D Qiu

Diffusion tensor imaging of normal white matter maturation from late childhood to young adulthood: Voxel-wise evaluation of mean diffusivity, fractional anisotropy, radial and axial diffusivities, and correlation with reading development

Using diffusion tensor MR imaging (DTI) and advanced voxel-wise analysis tools, we study diffusivity and anisotropy changes of white matter from late childhood to young adulthood, and correlate quantitative diffusion indices with Chinese and English reading performance scores. Seventy-five normal healthy school going ethnic Chinese students and young adults of three age groups were recruited (group 1, n=24, mean+/-SD=7.4+/-0.3 years; group 2, n=27, mean+/-SD=10.3+/-0.5 years; group 3, n=24, mean+/-SD=22.8+/-2.3 years). DTI was performed with 3 mm isotropic resolution to cover the entire brain. Voxel-wise analysis was performed using Tract-Based Spatial Statistics (TBSS) to localize regions of white matter showing significant changes of fractional anisotropy (FA), mean diffusivity (MD), and axial and radial diffusivities between groups. We found increased FA and decreased MD with increasing age in regions of cerebellar white matter, right temporal white matter, and a large portion of the superior frontal and parietal white matter driven by both the reduction of radial diffusivity and axial diffusivity with the former to a greater extent. Changes were continual from late childhood to young adulthood. Findings were confirmed by region-of-interest analysis in specific white matter tracts. After controlling for the effect of age, significant correlation was found between diffusion indices of the anterior limb of the left internal capsule and Chinese reading score (p=0.05), and of the corona radiata and English reading score (p=0.026 and p=0.029 for left and right, respectively). These DTI indices likely reflect the multiple biological processes that occur during brain development which provide the neural substrate for ongoing functional connectivity including for reading development.

White Matter Anisotropy in Post-Treatment Childhood Cancer Survivors: Preliminary Evidence of Association With Neurocognitive Function

PURPOSE We aim to determine if the loss of white matter fractional anisotropy (FA), measured by diffusion tensor magnetic resonance imaging (DTI), in post-treatment childhood medulloblastoma (MED) and acute lymphoblastic leukemia (ALL) survivors correlate with intelligence quotient (IQ) scores. MATERIALS AND METHODS MED and ALL survivors (n = 30; 20 male, 10 female; age range, 6.0 to 22.1 years; mean, 13.1 years) were recruited for DTI and IQ tests. In this cross-sectional study, age-matched normal control (n = 55; 32 male, 23 female; age range, 6.0 to 23 years; mean, 12.1 years) DTI was obtained to compute percentage difference in white matter FA (DeltaFA%) for each patient compared with the age-matched control group. Multivariate regression analysis was performed to determine the relationships between DeltaFA%, age at treatment, irradiation dose, time interval from treatment, and full-scale IQ (FSIQ), verbal IQ (VIQ), and performance IQ (PIQ). Receiver operating characteristics curves were used to determine the best DeltaFA% cutoffs for predicting FSIQ, VIQ, and PIQ of less than 85. RESULTS DeltaFA% had a significant effect on FSIQ (adjusted r2 = 0.439; P < .001), VIQ (adjusted r(2) = 0.237; P = .028), and PIQ (adjusted r(2) = 0.491; P < .001) after adjusting for the effects of age at treatment, irradiation dose, and time interval from treatment. The best DeltaFA% value to predict less than 85 scores in FSIQ, VIQ, and PIQ was -3.3% with specificities of 100% and sensitivities ranging from 77.8% to 87.5%. CONCLUSION Our preliminary findings suggest that white matter FA may be a clinically useful biomarker for the assessment of treatment-related neurotoxicity in post-treatment childhood cancer survivors.

White Matter Development in Adolescence: Diffusion Tensor Imaging and Meta-Analytic Results

BACKGROUND In light of the evidence for brain white matter (WM) abnormalities in schizophrenia, study of normal WM maturation in adolescence may provide critical insights relevant to the neurodevelopment of the disorder. Voxel-wise diffusion tensor imaging (DTI) studies have consistently demonstrated increases in fractional anisotropy (FA), a putative measure of WM integrity, from childhood into adolescence. However, the WM tracts that show FA increases have been variable across studies. Here, we aimed to assess which WM tracts show the most pronounced changes across adolescence. METHODS DTI was performed in 78 healthy subjects aged 8-21 years, and voxel-wise analysis conducted using tract-based spatial statistics (TBSS). In addition, we performed the first meta-analysis of TBSS studies on WM development in adolescence. RESULTS In our sample, we observed bilateral increases in FA with age, which were most significant in the left superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, and anterior thalamic radiation. These findings were confirmed by the meta-analysis, and FA increase in the bilateral SLF was the most consistent finding across studies. Moreover, in our sample, FA of the bilateral SLF showed a positive association with verbal working memory performance and partially mediated increases in verbal fluency as a function of increasing age. CONCLUSIONS These data highlight increasing connectivity in the SLF during adolescence. In light of evidence for compromised SLF integrity in high-risk and first-episode patients, these data suggest that abnormal maturation of the SLF during adolescence may be a key target in the neurodevelopment of schizophrenia.

