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After lesions of the somatosensory dorsal column (DC) pathway, the cortical hand representation can become unresponsive to tactile stimuli, but considerable responsiveness returns over weeks of post-lesion recovery. The reactivation suggests that preserved subthreshold sensory inputs become potentiated and axon sprouting occurs over time to mediate recovery. Here, we studied the recovery process in 3 squirrel monkeys, using high-resolution cerebral blood volume-based functional magnetic resonance imaging (CBV-fMRI) mapping of contralateral somatosensory cortex responsiveness to stimulation of distal finger pads with low and high level electrocutaneous stimulation (ES) before and 2, 4, and 6weeks after a mid-cervical level contralateral DC lesion. Both low and high intensity ES of digits revealed the expected somatotopy of the area 3b hand representation in pre-lesion monkeys, while in areas 1 and 3a, high intensity stimulation was more effective in activating somatotopic patterns. Six weeks post-lesion, and irrespective of the severity of loss of direct DC inputs (98%, 79%, 40%), somatosensory cortical area 3b of all three animals showed near complete recovery in terms of somatotopy and responsiveness to low and high intensity ES. However there was significant variability in the patterns and amplitudes of reactivation of individual digit territories within and between animals, reflecting differences in the degree of permanent and/or transient silencing of primary DC and secondary inputs 2weeks post-lesion, and their spatio-temporal trajectories of recovery between 2 and 6weeks. Similar variations in the silencing and recovery of somatotopy and responsiveness to high intensity ES in areas 3a and 1 are consistent with individual differences in damage to and recovery of DC and spinocuneate pathways, and possibly the potentiation of spinothalamic pathways. Thus, cortical deactivation and subsequent reactivation depends not only on the degree of DC lesion, but also on the severity and duration of loss of secondary as well as primary inputs revealed by low and high intensity ES., Competing Interests: The authors declare no competing financial interests., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Reliably differentiating brown adipose tissue (BAT) from other tissues using a non-invasive imaging method is an important step toward studying BAT in humans. Detecting BAT is typically confirmed by the uptake of the injected radioactive tracer 18F-Fluorodeoxyglucose (18F-FDG) into adipose tissue depots, as measured by positron emission tomography/computed tomography (PET-CT) scans after exposing the subject to cold stimulus. Fat-water separated magnetic resonance imaging (MRI) has the ability to distinguish BAT without the use of a radioactive tracer. To date, MRI of BAT in adult humans has not been co-registered with cold-activated PET-CT. Therefore, this protocol uses 18F-FDG PET-CT scans to automatically generate a BAT mask, which is then applied to co-registered MRI scans of the same subject. This approach enables measurement of quantitative MRI properties of BAT without manual segmentation. BAT masks are created from two PET-CT scans: after exposure for 2 hr to either thermoneutral (TN) (24 °C) or cold-activated (CA) (17 °C) conditions. The TN and CA PET-CT scans are registered, and the PET standardized uptake and CT Hounsfield values are used to create a mask containing only BAT. CA and TN MRI scans are also acquired on the same subject and registered to the PET-CT scans in order to establish quantitative MRI properties within the automatically defined BAT mask. An advantage of this approach is that the segmentation is completely automated and is based on widely accepted methods for identification of activated BAT (PET-CT). The quantitative MRI properties of BAT established using this protocol can serve as the basis for an MRI-only BAT examination that avoids the radiation associated with PET-CT.

Independent component analysis (ICA) has been successfully utilized for analysis of functional MRI (fMRI) data for task related as well as resting state studies. Although it holds the promise of becoming an unbiased data-driven analysis technique, a few choices have to be made prior to performing ICA, selection of a method for determining the number of independent components (nIC) being one of them. Choice of nIC has been shown to influence the ICA maps, and various approaches (mostly relying on information theoretic criteria) have been proposed and implemented in commonly used ICA analysis packages, such as MELODIC and GIFT. However, there has been no consensus on the optimal method for nIC selection, and many studies utilize arbitrarily chosen values for nIC. Accurate and reliable determination of true nIC is especially important in the setting where the signals of interest contribute only a small fraction of the total variance, i.e. very low contrast-to-noise ratio (CNR), and/or very focal response. In this study, we evaluate the performance of different model order selection criteria and demonstrate that the model order selected based upon bootstrap stability of principal components yields more reliable and accurate estimates of model order. We then demonstrate the utility of this fully data-driven approach to detect weak and focal stimulus-driven responses in real data. Finally, we compare the performance of different multi-run ICA approaches using pseudo-real data.

