Cardiac septal defects are known complications to blunt chest trauma. The incidence of a traumatic isolated atrial septal defect is unknown and the concurrent occurrence of nonlethal ventricular and atrial septal defects has not been reported. A healthy male sustained violent blunt chest trauma resulting in traumatic cardiac septal disruption in the atrium and ventricle. The defects were detected by echocardiography within 14 hours of the accident. The extent of damage was confirmed at the time of surgical repair. The patient recovered uneventfully. The diagnosis and management of concurrent ASD and VSD is similar to single septal injury.
This study aimed to replicate a previous study which showed that endogenous opioid release, following an oral dose of amphetamine, can be detected in the living human brain using [11C]carfentanil positron emission tomography (PET) imaging. Nine healthy volunteers underwent two [11C]carfentanil PET scans, one before and one 3 h following oral amphetamine administration (0.5 mg/kg). Regional changes in [11C]carfentanil BPND from pre- to post-amphetamine were assessed. The amphetamine challenge led to significant reductions in [11C]carfentanil BPND in the putamen, thalamus, frontal lobe, nucleus accumbens, anterior cingulate, cerebellum and insula cortices, replicating our earlier findings. None of the participants experienced significant euphoria/'high', supporting the use of oral amphetamine to characterize in vivo endogenous opioid release following a pharmacological challenge. [11C]carfentanil PET is able to detect changes in binding following an oral amphetamine challenge that reflects endogenous opioid release and is suitable to characterize the opioid system in neuropsychiatric disorders.
Ghrelin, which is a stomach-derived hormone, increases with fasting and energy restriction and may influence eating behaviors through brain hedonic reward-cognitive systems. Therefore, changes in plasma ghrelin might mediate counter-regulatory responses to a negative energy balance through changes in food hedonics.OBJECTIVE: We investigated whether ghrelin administration (exogenous hyperghrelinemia) mimics effects of fasting (endogenous hyperghrelinemia) on the hedonic response and activation of brain-reward systems to food.DESIGN: In a crossover design, 22 healthy, nonobese adults (17 men) underwent a functional magnetic resonance imaging (fMRI) food-picture evaluation task after a 16-h overnight fast (Fasted-Saline) or after eating breakfast 95 min before scanning (730 kcal, 14% protein, 31% fat, and 55% carbohydrate) and receiving a saline (Fed-Saline) or acyl ghrelin (Fed-Ghrelin) subcutaneous injection before scanning. One male subject was excluded from the fMRI analysis because of excess head motion, which left 21 subjects with brain-activation data.RESULTS: Compared with the Fed-Saline visit, both ghrelin administration to fed subjects (Fed-Ghrelin) and fasting (Fasted-Saline) significantly increased the appeal of high-energy foods and associated orbitofrontal cortex activation. Both fasting and ghrelin administration also increased hippocampus activation to high-energy- and low-energy-food pictures. These similar effects of endogenous and exogenous hyperghrelinemia were not explicable by consistent changes in glucose, insulin, peptide YY, and glucagon-like peptide-1. Neither ghrelin administration nor fasting had any significant effect on nucleus accumbens, caudate, anterior insula, or amygdala activation during the food-evaluation task or on auditory, motor, or visual cortex activation during a control task.CONCLUSIONS: Ghrelin administration and fasting have similar acute stimulatory effects on hedonic responses and the activation of corticolimbic reward-cognitive systems during food evaluations. Similar effects of recurrent or chronic hyperghrelinemia on an anticipatory food reward may contribute to the negative impact of skipping breakfast on dietary habits and body weight and the long-term failure of energy restriction for weight loss.
Pharmacokinetic parameters following modifications to antiretroviral therapy and sanctuary site exposure are often unknown for recently licensed antiretrovirals. We assessed plasma, CSF and seminal plasma (SP) exposure of rilpivirine after switching from nevirapine.
