A voxel-wise assessment of growth differences in infants developing autism spectrum disorder.

Autism Spectrum Disorder (ASD) is a phenotypically and etiologically heterogeneous developmental disorder typically diagnosed around 4 years of age. The development of biomarkers to help in earlier, presymptomatic diagnosis could facilitate earlier identification and therefore earlier intervention and may lead to better outcomes, as well as providing information to help better understand the underlying mechanisms of ASD. In this study, magnetic resonance imaging (MRI) scans of infants at high familial risk, from the Infant Brain Imaging Study (IBIS), at 6, 12 and 24 months of age were included in a morphological analysis, fitting a mixed-effects model to Tensor Based Morphometry (TBM) results to obtain voxel-wise growth trajectories. Subjects were grouped by familial risk and clinical diagnosis at 2 years of age. Several regions, including the posterior cingulate gyrus, the cingulum, the fusiform gyrus, and the precentral gyrus, showed a significant effect for the interaction of group and age associated with ASD, either as an increased or a decreased growth rate of the cerebrum. In general, our results showed increased growth rate within white matter with decreased growth rate found mostly in grey matter. Overall, the regions showing increased growth rate were larger and more numerous than those with decreased growth rate. These results detail, at the voxel level, differences in brain growth trajectories in ASD during the first years of life, previously reported in terms of overall brain volume and surface area.

A variation in the infant oxytocin receptor gene modulates infant hippocampal volumes in association with sex and prenatal maternal anxiety.

Genetic variants in the oxytocin receptor (OTR) have been linked to distinct social phenotypes, psychiatric disorders and brain volume alterations in adults. However, to date, it is unknown how OTR genotype shapes prenatal brain development and whether it interacts with maternal prenatal environmental risk factors on infant brain volumes. In 105 Finnish mother-infant dyads (44 female, 11-54 days old), the association of offspring OTR genotype rs53576 and its interaction with prenatal maternal anxiety (revised Symptom Checklist 90, gestational weeks 14, 24, 34) on infant bilateral amygdalar, hippocampal and caudate volumes were probed. A sex-specific main effect of rs53576 on infant left hippocampal volumes was observed. In boys compared to girls, left hippocampal volumes were significantly larger in GG-homozygotes compared to A-allele carriers. Furthermore, genotype rs53576 and prenatal maternal anxiety significantly interacted on right hippocampal volumes irrespective of sex. Higher maternal anxiety was associated both with larger hippocampal volumes in A-allele carriers than GG-homozygotes, and, though statistically weak, also with smaller right caudate volumes in GG-homozygotes than A-allele carriers. Our study results suggest that OTR genotype enhances hippocampal neurogenesis in male GG-homozygotes. Further, prenatal maternal anxiety might induce brain alterations that render GG-homozygotes compared to A-allele carriers more vulnerable to depression.

Partial Support for an Interaction Between a Polygenic Risk Score for Major Depressive Disorder and Prenatal Maternal Depressive Symptoms on Infant Right Amygdalar Volumes.

Psychiatric disease susceptibility partly originates prenatally and is shaped by an interplay of genetic and environmental risk factors. A recent study has provided preliminary evidence that an offspring polygenic risk score for major depressive disorder (PRS-MDD), based on European ancestry, interacts with prenatal maternal depressive symptoms (GxE) on neonatal right amygdalar (US and Asian cohort) and hippocampal volumes (Asian cohort). However, to date, this GxE interplay has only been addressed by one study and is yet unknown for a European ancestry sample. We investigated in 105 Finnish mother-infant dyads (44 female, 11-54 days old) how offspring PRS-MDD interacts with prenatal maternal depressive symptoms (Edinburgh Postnatal Depression Scale, gestational weeks 14, 24, 34) on infant amygdalar and hippocampal volumes. We found a GxE effect on right amygdalar volumes, significant in the main analysis, but nonsignificant after multiple comparison correction and some of the control analyses, whose direction paralleled the US cohort findings. Additional exploratory analyses suggested a sex-specific GxE effect on right hippocampal volumes. Our study is the first to provide support, though statistically weak, for an interplay of offspring PRS-MDD and prenatal maternal depressive symptoms on infant limbic brain volumes in a cohort matched to the PRS-MDD discovery sample.

