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Environmental hypoxia (fraction of inspired oxygen (F

Purpose Heating of gradient coils and passive shim components is a common cause of instability in the B0 field, especially when gradient intensive sequences are used. The aim of the study was to set a benchmark for typical drift encountered during MR spectroscopy (MRS) to assess the need for real-time field-frequency locking on MRI scanners by comparing field drift data from a large number of sites. Method A standardized protocol was developed for 80 participating sites using 99 3T MR scanners from 3 major vendors. Phantom water signals were acquired before and after an EPI sequence. The protocol consisted of: minimal preparatory imaging; a short pre-fMRI PRESS; a ten-minute fMRI acquisition; and a long post-fMRI PRESS acquisition. Both pre- and post-fMRI PRESS were non-water suppressed. Real-time frequency stabilization/adjustment was switched off when appropriate. Sixty scanners repeated the protocol for a second dataset. In addition, a three-hour post-fMRI MRS acquisition was performed at one site to observe change of gradient temperature and drift rate. Spectral analysis was performed using MATLAB. Frequency drift in pre-fMRI PRESS data were compared with the first 5:20 minutes and the full 30:00 minutes of data after fMRI. Median (interquartile range) drifts were measured and showed in violin plot. Paired t-tests were performed to compare frequency drift pre- and post-fMRI. A simulated in vivo spectrum was generated using FID-A to visualize the effect of the observed frequency drifts. The simulated spectrum was convolved with the frequency trace for the most extreme cases. Impacts of frequency drifts on NAA and GABA were also simulated as a function of linear drift. Data from the repeated protocol were compared with the corresponding first dataset using Pearson's and intraclass correlation coefficients (ICC). Results Of the data collected from 99 scanners, 4 were excluded due to various reasons. Thus, data from 95 scanners were ultimately analyzed. For the first 5:20 min (64 transients), median (interquartile range) drift was 0.44 (1.29) Hz before fMRI and 0.83 (1.29) Hz after. This increased to 3.15 (4.02) Hz for the full 30 min (360 transients) run. Average drift rates were 0.29 Hz/min before fMRI and 0.43 Hz/min after. Paired t-tests indicated that drift increased after fMRI, as expected (p < 0.05). Simulated spectra convolved with the frequency drift showed that the intensity of the NAA singlet was reduced by up to 26%, 44 % and 18% for GE, Philips and Siemens scanners after fMRI, respectively. ICCs indicated good agreement between datasets acquired on separate days. The single site long acquisition showed drift rate was reduced to 0.03 Hz/min approximately three hours after fMRI. Discussion This study analyzed frequency drift data from 95 3T MRI scanners. Median levels of drift were relatively low (5-min average under 1 Hz), but the most extreme cases suffered from higher levels of drift. The extent of drift varied across scanners which both linear and nonlinear drifts were observed.

Animal studies have shown that the striatal cholinergic system plays a role in behavioral flexibility but, until recently, this system could not be studied in humans due to a lack of appropriate noninvasive techniques. Using proton magnetic resonance spectroscopy, we recently showed that the concentration of dorsal striatal choline (an acetylcholine precursor) changes during reversal learning (a measure of behavioral flexibility) in humans. The aim of the present study was to examine whether regional average striatal choline was associated with reversal learning. A total of 22 participants (mean age = 25.2 years, range = 18–32 years, 13 female) reached learning criterion in a probabilistic learning task with a reversal component. We measured choline at rest in both the dorsal and ventral striatum using magnetic resonance spectroscopy. Task performance was described using a simple reinforcement learning model that dissociates the contributions of positive and negative prediction errors to learning. Average levels of choline in the dorsal striatum were associated with performance during reversal, but not during initial learning. Specifically, lower levels of choline in the dorsal striatum were associated with a lower number of perseverative trials. Moreover, choline levels explained interindividual variance in perseveration over and above that explained by learning from negative prediction errors. These findings suggest that the dorsal striatal cholinergic system plays an important role in behavioral flexibility, in line with evidence from the animal literature and our previous work in humans. Additionally, this work provides further support for the idea of measuring choline with magnetic resonance spectroscopy as a noninvasive way of studying human cholinergic neurochemistry. SIGNIFICANCE STATEMENT Behavioral flexibility is a crucial component of adaptation and survival. Evidence from the animal literature shows that the striatal cholinergic system is fundamental to reversal learning, a key paradigm for studying behavioral flexibility, but this system remains understudied in humans. Using proton magnetic resonance spectroscopy, we showed that choline levels at rest in the dorsal striatum are associated with performance specifically during reversal learning. These novel findings help to bridge the gap between animal and human studies by demonstrating the importance of cholinergic function in the dorsal striatum in human behavioral flexibility. Importantly, the methods described here cannot only be applied to furthering our understanding of healthy human neurochemistry, but also to extending our understanding of cholinergic disorders.