Purpose: To test the hypothesis that a whole-body fat-water MRI (FWMRI) protocol acquired at 3 Tesla combined with semi-automated image analysis techniques enables precise volume and mass quantification of adipose, lean, and bone tissue depots that agree with static scale mass and scale mass changes in the context of a longitudinal study of large-breed dogs placed on an obesogenic high-fat, high-fructose diet., Materials and Methods: Six healthy adult male dogs were scanned twice, at weeks 0 (baseline) and 4, of the dietary regiment. FWMRI-derived volumes of adipose tissue (total, visceral, and subcutaneous), lean tissue, and cortical bone were quantified using a semi-automated approach. Volumes were converted to masses using published tissue densities., Results: FWMRI-derived total mass corresponds with scale mass with a concordance correlation coefficient of 0.931 (95% confidence interval = [0.813, 0.975]), and slope and intercept values of 1.12 and -2.23 kg, respectively. Visceral, subcutaneous and total adipose tissue masses increased significantly from weeks 0 to 4, while neither cortical bone nor lean tissue masses changed significantly. This is evidenced by a mean percent change of 70.2% for visceral, 67.0% for subcutaneous, and 67.1% for total adipose tissue., Conclusion: FWMRI can precisely quantify and map body composition with respect to adipose, lean, and bone tissue depots. The described approach provides a valuable tool to examine the role of distinct tissue depots in an established animal model of human metabolic disease., (Copyright © 2013 Wiley Periodicals, Inc.)

Objective: Improved understanding of how depot-specific adipose tissue mass predisposes to obesity-related comorbidities could yield new insights into the pathogenesis and treatment of obesity as well as metabolic benefits of weight loss. We hypothesized that three-dimensional (3D) contiguous "fat-water" MR imaging (FWMRI) covering the majority of a whole-body field of view (FOV) acquired at 3 Tesla (3T) and coupled with automated segmentation and quantification of amount, type, and distribution of adipose and lean soft tissue would show great promise in body composition methodology., Design and Methods: Precision of adipose and lean soft tissue measurements in body and trunk regions were assessed for 3T FWMRI and compared to dual-energy X-ray absorptiometry (DXA). Anthropometric, FWMRI, and DXA measurements were obtained in 12 women with BMI 30-39.9 kg/m(2) ., Results: Test-retest results found coefficients of variation (CV) for FWMRI that were all under 3%: gross body adipose tissue (GBAT) 0.80%, total trunk adipose tissue (TTAT) 2.08%, visceral adipose tissue (VAT) 2.62%, subcutaneous adipose tissue (SAT) 2.11%, gross body lean soft tissue (GBLST) 0.60%, and total trunk lean soft tissue (TTLST) 2.43%. Concordance correlation coefficients between FWMRI and DXA were 0.978, 0.802, 0.629, and 0.400 for GBAT, TTAT, GBLST, and TTLST, respectively., Conclusions: While Bland-Altman plots demonstrated agreement between FWMRI and DXA for GBAT and TTAT, a negative bias existed for GBLST and TTLST measurements. Differences may be explained by the FWMRI FOV length and potential for DXA to overestimate lean soft tissue. While more development is necessary, the described 3T FWMRI method combined with fully-automated segmentation is fast (<30-min total scan and post-processing time), noninvasive, repeatable, and cost-effective., (Copyright © 2012 The Obesity Society.)

