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Find video protocols related to scientific articles indexed in Pubmed.
Automated quantification of myocardial salvage in a rat model of ischemia-reperfusion injury using 3D high-resolution magnetic resonance imaging (MRI).
J Am Heart Assoc
PUBLISHED: 07-23-2014
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Quantification of myocardial "area at risk" (AAR) and myocardial infarction (MI) zone is critical for assessing novel therapies targeting myocardial ischemia-reperfusion (IR) injury. Current "gold-standard" methods perfuse the heart with Evan's Blue and stain with triphenyl tetrazolium chloride (TTC), requiring manual slicing and analysis. We aimed to develop and validate a high-resolution 3-dimensional (3D) magnetic resonance imaging (MRI) method for quantifying MI and AAR.
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Diffusion tensor imaging predictors of treatment outcomes in major depressive disorder.
Br J Psychiatry
PUBLISHED: 06-26-2014
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Functional neuroimaging studies implicate anterior cingulate and limbic dysfunction in major depressive disorder (MDD) and responsiveness to antidepressants. Diffusion tensor imaging (DTI) enables characterisation of white matter tracts that relate to these regions.
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A pain in the throat: a 19-year history of symptoms relating to the carotid artery.
Wien. Klin. Wochenschr.
PUBLISHED: 05-20-2014
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A 38-year-old man presented with a 19-year history of sore throat and an ache radiating from the centre of the anterior neck to the both ears and the occiput. Computed tomography angiography revealed a tortuous submucosal right internal carotid artery, which was causing tonsillar displacement. The diagnosis of carotidynia has a controversial history within the literature and is currently not accepted as a distinct pathological entity by the International Headache Society. In this patient, the clinical and imaging features, in addition to the absence of any other pathology confers support to the diagnosis of carotidynia.
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Ultrasmall superparamagnetic iron oxide nanoparticle prelabelling of human neural precursor cells.
Biomaterials
PUBLISHED: 02-26-2014
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Stem cells prelabelled with iron oxide nanoparticles can be visualised using magnetic resonance imaging (MRI). This technique allows for noninvasive long-term monitoring of migration, integration and stem cell fate following transplantation into living animals. In order to determine biocompatibility, the present study investigated the biological impact of introducing ultrasmall superparamagnetic iron oxide nanoparticles (USPIOs) into primary human fetal neural precursor cells (hNPCs) in vitro. USPIOs with a mean diameter of 10-15 nm maghemite iron oxide core were sterically stabilised by 95% methoxy-poly(ethylene glycol) (MPEG) and either 5% cationic (NH2) end-functionalised, or 5% Rhodamine B end-functionalised, polyacrylamide. The stabilising polymer diblocks were synthesised by reversible addition-fragmentation chain transfer (RAFT) polymerisation. Upon loading, cellular viability, total iron capacity, differentiation, average distance of migration and changes in intracellular calcium ion concentration were measured to determine optimal loading conditions. Taken together we demonstrate that prelabelling of hNPCs with USPIOs has no significant detrimental effect on cell biology and that USPIOs, when utilised at an optimised dosage, are an effective means of noninvasively tracking prelabelled hNPCs.
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Gene-environment interaction demonstrates the vulnerability of the embryonic heart.
Dev. Biol.
PUBLISHED: 02-21-2014
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Mammalian embryos develop in a low oxygen environment. The transcription factor hypoxia inducible factor 1a (HIF1?) is a key element in the cellular response to hypoxia. Complete deletion of Hif1? from the mouse conceptus causes extensive placental, vascular and heart defects, resulting in embryonic lethality. However the precise role of Hif1? in each of these organ systems remains unknown. To further investigate, we conditionally-deleted Hif1? from mesoderm, vasculature and heart individually. Surprisingly, deletion from these tissues did not recapitulate the same severe heart phenotype or embryonic lethality. Placental insufficiency, such as occurs in the complete Hif1? null, results in elevated cellular hypoxia in mouse embryos. We hypothesized that subjecting the Hif1? conditional null embryos to increased hypoxic stress might exacerbate the effects of tissue-specific Hif1? deletion. We tested this hypothesis using a model system mimicking placental insufficiency. We found that the majority of embryos lacking Hif1? in the heart died when exposed to non-physiological hypoxia. This was a heart-specific phenomenon, as HIF1? protein accumulated predominantly in the myocardium of hypoxia-stressed embryos. Our study demonstrates the vulnerability of the heart to lowered oxygen levels, and that under such conditions of non-physiological hypoxia the embryo absolutely requires Hif1? to continue normal development. Importantly, these findings extend our understanding of the roles of Hif1? in cardiovascular development.
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Abnormal structural networks characterize major depressive disorder: a connectome analysis.