Proton Magnetic Resonance Spectroscopy ((1)H MRS) provides non-invasive, quantitative metabolite profiles of tissue and has been shown to aid the clinical management of several brain diseases. Whilst most modern clinical MR scanners support MRS capabilities, routine use is largely restricted to specialized centers with good access to MR research support. Widespread adoption has been slow for several reasons, and technical challenges towards obtaining reliable good-quality results have been identified as a contributing factor. Considerable progress has been made by the research community to address many of these challenges, and in this paper a consensus is presented on deficiencies in widely available MRS methodology and validated improvements that are currently in routine use at several clinical research institutions. In particular, the localization error for the popular point resolved spectroscopy (PRESS) localization sequence was found to be unacceptably high at 3T, and the use of the semi-adiabatic localization by adiabatic selective refocusing (semi-LASER) sequence is a recommended solution. The incorporation of simulated metabolite basis-sets into analysis routines is recommended for reliably capturing the full spectral detail available from short echo time acquisitions. In addition, the importance of achieving a highly homogenous static magnetic field (B(0)) in the acquisition region is emphasized, and the limitations of current methods and hardware are discussed. Most recommendations require only software improvements, greatly enhancing the capabilities of clinical MRS on existing hardware. We anticipate the implementation of these recommendations will strengthen current clinical applications and advance progress towards developing and validating new MRS biomarkers for clinical use.

Local changes in cerebral blood flow are thought to match changes in neuronal activity, a phenomenon termed neurovascular coupling. Hypoxia increases global resting cerebral blood flow, but regional cerebral blood flow (rCBF) changes are non-uniform. Hypoxia decreases baseline rCBF to the default mode network (DMN), which could reflect either decreased neuronal activity or altered neurovascular coupling. To distinguish between these hypotheses, we characterized the effects of hypoxia on baseline rCBF, task performance, and the hemodynamic (BOLD) response to task activity. During hypoxia, baseline CBF increased across most of the brain, but decreased in DMN regions. Performance on memory recall and motion detection tasks was not diminished, suggesting task-relevant neuronal activity was unaffected. Hypoxia reversed both positive and negative task-evoked BOLD responses in the DMN, suggesting hypoxia reverses neurovascular coupling in the DMN of healthy adults. The reversal of the BOLD response was specific to the DMN. Hypoxia produced modest increases in activations in the visual attention network (VAN) during the motion detection task, and had no effect on activations in the visual cortex during visual stimulation. This regional specificity may be particularly pertinent to clinical populations characterized by hypoxemia and may enhance understanding of regional specificity in neurodegenerative disease pathology.

Objective Previous work suggests that the perception of pain is subjective and dependent on individual differences in physiological, emotional, and cognitive states. Functional magnetic resonance imaging (FMRI) studies have used both stimulus-related (nociceptive properties) and percept-related (subjective experience of pain) models to identify the brain networks associated with pain. Our objective was to identify the network involved in processing subjective pain during cold stimuli. Methods The current FMRI study directly contrasted a stimulus-related model with a percept-related model during blocks of cold pain stimuli in healthy adults. Specifically, neuronal activation was modelled as a function of changes in stimulus intensity vs as a function of increasing/decreasing levels of subjective pain corresponding to changes in pain ratings. In addition, functional connectivity analyses were conducted to examine intrinsic correlations between three proposed subnetworks (sensory/discriminative, affective/motivational, and cognitive/evaluative) involved in pain processing. Results The percept-related model captured more extensive activation than the stimulus-related model and demonstrated an association between higher subjective pain and activation in expected cortical (dorsolateral prefrontal cortex, ventrolateral prefrontal cortex, insula, dorsal anterior cingulate cortex [dACC] extending into pre-supplementary motor area) and subcortical (thalamus, striatum) areas. Moreover, connectivity results supported the posited roles of dACC and insula as key relay sites during neural processing of subjective pain. In particular, anterior insula appeared to link sensory/discriminative regions with regions in the other subnetworks, and dACC appeared to serve as a hub for affective/motivational, cognitive/evaluative, and motor subnetworks. Conclusions Using a percept-related model, brain regions involved in the processing of subjective pain during the application of cold stimuli were identified. Connectivity analyses identified linkages between key subnetworks involved in processing subjective pain.

