Xiawei Ou

The radial diffusivity and magnetization transfer pool size ratio are sensitive markers for demyelination in a rat model of type III multiple sclerosis (MS) lesions.

Determining biophysical sensitivity and specificity of quantitative magnetic resonance imaging is essential to develop effective imaging metrics of neurodegeneration. Among these metrics, apparent pool size ratio (PSR) from quantitative magnetization transfer (qMT) imaging and radial diffusivity (RD) from diffusion tensor imaging (DTI) are both known to relate to histological measure of myelin density and integrity. However their relative sensitivities towards quantitative myelin detection are unknown. In this study, we correlated high-resolution quantitative magnetic resonance imaging measures of subvoxel tissue structures with corresponding quantitative myelin histology in a lipopolysaccharide (LPS) mediated animal model of MS. Specifically, we acquired quantitative magnetization transfer (qMT) and diffusion tensor imaging (DTI) metrics (on the same tissue sample) in an animal model system of type III oligodendrogliopathy which lacked prominent lymphocytic infiltration, a system that had not been previously examined with quantitative MRI. We find that the qMT measured apparent pool size ratio (PSR) showed the strongest correlation with a histological measure of myelin content. DTI measured RD showed the next strongest correlation, and other DTI and relaxation parameters (such as the longitudinal relaxation rate (R1f) or fractional anisotropy (FA)) showed considerably weaker correlations with myelin content.

Quantitative Magnetization Transfer Measured Pool Size Ratio Reflects Optic Nerve Myelin Content in ex vivo Mice

Optic nerves from mice that have undergone retinal ischemia were examined using a newly implemented quantitative magnetization transfer (qMT) technique. Previously published results indicate that the optic nerve from retinal ischemia mice suffered significant axon degeneration without detectable myelin injury at 3 days after reperfusion. At this time point, we acquired ex vivo qMT parameters from both shiverer mice (which have nearly no myelin) and control mice that have undergone retinal ischemia, and these qMT measures were compared with diffusion tensor imaging (DTI) results. Our findings suggests that the qMT estimated ratio of the pool sizes of the macromolecular and free water protons reflected the different myelin contents in the optic nerves between the shiverer and control mice. This pool size ratio was specific to myelin content only and was not significantly affected by the presence of axon injury in mouse optic nerve 3 days after retinal ischemia. Magn Reson Med 61:364–371, 2009.

MT effects and T1 quantification in single‐slice spoiled gradient echo imaging

We investigated magnetization transfer (MT) effects on the steady‐state MR signal for a sample subjected to a series of identical on‐resonance RF pulses, such as would be experienced while imaging a single slice using a spoiled gradient echo sequence. The MT coupling terms for a two‐pool system were added to the Bloch equations and we derived the resulting steady‐state signal equation and compared this result to the conventional signal equation without MT effects. The steady‐state signal is increased by a few percent of the equilibrium magnetization because of MT. One consequence of this MT effect is inaccuracy in T1 values determined via conventional steady‐state gradient echo methods. (Theory predicts greater than 10% errors in T1 for white matter when using short TR.) A second consequence is the ability to quantify the relaxation and MT parameters by fitting the gradient echo steady state signal to the signal equation appropriately modified to include MT effects. The theory was tested in samples of MnCl2, cross‐linked bovine serum albumin (BSA), and cross‐linked BSA + MnCl2. Magn Reson Med, 2008.

Breathing resistance and ultrafine particle deposition in nasal-laryngeal airways of a newborn, an infant, a child, and an adult.

As a human grows from birth to adulthood, both airway anatomy and breathing conditions vary, altering the deposition rate and pattern of inhaled aerosols. However, deposition studies have typically focused on adult subjects, results of which may not be readily extrapolated to children. This study numerically evaluated the age-related effects on the airflow and aerosol dynamics in image-based nose–throat models of a 10-day-old newborn, a 7-month-old infant, a 5-year-old child, and a 53-year-old adult. Differences in airway physiology, breathing resistance, and aerosol filtering efficiency among the four models were quantified and compared. A high-fidelity fluid-particle transport model was employed to simulate the multi-regime airflows and particle transport within the nasal–laryngeal airways. Ultrafine particles were evaluated under breathing conditions ranging from sedentary to heavy activities. Results of this study indicate that the nasal–laryngeal airways at different ages, albeit differ significantly in morphology and dimension, do not significantly affect the total deposition fractions or maximum local deposition enhancement for ultrafine aerosols. Further, the deposition partitioning in the sub-regions of interest is different among the four models. Results of this study corroborate the use of the in vivo-based diffusion parameter (D0.5Q−0.28) over the replica-based parameter in correlating nasal–laryngeal depositions of ultrafine aerosols. Improved correlations have been developed for the four age groups by implementing this in vivo-based diffusion parameter as well as the Cunningham correction factor.

