Age and disease related changes in the translocator protein (TSPO) system in the human brain: positron emission tomography measurements with [11C]vinpocetine.

PubMed

Gulyás, Balázs; Vas, Adám; Tóth, Miklós; Takano, Akihiro; Varrone, Andrea; Cselényi, Zsolt; Schain, Martin; Mattsson, Patrik; Halldin, Christer

2011-06-01

The main objectives of the present study were (i) to measure density changes of activated microglia and the peripheral benzodiazepine receptor/translocator protein (TSPO) system during normal ageing in the human brain with positron emission tomography (PET) using the TSPO molecular imaging biomarker [(11)C]vinpocetine and (ii) to compare the level and pattern of TSPO in Alzheimer (AD) patients with age matched healthy subjects, in order to assess the biomarker's usefulness as a diagnostic imaging marker in normal (ageing) and pathological (AD) up-regulation of microglia. PET measurements were made in healthy volunteers, aged between 25 and 78 years, and AD patients, aged between 67 and 82 years, using [(11)C]vinpocetine as the tracer. Global and regional quantitative parameters of tracer uptake and binding, including time activity curves (TAC) of standard uptake values (%SUV), binding affinity parameters, intensity spectrum and homogeneity of the uptake distribution were measured and analysed. Both %SUV and binding values increased with age linearly in the whole brain and in all brain regions. There were no significant differences between the %SUV values of the AD patients and age matched control subjects. There were, however, significant differences in %SUV values in a large number of brain regions between young subjects and old subjects, as well as young subjects and AD patients. The intensity spectrum analysis and homogeneity analysis of the voxel data show that the homogeneity of the %SUV values decreases with ageing and during the disease, whereas the centre of the intensity spectrum is shifted to higher %SUV values. These data indicate an inhomogeneous up-regulation of the TSPO system during ageing and AD. These changes were significant between the group of young subjects and old subjects, as well as young subjects and AD patients, but not between old subjects and AD patients. The present data indicate that [(11)C]vinpocetine may serve as a molecular imaging biomarker of the activity of the TSPO system and, consequently, of the up-regulation of microglia during ageing and in neuroinflammatory diseases. However, the global and regional brain %SUV values between AD patients and age matched controls are not different from each other. The disease specific changes, measured with [(11)C]vinpocetine in AD, are significantly different from those measured in age matched controls only if the inhomogeneities in the uptake pattern are explored with advanced mathematical techniques. For this reason, PET studies using [(11)C]vinpocetine, as molecular imaging biomarker, can efficiently visualise the activation of microglia and the up-regulation of TSPO during ageing and in diseased brains with the help of an appropriate inhomogeneity analysis of the radioligand's brain uptake pattern. Copyright © 2011 Elsevier Inc. All rights reserved.

The human parental brain: In vivo neuroimaging

PubMed Central

Swain, James E.

2015-01-01

Interacting parenting thoughts and behaviors, supported by key brain circuits, critically shape human infants’ current and future behavior. Indeed, the parent–infant relationship provides infants with their first social environment, forming templates for what they can expect from others, how to interact with them and ultimately how they go on to themselves to be parents. This review concentrates on magnetic resonance imaging experiments of the human parent brain, which link brain physiology with parental thoughts and behaviors. After reviewing brain imaging techniques, certain social cognitive and affective concepts are reviewed, including empathy and trust—likely critical to parenting. Following that is a thorough study-by-study review of the state-of-the-art with respect to human neuroimaging studies of the parental brain—from parent brain responses to salient infant stimuli, including emotionally charged baby cries and brief visual stimuli to the latest structural brain studies. Taken together, this research suggests that networks of highly conserved hypothalamic–midbrain–limbic–paralimbic–cortical circuits act in concert to support parental brain responses to infants, including circuits for limbic emotion response and regulation. Thus, a model is presented in which infant stimuli activate sensory analysis brain regions, affect corticolimbic limbic circuits that regulate emotional response, motivation and reward related to their infant, ultimately organizing parenting impulses, thoughts and emotions into coordinated behaviors as a map for future studies. Finally, future directions towards integrated understanding of the brain basis of human parenting are outlined with profound implications for understanding and contributing to long term parent and infant mental health. PMID:21036196

Learning Control Over Emotion Networks Through Connectivity-Based Neurofeedback.

PubMed

Koush, Yury; Meskaldji, Djalel-E; Pichon, Swann; Rey, Gwladys; Rieger, Sebastian W; Linden, David E J; Van De Ville, Dimitri; Vuilleumier, Patrik; Scharnowski, Frank

2017-02-01

Most mental functions are associated with dynamic interactions within functional brain networks. Thus, training individuals to alter functional brain networks might provide novel and powerful means to improve cognitive performance and emotions. Using a novel connectivity-neurofeedback approach based on functional magnetic resonance imaging (fMRI), we show for the first time that participants can learn to change functional brain networks. Specifically, we taught participants control over a key component of the emotion regulation network, in that they learned to increase top-down connectivity from the dorsomedial prefrontal cortex, which is involved in cognitive control, onto the amygdala, which is involved in emotion processing. After training, participants successfully self-regulated the top-down connectivity between these brain areas even without neurofeedback, and this was associated with concomitant increases in subjective valence ratings of emotional stimuli of the participants. Connectivity-based neurofeedback goes beyond previous neurofeedback approaches, which were limited to training localized activity within a brain region. It allows to noninvasively and nonpharmacologically change interconnected functional brain networks directly, thereby resulting in specific behavioral changes. Our results demonstrate that connectivity-based neurofeedback training of emotion regulation networks enhances emotion regulation capabilities. This approach can potentially lead to powerful therapeutic emotion regulation protocols for neuropsychiatric disorders. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Confocal microscopy for astrocyte in vivo imaging: Recycle and reuse in microscopy

PubMed Central

Pérez-Alvarez, Alberto; Araque, Alfonso; Martín, Eduardo D.

2013-01-01

In vivo imaging is one of the ultimate and fundamental approaches for the study of the brain. Two-photon laser scanning microscopy (2PLSM) constitutes the state-of-the-art technique in current neuroscience to address questions regarding brain cell structure, development and function, blood flow regulation and metabolism. This technique evolved from laser scanning confocal microscopy (LSCM), which impacted the field with a major improvement in image resolution of live tissues in the 1980s compared to widefield microscopy. While nowadays some of the unparalleled features of 2PLSM make it the tool of choice for brain studies in vivo, such as the possibility to image deep within a tissue, LSCM can still be useful in this matter. Here we discuss the validity and limitations of LSCM and provide a guide to perform high-resolution in vivo imaging of the brain of live rodents with minimal mechanical disruption employing LSCM. We describe the surgical procedure and experimental setup that allowed us to record intracellular calcium variations in astrocytes evoked by sensory stimulation, and to monitor intact neuronal dendritic spines and astrocytic processes as well as blood vessel dynamics. Therefore, in spite of certain limitations that need to be carefully considered, LSCM constitutes a useful, convenient, and affordable tool for brain studies in vivo. PMID:23658537

[Non-medical applications for brain MRI: Ethical considerations].