Animal studies support the role of the dopamine D3 receptor (DRD3) in alcohol reinforcement or liking. Sustained voluntary alcohol drinking in rats has been associated with an upregulation of striatal DRD3 gene expression and selective blockade of DRD3 reduces ethanol preference, consumption, and cue-induced reinstatement. In vivo measurement of DRD3 in the living human brain has not been possible until recently owing to a lack of suitable tools. In this study, DRD3 status was assessed for the first time in human alcohol addiction. Brain DRD3 availability was compared between 16 male abstinent alcohol-dependent patients and 13 healthy non-dependent age-matched males using the DRD3-preferring agonist positron emission tomography (PET) radioligand [(11)C]PHNO with and without blockade with a selective DRD3 antagonist (GSK598809 60 mg p.o.). In striatal regions of interest, where the [(11)C]PHNO PET signal represents primarily DRD2 binding, no differences were seen in [(11)C]PHNO binding between the groups at baseline. However, baseline [(11)C]PHNO binding was higher in alcohol-dependent patients in hypothalamus (VT: 16.5 ± 4 vs 13.7 ± 2.9, p = 0.040), a region in which the [(11)C]PHNO signal almost entirely reflects DRD3 availability. The reductions in regional receptor binding (VT) following a single oral dose of GSK598809 (60 mg) were consistent with those observed in previous studies across all regions. There were no differences in regional changes in VT following DRD3 blockade between the two groups, indicating that the regional fractions of DRD3 are similar in the two groups, and the increased [(11)C]PHNO binding in the hypothalamus in alcohol-dependent patients is explained by elevated DRD3 in this group. Although we found no difference between alcohol-dependent patients and controls in striatal DRD3 levels, increased DRD3 binding in the hypothalamus of alcohol-dependent patients was observed. This may be relevant to the development of future therapeutic strategies to treat alcohol abuse.
Following bilateral vestibular loss (BVL) patients gradually adapt to the loss of vestibular input and rely more on other sensory inputs. Here we examine changes in the way proprioceptive and visual inputs interact. We used functional magnetic resonance imaging (fMRI) to investigate visual responses in the context of varying levels of proprioceptive input in 12 BVL subjects and 15 normal controls. A novel metal-free vibrator was developed to allow vibrotactile neck proprioceptive input to be delivered in the MRI system. A high level (100 Hz) and low level (30 Hz) control stimulus was applied over the left splenius capitis; only the high frequency stimulus generates a significant proprioceptive stimulus. The neck stimulus was applied in combination with static and moving (optokinetic) visual stimuli, in a factorial fMRI experimental design. We found that high level neck proprioceptive input had more cortical effect on brain activity in the BVL patients. This included a reduction in visual motion responses during high levels of proprioceptive input and differential activation in the midline cerebellum. In early visual cortical areas, the effect of high proprioceptive input was present for both visual conditions but in lateral visual areas, including V5/MT, the effect was only seen in the context of visual motion stimulation. The finding of a cortical visuo-proprioceptive interaction in BVL patients is consistent with behavioural data indicating that, in BVL patients, neck afferents partly replace vestibular input during the CNS-mediated compensatory process. An fMRI cervico-visual interaction may thus substitute the known visuo-vestibular interaction reported in normal subject fMRI studies. The results provide evidence for a cortical mechanism of adaptation to vestibular failure, in the form of an enhanced proprioceptive influence on visual processing. The results may provide the basis for a cortical mechanism involved in proprioceptive substitution of vestibular function in BVL patients.
Anxiety has been linked to initiation, maintenance and relapse of alcohol dependence. Neurobiological models of anxiety have proposed important roles for amygdala-insula and amygdala-medial prefrontal cortex interactions in the generation and regulation of anxiety states, respectively.
Roux-en-Y gastric bypass (RYGB) has greater efficacy for weight loss in obese patients than gastric banding (BAND) surgery. We hypothesise that this may result from different effects on food hedonics via physiological changes secondary to distinct gut anatomy manipulations.
