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Find video protocols related to scientific articles indexed in Pubmed.
K-RasV14I recapitulates Noonan syndrome in mice.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 10-30-2014
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Noonan syndrome (NS) is an autosomal dominant genetic disorder characterized by short stature, craniofacial dysmorphism, and congenital heart defects. NS also is associated with a risk for developing myeloproliferative disorders (MPD), including juvenile myelomonocytic leukemia (JMML). Mutations responsible for NS occur in at least 11 different loci including KRAS. Here we describe a mouse model for NS induced by K-Ras(V14I), a recurrent KRAS mutation in NS patients. K-Ras(V14I)-mutant mice displayed multiple NS-associated developmental defects such as growth delay, craniofacial dysmorphia, cardiac defects, and hematologic abnormalities including a severe form of MPD that resembles human JMML. Homozygous animals had perinatal lethality whose penetrance varied with genetic background. Exposure of pregnant mothers to a MEK inhibitor rescued perinatal lethality and prevented craniofacial dysmorphia and cardiac defects. However, Mek inhibition was not sufficient to correct these defects when mice were treated after weaning. Interestingly, Mek inhibition did not correct the neoplastic MPD characteristic of these mutant mice, regardless of the timing at which the mice were treated, thus suggesting that MPD is driven by additional signaling pathways. These genetically engineered K-Ras(V14I)-mutant mice offer an experimental tool for studying the molecular mechanisms underlying the clinical manifestations of NS. Perhaps more importantly, they should be useful as a preclinical model to test new therapies aimed at preventing or ameliorating those deficits associated with this syndrome.
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Combination of Single-Photon Emission Computed Tomography and Magnetic Resonance Imaging to Track 111In-Oxine-Labeled Human Mesenchymal Stem Cells in Neuroblastoma-Bearing Mice.
Mol Imaging
PUBLISHED: 09-25-2014
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AbstractHoming is an inherent, complex, multistep process performed by cells such as human bone marrow mesenchymal stem cells (hMSCs) to travel from a distant location to inflamed or damaged tissue and tumors. This ability of hMSCs has been exploited as a tumor-targeting strategy in cell-based cancer therapy. The purpose of this study was to investigate the applicability of 111In-oxine for tracking hMSCs in vivo by combining single-photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI). 111In-labeled hMSCs (106 cells) were infused intraperitoneally in neuroblastoma-bearing mice, whereas a control group received a dose of free 111In-oxine. SPECT and MRI studies were performed 24 and 48 hours afterwards. Initially, the images showed similar activity in the abdomen in both controls and hMSC-injected animals. In general, abdominal activity decreases at 48 hours. hMSC-injected animals showed increased uptake in the tumor area at 48 hours, whereas the control group showed a low level of activity at 24 hours, which decreased at 48 hours. In conclusion, tracking 111In-labeled hMSCs combining SPECT and MRI is feasible and may be transferable to clinical research. The multimodal combination is essential to ensure appropriate interpretation of the images.
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Predictors of schizophrenia spectrum disorders in early-onset first episodes of psychosis: a support vector machine model.
Eur Child Adolesc Psychiatry
PUBLISHED: 08-11-2014
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Identifying early-onset schizophrenia spectrum disorders (SSD) at a very early stage remains challenging. To assess the diagnostic predictive value of multiple types of data at the emergence of early-onset first-episode psychosis (FEP), various support vector machine (SVM) classifiers were developed. The data were from a 2-year, prospective, longitudinal study of 81 patients (age 9-17 years) with early-onset FEP and a stable diagnosis during follow-up and 42 age- and sex-matched healthy controls (HC). The input was different combinations of baseline clinical, neuropsychological, magnetic resonance imaging brain volumetric and biochemical data, and the output was the diagnosis at follow-up (SSD vs. non-SSD, SSD vs. HC, and non-SSD vs. HC). Enhanced recursive feature elimination was performed for the SSD vs. non-SSD classifier to select and rank the input variables with the highest predictive value for a diagnostic outcome of SSD. After validation with a test set and considering all baseline variables together, the SSD vs. non-SSD, SSD vs. HC and non-SSD vs. HC classifiers achieved an accuracy of 0.81, 0.99 and 0.99, respectively. Regarding the SSD vs. non-SSD classifier, a combination of baseline clinical variables (severity of negative, disorganized symptoms and hallucinations or poor insight) and neuropsychological variables (impaired attention, motor coordination, and global cognition) showed the highest predictive value for a diagnostic outcome of SSD. Neuroimaging and biochemical variables at baseline did not add to the predictive value. Thus, comprehensive clinical/cognitive assessment remains the most reliable approach for differential diagnosis during early-onset FEP. SVMs may constitute promising multivariate tools in the search for predictors of diagnostic outcome in FEP.
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Response to deep brain stimulation in the lateral hypothalamic area in a rat model of obesity: in vivo assessment of brain glucose metabolism.
Mol Imaging Biol
PUBLISHED: 03-11-2014
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To investigate changes in glucose brain metabolism after deep brain stimulation (DBS) in the lateral hypothalamic area (LHA) in a rat model of obesity.
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Cerebral blood flow is an earlier indicator of perfusion abnormalities than cerebral blood volume in Alzheimer's disease.
J. Cereb. Blood Flow Metab.
PUBLISHED: 01-15-2014
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The purpose of this study was to elucidate whether cerebral blood flow (CBF) can better characterize perfusion abnormalities in predementia stages of Alzheimer's disease (AD) than cerebral blood volume (CBV) and whether cortical atrophy is more associated with decreased CBV or with decreased CBF. We compared measurements of CBV, CBF, and mean cortical thickness obtained from magnetic resonance images in a group of healthy controls, patients with mild cognitive impairment (MCI) who converted to AD after 2 years of clinical follow-up (MCI-c), and patients with mild AD. A significant decrease in perfusion was detected in the parietal lobes of the MCI-c patients with CBF parametric maps but not with CBV maps. In the MCI-c group, a negative correlation between CBF values and cortical thickness in the right parahippocampal gyrus suggests an increase in CBF that depends on cortical atrophy in predementia stages of AD. Our study also suggests that CBF deficits appear before CBV deficits in the progression of AD, as CBV abnormalities were only detected at the AD stage, whereas CBF changes were already detected in the MCI stage. These results confirm the hypothesis that CBF is a more sensitive parameter than CBV for perfusion abnormalities in MCI-c patients.
