Collapse or distention of the perioptic space in children - What does it mean to pediatric radiologists? Comprehensive review of perioptic space evaluation.

The perioptic space comprises the subarachnoid space [SAS] of the optic nerve communicating with the SAS of the central nervous system. Pressure variations in the SAS of the central nervous system can be transmitted to the optic papilla through the perioptic space. Variations in the diameter of the perioptic space serve as an important indicator for select intracranial pathologies in the pediatric population. Though the perioptic space can be evaluated using various imaging modalities, MRI is considered highly effective due to its superior soft tissue resolution. With advancement in MR imaging techniques, high-resolution images of the orbits can provide improved visualization of the perioptic space. It is imperative for the pediatric radiologist to routinely assess the perioptic space on brain and orbit MR imaging, as it can prompt exploration for additional features associated with select intracranial pathologies, thus improving diagnostic accuracy. This article reviews basic anatomy of the perioptic space, current understanding of the CSF dynamics between the perioptic space and central nervous system SAS, various imaging modalities utilized in the assessment of the perioptic space, MRI sequences and the optimal parameters of specific sequences, normal appearance of the perioptic space on MR imaging, and various common pediatric pathologies which cause alteration in the perioptic space.

Maternal Diet Quality during Pregnancy Is Associated with Neonatal Brain White Matter Development.

Maternal diet and nutrient intake are important for fetal growth and development. In this study, we aim to evaluate whether there are associations between maternal diet quality and the offspring's brain white matter development. Healthy pregnant women's (N = 44) nutrition intake was assessed by the Healthy Eating Index-2015 (HEI-2015) during the first, second, and third trimesters, respectively. Correlations between MRI diffusion tensor imaging measured fractional anisotropy (FA) of the neonatal brain and the HEI-2015 scores were evaluated using voxel-wise analysis with appropriate multiple comparisons correction and post hoc analysis based on regions of interest. Significant correlations were found between sodium scores at the first trimester of pregnancy and mean neonatal FA values in parietal white matter (R = 0.39, p = 0.01), anterior corona radiata (R = 0.43, p = 0.006), posterior limb of internal capsule (R = 0.53, p < 0.001), external capsule (R = 0.44, p = 0.004), and temporal white matter (R = 0.50, p = 0.001) of the left hemisphere. No other correlations were identified. In conclusion, the relationships between the maternal sodium intake score and the neonatal white matter microstructural development indicate sodium intake patterns better aligned with the Dietary Guidelines for Americans during early pregnancy are associated with greater white matter development in the offspring's brain.

Associations between mother's depressive symptoms during pregnancy and newborn's brain functional connectivity.

Depression during pregnancy is common and the prevalence further increased during the COVID pandemic. Recent findings have shown potential impact of antenatal depression on children's neurodevelopment and behavior, but the underlying mechanisms are unclear. Nor is it clear whether mild depressive symptoms among pregnant women would impact the developing brain. In this study, 40 healthy pregnant women had their depressive symptoms evaluated by the Beck Depression Inventory-II at ~12, ~24, and ~36 weeks of pregnancy, and their healthy full-term newborns underwent a brain MRI without sedation including resting-state fMRI for evaluation of functional connectivity development. The relationships between functional connectivities and maternal Beck Depression Inventory-II scores were evaluated by Spearman's rank partial correlation tests using appropriate multiple comparison correction with newborn's gender and gestational age at birth controlled. Significant negative correlations were identified between neonatal brain functional connectivity and mother's Beck Depression Inventory-II scores in the third trimester, but not in the first or second trimester. Higher depressive symptoms during the third trimester of pregnancy were associated with lower neonatal brain functional connectivity in the frontal lobe and between frontal/temporal lobe and occipital lobe, indicating a potential impact of maternal depressive symptoms on offspring brain development, even in the absence of clinical depression.

Utility of balanced steady-state field precession sequence in the evaluation of retinal and subdural hemorrhages in patients with abusive head trauma.