Short echo time localized proton magnetic resonance spectroscopy provides quantification of brain metabolites, including N-acetyl-aspartate, myo-inositol, creatine/phosphocreatine and choline-containing compounds, which may be useful biomarkers for monitoring Alzheimers disease. We aimed to quantify the rate of metabolite change in Alzheimers disease, to assess factors influencing changes and to investigate the potential for serial magnetic resonance spectroscopy as an Alzheimers disease trial biomarker. A total of 42 patients and 22 controls each had up to six magnetic resonance spectroscopy examinations over a 2-year period, using a midline posterior cingulate single-voxel point resolved spectroscopy sequence (1.5?T; time to repetition?=?2000?ms; echo time?=?30?ms; 192 averages). Metabolite ratios N-acetyl-aspartate:creatine/phosphocreatine, choline-containing compounds:creatine/phosphocreatine, and myo-inositol:creatine/phosphocreatine were measured using online software (PROBE-Q) and the N-acetyl-aspartate:myo-inositol ratio was derived. Baseline ratios were compared between patients and controls. A linear mixed model was used to quantify longitudinal changes and extended to assess the effect of age, disease severity and baseline use of acetylcholinesterase inhibitors. Patients and controls were matched for age (patients: 68.9?±?7.2 years; controls: 69.1?±?6.7 years); 71% of the patients were on acetylcholinesterase inhibitors at baseline; mean Mini-Mental State Examination for patients was 19.4?±?4.1. A total of 307 spectra were acquired. In cross-sectional analyses, patients were significantly different from controls for N-acetyl-aspartate:creatine/phosphocreatine (11% lower, P?0.001), N-acetyl-aspartate:myo-inositol (24% lower, P?0.001), and myo-inositol:creatine/phosphocreatine (17% higher, P?0.001). After adjustment for N-acetyl-aspartate:myo-inositol, none of the other variables differed significantly. In patients there was significant decline in N-acetyl-aspartate:creatine/phosphocreatine (mean: 2.2%/year; 95% confidence interval: 0.9-3.5) and N-acetyl-aspartate:myo-inositol (mean: 3.7%/year; 95% confidence interval: 1.7-5.7), with no evidence for influence by age, disease severity or acetylcholinesterase inhibitor use. There was significant excess decline in patients compared with controls only in N-acetyl-aspartate:myo-inositol (mean: 3.6%/year; 95% confidence interval: 0.8-6.4; P?=?0.014). Between-subject standard deviation for N-acetyl-aspartate:myo-inositol was 0% for controls and 3.5%/year for patients; within-subject standard deviation for a 1?year, two-time-point study was 9.2%/year for both patients and controls. These results confirm that magnetic resonance spectroscopy can be used to quantify excess metabolite decline in Alzheimers disease, which may provide a useful measure of disease progression. We found no evidence that age, disease severity or acetylcholinesterase inhibitor use influenced rate of decline, although numbers were small. The substantial variability in longitudinal measurements that drives sample size requirements is principally within-subject and technique related: technical developments to reduce this variability may make serial magnetic resonance spectroscopy a viable biomarker in clinical trials for Alzheimers disease.
The authors investigate the interplay between spatial attention and memory-based feature guidance of visual selection. Three types of guidance were tested: working memory, spatial cueing and passive memory. In all cases the memory-cue was not relevant to a subsequent search task, whilst the spatial cue always provided valid information. Behaviourally, search performance was influenced by spatial cueing and by feature-based cueing from the contents of working memory; both forms of guidance interacted, with feature guidance being more effective when the targets location was not pre-cued. Spatial cueing recruited the dorsal fronto-parietal network which was silent during the WM-only condition. Memory guidance of selection was reflected in activity in a frontal-temporal-occipital network. Interestingly, when spatial and memory guidance were pitted against each other, neural activity in this latter network was greatly attenuated. Connectivity analysis showed that the posterior parietal cortices inhibit the responses of occipital and temporal regions to the onset of memory-items in the search display. In the presence of a reliable spatial cue the posterior parietal cortex resumes control of attentional deployment. These results illustrate how different forms of attention guidance interact to optimise visual selection.