Automatic extraction of vertebral landmarks from ultrasound images: A pilot study.

Interpreting ultrasound (US) images of the spine is challenging due to the high variability of the contrast during freehand US acquisitions. In this paper, an automatic method to extract vertebral landmarks (spinous process and laminae) from US images acquired in the transverse plane is presented. Prior knowledge about the vertebral shape and the associated hyper-echoic property is incorporated using the horizontal and vertical projections of the image intensities. After detrending, the mean-value crossing of the projections is used to define the concept of mean boundary and locate landmarks without the need for thresholding or parameter adjustment. The method was evaluated using two datasets: a porcine cadaver dataset (PC) with CT data registered to the US data used as a gold standard, and a healthy human subjects dataset (HH) with a silver standard generated from manual landmarks located on the US data acquired with a curvilinear (6C2) and linear (14L5) probe. The mean sum of distances (MSD) of the landmark extraction to the gold and silver standards is respectively MSD=0.90±1.05 mm for PC, MSD=1.14±1.08 mm (6C2) and MSD=3.54±2.69 mm (14L5) for HH. Results are satisfying on PC and HH with 6C2. Variable contrast quality for 14L5 gives satisfying results for the spinous process but not for the laminae. The proposed approach has the potential to be used for different applications in the context of US spine imaging such as scoliosis follow-up and intra-operative surgical guidance.

Comparison of Multiple Sclerosis Cortical Lesion Types Detected by Multicontrast 3T and 7T MRI.

BACKGROUND AND PURPOSE: Our aims were the following: 1) to compare multicontrast cortical lesion detection using 3T and 7T MR imaging, 2) to compare cortical lesion type frequency in relapsing-remitting and secondary-progressive MS, and 3) to assess whether detectability is related to the magnetization transfer ratio, an imaging marker sensitive to myelin content. MATERIALS AND METHODS: Multicontrast 3T and 7T MR images from 10 participants with relapsing-remitting MS and 10 with secondary-progressive MS. We used the following 3T contrast sequences: 3D-T1-weighted, quantitative T1, FLAIR, magnetization-transfer, and 2D proton-density- and T2-weighted. We used the following 7T contrast sequences: 3D-T1-weighted, quantitative T1, and 2D-T2*-weighted. RESULTS: Cortical lesion counts at 7T were the following: 720 total cortical lesions, 420 leukocortical lesions (58%), 27 intracortical lesions (4%), and 273 subpial lesions (38%). Cortical lesion counts at 3T were the following: 424 total cortical, 393 leukocortical (93%), zero intracortical, and 31 subpial (7%) lesions. Total, intracortical, and subpial 3T lesion counts were significantly lower than the 7T counts (P < .002). Leukocortical lesion counts were not significantly different between scanners. Total and leukocortical lesion counts were significantly higher in secondary-progressive MS, at 3T and 7T (P ≤ .02). Subpial lesions were significantly higher in secondary-progressive MS at 7T (P = .006). The magnetization transfer ratio values of leukocortical lesions visible on both scanners were significantly lower than the magnetization transfer ratio values of leukocortical lesions visible only at 3T. No significant difference was found in magnetization transfer ratio values between subpial lesions visible only at 7T and subpial lesions visible on both 3T and 7T. CONCLUSIONS: Detection of leukocortical lesions at 3T is comparable with that at 7T MR imaging. Imaging at 3T is less sensitive to intracortical and subpial lesions. Leukocortical lesions not visible on 7T T2*-weighted MRI may be associated with less demyelination than those that are visible. Detectability of subpial lesions does not appear to be related to the degree of demyelination.

Predictive model of spread of Parkinson's pathology using network diffusion.

