Qinli Sun

Tract-based spatial statistics (TBSS): Application to detecting white matter tract variation in mild hypoxic-ischemic neonates

The aim of this study is to employ tract-based spatial statistics (TBSS) to analyze the voxel-wise differences in DTI parameters between normal and mild hypoxic-ischemic (HI) neonatal brains. Forty-one full term neonates (24 normal controls and 17 with mild HI injury) and 31 preterm neonates (20 normal controls and 11 with mild HI injury) underwent T1 weighted imaging, T2 weighted imaging and diffusion tensor imaging (DTI) within 28 days after birth. The voxel differences of fractional anisotropy (FA), λ1, λ2, and λ3 values between mild HI group and control group were analyzed in preterm and full term neonates respectively. The significantly decreased FA with increased λ2, λ3 in corticospinal tract, genu of corpus callosum (GCC), external capsule (EC) and splenium of the corpus callosum (SCC) in mild HI neonates suggested deficits or delays in both myelination and premyelination. Such impaired corticospinal tract, in both preterm and term neonates, may directly lead to the subsequent poor motor performance. Impaired EC and SCC, the additional injured sites observed in full term neonates with mild HI injury, may be causally responsible for the dysfunction in coordination and integration. In conclusion, TBSS provides an objective, independent and sensitive method for DTI data analysis of neonatal white matter alterations after mild HI injury.

Differentiating T2 hyperintensity in neonatal white matter by two-compartment model of diffusional kurtosis imaging.

In conventional neonatal MRI, the T2 hyperintensity (T2h) in cerebral white matter (WM) at term-equivalent age due to immaturity or impairment is still difficult to identify. To clarify such issue, this study used the metrics derived from a two-compartment WM model of diffusional kurtosis imaging (WM-DKI), including intra-axonal, extra-axonal axial and radial diffusivities (Da, De,// and De,⊥), to compare WM differences between the simple T2h and normal control for both preterm and full-term neonates, and between simple T2h and complex T2h with hypoxic-ischemic encephalopathy (HIE). Results indicated that compared with control, the simple T2h showed significantly increased De,// and De,⊥, but no significant change in Da in multiple premyelination regions, indicative of expanding extra-axonal diffusion microenvironment; while myelinated regions showed no changes. However, compared with simple T2h, the complex T2h with HIE had decreased Da, increased De,⊥ in both premyelination and myelinated regions, indicative of both intra- and extra-axonal diffusion alterations. While diffusion tensor imaging (DTI) failed to distinguish simple T2h from complex T2h with HIE. In conclusion, superior to DTI-metrics, WM-DKI metrics showed more specificity for WM microstructural changes to distinguish simple T2h from complex T2h with HIE.

Diffusion kurtosis imaging with tract-based spatial statistics reveals white matter alterations in preschool children

Diffusion kurtosis imaging (DKI), an extension of diffusion tensor imaging (DTI), provides a practical method to describe non-Gaussian water diffusion in neural tissues. The sensitivity of DKI to detect the subtle changes in several chosen brain structures has been studied. However, intuitive and holistic methods to validate the merits of DKI remain to be explored. In this paper, tract-based spatial statistics (TBSS) was used to demonstrate white matter alterations in both DKI and DTI parameters in preschool children (1-6 years; n=10). Correlation analysis was also performed in multiple regions of interest (ROIs). Fractional anisotropy, mean kurtosis, axial kurtosis and radial kurtosis increased with age, while mean diffusivity and radial diffusivity decreased significantly with age. Fractional anisotropy of kurtosis and axial diffusivity were found to be less sensitive to the changes with age. These preliminary findings indicated that TBSS could be used to detect subtle changes of DKI parameters on the white matter tract. Kurtosis parameters, except fractional anisotropy of kurtosis, demonstrated higher sensitivity than DTI parameters. TBSS may be a convenient method to yield higher sensitivity of DKI.

