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Our findings suggest that decreased working memory performance in bipolar patients reflects specific neurofunctional deficits. These deficits may represent primary areas of neuropathology or be secondary to neuropathology elsewhere in the working memory network. Continued research utilizing other imaging modalities may further clarify the underlying neuropathology involved in these cognitive deficits.

The potential benefits of functional magnetic resonance imaging (MRI) for the investigation of normal development have been limited by difficulties in its use with children. We describe the practical aspects, including failure rates, involved in conducting large-scale functional MRI studies with normal children. Two hundred and nine healthy children between the ages of 5 and 18 years participated in a functional MRI study of language development. Reliable activation maps were obtained across the age range. Younger children had significantly higher failure rates than older children and adolescents. It is concluded that it is feasible to conduct large-scale functional MRI studies of children as young as 5 years old. These findings can be used by other research groups to guide study design and plans for recruitment of young subjects.

A computationally efficient technique is described for the simultaneous removal of ghosting and geometrical distortion artifacts in echo-planar imaging (EPI) utilizing a multi-echo, gradient-echo reference scan.Nyquist ghosts occur in EPI reconstructions because odd and even lines of k-space are acquired with opposite polarity, and experimental imperfections such as gradient eddy currents, imperfect pulse sequence timing, B 0 field inhomogeneity, susceptibility, and chemical shift result in the even and odd lines of k-space being offset by different amounts relative to the true center of the acquisition window. Geometrical distortion occurs due to the limited bandwidth of the EPI images in the phaseencode direction. This distortion can be problematic when attempting to overlay an activation map from a functional MRI (fMRI) experiment generated from EPI data on a high-resolution anatomical image.The method described here corrects for geometrical distortion related to B 0 inhomogeneity, gradient eddy currents, radiofrequency pulse frequency offset, and chemical shift effect. The algorithm for removing ghost artifacts utilizes phase information in two dimensions and is thus more robust than conventional one-dimensional methods. An additional reference scan is required which takes approximately 2 minutes for a matrix size of 64 × 64 and a TR of 2 seconds. Results from a water phantom and a human brain at 3 Tesla demonstrate the effectiveness of the method for removing ghosts and geometric distortion artifacts.

These findings suggest that prefrontal white matter abnormalities are present early in bipolar disorder and may consist largely of axonal disorganization. The presence of changes in young first-episode patients also suggests that white matter pathology may represent an early marker of bipolar disorder.

Our findings suggest that a loss of bundle coherence is present in prefrontal white matter. This loss of coherence may contribute to prefrontal cortical pathology in patients with bipolar disorder.

Spatial normalization and morphological studies of pediatric brain imaging data based on adult reference data may not be appropriate due to the developmental differences between the two populations. In this study, we set out to create pediatric templates and a priori brain tissue data from a large collection of normal, healthy children to compare it to standard adult data available within a widely used imaging software solution (SPM99, WDOCN, London, UK). Employing four different processing strategies, we found considerable differences between our pediatric data and the adult data. We conclude that caution should be used when analyzing pediatric brain data using adult a priori information. To assess the effects of using pediatric a priori brain information, the data obtained in this study is available to the scientific community from our website (www.irc.cchmc.org).Magn MRI provides excellent spatial resolution and tissue contrast and is thus ideally suited for morphological analyses of the brain. To allow for the comparison of imaging studies across individuals, imaging data has to be spatially normalized. The most widely used approach to spatial frameworks is the one described by Talairach and Tournoux (1), based on a single (elderly) female brain, which is different from larger collections of normal brains used in later collections (2). Spatial normalization is generally based on adult data and thus poses special problems in children, since pediatric brains differ in size, composition, and shape from adult brains (3-5).With regard to morphological studies of the human brain, several methods utilize a priori brain information to classify brain tissue, including a widespread method for the systematic and automated analysis of structural brain data (voxel based morphometry, VBM) put forward by Ashburner and Friston (6). This method utilizes tissue a priori information from an adult reference population, and the applicability of this data to a pediatric population will depend on the differences between these populations.The question of how substantial the differences are between reference data derived from a normal pediatric population and adult data is the subject of this study. We set out to construct normative pediatric brain data and this dataset was compared to standard adult data, which is available in a widely used VBM software solution, SPM99 (Wellcome Department, University College, London, UK). MATERIALS AND METHODS SubjectsMR images of 200 healthy children were used in this study. Subjects were recruited as part of an ongoing study on normal language development (7). Institutional review board approval and informed consent were obtained for all subjects. Rigid exclusion criteria were applied to ensure a normal pediatric population (5). All MRI scans were read for structural abnormalities by a qualified pediatric neuroradiologist and excluded from further processing if abnormal findings were present. Data Acquisition and PreparationChildren were imaged with a Bruker Biospec 30/60 3 Tesla MRI scanner equ...

Objective-Functional MRI was used to determine differences in patterns of cortical activation between children who suffered perinatal left middle cerebral artery (MCA) stroke and healthy children performing a silent verb generation task.Methods-Ten children with prior perinatal left MCA stroke (age 6-16 years) and ten healthy age matched controls completed an executive language activation task. FMRI scans were acquired on a 3T scanner using T2* weighted gradient echo, echo-planar imaging (EPI) sequence. Random Effects Analysis and Independent Component Analysis (ICA) were used to compute activation maps.Results-Both analysis methods demonstrated alternative activation of cortical areas in children with perinatal stroke. Following perinatal stroke, typical left dominant productive language areas in the inferior frontal gyrus were displaced to anatomical identical areas in the right hemisphere (p=0.001). In addition, stroke patients showed more bilateral activation in superior temporal and anterior cingulate gyri and increased activation in primary visual cortex when compared to healthy controls. There was no relation between lesion size and the degree of right hemisphere activation. ICA analysis showed that the healthy controls had a negative correlation with the time course in the right inferior frontal gyrus in the same region that was activated in stroke subjects.Interpretation-This functional MRI study in children revealed novel patterns of cortical language reorganization following perinatal stroke. The addition of ICA is complementary to Random Effects analysis, allowing for the exploration of potential subtle differences in pathways in functional MRI data obtained from both healthy and pathological groups.