Growing evidence suggests that a "prion-like" mechanism underlies the pathogenesis of many neurodegenerative disorders, including Parkinson's disease (PD). We extend and tailor previously developed quantitative and predictive network diffusion model (NDM) to PD, by specifically modeling the trans-neuronal spread of alpha-synuclein outward from the substantia nigra (SN). The model demonstrated the spatial and temporal patterns of PD from neuropathological and neuroimaging studies and was statistically validated using MRI deformation of 232 Parkinson's patients. After repeated seeding simulations, the SN was found to be the most likely seed region, supporting its unique lynchpin role in Parkinson's pathology spread. Other alternative spread models were also evaluated for comparison, specifically, random spread and distance-based spread; the latter tests for Braak's original caudorostral transmission theory. We showed that the distance-based spread model is not as well supported as the connectivity-based model. Intriguingly, the temporal sequencing of affected regions predicted by the model was in close agreement with Braak stages III-VI, providing what we consider a "computational Braak" staging system. Finally, we investigated whether the regional expression patterns of implicated genes contribute to regional atrophy. Despite robust evidence for genetic factors in PD pathogenesis, NDM outperformed regional genetic expression predictors, suggesting that network processes are far stronger mediators of regional vulnerability than innate or cell-autonomous factors. This is the first finding yet of the ramification of prion-like pathology propagation in Parkinson's, as gleaned from in vivo human imaging data. The NDM is potentially a promising robust and clinically useful tool for diagnosis, prognosis and staging of PD.

Network connectivity determines cortical thinning in early Parkinson's disease progression.

Here we test the hypothesis that the neurodegenerative process in Parkinson's disease (PD) moves stereotypically along neural networks, possibly reflecting the spread of toxic alpha-synuclein molecules. PD patients (n = 105) and matched controls (n = 57) underwent T1-MRI at entry and 1 year later as part of the Parkinson's Progression Markers Initiative. Over this period, PD patients demonstrate significantly greater cortical thinning than controls in parts of the left occipital and bilateral frontal lobes and right somatomotor-sensory cortex. Cortical thinning is correlated to connectivity (measured functionally or structurally) to a "disease reservoir" evaluated by MRI at baseline. The atrophy pattern in the ventral frontal lobes resembles one described in certain cases of Alzheimer's disease. Our findings suggest that disease propagation to the cortex in PD follows neuronal connectivity and that disease spread to the cortex may herald the onset of cognitive impairment.

Increased Extra-axial Cerebrospinal Fluid in High-Risk Infants Who Later Develop Autism.

BACKGROUND: We previously reported that infants who developed autism spectrum disorder (ASD) had increased cerebrospinal fluid (CSF) in the subarachnoid space (i.e., extra-axial CSF) from 6 to 24 months of age. We attempted to confirm and extend this finding in a larger independent sample. METHODS: A longitudinal magnetic resonance imaging study of infants at risk for ASD was carried out on 343 infants, who underwent neuroimaging at 6, 12, and 24 months. Of these infants, 221 were at high risk for ASD because of an older sibling with ASD, and 122 were at low risk with no family history of ASD. A total of 47 infants were diagnosed with ASD at 24 months and were compared with 174 high-risk and 122 low-risk infants without ASD. RESULTS: Infants who developed ASD had significantly greater extra-axial CSF volume at 6 months compared with both comparison groups without ASD (18% greater than high-risk infants without ASD; Cohen's d = 0.54). Extra-axial CSF volume remained elevated through 24 months (d = 0.46). Infants with more severe autism symptoms had an even greater volume of extra-axial CSF from 6 to 24 months (24% greater at 6 months, d = 0.70; 15% greater at 24 months, d = 0.70). Extra-axial CSF volume at 6 months predicted which high-risk infants would be diagnosed with ASD at 24 months with an overall accuracy of 69% and corresponding 66% sensitivity and 68% specificity, which was fully cross-validated in a separate sample. CONCLUSIONS: This study confirms and extends previous findings that increased extra-axial CSF is detectable at 6 months in high-risk infants who develop ASD. Future studies will address whether this anomaly is a contributing factor to the etiology of ASD or an early risk marker for ASD.

Interplay of hippocampal volume and hypothalamus-pituitary-adrenal axis function as markers of stress vulnerability in men at ultra-high risk for psychosis.

