Reliability of MRI-derived cortical and subcortical morphometric measures: effects of pulse sequence, voxel geometry, and parallel imaging.

Advances in magnetic resonance imaging (MRI) have contributed greatly to the study of neurodegenerative processes, psychiatric disorders, and normal human development, but the effect of such improvements on the reliability of downstream morphometric measures has not been extensively studied. We examined how MRI-derived neurostructural measures are affected by three technological advancements: parallel acceleration, increased spatial resolution, and the use of a high bandwidth multiecho sequence. Test-retest data were collected from 11 healthy participants during 2 imaging sessions occurring approximately 2 weeks apart. We acquired 4 T1-weighted MP-RAGE sequences during each session: a non-accelerated anisotropic sequence (MPR), a non-accelerated isotropic sequence (ISO), an accelerated isotropic sequence (ISH), and an accelerated isotropic high bandwidth multiecho sequence (MEM). Cortical thickness and volumetric measures were computed for each sequence to assess test-retest reliability and measurement bias. Reliability was extremely high for most measures and similar across imaging parameters. Significant measurement bias was observed, however, between MPR and all isotropic sequences for all cortical regions and some subcortical structures. These results suggest that these improvements in MRI acquisition technology do not compromise data reproducibility, but that consistency should be maintained in choosing imaging parameters for structural MRI studies.

Brain asymmetries in autism and developmental language disorder: a nested whole-brain analysis.

We report a whole-brain MRI morphometric survey of asymmetry in children with high-functioning autism and with developmental language disorder (DLD). Subjects included 46 boys of normal intelligence aged 5.7-11.3 years (16 autistic, 15 DLD, 15 controls). Imaging analysis included grey-white segmentation and cortical parcellation. Asymmetry was assessed at a series of nested levels. We found that asymmetries were masked with larger units of analysis but progressively more apparent with smaller units, and that within the cerebral cortex the differences were greatest in higher-order association cortex. The larger units of analysis, including the cerebral hemispheres, the major grey and white matter structures and the cortical lobes, showed no asymmetries in autism or DLD and few asymmetries in controls. However, at the level of cortical parcellation units, autism and DLD showed more asymmetry than controls. They had a greater aggregate volume of significantly asymmetrical cortical parcellation units (leftward plus rightward), as well as a substantially larger aggregate volume of right-asymmetrical cortex in DLD and autism than in controls; this rightward bias was more pronounced in autism than in DLD. DLD, but not autism, showed a small but significant loss of leftward asymmetry compared with controls. Right : left ratios were reversed, autism and DLD having twice as much right- as left-asymmetrical cortex, while the reverse was found in the control sample. Asymmetry differences between groups were most significant in the higher-order association areas. Autism and DLD were much more similar to each other in patterns of asymmetry throughout the cerebral cortex than either was to controls; this similarity suggests systematic and related alterations rather than random neural systems alterations. We review these findings in relation to previously reported volumetric features in these two samples of brains, including increased total brain and white matter volumes and lack of increase in the size of the corpus callosum. Larger brain volume has previously been associated with increased lateralization. The sizeable right-asymmetry increase reported here may be a consequence of early abnormal brain growth trajectories in these disorders, while higher-order association areas may be most vulnerable to connectivity abnormalities associated with white matter increases.

Dissociations of cerebral cortex, subcortical and cerebral white matter volumes in autistic boys.

High-functioning autistic and normal school-age boys were compared using a whole-brain morphometric profile that includes both total brain volume and volumes of all major brain regions. We performed MRI-based morphometric analysis on the brains of 17 autistic and 15 control subjects, all male with normal intelligence, aged 7-11 years. Clinical neuroradiologists judged the brains of all subjects to be clinically normal. The entire brain was segmented into cerebrum, cerebellum, brainstem and ventricles. The cerebrum was subdivided into cerebral cortex, cerebral white matter, hippocampus-amygdala, caudate nucleus, globus pallidus plus putamen, and diencephalon (thalamus plus ventral diencephalon). Volumes were derived for each region and compared between groups both before and after adjustment for variation in total brain volume. Factor analysis was then used to group brain regions based on their intercorrelations. Volumes were significantly different between groups overall; and diencephalon, cerebral white matter, cerebellum and globus pallidus-putamen were significantly larger in the autistic group. Brain volumes were not significantly different overall after adjustment for total brain size, but this analysis approached significance and effect sizes and univariate comparisons remained notable for three regions, although not all in the same direction: cerebral white matter showed a trend towards being disproportionately larger in autistic boys, while cerebral cortex and hippocampus-amygdala showed trends toward being disproportionately smaller. Factor analysis of all brain region volumes yielded three factors, with central white matter grouping alone, and with cerebral cortex and hippocampus-amygdala grouping separately from other grey matter regions. This morphometric profile of the autistic brain suggests that there is an overall increase in brain volumes compared with controls. Additionally, results suggest that there may be differential effects driving white matter to be larger and cerebral cortex and hippocampus-amygdala to be relatively smaller in the autistic than in the typically developing brain. The cause of this apparent dissociation of cerebral cortical regions from subcortical regions and of cortical white from grey matter is unknown, and merits further investigation.

Metabolic fate and disposition of [14C]hydroquinone given orally to Sprague-Dawley rats.

Hydroquinone (HQ) is used widely in industry and in commerce and is considered to have a low degree of toxicity. Although the metabolism of HQ has been studied elsewhere, a complete materials balance has not been reported. We investigated the metabolism of HQ in naive and HQ pretreated male Sprague-Dawley rats. [14C]HQ was administered by gavage in single doses of 5, 30, or 200 mg/kg to naive rats. HQ was given repeatedly by gavage to male rats at 200 mg/kg for 4 consecutive days followed by a single dose with 200 mg/kg of [14C]HQ. In separate studies rats were fed 5.6% unlabeled HQ in the diet for 2 days or were dosed by gavage with 311 mg/kg [14C]HQ. The excretion patterns of [14C]HQ and its metabolites were similar for rats dosed singly or repeatedly. Rats given a single dose of 200 mg/kg of [14C]HQ excreted 91.9% of the dose in the urine within 2-4 days; 3.8% was excreted in the feces, about 0.4% was excreted in expired air, and 1.2% remained in the carcass. Radioactivity was widely distributed throughout the tissues with higher concentrations in the liver and kidneys. A decrease in 14C tissue concentrations occurred from 48 to 96 h. The only radiolabeled compounds in the urine were HQ (1.1-8.6% of the dose), hydroquinone monosulfate (25-42%), and hydroquinone monoglucuronide (56-66%). Similar findings were observed for rats given HQ in the feed. There were no significant increases from controls for absolute or relative liver weights, liver microsomal protein concentrations, cytochrome b-5, cytochrome P-450 or cytochrome c reductase activity in rats dosed repeatedly with 200 mg/kg HQ. Cytochrome P-450 values were slightly but significantly decreased in rats dosed repeatedly with HQ compared with controls.