Biol. Psychiatry
PUBLISHED: 02-12-2014
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Major depressive disorder (MDD) has been shown to be associated with a disrupted topological organization of functional brain networks. However, little is known regarding whether these changes have a structural basis. Diffusion tensor imaging (DTI) enables comprehensive whole-brain mapping of the white matter tracts that link regions distributed throughout the entire brain, the so-called human connectome.
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Clinical utility of magnetic resonance imaging in the follow-up of chronic aortic type B dissection.
Heart Lung Circ
PUBLISHED: 02-02-2014
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Several imaging modalities are utilised in the assessment of disease progression in chronic aortic dissection. We present the case of a 66 year-old male who underwent ascending aorta repair for Stanford type A aortic dissection. On follow-up the persisting dissection of the descending thoracic aorta was observed to regress on magnetic resonance imaging (MRI). MRI has several advantages over computed tomography (CT) scanning and echocardiography in the follow-up phase of this disease.
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Ophthalmological consequences of cyanotic congenital heart disease: vascular parameters and nerve fibre layer.
Clin. Experiment. Ophthalmol.
PUBLISHED: 02-01-2014
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This study investigated the long-term ophthalmological consequences of cyanotic congenital heart disease (CHD).
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Establishing the resting state default mode network derived from functional magnetic resonance imaging tasks as an endophenotype: A twins study.
Hum Brain Mapp
PUBLISHED: 01-22-2014
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The resting state default mode network (DMN) has been shown to characterize a number of neurological and psychiatric disorders. Evidence suggests an underlying genetic basis for this network and hence could serve as potential endophenotype for these disorders. Heritability is a defining criterion for endophenotypes. The DMN is measured either using a resting-state functional magnetic resonance imaging (fMRI) scan or by extracting resting state activity from task-based fMRI. The current study is the first to evaluate heritability of this task-derived resting activity. 250 healthy adult twins (79 monozygotic and 46 dizygotic same sex twin pairs) completed five cognitive and emotion processing fMRI tasks. Resting state DMN functional connectivity was derived from these five fMRI tasks. We validated this approach by comparing connectivity estimates from task-derived resting activity for all five fMRI tasks, with those obtained using a dedicated task-free resting state scan in an independent cohort of 27 healthy individuals. Structural equation modeling using the classic twin design was used to estimate the genetic and environmental contributions to variance for the resting-state DMN functional connectivity. About 9-41% of the variance in functional connectivity between the DMN nodes was attributed to genetic contribution with the greatest heritability found for functional connectivity between the posterior cingulate and right inferior parietal nodes (P<0.001). Our data provide new evidence that functional connectivity measures from the intrinsic DMN derived from task-based fMRI datasets are under genetic control and have the potential to serve as endophenotypes for genetically predisposed psychiatric and neurological disorders.
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Thalamic volume and thalamo-cortical white matter tracts correlate with motor and verbal memory performance.
Neuroimage
PUBLISHED: 01-05-2014
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Cognitive testing and diffusion tensor imaging data from 121 normal subjects were combined to investigate the relationship between thalamic connectivity and cognitive performance. Thalamic regions were segmented based on their cortical connectivity, and regions for both ipsilateral and contralateral thalamocortical connections were identified. White matter tracts corresponding to these regions were identified and the mean fractional anisotropy, and axial and radial diffusivities within each tract were measured. Motor task performance correlated with radial diffusivity in the dominant thalamo-precentral tract. Verbal memory corresponded with the thalamic volume connected to the left temporal lobe. These data support the use of diffusion tractography to identify functionally important regions within the thalamus. Our findings provide the first robust correlation between thalamic volumes and tract characteristics with cognitive performance data in normal subjects.
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Regular cocaine use is associated with increased systolic blood pressure, aortic stiffness and left ventricular mass in young otherwise healthy individuals.
PLoS ONE
PUBLISHED: 01-01-2014
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The cardiovascular impact of cocaine use in otherwise healthy individuals who consider themselves 'social' users is not well established.
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Brain volumetric, regional cortical thickness and radiographic findings in adults with cyanotic congenital heart disease.
Neuroimage Clin
PUBLISHED: 01-01-2014
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Chronic cyanosis in adults with congenital heart disease (CHD) may cause structural brain changes that could contribute to impaired neurological functioning. The extent of these changes has not been adequately characterized.
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Tractography of the brainstem in major depressive disorder using diffusion tensor imaging.
PLoS ONE
PUBLISHED: 01-01-2014
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The brainstem is the main region that innervates neurotransmitter release to the Hypothalamic-Pituitary Adrenal (HPA) axis and fronto-limbic circuits, two key brain circuits found to be dysfunctional in Major Depressive Disorder (MDD). However, the brainstem's role in MDD has only been evaluated in limited reports. Using Diffusion Tensor Imaging (DTI), we investigated whether major brainstem white matter tracts that relate to these two circuits differ in MDD patients compared to healthy controls.
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Selective inhibition of the master regulator transcription factor Egr-1 with catalytic oligonucleotides reduces myocardial injury and improves left ventricular systolic function in a preclinical model of myocardial infarction.