BACKGROUND: Altered hypothalamus-pituitary-adrenal (HPA) axis function and reduced hippocampal volume (HV) are established correlates of stress vulnerability. We have previously shown an attenuated cortisol awakening response (CAR) and associations with HV specifically in male first-episode psychosis patients. Findings in individuals at ultra-high risk (UHR) for psychosis regarding these neurobiological markers are inconsistent, and assessment of their interplay, accounting for sex differences, could explain incongruent results. METHOD: Study participants were 42 antipsychotic-naive UHR subjects (24 men) and 46 healthy community controls (23 men). Saliva samples for the assessment of CAR were collected at 0, 30 and 60 min after awakening. HV was determined from high-resolution structural magnetic resonance imaging scans using a semi-automatic segmentation protocol. RESULTS: Cortisol measures and HV were not significantly different between UHR subjects and controls in total, but repeated-measures multivariate regression analyses revealed reduced cortisol levels 60 min after awakening and smaller left HV in male UHR individuals. In UHR participants only, smaller left and right HV was significantly correlated with a smaller total CAR (ρ = 0.42, p = 0.036 and ρ = 0.44, p = 0.029, respectively), corresponding to 18% and 19% of shared variance (medium effect size). CONCLUSIONS: Our findings suggest that HV reduction in individuals at UHR for psychosis is specific to men and linked to reduced post-awakening cortisol concentrations. Abnormalities in the neuroendocrine circuitry modulating stress vulnerability specifically in male UHR subjects might explain increased psychosis risk and disadvantageous illness outcomes in men compared to women.

Improving recorded volume in mesial temporal lobe by optimizing stereotactic intracranial electrode implantation planning.

PURPOSE: Intracranial electrodes are sometimes implanted in patients with refractory epilepsy to identify epileptic foci and propagation. Maximal recording of EEG activity from regions suspected of seizure generation is paramount. However, the location of individual contacts cannot be considered with current manual planning approaches. We propose and validate a procedure for optimizing intracranial electrode implantation planning that maximizes the recording volume, while constraining trajectories to safe paths. METHODS: Retrospective data from 20 patients with epilepsy that had electrodes implanted in the mesial temporal lobes were studied. Clinical imaging data (CT/A and T1w MRI) were automatically segmented to obtain targets and structures to avoid. These data were used as input to the optimization procedure. Each electrode was modeled to assess risk, while individual contacts were modeled to estimate their recording capability. Ordered lists of trajectories per target were obtained. Global optimization generated the best set of electrodes. The procedure was integrated into a neuronavigation system. RESULTS: Trajectories planned automatically covered statistically significant larger target volumes than manual plans [Formula: see text]. Median volume coverage was [Formula: see text] for automatic plans versus [Formula: see text] for manual plans. Furthermore, automatic plans remained at statistically significant safer distance to vessels [Formula: see text] and sulci [Formula: see text]. Surgeon's scores of the optimized electrode sets indicated that 95% of the automatic trajectories would be likely considered for use in a clinical setting. CONCLUSIONS: This study suggests that automatic electrode planning for epilepsy provides safe trajectories and increases the amount of information obtained from the intracranial investigation.

Framework for integrated MRI average of the spinal cord white and gray matter: the MNI-Poly-AMU template.

The field of spinal cord MRI is lacking a common template, as existing for the brain, which would allow extraction of multi-parametric data (diffusion-weighted, magnetization transfer, etc.) without user bias, thereby facilitating group analysis and multi-center studies. This paper describes a framework to produce an unbiased average anatomical template of the human spinal cord. The template was created by co-registering T2-weighted images (N = 16 healthy volunteers) using a series of pre-processing steps followed by non-linear registration. A white and gray matter probabilistic template was then merged to the average anatomical template, yielding the MNI-Poly-AMU template, which currently covers vertebral levels C1 to T6. New subjects can be registered to the template using a dedicated image processing pipeline. Validation was conducted on 16 additional subjects by comparing an automatic template-based segmentation and manual segmentation, yielding a median Dice coefficient of 0.89. The registration pipeline is rapid (~15 min), automatic after one C2/C3 landmark manual identification, and robust, thereby reducing subjective variability and bias associated with manual segmentation. The template can notably be used for measurements of spinal cord cross-sectional area, voxel-based morphometry, identification of anatomical features (e.g., vertebral levels, white and gray matter location) and unbiased extraction of multi-parametric data.