Background Neuroimaging is an increasingly important tool in the diagnostic workup of dementia. Neurologists, geriatricians, and old-age psychiatrists are involved in key tasks in the diagnostic process, frequently referring patients with suspected dementia for neuroimaging. Methods The research design was a postal survey of all geriatricians, old-age psychiatrists, and neurologists in the Republic of Ireland (N = 176) as identified by the Irish Medical Directory 2011–2012 and supplementary listings. Results Almost 65% of specialists did not have access to 2-[18F]fluoro-2-deoxy-D-glucose positron emission (FDG-PET) or FDG-PET/computed tomography (CT), and 80.3% did not have access to perfusion hexamethylpropyleneamine oxime single-photon emission computed tomography (SPECT) or dopaminergic iodine-123-radiolabeled 2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl) nortropane SPECT. Most specialists (88.7%) referred patients with mild cognitive impairment or suspected dementia for magnetic resonance imaging (MRI), 81.7% referred for CT, and 26.8% for FDG-PET or FDG-PET/CT. Only 44.6% of respondents were aware of dementia-specific protocols for referrals for neuroimaging. Conclusion Specialist access to imaging modalities other than CT and MRI is restricted. Improved access may affect patient treatment and care.

Introduction Patients undergoing MRI often experience anxiety prior and during scanning. The aim of this study was to explore two simple, cost-effective and easily implemented interventions to reduce anxiety pre MRI scanning. Methods Seventy four patients attending first time for a MRI head, spine or cardiac scan were randomised into one of three interventions: video demonstration; telephone conversation with a radiographer; or routine MRI preparation (appointment letter). The State-Trait Anxiety Inventory (STAI) questionnaire was used to measure anxiety levels both pre and post intervention. Motion artefacts were visually assessed by 2 observers and a post scan survey was used to capture patient's satisfaction. Results ANCOVA revealed a significant reduction of anxiety in the video group (F = 13.664, p = 0.001), and also in the telephone group (F = 6.443, p = 0.015) compared to control patients. No significant difference was found between the two interventions (F = 0.665, p = 0.419). No difference was seen in motion artefacts between all three groups (Chi2 = 2.363 (p = 0.359) for observer 1 and Chi2 = 1.280 (p = 0.865) for observer 2). Fifty one percent (51.4%) of patients admitted to being anxious, with the possible outcome of the MRI results being the most common (18.9%) reason given for anxiety. Conclusion This study has demonstrated that either of the interventions used can significantly reduce pre-MRI anxiety, with the video performing slightly better than the phone call intervention. Importantly, the routine appointment letter did not contain enough information to satisfy most patients, which argues strongly for a change in current practice.

The application of magnetic resonance imaging (MRI) to experimental animal models is described. Areas of study have comprised central nervous system, cardiovascular, liver, kidney and the musculoskeletal systems. The study of tumour xenografts has also been possible. Evaluation of disease models and the effects of therapeutic interventions have been investigated.

Objective The study was undertaken to determine whether normobaric hypoxia causes elevated brain volume and intracranial pressure in individuals with symptoms consistent with acute mountain sickness (AMS). Methods Thirteen males age�=�(26 (sd 6)) years were exposed to normobaric hypoxia (12% O2) and normoxia (21% O2). After 2 and 10 hours, AMS symptoms were assessed alongside ventricular and venous vessel volumes, cerebral blood flow, regional brain volumes, and intracranial pressure, using high-resolution magnetic resonance imaging. Results In normoxia, neither lateral ventricular volume (R2�=�0.07, p�=�0.40) nor predominance of unilateral transverse venous sinus drainage (R2�=�0.07, p�=�0.45) was related to AMS symptoms. Furthermore, despite an increase in cerebral blood flow after 2 hours of hypoxia (hypoxia vs normoxia: I�148ml/min�1, 95% confidence interval [CI]�=�58 to 238), by 10 hours, when AMS symptoms had developed, cerebral blood flow was normal (I��51ml/min�1, 95% CI�=��141 to 39). Conversely, at 10 hours brain volume was increased (I�59ml, 95% CI�=�8 to 110), predominantly due to an increase in gray matter volume (I�73ml, 95% CI�=�25 to 120). Therefore, cerebral spinal fluid volume was decreased (I��40ml, 95% CI�=��67 to �14). The intracranial pressure response to hypoxia varied between individuals, and as hypothesized, the most AMS-symptomatic participants had the largest increases in intracranial pressure (AMS present, I�7mmHg, 95% CI�=��2.5 to 17.3; AMS not present, I��1mmHg, 95% CI�=��3.3 to 0.5). Consequently, there was a significant relationship between the change in intracranial pressure and AMS symptom severity (R2�=�0.71, p�=�0.002). Interpretation The data provide the strongest evidence to date to support the hypothesis that the �random� nature of AMS symptomology is explained by a variable intracranial pressure response to hypoxia. ANN NEUROL 2014