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Cortical morphology of adolescents with bipolar disorder and with schizophrenia.
Schizophr. Res.
PUBLISHED: 01-08-2014
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Recent evidence points to overlapping decreases in cortical thickness and gyrification in the frontal lobe of patients with adult-onset schizophrenia and bipolar disorder with psychotic symptoms, but it is not clear if these findings generalize to patients with a disease onset during adolescence and what may be the mechanisms underlying a decrease in gyrification.
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Meningiomas: A Comparative Study of 68Ga-DOTATOC, 68Ga-DOTANOC and 68Ga-DOTATATE for Molecular Imaging in Mice.
PLoS ONE
PUBLISHED: 01-01-2014
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The goal of this study was to compare the tumor uptake kinetics and diagnostic value of three 68Ga-DOTA-labeled somatostatin analogues (68Ga-DOTATOC, 68Ga-DOTANOC, and 68Ga-DOTATATE) using PET/CT in a murine model with subcutaneous meningioma xenografts.
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Comparison of total variation with a motion estimation based compressed sensing approach for self-gated cardiac cine MRI in small animal studies.
PLoS ONE
PUBLISHED: 01-01-2014
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Compressed sensing (CS) has been widely applied to prospective cardiac cine MRI. The aim of this work is to study the benefits obtained by including motion estimation in the CS framework for small-animal retrospective cardiac cine.
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Comparison of methods to reduce myocardial 18F-FDG uptake in mice: calcium channel blockers versus high-fat diets.
PLoS ONE
PUBLISHED: 01-01-2014
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Besides its application in oncology, 18F-FDG PET-CT imaging is also useful in the diagnosis of certain lung infections, inflammatory diseases, and atherosclerotic plaques. Myocardial uptake of 18F-FDG may hamper visualization of the lesions caused by these diseases. Two approaches have been proposed for reducing myocardial uptake in preclinical studies, namely, calcium channel blockers (verapamil) and high-fat diets such as commercial ketogenic diets and sunflower seed diets. The objective of this study was to compare the efficacy of these approaches in reducing myocardial uptake of 18F-FDG in mice.
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The human cerebral cortex flattens during adolescence.
J. Neurosci.
PUBLISHED: 09-20-2013
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The human cerebral cortex appears to shrink during adolescence. To delineate the dynamic morphological changes involved in this process, 52 healthy male and female adolescents (11-17 years old) were neuroimaged twice using magnetic resonance imaging, approximately 2 years apart. Using a novel morphometric analysis procedure combining the FreeSurfer and BrainVisa image software suites, we quantified global and lobar change in cortical thickness, outer surface area, the gyrification index, the average Euclidean distance between opposing sides of the white matter surface (gyral white matter thickness), the convex ("exposed") part of the outer cortical surface (hull surface area), sulcal length, depth, and width. We found that the cortical surface flattens during adolescence. Flattening was strongest in the frontal and occipital cortices, in which significant sulcal widening and decreased sulcal depth co-occurred. Globally, sulcal widening was associated with cortical thinning and, for the frontal cortex, with loss of surface area. For the other cortical lobes, thinning was related to gyral white matter expansion. The overall flattening of the macrostructural three-dimensional architecture of the human cortex during adolescence thus involves changes in gray matter and effects of the maturation of white matter.
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Targeted antifungal prophylaxis in heart transplant recipients.
Transplantation
PUBLISHED: 08-08-2013
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Antifungal prophylaxis after heart transplantation is usually targeted to high-risk recipients, but the duration is normally fixed and empirical. Our purpose was to assess the efficacy of a personalized prophylactic approach based on the duration of the risk factors.
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Organ-focused mutual information for nonrigid multimodal registration of liver CT and Gd-EOB-DTPA-enhanced MRI.
Med Image Anal
PUBLISHED: 08-07-2013
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Accurate detection of liver lesions is of great importance in hepatic surgery planning. Recent studies have shown that the detection rate of liver lesions is significantly higher in gadoxetic acid-enhanced magnetic resonance imaging (Gd-EOB-DTPA-enhanced MRI) than in contrast-enhanced portal-phase computed tomography (CT); however, the latter remains essential because of its high specificity, good performance in estimating liver volumes and better vessel visibility. To characterize liver lesions using both the above image modalities, we propose a multimodal nonrigid registration framework using organ-focused mutual information (OF-MI). This proposal tries to improve mutual information (MI) based registration by adding spatial information, benefiting from the availability of expert liver segmentation in clinical protocols. The incorporation of an additional information channel containing liver segmentation information was studied. A dataset of real clinical images and simulated images was used in the validation process. A Gd-EOB-DTPA-enhanced MRI simulation framework is presented. To evaluate results, warping index errors were calculated for the simulated data, and landmark-based and surface-based errors were calculated for the real data. An improvement of the registration accuracy for OF-MI as compared with MI was found for both simulated and real datasets. Statistical significance of the difference was tested and confirmed in the simulated dataset (p<0.01).
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Use of Split Bregman denoising for iterative reconstruction in fluorescence diffuse optical tomography.
