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Updated: May 1, 2026

Transcutaneous Microcirculatory Imaging in Preterm Neonates
Published on: December 31, 2015
Diffusion tensor imaging in extremely low birth weight infants managed with hypercapnic vs. normocapnic ventilation
Xiawei Ou1, Charles M Glasier, Raghu H Ramakrishnaiah
1Department of Radiology, University of Arkansas for Medical Sciences, Little Rock, AR, USA, ouxiawei@uams.edu.
Insights
Normocapnic ventilation may improve white matter development in extremely low birth weight (ELBW) infants compared to permissive hypercapnia. This subtle difference was not visible on conventional MRI but warrants further investigation in larger studies.
Area of Science:
- Neonatal neurology
- Pediatric critical care
- Neuroimaging
Background:
- Permissive hypercapnia is used to prevent lung injury in extremely low birth weight (ELBW) infants.
- High CO2 levels (hypercapnia) have been retrospectively linked to brain injury in ELBW infants.
Purpose of the Study:
- To compare brain white matter development at term-equivalent age.
- To assess ELBW infants randomized to hypercapnic versus normocapnic ventilation.
- To compare with healthy, non-ventilated term newborns.
Main Methods:
- Utilized magnetic resonance imaging (MRI) with diffusion tensor imaging (DTI).
- Analyzed white matter injury using conventional MRI and diffusion tensor imaging (DTI) fractional anisotropy (FA).
- Employed tract-based spatial statistics (TBSS) for DTI analysis in 22 ELBW infants and 10 controls.
Main Results:
- No significant difference in conventional MRI white matter scores between hypercapnic and normocapnic ELBW groups.
- TBSS revealed more widespread regions of lower FA in hypercapnic ELBW infants compared to controls.
- Normocapnic ELBW infants showed fewer and smaller regions of lower FA compared to controls.
Conclusions:
- Normocapnic ventilation may be associated with improved white matter development in ELBW infants.
- The observed effect on white matter development was subtle and not detected by conventional MRI.
- Larger studies are needed to confirm if permissive hypercapnia negatively impacts white matter development in ELBW infants.
Background:
Permissive hypercapnia is a ventilatory strategy used to prevent lung injury in ventilated extremely low birth weight (ELBW, birth weight ≤1,000 g) infants. However, there is retrospective evidence showing that high CO2 is associated with brain injury.
Objective:
The objective of this study was to compare brain white matter development at term-equivalent age in ELBW infants randomized to hypercapnic vs. normocapnic ventilation during the first week of life and in healthy non-ventilated term newborns.
Materials And Methods:
Twenty-two ELBW infants from a randomized controlled trial were included in this study; 11 received hypercapnic (transcutaneous PCO2 [tcPCO2] 50-60 mmHg) ventilation and 11 normocapnic (tcPCO2 35-45 mmHg) ventilation during the first week of life while still intubated. In addition, ten term healthy newborns served as controls. Magnetic resonance imaging (MRI) with diffusion tensor imaging (DTI) was performed at term-equivalent age for the ELBW infants and at approximately 2 weeks of age for the control infants. White matter injury on conventional MRI was graded in the ELBW and control infants using a scoring system adopted from literature. Tract-based spatial statistics (TBSS) was used to evaluate for differences in DTI measured fractional anisotropy (FA, spatially normalized to a customized template) among the ELBW and term control infants.
Results:
Conventional MRI white matter scores were not different (7.3 ± 1.7 vs. 6.9 ± 1.4, P = 0.65) between the hypercapnic and normocapnic ELBW infants. TBSS analysis did not show significant differences (P < 0.05, corrected) between the two ELBW infant groups, although before multiple comparisons correction, hypercapnic infants had many regions with lower FA and no regions with higher FA (P < 0.05, uncorrected) compared to normocapnic infants. When compared to the control infants, normocapnic ELBW infants had a few small regions with significantly lower FA, while hypercapnic ELBW infants had more widespread regions with significantly lower FA (P < 0.05, fully corrected for multiple comparisons).
Conclusions:
Normocapnic ventilation vs. permissive hypercapnia may be associated with improved white matter development at term-equivalent age in ELBW infants. This effect, however, was small and was not apparent on conventional MRI. Further research is needed using larger sample sizes to assess if permissive hypercapnic ventilation in ELBW infants is associated with worse white matter development.