J Am Heart Assoc
PUBLISHED: 08-02-2013
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Egr-1 is implicated in the pathogenesis of myocardial ischemia-reperfusion injury. The aim of this study was to ascertain the effectiveness of intracoronary delivery of DNAzyme targeting the transcription factor Egr-1 at reperfusion following experimental myocardial ischemia.
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Body mass index and brain structure in healthy children and adolescents.
Int. J. Neurosci.
PUBLISHED: 07-19-2013
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Obesity is associated with cognitive dysfunction in children and adolescents, although the mechanisms underlying these deficits remain unclear. This study examined the associations between body mass index (BMI) and regional gray matter volume and white matter integrity in 120 healthy children and adolescents (6-18 years of age) who underwent magnetic resonance and diffusion tensor imaging. Bonferroni-corrected partial correlation analyses controlling for demographic and clinical characteristics revealed significant inverse associations between demographically standardized BMI values and gray matter volume of frontal (r = -0.31) and limbic (r = -0.35) brain regions. No such pattern emerged for fractional anisotropy of white matter tracts. Subsequent hierarchical regression analyses indicated that the relationship between standardized BMI and structural gray and white matter brain indices did not vary with age. These findings suggest that obesity in children and adolescents is associated with decreased volume of frontal and limbic cerebral gray matter regions. Further research is much needed to better elucidate possible brain-based mechanisms for cognitive dysfunction associated with obesity.
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Higher education is an age-independent predictor of white matter integrity and cognitive control in late adolescence.
Dev Sci
PUBLISHED: 04-10-2013
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Socioeconomic status is an important predictor of cognitive development and academic achievement. Late adolescence provides a unique opportunity to study how the attainment of socioeconomic status (in the form of years of education) relates to cognitive and neural development, during a time when age-related cognitive and neural development is ongoing. During late adolescence it is possible to disambiguate age- and education-related effects on the development of these processes. Here we assessed the degree to which higher educational attainment was related to performance on a cognitive control task, controlling for age. We then used diffusion tensor imaging (DTI) to assess the degree to which white matter microstructure might mediate this relationship. When covarying age, significant associations were found between educational attainment and fractional anisotropy (FA) in the superior longitudinal fasciculus (SLF) and cingulum bundle (CB). Further, when covarying age, FA in these regions was associated with cognitive control. Finally, mediation analyses revealed that the age-independent association between educational attainment and cognitive control was completely accounted for by FA in these regions. The uncinate fasciculus, a late-myelinated control region not implicated in cognitive control, did not mediate this effect.
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Brain imaging predictors and the international study to predict optimized treatment for depression: study protocol for a randomized controlled trial.
Trials
PUBLISHED: 02-04-2013
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Approximately 50% of patients with major depressive disorder (MDD) do not respond optimally to antidepressant treatments. Given this is a large proportion of the patient population, pretreatment tests that predict which patients will respond to which types of treatment could save time, money and patient burden. Brain imaging offers a means to identify treatment predictors that are grounded in the neurobiology of the treatment and the pathophysiology of MDD.
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Stoichiometric relationship between Na(+) ions transported and glucose consumed in human erythrocytes: Bayesian analysis of (23)Na and (13)C NMR time course data.
Biophys. J.
PUBLISHED: 01-13-2013
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We examined the response of Na(+),K(+)-ATPase (NKA) to monensin, a Na(+) ionophore, with and without ouabain, an NKA inhibitor, in suspensions of human erythrocytes (red blood cells). A combination of (13)C and (23)Na NMR methods allowed the recording of intra- and extracellular Na(+), and (13)C-labeled glucose time courses. The net influx of Na(+) and the consumption of glucose were measured with and without NKA inhibited by ouabain. A Bayesian analysis was used to determine probability distributions of the parameter values of a minimalist mathematical model of the kinetics involved, and then used to infer the rates of Na(+) transported and glucose consumed. It was estimated that the numerical relationship between the number of Na(+) ions transported by NKA per molecule of glucose consumed by a red blood cell was close to the ratio 6.0:1.0, agreeing with theoretical prediction.
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Utility of cardiac magnetic resonance in assessing right-sided heart failure in sarcoidosis.
BMC Med Imaging
PUBLISHED: 01-11-2013
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Cardiac involvement in sarcoidosis is associated with a poor prognosis. In patients with right sided heart failure, differentiating between cor-pulmonale, or cardiac sarcoidosis has important implications to management.
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Widespread reductions in gray matter volume in depression.