J Biomed Opt
PUBLISHED: 07-19-2013
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Fluorescence diffuse optical tomography (fDOT) is a noninvasive imaging technique that makes it possible to quantify the spatial distribution of fluorescent tracers in small animals. fDOT image reconstruction is commonly performed by means of iterative methods such as the algebraic reconstruction technique (ART). The useful results yielded by more advanced l1-regularized techniques for signal recovery and image reconstruction, together with the recent publication of Split Bregman (SB) procedure, led us to propose a new approach to the fDOT inverse problem, namely, ART-SB. This method alternates a cost-efficient reconstruction step (ART iteration) with a denoising filtering step based on minimization of total variation of the image using the SB method, which can be solved efficiently and quickly. We applied this method to simulated and experimental fDOT data and found that ART-SB provides substantial benefits over conventional ART.
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Automatic TAC extraction from dynamic cardiac PET imaging using iterative correlation from a population template.
Comput Methods Programs Biomed
PUBLISHED: 04-01-2013
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This work describes a new iterative method for extracting time-activity curves (TAC) from dynamic imaging studies using a priori information from generic models obtained from TAC templates. Analytical expressions of the TAC templates were derived from TACs obtained by manual segmentation of three (13)NH3 pig studies (gold standard). An iterative method for extracting both ventricular and myocardial TACs using models of the curves obtained as an initial template was then implemented and tested. These TACs were extracted from masked and unmasked images; masking was applied to remove the lungs and surrounding non-relevant structures. The resulting TACs were then compared with TACs obtained manually; the results of kinetic analysis were also compared. Extraction of TACs for each region was sensitive to the presence of other organs (e.g., lungs) in the image. Masking the volume of interest noticeably reduces error. The proposed method yields good results in terms of TAC definition and kinetic parameter estimation, even when the initial TAC templates do not accurately match specific tracer kinetics.
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Comparison of different methods of spatial normalization of FDG-PET brain images in the voxel-wise analysis of MCI patients and controls.
Ann Nucl Med
PUBLISHED: 03-27-2013
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One of the most interesting clinical applications of 18F-FDG PET imaging in neurodegenerative pathologies is that of establishing the prognosis of patients with mild cognitive impairment (MCI), some of whom have a high risk of progressing to Alzheimers disease (AD). One method of analyzing these images is to perform statistical parametric mapping (SPM) analysis. Spatial normalization is a critical step in such an analysis. The purpose of this study was to assess the effect of using different methods of spatial normalization on the results of SPM analysis of 18F-FDG PET images by comparing patients with MCI and controls.
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White matter microstructure correlates of mathematical giftedness and intelligence quotient.
Hum Brain Mapp
PUBLISHED: 02-20-2013
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Recent functional neuroimaging studies have shown differences in brain activation between mathematically gifted adolescents and controls. The aim of this study was to investigate the relationship between mathematical giftedness, intelligent quotient (IQ), and the microstructure of white matter tracts in a sample composed of math-gifted adolescents and aged-matched controls. Math-gifted subjects were selected through a national program based on detecting enhanced visuospatial abilities and creative thinking. We used diffusion tensor imaging to assess white matter microstructure in neuroanatomical connectivity. The processing included voxel-wise and region of interest-based analyses of the fractional anisotropy (FA), a parameter which is purportedly related to white matter microstructure. In a whole-sample analysis, IQ showed a significant positive correlation with FA, mainly in the corpus callosum, supporting the idea that efficient information transfer between hemispheres is crucial for higher intellectual capabilities. In addition, math-gifted adolescents showed increased FA (adjusted for IQ) in white matter tracts connecting frontal lobes with basal ganglia and parietal regions. The enhanced anatomical connectivity observed in the forceps minor and splenium may underlie the greater fluid reasoning, visuospatial working memory, and creative capabilities of these children. Hum Brain Mapp, 2013. © 2013 Wiley Periodicals, Inc.
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Application of the compressed sensing technique to self-gated cardiac cine sequences in small animals.
Magn Reson Med
PUBLISHED: 01-12-2013
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Self-gated cine sequences are a common choice for cardiac MRI in preclinical applications. The aims of our work were to apply the compressed sensing technique to IntraGateFLASH cardiac MRI studies on rats and to find the maximum acceleration factor achievable with this technique.
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Is the Cerebellum the Optimal Reference Region for Intensity Normalization of Perfusion MR Studies in Early Alzheimers Disease?
PLoS ONE
PUBLISHED: 01-01-2013
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The cerebellum is the region most commonly used as a reference when normalizing the intensity of perfusion images acquired using magnetic resonance imaging (MRI) in Alzheimers disease (AD) studies. In addition, the cerebellum provides unbiased estimations with nuclear medicine techniques. However, no reports confirm the cerebellum as an optimal reference region in MRI studies or evaluate the consequences of using different normalization regions. In this study, we address the effect of using the cerebellum, whole-brain white matter, and whole-brain cortical gray matter in the normalization of cerebral blood flow (CBF) parametric maps by comparing patients with stable mild cognitive impairment (MCI), patients with AD and healthy controls. According to our results, normalization by whole-brain cortical gray matter enables more sensitive detection of perfusion abnormalities in AD patients and reveals a larger number of affected regions than data normalized by the cerebellum or whole-brain white matter. Therefore, the cerebellum is not the most valid reference region in MRI studies for early stages of AD. After normalization by whole-brain cortical gray matter, we found a significant decrease in CBF in both parietal lobes and an increase in CBF in the right medial temporal lobe. We found no differences in perfusion between patients with stable MCI and healthy controls either before or after normalization.
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jClustering, an open framework for the development of 4D clustering algorithms.
PLoS ONE
PUBLISHED: 01-01-2013
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We present jClustering, an open framework for the design of clustering algorithms in dynamic medical imaging. We developed this tool because of the difficulty involved in manually segmenting dynamic PET images and the lack of availability of source code for published segmentation algorithms. Providing an easily extensible open tool encourages publication of source code to facilitate the process of comparing algorithms and provide interested third parties with the opportunity to review code. The internal structure of the framework allows an external developer to implement new algorithms easily and quickly, focusing only on the particulars of the method being implemented and not on image data handling and preprocessing. This tool has been coded in Java and is presented as an ImageJ plugin in order to take advantage of all the functionalities offered by this imaging analysis platform. Both binary packages and source code have been published, the latter under a free software license (GNU General Public License) to allow modification if necessary.
