Chronic fetal hypoxia affects axonal maturation in guinea pigs during development: a longitudinal Diffusion Tensor Imaging and T2 mapping study

Kim, Jieun; Choi, In-Young; Dong, Yafeng; Wang, Wen-Tung; Brooks, William M.; Weiner, Carl P.; Lee, Phil

doi:10.1002/jmri.24825

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Chronic fetal hypoxia affects axonal maturation in guinea pigs during development: a longitudinal Diffusion Tensor Imaging and T2 mapping study

Published Date:

Dec 15 2014

Publisher's site:

http://dx.doi.org/10.1002/jmri.24825 New Site Icon

Source:

J Magn Reson Imaging. 42(3):658-665.

[PDF-1.71 MB]

Details:

Personal Authors:

Kim, Jieun ; Choi, In-Young ; Dong, Yafeng ; Wang, Wen-Tung ; Brooks, William M. ; ... More ▼

Keywords:

[+]

Pubmed ID:

25504885

Pubmed Central ID:

PMC4468050

Description:

Purpose

Chronic hypoxemia is the prime cause of fetal brain injury and long-term sequelae such as neurodevelopmental compromise, seizures and cerebral palsy. This study aims to investigate the impact of chronic hypoxemia on neonatal brains, and follow developmental alterations and adaptations non-invasively in a guinea pig model.

Materials and Methods

Thirty guinea pigs underwent either normoxic and hypoxemic conditions during the critical stage of brain development (0.7 gestation) and studied prenatally (n=16) or perinatally (n=14). Fourteen newborns (7 hypoxia and 7 normoxia group) were scanned longitudinally to characterize physiological and morphological alterations, and axonal myelination and injury using in vivo DTI, T2 mapping, and T2-weighted MRI. Sixteen fetuses (8 hypoxia and 8 normoxia) were studied ex vivo to assess hypoxia-induced neuronal injury/loss using Nissl staining and quantitative reverse transcriptase Polymerase Chain Reaction methods.

Results

Developmental brains in the hypoxia group showed lower fractional anisotropy in the corpus callosum (−12%, p=0.02) and lower T2 values in the hippocampus (−16%, p=0.003) compared with the normoxia group with no differences in the cortex (p>0.07), indicating vulnerability of the hippocampus and cerebral white matter during early development. Fetal guinea pig brains with chronic hypoxia demonstrated an over-tenfold increase in expression levels of hypoxia index genes such as erythropoietin and HIF-1α, and an over 40% reduction in neuronal density, confirming prenatal brain damage.

Conclusion

In vivo MRI measurement, such as DTI and T2 mapping, provides quantitative parameters to characterize neuro-developmental abnormalities and to monitor the impact of prenatal insult on the postnatal brain maturation of guinea pigs.

Document Type:

Journal Article

Collection(s):

CDC Public Access

Funding:

Main Document Checksum:

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Supporting Files:

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