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Cerebral oxygen metabolism during and after therapeutic hypothermia in neonatal hypoxic–ischemic encephalopathy: a feasibility study using magnetic resonance imaging

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Abstract

Background

Therapeutic hypothermia is the standard-of-care treatment for infants diagnosed with moderate-to-severe hypoxic–ischemic encephalopathy (HIE). MRI for assessing brain injury is usually performed after hypothermia because of logistical challenges in bringing acutely sick infants receiving hypothermia from the neonatal intensive care unit (NICU) to the MRI suite. Perhaps examining and comparing early cerebral oxygen metabolism disturbances to those after rewarming will lead to a better understanding of the mechanisms of brain injury in HIE and the effects of therapeutic hypothermia.

Objective

The objectives were to assess the feasibility of performing a novel T2-relaxation under spin tagging (TRUST) MRI technique to measure venous oxygen saturation very early in the time course of treatment, 18–24 h after the initiation of therapeutic hypothermia, to provide a framework to measure neonatal cerebral oxygen metabolism noninvasively, and to compare parameters between early and post-hypothermia MRIs.

Materials and methods

Early (18–24 h after initiating hypothermia) MRIs were performed during hypothermia treatment in nine infants with HIE (six with moderate and three with severe HIE). Six infants subsequently had an MRI after hypothermia. Mean values of cerebral blood flow, oxygen extraction fraction, and cerebral metabolic rate of oxygen from MRIs during hypothermia were compared between infants with moderate and severe HIE; and in those with moderate HIE, we compared cerebral oxygen metabolism parameters between MRIs performed during and after hypothermia.

Results

During the initial hypothermia MRI at 23.5±5.2 h after birth, infants with severe HIE had lower oxygen extraction fraction (P=0.04) and cerebral metabolic rate of oxygen (P=0.03) and a trend toward lower cerebral blood flow (P=0.33) compared to infants with moderate HIE. In infants with moderate HIE, cerebral blood flow decreased and oxygen extraction fraction increased between MRIs during and after hypothermia (although not significantly); cerebral metabolic rate of oxygen (P=0.93) was not different.

Conclusion

Early MRIs were technically feasible while maintaining hypothermic goal temperatures in infants with HIE. Cerebral oxygen metabolism early during hypothermia is more disturbed in severe HIE. In infants with moderate HIE, cerebral blood flow decreased and oxygen extraction fraction increased between early and post-hypothermia scans. A comparison of cerebral oxygen metabolism parameters between early and post-hypothermia MRIs might improve our understanding of the evolution of HIE and the benefits of hypothermia. This approach could guide the use of adjunctive neuroprotective strategies in affected infants.

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References

  1. Shankaran S, Laptook AR, Ehrenkranz RA et al (2005) Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med 353:1574–1584

    Article  CAS  PubMed  Google Scholar 

  2. Gluckman PD, Wyatt JS, Azzopardi D et al (2005) Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomized trial. Lancet 365:663–670

    Article  PubMed  Google Scholar 

  3. Azzopardi D, Brocklehurst P, Edwards D et al (2008) The TOBY study. Whole body hypothermia for the treatment of perinatal asphyxial encephalopathy: a randomized controlled trial. BMC Pediatr 8:17

    Article  PubMed  PubMed Central  Google Scholar 

  4. Bonifacio SL, Glass HC, VanderPluym J et al (2011) Perinatal events and early MRI in therapeutic hypothermia. J Pediatr 158:360–365

    Article  PubMed  Google Scholar 

  5. Gano D, Chau V, Poskitt KJ et al (2013) Evolution of pattern of injury and quantitative MRI on days 1 and 3 in term newborns with hypoxic-ischemic encephalopathy. Pediatr Res 74:82–87

    Article  CAS  PubMed  Google Scholar 

  6. Boudes E, Tan X, Saint-Martin C et al (2015) MRI obtained during versus after hypothermia in asphyxiated newborns. Arch Dis Child Fetal Neonatal Ed 100:F238–F242

    Article  PubMed  Google Scholar 

  7. Agut T, Leon M, Rebollo M et al (2014) Early identification of brain injury in infants with hypoxic-ischemic encephalopathy at high risk for severe impairments: accuracy of MRI performed in the first days of life. BMC Pediatr 14:177–183

    Article  PubMed  PubMed Central  Google Scholar 

  8. Wintermark P, Hansen A, Soul J et al (2011) Early versus late MRI in asphyxiated newborns treated with hypothermia. Arch Dis Child Fetal Neonatal Ed 96:F36–F44