PubMed

Sarrazin, S; Fagot-Largeault, A; Leboyer, M; Houenou, J

2015-04-01

The recent neuroimaging techniques offer the possibility to better understand complex cognitive processes that are involved in mental disorders and thus have become cornerstone tools for research in psychiatry. The performances of functional magnetic resonance imaging are not limited to medical research and are used in non-medical fields. These recent applications represent new challenges for bioethics. In this article we aim at discussing the new ethical issues raised by the applications of the latest neuroimaging technologies to non-medical fields. We included a selection of peer-reviewed English medical articles after a search on NCBI Pubmed database and Google scholar from 2000 to 2013. We screened bibliographical tables for supplementary references. Websites of governmental French institutions implicated in ethical questions were also screened for governmental reports. Findings of brain areas supporting emotional responses and regulation have been used for marketing research, also called neuromarketing. The discovery of different brain activation patterns in antisocial disorder has led to changes in forensic psychiatry with the use of imaging techniques with unproven validity. Automated classification algorithms and multivariate statistical analyses of brain images have been applied to brain-reading techniques, aiming at predicting unconscious neural processes in humans. We finally report the current position of the French legislation recently revised and discuss the technical limits of such techniques. In the near future, brain imaging could find clinical applications in psychiatry as diagnostic or predictive tools. However, the latest advances in brain imaging are also used in non-scientific fields raising key ethical questions. Involvement of neuroscientists, psychiatrists, physicians but also of citizens in neuroethics discussions is crucial to challenge the risk of unregulated uses of brain imaging. Copyright © 2014 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

Neurophysiological, metabolic and cellular compartments that drive neurovascular coupling and neuroimaging signals

PubMed Central

Moreno, Andrea; Jego, Pierrick; de la Cruz, Feliberto; Canals, Santiago

2013-01-01

Complete understanding of the mechanisms that coordinate work and energy supply of the brain, the so called neurovascular coupling, is fundamental to interpreting brain energetics and their influence on neuronal coding strategies, but also to interpreting signals obtained from brain imaging techniques such as functional magnetic resonance imaging. Interactions between neuronal activity and cerebral blood flow regulation are largely compartmentalized. First, there exists a functional compartmentalization in which glutamatergic peri-synaptic activity and its electrophysiological events occur in close proximity to vascular responses. Second, the metabolic processes that fuel peri-synaptic activity are partially segregated between glycolytic and oxidative compartments. Finally, there is cellular segregation between astrocytic and neuronal compartments, which has potentially important implications on neurovascular coupling. Experimental data is progressively showing a tight interaction between the products of energy consumption and neurotransmission-driven signaling molecules that regulate blood flow. Here, we review some of these issues in light of recent findings with special attention to the neuron-glia interplay on the generation of neuroimaging signals. PMID:23543907

Technical advances power neuroscience

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barinaga, M.

New techniques are helping researchers study the development of nerve cells in cell cultures and in vivo. These new methods are offering insights into the brain that were not available even a couple of years ago. Among the new advances discussed are imaging technology for evaluating the thinking human brain. One area in which researchers have made recent progress is the quest for ways to create immortal cell lines from specific types of nerve cells. Other projects using genetically engineered retroviruses and tumor-inducing genes, as well as gene regulation are discussed. Recent advances in neuroscience techniques apply not only tomore » neurons, but also to whole brains as well. One example is a high-resulution electroencephalogram (EEG). Although the EEG cannot pin down the actual sites of activity as precisely as static brain imaging methods, it complements them with real-time recording that can keep up with the very rapid pace of brain activity.« less

Live imaging of mitosis in the developing mouse embryonic cortex.

PubMed

Pilaz, Louis-Jan; Silver, Debra L

2014-06-04

Although of short duration, mitosis is a complex and dynamic multi-step process fundamental for development of organs including the brain. In the developing cerebral cortex, abnormal mitosis of neural progenitors can cause defects in brain size and function. Hence, there is a critical need for tools to understand the mechanisms of neural progenitor mitosis. Cortical development in rodents is an outstanding model for studying this process. Neural progenitor mitosis is commonly examined in fixed brain sections. This protocol will describe in detail an approach for live imaging of mitosis in ex vivo embryonic brain slices. We will describe the critical steps for this procedure, which include: brain extraction, brain embedding, vibratome sectioning of brain slices, staining and culturing of slices, and time-lapse imaging. We will then demonstrate and describe in detail how to perform post-acquisition analysis of mitosis. We include representative results from this assay using the vital dye Syto11, transgenic mice (histone H2B-EGFP and centrin-EGFP), and in utero electroporation (mCherry-α-tubulin). We will discuss how this procedure can be best optimized and how it can be modified for study of genetic regulation of mitosis. Live imaging of mitosis in brain slices is a flexible approach to assess the impact of age, anatomy, and genetic perturbation in a controlled environment, and to generate a large amount of data with high temporal and spatial resolution. Hence this protocol will complement existing tools for analysis of neural progenitor mitosis.

EBG Based Microstrip Patch Antenna for Brain Tumor Detection via Scattering Parameters in Microwave Imaging System.

PubMed

Inum, Reefat; Rana, Md Masud; Shushama, Kamrun Nahar; Quader, Md Anwarul

2018-01-01

A microwave brain imaging system model is envisaged to detect and visualize tumor inside the human brain. A compact and efficient microstrip patch antenna is used in the imaging technique to transmit equivalent signal and receive backscattering signal from the stratified human head model. Electromagnetic band gap (EBG) structure is incorporated on the antenna ground plane to enhance the performance. Rectangular and circular EBG structures are proposed to investigate the antenna performance. Incorporation of circular EBG on the antenna ground plane provides an improvement of 22.77% in return loss, 5.84% in impedance bandwidth, and 16.53% in antenna gain with respect to the patch antenna with rectangular EBG. The simulation results obtained from CST are compared to those obtained from HFSS to validate the design. Specific absorption rate (SAR) of the modeled head tissue for the proposed antenna is determined. Different SAR values are compared with the established standard SAR limit to provide a safety regulation of the imaging system. A monostatic radar-based confocal microwave imaging algorithm is applied to generate the image of tumor inside a six-layer human head phantom model. S -parameter signals obtained from circular EBG loaded patch antenna in different scanning modes are utilized in the imaging algorithm to effectively produce a high-resolution image which reliably indicates the presence of tumor inside human brain.