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Regional specificity of thalamic volume deficits in male adolescents with early-onset psychosis.
Br J Psychiatry
PUBLISHED: 11-24-2011
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Thalamic volume deficits are associated with psychosis but it is unclear whether the volume reduction is uniformly distributed or whether it is more severe in particular thalamic regions.
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Optimal multiresolution 3D level-set method for liver segmentation incorporating local curvature constraints.
Conf Proc IEEE Eng Med Biol Soc
PUBLISHED: 08-29-2011
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Advanced liver surgery requires a precise pre-operative planning, where liver segmentation and remnant liver volume are key elements to avoid post-operative liver failure. In that context, level-set algorithms have achieved better results than others, especially with altered liver parenchyma or in cases with previous surgery. In order to improve functional liver parenchyma volume measurements, in this work we propose two strategies to enhance previous level-set algorithms: an optimal multi-resolution strategy with fine details correction and adaptive curvature, as well as an additional semiautomatic step imposing local curvature constraints. Results show more accurate segmentations, especially in elongated structures, detecting internal lesions and avoiding leakages to close structures.
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Split operator method for fluorescence diffuse optical tomography using anisotropic diffusion regularisation with prior anatomical information.
Biomed Opt Express
PUBLISHED: 07-07-2011
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Fluorescence diffuse optical tomography (fDOT) is an imaging modality that provides images of the fluorochrome distribution within the object of study. The image reconstruction problem is ill-posed and highly underdetermined and, therefore, regularisation techniques need to be used. In this paper we use a nonlinear anisotropic diffusion regularisation term that incorporates anatomical prior information. We introduce a split operator method that reduces the nonlinear inverse problem to two simpler problems, allowing fast and efficient solution of the fDOT problem. We tested our method using simulated, phantom and ex-vivo mouse data, and found that it provides reconstructions with better spatial localisation and size of fluorochrome inclusions than using the standard Tikhonov penalty term.
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Feasibility of U-curve method to select the regularization parameter for fluorescence diffuse optical tomography in phantom and small animal studies.
Opt Express
PUBLISHED: 07-01-2011
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When dealing with ill-posed problems such as fluorescence diffuse optical tomography (fDOT) the choice of the regularization parameter is extremely important for computing a reliable reconstruction. Several automatic methods for the selection of the regularization parameter have been introduced over the years and their performance depends on the particular inverse problem. Herein a U-curve-based algorithm for the selection of regularization parameter has been applied for the first time to fDOT. To increase the computational efficiency for large systems an interval of the regularization parameter is desirable. The U-curve provided a suitable selection of the regularization parameter in terms of Picards condition, image resolution and image noise. Results are shown both on phantom and mouse data.
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The application of nanoparticles in gene therapy and magnetic resonance imaging.
Microsc. Res. Tech.
PUBLISHED: 04-11-2011
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The combination of nanoparticles, gene therapy, and medical imaging has given rise to a new field known as gene theranostics, in which a nanobioconjugate is used to diagnose and treat the disease. The process generally involves binding between a vector carrying the genetic information and a nanoparticle, which provides the signal for imaging. The synthesis of this probe generates a synergic effect, enhancing the efficiency of gene transduction and imaging contrast. We discuss the latest approaches in the synthesis of nanoparticles for magnetic resonance imaging, gene therapy strategies, and their conjugation and in vivo application.
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Influence of resting energy expenditure on weight gain in adolescents taking second-generation antipsychotics.
Clin Nutr
PUBLISHED: 03-11-2011
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Weight gain is an undesirable side effect of second-generation antipsychotics (SGAs). We performed this study to examine the influence of SGAs on resting energy expenditure (REE) and the relationship of REE to weight gain in adolescent patients.
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Constitutive activation of B-Raf in the mouse germ line provides a model for human cardio-facio-cutaneous syndrome.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 03-07-2011
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RASopathies are a class of developmental syndromes that result from congenital mutations in key elements of the RAS/RAF/MEK signaling pathway. A well-recognized RASopathy is the cardio-facio-cutaneous (CFC) syndrome characterized by a distinctive facial appearance, heart defects, and mental retardation. Clinically diagnosed CFC patients carry germ-line mutations in four different genes, B-RAF, MEK1, MEK2, and K-RAS. B-RAF is by far the most commonly mutated locus, displaying mutations that most often result in constitutive activation of the B-RAF kinase. Here, we describe a mouse model for CFC generated by germ-line expression of a B-RafLSLV600E allele. This targeted allele allows low levels of expression of B-RafV600E, a constitutively active B-Raf kinase first identified in human melanoma. B-Raf+/LSLV600E mice are viable and display several of the characteristic features observed in CFC patients, including reduced life span, small size, facial dysmorphism, cardiomegaly, and epileptic seizures. These mice also show up-regulation of specific catecholamines and cataracts, two features detected in a low percentage of CFC patients. In addition, B-Raf+/LSLV600E mice develop neuroendocrine tumors, a pathology not observed in CFC patients. These mice may provide a means of better understanding the pathophysiology of at least some of the clinical features present in CFC patients. Moreover, they may serve as a tool to evaluate the potential therapeutic efficacy of B-RAF inhibitors and establish the precise window at which they could be effective against this congenital syndrome.
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Mathematically gifted adolescents use more extensive and more bilateral areas of the fronto-parietal network than controls during executive functioning and fluid reasoning tasks.