Magnetic resonance imaging (MRI) provides essential information on anatomical location and morphology for diagnosis, therapy planning, and treatment evaluation in brain tumors, but lacks biological specificity. "Advanced" quantitative MRI methods yield additional metabolic and physiological indices relevant to tumor growth, vasculature, and ultrastructure; these improve lesion characterization and delineation, and provide potential biomarkers of treatment susceptibility and response. Validation and standardization of relevant parameters is required for use across multiple centers for large scale clinical trials of novel therapeutic regimens and to guide clinical management of individual patients.
Quantitative magnetisation transfer imaging (qMTI) is an extension of conventional MT techniques and allows the measurement of parameters that reflect tissue ultrastructure through the properties of macromolecule-bound protons; these include the bound proton fraction and the relaxation times of free and bound proton pools. It has been used in multiple sclerosis and Alzheimers disease, and has shown changes in some of the parameters, particularly the bound proton fraction. The purpose of this pilot study was to assess whether qMTI could distinguish between gliomas and normal brain tissue, and provide proof of principle for its use in tumour characterisation. Eight subjects [three men, five women; mean age, 44 years; range, 27-66 years; seven World Health Organization (WHO) Grade II, one Grade III] with biopsy-proven glioma were imaged with a structural MRI protocol that included three-dimensional qMTI. qMTI parameters were extracted from regions of interest selected from different tumour components visible on conventional MR sequences, normal-appearing peritumoral tissue and distant normal-appearing white matter. All patients gave informed consent and the study was approved by the Local Research Ethics Committee. Almost all of the qMTI parameters detected abnormalities in both glioma and the peritumoral region relative to the distant white matter. In particular, the bound proton fraction was reduced significantly from 6.0 percentage units (pu) [standard deviation (SD), 0.5 pu] in normal-appearing white matter to 1.7 pu (SD?=?0.5 pu) in solid tumour and 2.2 pu (SD?=?0.5 pu) in peritumoral areas. This work shows that qMTI reveals abnormalities, not only in glioma, but also in the apparently normal tissue surrounding the conventionally defined tumour. Thus, qMTI shows promise for tumour characterisation and for studying tumour boundaries. These preliminary data justify larger studies in a range of different tumour types and grades.
Nutritional state (e.g. fasted vs. fed) and different food stimuli (e.g. high-calorie vs. low-calorie, or appetizing vs. bland foods) are both recognized to change activity in brain reward systems. Using functional magnetic resonance imaging, we have studied the interaction between nutritional state and different food stimuli on brain food reward systems. We examined how blood oxygen level-dependent activity within a priori regions of interest varied while viewing pictures of high-calorie and low-calorie foods. Pictures of non-food household objects were included as control stimuli. During scanning, subjects rated the appeal of each picture. Twenty non-obese healthy adults [body mass index 22.1 +/- 0.5 kg/m(2) (mean +/- SEM), age range 19-35 years, 10 male] were scanned on two separate mornings between 11:00 and 12:00 h, once after eating a filling breakfast (fed: 1.6 +/- 0.1 h since breakfast), and once after an overnight fast but skipping breakfast (fasted: 15.9 +/- 0.3 h since supper) in a randomized cross-over design. Fasting selectively increased activation to pictures of high-calorie over low-calorie foods in the ventral striatum, amygdala, anterior insula, and medial and lateral orbitofrontal cortex (OFC). Furthermore, fasting enhanced the subjective appeal of high-calorie more than low-calorie foods, and the change in appeal bias towards high-calorie foods was positively correlated with medial and lateral OFC activation. These results demonstrate an interaction between homeostatic and hedonic aspects of feeding behaviour, with fasting biasing brain reward systems towards high-calorie foods.
To prospectively compare tumor volume, relative cerebral blood volume (rCBV), and apparent diffusion coefficient (ADC) and short-term changes of these parameters as predictors of time to malignant transformation and time to death in patients with low-grade gliomas (LGGs).