Neuroimage Clin
PUBLISHED: 01-01-2013
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Abnormalities in functional limbic-anterior cingulate-prefrontal circuits associated with emotional reactivity, evaluation and regulation have been implicated in the pathophysiology of major depressive disorder (MDD). However, existing knowledge about structural alterations in depression is equivocal and based on cohorts of limited sample size. This study used voxel-based morphometry (VBM) and surface-based cortical thickness to investigate the structure of these circuits in a large and well-characterized patient cohort with MDD. Non-geriatric MDD outpatients (n = 102) and age- and gender-matched healthy control participants (n = 34) provided T1-weighted magnetic resonance imaging data during their baseline visit as part of the International Study to Predict Optimized Treatment for Depression. Whole-brain VBM volumetric and surface-based cortical thickness assessments were performed voxel-wise and compared (at p < 0.05 corrected for multiple comparisons) between the MDD and control groups. MDD participants had reduced gray matter volume in the anterior cingulate cortex, regions of the prefrontal circuits, including dorsolateral and dorsomedial prefrontal cortices, and lateral and medial orbitofrontal cortices, but not in limbic regions. Additional reductions were observed cortically in the posterior temporal and parieto-occipital cortices and, subcortically in the basal ganglia and cerebellum. Focal cortical thinning in the medial orbitofrontal cortex was also observed for the MDD group. These alterations in volume and cortical thickness were not associated with severity of depressive symptoms. The findings demonstrate that widespread gray matter structural abnormalities are present in a well-powered study of patients with depression. The patterns of gray matter loss correspond to the same brain functional network regions that were previously established to be abnormal in MDD, which may support an underlying structural abnormality for these circuits.
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Early exposure to traumatic stressors impairs emotional brain circuitry.
PLoS ONE
PUBLISHED: 01-01-2013
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Exposure to early life trauma (ELT) is known to have a profound impact on mental development, leading to a higher risk for depression and anxiety. Our aim was to use multiple structural imaging methods to systematically investigate how traumatic stressors early in life impact the emotional brain circuits, typically found impaired with clinical diagnosis of depression and anxiety, across the lifespan in an otherwise healthy cohort. MRI data and self-reported histories of ELT from 352 healthy individuals screened for no psychiatric disorders were analyzed in this study. The volume and cortical thickness of the limbic and cingulate regions were assessed for all participants. A large subset of the cohort also had diffusion tensor imaging data, which was used to quantify white matter structural integrity of these regions. We found a significantly smaller amygdala volume and cortical thickness in the rostral anterior cingulate cortex associated with higher ELT exposure only for the adolescence group. White matter integrity of these regions was not affected. These findings demonstrate that exposure to early life trauma is associated with alterations in the gray matter of cingulate-limbic regions during adolescence in an otherwise healthy sample. These findings are interesting in the context that the affected regions are central neuroanatomical components in the psychopathology of depression, and adolescence is a peak period for risk and onset of the disorder.
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Testing the white matter retrogenesis hypothesis of cognitive aging.
Neurobiol. Aging
PUBLISHED: 05-16-2011
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The retrogenesis hypothesis postulates that late-myelinated white matter fibers are most vulnerable to age- and disease-related degeneration, which in turn mediate cognitive decline. While recent evidence supports this hypothesis in the context of Alzheimers disease, it has not been tested systematically in normal cognitive aging. In the current study, we examined the retrogenesis hypothesis in a group (n = 282) of cognitively normal individuals, ranging in age from 7 to 87 years, from the Brain Resource International Database. Participants were evaluated with a comprehensive neuropsychological battery and were imaged with diffusion tensor imaging. Fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (DA), measures of white matter coherence, were computed in 2 prototypical early-myelinated fiber tracts (posterior limb of the internal capsule, cerebral peduncles) and 2 prototypical late-myelinated fiber tracts (superior longitudinal fasciculus, inferior longitudinal fasciculus) chosen to parallel previous studies; mean summary values were also computed for other early- and late-myelinated fiber tracts. We examined age-associated differences in FA, RD, and DA in the developmental trajectory (ages 7-30 years) and degenerative trajectory (ages 31-87 years), and tested whether the measures of white matter coherence mediated age-related cognitive decline in the older group. FA and DA values were greater for early-myelinated fibers than for late-myelinated fibers, and RD values were lower for early-myelinated than late-myelinated fibers. There were age-associated differences in FA, RD, and DA across early- and late-myelinated fiber tracts in the younger group, but the magnitude of differences did not vary as a function of early or late myelinating status. FA and RD in most fiber tracts showed reliable age-associated differences in the older age group, but the magnitudes were greatest for the late-myelinated tract summary measure, inferior longitudinal fasciculus (late fiber tract), and cerebral peduncles (early fiber tract). Finally, FA in the inferior longitudinal fasciculus and cerebral peduncles and RD in the cerebral peduncles mediated age-associated differences in an executive functioning factor. Taken together, the findings highlight the importance of white matter coherence in cognitive aging and provide some, but not complete, support for the white matter retrogenesis hypothesis in normal cognitive aging.
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Cardiac magnetic resonance imaging for the interventional cardiologist.
