Magnetic resonance spectroscopy markers of axons and astrogliosis in relation to specific features of white matter injury in preterm infants
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Punctate white matter lesions (pWMLs) and diffuse excessive high signal intensity (DEHSI) are commonly observed signal abnormalities on MRI scans of high-risk preterm infants near term-equivalent age. To establish whether these features are indicative abnormalities in axonal development or astroglia, we compared pWMLs and DEHSI to markers of axons and astrogliosis, derived from magnetic resonance spectroscopy (MRS).
Data from 108 preterm infants (gestational age at birth 31.0 weeks ± 4.3; age at scan 41.2 weeks ± 6.0) who underwent MR examinations under clinical indications were included in this study. Linear regression analyses were used to test the effects of pWMLs and DEHSI on N-acetyl-aspartate (NAA) and myoinositol concentrations, respectively.
Across the full sample, pWMLs were associated with a reduction in NAA whereas moderate to severe DEHSI altered the normal age-dependent changes in myoinositol such that myoinositol levels were lower at younger ages with no change during the perinatal period. Subgroup analyses indicated that the above associations were driven by the subgroup of neonates with both pWMLs and moderate to severe DEHSI.
Overall, these findings suggest that pWMLs in conjunction with moderate/severe DEHSI may signify a population of infants at risk for long-term adverse neurodevelopmental outcome due to white matter injury and associated axonopathy. The loss of normal age-associated changes in myoinositol further suggests disrupted astroglial function and/or osmotic dysregulation.
KeywordsPreterm birth Diffuse excessive high signal intensity (DEHSI) Magnetic Resonance Spectroscopy N-acetyl-aspartate Myoinositol
Support is provided by the National Institutes of Health (K23NS063371), the Rudi Schulte Research Institute, The Ian Harrison Neonatal Neurology Program at the Children's Hospital of Pittsburgh of UPMC, and the Children's Hospital of Pittsburgh Foundation. The authors would like to thank Hannah Kinney for her helpful comments on earlier drafts of this manuscript and Julia Castro for organizing the data.
Ethical standards and patient consent
We declare that all human and animal studies have been approved by the Children's Hospital Los Angeles and the University of Pittsburgh and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. We declare that all patients gave informed consent prior to inclusion in this study.
Conflict of interest
We declare that we have no conflict of interest.
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