Sílvia Delgado Olabarriaga

Relation Between Structural and Functional Connectivity in Major Depressive Disorder

BACKGROUND Major depressive disorder (MDD) is characterized by abnormalities in both brain structure and function within a frontolimbic network. However, little is known about the relation between structural and functional abnormalities in MDD. Here, we used a multimodal neuroimaging approach to investigate the relation between structural connectivity and functional connectivity within the frontolimbic network. METHODS Eighteen MDD and 24 healthy control subjects were included, of which the integrity of the uncinate fasciculus was assessed that connects the subgenual anterior cingulate cortex (ACC) to the medial temporal lobe (MTL) with diffusion tensor imaging. Furthermore, we assessed the functional connectivity between these brain regions with functional magnetic resonance imaging. RESULTS The results showed that white matter integrity of the uncinate fasciculus was reduced and that functional connectivity between the subgenual ACC and MTL was enhanced in MDD. Importantly, we identified a negative correlation between uncinate fasciculus integrity and subgenual ACC functional connectivity with the bilateral hippocampus in MDD but not in healthy control subjects. Moreover, this negative structure-function relation in MDD was positively associated with depression severity. CONCLUSIONS These findings suggest that structural abnormalities in MDD are associated with increased functional connectivity between subgenual ACC and MTL and that these changes are concomitant with severity of depressive symptoms. This association indicates that structural abnormalities in MDD contribute to increased functional connectivity within the frontolimbic network.

Sustained effects of ecstasy on the human brain : a prospective neuroimaging study in novel users

Previous studies have suggested toxic effects of recreational ecstasy use on the serotonin system of the brain. However, it cannot be excluded that observed differences between users and non-users are the cause rather than the consequence of ecstasy use. As part of the Netherlands XTC Toxicity (NeXT) study, we prospectively assessed sustained effects of ecstasy use on the brain in novel ecstasy users using repeated measurements with a combination of different neuroimaging parameters of neurotoxicity. At baseline, 188 ecstasy-naive volunteers with high probability of first ecstasy use were examined. After a mean period of 17 months follow-up, neuroimaging was repeated in 59 incident ecstasy users and 56 matched persistent ecstasy-naives and their outcomes were compared. Neuroimaging included [(123)I]beta-carbomethoxy-3beta-(4-iodophenyl)tropane (CIT) SPECT to measure serotonin transporter densities as indicators of serotonergic function; (1)H-MR spectroscopy ((1)H-MRS) to measure brain metabolites as indicators of neuronal damage; diffusion tensor imaging (DTI) to measure the apparent diffusion coefficient and fractional anisotropy (FA) of the diffusional motion of water molecules in the brain as indicators of axonal integrity; and perfusion weighted imaging (PWI) to measure regional relative cerebral blood volume (rrCBV) which indicates brain perfusion. With this approach, both structural ((1)H-MRS and DTI) and functional ([(123)I]beta-CIT SPECT and PWI) aspects of neurotoxicity were combined. Compared to persistent ecstasy-naives, novel low-dose ecstasy users (mean 6.0, median 2.0 tablets) showed decreased rrCBV in the globus pallidus and putamen; decreased FA in thalamus and frontoparietal white matter; increased FA in globus pallidus; and increased apparent diffusion coefficient in the thalamus. No changes in serotonin transporter densities and brain metabolites were observed. These findings suggest sustained effects of ecstasy on brain microvasculature, white matter maturation and possibly axonal damage due to low dosages of ecstasy. Although we do not know yet whether these effects are reversible or not, we cannot exclude that ecstasy even in low doses is neurotoxic to the brain.