Neuroimage
PUBLISHED: 03-01-2011
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The main goal of this study was to investigate the neural substrates of fluid reasoning and visuospatial working memory in adolescents with precocious mathematical ability. The study population comprised two groups of adolescents: 13 math-gifted adolescents and 14 controls with average mathematical skills. Patterns of activation specific to reasoning tasks in math-gifted subjects were examined using functional magnetic resonance images acquired while the subjects were performing Ravens Advanced Progressive Matrices (RAPM) and the Tower of London (TOL) tasks. During the tasks, both groups showed significant activations in the frontoparietal network. In the math-gifted group, clusters of activation were always bilateral and more regions were recruited, especially in the right hemisphere. In the TOL task, math-gifted adolescents showed significant hyper-activations relative to controls in the precuneus, superior occipital lobe (BA 19), and medial temporal lobe (BA 39). The maximum differences between the groups were detected during RAPM tasks at the highest level of difficulty, where math-gifted subjects showed significant activations relative to controls in the right inferior parietal lobule (BA 40), anterior cingulated gyrus (BA 32), and frontal (BA 9, and BA 6) areas. Our results support the hypothesis that greater ability for complex mathematical reasoning may be related to more bilateral patterns of activation and that increased activation in the parietal and frontal regions of math-gifted adolescents is associated with enhanced skills in visuospatial processing and logical reasoning.
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A novel approach to investigate neuronal network activity patterns affected by deep brain stimulation in rats.
J Psychiatr Res
PUBLISHED: 01-12-2011
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The establishment of new therapeutic indications for deep brain stimulation (DBS) is ambitiously promoted though the underlying mechanisms remain contested. Here, we report that PET-imaging and subsequent c-Fos-immunostaining in rats constitute a new translational approach to further understand DBS-mechanisms and -effectiveness.
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Dopamine D4 receptors modulate brain metabolic activity in the prefrontal cortex and cerebellum at rest and in response to methylphenidate.
Eur. J. Neurosci.
PUBLISHED: 07-16-2010
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Methylphenidate (MP) is widely used to treat attention deficit hyperactivity disorder (ADHD). Variable number of tandem repeats polymorphisms in the dopamine D4 receptor (D(4)) gene have been implicated in vulnerability to ADHD and the response to MP. Here we examined the contribution of dopamine D4 receptors (D4Rs) to baseline brain glucose metabolism and to the regional metabolic responses to MP. We compared brain glucose metabolism (measured with micro-positron emission tomography and [(18)F]2-fluoro-2-deoxy-D-glucose) at baseline and after MP (10 mg/kg, i.p.) administration in mice with genetic deletion of the D(4). Images were analyzed using a novel automated image registration procedure. Baseline D(4)(-/-) mice had lower metabolism in the prefrontal cortex (PFC) and greater metabolism in the cerebellar vermis (CBV) than D(4)(+/+) and D(4)(+/-) mice; when given MP, D(4)(-/-) mice increased metabolism in the PFC and decreased it in the CBV, whereas in D(4)(+/+) and D(4)(+/-) mice, MP decreased metabolism in the PFC and increased it in the CBV. These findings provide evidence that D4Rs modulate not only the PFC, which may reflect the activation by dopamine of D4Rs located in this region, but also the CBV, which may reflect an indirect modulation as D4Rs are minimally expressed in this region. As individuals with ADHD show structural and/or functional abnormalities in these brain regions, the association of ADHD with D4Rs may reflect its modulation of these brain regions. The differential response to MP as a function of genotype could explain differences in brain functional responses to MP between patients with ADHD and healthy controls and between patients with ADHD with different D(4) polymorphisms.
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Multicenter study of brain volume abnormalities in children and adolescent-onset psychosis.
Schizophr Bull
PUBLISHED: 05-16-2010
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The goal of the study is to determine the extent of structural brain abnormalities in a multicenter sample of children and adolescents with a recent-onset first episode of psychosis (FEP), compared with a sample of healthy controls. Total brain and lobar volumes and those of gray matter (GM), white matter, and cerebrospinal fluid (CSF) were measured in 92 patients with a FEP and in 94 controls, matched for age, gender, and years of education. Male patients (n = 64) showed several significant differences when compared with controls (n = 61). GM volume in male patients was reduced in the whole brain and in frontal and parietal lobes compared with controls. Total CSF volume and frontal, temporal, and right parietal CSF volumes were also increased in male patients. Within patients, those with a further diagnosis of "schizophrenia" or "other psychosis" showed a pattern similar to the group of all patients relative to controls. However, bipolar patients showed fewer differences relative to controls. In female patients, only the schizophrenia group showed differences relative to controls, in frontal CSF. GM deficit in male patients with a first episode correlated with negative symptoms. Our study suggests that at least part of the GM deficit in children and adolescent-onset schizophrenia and in other psychosis occurs before onset of the first positive symptoms and that, contrary to what has been shown in children-onset schizophrenia, frontal GM deficits are probably present from the first appearance of positive symptoms in children and adolescents.
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Variations in the shape of the frontobasal brain region in obsessive-compulsive disorder.
Hum Brain Mapp
PUBLISHED: 01-09-2010
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Obsessive-compulsive disorder (OCD) emerges during childhood through young adulthood coinciding with the late phases of postnatal brain development when fine remodeling of brain anatomy takes place. Previous research has suggested the existence of subtle anatomical alterations in OCD involving focal volume variations in different brain regions including the frontal lobes and basal ganglia. We investigated whether anatomical changes might also involve variations in the shape of the frontobasal region. A total of 101 OCD patients and 101 control subjects were examined using magnetic resonance imaging. A cross-sectional image highly representative of frontal-basal ganglia anatomy was selected in each individual and 25 reliable anatomical landmarks were identified to assess shape changes. A pixel-wise morphing approach was also used to dynamically illustrate the findings. We found significant group differences for overall landmark position and for most individual landmarks delimiting the defined frontobasal region. OCD patients showed a deformation pattern involving shortening of the anterior-posterior dimension of the frontal lobes and basal ganglia, and enlargement of cerebrospinal fluid spaces around the frontal opercula. In addition, we observed significant correlation of brain tissue shape variation with frontal sinus size. Identification of a global change in the shape of the frontobasal region may further contribute to characterizing the nature of brain alterations in OCD. The coincidence of brain shape variations with morphological changes in the frontal sinus indicates a potential association of OCD to late development disturbances, as the frontal sinus macroscopically emerges during the transition between childhood and adulthood.