JACC Cardiovasc Interv
PUBLISHED: 02-26-2011
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Cardiac magnetic resonance imaging is a noninvasive technique for assessing heart structure and function without the need for ionizing radiation. Its ability to precisely outline regions of myocardial ischemia and infarction gives it an important role in guiding interventional cardiologists in revascularization. Its ability to characterize and precisely quantify abnormal regurgitant flow volumes or abnormal shunts also makes it a valuable tool for many noncoronary interventions. This review will discuss the evidence for cardiac magnetic resonance in guiding complex therapies in the catheter laboratory, as well as practical issues that need to be addressed to allow the application of this powerful tool to an increasing number of our patients.
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Imaging of endolymphatic hydrops in Menieres disease at 1.5 T using phase-sensitive inversion recovery: (1) demonstration of feasibility and (2) overcoming the limitations of variable gadolinium absorption.
Eur J Radiol
PUBLISHED: 01-10-2011
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Endolymphatic hydrops is the primary histopathological finding in Menieres disease. We demonstrate the feasibility of imaging endolymphatic hydrops at 1.5 T using phase-sensitive inversion recovery (PS-IR) MRI following intratympanic injection of gadolinium (Gd). PS-IR data were imaged using real reconstruction to enable visualization of the phase of the signal permitting clear definition between bone, unopacified endolymph and perilymph. Data were obtained 24h following injection in 2 control subjects and in 13 successive patients with Menieres disease. In 11 out of 13 patients, dilated endolymphatic structures were clearly identified as filling defects within the opacified perilymph allowing identification of endolymphatic hydrops. There was a large range in the degree of perilymphatic signal enhancement due to variability in absorption of Gd from the middle ear into the perilymph. The use of multiple TI values allowed confident identification of endolymphatic hydrops in Menieres patients even when perilymph opacification was suboptimal at one TI value. This is the first time endolymphatic hydrops has been demonstrated at 1.5 T in humans. The methods presented are of significant practical importance and will permit broader application of endolymphatic imaging and may also act to reduce the frequency of failed exams due to inadequate Gd uptake.
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Regional heterogeneity in limbic maturational changes: evidence from integrating cortical thickness, volumetric and diffusion tensor imaging measures.
Neuroimage
PUBLISHED: 01-09-2011
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Magnetic resonance imaging (MRI) studies of structural brain development have suggested that the limbic system is relatively preserved in comparison to other brain regions with healthy aging. The goal of this study was to systematically investigate age-related changes of the limbic system using measures of cortical thickness, volumetric and diffusion characteristics. We also investigated if the "relative preservation" concept is consistent across the individual sub-regions of the limbic system. T1 weighted structural MRI and Diffusion Tensor Imaging data from 476 healthy participants from the Brain Resource International Database was used for this study. Age-related changes in grey matter (GM)/white matter (WM) volume, cortical thickness, diffusional characteristics for the pericortical WM and for the fiber tracts associated with the limbic regions were quantified. A regional variability in the aging patterns across the limbic system was present. Four important patterns of age-related changes were highlighted for the limbic sub-regions: 1. early maturation of GM with late loss in the hippocampus and amygdala; 2. an extreme pattern of GM preservation in the entorhinal cortex; 3. a flat pattern of reduced GM loss in the anterior cingulate and the parahippocampus and; 4. accelerated GM loss in the isthmus and posterior cingulate. The GM volumetric data and cortical thickness measures proved to be internally consistent, while the diffusional measures provided complementary data that seem consistent with the GM trends identified. This heterogeneity can be hypothesized to be associated with age-related changes of cognitive function specialized for that region and direct connections to the other brain regions sub-serving these functions.
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Obesity is associated with reduced white matter integrity in otherwise healthy adults.
Obesity (Silver Spring)
PUBLISHED: 12-23-2010
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Existing work demonstrates that obesity is independently associated with cognitive dysfunction and macrostructural brain changes; however, little is known about the association between obesity and white matter (WM) integrity. We explore this relationship in a large cohort of otherwise healthy subjects. The present study classified 103 adult participants from the Brain Resource International Database between 21 and 86 years of age without history of neurological, medical, or psychiatric illness according to BMI (normal weight, overweight, obese) and subjected them to diffusion tensor imaging (DTI). Resulting fractional anisotropy (FA) indexes for the corpus callosum and fornix were examined in relation to BMI and age in a multiple regression framework. Results indicated that increasing BMI was independently associated with lower FA in the genu, splenium, and fornix, and a BMI × age interaction emerged for FA in the splenium and body of the corpus callosum. When categorized, obese persons demonstrated lower FA than normal and overweight persons for all WM indexes, but no FA differences emerged between overweight and normal persons. Results indicate both a direct association between obesity and reduced WM tract integrity and an interaction between obesity and aging processes on certain WM tracts in otherwise healthy adults. While such findings suggest a possible role for adiposity in WM dysfunction and associated cognitive deficits, prospective studies are needed to clarify the nature of these relationships and elucidate underlying mechanisms.