Childhood cognitive ability accounts for associations between cognitive ability and brain cortical thickness in old age.

Associations between brain cortical tissue volume and cognitive function in old age are frequently interpreted as suggesting that preservation of cortical tissue is the foundation of successful cognitive aging. However, this association could also, in part, reflect a lifelong association between cognitive ability and cortical tissue. We analyzed data on 588 subjects from the Lothian Birth Cohort 1936 who had intelligence quotient (IQ) scores from the same cognitive test available at both 11 and 70 years of age as well as high-resolution brain magnetic resonance imaging data obtained at approximately 73 years of age. Cortical thickness was estimated at 81 924 sampling points across the cortex for each subject using an automated pipeline. Multiple regression was used to assess associations between cortical thickness and the IQ measures at 11 and 70 years. Childhood IQ accounted for more than two-third of the association between IQ at 70 years and cortical thickness measured at age 73 years. This warns against ascribing a causal interpretation to the association between cognitive ability and cortical tissue in old age based on assumptions about, and exclusive reference to, the aging process and any associated disease. Without early-life measures of cognitive ability, it would have been tempting to conclude that preservation of cortical thickness in old age is a foundation for successful cognitive aging when, instead, it is a lifelong association. This being said, results should not be construed as meaning that all studies on aging require direct measures of childhood IQ, but as suggesting that proxy measures of prior cognitive function can be useful to take into consideration.

A new method for structural volume analysis of longitudinal brain MRI data and its application in studying the growth trajectories of anatomical brain structures in childhood.

Cross-sectional analysis of longitudinal anatomical magnetic resonance imaging (MRI) data may be suboptimal as each dataset is analyzed independently. In this study, we evaluate how much variability can be reduced by analyzing structural volume changes in longitudinal data using longitudinal analysis. We propose a two-part pipeline that consists of longitudinal registration and longitudinal classification. The longitudinal registration step includes the creation of subject-specific linear and nonlinear templates that are then registered to a population template. The longitudinal classification step comprises a four-dimensional expectation-maximization algorithm, using a priori classes computed by averaging the tissue classes of all time points obtained cross-sectionally. To study the impact of these two steps, we apply the framework completely ("LL method": Longitudinal registration and Longitudinal classification) and partially ("LC method": Longitudinal registration and Cross-sectional classification) and compare these with a standard cross-sectional framework ("CC method": Cross-sectional registration and Cross-sectional classification). The three methods are applied to (1) a scan-rescan database to analyze reliability and (2) the NIH pediatric population to compare gray matter growth trajectories evaluated with a linear mixed model. The LL method, and the LC method to a lesser extent, significantly reduced the variability in the measurements in the scan-rescan study and gave the best-fitted gray matter growth model with the NIH pediatric MRI database. The results confirm that both steps of the longitudinal framework reduce variability and improve accuracy in comparison with the cross-sectional framework, with longitudinal classification yielding the greatest impact. Using the improved method to analyze longitudinal data, we study the growth trajectories of anatomical brain structures in childhood using the NIH pediatric MRI database. We report age- and gender-related growth trajectories of specific regions of the brain during childhood that could be used as a reference in studying the impact of neurological disorders on brain development.

Magnetic resonance imaging predictors of executive functioning in patients with pediatric-onset multiple sclerosis.

Executive functions (EFs) are vulnerable to disruption in pediatric-onset multiple sclerosis (MS) patients. We describe the pattern and correlates of executive dysfunction in 34 adolescents with MS on neuropsychological tests and the parent version of the Behavior Rating Inventory of Executive Function (BRIEF). The adolescents with MS performed lower than age-matched controls in several areas of executive functioning, with 44% of patients being impaired on the Trail Making Test-Part B. On the BRIEF, problems in working memory and planning/organization were identified in the patient group compared with controls, particularly in patients with a younger age at disease onset. Task performance and parent-ratings of EF skills were strongly related to whole brain and regional brain volume metrics and, to a lesser extent, T(2)-weighted lesion volume. Working memory and attention switching are at greatest risk of impairment. Results support the inclusion of neuropsychological assessment alongside parent-report measures of EF skills in childhood-onset MS.