Functional magnetic resonance imaging (fMRI) at high magnetic field strength can suffer from serious degradation of image quality because of motion and physiological noise, as well as spatial distortions and signal losses due to susceptibility effects. Overcoming such limitations is essential for sensitive detection and reliable interpretation of fMRI data. These issues are particularly problematic in studies of awake animals. As part of our initial efforts to study functional brain activations in awake, behaving monkeys using fMRI at 4.7 T, we have developed acquisition and analysis procedures to improve image quality with encouraging results. We evaluated the influence of two main variables on image quality. First, we show how important the level of behavioral training is for obtaining good data stability and high temporal signal-to-noise ratios. In initial sessions, our typical scan session lasted 1.5 h, partitioned into short (<10 min) runs. During reward periods and breaks between runs, the monkey exhibited movements resulting in considerable image misregistrations. After a few months of extensive behavioral training, we were able to increase the length of individual runs and the total length of each session. The monkey learned to wait until the end of a block for fluid reward, resulting in longer periods of continuous acquisition. Each additional 60 training sessions extended the duration of each session by 60 min, culminating, after about 140 training sessions, in sessions that last about 4 h. As a result, the average translational movement decreased from over 500 μm to less than 80 μm, a displacement close to that observed in anesthetized monkeys scanned in a 7-T horizontal scanner. Another major source of distortion at high fields arises from susceptibility variations. To reduce such artifacts, we used segmented gradient-echo echo-planar imaging (EPI) sequences. Increasing the number of segments significantly decreased susceptibility artifacts and image distortion. Comparisons of images from functional runs using four segments with those using a single-shot EPI sequence revealed a roughly twofold improvement in functional signal-to-noise-ratio and 50% decrease in distortion. These methods enabled reliable detection of neural activation and permitted blood-oxygenation-level-dependent-based mapping of early visual areas in monkeys using a volume coil. In summary, both extensive behavioral training of monkeys and application of segmented gradient-echo EPI sequence improved signal-to-noise ratio and image quality. Understanding the effects these factors have is important for the application of high field imaging methods to the detection of submillimeter functional structures in the awake monkey brain., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Dynamic B(0) shimming (DS) can produce better field homogeneity than static global shimming by dynamically updating slicewise shim values in a multislice acquisition. The performance of DS however is limited by eddy current fields produced by the switching of 2nd and 3rd order unshielded shims. In this work, we present a novel method of eddy field compensation (EFC) applied to higher order shim induced eddy current fields in multislice DS. This method does not require shim shielding, extra hardware for eddy current compensation or subject specific prescanning. The interactions between shim harmonics are modeled assuming steady state of the medium and long time constant, cross and self term eddy fields in a DS experiment and 'correction factors' characterizing the entire set of shim interactions are derived. The correction factors for a given time between shim switches are shown to be invariable with object scanned, shim switching pattern and actual shim values, allowing for their generalized prospective use. Phantom and human head, 2nd and 3rd order DS experiments performed without any hardware eddy current compensation using the technique show large reductions in field gradients and offsets leading to significant improvements in image quality. This method holds promise as an alternative to expensive hardware based eddy current compensation required in 2nd and 3rd order DS., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Dynamic slice-wise shimming improves B0 field homogeneity by updating shim coil currents for every slice in a multislice acquisition, producing better field homogeneity over a volume than can be obtained by a single static global shim. The first aim of this work was to evaluate the performance of slice-wise field-map-based second-order dynamic shimming in a human high-field 7 T clinical scanner vis-à-vis image based second order static global shimming. Another goal was to characterize eddy currents induced by second and third order shim switching. A final aim was to compare global and dynamic shimming through shim orders to elucidate the relative benefits of going to higher orders and to dynamic shim updating from a static shimming regime. An external hardware module was used to store and dynamically update slice-optimized shim values during multislice data acquisition. High-bandwidth multislice gradient echo scans with B0 field mapping and low-bandwidth single-shot echo planar scans were performed on phantoms and humans using second-order dynamic and static global shims. For the measurement of second and third order shim induced eddy currents, step response temporal phase changes of individual shims were measured and fit to shim harmonics spatially and to multiexponential decay functions temporally. Finally, an order-wise field-map-based comparison was performed with first, second and third order global static shimming, first and second order dynamic shimming, as well as combined second or third order global and first order dynamic shim. Dynamic shimming considerably improved B0 homogeneity compared to static global shimming both in phantoms and in human subjects, reducing image distortion and signal dropout. The unshielded second and third order shims generated strong B0 and self and cross-term eddy fields, with multiple time constants ranging from milliseconds to seconds. Field homogeneity improved with increasing order of shim, with dynamic shimming performing better than global shimming. Hybrid global and dynamic shimming approach yielded field homogeneity better than global static shims but worse than dynamic shims., (Copyright © 2011 Elsevier Inc. All rights reserved.)

We consider 3-D brain structures as continuous parameterized surfaces and present a metric for their comparisons that is invariant to the way they are parameterized. Past comparisons of such surfaces involve either volume deformations or nonrigid matching under fixed parameterizations of surfaces. We propose a new mathematical representation of surfaces, called q-maps, such that L² distances between such maps are invariant to re-parameterizations. This property allows for removing the parameterization variability by optimizing over the re-parameterization group, resulting in a proper parameterization-invariant distance between shapes of surfaces. We demonstrate this method in shape analysis of multiple brain structures, for 34 subjects in the Detroit Fetal Alcohol and Drug Exposure Cohort study, which results in a 91% classification rate for attention deficit hyperactivity disorder cases and controls. This method outperforms some existing techniques such as spherical harmonic point distribution model (SPHARM-PDM) or iterative closest point (ICP).

We consider the task of computing shape statistics and classification of 3D anatomical structures (as continuous, parameterized surfaces). This requires a Riemannian metric that allows re-parameterizations of surfaces by isometries, and computations of geodesics. This allows computing Karcher means and covariances of surfaces, which involves optimal re-parameterizations of surfaces and results in a superior alignment of geometric features across surfaces. The resulting means and covariances are better representatives of the original data and lead to parsimonious shape models. These two moments specify a normal probability model on shape classes, which are used for classifying test shapes into control and disease groups. We demonstrate the success of this model through improved random sampling and a higher classification performance. We study brain structures and present classification results for Attention Deficit Hyperactivity Disorder. Using the mean and covariance structure of the data, we are able to attain an 88% classification rate.