Longitudinal diffusion tensor magnetic resonance imaging study of radiation induced white matter damage in a rat model

Radiation-induced white matter (WM) damage is a major side effect of whole brain irradiation among childhood cancer survivors. We evaluate longitudinally the diffusion characteristics of the late radiation-induced WM damage in a rat model after 25 and 30 Gy irradiation to the hemibrain at 8 time points from 2 to 48 weeks postradiation. We hypothesize that diffusion tensor magnetic resonance imaging (DTI) indices including fractional anisotropy (FA), trace, axial diffusivity (lambda(//)), and radial diffusivity (lambda( perpendicular)) can accurately detect and monitor the histopathologic changes of radiation-induced WM damage, measured at the EC, and that these changes are dose and time dependent. Results showed a progressive reduction of FA, which was driven by reduction in lambda(//) from 4 to 40 weeks postradiation, and an increase in lambda( perpendicular) with return to baseline in lambda(//) at 48 weeks postradiation. Histologic evaluation of irradiated WM showed reactive astrogliosis from 4 weeks postradiation with reversal at 36 weeks, and demyelination, axonal degeneration, and necrosis at 48 weeks postradiation. Moreover, changes in lambda(//) correlated with reactive astrogliosis (P < 0.01) and lambda( perpendicular) correlated with demyelination (P < 0.01). Higher radiation dose (30 Gy) induced earlier and more severe histologic changes than lower radiation dose (25 Gy), and these differences were reflected by the magnitude of changes in lambda(//) and lambda( perpendicular). DTI indices reflected the histopathologic changes of WM damage and our results support the use of DTI as a biomarker to noninvasively monitor radiation-induced WM damage.

White Matter Volume and Anisotropy in Preterm Children: A Pilot Study of Neurocognitive Correlates

The objectives of this study were to evaluate the differences in whole brain white matter (WM) volume and anisotropy between preterm and term children and to determine the relationships with cognitive outcome. Twenty-five low birth weight (BW), preterm, neurologically normal children between 8.8 and 11.5 y of age were recruited for volumetric and diffusion-tensor magnetic resonance imaging (DTI), together with 13 age-matched term control subjects. Subsequent intelligence quotient (IQ) testing was performed for 21 preterm children within 6 mo of imaging studies. We computed the mean volume and fractional anisotropy (FA) of the whole brain WM and compared the differences between the two groups. Mean WM volume and FA were significantly lower in the preterm group (p = 0.014 and p < 0.001, respectively). Multiple regression analysis found both WM volume and FA to be independent variables significantly affecting full scale IQ (FSIQ) (r2 = 0.407, p = 0.021 and r2 = 0.496, p = 0.005, respectively) after adjusting for BW, gestational age (GA), and gender. In the evaluation of the whole brain WM of preterm children, we found that both volume and FA remain reduced at late childhood with both parameters significantly affecting long-term cognitive outcome.

Mapping radiation dose distribution on the fractional anisotropy map: Applications in the assessment of treatment-induced white matter injury

We describe a method to map whole brain radiation dose distribution on to diffusion tensor MR (DT-MR) fractional anisotropy (FA) images and illustrate its applications for studying dose-effect relationships and regional susceptibility in two childhood medulloblastoma survivors. To determine the FA changes voxel-by-voxel in white matter, the post-treatment follow-up FA maps were coregistered to baseline pre-treatment FA maps and automatic segmentation for white matter was carried out. DeltaFA maps representing relative FA change in white matter were hence generated for visual inspection and quantitative analysis. The radiation dose distribution, calculated from radiotherapy plan and exported as images, was coregistered to baseline FA images. DT-MR imaging and processing noise was small with root mean square value of 1.49% for mean DeltaFA. We evaluated the mean DeltaFA changes of regions-of-interest according to radiation dose regions to provide an estimate of the dose-response and found increasing reduction in mean DeltaFA with increasing radiation dose up to 45 Gy after which there was a reversal in the mean FA trend and mean FA approached baseline value. We also found more severe mean FA reduction in the frontal lobes compared to the parietal lobes despite the same radiation dose, suggesting regional susceptibility in the frontal lobe, and mean FA increase in the brainstem after radiation in both patients. We conclude that the method described may be useful in estimating dose-effect relationships and studying regional susceptibility of the brain to radiation in medulloblastoma survivors.

Lateralization of the arcuate fasciculus and its differential correlation with reading ability between young learners and experienced readers: a diffusion tensor tractography study in a Chinese cohort.

As Chinese reading engages a different neural network from alphabetic language reading, we investigate whether leftward lateralization of the arcuate fasciculus (AF), as observed in the Western population, is also present in the Chinese population and if it does, whether it is associated with better reading ability. Diffusion tensor tractography analysis on 75 Chinese subjects of three age groups (first graders, fourth graders, and college students) showed that 70–83% of them had leftward lateralization of the AF. The pattern of lateralization did not differ significantly among the three groups, suggesting that lateralization of the AF is formed at an early age and before one enters first grade. Among the first graders, who had just started to learn to read, subjects with strongly leftward lateralized AF scored significantly higher than those with other defined lateralization patterns in Chinese (P = 0.001) and English (P = 0.036) reading tasks. This association was not observed among the fourth graders and college students who were experienced Chinese readers. Among the fourth graders, females were found to obtain significantly higher Chinese (P = 0.033) and English reading scores than males (P = 0.002). Our study suggests a differential effect of leftward lateralization of the AF on reading ability at different stages of reading development in the Chinese population. Hum Brain Mapp, 2011.

Comparing diffusion-weighted and T2-weighted MR imaging for the quantification of infarct size in a neonatal rat hypoxic-ischemic model at 24 h post-injury

In a neonatal rat model of hypoxic–ischemic (HI) brain injury, using T2‐weighted imaging (T2WI) and diffusion‐weighted imaging (DWI), we aim to determine the best MRI method of lesion quantification that reflects infarct size.