Abusive head trauma is the leading cause of physical child abuse deaths in children under 5 years of age in the United States. To evaluate suspected child abuse, radiologic studies are typically the first to identify hallmark findings of abusive head trauma including intracranial hemorrhage, cerebral edema, and ischemic injury. Prompt evaluation and diagnosis are necessary as findings may change rapidly. Current imaging recommendations include brain magnetic resonance imaging with the addition of a susceptibility weighted imaging (SWI) sequence which can detect additional findings that suggest abusive head trauma including cortical venous injury and retinal hemorrhages. However, SWI is limited due to blooming artifacts and artifacts from the adjacent skull vault or retroorbital fat, which can affect the evaluation of retinal, subdural, and subarachnoid hemorrhages. This work explores the utility of the high-resolution, heavily T2 weighted balanced steady-state field precession (bSSFP) sequence to identify and characterize retinal hemorrhage and cerebral cortical venous injury in children with abusive head trauma. The bSSFP sequence provides distinct anatomical images to improve the identification of retinal hemorrhage and cortical venous injury.

Mother's physical activity during pregnancy and newborn's brain cortical development.

Background: Physical activity is known to improve mental health, and is regarded as safe and desirable for uncomplicated pregnancy. In this novel study, we aim to evaluate whether there are associations between maternal physical activity during pregnancy and neonatal brain cortical development. Methods: Forty-four mother/newborn dyads were included in this longitudinal study. Healthy pregnant women were recruited and their physical activity throughout pregnancy were documented using accelerometers worn for 3-7 days for each of the 6 time points at 4-10, ∼12, ∼18, ∼24, ∼30, and ∼36 weeks of pregnancy. Average daily total steps and daily total activity count as well as daily minutes spent in sedentary/light/moderate/vigorous activity modes were extracted from the accelerometers for each time point. At ∼2 weeks of postnatal age, their newborns underwent an MRI examination of the brain without sedation, and 3D T1-weighted brain structural images were post-processed by the iBEAT2.0 software utilizing advanced deep learning approaches. Cortical surface maps were reconstructed from the segmented brain images and parcellated to 34 regions in each brain hemisphere, and mean cortical thickness for each region was computed for partial correlation analyses with physical activity measures, with appropriate multiple comparison corrections and potential confounders controlled. Results: At 4-10 weeks of pregnancy, mother's daily total activity count positively correlated (FDR corrected P ≤ 0.05) with newborn's cortical thickness in the left caudal middle frontal gyrus (rho = 0.48, P = 0.04), right medial orbital frontal gyrus (rho = 0.48, P = 0.04), and right transverse temporal gyrus (rho = 0.48, P = 0.04); mother's daily time in moderate activity mode positively correlated with newborn's cortical thickness in the right transverse temporal gyrus (rho = 0.53, P = 0.03). At ∼24 weeks of pregnancy, mother's daily total activity count positively correlated (FDR corrected P ≤ 0.05) with newborn's cortical thickness in the left (rho = 0.56, P = 0.02) and right isthmus cingulate gyrus (rho = 0.50, P = 0.05). Conclusion: We identified significant relationships between physical activity in healthy pregnant women during the 1st and 2nd trimester and brain cortical development in newborns. Higher maternal physical activity level is associated with greater neonatal brain cortical thickness, presumably indicating better cortical development.

Associations Between White Matter Microstructures and Cognitive Functioning in 8-Year-Old Children: A Track-Weighted Imaging Study.

PURPOSE: Quantitative tractography using diffusion-weighted magnetic resonance imaging data is widely used in characterizing white matter microstructure throughout childhood, but more studies are still needed to investigate comprehensive brain-behavior relationships between tract-specific white matter measures and multiple cognitive functions in children. METHODS: In this study, we analyzed diffusion-weighted MRI data of 71 healthy 8-year-old children utilizing white matter tract-specific quantitative measures derived from diffusion-weighted MRI tractography based on a novel track-weighted imaging approach. Track density imaging, average path length map and 4 track-weighted diffusion tensor imaging measures including: mean diffusivity, fractional anisotropy, axial diffusivity, and radial diffusivity were computed for 63 white matter tracts. The track-weighted imaging measures were then correlated with a comprehensive set of neuropsychological test scores in different cognitive domains including intelligence, language, memory, academic skills, and executive functions to identify tract-specific brain-behavior relationships. RESULTS: Significant correlations (P < .05, false discovery rate corrected; r = 0.27-0.57) were found in multiple white matter tracts, with a total of 40 correlations identified between various track-weighted imaging measures including average path length map, track-weighted imaging-fractional anisotropy, and neuropsychological test scores and subscales. Specifically, track-weighted imaging measures indicative of better white matter connectivity and/or microstructural development significantly correlated with higher IQ and better language abilities. CONCLUSION: Our findings demonstrate the ability of track-weighted imaging measures in establishing associations between white matter and cognitive functioning in healthy children and can serve as a reference for normal brain/cognition relationships in young school-age children and further aid in identifying imaging biomarkers predictive of adverse neurodevelopmental outcomes.