Brain gray and white matter differences in healthy normal weight and obese children

To compare brain gray and white matter development in healthy normal weight and obese children.

Maternal adiposity negatively influences infant brain white matter development

To study potential effects of maternal body composition on central nervous system (CNS) development of newborn infants.

Sex-specific association between infant diet and white matter integrity in 8-y-old children

Background:The American Academy of Pediatrics recommends breastfeeding, which is well known to promote cognitive and behavioral development. The evidence for why this occurs is not well understood.Methods:Fifty-six 7.5- to 8.5-y-old healthy children were breastfed (BF; n = 22, 10 males) or formula-fed (FF; n = 34, 16 males) as infants. All children were administered: the Reynolds Intellectual Assessment Scale (RIAS); the Clinical Evaluation of Language Fundamentals (CELF-4) tests; and magnetic resonance imaging of the brain. Diffusion tensor imaging (DTI) measured fractional anisotropy (FA) values were correlated with RIAS and CELF-4 scores.Results:DTI tract-based spatial statistics (TBSS) analyses showed multiple white matter regions in the left hemisphere with significantly higher FA (P < 0.05, corrected) values in BF than FF males, but no significant group differences in females. Males who were exclusively BF for at least 1 y appeared to have the greatest differences in FA. Mean FA values positively correlated with composite scores of RIAS (P = 0.03) and CELF-4 (P = 0.02).Conclusion:Breastfeeding during infancy was associated with better white matter development at 8 y of age in boys. A similar association was not observed in girls.

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 evaluation of white matter in adolescents with myelomeningocele and Chiari II malformation.

BackgroundMacrostructural abnormalities in cerebral white matter in patients with myelomeningocele are well known, but microstructural abnormalities are not as well studied.ObjectiveThe aim of this study was to evaluate cerebral white matter in adolescents with myelomeningocele using diffusion tensor imaging (DTI), and to investigate the effects of ventricular dilation and CSF shunt presence on white matter microstructure in these patients.Materials and methodsDTI and T1-weighted 3-D (T1-3-D) MRI were performed on nine adolescents with myelomeningocele and Chiari II malformation and nine age-matched controls. The fractional anisotropy (FA) and mean diffusivity (MD) values were measured and compared.ResultsSignificantly decreased FA and increased MD values were observed in most white matter regions and fibers in adolescents with myelomeningocele compared to controls. Further analysis in patients revealed significant changes in DTI parameters in hemispheres with enlarged lateral ventricles compared to those with normal ventricle size. In addition, a significant difference in FA values in the posterior limb of the internal capsule was found in the comparison of hemispheres in patients with or without CSF shunt catheters.ConclusionThis study revealed widespread microstructural abnormalities in white matter in adolescents with myelomeningocele and Chiari II malformation. Ventricular dilation may have additional effects on white matter microstructure in this patient population. CSF shunt diversion effects on white matter may be multifactorial and need further investigation.

Voxel-Based Morphometry and fMRI Revealed Differences in Brain Gray Matter in Breastfed and Milk Formula–Fed Children

BACKGROUND AND PURPOSE: Infant diets may have significant impact on brain development in children. The aim of this study was to evaluate brain gray matter structure and function in 8-year-old children who were predominantly breastfed or fed cows milk formula as infants. MATERIALS AND METHODS: Forty-two healthy children (breastfed: n = 22, 10 boys and 12 girls; cows milk formula: n = 20, 10 boys and 10 girls) were studied by using structural MR imaging (3D T1-weighted imaging) and blood oxygen level–dependent fMRI (while performing tasks involving visual perception and language functions). They were also administered standardized tests evaluating intelligence (Reynolds Intellectual Assessment Scales) and language skills (Clinical Evaluation of Language Fundamentals). RESULTS: Total brain gray matter volume did not differ between the breastfed and cows milk formula groups. However, breastfed children had significantly higher (P < .05, corrected) regional gray matter volume measured by voxel-based morphometry in the left inferior temporal lobe and left superior parietal lobe compared with cows milk formula–fed children. Breastfed children showed significantly more brain activation in the right frontal and left/right temporal lobes on fMRI when processing the perception task and in the left temporal/occipital lobe when processing the visual language task than cows milk formula–fed children. The imaging findings were associated with significantly better performance for breastfed than cows milk formula–fed children on both tasks. CONCLUSIONS: Our findings indicated greater regional gray matter development and better regional gray matter function in breastfed than cows milk formula–fed children at 8 years of age and suggested that infant diets may have long-term influences on brain development in children.