EBG Based Microstrip Patch Antenna for Brain Tumor Detection via Scattering Parameters in Microwave Imaging System

PubMed Central

Rana, Md. Masud; Shushama, Kamrun Nahar; Quader, Md. Anwarul

2018-01-01

A microwave brain imaging system model is envisaged to detect and visualize tumor inside the human brain. A compact and efficient microstrip patch antenna is used in the imaging technique to transmit equivalent signal and receive backscattering signal from the stratified human head model. Electromagnetic band gap (EBG) structure is incorporated on the antenna ground plane to enhance the performance. Rectangular and circular EBG structures are proposed to investigate the antenna performance. Incorporation of circular EBG on the antenna ground plane provides an improvement of 22.77% in return loss, 5.84% in impedance bandwidth, and 16.53% in antenna gain with respect to the patch antenna with rectangular EBG. The simulation results obtained from CST are compared to those obtained from HFSS to validate the design. Specific absorption rate (SAR) of the modeled head tissue for the proposed antenna is determined. Different SAR values are compared with the established standard SAR limit to provide a safety regulation of the imaging system. A monostatic radar-based confocal microwave imaging algorithm is applied to generate the image of tumor inside a six-layer human head phantom model. S-parameter signals obtained from circular EBG loaded patch antenna in different scanning modes are utilized in the imaging algorithm to effectively produce a high-resolution image which reliably indicates the presence of tumor inside human brain. PMID:29623087

Childhood poverty and recruitment of adult emotion regulatory neurocircuitry.

PubMed

Liberzon, Israel; Ma, Sean T; Okada, Go; Ho, S Shaun; Swain, James E; Evans, Gary W

2015-11-01

One in five American children grows up in poverty. Childhood poverty has far-reaching adverse impacts on cognitive, social and emotional development. Altered development of neurocircuits, subserving emotion regulation, is one possible pathway for childhood poverty's ill effects. Children exposed to poverty were followed into young adulthood and then studied using functional brain imaging with an implicit emotion regulation task focused. Implicit emotion regulation involved attention shifting and appraisal components. Early poverty reduced left dorsolateral prefrontal cortex recruitment in the context of emotional regulation. Furthermore, this emotion regulation associated brain activation mediated the effects of poverty on adult task performance. Moreover, childhood poverty also predicted enhanced insula and reduced hippocampal activation, following exposure to acute stress. These results demonstrate that childhood poverty can alter adult emotion regulation neurocircuitry, revealing specific brain mechanisms that may underlie long-term effects of social inequalities on health. The role of poverty-related emotion regulatory neurocircuitry appears to be particularly salient during stressful conditions. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Physiological self-regulation of regional brain activity using real-time functional magnetic resonance imaging (fMRI): methodology and exemplary data.

PubMed

Weiskopf, Nikolaus; Veit, Ralf; Erb, Michael; Mathiak, Klaus; Grodd, Wolfgang; Goebel, Rainer; Birbaumer, Niels

2003-07-01

A brain-computer interface (BCI) based on real-time functional magnetic resonance imaging (fMRI) is presented which allows human subjects to observe and control changes of their own blood oxygen level-dependent (BOLD) response. This BCI performs data preprocessing (including linear trend removal, 3D motion correction) and statistical analysis on-line. Local BOLD signals are continuously fed back to the subject in the magnetic resonance scanner with a delay of less than 2 s from image acquisition. The mean signal of a region of interest is plotted as a time-series superimposed on color-coded stripes which indicate the task, i.e., to increase or decrease the BOLD signal. We exemplify the presented BCI with one volunteer intending to control the signal of the rostral-ventral and dorsal part of the anterior cingulate cortex (ACC). The subject achieved significant changes of local BOLD responses as revealed by region of interest analysis and statistical parametric maps. The percent signal change increased across fMRI-feedback sessions suggesting a learning effect with training. This methodology of fMRI-feedback can assess voluntary control of circumscribed brain areas. As a further extension, behavioral effects of local self-regulation become accessible as a new field of research.

Food can lift mood by affecting mood-regulating neurocircuits via a serotonergic mechanism.

PubMed

Kroes, Marijn C W; van Wingen, Guido A; Wittwer, Jonas; Mohajeri, M Hasan; Kloek, Joris; Fernández, Guillén

2014-01-01

It is commonly assumed that food can affect mood. One prevalent notion is that food containing tryptophan increases serotonin levels in the brain and alters neural processing in mood-regulating neurocircuits. However, tryptophan competes with other long-neutral-amino-acids (LNAA) for transport across the blood-brain-barrier, a limitation that can be mitigated by increasing the tryptophan/LNAA ratio. We therefore tested in a double-blind, placebo-controlled crossover study (N=32) whether a drink with a favourable tryptophan/LNAA ratio improves mood and modulates specific brain processes as assessed by functional magnetic resonance imaging (fMRI). We show that one serving of this drink increases the tryptophan/LNAA ratio in blood plasma, lifts mood in healthy young women and alters task-specific and resting-state processing in brain regions implicated in mood regulation. Specifically, Test-drink consumption reduced neural responses of the dorsal caudate nucleus during reward anticipation, increased neural responses in the dorsal cingulate cortex during fear processing, and increased ventromedial prefrontal-lateral prefrontal connectivity under resting-state conditions. Our results suggest that increasing tryptophan/LNAA ratios can lift mood by affecting mood-regulating neurocircuits. © 2013 Elsevier Inc. All rights reserved.

Reduced prefrontal and increased subcortical brain functioning assessed using positron emission tomography in predatory and affective murderers.

PubMed

Raine, A; Meloy, J R; Bihrle, S; Stoddard, J; LaCasse, L; Buchsbaum, M S

1998-01-01

There appear to be no brain imaging studies investigating which brain mechanisms subserve affective, impulsive violence versus planned, predatory violence. It was hypothesized that affectively violent offenders would have lower prefrontal activity, higher subcortical activity, and reduced prefrontal/subcortical ratios relative to controls, while predatory violent offenders would show relatively normal brain functioning. Glucose metabolism was assessed using positron emission tomography in 41 comparisons, 15 predatory murderers, and nine affective murderers in left and right hemisphere prefrontal (medial and lateral) and subcortical (amygdala, midbrain, hippocampus, and thalamus) regions. Affective murderers relative to comparisons had lower left and right prefrontal functioning, higher right hemisphere subcortical functioning, and lower right hemisphere prefrontal/subcortical ratios. In contrast, predatory murderers had prefrontal functioning that was more equivalent to comparisons, while also having excessively high right subcortical activity. Results support the hypothesis that emotional, unplanned impulsive murderers are less able to regulate and control aggressive impulses generated from subcortical structures due to deficient prefrontal regulation. It is hypothesized that excessive subcortical activity predisposes to aggressive behaviour, but that while predatory murderers have sufficiently good prefrontal functioning to regulate these aggressive impulses, the affective murderers lack such prefrontal control over emotion regulation.

Sex steroid hormones and brain function: PET imaging as a tool for research.