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3D liver segmentation in preoperative CT images using a level-sets active surface method.
Conf Proc IEEE Eng Med Biol Soc
PUBLISHED: 12-08-2009
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In this work we propose an active surface method to segment complete liver volumes from preoperative CT abdominal images. The method finds the surface that minimizes an energy function combining intensity inside and outside the surface, gradient information and curvature restrictions. The implementation is based on a level set technique following a multi-resolution strategy to reduce computing time. It requires only a single seed point inside the liver to initialize the active surface. The algorithm has been validated on a set of previously diagnosed livers. Resulting segmentations have been supervised by clinicians and radiologists, and numerically evaluated in terms of volume measurements with respect to those obtained from radiologists manual segmentations. Additionally, radiologists analyzed the necessity of additional corrections on segmenting volumes.
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A novel R-package graphic user interface for the analysis of metabonomic profiles.
BMC Bioinformatics
PUBLISHED: 10-29-2009
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Analysis of the plethora of metabolites found in the NMR spectra of biological fluids or tissues requires data complexity to be simplified. We present a graphical user interface (GUI) for NMR-based metabonomic analysis. The "Metabonomic Package" has been developed for metabonomics research as open-source software and uses the R statistical libraries.
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Automated method for small-animal PET image registration with intrinsic validation.
Mol Imaging Biol
PUBLISHED: 09-18-2009
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We propose and compare different registration approaches to align small-animal PET studies and a procedure to validate the results by means of objective registration consistency measurements.
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Brain morphology and neurological soft signs in adolescents with first-episode psychosis.
Br J Psychiatry
PUBLISHED: 09-02-2009
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Adolescents with first-episode psychosis have increased severity of neurological soft signs when compared with controls, but it is unclear whether increased severity of neurological soft signs is an expression of specific structural brain deficits.
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Automatic quantification of histological studies in allergic asthma.
Cytometry A
PUBLISHED: 06-23-2009
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The evaluation of new therapies to treat allergic asthma makes frequent use of histological studies. Some of them are based on microscope observation of stained paraffin lung sections to quantify cellular infiltrate, an effect directly related to allergic processes. Currently, there is no software tool available for doing this quantification automatically. This paper presents a methodology and a software tool for the quantification of cellular infiltrate in lung tissue images in an allergic asthma mouse model. The image is divided into regions of equal size, which are then classified by means of a segmentation algorithm based on texture analysis. The classification uses three discriminant functions, built from parameters derived from the histogram and the co-occurrence matrix. These functions were calculated by means of a stepwise discriminant analysis on 79 samples from a training set. Results provided a correct classification of 96.8% on an independent test set of 251 samples labeled manually. Regression analysis showed a good agreement between automatic and manual methods. A reliable and easy to implement method has been developed to provide an automatic method for quantifying microscopy images of lung histological studies. Results showed similar accuracy to that provided by an expert, while allowing analyzing a much larger number of fields in a repeatable way.
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Assessment of the increase in variability when combining volumetric data from different scanners.
Hum Brain Mapp
PUBLISHED: 04-10-2009
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In multicenter MRI studies, pooling of volumetric data requires a prior evaluation of compatibility between the different machines used. We tested the compatibility of five different scanners (2 General Electric Signa, 2 Siemens Symphony, and a Philips Gyroscan) at five different sites by repeating the scans of five volunteers at each of the sites. Using a semiautomatic method based on the Talairach atlas, and SPM algorithms for tissue segmentation (multimodal T1 and T2, or T1-only), we obtained volume measurements of the main brain lobes (frontal, parietal, occipital, temporal) and for each tissue type. Our results suggest that pooling of multisite data adds small error for whole brain measurements, intersite coefficient of variation (CV) ranging from 1.8 to 5.2%, respectively, for GM and CSF. However, in the occipital lobe, intersite CV can be as high as 11.7% for WM and 17.3% for CSF. Compared with the intersite, intrasite CV values were always much lower. Whenever possible, T1 and T2 tissue segmentation methods should be used because they yield more consistent volume measurements between sites than T1-only, especially when some of the scans were obtained with different sequence parameters and pixel size from those of the other sites. Our study shows that highest compatibility among scanners would be obtained using equipments of the same manufacturer and also image acquisition parameters as similar as possible. After validation, data from a specific ROI or scanner showing values markedly different from the other sites might be excluded from the analysis.
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Gyral and sulcal cortical thinning in adolescents with first episode early-onset psychosis.
Biol. Psychiatry
PUBLISHED: 03-31-2009
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Psychosis is associated with volumetric decreases of cortical structures. Whether these volumetric decreases imply abnormalities in cortical thickness, surface, or cortical folding is not clear. Due to differences in cytoarchitecture, cortical gyri and sulci might be differentially affected by psychosis. Therefore, we examined differences in gyral and sulcal cortical thickness, surface, folding, and volume between a minimally treated male adolescent population with early-onset first-episode psychosis (EOP) and a healthy control group, with surface-based morphometry.
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Progression of brain volume changes in adolescent-onset psychosis.