Conventional structural imaging provides limited information on tumor characterization and prognosis. Advances in neurosurgical techniques, radiotherapy planning and novel drug treatments for brain tumors have generated increasing need for reproducible, noninvasive, quantitative imaging biomarkers. This Review considers the role of physiological MRI and PET molecular imaging in understanding metabolic processes associated with tumor growth, blood flow and ultrastructure. We address the utility of various techniques in distinguishing between tumors and non-neoplastic processes, in tumor grading, in defining anatomical relationships between tumor and eloquent brain regions and in determining the biological substrates of treatment response. Much of the evidence is derived from limited case series in individual centers. Despite their added value, the effect of these techniques as an adjunct to structural imaging in clinical research and practice remains limited.
It is well known that the global population is aging and that those over the age of 80 are the fastest growing part of this expansion. Also known is that prevalence of hypertension and cognitive decline both increase with increasing age.
The prognostic value of defining subcategories of gliomas is still controversial. This study aims to determine the utility of relative cerebral blood volume (rCBV) in predicting clinical response in patients with low-grade glioma at multiple institutions.
Adult low-grade gliomas (LGG) grow slowly, but most eventually undergo malignant transformation. The relationship between tumour volume, growth rate and the likelihood of transformation is unknown. Twenty-seven patients with biopsy-proven, untreated LGG had at least three MRI studies at 6 monthly intervals. Tumour volumes and growth rates were calculated using semi-automated segmentation, and analysed in a hierarchical regression model. In a 3-year period, patients who showed clinical deterioration and/or new (or significantly increased) contrast enhancement were classified as transformers (T), whilst non-transformers (NT) remained stable clinically and by conventional radiological criteria. All LGG showed progressive growth. Volumes at study entry were smaller in 9NT (57 ml, 95% CI 35-80 ml) than in 18T (83 ml, 95% CI 70-96 ml) (p=0.03). Average annual growth rates were lower in NT (16% (95% CI 9-23%)) than in T (26% (95% CI 20-31%)) (p=0.046), until the penultimate study. Growth in T increased to 56% p.a. (95% CI 20-92%) in the 6 months prior to transformation. In T, tumour volume was the most significant predictor of transformation in the following 12 months. Sequential measurement of LGG volume allows accurate determination of growth rates and identification of patients whose tumours are at high risk of early transformation.
Imaging is a key component in the management of brain tumours, with MRI being the preferred modality for most clinical scenarios. However, although conventional MRI provides mainly structural information, such as tumour size and location, it leaves many important clinical questions, such as tumour type, aggressiveness and prognosis, unanswered. An increasing number of studies have shown that additional information can be obtained using functional imaging methods (which probe tissue properties), and that these techniques can give key information of clinical importance. These techniques include diffusion imaging, which can assess tissue structure, and perfusion imaging and magnetic resonance spectroscopy, which measures tissue metabolite profiles. Tumour metabolism can also be investigated using PET, with 18F-deoxyglucose being the most readily available tracer. This Review discusses these methods and the studies that have investigated their clinical use. A strong emphasis is placed on the measurement of quantitative parameters, which is a move away from the qualitative nature of conventional radiological reporting and presents major challenges, particularly for multicentre studies.
Activated microglia are thought to play a major role in cortical gray matter (GM) demyelination in multiple sclerosis (MS). Our objective was to evaluate microglial activation in cortical GM of patients with MS in vivo and to explore its relationship to measures of disability.
We aimed to demonstrate a pharmacologically stimulated endogenous opioid release in the living human brain by evaluating the effects of amphetamine administration on [(11)C]carfentanil binding with positron emission tomography (PET).
There have been substantial advances in pituitary imaging in the last half-century. In particular, magnetic resonance imaging is now established as the imaging modality of choice, providing high quality images of the hypothalamic-pituitary axis and adjacent structures. More recent technological advances, such as the emergence of 3 Tesla MRI, are already being widely incorporated into imaging practice. However, other advanced techniques, including a variety of potential imaging biomarkers, still require further research to evaluate their potential and define their precise role. The recent development of intraoperative MRI appears promising and may have the potential to improve the outcome of pituitary surgery. Modern high quality imaging inevitably leads to the discovery of incidental lesions, including those within the pituitary gland, although it also plays a central role in their subsequent evaluation and management.
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