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Emerging cellular and molecular studies are providing compelling evidence that altered brain development contributes to the pathogenesis of Huntington's disease (HD). There has been lacking longitudinal system-level data obtained from in vivo HD models supporting this hypothesis. Our human MRI study in children and adolescents with HD indicates that striatal development differs between the HD and control groups, with initial hypertrophy and more rapid volume decline in HD group. In this study, we aimed to determine whether brain development recapitulates the human HD during the postnatal period. Longitudinal structural MRI scans were conducted in the heterozygous zQ175 HD mice and their littermate controls. We found that male zQ175 HD mice recapitulated the region-specific abnormal volume development in the striatum and globus pallidus, with early hypertrophy and then rapidly decline in the regional volume. In contrast, female zQ175 HD mice did not show significant difference in brain volume development with their littermate controls. This is the first longitudinal study of brain volume development at the system level in HD mice. Our results suggest that altered brain development may contribute to the HD pathogenesis. The potential effect of gene therapies targeting on neurodevelopmental event is worth to consider for HD therapeutic intervention. [ABSTRACT FROM AUTHOR]

Recent evidence indicates that measures from cerebrospinal fluid, MRI scans and cognitive testing obtained from cognitively normal individuals can be used to predict likelihood of progression to mild cognitive impairment several years later, for groups of individuals. However, it remains unclear whether these measures are useful for predicting likelihood of progression for an individual. The increasing focus on early intervention in clinical trials for Alzheimer's disease emphasizes the importance of improving the ability to identify which cognitively normal individuals are more likely to progress over time, thus allowing researchers to efficiently screen participants, as well as determine the efficacy of any treatment intervention. The goal of this study was to determine which measures, obtained when individuals were cognitively normal, predict on an individual basis, the onset of clinical symptoms associated with a diagnosis of mild cognitive impairment due to Alzheimer's disease. Cognitively normal participants (n = 224, mean baseline age = 57 years) were evaluated with a range of measures, including: cerebrospinal fluid amyloid-β and phosphorylated-tau, hippocampal and entorhinal cortex volume, cognitive tests scores and APOE genotype. They were then followed to determine which individuals developed mild cognitive impairment over time (mean follow-up = 11 years). The primary outcome was progression from normal cognition to the onset of clinical symptoms of mild cognitive impairment due to Alzheimer's disease at 5 years post-baseline. Time-dependent receiver operating characteristic analyses examined the sensitivity and specificity of individual measures, and combinations of measures, as predictors of the outcome. Six measures, in combination, were the most parsimonious predictors of transition to mild cognitive impairment 5 years after baseline (area under the curve = 0.85; sensitivity = 0.80, specificity = 0.75). The addition of variables from each domain significantly improved the accuracy of prediction. The incremental accuracy of prediction achieved by adding individual measures or sets of measures successively to one another was also examined, as might be done when enrolling individuals in a clinical trial. The results indicate that biomarkers obtained when individuals are cognitively normal can be used to predict which individuals are likely to develop clinical symptoms at 5 years post-baseline. As a number of the measures included in the study could also be used as subject selection criteria in a clinical trial, the findings also provide information about measures that would be useful for screening in a clinical trial aimed at individuals with preclinical Alzheimer's disease. [ABSTRACT FROM AUTHOR]

With the ever-increasing amount of anatomical information radiologists have to evaluate for routine diagnoses, computational support that facilitates more efficient education and clinical decision making is highly desired. Despite the rapid progress of image analysis technologies for magnetic resonance imaging of the human brain, these methods have not been widely adopted for clinical diagnoses. To bring computational support into the clinical arena, we need to understand the decision-making process employed by well-trained clinicians and develop tools to simulate that process. In this review, we discuss the potential of atlas-based clinical neuroinformatics, which consists of annotated databases of anatomical measurements grouped according to their morphometric phenotypes and coupled with the clinical informatics upon which their diagnostic groupings are based. As these are indexed via parametric representations, we can use image retrieval tools to search for phenotypes along with their clinical metadata. The review covers the current technology, preliminary data, and future directions of this field. [ABSTRACT FROM AUTHOR]