Reduced head and brain size for age and disproportionately smaller thalami in child-onset MS.

OBJECTIVE: Whole brain and regional volume measurement methods were used to quantify white matter, gray matter, and deep gray matter structure volumes in a population of patients with pediatric-onset multiple sclerosis (MS). METHODS: Subjects included 38 patients (mean age 15.2 ± 2.4 years) and 33 age- and sex-matched healthy control (HC) participants. MRI measures included intracranial volume, normalized brain volume, normalized white and gray matter volume, and volumes of the thalamus, globus pallidus, putamen, and caudate. Because these volumes vary across age and sex in children, we normalized the volume measurements for MS and control groups by computing z scores using normative values obtained from healthy children enrolled in the MRI Study of Normal Brain Development. RESULTS: The intracranial volume z score was significantly lower in the patients with MS (-0.45 ± 1.16; mean ± SD) compared with the HC participants (+0.25 ± 0.98; p = 0.01). Patients with MS also demonstrated significant decreases in normalized brain volume z scores (-1.09 ± 1.49 vs -0.05 ± 1.22; p = 0.002). After correction for global brain volume, thalamic volumes in the MS population remained lower than those of HCs (-0.68 ± 1.72 vs 0.15 ± 1.35; p = 0.02), indicating an even greater loss of thalamic tissue relative to more global brain measures. Moderate correlations were found between T2-weighted lesion load and normalized thalamic volumes (r = -0.44, p < 0.01) and normalized brain volume (r = -0.47, p < 0.01) and between disease duration and normalized thalamic volume (r = -0.58, p < 0.001) and normalized brain volume (r = -0.46, p < 0.01). CONCLUSIONS: When compared with age- and sex-matched control subjects, the onset of MS during childhood is associated with a smaller overall head size, brain volume, and an even smaller thalamic volume.

Genetic influences on thinning of the cerebral cortex during development.

During development from childhood to adulthood the human brain undergoes considerable thinning of the cerebral cortex. Whether developmental cortical thinning is influenced by genes and if independent genetic factors influence different parts of the cortex is not known. Magnetic resonance brain imaging was done in twins at age 9 (N = 190) and again at age 12 (N = 125; 113 repeated measures) to assess genetic influences on changes in cortical thinning. We find considerable thinning of the cortex between over this three year interval (on average 0.05 mm; 1.5%), particularly in the frontal poles, and orbitofrontal, paracentral, and occipital cortices. Cortical thinning was highly heritable at age 9 and age 12, and the degree of genetic influence differed for the various areas of the brain. One genetic factor affected left inferior frontal (Broca's area), and left parietal (Wernicke's area) thinning; a second factor influenced left anterior paracentral (sensory-motor) thinning. Two factors influenced cortical thinning in the frontal poles: one of decreasing influence over time, and another independent genetic factor emerging at age 12 in left and right frontal poles. Thus, thinning of the cerebral cortex is heritable in children between the ages 9 and 12. Furthermore, different genetic factors are responsible for variation in cortical thickness at ages 9 and 12, with independent genetic factors acting on cortical thickness across time and between various brain areas during childhood brain development.

MRI correlates of cognitive impairment in childhood-onset multiple sclerosis.

OBJECTIVE: Brain MRI measures were correlated with neuropsychological function in 35 pediatric-onset multiple sclerosis (MS) patients and 33 age- and sex-matched healthy controls. METHOD: Mean age of MS patients was 16.3 ± 2.3 years with average disease duration of 4.3 ± 3.1 years. Cortical gray matter, thalamic, and global brain volumes were calculated for all participants using a scaling factor computed using normalization of atrophy method to normalize total and regional brain volumes for head size. T1- and T2-weighted lesion volumes were calculated for MS patients. RESULTS: Cognitive impairment (CI) was identified in 29% of the MS cohort. Cognitive deficits predominantly involved attention and processing speed, expressive language, and visuomotor integration. Relative to controls, the MS group showed significantly lower thalamic volume (p < .001), total brain volume (p < .008), and gray matter volume (p < .015). Corpus callosum area and thalamic volume differentiated patients identified as having CI from those without CI (p < .05). Regression models controlling for disease duration and age indicated that thalamic volume accounted for significant incremental variance in predicting global IQ, processing speed, and expressive vocabulary (ΔR2 ranging from .43 to .60) and was the most robust MRI predictor of cognition relative to other MRI metrics. CONCLUSIONS: The robust association between cognitive function and reduced size of thalamus and global brain volume in pediatric-onset MS patients implicate neurodegenerative processes early in the disease course, and suggest that plasticity of an immature central nervous system is not sufficient to protect patients from the deleterious consequences of MS on cognitive neural networks. (PsycINFO Database Record (c) 2011 APA, all rights reserved).

