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  • Clinical Research Article
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Differences between early and late MRI in infants with neonatal encephalopathy following therapeutic hypothermia

Pediatric Research volume 94, pages 1011–1017 (2023)Cite this article

Abstract

Background

MRI is the gold standard test to define brain injury in infants with neonatal encephalopathy(NE). As imaging findings evolve considerably over the first week, early imaging may not fully reflect the final nature of the injury. This study aimed to compare day 4 versus second week MRI in infants with NE.

Methods

Retrospective cohort study including infants who received therapeutic hypothermia(TH) for NE and had two MRIs: early (≤7days) and late (>7days). MRIs were clinically reported and also reviewed by study investigators.

Results

94infants with NE were included (40mild,49moderate,5severe). Twenty-four infants(26%) had a normal early scan of which 3/24(13%) had injury noted on repeat MRI. Seventy infants(74%) had abnormal findings noted on early MRI, of which 4/70(6%) had further evolution of injury while 11/70(16%) had complete resolution of findings. Applying a grading system resulted in a change of grade in 7 infants.

Conclusion

In infants who received TH for NE, 19% had changes noted between their early and late MRIs. While the impact on predicting neurodevelopmental outcome was not studied, relying solely on early MRI may overestimate injury in a proportion of infants and miss injury in others. Combining early and late MRI allows for better characterization of injury.

Impact

  • MRI is the gold standard tool to define brain injury in infants with NE, however, imaging findings evolve considerably over the first week of life.

  • Most centers perform a single MRI on day 4 after rewarming.

  • In our cohort, 19% of infants had a notable change in their MRI findings between early (within the first week) and late (beyond the first week) scans.

  • Relying solely on early MRI may overestimate injury in a proportion of infants and miss injury in others.

  • Combining early and late MRI following hypothermia allows for better characterization of brain injury.

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Fig. 1: Example of MRI images of normal early scan and abnormal late scan.
Fig. 2: Example of MRI images of abnormal early scan and normal late scan.
Fig. 3: Example of MRI images of abnormal early scan and evolved abnormalities on the late scan.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

References

  1. Kurinczuk, J. J., White-Koning, M. & Badawi, N. Epidemiology of neonatal encephalopathy and hypoxic-ischaemic encephalopathy. Early Hum. Dev. 86, 329–338 (2010).

    Article  PubMed  Google Scholar 

  2. Conway, J. M., Walsh, B. H., Boylan, G. B. & Murray, D. M. Mild hypoxic ischaemic encephalopathy and long term neurodevelopmental outcome - A systematic review. Early Hum. Dev. 120, 80–87 (2018). May.

    Article  CAS  PubMed  Google Scholar 

  3. van Kooij, B. J. et al. Serial MRI and neurodevelopmental outcome in 9- to 10-year-old children with neonatal encephalopathy. J. Pediatr. 157, 221–227.e2 (2010).

    Article  PubMed  Google Scholar 

  4. Jacobs, S. E. et al. Cooling for newborns with hypoxic ischaemic encephalopathy. Cochrane Database Syst Rev. 2013, CD003311 (2013).

  5. Barkovich, A. J. et al. Prediction of neuromotor outcome in perinatal asphyxia: evaluation of MR scoring systems. AJNR 19, 143–149 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Weeke, L. C. et al. A Novel Magnetic Resonance Imaging Score Predicts Neurodevelopmental Outcome After Perinatal Asphyxia and Therapeutic Hypothermia. J. Pediatr. 192, 33–40.e2 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  7. Rutherford, M., Pennock, J., Schwieso, J., Cowen, F. & Dubowitz, L. Hypoxic-ischaemic encephalopathy: early and late magnetic resonance imaging findings in relation to outcome. Arch. Dis. Child Fetal Neonatal Ed. 75, F145–F151 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Rutherford, M. A. et al. Abnormal magnetic resonance signal in the internal capsule predicts poor neurodevelopmental outcome in infants with hypoxic-ischemic encephalopathy. Pediatrics 102, 323–328 (1998).

    Article  CAS  PubMed  Google Scholar 

  9. Hayes, B. C. et al. Brain magnetic resonance imaging and outcome after hypoxic ischaemic encephalopathy. J. Matern Fetal Neonatal Med 29, 777–782 (2016).

    Article  CAS  PubMed  Google Scholar 

  10. Mercuri, E. et al. Head growth in infants with hypoxic-ischemic encephalopathy: correlation with neonatal magnetic resonance imaging. Pediatrics 106, 235–243 (2000).

    Article  CAS  PubMed  Google Scholar 

  11. Steinman, K. J. et al. Neonatal Watershed Brain Injury on MRI Correlates with Verbal IQ at Four Years. Pediatrics 123, 1025–1030 (2009).

    Article  PubMed  Google Scholar 

  12. Miller, S. P. et al. Patterns of brain injury in term neonatal encephalopathy. J. Pediatr. 146, 453–460 (2005).

    Article  PubMed  Google Scholar 

  13. Shankaran, S. et al. Brain injury following trial of hypothermia for neonatal hypoxic-ischaemic encephalopathy. Arch. Dis. Child Fetal Neonatal Ed. 97, F398–F404 (2012).

    PubMed  Google Scholar 

  14. Ferrari, F. et al. General movements in full-term infants with perinatal asphyxia are related to Basal Ganglia and thalamic lesions. J. Pediatr. 158, 904–911 (2011).

    Article  PubMed  Google Scholar 

  15. Wisnowski, J. L. et al. Neuroimaging in the term newborn with neonatal encephalopathy. Semin Fetal Neonatal Med 26, 101304 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  16. Rutherford, M. et al. Magnetic resonance imaging in perinatal brain injury: clinical presentation, lesions and outcome. Pediatr. Radio. 36, 582–592 (2006).

