To achieve a deeper understanding of the brain, scientists, and clinicians use electroencephalography (EEG) and magnetoencephalography (MEG) inverse methods to reconstruct sources in the cortical sheet of the human brain. The influence of structural and electrical anisotropy in both the skull and the white matter on the EEG and MEG source reconstruction is not well understood.In this paper, we report on a study of the sensitivity to tissue anisotropy of the EEG/MEG forward problem for deep and superficial neocortical sources with differing orientation components in an anatomically accurate model of the human head.The goal of the study was to gain insight into the effect of anisotropy of skull and white matter conductivity through the visualization of field distributions, isopotential surfaces, and return current flow and through statistical error measures. One implicit premise of the study is that factors that affect the accuracy of the forward solution will have at least as strong an influence over solutions to the associated inverse problem.Major findings of the study include (1) anisotropic white matter conductivity causes return currents to flow in directions parallel to the white matter fiber tracts; (2) skull anisotropy has a smearing effect on the forward potential computation; and (3) the deeper a source lies and the more it is surrounded by anisotropic tissue, the larger the influence of this anisotropy on the resulting electric and magnetic fields. Therefore, for the EEG, the presence of tissue anisotropy both for the skull and white matter compartment substantially compromises the forward potential computation and as a consequence, the inverse source reconstruction. In contrast, for the MEG, only the anisotropy of the white matter compartment has a significant effect. Finally, return currents with high amplitudes were found in the highly conducting cerebrospinal fluid compartment, underscoring the need for accurate modeling of this space. D

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This article examines functional and anatomical connectivity in healthy human subjects measured with magnetic resonance imaging methods. Anatomical connectivity in white matter is obtained from measurements of the diffusion tensor. A Monte-Carlo simulation determines the probability that a particle diffuses between two points, with the probability of a jump in a particular direction from a given voxel being based on the local value of the diffusion tensor components. Functional connectivity between grey matter pixels is assessed without recourse to a specific activation paradigm, by calculating the correlation coefficient between random fluctuations in the blood oxygenation level-dependent signal time course in different pixels. The methods are used to examine the anatomical and functional connectivities between crowns of adjacent gyri. A high functional connectivity was found between grey matter pixels, with white matter displaying only very low correlation. A comparison of the measurements of anatomical and functional connectivity found that there is no simple correlation between these measures, except that low values of functional connectivity were not found together with high values of anatomical connectivity. Furthermore pairs of regions situated around the central sulcus indicated a dependence of the two connectivity measures on each other. These results are in accordance with an interpretation that regions which are clearly directly linked by white matter fiber tracts should show high functional connectivity, but that the inverse need not be true as functional connectivity may also be indirectly mediated via more distant grey matter regions. © 2002 Elsevier Science (USA)

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Neuroendocrine tumours (NET) of the gastroenteropancreatic system comprise a malignant entity with a low incidence. Only limited information is available on long-term clinical outcome and clinically applicable prognostic factors. We performed a retrospective analysis of a large, wellcharacterized centre-based patient cohort of 399 patients with histologically proven NET. Data were analysed according to epidemiological, clinical and histopathological characteristics. Detailed survival analyses using the Kaplan-Meier method were performed. Prognostic factors were tested by log-rank testing and independent risk factors were analysed using a Cox regression model. In the studied cohort, primary tumours originated in the fore-, mid-and hindgut in 46.1, 37.1 and 4.5% respectively. Extra-intestinal or unknown primary tumours were present in 8.4 and 10.5% respectively. Distant metastasis was present at initial diagnosis in 69.4%. Most frequent metastatic sites were liver (85%), peritoneal cavity (18%), bones (8%), other intraabdominal sites (6%) and lungs (4%). Overall, 5-and 10-year survival rates were 78 and 63% respectively. Time to progression after initial diagnosis was significantly shorter in pancreatic as compared with ileal NET. Survival analysis revealed significantly better clinical outcome for primary tumours smaller than 25 mm, absence of metastasis, absence of any clinical symptoms, positive immunohistochemical staining for chromogranin A and a lower Ki67 index. These results were confirmed as independent by multivariate analysis. Therefore, this large retrospective analysis of a well-documented cohort of patients with NET demonstrates several prognostic factors of clinical relevance and wide availability, which should be considered for risk stratification in the management of NET.