PubMed

Moraga-Amaro, R; van Waarde, A; Doorduin, J; de Vries, E F J

2018-02-01

Sex steroid hormones are major regulators of sexual characteristic among species. These hormones, however, are also produced in the brain. Steroidal hormone-mediated signalling via the corresponding hormone receptors can influence brain function at the cellular level and thus affect behaviour and higher brain functions. Altered steroid hormone signalling has been associated with psychiatric disorders, such as anxiety and depression. Neurosteroids are also considered to have a neuroprotective effect in neurodegenerative diseases. So far, the role of steroid hormone receptors in physiological and pathological conditions has mainly been investigated post mortem on animal or human brain tissues. To study the dynamic interplay between sex steroids, their receptors, brain function and behaviour in psychiatric and neurological disorders in a longitudinal manner, however, non-invasive techniques are needed. Positron emission tomography (PET) is a non-invasive imaging tool that is used to quantitatively investigate a variety of physiological and biochemical parameters in vivo. PET uses radiotracers aimed at a specific target (eg, receptor, enzyme, transporter) to visualise the processes of interest. In this review, we discuss the current status of the use of PET imaging for studying sex steroid hormones in the brain. So far, PET has mainly been investigated as a tool to measure (changes in) sex hormone receptor expression in the brain, to measure a key enzyme in the steroid synthesis pathway (aromatase) and to evaluate the effects of hormonal treatment by imaging specific downstream processes in the brain. Although validated radiotracers for a number of targets are still warranted, PET can already be a useful technique for steroid hormone research and facilitate the translation of interesting findings in animal studies to clinical trials in patients. © 2017 The Authors. Journal of Neuroendocrinology published by John Wiley & Sons Ltd on behalf of British Society for Neuroendocrinology.

APPROACHING THE BIOLOGY OF HUMAN PARENTAL ATTACHMENT: BRAIN IMAGING, OXYTOCIN AND COORDINATED ASSESSMENTS OF MOTHERS AND FATHERS

PubMed Central

Swain, JE; Kim, P; Spicer, J; Ho, SS; Dayton, CJ; Elmadih, A; Abel, KM

2014-01-01

Brain networks that govern parental response to infant signals have been studied with imaging techniques over the last 15 years. The complex interaction of thoughts and behaviors required for sensitive parenting of offspring enable formation of each individual’s first social bonds and critically shape infants’ behavior. This review concentrates on magnetic resonance imaging experiments which directly examine the brain systems involved in parental responses to infant cues. First, we introduce themes in the literature on parental brain circuits studied to date. Next, we present a thorough chronological review of state-of-the-art fMRI studies that probe the parental brain with a range of baby audio and visual stimuli. We also highlight the putative role of oxytocin and effects of psychopathology, as well as the most recent work on the paternal brain. Taken together, a new model emerges in which we propose that cortico-limbic networks interact to support parental brain responses to infants for arousal/salience/motivation/reward, reflexive/instrumental caring, emotion response/regulation and integrative/complex cognitive processing. Maternal sensitivity and the quality of caregiving behavior are likely determined by the responsiveness of these circuits toward long-term influence of early-life experiences on offspring. The function of these circuits is modifiable by current and early-life experiences, hormonal and other factors. Known deviation from the range of normal function in these systems is particularly associated with (maternal) mental illnesses – commonly, depression and anxiety, but also schizophrenia and bipolar disorder. Finally, we discuss the limits and extent to which brain imaging may broaden our understanding of the parental brain, and consider a current model and future directions that may have profound implications for intervention long term outcomes in families across risk and resilience profiles. PMID:24637261

Variation in orbitofrontal cortex volume: relation to sex, emotion regulation and affect.

PubMed

Welborn, B Locke; Papademetris, Xenophon; Reis, Deidre L; Rajeevan, Nallakkandi; Bloise, Suzanne M; Gray, Jeremy R

2009-12-01

Sex differences in brain structure have been examined extensively but are not completely understood, especially in relation to possible functional correlates. Our two aims in this study were to investigate sex differences in brain structure, and to investigate a possible relation between orbitofrontal cortex subregions and affective individual differences. We used tensor-based morphometry to estimate local brain volume from MPRAGE images in 117 healthy right-handed adults (58 female), age 18-40 years. We entered estimates of local brain volume as the dependent variable in a GLM, controlling for age, intelligence and whole-brain volume. Men had larger left planum temporale. Women had larger ventromedial prefrontal cortex (vmPFC), right lateral orbitofrontal (rlOFC), cerebellum, and bilateral basal ganglia and nearby white matter. vmPFC but not rlOFC volume covaried with self-reported emotion regulation strategies (reappraisal, suppression), expressivity of positive emotions (but not of negative), strength of emotional impulses, and cognitive but not somatic anxiety. vmPFC volume statistically mediated sex differences in emotion suppression. The results confirm prior reports of sex differences in orbitofrontal cortex structure, and are the first to show that normal variation in vmPFC volume is systematically related to emotion regulation and affective individual differences.

Imaging biomarkers of angiogenesis and the microvascular environment in cerebral tumours

PubMed Central

Thompson, G; Mills, S J; Coope, D J; O’connor, J P B; Jackson, A

2011-01-01

Conventional contrast-enhanced CT and MRI are now in routine clinical use for the diagnosis, treatment and monitoring of diseases in the brain. The presence of contrast enhancement is a proxy for the pathological changes that occur in the normally highly regulated brain vasculature and blood-brain barrier. With recognition of the limitations of these techniques, and a greater appreciation for the nuanced mechanisms of microvascular change in a variety of pathological processes, novel techniques are under investigation for their utility in further interrogating the microvasculature of the brain. This is particularly important in tumours, where the reliance on angiogenesis (new vessel formation) is crucial for tumour growth, and the resulting microvascular configuration and derangement has profound implications for diagnosis, treatment and monitoring. In addition, novel therapeutic approaches that seek to directly modify the microvasculature require more sensitive and specific biological markers of baseline tumour behaviour and response. The currently used imaging biomarkers of angiogenesis and brain tumour microvascular environment are reviewed. PMID:22433824

Neurological consequences of systemic inflammation in the premature neonate.

PubMed

Patra, Aparna; Huang, Hong; Bauer, John A; Giannone, Peter J

2017-06-01

Despite substantial progress in neonatal care over the past two decades leading to improved survival of extremely premature infants, extreme prematurity continues to be associated with long term neurodevelopmental impairments. Cerebral white matter injury is the predominant form of insult in preterm brain leading to adverse neurological consequences. Such brain injury pattern and unfavorable neurologic sequelae is commonly encountered in premature infants exposed to systemic inflammatory states such as clinical or culture proven sepsis with or without evidence of meningitis, prolonged mechanical ventilation, bronchopulmonary dysplasia, necrotizing enterocolitis and chorioamnionitis. Underlying mechanisms may include cytokine mediated processes without direct entry of pathogens into the brain, developmental differences in immune response and complex neurovascular barrier system that play a critical role in regulating the cerebral response to various systemic inflammatory insults in premature infants. Understanding of these pathologic mechanisms and clinical correlates of such injury based on serum biomarkers or brain imaging findings on magnetic resonance imaging will pave way for future research and translational therapeutic opportunities for the developing brain.