Beauty is in the eye of the beholder. How attractive someone is perceived to be depends on the individual or cultural standards to which this person is compared. But although comparisons play a central role in the way people judge the appearance of others, the brain processes underlying attractiveness comparisons remain unknown. In the present experiment, we tested the hypothesis that attractiveness comparisons rely on the same cognitive and neural mechanisms as comparisons of simple nonsocial magnitudes such as size. We recorded brain activity with functional magnetic resonance imaging (fMRI) while participants compared the beauty or height of two women or two dogs. Our data support the hypothesis of a common process underlying these different types of comparisons. First, we demonstrate that the distance effect characteristic of nonsocial comparisons also holds for attractiveness comparisons. Behavioral results indicated, for all our comparisons, longer response times for near than far distances. Second, the neural correlates of these distance effects overlapped in a frontoparietal network known for its involvement in processing simple nonsocial quantities. These results provide evidence for overlapping processes in the comparison of physical attractiveness and nonsocial magnitudes.

Objectives While early diagnosis of dementia is important, the question arises whether general practitioners (GPs) should engage in direct referrals. The current study investigated current referral practices for neuroimaging in dementia, access to imaging modalities and investigated related GP training in Ireland and North Wales. Methods A questionnaire was distributed to GPs in the programme regions which included approximately two thirds of all GPs in the Republic of Ireland and all general practitioners in North Wales. A total of 2,093 questionnaires were issued. Results 48.6% of Irish respondents and 24.3% of Welsh respondents directly referred patients with suspected dementia for neuroimaging. Irish GPs reported greater direct access to neuroimaging than their Welsh counterparts. A very small percentage of Irish and Welsh GPs (4.7% and 10% respectively) had received training in neuroimaging and the majority who referred patients for neuroimaging were not aware of any dementia-specific protocols for referrals (93.1% and 95% respectively). Conclusions The benefits of direct GP access to neuroimaging investigations for dementia have yet to be established. Our findings suggest that current GP speciality training in Ireland and Wales is deficient in dementia-specific and neuroimaging training with the concern being that inadequate training will lead to inadequate referrals. Further training would complement guidelines and provide a greater understanding of the role and appropriateness of neuroimaging techniques in the diagnosis of dementia.

With the prevalence of Alzheimer's disease (AD) predicted to increase substantially over the coming decades, the development of effective biomarkers for the early detection of the disease is paramount. In this short review, the main neuroimaging techniques which have shown potential as biomarkers for AD are introduced, with a focus on MRI. Structural MRI measures of the hippocampus and medial temporal lobe are still the most clinically validated biomarkers for AD, but newer techniques such as functional MRI and diffusion tensor imaging offer great scope in tracking changes in the brain, particularly in functional and structural connectivity, which may precede gray matter atrophy. These new advances in neuroimaging methods require further development and crucially, standardization; however, before they are used as biomarkers to aid in the diagnosis of AD.