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Impact of the HTR3A gene with early life trauma on emotional brain networks and depressed mood.
Depress Anxiety
PUBLISHED: 08-10-2010
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The risk for mental illnesses such as depression is increasingly conceptualized as the product of gene-environment interactions and their impact on brain structure and function. The role of serotonin 3A receptor gene (HTR3A -42C>T polymorphism) and its interaction with early life stress (ELS) was investigated in view of the receptors localization to brain regions central to emotion processing.
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Loss of white matter integrity in major depressive disorder: evidence using tract-based spatial statistical analysis of diffusion tensor imaging.
Hum Brain Mapp
PUBLISHED: 07-05-2010
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White matter (WM) has been shown to be affected in elderly patients with major depressive disorders (MDD). There is only limited evidence of WM structural abnormalities in nongeriatric MDD patients. This study investigates WM microstructural integrity in nongeriatric MDD patients recruited as part of the International Study to Predict Optimized Treatment in Depression clinical trial and establishes the validity of diffusion tensor imaging measures for the investigation of depression. Baseline diffusion tensor imaging data from 29 nongeriatric MDD participants (11 with melancholia) and 39 healthy control participants were used in this analysis. We performed tract-based spatial statistics analyses to evaluate WM microstructural integrity (1) between all healthy controls and all MDD participants, (2) between melancholic and nonmelancholic MDD participants, and (3) between each subgroup (melancholic and nonmelancholic) and controls. Significant WM integrity deficits were seen only for the melancholic MDD participants compared with controls. Compared with controls, melancholic participants showed an average reduction of 7.8% in fractional anisotropy over WM regions associated with the limbic system, dorsolateral prefrontal cortex, thalamic projection fibers, corpus callosum, and other association fibers. These fractional anisotropy deficits were also associated with decreased axial and increased radial diffusivity in these WM regions, suggesting a pattern of decreased myelination or other degeneration change. Our findings of WM structural abnormalities associated with the limbic system, the frontal cortex, and the thalamus support the prevailing theory of limbic-dorsolateral prefrontal cortex-thalamic dysfunction in depression. Our results also suggest that these deficits are most prominent in the melancholic subtype of MDD.
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COMT Val(108/158)Met polymorphism effects on emotional brain function and negativity bias.
Neuroimage
PUBLISHED: 01-22-2010
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Biases toward processing negative versus positive information vary as a function of level of awareness, and are modulated by monoamines. Excessive biases are associated with individual differences in mood and emotional stability, and emotional disorder. Here, we examined the impact of the catechol-O-methyltransferase (COMT) Val(108/158)Met polymorphism, involved in dopamine and norepinephrine catabolism, on both emotional brain function and self-reported negativity bias. COMT genotyping and self-reported level of negativity bias were completed for 46 healthy participants taking part in the Brain Resource International Database. Functional MRI was undertaken during perception of facial expressions of fear and happiness presented under unmasked (consciously identified) and masked (to prevent conscious detection) conditions. Structural MR images were also acquired. A greater number of COMT Met alleles predicted increased activation in brainstem, amygdala, basal ganglia and medial prefrontal regions for conscious fear, but decreased activation for conscious happiness. This pattern was also apparent for brainstem activation for the masked condition. Effects were most apparent for females. These differences could not be explained by gray matter variations. The Met-related profile of activation, particularly prefrontally, predicted greater negativity bias associated with risk for emotional disorder. The findings suggest that the COMT Met allele modulates neural substrates of negative versus positive emotion processing. This effect may contribute to negativity biases, which confer susceptibility for emotional disorders.
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Relative contributions of the cerebellar vermis and prefrontal lobe volumes on cognitive function across the adult lifespan.
Neurobiol. Aging
PUBLISHED: 12-16-2009
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Recent research has revealed significant relationships between the vermian regions of the cerebellum and cognitive functions typically associated with prefrontal lobe function. These relationships are believed to be supported by anatomical connections between the distant brain regions. Recent evidence also suggests that age-related reductions in the posterior vermis are associated with age-related decline in frontal lobe cognitive functions, but these studies did not consider concomitant age-related atrophy of the prefrontal lobes. In the present study we addressed this issue by examining cognitive and structural MRI data obtained from 251 adults ranging in age from 18 to 79. Cognition was examined with a computerized cognitive battery and volumes of the cerebellar vermian regions and the prefrontal lobes were determined using quantitative morphometry. Results of the study revealed that both prefrontal and vermian volumes were smaller in older adults compared to younger adults, and both volumes correlated with cognitive performances in the older individuals. However, after controlling for prefrontal volume, the relationships between cognitive function and vermian volumes were eliminated, whereas prefrontal lobe volume remained significantly related to cognitive function after controlling for vermian volumes. These results suggest that while a reduction in cerebellar vermian volume does not significantly relate to normal age-related cognitive decline, prefrontal volume is significantly related to cognitive aging. Our results are consistent with the frontal aging hypothesis.