The parkinsonian symptoms and increased Mn accumulation in dopaminergic (DAergic) neurons of the basal ganglia implicate impaired dopamine signaling in the neurotoxic effects of chronic manganese overexposure. Using blood oxygenation level-dependent (BOLD) pharmacological magnetic resonance imaging (phMRI), we mapped brain responses to acute amphetamine (AMPH; 3 mg/kg, ip), which stimulates midbrain DAergic systems, in male Sprague-Dawley rats following 6 weeks of chronic MnCl(2) (5 mg Mn/kg, one per week, iv) or saline treatment. Plasma Mn content, measured immediately following phMRI, was elevated twofold in Mn-treated animals (p < 0.05), but the twofold increase in mean striatal Mn content did not reach significance. In saline-treated animals, AMPH stimulated robust positive BOLD responses throughout the basal ganglia and their reciprocally innervated connections. In contrast, acute AMPH stimulated a negative BOLD response in many of these structures in the Mn-treated group, resulting in significant differences between saline- and Mn-treated AMPH-evoked BOLD responses within caudate putamen, globus pallidus, substantia nigra, mediodorsal thalamic nucleus, and somatosensory cortex. These results demonstrate the utility of AMPH-evoked phMRI as readout of the DAergic signaling in vivo and confirm the vulnerability of DAergic systems to Mn.

Sparse-spokes pulses are 2D slice-selective pulses that effectively mitigate inhomogeneities in the transmitted RF field and reduce unwanted RF artifacts in MR images. Here we consider the practical design of such pulses for high-field MRI and demonstrate limitations of the technique. We analyze the performance of pulses considering input noise as well as other effects such as saturation and T2( *) relaxation. We discuss in detail the correspondence between the reduction of RF inhomogeneities and the fidelity of the input parameters, such as the transmit B1+ field map and combined phase of the main B0 field and eddy-currents. Results include simulations, utilizing 7 T field maps acquired in phantoms and in-vivo, as well as in-vivo experiments. The necessary performance of system hardware components to achieve significant improvements is described., (2010 Elsevier Inc. All rights reserved.)

Manganese (Mn) and iron (Fe) are both paramagnetic species that can affect magnetic resonance relaxation rates. They also share common transport systems in vivo and thus in experimental models of metal exposure their effects on relaxation rates may interact in a complex fashion. Here we present a novel model to interpret the combined effects of Mn and Fe on MRI relaxation rates. To achieve varying levels of both metals, adult rats were separated into four groups; a control group and three groups treated with weekly intravenous injections of 3 mg Mn/kg body for 14 weeks. The three treated groups were fed either a normal diet, Fe deficient or Fe enriched diet. All rats were scanned using MRI at the 14th week to measure regional water relaxation rates. Rat brains were removed at the end of the study (14th week) and dissected into regions for measurement of Mn and Fe by atomic absorption spectroscopy. For the normal diet groups, R(1) was strongly correlated with tissue Mn concentrations. However, the slopes of the linear regression fits varied significantly among different brain regions, and a simple linear model failed to explain the changes in relaxation rate when both Mn and Fe contents changed. We propose a competition model, which is based on the ability of Mn and Fe to compete in vivo for common binding sites. The combined effect of Mn and Fe on the relaxation rates is complicated and additional studies will be necessary to explain how MRI signals are affected when the levels of both metals are varied.

We report studies of the nonlinear nature of blood oxygen level-dependent (BOLD) responses to short transient deactivations in human visual cortex. Both functional magnetic resonance imaging (fMRI) and near-infrared spectroscopy (NIRS) have been used to compare and contrast the hemodynamic response functions (HRFs) associated with transient activation and deactivation in primary visual cortex. We show that signal decreases for short duration deactivations are smaller than corresponding signal increases in activation studies. Moreover, the standard balloon model of BOLD effects may be modified to account for the observed nonlinear nature of deactivations by appropriate changes to simple hemodynamic parameters without recourse to new assumptions about the nature of the coupling between activity and oxygen use.

Background: Manganism is a central nervous system disorder caused by toxic exposure to manganese. Manganism has been related to occupational exposures, liver diseases, prolonged parenteral nutrition, and abuse of illicit drugs. Initially manifested by a reversible neuropsychiatric syndrome (locura manganica), the main symptoms and signs of manganism are emotional lability, compulsive behavior and visual hallucinations. Locura manganica is followed by an irreversible extrapyramidal syndrome, the onset of which occurs years after chronic exposure., Objectives: To characterize the regional distribution of Mn in the rat brain after subchronic exposure to Mn. This animal model holds special clinical relevance, reflecting the earlier clinical stages of manganism before chronic exposure to Mn exerts its irreversible effects., Methods: Sprague-Dawley rats were intravenously injected with MnCl2 weekly, for a total of 14 weeks - approximately 1/10 of the lifetime of the rat. T1-weighted magnetic resonance imaging was used to detect the distribution of Mn deposition in brain tissues, as evidenced by areas of T1-weighted hyperintense signals., Results: A consistent region-specific pattern of T1-weighted hyperintensities was observed in the brains of Mn-treated rats. Cortical hyperintensities were prominent in the hippocampus and dentate gyrus. Hyperintensities were also observed in the olfactory bulbs, pituitary gland, optic nerves and chiasma, pons, midbrain tegmentum, habenula, lentiform and caudate nuclei, thalamus, chorioid plexus and cerebellar hemispheres., Conclusions: Prominent Mn depositions, evidenced by T1-weighted hyperintensities in the hippocampus after subacute exposure to Mn, are compatible with the clinical picture of manganism during its early stages, and may explain its pathophysiology.