Segmentation of thrombus in abdominal aortic aneurysms from CTA with nonparametric statistical grey level appearance modeling

This paper presents a new method for deformable model-based segmentation of lumen and thrombus in abdominal aortic aneurysms from computed tomography (CT) angiography (CTA) scans. First the lumen is segmented based on two positions indicated by the user, and subsequently the resulting surface is used to initialize the automated thrombus segmentation method. For the lumen, the image-derived deformation term is based on a simple grey level model (two thresholds). For the more complex problem of thrombus segmentation, a grey level modeling approach with a nonparametric pattern classification technique is used, namely k-nearest neighbors. The intensity profile sampled along the surface normal is used as classification feature. Manual segmentations are used for training the classifier: samples are collected inside, outside, and at the given boundary positions. The deformation is steered by the most likely class corresponding to the intensity profile at each vertex on the surface. A parameter optimization study is conducted, followed by experiments to assess the overall segmentation quality and the robustness of results against variation in user input. Results obtained in a study of 17 patients show that the agreement with respect to manual segmentations is comparable to previous values reported in the literature, with considerable less user interaction.

A Prospective Cohort Study on Sustained Effects of Low-Dose Ecstasy Use on the Brain in New Ecstasy Users

It is debated whether ecstasy use has neurotoxic effects on the human brain and what the effects are of a low dose of ecstasy use. We prospectively studied sustained effects (>2 weeks abstinence) of a low dose of ecstasy on the brain in ecstasy-naive volunteers using a combination of advanced MR techniques and self-report questionnaires on psychopathology as part of the NeXT (Netherlands XTC Toxicity) study. Outcomes of proton magnetic resonance spectroscopy (1H-MRS), diffusion tensor imaging (DTI), perfusion-weighted imaging (PWI), and questionnaires on depression, impulsivity, and sensation seeking were compared in 30 subjects (12M, 21.8±3.1 years) in two sessions before and after first ecstasy use (1.8±1.3 tablets). Interval between baseline and follow-up was on average 8.1±6.5 months and time between last ecstasy use and follow-up was 7.7±4.4 weeks. Using 1H-MRS, no significant changes were observed in metabolite concentrations of N-acetylaspartate (NAA), choline (Cho), myo-inositol (mI), and creatine (Cr), nor in ratios of NAA, Cho, and mI relative to Cr. However, ecstasy use was followed by a sustained 0.9% increase in fractional anisotropy (FA) in frontoparietal white matter, a 3.4% decrease in apparent diffusion (ADC) in the thalamus and a sustained decrease in relative regional cerebral blood volume (rrCBV) in the thalamus (−6.2%), dorsolateral frontal cortex (−4.0%), and superior parietal cortex (−3.0%) (all significant at p<0.05, paired t-tests). After correction for multiple comparisons, only the rrCBV decrease in the dorsolateral frontal cortex remained significant. We also observed increased impulsivity (+3.7% on the Barratt Impulsiveness Scale) and decreased depression (−28.0% on the Beck Depression Inventory) in novel ecstasy users, although effect sizes were limited and clinical relevance questionable. As no indications were found for structural neuronal damage with the currently used techniques, our data do not support the concern that incidental ecstasy use leads to extensive axonal damage. However, sustained decreases in rrCBV and ADC values may indicate that even low ecstasy doses can induce prolonged vasoconstriction in some brain areas, although it is not known whether this effect is permanent. Additional studies are needed to replicate these findings.

A Virtual Laboratory for Medical Image Analysis

This paper presents the design, implementation, and usage of a virtual laboratory for medical image analysis. It is fully based on the Dutch grid, which is part of the Enabling Grids for E-sciencE (EGEE) production infrastructure and driven by the gLite middleware. The adopted service-oriented architecture enables decoupling the user-friendly clients running on the users workstation from the complexity of the grid applications and infrastructure. Data are stored on grid resources and can be browsed/viewed interactively by the user with the Virtual Resource Browser (VBrowser). Data analysis pipelines are described as Scufl workflows and enacted on the grid infrastructure transparently using the MOTEUR workflow management system. VBrowser plug-ins allow for easy experiment monitoring and error detection. Because of the strict compliance to the grid authentication model, all operations are performed on behalf of the user, ensuring basic security and facilitating collaboration across organizations. The system has been operational and in daily use for eight months (December 2008), with six users, leading to the submission of 9000 jobs/month in average and the production of several terabytes of data.