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Syringomyelia: a rare extracardiac contributor to syncope detected incidentally by CMR.
Int. J. Cardiol.
PUBLISHED: 10-07-2009
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We describe an extracardiac finding of syringomyelia in CMR study of a patient who was being investigated to exclude an infiltrative cause for presumptive cardiogenic syncope. Extension of a syrinx to involve the sympathetic structures in the intermediolateral column of the spinal cord can lead to well-recognised autonomic disturbances including Horners syndrome. Autonomic control of the heart has also been shown to be impaired in patients with syringomyelia. We investigated a 20 year old man presented with a history of recurrent syncope triggered by pain, micturition and defaecation. The cardiac MRI findings were normal, however close inspection of the scout images was suggestive of a lower thoracic spinal cord syrinx - a finding later confirmed by dedicated spinal MRI. Subsequent neurological investigations were essentially normal. We suggest that syringomyelia-induced disruption of sympathetic fibres in the thoracic spinal cord is a plausible, but rare mechanism of syncope.
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Brain derived neurotrophic factor Val66Met polymorphism, the five factor model of personality and hippocampal volume: Implications for depressive illness.
Hum Brain Mapp
PUBLISHED: 06-11-2009
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Altered hippocampal volume, the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism, and neuroticism have each been implicated in the etiology of psychiatric disorders, especially depression. However, the relationship between these variables is not well understood. Here, we determined the effects of the BDNF Val66met polymorphism on the five-factor personality dimensions (assessed using the NEO-FFI), trait depression (assessed with the DASS-21) in a cross-sectional cohort of 467 healthy volunteers. A large matched subset of this cohort was also assessed for grey matter volume of the hippocampus and contiguous temporal cortical regions using magnetic resonance imaging. In Met carriers, elevations in neuroticism and trait depression and stress were associated with lower mean hippocampal volume, but there were no such associations in Val homozygotes. Trait depression, in particular, was found to moderate the effects of BDNF genotypes on hippocampal volume. Met carriers with high trait depression showed a reduction in grey matter volume of the mean hippocampus compared with Val homozygotes. These findings suggest that even in otherwise healthy subjects, trait depression may contribute to the susceptibility of Met carriers to hippocampal grey matter loss.
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Disturbances in selective information processing associated with the BDNF Val66Met polymorphism: evidence from cognition, the P300 and fronto-hippocampal systems.
Biol Psychol
PUBLISHED: 05-09-2009
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In this study, we examined whether the Met allele of the BDNF Val66Met polymorphism is associated with selective disruptions to task-relevant information processing. In 475 non-clinical participants for whom BDNF genotype status was determined we used the IntegNeuro computerized battery of neuropsychological tests to assess cognitive performance, an auditory oddball task to elicit the P300 event-related potential (ERP) and, in smaller subsets of these subjects, high resolution structural MRI imaging to quantify fronto-hippocampal grey matter (n=161), and functional magnetic resonance imaging to assess fronto-hippocampal BOLD activation (n=37). Met/Met (MM) homozygotes had higher verbal recall errors, in the absence of differences in attention, executive function, verbal ability or sensori-motor function. Further, MM homozygotes demonstrated a slowed P300 ERP during the oddball task, with corresponding alterations in hippocampal and lateral prefrontal activation, and a localized reduction in hippocampal grey matter. These results are consistent with a subtle impact of the Met allele on fronto-hippocampal systems involved in selective information processing of stimulus context and memory updating within the normal population. The findings also indicate that heritable endophenotypes such as the P300 have value in elucidating genotype-phenotype relationships.
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Using standardized fMRI protocols to identify patterns of prefrontal circuit dysregulation that are common and specific to cognitive and emotional tasks in major depressive disorder: first wave results from the iSPOT-D study.
Neuropsychopharmacology
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Functional neuroimaging studies have implicated dysregulation of prefrontal circuits in major depressive disorder (MDD), and these circuits are a viable target for predicting treatment outcomes. However, because of the heterogeneity of tasks and samples used in studies to date, it is unclear whether the central dysfunction is one of prefrontal hyperreactivity or hyporeactivity. We used a standardized battery of tasks and protocols for functional magnetic resonance imaging, to identify the common vs the specific prefrontal circuits engaged by these tasks in the same 30 outpatients with MDD compared with 30 matched, healthy control participants, recruited as part of the International Study to Predict Optimized Treatment in Depression (iSPOT-D). Reflecting cognitive neuroscience theory and established evidence, the battery included cognitive tasks designed to assess functions of selective attention, sustained attention-working memory and response inhibition, and emotion tasks to assess explicit conscious and implicit nonconscious viewing of facial emotion. MDD participants were distinguished by a distinctive biosignature of: hypoactivation of the dorsolateral prefrontal cortex during working memory updating and during conscious negative emotion processing; hyperactivation of the dorsomedial prefrontal cortex during working memory and response inhibition cognitive tasks and hypoactivation of the dorsomedial prefrontal during conscious processing of positive emotion. These results show that the use of standardized tasks in the same participants provides a way to tease out prefrontal circuitry dysfunction related to cognitive and emotional functions, and not to methodological or sample variations. These findings provide the frame of reference for identifying prefrontal biomarker predictors of treatment outcomes in MDD.
