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Magnetic resonance imaging and spectroscopy in neonatal encephalopathy: current consensus position and future opportunities

Pediatric Research (2025)Cite this article

Abstract

Neonatal encephalopathy (NE) is a significant global health concern. It is a leading cause of long-term neurodevelopmental impairment, with hypoxic-ischaemic perinatal brain injury being the most common underlying contributor. Although therapeutic hypothermia has reduced mortality and improved outcomes for some affected infants, many survivors experience neurodevelopmental disability, including cerebral palsy and/or deficits in cognition, behaviour, and executive functioning. Early and accurate prognostication and identification of injury severity remain a challenge due to evolving clinical signs and multiple etiologies. Magnetic resonance imaging (MRI) is the gold standard for characterizing NE-related brain injury. Diffusion-weighted imaging (DWI) enables early detection of injury, and proton magnetic resonance spectroscopy (1H-MRS), specifically the Lac/NAA peak area ratio from basal ganglia and thalamus, provides robust prognostic indicators of two-year neurodevelopmental outcomes. MRI scoring systems incorporating multiple modalities correlate well with later neurodevelopmental outcomes. Advanced imaging modalities, such as diffusion tensor imaging (DTI), arterial spin labelling (ASL), and blood oxygen level-dependent (BOLD) imaging, offer further insights into microstructural integrity, perfusion, and functional connectivity. By standardizing acquisition protocols and post-processing, MRI biomarkers can serve as reliable, early surrogate endpoints in neuroprotection trials, allowing smaller sample sizes and accelerating clinical translation. MRI and 1H-MRS integration enhances prognostication, guides clinical management, and supports informed decision-making in NE care.

Impact

  • This article highlights the importance of state-of-the-art MRI and MRS techniques for assessing neonatal encephalopathy (NE), emphasizing optimized protocols, accurate interpretation, and the use of MRI scoring systems to enhance clinical decision-making. It provides a comprehensive guide to advanced MRI/MRS acquisition and interpretation in neonates with NE, addressing current limitations and future directions. By optimizing neonatal MRI/MRS practices, this work aims to improve early diagnosis and prognostication, guide treatment strategies, and ultimately improve the management of neonates with NE.

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Fig. 1: Evolution of hypoxic-ischaemic brain injury.
Fig. 2: Examples of injury in neonatal encephalopathy on T1- and T2-weighted images and comparison to injury on diffusion weighted images (DWI).
Fig. 3: Diffusion eighted imaging in neonatal encephalopathy.
Fig. 4: Representative 1H-MRS spectra acquired from two term newborn babies with Neonatal Encephalopathy using PRESS at TE 288 ms (basal ganglia & thalamus voxel shown in sagittal and axial planes).
Fig. 5: Thalamic [NAA] as a surrogate biomarker in clinical trials of neuroprotective interventions.

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Data availability

Data sharing not applicable to this article as no datasets were generated or analysed during the current study.

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Acknowledgements

We would like to thank Paediatric Research for editorial support and Prof. Deirdre Murray for supporting the series as Chair of the Brain, Development, and Imaging section of the European Society of Paediatric Research.

Funding

No financial assistance was received in support of the study

Author information

Authors and Affiliations

  1. Department of Pediatrics, Warren Alpert Medical School, Brown University, Providence, RI, USA

    Abbot Laptook

  2. Department of Neonatology, Cork University Maternity Hospital, Cork, Ireland

    Aisling A. Garvey

  3. INFANT Research Centre, University College Cork, Cork, Ireland

    Aisling A. Garvey

  4. Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA

    Caroline Adams & Misun Hwang

  5. Department of Radiology and Department of Pediatrics, Boston Children’s Hospital, Boston, MA, USA

    Patricia Ellen Grant

  6. Harvard Medical School, Boston, MA, USA

    Patricia Ellen Grant

  7. Discipline of Paediatrics, Trinity Translational Medicine Institute (TTMI) & Trinity Research in Childhood Centre (TRiCC), Trinity College Dublin, Ireland

    Eleanor J. Molloy

  8. Neonatology & Neurodisability, Children’s Health Ireland (CHI); Paediatrics, Coombe Hospital, Dublin, Ireland

    Eleanor J. Molloy

  9. Department of Neonatology, Wilhelmina Children’s Hospital, University Medical Center Utrecht and Utrecht University, Lundlaan 6, Utrecht, The Netherlands

    Floris Groenendaal & Manon Benders

  10. Department of Neonatology, Radboudumc, Nijmegen, the Netherlands

    Lauren C. Weeke

  11. Department of Radiology, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Misun Hwang & Marcus Meneses

  12. Division of Newborn Medicine, Department of Pediatrics, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Mohamed El-Dib

  13. Grace Centre for Newborn Intensive Care, The Children’s Hospital at Westmead, Sydney, NSW, Australia

    Nadia Badawi

  14. Cerebral Palsy Alliance Research Institute, Sydney Medical School, The University of Sydney, Sydney, NSW, Australia

    Nadia Badawi

  15. Institute for Women’s Health, University College London, WC1E 6HX, 74 Huntley Street, London, UK

    Nicola J. Robertson & Raymand Pang

  16. Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK

    Nicola J. Robertson

  17. Department of Brain Sciences, Imperial College, London, UK

    Sudhin Thayyil

  18. Center for Neonatal Research, Childrens Hospital of Orange County, California, University of California, Irvine, CA, USA