    Article  PubMed  Google Scholar 

  9. Wintermark P, Hansen A, Warfield SK et al (2014) Near-infrared spectroscopy versus magnetic resonance imaging to study brain perfusion in neonates with hypoxic-ischemic encephalopathy treated with hypothermia. Neuroimage 85:287–293

    Article  CAS  PubMed  Google Scholar 

  10. Liu P, Huang H, Rollins N et al (2014) Quantitative assessment of the global cerebral metabolic rate of oxygen (CMRO2) in neonates using MRI. NMR Biomed 27:332–340

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Adams JA, Fernandes CJ (eds) (2017) Guidelines for acute care of the neonate, 25th edn. Section of Neonatology, Department of Pediatrics, Baylor College of Medicine, Houston

  12. Stafford TD, Hagan JL, Sitler CG et al (2017) Therapeutic hypothermia during neonatal transport: active cooling helps reach the target. Ther Hypothermia Temp Manag 7:88–94

    Article  PubMed  Google Scholar 

  13. Liu P, Qi Y, Lin Z et al (2018) Assessment of cerebral blood flow in neonates and infants: a phase-contrast MRI study. Neuroimage. https://doi.org/10.1016/j.neuroimage.2018.03.020

  14. Kety SS, Schmidt CF (1945) The determination of cerebral blood flow in man by the use of nitrous oxide in low concentrations. Am J Phys 143:55–63

    Google Scholar 

  15. Xu F, Ge Y, Lu H (2009) Noninvasive quantification of whole-brain cerebral metabolic rate of oxygen (CMRO2) by MRI. Magn Reson Med 62:141–148

    Article  PubMed  PubMed Central  Google Scholar 

  16. Lu H, Ge Y (2008) Quantitative evaluation of oxygenation in venous vessels using T2-relaxation-under-spin-tagging MRI. Magn Reson Med 60:357–363

    Article  PubMed  PubMed Central  Google Scholar 

  17. Golay X, Silvennoinen MJ, Zhou J et al (2001) Measurement of tissue oxygen extraction ratios from venous blood T2: increased precision and validation of principle. Magn Reson Med 46:282–291

    Article  CAS  PubMed  Google Scholar 

  18. Federov A, Beichel R, Kalpathy-Cramer J et al (2012) 3D slicer as an image computing platform for the quantitative imaging network. Magn Reson Imaging 30:1323–1341

    Article  Google Scholar 

  19. Herscovitch P, Raichle ME (1985) What is the correct value for the brain-blood partition-coefficient for water? J Cereb Blood Flow Metab 5:65–69

    Article  CAS  PubMed  Google Scholar 

  20. De Vis JB, Petersen ET, Alderliesten T et al (2014) Non-invasive MRI measurements of venous oxygen, oxygen extraction fraction and oxygen consumption in neonates. Neuroimage 95:185–192

    Article  PubMed  Google Scholar 

  21. Dehaes M, Aggarwal A, Lin PY et al (2014) Cerebral oxygen metabolism in neonatal hypoxic-ischemic encephalopathy during and after therapeutic hypothermia. J Cereb Blood Flow Metab 34:87–94

    Article  CAS  PubMed  Google Scholar 

  22. Ilves P, Talvik R, Talvik T (1998) Changes in Doppler ultrasonography in asphyxiated term infants with hypoxic-ischaemic encephalopathy. Acta Paediatr 87:680–684

    Article  CAS  PubMed  Google Scholar 

  23. Wisnowski JL, Wu TW, Reitman AJ et al (2015) 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 Metab 36:1075–1086

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Wu T-W, Tamrazi B, Hsu K-H et al (2018) Cerebral lactate concentration in neonatal hypoxic-ischemic encephalopathy: in relation to time, characteristic of injury, and serum lactate concentration. Front Neurol 9:293

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

This research was supported in part by a grant from the Evangelina “Evie” Whitlock Foundation and the Baylor College of Medicine Clinician-Scientist Training Program (awarded to A.M.L.) and by the National Institutes of Health (NIH R21 NS085634 to P.L.). The authors wish to thank the neonatal team responsible for infant transport between the NICU and MRI suite and the MR technicians responsible for operating the scanner.

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Correspondence to Anil N. Shetty.

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Shetty, A.N., Lucke, A.M., Liu, P. et al. Cerebral oxygen metabolism during and after therapeutic hypothermia in neonatal hypoxic–ischemic encephalopathy: a feasibility study using magnetic resonance imaging. Pediatr Radiol 49, 224–233 (2019). https://doi.org/10.1007/s00247-018-4283-9

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  • DOI: https://doi.org/10.1007/s00247-018-4283-9

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