    Article  Google Scholar 

  17. Douglas-Escobar, M. & Weiss, M. D. Hypoxic-Ischemic Encephalopathy: A Review for the Clinician. JAMA Pediatr. 169, 397–403 (2015).

  18. Chakkarapani, E. et al. Reliability of Early Magnetic Resonance Imaging (MRI) and Necessity of Repeating MRI in Noncooled and Cooled Infants With Neonatal Encephalopathy. J. Child Neurol. 31, 553–559 (2016).

    Article  PubMed  Google Scholar 

  19. Skranes, J. H. et al. Brain imaging in cooled encephalopathic neonates does not differ between four and 11 days after birth. Acta Paediatr. 104, 752–758 (2015).

    Article  PubMed  Google Scholar 

  20. McKinstry, R. C. et al. A prospective, longitudinal diffusion tensor imaging study of brain injury in newborns. Neurology 59, 824–833 (2002).

    Article  CAS  PubMed  Google Scholar 

  21. Barkovich, A. J. et al. MR imaging, MR spectroscopy, and diffusion tensor imaging of sequential studies in neonates with encephalopathy. AJNR 27, 533–547 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Executive summary: Neonatal encephalopathy and neurologic outcome, second edition. Report of the American College of Obstetricians and Gynecologists’ Task Force on Neonatal Encephalopathy. Obstet. Gynecol. 123, 896–901 (2014).

    Google Scholar 

  23. Walsh, B. H. et al. Differences in standardized neonatal encephalopathy exam criteria may impact therapeutic hypothermia eligibility. Pediatr Res. 92, 791–798 (2022).

  24. Finelli, P. F. Diagnostic approach to restricted-diffusion patterns on MR imaging. Neurol. Clin. Pr. 2, 287–93 (2012).

    Article  Google Scholar 

  25. Lo, L., Tan, A. C., Umapathi, T. & Lim, C. C. Diffusion-weighted MR imaging in early diagnosis and prognosis of hypoglycemia. AJNR 27, 1222–1224 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Schaefer, P. W., Grant, P. E. & Gonzalez, R. G. Diffusion-weighted MR imaging of the brain. Radiology 217, 331–345 (2000).

    Article  CAS  PubMed  Google Scholar 

  27. Lawrence, R. K. & Inder, T. E. Anatomic changes and imaging in assessing brain injury in the term infant. Clin. Perinatol. 35, 679–693 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  28. Bednarek, N. et al. Impact of therapeutic hypothermia on MRI diffusion changes in neonatal encephalopathy. Neurology 78, 1420–1427 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Al Amrani, F. et al. Prediction of outcome in asphyxiated newborns treated with hypothermia: Is a MRI scoring system described before the cooling era still useful? Eur. J. Paediatr. Neurol. 22, 387–95 (2018).

    Article  PubMed  Google Scholar 

  30. Shankaran, S. et al. Neonatal Magnetic Resonance Imaging Pattern of Brain Injury as a Biomarker of Childhood Outcomes following a Trial of Hypothermia for Neonatal Hypoxic-Ischemic Encephalopathy. J. Pediatr. 167, 987–993.e3 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  31. O’Kane, A. et al. Early Versus Late Brain Magnetic Resonance Imaging after Neonatal Hypoxic Ischemic Encephalopathy Treated with Therapeutic Hypothermia. J. Pediatr. 232, 73–9.e2 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

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

    Article  PubMed  Google Scholar 

  33. Ouwehand, S. et al. Predictors of Outcomes in Hypoxic-Ischemic Encephalopathy following Hypothermia: A Meta-Analysis. Neonatology 117, 411–27. (2020).

    Article  CAS  PubMed  Google Scholar 

  34. Charon, V. et al. Early MRI in neonatal hypoxic-ischaemic encephalopathy treated with hypothermia: Prognostic role at 2-year follow-up. Eur. J. Radio. 85, 1366–1374 (2016).

    Article  Google Scholar 

  35. Moss, H. G., Jenkins, D. D., Yazdani, M. & Brown, T. R. Identifying the translational complexity of magnetic resonance spectroscopy in neonates and infants. NMR Biomed. 32, e4089 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

All of the infants and families included in this study. Staff of the Brigham and Women’s Hospital.

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Authors and Affiliations

  1. Department of Pediatric Newborn Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Aisling A. Garvey, Hoda El-Shibiny, Terrie E. Inder & Mohamed El-Dib

  2. Harvard Medical School, Boston, MA, USA

    Aisling A. Garvey, Terrie E. Inder & Mohamed El-Dib

  3. INFANT Research Centre, Cork, Ireland

    Aisling A. Garvey

  4. Department of Radiology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA

    Edward Yang

  5. Childrens Hospital of Orange County, University of California Irvine, Irvine, CA, USA

    Terrie E. Inder

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Contributions

A.G., T.I., M.E.-D. made substantial contributions to the conception and design of the study. A.G. and H.E.-S. made substantial contributions to the acquisition of data. A.G., E.Y. and M.E.-D. made significant contributions to the analysis and interpretation of the data. All authors were involved in drafting and revising of the manuscript and approve the final version to be published.

Corresponding author

Correspondence to Mohamed El-Dib.

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The authors declare no competing interests.

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Patient consent was not required. This was a retrospective data study and institutional review board approval waived consent.

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Garvey, A.A., El-Shibiny, H., Yang, E. et al. Differences between early and late MRI in infants with neonatal encephalopathy following therapeutic hypothermia. Pediatr Res 94, 1011–1017 (2023). https://doi.org/10.1038/s41390-023-02580-8

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