Purpose: To describe an initial experience imaging the human hippocampus in vivo using a 7T magnetic resonance (MR) scanner and a protocol developed for very high field neuroimaging., Materials and Methods: Six normal subjects were scanned on a 7T whole body MR scanner equipped with a 16-channel head coil. Sequences included a full field of view T1-weighted 3D turbo field echo (T1W 3D TFE: time of acquisition (TA)=08:58), T2*-weighted 2D fast field echo (T2*W 2D FFE: TA=05:20), and susceptibility-weighted imaging (SWI: TA=04:20). SWI data were postprocessed using a minimum intensity projection (minIP) algorithm. Total imaging time was 23 minutes., Results: T1W 3D TFE images with 700 microm isotropic voxels provided excellent anatomic depiction of macroscopic hippocampal structures. T2*W 2D FFE images with 0.5 mm in-plane resolution and 2.5 mm slice thickness provided clear discrimination of the Cornu Ammonis and the compilation of adjacent sublayers of the hippocampus. SWI images (0.5 mm in-plane resolution, 1.0 mm slice thickness) delineated microvenous anatomy of the hippocampus., Conclusion: In vivo 7T MR imaging can take advantage of higher signal-to-noise and novel contrast mechanisms to provide increased conspicuity of hippocampal anatomy., (Copyright (c) 2008 Wiley-Liss, Inc.)

Functional magnetic resonance imaging (fMRI) has become the method of choice for mapping brain activity in human subjects and detects changes in regional blood oxygenation and volume associated with local changes in neuronal activity. While imaging based on blood oxygenation level dependent (BOLD) contrast has good spatial resolution and sensitivity, the hemodynamic signal develops relatively slowly and is only indirectly related to neuronal activity. An alternative approach termed magnetic source magnetic resonance imaging (msMRI) is based on the premise that neural activity may be mapped by magnetic resonance imaging (MRI) with greater temporal resolution by detecting the local magnetic field perturbations associated with local neuronal electric currents. We used a hybrid ms/BOLD MRI method to investigate whether msMRI could detect signal changes that occur simultaneously at the time of the production of well-defined event-related potentials, the P300 and N170, in regions that previously have been identified as generators of these electrical signals. Robust BOLD activations occurred after some seconds, but we were unable to detect any significant changes in the T2*-weighted signal in these locations that correlated temporally with the timings of the evoked response potentials (ERPs).

Chronic exposure to manganese (Mn) may lead to a movement disorder due to preferential Mn accumulation in the globus pallidus and other basal ganglia nuclei. Iron (Fe) deficiency also results in increased brain Mn levels, as well as dysregulation of other trace metals. The relationship between Mn and Fe transport has been attributed to the fact that both metals can be transported via the same molecular mechanisms. It is not known, however, whether brain Mn distribution patterns due to increased Mn exposure vs. Fe deficiency are the same, or whether Fe supplementation would reverse or inhibit Mn deposition. To address these questions, we utilized four distinct experimental populations. Three separate groups of male Sprague-Dawley rats on different diets (control diet [MnT], Fe deficient [FeD], or Fe supplemented [FeS]) were given weekly intravenous Mn injections (3 mg Mn/kg body mass) for 14 weeks, whereas control (CN) rats were fed the control diet and received sterile saline injections. At the conclusion of the study, both blood and brain Mn and Fe levels were determined by atomic absorption spectroscopy and magnetic resonance imaging. The data indicate that changes in dietary Fe levels (either increased or decreased) result in regionally specific increases in brain Mn levels compared with CN or MnT animals. Furthermore, there was no difference in either Fe or Mn accumulation between FeS or FeD animals. These data suggest that dietary Fe manipulation, whether increased or decreased, may contribute to brain Mn deposition in populations vulnerable to increased Mn exposure.

Although blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) has been widely used to explore human brain function, questions remain regarding the ultimate spatial resolution of positive BOLD fMRI, and indeed the extent to which functional maps revealed by positive BOLD correlate spatially with maps obtained with other high-spatial-resolution mapping techniques commonly used in animals, such as optical imaging of intrinsic signal (OIS) and single-unit electrophysiology. Here, we demonstrate that the positive BOLD signal at 9.4T can reveal the fine topography of individual fingerpads in single-condition activation maps in nonhuman primates. These digit maps are similar to maps obtained from the same animal using intrinsic optical imaging. Furthermore, BOLD fMRI reliably resolved submillimeter spatial shifts in activation in area 3b previously identified with OIS (Chen et al., 2003) as neural correlates of the "funneling illusion." These data demonstrate that at high field, high-spatial-resolution topographic maps can be achieved using the positive BOLD signal, weakening previous notions regarding the spatial specificity of the positive BOLD signal.