Schizophr Bull
PUBLISHED: 03-31-2009
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Little is known about the changes that take place in the adolescent brain over the first few years following the onset of psychosis. The present longitudinal study builds on an earlier cross-sectional report demonstrating brain abnormalities in adolescent-onset psychosis patients with a recent-onset first episode of psychosis. Magnetic resonance imaging studies were obtained at baseline and 2 years later from 21 adolescents with psychosis and 34 healthy controls matched for age, gender, and years of education. Whole-brain volumes and gray matter (GM) and cerebrospinal fluid (CSF) volumes of the frontal, parietal, temporal, and occipital lobes were measured at baseline and at 2-year follow-up. In the frontal lobe, the rate of GM volume loss was significantly higher in male patients (2.9% and 2.0%, respectively, for left and right) than in controls (1.2% and 0.7%, respectively, for left and right). In the left frontal lobe, male patients showed a significantly higher rate of CSF volume increase than controls (8.6% vs 6.4%). These differences in rates of volume change were observed in male and female patients, although only males showed significant time x diagnosis interactions. This negative finding in females should be interpreted with caution as the study was underpowered to detect change in women due to limited sample size. An exploratory analysis revealed that schizophrenia and nonschizophrenia psychotic disorders showed similar volume change patterns relative to controls. Change in clinical status was not correlated with longitudinal brain changes. Our results support progression of frontal lobe changes in males with adolescent-onset psychosis.
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Incidence and risk factors for ventilator-associated pneumonia after major heart surgery.
Intensive Care Med
PUBLISHED: 03-06-2009
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Major heart surgery (MHS) patients are a particularly high-risk population for nosocomial infections. Our objective was to identify risk factors for ventilator-associated pneumonia (VAP) in patients undergoing MHS.
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The chemokine receptor CXCR4 and the metalloproteinase MT1-MMP are mutually required during melanoma metastasis to lungs.
Am. J. Pathol.
PUBLISHED: 01-15-2009
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Melanoma is the most aggressive skin cancer once metastasis begins; therefore, it is important to characterize the molecular players involved in melanoma dissemination. The chemokine receptor CXCR4 and the membrane-bound metalloproteinase MT1-MMP are expressed on melanoma cells and represent candidate molecules for the control of metastasis. Using human melanoma transfectants that either overexpress or silence CXCR4 or MT1-MMP, or that have a combination of overexpression and interference of these proteins, we show that CXCR4 and MT1-MMP coordinate their activities at different steps along melanoma cell metastasis into the lungs. Results from in vivo xenograft mouse models of melanoma lung colonization and mice survival and short-term, homing nested polymerase chain reaction experiments from lung samples indicated that CXCR4 is required at early phases of melanoma cell arrival in the lungs. In contrast, MT1-MMP is not needed for these initial steps but promotes subsequent invasion and dissemination of the tumor with CXCR4. Investigation of potential cross talk between CXCR4 and MT1-MMP revealed that MT1-MMP accumulates intracellularly after melanoma cell stimulation with the CXCR4 ligand CXCL12, and that this process involves the activation of the Rac-Erk1/2 pathway. Subsequent to cell contact with specific basement membrane proteins, MT1-MMP redistributes to the cell membrane in a phosphatidylinositol 3-kinase-dependent manner. These results suggest that combination therapies that target CXCR4 and MT1-MMP should improve the limitations of the current therapies for metastatic melanoma.
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Live imaging of mouse endogenous neural progenitors migrating in response to an induced tumor.
PLoS ONE
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Adult neurogenesis is restricted to specific brain regions. Although involved in the continuous supply of interneurons for the olfactory function, the role of neural precursors in brain damage-repair remains an open question. Aiming to in vivo identify endogenous neural precursor cells migrating towards a brain damage site, the monoclonal antibody Nilo2 recognizing cell surface antigens on neuroblasts, was coupled to magnetic glyconanoparticles (mGNPs). The Nilo2-mGNP complexes allowed, by magnetic resonance imaging in living animals, the in vivo identification of endogenous neural precursors at their niche, as well as their migration to a lesion site (induced brain tumor), which was fast (within hours) and orderly. Interestingly, the rapid migration of neuroblasts towards a damage site is a characteristic that might be exploited to precisely localize early damage events in neurodegenerative diseases. In addition, it might facilitate the study of regenerative mechanisms through the activation of endogenous neural cell precursors. A similar approach, combining magnetic glyconanoparticles linked to appropriate antibodies could be applied to flag other small cell subpopulations within the organism, track their migration, localize stem cell niches, cancer stem cells or even track metastatic cells.
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Waking-like brain function in embryos.
Curr. Biol.
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Experience-dependent plastic changes in the brain underlying complex forms of learning are generally initiated when organisms are awake, and this may limit the earliest developmental time at which learning about external events can take place. It is not known whether waking-like brain function is present prenatally in higher vertebrate (bird or mammal) embryos, or whether embryos have brain circuitry that can selectively turn on a waking-like state in response to salient external sensory stimulation.
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Influence of absorption and scattering on the quantification of fluorescence diffuse optical tomography using normalized data.
J Biomed Opt
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Reconstruction algorithms for imaging fluorescence in near infrared ranges usually normalize fluorescence light with respect to excitation light. Using this approach, we investigated the influence of absorption and scattering heterogeneities on quantification accuracy when assuming a homogeneous model and explored possible reconstruction improvements by using a heterogeneous model. To do so, we created several computer-simulated phantoms: a homogeneous slab phantom (P1), slab phantoms including a region with a two- to six-fold increase in scattering (P2) and in absorption (P3), and an atlas-based mouse phantom that modeled different liver and lung scattering (P4). For P1, reconstruction with the wrong optical properties yielded quantification errors that increased almost linearly with the scattering coefficient while they were mostly negligible regarding the absorption coefficient. This observation agreed with the theoretical results. Taking the quantification of a homogeneous phantom as a reference, relative quantification errors obtained when wrongly assuming homogeneous media were in the range +41 to +94% (P2), 0.1 to -7% (P3), and -39 to +44% (P4). Using a heterogeneous model, the overall error ranged from -7 to 7%. In conclusion, this work demonstrates that assuming homogeneous media leads to noticeable quantification errors that can be improved by adopting heterogeneous models.