BACKGROUND. Neuroendocrine tumors (NETs) of the gastroenteropancreatic (GEP) system comprise a rare but challenging group of malignant neoplasms and occur at virtually any site of the GEP system. In 2006, a new TNM classification system was proposed for the staging and grading of upper GEP NETs. METHODS. The prognostic relevance of the TNM classification system was analyzed retrospectively in 202 patients from a referral center with histologically proven foregut NET. Patients were classified according to previous classification systems and the TNM classification. Survival data were acquired and statistical analyses were performed by using log‐rank and Cox regression testing. RESULTS. Primary tumors were gastric (n = 48), duodenal (n = 23), and pancreatic (n = 131). During the observation period, 21% of patients died. The overall 5‐ and 10‐year survival rates were 75% and 64%, respectively. Previous classification systems discriminated between low‐grade and high‐grade malignant NETs but did not allow further prognostic differentiation. In contrast, the proposed TNM classification was able to differentiate significantly between different tumor stages (stages I‐III vs stage IV; P < .01) and cellular proliferation rates according to Ki‐67 labeling (grade 1 vs grade 2, P = .04; grade 1 vs grade 3 and grade 2 vs grade 3, P < .01). Cox regression analysis confirmed an increased risk of reduced survival for patients with stage III or IV NET and grade 2 or 3 NET. CONCLUSIONS. The current results demonstrated the prognostic relevance of the newly proposed TNM classification system for foregut NETs with statistical significance for the subgroups of both the staging classification and the grading system. Thus, the new classification system provides a valid and powerful tool for prognostic stratification of GEP NETs in clinical practice and research. Cancer 2008. © 2008 American Cancer Society.

Language ability and handedness are likely to be associated with asymmetry of the cerebral cortex (grey matter) and connectivity (white matter). Grey matter asymmetry, most likely linked to language has been identified with voxel-based morphometry (VBM) using T(1)-weighted images. Differences in white matter obtained with this technique are less consistent, probably due to the relative insensitivity of the T(1) contrast to the ultrastructure of white matter. Furthermore, previous VBM studies failed to find differences related to handedness in either grey or white matter. We revisited these issues and investigated two independent groups of subjects with diffusion-tensor imaging (DTI) for asymmetries in white matter composition. Using voxel-based statistical analyses an asymmetry of the arcuate fascicle was observed, with higher fractional anisotropy in the left hemisphere. In addition, we show differences related to handedness in the white matter underneath the precentral gyrus contralateral to the dominant hand. Remarkably, these findings were very robust, even when investigating small groups of subjects. This highlights the sensitivity of DTI for white matter tissue differences, making it an ideal tool to study small patient populations.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative system disorder affecting both upper and lower motor neurons. Despite supportive electrophysiological investigations, the involvement of the upper motor neuron is often difficult to assess at an early stage of disease. Diffusion tensor MRI provides an estimate of the orientation of fibre bundles in white matter on the basis of the diffusion characteristics of water. Diffusivity is generally higher in directions along fibre tracts than perpendicular to them. This degree of directionality of diffusion can be measured as fractional anisotropy. Changes in tissue structure due to degeneration of the corticospinal fibres can lead to a modification of the degree of directionality which can be detected by diffusion tensor MRI. We investigated 15 patients with ALS, six of whom had no clinical signs of upper motor neuron involvement at the time of MRI investigation, but developed pyramidal tract symptoms later in the course of their disease. These patients met the El Escorial criteria as their disease progressed. We found a decrease in fractional anisotropy in the corticospinal tract, corpus callosum and thalamus in all 15 ALS patients, including the patients without clinical signs of upper motor neuron lesion, compared with healthy controls. Regression analysis showed a negative correlation between fractional anisotropy and central motor conduction time obtained by transcranial magnetic stimulation, allowing spatial differentiation between the degenerated corticospinal tract fibres that supply the upper and lower extremities. Thus, diffusion tensor MRI can be used to assess upper motor neuron involvement in ALS patients before clinical symptoms of corticospinal tract lesion become apparent, and it may therefore contribute to earlier diagnosis of motor neuron disease.