Recently, we have demonstrated that the fine-digit topography (millimeter sized) previously identified in the primary somatosensory cortex (SI), using electrophysiology and intrinsic signal optical imaging, can also be mapped with submillimeter resolution using blood-oxygenation-level-dependent (BOLD) functional magnetic resonance imaging at high field. In the present study, we have examined the dependence of BOLD signal response on stimulus intensity in two subregions of SI, Areas 3b and 1. In a region(s)-of-interest (ROI) analysis of Area 3b, BOLD signal amplitude increased linearly with increasing amplitude of an 8-Hz vibrotactile stimulus, and BOLD signal was sustained throughout the stimulation period. In contrast, in Area 1, a significant BOLD signal response was only observed with more intense stimuli, and ROI analysis of the dependence of BOLD response showed no significant dependence on stimulus intensity. In addition, activation was not sustained throughout the period of stimulation. Differing responses of Areas 3b and 1 suggest potentially divergent roles for subregions of SI cortices in vibrotactile intensity encoding. Moreover, this study underscores the importance of imaging at small spatial scales. In this case, such high-resolution imaging allows differentiation between area-specific roles in intensity encoding and identifies anatomic targets for detailed electrophysiological studies of somatosensory neuronal populations with different coding properties. These experiments illustrate the value of nonhuman primates for characterizing the dependence of the BOLD signal response on stimulus parameters and on underlying neural response properties.

Manganese (Mn), an element found in many foods, is an important and essential nutrient for proper health and maintenance. It is toxic in high doses, however, and exposure to excessive levels can result in the onset of a neurological disorder similar to, but distinct from, Parkinson's disease. Historically, Mn neurotoxicity was most commonly associated with various occupations, such as Mn mining, welding and steel production. More recently, increases in both blood and brain Mn levels have been observed in persons with liver disease or those receiving prolonged parenteral nutrition. Additionally, rodent data suggest that iron deficiency and anemia may be risk factors for Mn neurotoxicity. Clinically, brain Mn accumulation can be monitored in vivo using non-invasive magnetic resonance imaging (MRI) due to the paramagnetic nature of this element. Indeed, MRI has been used in a variety of settings to evaluate the brain Mn deposition in various populations. This review focuses on the use of MRI technology in studies related specifically to Mn neurotoxicity. Thus, we will examine reports using MRI to confirm brain Mn accumulation in human populations, and conclude with data from non-human primate and rodent models of Mn neurotoxicity.

This work presents a robust and comprehensive approach for the in vivo automated segmentation and quantitative tissue volume measurement of normal brain composition from multispectral magnetic resonance imaging (MRI) data. Statistical pattern recognition methods based on a finite mixture model are used to partition the intracranial volume into gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) spaces. A masking algorithm initially extracts the brain volume from surrounding extrameningeal tissue. Radio frequency (RF) field inhomogeneity effects in the images are then removed using a recursive method that adapts to the intrinsic local tissue contrast. Our technique supports heterogeneous data with multispectral MR images of different contrast and intensity weighting acquired at varying spatial resolution and orientation. The proposed image segmentation methods have been tested using multispectral T1-, proton density-, and T2-weighted MRI data from young and aged non-human primates as well as from human subjects.

HIV dementia (HIVD) is among the most common and most feared neurological complications of AIDS. In vitro studies have identified a constellation of potentially neurotoxic inflammatory and non-inflammatory pathways, one or more of which could underlie HIVD. Magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI) studies can distinguish between inflammatory and non-inflammatory pathways in vivo and suggest that either or both might be active in different patients or at different times in the same patient. This could perhaps explain the variability in HIVD development, progression and response to therapy. These findings also suggest that MRI and MRS can identify patients at risk for HIVD and predict response to therapy.

Objective: We have previously demonstrated that insulin signaling, through the downstream signaling kinase Akt, is a potent modulator of dopamine transporter (DAT) activity, which fine-tunes dopamine (DA) signaling at the synapse. This suggests a mechanism by which impaired neuronal insulin receptor signaling, a hallmark of diet-induced obesity, may contribute to impaired DA transmission. We tested whether a short-term (two-week) obesogenic high-fat (HF) diet could reduce striatal Akt activity, a marker of central insulin, receptor signaling and blunt striatal and dopaminergic network responsiveness to amphetamine (AMPH). Methods: We examined the effects of a two-week HF diet on striatal DAT activity in rats, using AMPH as a probe in a functional magnetic resonance imaging (fMRI) assay, and mapped the disruption in AMPH-evoked functional connectivity between key dopaminergic targets and their projection areas using correlation and permutation analyses. We used phosphorylation of the Akt substrate GSK3α in striatal extracts as a measure of insulin receptor signaling. Finally, we confirmed the impact of HF diet on striatal DA D2 receptor (D2R) availability using [18F]fallypride positron emission tomography (PET). Results: We found that rats fed a HF diet for only two weeks have reductions in striatal Akt activity, a marker of decreased striatal insulin receptor signaling and blunted striatal responsiveness to AMPH. HF feeding also reduced interactions between elements of the mesolimbic (nucleus accumbens–anterior cingulate) and sensorimotor circuits (caudate/putamen–thalamus–sensorimotor cortex) implicated in hedonic feeding. D2R availability was reduced in HF-fed animals. Conclusion: These studies support the hypothesis that central insulin signaling and dopaminergic neurotransmission are already altered after short-term HF feeding. Because AMPH induces DA efflux and brain activation, in large part via DAT, these findings suggest that blunted central nervous system insulin receptor signaling through a HF diet can impair DA homeostasis, thereby disrupting cognitive and reward circuitry involved in the regulation of hedonic feeding. [ABSTRACT FROM AUTHOR]