    Terrie Inder

  19. Department of Clinical Medicine, Aarhus University, Aarhus, Denmark

    Ted Carl Kejlberg Andelius & Kasper Jacobsen Kyng

  20. Department of Pediatrics, Aarhus University Hospital, Aarhus, Denmark

    Ted Carl Kejlberg Andelius & Kasper Jacobsen Kyng

  21. Department of Pediatrics, Aichi Medical University, Aichi, Japan

    Akihisa Okumura

  22. Department of Neonatology, Hospital Sant Joan de Déu and Hospital Clínic BCNatal (Barcelona Centre for Maternal, Foetal and Neonatal Medicine); Institut de Recerca Sant Joan de Déu, Barcelona, Spain

    Ana Alarcon Allen

  23. Department of Surgery and Medical-Surgical Specialties, Faculty of Medicine and Health Sciences, Universitat de Barcelona, Barcelona, Spain

    Ana Alarcon Allen

  24. Department of Radiology (Neuroradiology), Children’s Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA, USA

    Arastoo Vossough

  25. Department of Radiology and Nuclear medicine, Ghent University Hospital, C. Heymanslaan 10, Gent, Belgium

    Caroline Vande Walle

  26. Departments of Neurology and Pediatrics, UCSF Weill Institute for Neurosciences, San Francisco, CA, USA

    Donna M. Ferriero

  27. Division of Developmental Paediatrics, Department of Paediatrics and Child Health, Red Cross War Memorial Hospital, University of Cape Town, Cape Town, South Africa

    Kirsten A. Donald

  28. Neuroscience Institute, University of Cape Town, Cape Town, South Africa

    Kirsten A. Donald

  29. Leids Universitair Medisch Centrum, Intensive Care Neonatologie (ICN), Leiden, The Netherlands

    Linda S. de Vries

  30. Radiology, University of Missouri, Columbia, USA

    Mai-Lan Ho

  31. Neurology and Neurotherapeutics, Division of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, USA

    Michelle Machie

  32. Dep of Neonatology, Wilhelmina Children’s Hospital, Utrecht, The Netherlands

    Niek van der Aa

  33. Division of Development and Growth, Department of Paediatrics, Gynaecology and Obstetrics, Geneva University Hospitals, Geneva, Switzerland

    Petra Huppi

  34. Department of Pediatrics, McGill University, Montreal, Quebec, Canada; Montreal Children’s Hospital, Montreal, Quebec, Canada

    Pia Wintermark

  35. Department of Neurology & Neurological Sciences, Stanford School of Medicine, Stanford, CA, USA

    Sarah Lee

  36. Division of Neuroradiology, Children’s Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Sara Reis Teixeira

  37. Division of Neurology & Pediatrics, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Sonika Agarwal

  38. Division of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA

    Sonika Agarwal

  39. Willem-Alexander Children’s Hospital, Department of Pediatrics, Division of Neonatology, Leiden University Medical Center, Leiden, the Netherlands

    Sylke J. Steggerda

  40. Department of Pediatrics (Neurology), The Hospital for Sick Children, Toronto, ON, Canada

    Vann Chau

  41. University of Toronto, Toronto, ON, Canada

    Vann Chau

  42. Department of Radiology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China

    Xiaoxi Chen

Authors
  1. Abbot Laptook
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  2. Aisling A. Garvey
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  3. Caroline Adams
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  4. Patricia Ellen Grant
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  5. Eleanor J. Molloy
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  6. Floris Groenendaal
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  7. Lauren C. Weeke
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  8. Manon Benders
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  9. Misun Hwang
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  10. Mohamed El-Dib
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  11. Nadia Badawi
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  12. Nicola J. Robertson
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  13. Raymand Pang
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  14. Sudhin Thayyil
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  15. Terrie Inder
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  16. Ted Carl Kejlberg Andelius
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  17. Kasper Jacobsen Kyng
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Consortia

on behalf of the Neonatal MRI group; Brain, Development, and Imaging section of the European Society of Pediatric Research (ESPR)

  • Abbot Laptook
  • , Aisling A. Garvey
  • , Caroline Adams
  • , Patricia Ellen Grant
  • , Eleanor J. Molloy
  • , Floris Groenendaal
  • , Lauren C. Weeke
  • , Manon Benders
  • , Misun Hwang
  • , Mohamed El-Dib
  • , Nadia Badawi
  • , Nicola J. Robertson
  • , Raymand Pang
  • , Sudhin Thayyil
  • , Terrie Inder
  • , Ted Carl Kejlberg Andelius
  • , Kasper Jacobsen Kyng
  • , Akihisa Okumura
  • , Ana Alarcon Allen
  • , Arastoo Vossough
  • , Caroline Vande Walle
  • , Donna M. Ferriero
  • , Kirsten A. Donald
  • , Linda S. de Vries
  • , Mai-Lan Ho
  • , Marcus Meneses
  • , Michelle Machie
  • , Niek van der Aa
  • , Petra Huppi
  • , Pia Wintermark
  • , Sarah Lee
  • , Sara Reis Teixeira
  • , Sonika Agarwal
  • , Sylke J. Steggerda
  • , Vann Chau
  •  & Xiaoxi Chen

Contributions

This manuscript follows the Paediatric Research Author instructions for consortia formatting. All main authors have individually contributed to drafting the manuscript. All main authors and individually named consortia authors have revised the manuscript and approved the final version. Kasper Jacobsen Kyng and Ted Carl Kejlberg Andelius have conceptualized and designed the Magnetic Resonance Imaging and Spectroscopy in the Neonate series - European Society for Paediatric Research (ESPR). Kasper Jacobsen Kyng has edited and finalized the submitted version of the manuscript.

Corresponding author

Correspondence to Kasper Jacobsen Kyng.

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Laptook, A., Garvey, A.A., Adams, C. et al. Magnetic resonance imaging and spectroscopy in neonatal encephalopathy: current consensus position and future opportunities. Pediatr Res (2025). https://doi.org/10.1038/s41390-025-04448-5

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