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Hippocampal volume varies with educational attainment across the life-span.
Front Hum Neurosci
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Socioeconomic disparities-and particularly differences in educational attainment-are associated with remarkable differences in cognition and behavior across the life-span. Decreased educational attainment has been linked to increased exposure to life stressors, which in turn have been associated with structural differences in the hippocampus and the amygdala. However, the degree to which educational attainment is directly associated with anatomical differences in these structures remains unclear. Recent studies in children have found socioeconomic differences in regional brain volume in the hippocampus and amygdala across childhood and adolescence. Here we expand on this work, by investigating whether disparities in hippocampal and amygdala volume persist across the life-span. In a sample of 275 individuals from the BRAINnet Foundation database ranging in age from 17 to 87, we found that socioeconomic status (SES), as operationalized by years of educational attainment, moderates the effect of age on hippocampal volume. Specifically, hippocampal volume tended to markedly decrease with age among less educated individuals, whereas age-related reductions in hippocampal volume were less pronounced among more highly educated individuals. No such effects were found for amygdala volume. Possible mechanisms by which education may buffer age-related effects on hippocampal volume are discussed.
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Cardiac magnetic resonance imaging of rapid VCAM-1 up-regulation in myocardial ischemia-reperfusion injury.
Eur. Biophys. J.
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Inflammatory response plays an important role in myocardial ischaemia-reperfusion (IR) injury. Up-regulation of vascular cell adhesion molecule-1 (VCAM) contributes to this. We examined the feasibility of using intravenously administered VCAM-MPIO (microparticle iron oxide) to characterize VCAM expression patterns in myocardial IR injury. Myocardial ischemia was simulated by 30 min of transient ligation of the left coronary vessel in rats. Purified, monoclonal, rat-specific, mouse VCAM antibody coupled to MPIO was administered through the tail vein at 3 h post reperfusion and the rats were sacrificed 1 h later. High resolution 3D ex vivo MRI images were acquired at 9.4 Tesla. Extensive foci of signal voids were observed on T2*-weighted gradient-echo sequences, which corresponded to focal deposits of MPIOs observed in histological sections. The spatial density of the signal voids (expressed as a percentage of pixels below a threshold value) was increased in the peri-infarct zone compared with non-infarct zone (32.5 ± 4% vs. 13.9 ± 5%; n = 6; p < 0.05) and was substantially greater than the signal loss due to non-specific binding seen in rats administered IgG control MPIO (2.0 ± 1%; n = 6; p < 0.05). The VCAM-specific MPIO signal was also seen in myocardium and pericardium in segments remote from the IR injury, but not in rats undergoing a sham operation. In conclusion, molecular imaging in a model of myocardial IR injury is possible using high field MRI and VCAM-MPIOs and may provide novel insights beyond those achieved by standard histological and molecular analysis.
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Mapping inter-regional connectivity of the entire cortex to characterize major depressive disorder: a whole-brain diffusion tensor imaging tractography study.
Neuroreport
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Diffusion tensor imaging (DTI) can be used to study the organization of brain white matter noninvasively. The aim of this study was to present a proof of concept for integrating DTI with high-resolution anatomical (T1) images to map and assess inter-regional connectivity across the entire cortex in a cohort of healthy participants and compared with patients with major depressive disorder. We used MRI data of 23 patients and 23 matched controls, assessed as part of baseline testing in the International Study to Predict Optimized Treatment in Depression (iSPOT-D). Freesurfer was used to analyze the T1 images to automatically label 35 gyral-based areas for each hemisphere. DTI tractography was performed to parcellate intercortical tracts using each of these areas in seed-target combinations. We quantified fractional anisotropy, number-of-fiber connections, and fiber path length for each DTI connection, with the goal of identifying the best measure or combination of measures to characterize major depression. The best classification accuracy for the individual measures was achieved using the number-of-fibers data, whereas the combination model provided a slight improvement. The most discriminant features between the two groups were for white matter associated with the limbic, frontal, and thalamic projection fibers and as part of cortical connections between the left inferior temporal and the postcentral cortex; the left parstriangularis and the left superior frontal; the left cuneus and the corpus callosum; the left lingual and the right lateral occipital, the right superior parietal and the right superior temporal cortices; and the right inferior parietal and the right insula and postcentral cortices.
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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.

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

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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.