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A Novel Fixel-Based Approach for Resolving Neonatal White Matter Microstructure from Clinical Diffusion MRI
Benjamin T Newman1,2, Meghan H Puglia3
1Department of Radiology and Medical Imaging, University of Virginia, Charlottesville, Virginia, USA.
Medrxiv : the Preprint Server for Health Sciences
|April 3, 2026
Summary
This study introduces an advanced diffusion MRI technique to analyze white matter development in premature infants. The method successfully maps brain structure, revealing links between early development, illness severity, and neurodevelopmental outcomes.
Area of Science:
- Neuroimaging
- Developmental Neuroscience
- Medical Physics
Background:
- Preterm birth disrupts neonatal brain development, leading to neurodevelopmental disorders.
- Neonatal brain imaging is challenging due to data quality and immature tissue.
- Current neuroimaging methods often fail with underdeveloped neonatal brains.
Purpose of the Study:
- To develop and validate an advanced diffusion MRI method for assessing white matter microstructure in premature neonates.
- To examine the relationship between white matter development, postmenstrual age, and neonatal illness severity.
- To establish a practical framework for clinical neonatal brain research.
Main Methods:
- Developed a novel diffusion MRI approach resolving multiple tissue compartments.
- Quantified white matter fiber orientation and tissue signal fraction.
- Employed automated segmentation for analyzing key brain tracts and regions.
Main Results:
- Successfully segmented and reconstructed neonatal white matter tracts.
- Demonstrated tract-specific developmental trajectories, with early pathways showing greater organization.
- Found modest, tissue-specific associations between neonatal illness severity and microstructural properties.
Conclusions:
- Advanced microstructural MRI can yield valuable white matter data from clinical scans.
- This method offers a practical approach for studying neonatal brain development in hospital settings.
- Enables early, non-invasive study of vulnerable preterm infants before clinical assessments are feasible.