Central insulin resistance (IR) influences striatal dopamine (DA) tone, an important determinant of behavioral self-regulation. We hypothesized that an association exists between the degree of peripheral IR and impulse control, mediated by the impact of IR on brain circuits controlling the speed of executing “go” and/or “stop” responses. We measured brain activation and associated performance on a stop signal task (SST) in obese adults with type 2 diabetes (age, 48.1 ± 6.9 yrs (mean ± SD); BMI, 36.5 ± 4.0 kg/m2; HOMA-IR, 7.2 ± 4.1; 12 male, 18 female). Increasing IR, but not BMI, was a predictor of shorter critical stop signal delay (cSSD), a measure of the time window during which a go response can be successfully countermanded (R2 = 0.12). This decline was explained by an IR-associated increase in go speed (R2 = 0.13) with little impact of IR or BMI on stop speed. Greater striatal fMRI activation contrast in stop error (SE) compared with stop success (SS) trials (CONSE>SS) was a significant predictor of faster go speeds (R2 = 0.33, p = 0.002), and was itself predicted by greater IR (CONSE>SS vs HOMA-IR: R2 = 0.10, p = 0.04). Furthermore, this impact of IR on striatal activation was a significant mediator of the faster go speeds and greater impulsivity observed with greater IR. These findings suggest a neural mechanism by which IR may increase impulsivity and degrade behavioral self-regulation. [ABSTRACT FROM AUTHOR]

Activated brown adipose tissue (BAT) plays an important role in thermogenesis and whole body metabolism in mammals. Positron emission tomography (PET)-computed tomography (CT) imaging has identified depots of BAT in adult humans, igniting scientific interest. The purpose of this study is to characterize both active and inactive supraclavicular BAT in adults and compare the values to those of subcutaneous white adipose tissue (WAT). We obtained [18F]fluorodeoxyglucose ([18F]FDG) PET-CT and magnetic resonance imaging (MRI) scans of 25 healthy adults. Unlike [18F]FDG PET, which can detect only active BAT, MRI is capable of detecting both active and inactive BAT. The MRI-derived fat signal fraction (FSF) of active BAT was significantly lower than that of inactive BAT (means ± SD; 60.2 ± 7.6 vs. 62.4 ± 6.8%, respectively). This change in tissue morphology was also reflected as a significant increase in Hounsfield units (HU; -69.4 ± 11.5 vs. -74.5 ± 9.7 HU, respectively). Additionally, the CT HU, MRI FSF, and MRI R2* values are significantly different between BAT and WAT, regardless of the activation status of BAT. To the best of our knowledge, this is the first study to quantify PET-CT and MRI FSF measurements and utilize a semiautomated algorithm to identify inactive and active BAT in the same adult subjects. Our findings support the use of these metrics to characterize and distinguish between BAT and WAT and lay the foundation for future MRI analysis with the hope that some day MRI-based delineation of BAT can stand on its own. [ABSTRACT FROM AUTHOR]

Background Many children with heavy exposure to alcohol in utero display characteristic alterations in brain size and structure. However, the long-term effects of low-to-moderate alcohol exposure on these outcomes are unknown. Methods Using voxel-based morphometry and region-of-interest analyses, we examined the influence of lower doses of alcohol on gray and white matter composition in a prospectively recruited, homogeneous, well-characterized cohort of alcohol-exposed ( n = 11, age 19.5 ± 0.3 years) and control ( n = 9, age 19.6 ± 0.5 years) young adults. A large proportion of the exposed individuals were born to mothers whose alcohol consumption during pregnancy was in the low-to-moderate range. Results There were no differences in total brain volume or total gray or white matter volume between the exposed and control groups. However, gray matter volume was reduced in alcohol-exposed individuals in several areas previously reported to be affected by high levels of exposure, including the left cingulate gyrus, bilateral middle frontal gyri, right middle temporal gyrus, and right caudate nucleus. Notably, this gray matter loss was dose dependent, with higher exposure producing more substantial losses. Conclusions These results indicate that even at low doses, alcohol exposure during pregnancy impacts brain development and that these effects persist into young adulthood. [ABSTRACT FROM AUTHOR]