Associations between Cortical Asymmetry and Domain Specific Cognitive Functions in Healthy Children.

Cortical asymmetry and functional lateralization form intriguing and fundamental features of human brain organization, and is complicated by individual differences and evolvement with age. While many studies have investigated neuroanatomical differences between hemispheres as well as functional lateralization of the brain for different age groups, few have looked into the associations between cortical asymmetry and development of cognitive functions in children. In this study, we aimed to identify relationships between hemispheric asymmetry in brain cortex measured by MRI and cognitive development in healthy young children evaluated by a comprehensive battery of neuropsychological tests. Structural MRI data were obtained from 71 children in the age range of 7.5 to 8.5 years. Structural lateralization index (SLI), a reflection of the brain asymmetry, was computed for each of the 3 cortical morphometry measurements: cortical thickness, surface area and gray matter volume. A total of 34 bilateral regions were studied for the whole brain cortex as defined by the Desikan atlas. Region-wise SLI was correlated with domain specific cognitive scores using partial correlation analysis controlled for the potential confounding effects of age and sex. Significant correlations were identified between test scores of multiple cognitive domains and SLI of several cortical regions. Specifically, SLI of total surface area of precuneus and insula significantly correlated with measures of executive function behavior; significant relationships were also found between SLI of mean cortical thickness of superior parietal cortex and memory and language tests scores; in addition, SLI of parahippocampal gyrus also showed significant correlations with language test scores for all 3 morphometry features. These findings revealed regional hemispheric asymmetries that may be linked to specific cognitive abilities in children.Clinical relevance- This study shows associations between structural lateralization in different brain cortical regions and variations in specific cognitive functions in healthy children.

Fatal Cerebral Vasospasm following a Haemophilus influenzae Meningitis in a Young Child with Ventriculoperitoneal Shunt.

INTRODUCTION: Despite the successful implementation of Haemophilus influenzae vaccination, invasive serotypes still lead to a fatal infection. We recently cared for a patient with a ventriculoperitoneal shunt (VPS) and H. influenzae meningitis and septicemia complicated by vasospasm. Vasospasm caused by Haemophilus central nervous system infection has not been previously reported. CASE PRESENTATION: A 34-month-old patient with a recent VPS presented with H. influenzae meningitis and sepsis. Despite the explant of hardware, followed by maximum medical management, the patient developed stroke due to severe vasospasm, which led to diffused anoxic brain injury. CONCLUSIONS: We aim to alert for the possible critical condition caused by H. influenzae. It is essential to treat the underlying illness, despite the presence of a VPS. Surgical implant tends to be overlooked by other subspecialists. Being vaccinated to H. influenzae does not protect from different subtypes like non-typeable H. influenzae. The cause of vasospasm remains unclear.

Diffusion Tensor MRI of White Matter of Healthy Full-term Newborns: Relationship to Neurodevelopmental Outcomes.

