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Radiologic-pathologic evidence of brain injury: hypoperfusion in the Papez circuit results in poor neurodevelopmental outcomes in neonatal hypoxic ischemic encephalopathy

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Abstract

Purpose

To provide radiologic-pathologic correlation of brain injury in the Papez circuit in hypoxic-ischemic encephalopathy (HIE) neonates and correlate radiologic findings with long-term neurodevelopmental outcomes.

Methods

Twenty full-term HIE neonates were evaluated. Cerebral blood flow (CBF) values, obtained through pulsed arterial spin labeling (ASL) perfusion-weighted MRI, were compared by permutation test to identify brain regions with statistically significant perfusion changes between 14 HIE neonates without evidence of developmental delay by Bayley-III (mean age 8.2 ± 7.2 days) and 6 HIE neonates with evidence of developmental delay (mean age 13.1 ± 8.0 days). Four histopathologic studies on specimens were taken from post-mortem brains of another group of infants (mean age 10 ± 6.8 days) with HIE. The infants were not the same ones who had MRIs.

Results

Significantly decreased perfusion in Papez circuit was found in HIE neonates with developmental delay compared with HIE neonates without delay. Decreased ASL perfusion values were seen in Papez circuit structures of the fornix (p = 0.002), entorhinal cortex (p = 0.048), amygdala (p = 0.036), hippocampus (p = 0.033), and thalamus (p = 0.036). In autopsy specimens of neonates with HIE, anoxic (eosinophilic) neurons, reactive astrocytes, and white matter rarefaction were observed in these regions, providing pathology correlation to the imaging findings of HIE.

Conclusion

The Papez circuit is susceptible to hypoxic-ischemic injury in neonates as demonstrated by perfusion-weighted imaging and histopathology. This sheds new light onto a possible non-familial mechanism of neuropsychiatric disease evolution initiated in the infant period and raises the potential for early identification of at-risk children.

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Funding

This work was supported by National Institutes of Health (KL2TR001879), National Natural Science Foundation of China (61802330, 61802331), and Natural Science Foundation of Shandong (ZR2018BF008).

Author information

Authors and Affiliations

  1. School of Computer and Control Engineering, Yantai University, Yantai, China

    Qiang Zheng

  2. Department of Radiology, Children’s Hospital of Philadelphia, 3401 Civic Center Boulevard, Philadelphia, PA, 19104, USA

    Qiang Zheng & Misun Hwang

  3. Department of Pathology and Laboratory Medicine, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Angela N. Viaene

  4. Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Angela N. Viaene

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

    Colbey W. Freeman & Misun Hwang

Authors
  1. Qiang Zheng
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  2. Angela N. Viaene
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  3. Colbey W. Freeman
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  4. Misun Hwang
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Contributions

All authors have made substantial contributions to all of the following: (1) the conception and design of the study, or acquisition of data, or analysis and interpretation of data, (2) drafting the article or revising it critically for important intellectual content, (3) final approval of the version to be submitted.

Corresponding author

Correspondence to Misun Hwang.

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The authors have no conflict of interest.

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The retrospective case-control study followed an IRB-approved protocol.

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A waiver of consent/parental permission, assent, and HIPAA authorization was approved by our institutional review board.

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Zheng, Q., Viaene, A.N., Freeman, C.W. et al. Radiologic-pathologic evidence of brain injury: hypoperfusion in the Papez circuit results in poor neurodevelopmental outcomes in neonatal hypoxic ischemic encephalopathy. Childs Nerv Syst 37, 63–68 (2021). https://doi.org/10.1007/s00381-020-04795-0

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  • DOI: https://doi.org/10.1007/s00381-020-04795-0

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