Regional brain atrophy in children with multiple sclerosis.

We used cross-sectional tensor-based morphometry to visualize reduced volume in the whole brains of pediatric patients with multiple sclerosis, relative to healthy controls. As a marker of local volume difference, we used the Jacobian determinant of the deformation field that maps each subject to a standard space. To properly assess abnormal differences in volume in this age group, it is necessary to account for the normal, age-related differences in brain volume. This was accomplished by computing normalized z-score Jacobian determinant values at each voxel to represent the local volume difference (in standard deviations) between an individual subject and an age- and sex-matched healthy normal population. Compared with healthy controls, pediatric patients with multiple sclerosis exhibited significantly reduced volumes within the thalamus and the splenium of the corpus callosum and significant expansions in the ventricles. While T2-weighted lesion volume was correlated with reduced splenium volume, no correlation was found between T2-weighted lesion volume and reduced thalamic volume. Reduced volumes of the optic pathways, including that of the optic tracts and optic radiations, correlated with disease duration. Our results suggest that focal inflammatory lesions may play an important role in tract degeneration, including transsynaptic degeneration.

White-matter diffusion abnormalities in temporal-lobe epilepsy with and without mesial temporal sclerosis.

BACKGROUND: Although epilepsy is considered a grey-matter disorder, changes in the underlying brain connectivity have important implications in seizure generation and propagation. Abnormalities in the temporal and extratemporal white matter of patients with temporal-lobe epilepsy (TLE) and mesial temporal sclerosis (MTS) have previously been identified. Patients with TLE but without MTS often show a different course of the disorder and worse surgical outcome than patients with MTS. The purpose of this study was to determine if said white-matter abnormalities are related to the presence of MTS or if they are also present in non-lesional TLE. METHODS: Seventeen patients with TLE and MTS (TLE+uMTS), 13 patients with non-lesional TLE (nl-TLE) and 25 controls were included in the study. Diffusion tensor imaging (DTI) was used to assess tract integrity of the fornix, cingulum, external capsules and the corpus callosum. RESULTS: The white-matter abnormalities seen in the fornix appear to be exclusive to patients with MTS. Although the cingulum showed an abnormally high overall diffusivity in both TLE groups, its anisotropy was decreased only in the TLE+uMTS group in a pattern similar to the fornix. The frontal and temporal components of the corpus callosum, as well as the external capsules, demonstrated reduced anisotropy in TLE regardless of MTS. CONCLUSIONS: While some white-matter bundles are affected equally in both forms of TLE, abnormalities of the bundles directly related to the mesial temporal structures (ie, the fornix and cingulum) appear to be unique to TLE+uMTS.

Human brain myelination from birth to 4.5 years.

The myelination of white matter from birth through the first years of life has been studied qualitatively and it is well know the myelination occurs in a orderly and predictable manner, proceeding in a caudocranial direction, from deep to superficial and from posterior to anterior. Even if the myelination is a continuous process, it is useful to characterize myelination evolution in normal brain development in order to better study demyelinating diseases. The quantification of myelination has only been studied for neonates. The original contribution of this study is to develop a method to characterize and visualize the myelination pattern using MRI data from a group of normal subjects from birth to just over 4 years of age. The method includes brain extraction and tissue classification in addition to the analysis of T2 relaxation times to attempt to separate myelinated and unmyelinated white matter. The results agree previously published qualitative observations.