Manganese (Mn) is an essential metal required for normal homeostasis. Humans chronically exposed to high Mn levels, however, may exhibit psychomotor signs secondary to increased brain Mn. As Mn and iron (Fe) share several cellular membrane transporters, decreased Fe levels resulting from Fe deficiency or anemia lead to increased brain Mn deposition. Conversely, decreased Mn levels are associated with abnormal brain Fe accumulation. To reduce potential Mn toxicity resulting from brain Mn accumulation, we proposed that increased dietary Fe would attenuate brain Mn deposition. To test this hypothesis, three groups of Sprague-Dawley rats were injected weekly (14 weeks) with Mn (3 mg/kg) and fed normal Fe (TX), Fe-supplemented (FeS), or Fe-deficient (FeD) chow. Control (CN) rats received normal dietary Fe and saline injections. Using magnetic resonance imaging, rats were imaged biweekly for 14 weeks to qualitatively monitor brain Mn and Fe accumulation. Both FeS and FeD had greater brain Mn deposition than TX rats. By week 3, R1 values, which correlate with Mn deposition, were statistically significantly increased (p < 0.05) in brain stem, cerebellum, cortex, midbrain, and striatum compared with CN or TX animals. By week 14, R1 values for all brain regions in FeS and FeD animals were statistically significantly increased (p < 0.05). By the end of the study, similar results were obtained for R2 values, a marker of Fe accumulation. These data suggest that Fe supplementation does not effectively protect and may even exacerbate brain Mn accumulation in mammals subchronically exposed to Mn. [ABSTRACT FROM AUTHOR]

Abstract: γ-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in human brain and has been implicated in several neuropsychiatric disorders. In vivo human brain GABA concentrations are near the detection limit for magnetic resonance spectroscopy (∼1 mM), and because of overlap with more abundant compounds, spectral editing is generally necessary to detect GABA. In previous reports, GABA spectra edited by J-difference spectroscopy vary considerably in appearance. We have evaluated the factors that affect GABA spectra and the conditions necessary for robust acquisition of J-difference spectra from arbitrary brain regions. In particular, we demonstrate that variations in spectral quality can be explained in part by the incoherent addition of transients that results from shot to shot frequency and phase variations. An automated time-domain spectral alignment strategy that enables reproducible acquisition of high-quality GABA spectra at 3 T with a standard 30-cm T/R volume coil is presented. Representative GABA spectra from human frontal lobe, an area where susceptibility-induced frequency and phase variations are especially troublesome, that demonstrate the robustness of the acquisition and data handling strategy used in this study are presented. [Copyright &y& Elsevier]

Abstract: The mechanisms underlying blood–brain barrier (BBB) compromise in human immunodeficiency virus (HIV) infection and the ways in which BBB compromise might impair neurocognitive function remain poorly understood. This study had two aims: (1) to examine the relationship between BBB breakdown, measured using contrast-enhanced magnetic resonance imaging (CE-MRI), plasma viral load, and neurological status; and (2) to examine the influence of highly active antiretroviral therapy (HAART) on the relationship between neuroinflammation using myoinositol/creatine (mI/Cr), a surrogate marker of glial activation as measured by magnetic resonance spectroscopy (MRS), and BBB compromise determined by CE-MRI. In 25 HIV-infected patients, we found that: (1) the severity of neurocognitive impairment correlated with the degree of BBB breakdown in the basal ganglia; (2) for any given degree of BBB compromise, patients with high plasma viral load were more severely impaired; (3) BBB compromise correlated with mI/Cr in the basal ganglia; and (4) for any given level of mI/Cr, the severity of BBB compromise and the severity of neurocognitive impairment were significantly less in patients on HAART than in those who were HAART-naïve. These results confirm a role for BBB compromise in the pathogenesis of HIV-associated neurocognitive impairment and suggest that elevated plasma viral load in the presence of BBB compromise may increase the risk for development of HIV-associated dementia (HAD). Additionally, they suggest a salutary effect of HAART on the incidence and severity of HAD, which may, in part, be due to protection of BBB integrity. [Copyright &y& Elsevier]

Increased postcontrast enhancement in contrast-enhanced magnetic resonance imaging (CE-MRI) of the central nervous system (CNS) is a predictor of human immunodeficiency virus (HIV) dementia severity in HIV-infected subjects. The present study confirms this earlier finding in a mildly impaired patient cohort, and demonstrates that the increased postcontrast enhancement is correlated with increased cerebrospinal fluid (CSF) levels of monocyte chemoattractant protein (MCP)-1, an inflammatory chemokine, and increased CNS levels of mI, a microglial marker. These results suggest that early CNS inflammation may underlie the microvascular changes observed, and may be a factor in the development of HIV dementia. [ABSTRACT FROM AUTHOR]