Research highlights that internal visual, external visual and kinesthetic imagery differentially effect motor performance (White & Hardy, 1995; Hardy & Callow, 1999). However, patterns of brain activation subserving these different imagery perspectives and modalities have not yet been established. In the current study, we applied the Vividness of Movement Imagery Questionnaire-2 (VMIQ-2) to study the brain activation underpinning these types of imagery. Participants with high imagery ability (using the VMIQ-2) were selected to participate in the study. The experimental conditions involved imagining an action (one item from the VMIQ-2) using internal visual imagery, external visual imagery, kinesthetic imagery and a perceptual control condition involved looking at a fixation cross. The imagery conditions were presented using a block design and the participants' brain activation was recorded using 3T fMRI. A post-experimental questionnaire was administered to test if participants were able to maintain the imagery during the task and if they switched between the imagery perspective/modalities. Four participants failed to adhere to the imagery conditions, and their data was excluded from analysis. As hypothesized, the different perspectives and modalities of imagery elicited both common areas of activation (in the right supplementary motor area, BA6) and dissociated areas of activation. Specifically, internal visual imagery activated occipital, parietal and frontal brain areas (i.e., the dorsal stream) while external visual imagery activated occipital ventral stream areas and kinesthetic imagery activated caudate and cerebellum areas. These results provide the first central evidence for the visual perspectives and modalities delineated in the VMIQ-2, and, initial biological validity for the VMIQ-2. However, given that only one item from the VMIQ-2 was employed, future fMRI research needs to explore all items to further examine these contentions.

With the advent of new analysis methods in neuroimaging that involve independent component analysis (ICA) and dynamic causal modelling (DCM), investigations have focused on measuring both the activity and connectivity of specific brain networks. In this study we combined DCM with spatial ICA to investigate network switching in the brain. Using time courses determined by ICA in our dynamic causal models, we focused on the dynamics of switching between the default mode network (DMN), the network which is active when the brain is not engaging in a specific task, and the central executive network (CEN), which is active when the brain is engaging in a task requiring attention. Previous work using Granger causality methods has shown that regions of the brain which respond to the degree of subjective salience of a stimulus, the salience network, are responsible for switching between the DMN and the CEN (Sridharan et al., 2008). In this work we apply DCM to ICA time courses representing these networks in resting state data. In order to test the repeatability of our work we applied this to two independent datasets. This work confirms that the salience network drives the switching between default mode and central executive networks and that our novel technique is repeatable. © 2014 .

The study was undertaken to determine whether normobaric hypoxia causes elevated brain volume and intracranial pressure in individuals with symptoms consistent with acute mountain sickness (AMS).Thirteen males age = (26 (sd 6)) years were exposed to normobaric hypoxia (12% O2 ) and normoxia (21% O2 ). After 2 and 10 hours, AMS symptoms were assessed alongside ventricular and venous vessel volumes, cerebral blood flow, regional brain volumes, and intracranial pressure, using high-resolution magnetic resonance imaging.In normoxia, neither lateral ventricular volume (R(2) = 0.07, p = 0.40) nor predominance of unilateral transverse venous sinus drainage (R(2) = 0.07, p = 0.45) was related to AMS symptoms. Furthermore, despite an increase in cerebral blood flow after 2 hours of hypoxia (hypoxia vs normoxia: Δ148ml/min(-1) , 95% confidence interval [CI] = 58 to 238), by 10 hours, when AMS symptoms had developed, cerebral blood flow was normal (Δ-51ml/min(-1) , 95% CI = -141 to 39). Conversely, at 10 hours brain volume was increased (Δ59ml, 95% CI = 8 to 110), predominantly due to an increase in gray matter volume (Δ73ml, 95% CI = 25 to 120). Therefore, cerebral spinal fluid volume was decreased (Δ-40ml, 95% CI = -67 to -14). The intracranial pressure response to hypoxia varied between individuals, and as hypothesized, the most AMS-symptomatic participants had the largest increases in intracranial pressure (AMS present, Δ7mmHg, 95% CI = -2.5 to 17.3; AMS not present, Δ-1mmHg, 95% CI = -3.3 to 0.5). Consequently, there was a significant relationship between the change in intracranial pressure and AMS symptom severity (R(2) = 0.71, p = 0.002).The data provide the strongest evidence to date to support the hypothesis that the "random" nature of AMS symptomology is explained by a variable intracranial pressure response to hypoxia.