Semi-quantitative assessment of brain maturation by conventional magnetic resonance imaging in neonates with clinically mild hypoxic-ischemic encephalopathy

Background: Mild hypoxic-ischemic encephalopathy (HIE) injury is becoming the major type in neonatal brain diseases. The aim of this study was to assess brain maturation in mild HIE neonatal brains using total maturation score (TMS) based on conventional magnetic resonance imaging (MRI). Methods: Totally, 45 neonates with clinically mild HIE and 45 matched control neonates were enrolled. Gestated age, birth weight, age after birth and postmenstrual age at magnetic resonance (MR) scan were homogenous in the two groups. According to MR findings, mild HIE neonates were divided into three subgroups: Pattern I, neonates with normal MR appearance; Pattern II, preterm neonates with abnormal MR appearance; Pattern III, full-term neonates with abnormal MR appearance. TMS and its parameters, progressive myelination (M), cortical infolding (C), involution of germinal matrix tissue (G), and glial cell migration bands (B), were employed to assess brain maturation and compare difference between HIE and control groups. Results: The mean of TMS was significantly lower in mild HIE group than it in the control group (mean ± standard deviation [SD] 11.62 ± 1.53 vs. 12.36 ± 1.26, P < 0.001). In four parameters of TMS scores, the M and C scores were significantly lower in mild HIE group. Of the three patterns of mild HIE, Pattern I (10 cases) showed no significant difference of TMS compared with control neonates, while Pattern II (22 cases), III (13 cases) all had significantly decreased TMS than control neonates (mean ± SD 10.56 ± 0.93 vs. 11.48 ± 0.55, P < 0.05; 12.59 ± 1.28 vs. 13.25 ± 1.29, P < 0.05). It was M, C, and GM scores that significantly decreased in Pattern II, while for Pattern III, only C score significantly decreased. Conclusions: The TMS system, based on conventional MRI, is an effective method to detect delayed brain maturation in clinically mild HIE. The conventional MRI can reveal the different retardations in subtle structures and development processes among the different patterns of mild HIE.

Proper timing for the evaluation of neonatal brain white matter development: a diffusion tensor imaging study

ObjectiveWe aimed to determine the timing for assessing birth status of the developing brain (i.e. brain maturity at birth) by exploring the postnatal age-related changes in neonatal brain white matter (WM).MethodsThe institutional review board approved this study and all informed parental consents were obtained. 133 neonates (gestational age, 30–42 weeks) without abnormalities on MRI were studied with regard to WM development by diffusion tensor imaging-derived fractional anisotropy (FA). Tract-based spatial statistics (TBSS), locally-weighted scatterplot smoothing (LOESS) and piecewise linear-fitting were used to investigate the relationship between FA and postnatal age. FA along corticospinal tract (CST), optic radiation (OR), auditory radiation (AR) and thalamus-primary somatosensory cortex (thal-PSC) were extracted by automated fibre-tract quantification; their differences and associations with neonatal neurobehavioural scores at various postnatal age ranges were analysed by Wilcoxon’s rank-sum test and Pearson’s correlation.ResultsUsing TBSS, postnatal age (days 1–28) positively correlated with FA in multiple WMs, including CST, OR, AR and thal-PSC (p<0.05). On the other hand, when narrowing the postnatal age window to days 1–14, no significant correlation was found, suggesting a biphasic WM development. LOESS and piecewise linear-fitting indicated that FA increased mildly before day 14 and its growth accelerated thereafter. Both FA and correlations with neurobehavioural scores in postnatal age range 2 (days 15–28) were significantly higher than in range 1 (days 1–14) (FA comparison: p<0.05; maximal correlation-coefficient: 0.693 vs. 0.169).ConclusionBrain WM development during the neonatal stage includes two phases, i.e. a close-to-birth period within the first 14 days and a following accelerated maturation period. Therefore, evaluations of birth status should preferably be performed during the first period.Key Points• Brain white matter development within the first two postnatal weeks resembles a close-to-birth maturation.• Brain white matter development in the audio-visual, sensorimotor regions accelerates after two postnatal weeks.• Postnatal age-related effects should be considered in comparing preterm and term neonates.