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Reduced thalamic volume in preterm infants is associated with abnormal white matter metabolism independent of injury

  • Paediatric Neuroradiology
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Abstract

Introduction

Altered thalamocortical development is hypothesized to be a key substrate underlying neurodevelopmental disabilities in preterm infants. However, the pathogenesis of this abnormality is not well-understood. We combined magnetic resonance spectroscopy of the parietal white matter and morphometric analyses of the thalamus to investigate the association between white matter metabolism and thalamic volume and tested the hypothesis that thalamic volume would be associated with diminished N-acetyl-aspartate (NAA), a measure of neuronal/axonal maturation, independent of white matter injury.

Methods

Data from 106 preterm infants (mean gestational age at birth: 31.0 weeks ± 4.3; range 23–36 weeks) who underwent MR examinations under clinical indications were included in this study.

Results

Linear regression analyses demonstrated a significant association between parietal white matter NAA concentration and thalamic volume. This effect was above and beyond the effect of white matter injury and age at MRI and remained significant even when preterm infants with punctate white matter lesions (pWMLs) were excluded from the analysis. Furthermore, choline, and among the preterm infants without pWMLs, lactate concentrations were also associated with thalamic volume. Of note, the associations between NAA and choline concentration and thalamic volume remained significant even when the sample was restricted to neonates who were term-equivalent age or older.

Conclusion

These observations provide convergent evidence of a neuroimaging phenotype characterized by widespread abnormal thalamocortical development and suggest that the pathogenesis may involve impaired axonal maturation.

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Acknowledgments

The authors would like to thank Julia Castro for organizing the data, the NICU and Radiology staff at Children’s Hospital Los Angeles, and the families for their participation in our research studies.

Ethical standards and patient consent

We declare that all human and animal studies have been approved by the Children’s Hospital Los Angeles Committee on Clinical Investigations 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 the study.

Conflict of interest

We declare that we have no conflict of interest.

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Authors and Affiliations

  1. Department of Radiology, Children’s Hospital Los Angeles, 4650 Sunset Blvd., MS #81, Los Angeles, CA, 90027, USA

    Jessica L. Wisnowski, Marvin D. Nelson, Stefan Blüml & Ashok Panigrahy

  2. Department of Pediatric Radiology, Children’s Hospital of Pittsburgh of UPMC, University of Pittsburgh, Pittsburgh, PA, USA

    Jessica L. Wisnowski, Rafael C. Ceschin, Vincent J. Schmithorst & Ashok Panigrahy

  3. Brain and Creativity Institute, University of Southern California, Los Angeles, CA, USA

    Jessica L. Wisnowski & So Young Choi

  4. Department of Biomedical Informatics, University of Pittsburgh, Pittsburgh, PA, USA

    Rafael C. Ceschin

  5. Department of Pediatrics, Division of Neurology, Childrens Hospital of Pittsburgh of UPMC, University of Pittsburgh, Pittsburgh, PA, USA

    Michael J. Painter

  6. Rudi Schulte Research Institute, Santa Barbara, CA, USA

    Stefan Blüml

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  1. Jessica L. Wisnowski
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  2. Rafael C. Ceschin
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  3. So Young Choi
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  4. Vincent J. Schmithorst
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  6. Marvin D. Nelson
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Correspondence to Jessica L. Wisnowski.

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Wisnowski, J.L., Ceschin, R.C., Choi, S.Y. et al. Reduced thalamic volume in preterm infants is associated with abnormal white matter metabolism independent of injury. Neuroradiology 57, 515–525 (2015). https://doi.org/10.1007/s00234-015-1495-7

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  • DOI: https://doi.org/10.1007/s00234-015-1495-7

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