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Accuracy of CT-based attenuation correction in PET/CT bone imaging.
Phys Med Biol
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We evaluate the accuracy of scaling CT images for attenuation correction of PET data measured for bone. While the standard tri-linear approach has been well tested for soft tissues, the impact of CT-based attenuation correction on the accuracy of tracer uptake in bone has not been reported in detail. We measured the accuracy of attenuation coefficients of bovine femur segments and patient data using a tri-linear method applied to CT images obtained at different kVp settings. Attenuation values at 511 keV obtained with a (68)Ga/(68)Ge transmission scan were used as a reference standard. The impact of inaccurate attenuation images on PET standardized uptake values (SUVs) was then evaluated using simulated emission images and emission images from five patients with elevated levels of FDG uptake in bone at disease sites. The CT-based linear attenuation images of the bovine femur segments underestimated the true values by 2.9 ± 0.3% for cancellous bone regardless of kVp. For compact bone the underestimation ranged from 1.3% at 140 kVp to 14.1% at 80 kVp. In the patient scans at 140 kVp the underestimation was approximately 2% averaged over all bony regions. The sensitivity analysis indicated that errors in PET SUVs in bone are approximately proportional to errors in the estimated attenuation coefficients for the same regions. The variability in SUV bias also increased approximately linearly with the error in linear attenuation coefficients. These results suggest that bias in bone uptake SUVs of PET tracers ranges from 2.4% to 5.9% when using CT scans at 140 and 120 kVp for attenuation correction. Lower kVp scans have the potential for considerably more error in dense bone. This bias is present in any PET tracer with bone uptake but may be clinically insignificant for many imaging tasks. However, errors from CT-based attenuation correction methods should be carefully evaluated if quantitation of tracer uptake in bone is important.
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[Resveratrol: a neuroprotective polyphenol in the Mediterranean diet].
Rev Neurol
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Resveratrol is a polyphenol present in grapes, some nuts and dried fruits, and red wine. A number of beneficial properties have been attributed to this compound. Its potential neuroprotective effects are the subject of much research today.
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An innovative tool for intraoperative electron beam radiotherapy simulation and planning: description and initial evaluation by radiation oncologists.
Int. J. Radiat. Oncol. Biol. Phys.
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Intraoperative electron beam radiation therapy (IOERT) involves a modified strategy of conventional radiation therapy and surgery. The lack of specific planning tools limits the spread of this technique. The purpose of the present study is to describe a new simulation and planning tool and its initial evaluation by clinical users.
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Decreased glutathione levels predict loss of brain volume in children and adolescents with first-episode psychosis in a two-year longitudinal study.
Schizophr. Res.
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Progressive loss of cortical gray matter (GM), as measured by magnetic resonance imaging, has been described early in the course of first-episode psychosis. This study aims to assess the relationship between oxidative balance and progression of cortical GM changes in a multicenter sample of first-episode early-onset psychosis (EOP) patients from baseline to two-year follow-up. A total of 48 patients (13 females, mean age 15.9±1.5 years) and 56 age- and gender-matched healthy controls (19 females, 15.3±1.5 years) were assessed. Magnetic resonance imaging (MRI) scans performed both at the time of the first psychotic episode and 2 years later were used for volumetric measurements of left and right gray matter regions (frontal, parietal, and temporal lobes) and total sulcal cerebrospinal fluid (CSF). Total glutathione (GSH) blood levels were determined at baseline. In patients, after controlling for possible confounding variables, lower baseline GSH levels were significantly associated with greater volume decrease in left frontal (B=0.034, 95% confidence interval (CI): 0.011 to 0.056, r=0.620, p=0.006), parietal (B=0.039, 95% CI: 0.020 to 0.059, r=0.739, p=0.001), temporal (B=0.026, 95% CI: 0.016 to 0.036, r=0.779, p<0.001), and total (B=0.022, 95% CI: 0.014 to 0.031, r=0.803, p<0.001) gray matter, and with greater increase in total CSF (B=-0.560, 95% CI: -0.270 to -0.850, r=-0.722, p=0.001). Controls did not show significant associations between brain volume changes and GSH levels. GSH deficit during the first psychotic episode was related to greater loss of cortical GM two years later in patients with first-episode EOP, suggesting that oxidative damage may contribute to the progressive loss of cortical GM found in patients with first-episode psychosis.
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Comparative evaluation of autofocus algorithms for a real-time system for automatic detection of Mycobacterium tuberculosis.
Cytometry A
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Microscopy images must be acquired at the optimal focal plane for the objects of interest in a scene. Although manual focusing is a standard task for a trained observer, automatic systems often fail to properly find the focal plane under different microscope imaging modalities such as bright field microscopy or phase contrast microscopy. This article assesses several autofocus algorithms applied in the study of fluorescence-labeled tuberculosis bacteria. The goal of this work was to find the optimal algorithm in order to build an automatic real-time system for diagnosing sputum smear samples, where both accuracy and computational time are important. We analyzed 13 focusing methods, ranging from well-known algorithms to the most recently proposed functions. We took into consideration criteria that are inherent to the autofocus function, such as accuracy, computational cost, and robustness to noise and to illumination changes. We also analyzed the additional benefit provided by preprocessing techniques based on morphological operators and image projection profiling.
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Approach to assessing myocardial perfusion in rats using static [13N]-ammonia images and a small-animal PET.
Mol Imaging Biol
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Semi-quantitative, static positron emission tomography (PET) has been used to perform an initial approach to the assessment of [13N]-ammonia perfusion studies aimed to elucidating the effect of injecting human embryonic stem cell-derived (hES) hemangioblasts on infarcted rat hearts.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.