Abstract Introduction  Hypertonic saline (HS) solutions are increasingly being utilized as osmotherapeutic agents for the treatment of cerebral edema associated with brain injury from diverse etiologies. Methods  In a rat model of permanent focal ischemia, we (1) determined the effect of HS therapy on regional brain water content with T1- and T2-weighted magnetic resonance imaging (MRI) and (2) tested the hypothesis that HS therapy modulates the expression of aquaporin-4 (AQP4) in the ischemic brain. Results  Halothane-anesthetized male Wistar rats were subjected to permanent middle cerebral artery occlusion (MCAO) and at 6 hr post-MCAO were treated with either continuous intravenous infusion of 0.9% saline (NS) or 7.5% HS for 18 hr. While lesion size measured on T2-weighted imaging did not differ between NS (580 � 217 mm3; mean � SD) and HS (460 � 86 mm3) treatments, there was a correlation between T2 values and tissue water content as determined by wet-to-dry ratio in the caudoputamen (CP) complex of ischemic core (r = 0.612, P 1 values with treatment in the ischemic cortex (NS: 2.08 � 0.13; HS: 1.78 � 0.20) and CP complex (NS: 2.09 � 0.14; HS: 1.77 � 0.22), but there was no correlation between T2 values and regional brain tissue water content in the peri-infarct regions and the non-ischemic hemisphere. There were significant differences in AQP4 protein expression in the ischemic hemisphere between NS and HS-treated rats. Conclusions  These data demonstrate that (1) T2-weighted MRI imaging correlates with tissue water content in the ischemic core but not in the peri-infarct regions, and (2) attenuation of ischemia-evoked cerebral edema involves the modulation of AQP4 channels in the brain. [ABSTRACT FROM AUTHOR]

A method for the spatial normalization and reorientation of diffusion tensor (DT) fields is presented. Spatial normalization of tensor fields requires an appropriate reorientation of the tensor on each voxel, in addition to its relocation into the standardized space. This appropriate tensor reorientation is determined from the spatial normalization transformation and from an estimate of the underlying fiber direction. The latter is obtained by treating the principal eigenvectors of the tensor field around each voxel as random samples drawn from the probability distribution that represents the direction of the underlying fiber. This approach was applied to DT images from nine normal volunteers, and the results show a significant improvement in signal-to-noise ratio (SNR) after spatial normalization and averaging of tensor fields across individuals. The statistics of the spatially normalized tensor field, which represents the tensor characteristics of normal individuals, may be useful for quantitatively characterizing individual variations of white matter structures revealed by DT imaging (DTI) and deviations caused by pathology. Simulated experiments using this methodology are also described. Magn Reson Med 50:175–182, 2003. © 2003 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Inflammation, demyelination, gliosis and axonal degeneration are pathological hallmarks of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis. Axonal damage is thought to contribute to irreversible damage and functional impairment, but is difficult to quantify. Conventional MRI has been used to assess the inflammatory and demyelinating aspects of MS lesions, but more sensitive and specific methods are needed to identify axonal damage to monitor disease progression and to determine efficacy of putative neuroprotective agents. We used high resolution diffusion tensor imaging (DTI) and fibre tracking to examine the spinal cord in rats with focal dorsal column inflammatory or demyelinating lesions to determine whether DTI measures can be used to detect pathology at the site of the focal lesion and to measure axonal damage in tracts distal to the focal lesion. Distant from the focal lesion, total axon counts, degenerating axon counts and SMI-31 staining, but not Luxol fast blue staining, were significantly correlated with fractional anisotropy, axial diffusivity and radial diffusivity, all of which are derived from the DTI data. These data suggest that high resolution DTI may be a more sensitive method than conventional imaging for detecting axonal damage at sites distant from inflammation. [ABSTRACT FROM AUTHOR]