Imaging Live Drosophila Brain with Two-Photon Fluorescence Microscopy

NASA Astrophysics Data System (ADS)

Ahmed, Syeed Ehsan

Two-photon fluorescence microscopy is an imaging technique which delivers distinct benefits for in vivo cellular and molecular imaging. Cyclic adenosine monophosphate (cAMP), a second messenger molecule, is responsible for triggering many physiological changes in neural system. However, the mechanism by which this molecule regulates responses in neuron cells is not yet clearly understood. When cAMP binds to a target protein, it changes the structure of that protein. Therefore, studying this molecular structure change with fluorescence resonance energy transfer (FRET) imaging can shed light on the cAMP functioning mechanism. FRET is a non-radiative dipole-dipole coupling which is sensitive to small distance change in nanometer scale. In this study we have investigated the effect of dopamine in cAMP dynamics in vivo. In our study two-photon fluorescence microscope was used for imaging mushroom bodies inside live Drosophila melanogaster brain and we developed a method for studying the change in cyclic AMP level.

Toward Dysfunctional Connectivity: A Review of Neuroimaging Findings in Pediatric Major Depressive Disorder

PubMed Central

Hulvershorn, Leslie; Cullen, Kathryn; Anand, Amit

2011-01-01

Child and adolescent psychiatric neuroimaging research typically lags behind similar advances in adult disorders. While the pediatric depression imaging literature is less developed, a recent surge in interest has created the need for a synthetic review of this work. Major findings from pediatric volumetric and functional magnetic resonance imaging (fMRI), magnetic resonance spectroscopy (MRS), diffusion tensor imaging (DTI) and resting state functional connectivity studies converge to implicate a corticolimbic network of key areas that work together to mediate the task of emotion regulation. Imaging the brain of children and adolescents with unipolar depression began with volumetric studies of isolated brain regions that served to identify key prefrontal, cingulate and limbic nodes of depression-related circuitry elucidated from more recent advances in DTI and functional connectivity imaging. Systematic review of these studies preliminarily suggests developmental differences between findings in youth and adults, including prodromal neurobiological features, along with some continuity across development. PMID:21901425

Increased gray matter volume in the right angular and posterior parahippocampal gyri in loving-kindness meditators.

PubMed

Leung, Mei-Kei; Chan, Chetwyn C H; Yin, Jing; Lee, Chack-Fan; So, Kwok-Fai; Lee, Tatia M C

2013-01-01

Previous voxel-based morphometry (VBM) studies have revealed that meditation is associated with structural brain changes in regions underlying cognitive processes that are required for attention or mindfulness during meditation. This VBM study examined brain changes related to the practice of an emotion-oriented meditation: loving-kindness meditation (LKM). A 3 T magnetic resonance imaging (MRI) scanner captured images of the brain structures of 25 men, 10 of whom had practiced LKM in the Theravada tradition for at least 5 years. Compared with novices, more gray matter volume was detected in the right angular and posterior parahippocampal gyri in LKM experts. The right angular gyrus has not been previously reported to have structural differences associated with meditation, and its specific role in mind and cognitive empathy theory suggests the uniqueness of this finding for LKM practice. These regions are important for affective regulation associated with empathic response, anxiety and mood. At the same time, gray matter volume in the left temporal lobe in the LKM experts appeared to be greater, an observation that has also been reported in previous MRI meditation studies on meditation styles other than LKM. Overall, the findings of our study suggest that experience in LKM may influence brain structures associated with affective regulation.

Evaluation of spontaneous low-frequency oscillations in cerebral hemodynamics with time-series red-green-blue images

NASA Astrophysics Data System (ADS)

Nishidate, Izumi; Mustari, Afrina; Nakamura, Naoki; Kawauchi, Satoko; Sato, Shunichi; Sato, Manabu; Kokubo, Yasuaki

2017-02-01

The brain relies on a continuous and adequate supply of blood flow, bringing the nutrients that it needs and removing the waste products of metabolism. It is thus one of the most tightly regulated systems in the body, whereby a whole range of mechanisms act to maintain this supply, despite changes in blood pressure etc. Failure of these mechanisms is found in a number of devastating cerebral diseases, including stroke, vascular dementia and brain injury and trauma. Spontaneous contraction and relaxation of arterioles (and in some instances venules) termed vasomotion has been observed in an extensive variety of tissues and species. Vasomotion has a beneficial effect on tissue oxygenation and enhance blood flow. Although vasomotion is strictly a local phenomenon, the regulation of contractile activity of vascular smooth muscle cells is dependent on the complex interplay between vasodilator and vasoconstrictor stimuli from circulating hormones, neurotransmitters, endothelial derived factors, and blood pressure. Therefore, evaluation of the spontaneous oscillations in cerebral vasculatures might be a useful tool for assessing risk and investigating different treatment strategies in neurological disorders, such as traumatic brain injury, seizure, ischemia, and stroke. In the present study, we newly propose a method to visualize the spontaneous low-frequency oscillation of cerebral blood volume based on the sequential RGB images of exposed brain.

Neural indicators of emotion regulation via acceptance vs reappraisal in remitted major depressive disorder

PubMed Central

Keng, Shian-Ling; Ji, Jie Lisa; Moore, Tyler; Minkel, Jared; Dichter, Gabriel S.

2015-01-01

Mood disorders are characterized by impaired emotion regulation abilities, reflected in alterations in frontolimbic brain functioning during regulation. However, little is known about differences in brain function when comparing regulatory strategies. Reappraisal and emotional acceptance are effective in downregulating negative affect, and are components of effective depression psychotherapies. Investigating neural mechanisms of reappraisal vs emotional acceptance in remitted major depressive disorder (rMDD) may yield novel mechanistic insights into depression risk and prevention. Thirty-seven individuals (18 rMDD, 19 controls) were assessed during a functional magnetic resonance imaging task requiring reappraisal, emotional acceptance or no explicit regulation while viewing sad images. Lower negative affect was reported following reappraisal than acceptance, and was lower following acceptance than no explicit regulation. In controls, the acceptance > reappraisal contrast revealed greater activation in left insular cortex and right prefrontal gyrus, and less activation in several other prefrontal regions. Compared with controls, the rMDD group had greater paracingulate and right midfrontal gyrus (BA 8) activation during reappraisal relative to acceptance. Compared with reappraisal, acceptance is associated with activation in regions linked to somatic and emotion awareness, although this activation is associated with less reduction in negative affect. Additionally, a history of MDD moderated these effects. PMID:25617820

Acquired self-control of insula cortex modulates emotion recognition and brain network connectivity in schizophrenia.

