena Sanz Cortes
    • 3
  1. 1.Fetal Medicine InstituteChildren’s National Health SystemWashingtonUSA
  2. 2.Department of Pediatrics (Neonatology)Baylor College of MedicineHoustonUSA
  3. 3.Department of Obstetrics and Gynecology, Baylor College of MedicineTexas Children’s Hospital Pavilion for WomenHoustonUSA
  4. 4.Department of RadiologyBaylor College of MedicineHoustonUSA
  5. 5.Departments of Pediatrics (Neonatal-Perinatal Medicine) and Obstetrics and GynecologyPenn State Health Children’s HospitalHersheyUSA

Personalised recommendations