BACKGROUND: Apoptosis plays an important pathophysiologic role in neuronal cell loss and associated neurologic deficits following traumatic brain injury (TBI). DNA fragmentation represents one of the characteristic biochemical features of neuronal apoptosis and is observed after experimental TBI. DFF45 and DFF40 are essential for DNA fragmentation in various models of apoptosis. MATERIALS AND METHODS: We used mice deficient in DFF45 and wild-type controls. Oligonucleosomal DNA fragmentation induced by TBI was analyzed using in vivo and in vitro assays. Expression and integrity of DFF45 and DFF40 proteins was assessed by Western analysis. Other outcome measurements included neurologic scoring, learning/memory tests, lesion volume measurements (MRI), and assessment of cell viability in vitro among others. RESULTS: We compared the effects of controlled cortical impact (CCI) trauma in DFF45 knockout mice and wild-type controls. Analysis of TBI-induced DNA fragmentation in brain cortex from wild-type and DFF45 knockout mice indicates that, although somewhat delayed, oligonucleosomal cleavage of DNA occurs after TBI in DFF45 knockout mice. DFF45 knockouts showed no significant differences in behavioral outcomes or lesion volumes after TBI as compared to wild-type controls. Using an in vitro reconstitution system, we also demonstrated that cleavage of DFF45 by caspase-3 is not sufficient for DNA fragmentation induced by protein extracts from rat brain cortex. We found that endonuclease activity induced in rat brain cortex following TBI depends on the presence of Mg2+ and Ca2+, but is not inhibited by Zn2+. Primary neuronal cultures from DFF45 knockouts failed to show DNA laddering in response to staurosporine, but did show prominent, albeit delayed, DNA fragmentation following treatment with etoposide. In contrast, primary neurons from wild-type animals demonstrated marked DNA fragmentation following treatment with staurosporine or etoposide. CONCLUSIONS: The results of this study suggest that, in addition to DFF45/40, other endonucleases may be essential for chromatin degradation during neuronal apoptosis in adult brain after TBI.

Ischaemic preconditioning in rats was studied using MRI. Ischaemic preconditioning was induced, using an intraluminal filament method, by 30 min middle cerebral artery occlusion (MCAO), and imaged 24 h later. The secondary insult of 100 min MCAO was induced 3 days following preconditioning and imaged 24 and 72 h later. Twenty-four hours following ischaemic preconditioning most rats showed small sub-cortical hyperintense regions not seen in sham-preconditioned rats. Twenty-four hours and 72 h following the secondary insult preconditioned animals showed significantly smaller lesions (24 h = 112 +/- 31 mm(3), mean +/- standard error; 72 h = 80 +/- 35 mm(3)), which were confined to the striatum, than controls (24 h = 234 +/- 32 mm(3), p = 0.026; 72 h = 275 +/- 37 mm(3), p = 0.003). In addition during lesion maturation from 24 to 72 h post-secondary MCAO, preconditioned rats displayed an average reduction in lesion size as measured by MRI whereas sham-preconditioned rats displayed increases in lesion size; this is the first report of such differential lesion volume evolution in cerebral ischaemic preconditioning.

Elevated brain water is a common finding in individuals with severe forms of altitude illness. However, the location, nature, and a causative link between brain edema and symptoms of acute mountain sickness such as headache remains unknown. We examined indices of brain white matter water mobility in 13 participants after 2 and 10 hours in normoxia (21% O2) and hypoxia (12% O2) using magnetic resonance imaging. Using a whole-brain analysis (tract-based spatial statistics (TBSS)), mean diffusivity was reduced in the left posterior hemisphere after 2 hours and globally reduced throughout cerebral white matter by 10 hours in hypoxia. However, no changes in T2 relaxation time (T2) or fractional anisotropy were observed. The TBSS identified an association between changes in mean diffusivity, fractional anisotropy, and T2 both supra and subtentorially after 2 and 10 hours, with headache score after 10 hours in hypoxia. Region of interest-based analyses generally confirmed these results. These data indicate that acute periods of hypoxemia cause a shift of water into the intracellular space within the cerebral white matter, whereas no evidence of brain edema (a volumetric enlargement) is identifiable. Furthermore, these changes in brain water mobility are related to the intensity of high-altitude headache.