PubMed

Ruiz, Sergio; Lee, Sangkyun; Soekadar, Surjo R; Caria, Andrea; Veit, Ralf; Kircher, Tilo; Birbaumer, Niels; Sitaram, Ranganatha

2013-01-01

Real-time functional magnetic resonance imaging (rtfMRI) is a novel technique that has allowed subjects to achieve self-regulation of circumscribed brain regions. Despite its anticipated therapeutic benefits, there is no report on successful application of this technique in psychiatric populations. The objectives of the present study were to train schizophrenia patients to achieve volitional control of bilateral anterior insula cortex on multiple days, and to explore the effect of learned self-regulation on face emotion recognition (an extensively studied deficit in schizophrenia) and on brain network connectivity. Nine patients with schizophrenia were trained to regulate the hemodynamic response in bilateral anterior insula with contingent rtfMRI neurofeedback, through a 2-weeks training. At the end of the training stage, patients performed a face emotion recognition task to explore behavioral effects of learned self-regulation. A learning effect in self-regulation was found for bilateral anterior insula, which persisted through the training. Following successful self-regulation, patients recognized disgust faces more accurately and happy faces less accurately. Improvements in disgust recognition were correlated with levels of self-activation of right insula. RtfMRI training led to an increase in the number of the incoming and outgoing effective connections of the anterior insula. This study shows for the first time that patients with schizophrenia can learn volitional brain regulation by rtfMRI feedback training leading to changes in the perception of emotions and modulations of the brain network connectivity. These findings open the door for further studies of rtfMRI in severely ill psychiatric populations, and possible therapeutic applications. Copyright © 2011 Wiley Periodicals, Inc.

Neural processing of negative word stimuli concerning body image in patients with eating disorders: an fMRI study.

PubMed

Miyake, Yoshie; Okamoto, Yasumasa; Onoda, Keiichi; Shirao, Naoko; Okamoto, Yuri; Otagaki, Yoko; Yamawaki, Shigeto

2010-04-15

Eating disorders (EDs) are associated with abnormalities of body image perception. The aim of the present study was to investigate the functional abnormalities in brain systems during processing of negative words concerning body images in patients with EDs. Brain responses to negative words concerning body images (task condition) and neutral words (control condition) were measured using functional magnetic resonance imaging in 36 patients with EDs (12 with the restricting type anorexia nervosa; AN-R, 12 with the binging-purging type anorexia nervosa; AN-BP, and 12 with bulimia nervosa; BN) and 12 healthy young women. Participants were instructed to select the most negative word from each negative body-image word set and to select the most neutral word from each neutral word set. In the task relative to the control condition, the right amygdala was activated both in patients with AN-R and in patients with AN-BP. The left medial prefrontal cortex (mPFC) was activated both in patients with BN and in patients with AN-BP. It is suggested that these brain activations may be associated with abnormalities of body image perception. Amygdala activation may be involved in fearful emotional processing of negative words concerning body image and strong fears of gaining weight. One possible interpretation of the finding of mPFC activation is that it may reflect an attempt to regulate the emotion invoked by the stimuli. These abnormal brain functions may help provide better accounts of the psychopathological mechanisms underlying EDs. Copyright 2009 Elsevier Inc. All rights reserved.

Brain regulation of food craving: relationships with weight status and eating behavior.

PubMed

Dietrich, A; Hollmann, M; Mathar, D; Villringer, A; Horstmann, A

2016-06-01

Food craving is a driving force for overeating and obesity. However, the relationship between brain mechanisms involved in its regulation and weight status is still an open issue. Gaps in the studied body mass index (BMI) distributions and focusing on linear analyses might have contributed to this lack of knowledge. Here, we investigated brain mechanisms of craving regulation using functional magnetic resonance imaging in a balanced sample including normal-weight, overweight and obese participants. We investigated associations between characteristics of obesity, eating behavior and regulatory brain function focusing on nonlinear relationships. Forty-three hungry female volunteers (BMI: 19.4-38.8 kg m(-2), mean: 27.5±5.3 s.d.) were presented with visual food stimuli individually pre-rated according to tastiness and healthiness. The participants were instructed to either admit to the upcoming craving or regulate it. We analyzed the relationships between regulatory brain activity as well as functional connectivity and BMI or eating behavior (Three-Factor Eating Questionnaire, scales: Cognitive Restraint, Disinhibition). During regulation, BMI correlated with brain activity in the left putamen, amygdala and insula in an inverted U-shaped manner. Functional connectivity between the putamen and the dorsolateral prefrontal cortex (dlPFC) correlated positively with BMI, whereas that of amygdala with pallidum and lingual gyrus was nonlinearly (U-shaped) associated with BMI. Disinhibition correlated negatively with the strength of functional connectivity between amygdala and dorsomedial prefrontal (dmPFC) cortex as well as caudate. This study is the first to reveal quadratic relationships of food-related brain processes and BMI. Reported nonlinear associations indicate inverse relationships between regulation-related motivational processing in the range of normal weight/overweight compared with the obese range. Connectivity analyses suggest that the need for top-down (dlPFC) adjustment of striatal value representations increases with BMI, whereas the interplay of self-monitoring (dmPFC) or eating-related strategic action planning (caudate) and salience processing (amygdala) might be hampered with high Disinhibition.

Trojan Horse Transit Contributes to Blood-Brain Barrier Crossing of a Eukaryotic Pathogen.

PubMed

Santiago-Tirado, Felipe H; Onken, Michael D; Cooper, John A; Klein, Robyn S; Doering, Tamara L

2017-01-31

The blood-brain barrier (BBB) protects the central nervous system (CNS) by restricting the passage of molecules and microorganisms. Despite this barrier, however, the fungal pathogen Cryptococcus neoformans invades the brain, causing a meningoencephalitis that is estimated to kill over 600,000 people annually. Cryptococcal infection begins in the lung, and experimental evidence suggests that host phagocytes play a role in subsequent dissemination, although this role remains ill defined. Additionally, the disparate experimental approaches that have been used to probe various potential routes of BBB transit make it impossible to assess their relative contributions, confounding any integrated understanding of cryptococcal brain entry. Here we used an in vitro model BBB to show that a "Trojan horse" mechanism contributes significantly to fungal barrier crossing and that host factors regulate this process independently of free fungal transit. We also, for the first time, directly imaged C. neoformans-containing phagocytes crossing the BBB, showing that they do so via transendothelial pores. Finally, we found that Trojan horse crossing enables CNS entry of fungal mutants that cannot otherwise traverse the BBB, and we demonstrate additional intercellular interactions that may contribute to brain entry. Our work elucidates the mechanism of cryptococcal brain invasion and offers approaches to study other neuropathogens. The fungal pathogen Cryptococcus neoformans invades the brain, causing a meningoencephalitis that kills hundreds of thousands of people each year. One route that has been proposed for this brain entry is a Trojan horse mechanism, whereby the fungus crosses the blood-brain barrier (BBB) as a passenger inside host phagocytes. Although indirect experimental evidence supports this intriguing mechanism, it has never been directly visualized. Here we directly image Trojan horse transit and show that it is regulated independently of free fungal entry, contributes to cryptococcal BBB crossing, and allows mutant fungi that cannot enter alone to invade the brain. Copyright © 2017 Santiago-Tirado et al.