Background It is well known that white matter injuries observed at birth are associated with adverse neurodevelopmental outcomes later in life. Whether white matter developmental variations in healthy newborns are also associated with changes in later neurodevelopment remains to be established. Purpose To evaluate whether developmental variations of white matter microstructures identified by MRI correlate with neurodevelopmental outcomes in healthy full-term infants. Materials and Methods In this prospective study, pregnant women were recruited and their healthy full-term newborns underwent a brain MRI including diffusion tensor imaging at approximately 2 weeks of age. These infants were tested at approximately 2 years of age with the Bayley Scales of Infant Development (BSID). Voxel-wise correlation analyses of fractional anisotropy (FA), measured with diffusion tensor MRI, and neurodevelopmental test scores, measured by using BSID, were performed by using tract-based spatial statistics (TBSS), followed by region-of-interest (ROI) analyses of correlations between mean FA in selected white matter ROIs and each BSID subscale score. Results Thirty-eight full-term infants (20 boys, 18 girls) underwent MRI examination at 2 weeks of age (14.3 days ± 1.6) and BSID measurement at 2 years of age (732 days ± 6). TBSS analyses showed widespread clusters in major white matter tracts, with positive correlations (P ≤ .05, corrected for the voxel-wise multiple comparisons) between FA values and multiple BSID subscale scores. These correlations were largely independent of several demographic parameters as well as family environment. Gestational age at birth appeared to be a confounding factor as TBSS-observed correlations weakened when it was included as a covariate; however, after controlling for gestational age at birth, ROI analyses still showed positive correlations (P ≤ .05, R = 0.35 to 0.48) between mean FA in many white matter ROIs and BSID cognitive, language, and motor scores. Conclusion There were significant associations between white matter microstructure developmental variations in healthy full-term newborns and their neurodevelopmental outcomes. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Hu and McAllister in this issue.

Injured Children Receive Twice the Radiation Dose at Nonpediatric Trauma Centers Compared With Pediatric Trauma Centers.

BACKGROUND: Use of cranial CT scans in children has been increasing, in part due to increased awareness of sports-related concussions. CT is the largest contributor to medical radiation exposure, a risk factor for cancer. Long-term cancer risks of CT scans can be two to three times higher for children than for adults because children are more radiosensitive and have a longer lifetime in which to accumulate exposure from multiple scans. STUDY AIM: To compare the radiation exposure injured children receive when imaged at nonpediatric hospitals (NPHs) versus pediatric hospitals. METHODS: Injured children younger than 18 years who received a CT scan at a referring hospital during calendar years (CYs) 2010 and 2013 were included. Patient-level factors included demographics, mode of transportation, and Injury Severity Score, and hospital-level factors included region of state, radiology services, and hospital type and size. Our primary outcome of interest was the effective radiation dose. RESULTS: Four hundred eighty-seven children were transferred to the pediatric trauma center during CYs 2010 and 2013, with a median age of 7.2 years (interquartile range 5-13). The median effective radiation dose received at NPHs was twice that received at the pediatric trauma center (3.8 versus 1.6 mSv, P < .001). Results were confirmed in independent and paired analyses, after controlling for mode of transportation, emergency department disposition, level of injury severity, and at the NPH trauma center level, hospital type, size, region, and radiology services location. CONCLUSION: NPHs have the potential to substantially reduce the medical radiation received by injured children. Pediatric CT protocols should be considered.

Maternal Adiposity Influences Neonatal Brain Functional Connectivity.

The neural mechanisms associated with obesity have been extensively studied, but the impact of maternal obesity on fetal and neonatal brain development remains poorly understood. In this study of full-term neonates, we aimed to detect potential neonatal functional connectivity alterations associated with maternal adiposity, quantified via body-mass-index (BMI) and body-fat-mass (BFM) percentage, based on seed-based and graph theoretical analysis using resting-state fMRI data. Our results revealed significant neonatal functional connectivity alterations in all four functional domains that are implicated in adult obesity: sensory cue processing, reward processing, cognitive control, and motor control. Moreover, some of the detected areas showing regional functional connectivity alterations also showed global degree and efficiency differences. These findings provide important clues to the potential neural basis for cognitive and mental health development in offspring of obese mothers and may lead to the derivation of imaging-based biomarkers for the early identification of risks for timely intervention.

The Clinical Impact of a Web-Based Image Repository on Radiation Exposure in Injured Children.

