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Related Experiment Video

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Advanced Diffusion Imaging in The Hippocampus of Rats with Mild Traumatic Brain Injury
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Exploring the multiple-hit hypothesis of preterm white matter damage using diffusion MRI.

Madeleine L Barnett1, Nora Tusor1, Gareth Ball1

  • 1Centre for the Developing Brain, Division of Imaging Sciences & Biomedical Engineering, King's College London, London SE1 7EH, UK.

Neuroimage. Clinical
|December 14, 2017
PubMed
Summary

Multiple perinatal risk factors increase the risk of white matter injury in preterm infants. Cumulative exposure to these factors exacerbates this injury, supporting the multiple hit hypothesis.

Keywords:
ALIC, anterior limb of the internal capsuleBSITD-III, Bayley Scales of Infant and Toddler Development Third EditionBrainDevelopmentDiffusion MRIGA, gestational ageIMD, index of multiple deprivationMultiple hit hypothesisPLIC, posterior limb of the internal capsulePMA, postmenstrual agePrematuritySLF, superior longitudinal fasciculusdMRI, diffusion magnetic resonance imaging

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Area of Science:

  • Neonatal neuroscience
  • Perinatal medicine
  • Neuroimaging

Background:

  • Preterm infants face high risks of diffuse white matter injury and poor neurodevelopmental outcomes.
  • The multiple hit hypothesis posits that cumulative perinatal risk factors amplify white matter injury risk.
  • Diffusion weighted magnetic resonance imaging (dMRI) is crucial for assessing white matter integrity.

Purpose of the Study:

  • To test the multiple hit hypothesis in a large cohort of preterm infants.
  • To investigate the association between dMRI measures and perinatal risk factors.
  • To determine if white matter integrity at term equivalent age predicts neurodevelopmental performance.

Main Methods:

  • 491 preterm infants (<34 weeks GA) without focal brain lesions underwent structural and dMRI.
  • Tract-based spatial statistics analyzed dMRI data, assessing fractional anisotropy (FA) and diffusivity measures (RD, AD, MD).
  • Neurodevelopment was evaluated using the Bayley Scales of Infant and Toddler Development (BSITD-III) in a subset of infants.

Main Results:

  • Lower gestational age, fetal growth restriction, prolonged ventilation/parenteral nutrition, necrotizing enterocolitis, and male sex were risk factors for white matter injury.
  • Fetal growth restriction, extended ventilation, and parenteral nutrition were independently linked to lower FA.
  • Cumulative risk factor exposure correlated with reduced white matter FA, which predicted neurodevelopmental outcomes.

Conclusions:

  • Multiple perinatal risk factors are independently associated with diffuse white matter injury in preterm infants.
  • Cumulative exposure to these factors worsens dMRI-defined white matter injury.
  • Findings support the multiple hit hypothesis for preterm white matter injury.