Strategies to improve drug delivery across the blood-brain barrier.

PubMed

de Boer, Albertus G; Gaillard, Pieter J

2007-01-01

The blood-brain barrier (BBB), together with the blood-cerebrospinal-fluid barrier, protects and regulates the homeostasis of the brain. However, these barriers also limit the transport of small-molecule and, particularly, biopharmaceutical drugs such as proteins, genes and interference RNA to the brain, thereby limiting the treatment of many brain diseases. As a result, various drug delivery and targeting strategies are currently being developed to enhance the transport and distribution of drugs into the brain. In this review, we discuss briefly the biology and physiology of the BBB as the most important barrier for drug transport to the brain and, in more detail, the possibilities for delivering large-molecule drugs, particularly genes, by receptor-mediated nonviral drug delivery to the (human) brain. In addition, the systemic and intracellular pharmacokinetics of nonviral gene delivery, together with targeted brain imaging, are reviewed briefly.

Approaching the biology of human parental attachment: brain imaging, oxytocin and coordinated assessments of mothers and fathers.

PubMed

Swain, J E; Kim, P; Spicer, J; Ho, S S; Dayton, C J; Elmadih, A; Abel, K M

2014-09-11

Brain networks that govern parental response to infant signals have been studied with imaging techniques over the last 15 years. The complex interaction of thoughts and behaviors required for sensitive parenting enables the formation of each individual's first social bonds and critically shapes development. This review concentrates on magnetic resonance imaging experiments which directly examine the brain systems involved in parental responses to infant cues. First, we introduce themes in the literature on parental brain circuits studied to date. Next, we present a thorough chronological review of state-of-the-art fMRI studies that probe the parental brain with a range of baby audio and visual stimuli. We also highlight the putative role of oxytocin and effects of psychopathology, as well as the most recent work on the paternal brain. Taken together, a new model emerges in which we propose that cortico-limbic networks interact to support parental brain responses to infants. These include circuitry for arousal/salience/motivation/reward, reflexive/instrumental caring, emotion response/regulation and integrative/complex cognitive processing. Maternal sensitivity and the quality of caregiving behavior are likely determined by the responsiveness of these circuits during early parent-infant experiences. The function of these circuits is modifiable by current and early-life experiences, hormonal and other factors. Severe deviation from the range of normal function in these systems is particularly associated with (maternal) mental illnesses - commonly, depression and anxiety, but also schizophrenia and bipolar disorder. Finally, we discuss the limits and extent to which brain imaging may broaden our understanding of the parental brain given our current model. Developments in the understanding of the parental brain may have profound implications for long-term outcomes in families across risk, resilience and possible interventions. This article is part of a Special Issue entitled Oxytocin and Social Behav. Copyright © 2014 Elsevier B.V. All rights reserved.

Proton Chemical Shift Imaging of the Brain in Pediatric and Adult Developmental Stuttering.

PubMed

O'Neill, Joseph; Dong, Zhengchao; Bansal, Ravi; Ivanov, Iliyan; Hao, Xuejun; Desai, Jay; Pozzi, Elena; Peterson, Bradley S

2017-01-01

Developmental stuttering is a neuropsychiatric condition of incompletely understood brain origin. Our recent functional magnetic resonance imaging study indicates a possible partial basis of stuttering in circuits enacting self-regulation of motor activity, attention, and emotion. To further characterize the neurophysiology of stuttering through in vivo assay of neurometabolites in suspect brain regions. Proton chemical shift imaging of the brain was performed in a case-control study of children and adults with and without stuttering. Recruitment, assessment, and magnetic resonance imaging were performed in an academic research setting. Ratios of N-acetyl-aspartate plus N-acetyl-aspartyl-glutamate (NAA) to creatine (Cr) and choline compounds (Cho) to Cr in widespread cerebral cortical, white matter, and subcortical regions were analyzed using region of interest and data-driven voxel-based approaches. Forty-seven children and adolescents aged 5 to 17 years (22 with stuttering and 25 without) and 47 adults aged 21 to 51 years (20 with stuttering and 27 without) were recruited between June 2008 and March 2013. The mean (SD) ages of those in the stuttering and control groups were 12.2 (4.2) years and 13.4 (3.2) years, respectively, for the pediatric cohort and 31.4 (7.5) years and 30.5 (9.9) years, respectively, for the adult cohort. Region of interest-based findings included lower group mean NAA:Cr ratio in stuttering than nonstuttering participants in the right inferior frontal cortex (-7.3%; P = .02), inferior frontal white matter (-11.4%; P < .001), and caudate (-10.6%; P = .04), while the Cho:Cr ratio was higher in the bilateral superior temporal cortex (left: +10.0%; P = .03 and right: +10.8%; P = .01), superior temporal white matter (left: +14.6%; P = .003 and right: +9.5%; P = .02), and thalamus (left: +11.6%; P = .002 and right: +11.1%; P = .001). False discovery rate-corrected voxel-based findings were highly consistent with region of interest findings. Additional voxel-based findings in the stuttering sample included higher NAA:Cr and Cho:Cr ratios (regression coefficient, 197.4-275; P < .001) in the posterior cingulate, lateral parietal, hippocampal, and parahippocampal cortices and amygdala, as well as lower NAA:Cr and Cho:Cr ratios (regression coefficient, 119.8-275; P < .001) in the superior frontal and frontal polar cortices. Affected regions comprised nodes of the Bohland speech-production (motor activity regulation), default-mode (attention regulation), and emotional-memory (emotion regulation) networks. Regional correlations were also observed between local metabolites and stuttering severity (r = 0.40-0.52; P = .001-.02). This spectroscopy study of stuttering demonstrates brainwide neurometabolite alterations, including several regions implicated by other neuroimaging modalities. Prior ascription of a role in stuttering to inferior frontal and superior temporal gyri, caudate, and other structures is affirmed. Consistent with prior functional magnetic resonance imaging findings, these results further intimate neurometabolic aberrations in stuttering in brain circuits subserving self-regulation of speech production, attention, and emotion.

Circulating angiotensin II gains access to the hypothalamus and brain stem during hypertension via breakdown of the blood-brain barrier.