PURPOSE: The long-term cancer risks for children exposed to radiologic images can be two to three times higher than for adults because children are more sensitive to radiation and have a longer lifetime in which to accumulate exposure from CT scans. Injured children often undergo repeat CT imaging if they are transferred from non-pediatric hospitals to a Level I pediatric trauma center (PTC). This study determined the impact of a statewide web-based image repository (WBIR) on repeat imaging among transferred injured children. METHODS: All injured children who underwent CT imaging and were transferred to the PTC in 2010 (pre-WBIR) and 2013 (post-WBIR) were included. Patient-level factors studied included demographics, body region of scan, Injury Severity Score, and Emergency Department (ED) disposition. Change from pre to post on rate of repeat imaging was assessed. RESULTS: Two hundred fifty-four and 233 children, with a median age of 7.3 years, were transferred to the Children's Hospital in 2010 and 2013, respectively. Repeat imaging levels at the PTC were lower post-WBIR than pre-WBIR (20% versus 33%, odds ratio [OR] 0.54, P = .005). Images of the head decreased most significantly (60% versus 33%, OR 0.33). Images performed at Level II and III trauma centers were repeated less often after WBIR. CONCLUSIONS: The WBIR significantly reduced repeat imaging among injured children transferred to a PTC, especially children transferred from Level II and Level III trauma centers, children with lower-acuity injuries, and children with initial scans of the head. Radiation savings are expected to be beneficial to children.

Compression of the posterior fossa venous sinuses by epidural hemorrhage simulating venous sinus thrombosis: CT and MR findings.

BACKGROUND: Posterior fossa dural venous sinus thrombus is a well-described complication of head trauma, especially when fracture crosses the dural sinus grooves or in association with epidural hemorrhage. We have found that post-traumatic posterior fossa epidural hematoma compressing a dural venous sinus can mimic dural venous thrombus. OBJECTIVE: To discuss the CT and MRI findings of posterior fossa epidural hemorrhages simulating sinus thrombosis, to make radiologists aware of this important imaging pitfall. MATERIALS AND METHODS: We describe radiologic findings in four children in whom a posterior fossa epidural hemorrhage mimicked dural venous sinus thrombus. Routine CT head and CT venography were obtained on Toshiba volume and helical CT scanners. MRI and MR venography were performed on a Philips scanner. RESULTS: In all cases there was medial displacement and compression of the posterior fossa dural venous sinuses without intraluminal thrombosis. The epidural hemorrhage was seen tracking along sinus grooves in the occipital bone, peeling the dura containing the sinuses from the calvarium and compressing the sinus, simulating thrombosis on axial CT views. CONCLUSION: Both venous sinus thrombosis and posterior fossa epidural hemorrhages in children are well-described complications of head trauma. Posterior fossa epidural hemorrhage can mimic a sinus thrombus by compressing and displacing the sinuses. It is important to recognize this pitfall because treatment of a suspected thrombus with anticoagulation can worsen epidural hemorrhage.

Strategies for Computed Tomography Radiation Dose Reduction in Pediatric Neuroimaging.

BACKGROUND: Radiation exposure from diagnostic imaging is a significant concern, particularly in the care of pediatric patients. Computed tomography (CT) scanning is a significant source of radiation. OBJECTIVE: To demonstrate that diagnostic quality CT images can be obtained while minimizing the effective radiation dose to the patient. METHODS: In this retrospective cross-sectional study, noncontrast head CT scan data were reviewed, and indications for scans and estimated radiation dose delivered were recorded. The estimated effective radiation dose (EERD) for each CT protocol was reviewed. RESULTS: We identified 251 head CT scans in a single month. Of these, 96 scans were using a low-dose shunt protocol with a mean EERD of 0.82 mSv. The remaining 155 scans were performed using the standard protocol, and the mean EERD was 1.65 mSv. Overall, the EERD was minimized while maintaining diagnostic scan quality. CONCLUSION: Although replacing a CT with magnetic resonance imaging is ideal to completely avoid ionizing radiation, this is not always practical or preferred. Therefore, it is important to have CT protocols in place that minimize radiation dose without sacrificing diagnostic quality. The protocols in place at our institution could be replicated at other academic and community hospitals and imaging centers.

Amplitude-integrated EEG in newborns with critical congenital heart disease predicts preoperative brain magnetic resonance imaging findings.