Minimum Cost Path Algorithm for Coronary Artery Central Axis Tracking in CT Images

The quality of cardiac images acquired with multi-detector CT scanners has improved significantly, to the point where minimally invasive examination of the coronary arteries became reality. The interpretation of such images requires efficient post-processing tools to isolate the vessels from other structures, such that they can be properly analyzed quantitatively or visually. In this paper we evaluate a method for semi-automated extraction of the central axis of coronary arteries in these images. First the vessels are enhanced with a local filter that analyzes the main modes of second-order variation in image intensity to determine the type of local structure. Secondly, the extremities of the axis are indicated by the user. Finally, a connected path between the given points is automatically determined with a minimum cost path algorithm, where the cost corresponds to the reciprocal of the enhanced image. The results obtained with different vessel enhancement filters are compared with manually traced axes in the evaluation of 15 cases.

Persistent and reversible consequences of combat stress on the mesofrontal circuit and cognition

Prolonged stress can have long-lasting effects on cognition. Animal models suggest that deficits in executive functioning could result from alterations within the mesofrontal circuit. We investigated this hypothesis in soldiers before and after deployment to Afghanistan and a control group using functional and diffusion tensor imaging. Combat stress reduced midbrain activity and integrity, which was associated to compromised sustained attention. Long-term follow-up showed that the functional and structural changes had normalized within 1.5 y. In contrast, combat stress induced a persistent reduction in functional connectivity between the midbrain and prefrontal cortex. These results demonstrate that combat stress has adverse effects on the human mesofrontal circuit and suggests that these alterations are partially reversible.

Polyunsaturated Fatty Acid Concentration Predicts Myelin Integrity in Early-Phase Psychosis

BACKGROUND White matter (WM) abnormalities have been implicated in schizophrenia, yet the mechanisms underlying these abnormalities are not fully understood. Several lines of evidence suggest that polyunsaturated fatty acids (PUFAs) play a role in myelination, and there is substantial evidence documenting decreased PUFA concentrations in schizophrenia. We therefore hypothesized that lower membrane PUFA concentrations may be related to reduced WM integrity in schizophrenia and related disorders. METHODS In 30 male patients with a recent-onset psychotic disorder, erythrocyte membrane PUFA concentrations were assessed and diffusion tensor imaging was performed with voxelwise analysis. RESULTS Lower total PUFA concentration was associated with lower fractional anisotropy (FA) throughout the corpus callosum and bilateral parietal, occipital, temporal and frontal WM (P < .05, corrected). Of the individual PUFAs, lower arachidonic acid concentration, and to a lesser extent, lower nervonic acid, linoleic acid, and docosapentaenoic acid concentration were significantly associated with lower FA. PUFA concentrations were inversely associated with radial diffusivity but showed little association with axial diffusivity. Greater severity of negative symptoms was associated with lower nervonic acid concentration and lower FA values. CONCLUSIONS Membrane PUFA concentrations appear to be robustly related to brain WM integrity in early phase psychosis. These findings may provide a basis for studies to investigate the effects of PUFA supplementation on WM integrity and associated symptomatology in early psychosis.

Do mixture models in chromaticity space improve skin detection

This note reports an experiment where a single Gaussian model and several Gaussian mixture models were used to model skin color in the rg chromaticity space. By using training and test databases containing millions of skin pixels, we show that mixture models can improve skin detection, but not always. There is a relevant operating region where no performance gain is observed.

Evaluation of Hessian-based filters to enhance the axis of coronary arteries in CT images.

Abstract This work describes an evaluation of three Hessian-based filters for enhancement of the central axis of coronary arteries in multi-detector CT images acquired with contrast injection. These filters analyze the main modes of 2nd-order variation in image intensity to determine the type of local structure present in the image (tubular-like). The average filter response obtained with different parameter configurations was measured at fixed distances from a reference central axis determined manually. Results were compared with two objective measures, namely the response decay rate at the center and the overall response within 5 mm.