As acute ethanol exposure inhibits N-methyl-D-aspartate glutamate (Glu) receptors, sudden withdrawal from chronic alcohol use may lead to an increased activation of these receptors with excitotoxic effects. In the longer term, brain levels of Glu and its metabolites, such as glutamine (Gln), are likely to be chronically altered by alcohol, possibly providing a measure of overall abnormal Glu-Gln cycling. However, few studies have assessed concentrations of these metabolites in clinical populations of individuals with alcohol use disorders. Glu and Gln levels were compared in groups of 17 healthy controls and in 13 participants with alcohol dependence. Within the alcohol-dependent group, seven participants had current alcohol use disorder (AUD), and six had AUD in remission for at least 1 year (AUD-R). Neurometabolite concentrations were measured with proton magnetic resonance spectroscopy ((1)H-MRS) in a predominantly gray matter voxel that included the bilateral anterior cingulate gyri. Tissue segmentation provided an assessment of the proportion of gray matter in the (1)H-MRS voxel. The Drinker Inventory of Consequences (DrInC) and Form-90 were administered to all participants to quantify alcohol consequences and use. Glu level was lower and Gln level was higher in the AUD and AUD-R groups relative to the control group; creatine, choline, myo-inositol, and total N-acetyl groups, primarily N-acetylaspartate did not differ across groups. These results were not confounded by age, sex, or proportion of gray matter in the (1)H-MRS voxel. Neurometabolite concentrations did not differ between AUD and AUD-R groups. Subsequent regressions in the combined clinical group, treating voxel gray matter proportion as a covariate, revealed that total score on the DrInC was positively correlated with Gln but negatively correlated with both Glu and gray matter proportion. Regression analyses, including DrInC scores and smoking variables, identified a marginal independent effect of smoking on Gln. The current findings of higher Gln and lower Glu in the combined AUD and AUD-R groups might indicate a perturbation of the Glu-Gln cycle in alcohol use disorders. The absence of differences in mean Glu and Gln between the AUD and AUD-R groups suggests that altered Glu-Gln metabolism may either predate the onset of abuse or persist during prolonged abstinence.

Objective.Studies that have examined abnormalities in cerebral blood flow (CBF) in patients with systemic lupus erythematosus (SLE) reported CBF relative to a region assumed to be normal in the brain. We examined the absolute differences in both regional CBF and cerebral blood volume (CBV) between patients with SLE and healthy controls.Methods.CBF and CBV were measured with dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI), a technique that provides an alternative to radionuclide perfusion studies and permits quantitative anatomic, CBF, and CBV imaging in a single scanning session. CBF and CBV were measured in lesions and in normal-appearing tissue in the major cerebral and subcortical brain regions. Unlike most perfusion studies in SLE, CBF and CBV values were not normalized to a region of the brain assumed to be healthy.Results.CBF and CBV within MRI-visible lesions were markedly reduced relative to surrounding normal-appearing white matter. CBF and CBV in normal-appearing tissue were both higher in SLE patient groups, with or without lesions, relative to the control group.Conclusion.DSC MRI, without normalization to a region presumed to be healthy, revealed that CBF and CBV in normal-appearing tissue in patients with SLE was higher than CBF and CBV in controls. Since this finding was made in subgroups of patients with and without lesions, the higher CBF and CBV appear to precede lesion pathology.

Improved detection of J-coupled neurometabolites through the use of modified proton magnetic resonance spectroscopy (1H-MRS) techniques has recently been reported. TE-averaged point-resolved spectroscopy (PRESS) uses the J modulation effects by averaging FIDs with differing echo times to improve detection of glutamate, while standard PRESS detection of glutamate can be improved by using an appropriate single echo determined from J-modulation simulations. In the present study, the reliabilities of TE-averaged PRESS, standard PRESS with TE = 40 ms, and standard PRESS with TE = 30 ms in detecting metabolite levels in the cingulate gyrus of the human brain at 3T were compared in six subjects. TE-averaged PRESS measures showed a mean variability of 9% for N-acetyl aspartate, choline, and creatine, compared with < 4% for the 30- and 40-ms PRESS techniques. The coefficients of variation for glutamate were 10%, 7%, and 5% for TE-averaged, 30-ms, and 40-ms PRESS, respectively. PRESS with a TE of 40 ms also demonstrated improved reliability for GABA and glutamine concentrations. These results show that with the appropriate selection of echo time standard PRESS can be a reliable (1)H-MRS technique for the measurement of J-coupled neurometabolites in the human brain and, moreover, compares favorably with at least one J-edited technique.

A strategy for using tissue water as a concentration standard in (1)H magnetic resonance spectroscopic imaging studies on the brain is presented, and the potential errors that may arise when the method is used are examined. The sensitivity of the method to errors in estimates of the different water compartment relaxation times is shown to be small at short echo times (TEs). Using data from healthy human subjects, it is shown that different image segmentation approaches that are commonly used to account for partial volume effects (SPM2, FSL's FAST, and K-means) lead to different estimates of metabolite levels, particularly in gray matter (GM), owing primarily to variability in the estimates of the cerebrospinal fluid (CSF) fraction. While consistency does not necessarily validate a method, a multispectral segmentation approach using FAST yielded the lowest intersubject variability in the estimates of GM metabolites. The mean GM and white matter (WM) levels of N-acetyl groups (NAc, primarily N-acetylaspartate), choline (Ch), and creatine (Cr) obtained in these subjects using the described method with FAST multispectral segmentation are reported: GM [NAc] = 17.16 +/- 1.19 mM; WM [NAc] = 14.26 +/- 1.38 mM; GM [Ch] = 3.27 +/- 0.47 mM; WM [Ch] = 2.65 +/- 0.25 mM; GM [Cr] = 13.98 +/- 1.20 mM; and WM [Cr] = 7.10 +/- 0.67 mM.