OBJECTIVE: The study aims are to evaluate cerebral background patterns using amplitude-integrated electroencephalography in newborns with critical congenital heart disease, determine if amplitude-integrated electroencephalography is predictive of preoperative brain injury, and assess the incidence of preoperative seizures. We hypothesize that amplitude-integrated electroencephalography will show abnormal background patterns in the early preoperative period in infants with congenital heart disease that have preoperative brain injury on magnetic resonance imaging. METHODS: Twenty-four newborns with congenital heart disease requiring surgery at younger than 30 days of age were prospectively enrolled within the first 3 days of age at a tertiary care pediatric hospital. Infants had amplitude-integrated electroencephalography for 24 hours beginning close to birth and preoperative brain magnetic resonance imaging. The amplitude-integrated electroencephalographies were read to determine if the background pattern was normal, mildly abnormal, or severely abnormal. The presence of seizures and sleep-wake cycling were noted. The preoperative brain magnetic resonance imaging scans were used for brain injury and brain atrophy assessment. RESULTS: Fifteen of 24 infants had abnormal amplitude-integrated electroencephalography at 0.71 (0-2) (mean [range]) days of age. In five infants, the background pattern was severely abnormal. (burst suppression and/or continuous low voltage). Of the 15 infants with abnormal amplitude-integrated electroencephalography, 9 (60%) had brain injury. One infant with brain injury had a seizure on amplitude-integrated electroencephalography. A severely abnormal background pattern on amplitude-integrated electroencephalography was associated with brain atrophy (P = 0.03) and absent sleep-wake cycling (P = 0.022). CONCLUSION: Background cerebral activity is abnormal on amplitude-integrated electroencephalography following birth in newborns with congenital heart disease who have findings of brain injury and/or brain atrophy on preoperative brain magnetic resonance imaging.

Brain ketones detected by proton magnetic resonance spectroscopy in an infant with Ohtahara syndrome treated with ketogenic diet.

Atypical resonances on proton magnetic resonance spectroscopy (MRS) examinations are occasionally found in children undergoing a metabolic evaluation for neurological conditions. While a radiologist's first instinct is to suspect a pathological metabolite, usually the origin of the resonance arises from an exogenous source. We report the appearance of distinct resonances associated with a ketogenic diet in a male infant presenting with Ohtahara syndrome. These resonances can be confused in interpretation with lactate and glutamate. To confirm assignments, the basis set for quantification was supplemented with simulations of ß-hydroxybutyrate, acetone and acetoacetate in LCModel spectroscopy processing software. We were able to quantitate the levels of end products of a ketogenic diet and illustrate how to distinguish these resonances.

White matter injury in newborns with congenital heart disease: a diffusion tensor imaging study.

BACKGROUND: Brain injury is observed on cranial magnetic resonance imaging preoperatively in up to 50% of newborns with congenital heart disease. Newer imaging techniques such as diffusion tensor imaging provide sensitive measures of the white matter integrity. The objective of this study was to evaluate the diffusion tensor imaging analysis technique of tract-based spatial statistics in newborns with congenital heart disease. METHODS: Term newborns with congenital heart disease who would require surgery at less than 1 month of age were prospectively enrolled (n = 19). Infants underwent preoperative and postoperative brain magnetic resonance imaging with diffusion tensor imaging. Tract-based spatial statistics, an objective whole-brain diffusion tensor imaging analysis technique, was used to determine differences in white matter fractional anisotropy between infant groups. Term control infants were also compared with congenital heart disease infants. Postmenstrual age was equivalent between congenital heart disease infant groups and between congenital heart disease and control infants. RESULTS: Ten infants had preoperative brain injury, either infarct or white matter injury, by conventional brain magnetic resonance imaging. The technique of tract-based spatial statistics showed significantly lower fractional anisotropy (P < 0.05, corrected) in multiple major white matter tracts in the infants with preoperative brain injury compared with infants without preoperative brain injury. Fractional anisotropy values increased in the white matter tracts from the preoperative to the postoperative brain magnetic resonance imaging correlating with brain maturation. Control infants had higher fractional anisotropy in multiple white matter tracts compared with infants with congenital heart disease. CONCLUSION: Tract-based spatial statistics is a valuable diffusion tensor imaging analysis technique that may have better sensitivity in detecting white matter injury compared with conventional brain magnetic resonance imaging in term newborns with congenital heart disease.

Diffusion tensor imaging in extremely low birth weight infants managed with hypercapnic vs. normocapnic ventilation.

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.