Glutamate, a major excitatory neurotransmitter, has been implicated as an important mediator in the neurotransmission, potentiation, and negative affect associated with pain. We present results showing that a painful stimulus elicits a dynamic increase in glutamate (9.3% from baseline) concentrations in the anterior cingulate cortex, detectable using proton Magnetic Resonance Spectroscopy ((1)H-MRS). Increases in glutamine levels were also seen, which correlate strongly with the subjective level of pain experienced by participants (r(2) = 0.58, P0.01). These novel findings are the first time a dynamic change in glutamate and glutamine levels from baseline in response to an external stimuli has been measured in a single proton MRS scanning session. As such, this report demonstrates the efficacy of (1)H-MRS as a non-invasive tool for the study of neural responses to pain in vivo. The paradigm used in this study demonstrates that dynamic glutamate/glutamine changes due to stimulation are measurable by proton MRS, and could provide a means of testing novel pharmaceutical agents and other treatments for chronic pain.

Victims of minimal traumatic brain injury (mTBI) do not show clear morphological brain defects, but frequently suffer lasting cognitive deficits, emotional difficulties and behavioral disturbances. In the present study we adopted a non-invasive closed-head weight-drop mouse model to produce mTBI. We examined the effects of 20, 25, or 30 g weight drop 7, 30, 60 and 90 days following injury on mice's ability to perform the Morris water maze. The mice suffered profound long-lasting learning and memory deficits that were force- and time-dependent. Although the injured mice could acquire the task, they could not improve their initial escape latency by more than 50%, while normal mice improved by up to 450% (P

Previous studies have shown that location and direction of injury may affect outcome in experimental models of traumatic brain injury. Significant variability in outcome data has also been noted in studies using the lateral fluid percussion brain injury model (FPI) in rats. In recent studies from our laboratory, we observed considerable variability in localization and severity of tissue damage as a function of small changes in craniotomy position. To further address this issue, we examined the relationship between craniotomy position and brain lesion size/location in rats subjected to moderate FPI (2.28 +/- 0.18 atmospheres). With placement of a 5-mm craniotomy adjacent to the sagittal suture, there was both ipsilateral and contralateral damage as detected at 3 weeks posttrauma using T2-weighted magnetic resonance imaging (MRI). The MRI lesions were generally restricted to the hippocampus and subcortical layers. Shifting of the craniotomy site laterally was associated with increased ipsilateral tissue damage and a greater cortical component that correlated with distance from the sagittal suture. In contrast, the contralateral MRI lesion did not change significantly in size or location unless the center of the craniotomy was placed more than 3.5 mm from the sagittal suture, under which condition contralateral damage could no longer be detected. Ipsilateral tissue damage as determined from the MRI scans was linearly correlated to motor outcome but not with cognitive outcome as assessed by the Morris Water Maze. We conclude that craniotomy position is critical in determining extent and location of tissue injury produced during the lateral FPI model in rats. Addressing such potential variability is essential for studies that address either injury mechanisms or therapeutic treatments.

Health professionals should be aware of medical procedures that cause vascular access complications. This case describes a haemodialysis patient who experienced pain, swelling and bruising over a radiocephalic fistula following MRI. Exactly the same signs and symptoms were evident following a second scan performed 3emsp14;months later. Plausible explanations include a radio frequency-induced electrical current being formed at the arteriovenous fistula, or varying gradients of the MRI sequence stimulating peripheral nerves, leading to a site of increased tissue stimulation. Of note, a juxta-anastomotic venous stenosis was confirmed by fistulogram 4emsp14;days after the second scan, although whether this access failure was due to the MRI scan per se could not be ascertained. Nevertheless, these previously undocumented observations suggest that careful patient and fistula monitoring is required when completing MRI scans in those with an arteriovenous fistula.