PubMed

Biancardi, Vinicia Campana; Son, Sook Jin; Ahmadi, Sahra; Filosa, Jessica A; Stern, Javier E

2014-03-01

Angiotensin II-mediated vascular brain inflammation emerged as a novel pathophysiological mechanism in neurogenic hypertension. However, the precise underlying mechanisms and functional consequences in relation to blood-brain barrier (BBB) integrity and central angiotensin II actions mediating neurohumoral activation in hypertension are poorly understood. Here, we aimed to determine whether BBB permeability within critical hypothalamic and brain stem regions involved in neurohumoral regulation was altered during hypertension. Using digital imaging quantification after intravascularly injected fluorescent dyes and immunohistochemistry, we found increased BBB permeability, along with altered key BBB protein constituents, in spontaneously hypertensive rats within the hypothalamic paraventricular nucleus, the nucleus of the solitary tract, and the rostral ventrolateral medulla, all critical brain regions known to contribute to neurohumoral activation during hypertension. BBB disruption, including increased permeability and downregulation of constituent proteins, was prevented in spontaneously hypertensive rats treated with the AT1 receptor antagonist losartan, but not with hydralazine, a direct vasodilator. Importantly, we found circulating angiotensin II to extravasate into these brain regions, colocalizing with neurons and microglial cells. Taken together, our studies reveal a novel angiotensin II-mediated feed-forward mechanism during hypertension, by which circulating angiotensin II evokes increased BBB permeability, facilitating in turn its access to critical brain regions known to participate in blood pressure regulation.

Non-invasive fluorescent imaging of gliosis in transgenic mice for profiling developmental neurotoxicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ho, Gideon; Zhang Chunyan; Zhuo Lang

2007-05-15

Gliosis is a universal response of Brain to almost all types of neural insults, including neurotoxicity, neurodegeneration, viral infection, and stroke. A hallmark of gliotic reaction is the up-regulation of the astrocytic biomarker GFAP (glial fibrillary acidic protein), which often precedes the anatomically apparent damages in Brain. In this study, neonatal transgenic mice at postnatal day (PD) 4 expressing GFP (green fluorescent protein) under the control of a widely used 2.2-kb human GFAP promoter in Brain are treated with two model neurotoxicants, 1-methyl-4(2'-methylphenyl)-1,2,3,6-tetrahydropyridine (2'-CH{sub 3}-MPTP), and kainic acid (KA), respectively, to induce gliosis. Here we show that the neurotoxicant-induced acutemore » gliosis can be non-invasively imaged and quantified in Brain of conscious (un-anesthetized) mice in real-time, at 0, 2, 4, 6, and 8 h post-toxicant dosing. Therefore the current methodology could be a useful tool for studying the developmental aspects of neuropathies and neurotoxicity.« less

Metabolic Brain Network Analysis of Hypothyroidism Symptom Based on [18F]FDG-PET of Rats.

PubMed

Wan, Hongkai; Tan, Ziyu; Zheng, Qiang; Yu, Jing

2018-03-12

Recent researches have demonstrated the value of using 2-deoxy-2-[ 18 F]fluoro-D-glucose ([ 18 F]FDG) positron emission tomography (PET) imaging to reveal the hypothyroidism-related damages in local brain regions. However, the influence of hypothyroidism on the entire brain network is barely studied. This study focuses on the application of graph theory on analyzing functional brain networks of the hypothyroidism symptom. For both the hypothyroidism and the control groups of Wistar rats, the functional brain networks were constructed by thresholding the glucose metabolism correlation matrices of 58 brain regions. The network topological properties (including the small-world properties and the nodal centralities) were calculated and compared between the two groups. We found that the rat brains, like human brains, have typical properties of the small-world network in both the hypothyroidism and the control groups. However, the hypothyroidism group demonstrated lower global efficiency and decreased local cliquishness of the brain network, indicating hypothyroidism-related impairment to the brain network. The hypothyroidism group also has decreased nodal centrality in the left posterior hippocampus, the right hypothalamus, pituitary, pons, and medulla. This observation accorded with the hypothyroidism-related functional disorder of hypothalamus-pituitary-thyroid (HPT) feedback regulation mechanism. Our research quantitatively confirms that hypothyroidism hampers brain cognitive function by causing impairment to the brain network of glucose metabolism. This study reveals the feasibility and validity of applying graph theory method to preclinical [ 18 F]FDG-PET images and facilitates future study on human subjects.

Neural indicators of emotion regulation via acceptance vs reappraisal in remitted major depressive disorder.

PubMed

Smoski, Moria J; Keng, Shian-Ling; Ji, Jie Lisa; Moore, Tyler; Minkel, Jared; Dichter, Gabriel S

2015-09-01

Mood disorders are characterized by impaired emotion regulation abilities, reflected in alterations in frontolimbic brain functioning during regulation. However, little is known about differences in brain function when comparing regulatory strategies. Reappraisal and emotional acceptance are effective in downregulating negative affect, and are components of effective depression psychotherapies. Investigating neural mechanisms of reappraisal vs emotional acceptance in remitted major depressive disorder (rMDD) may yield novel mechanistic insights into depression risk and prevention. Thirty-seven individuals (18 rMDD, 19 controls) were assessed during a functional magnetic resonance imaging task requiring reappraisal, emotional acceptance or no explicit regulation while viewing sad images. Lower negative affect was reported following reappraisal than acceptance, and was lower following acceptance than no explicit regulation. In controls, the acceptance > reappraisal contrast revealed greater activation in left insular cortex and right prefrontal gyrus, and less activation in several other prefrontal regions. Compared with controls, the rMDD group had greater paracingulate and right midfrontal gyrus (BA 8) activation during reappraisal relative to acceptance. Compared with reappraisal, acceptance is associated with activation in regions linked to somatic and emotion awareness, although this activation is associated with less reduction in negative affect. Additionally, a history of MDD moderated these effects. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Sexual selection predicts brain structure in dragon lizards.

PubMed

Hoops, D; Ullmann, J F P; Janke, A L; Vidal-Garcia, M; Stait-Gardner, T; Dwihapsari, Y; Merkling, T; Price, W S; Endler, J A; Whiting, M J; Keogh, J S

2017-02-01

Phenotypic traits such as ornaments and armaments are generally shaped by sexual selection, which often favours larger and more elaborate males compared to females. But can sexual selection also influence the brain? Previous studies in vertebrates report contradictory results with no consistent pattern between variation in brain structure and the strength of sexual selection. We hypothesize that sexual selection will act in a consistent way on two vertebrate brain regions that directly regulate sexual behaviour: the medial preoptic nucleus (MPON) and the ventromedial hypothalamic nucleus (VMN). The MPON regulates male reproductive behaviour whereas the VMN regulates female reproductive behaviour and is also involved in male aggression. To test our hypothesis, we used high-resolution magnetic resonance imaging combined with traditional histology of brains in 14 dragon lizard species of the genus Ctenophorus that vary in the strength of precopulatory sexual selection. Males belonging to species that experience greater sexual selection had a larger MPON and a smaller VMN. Conversely, females did not show any patterns of variation in these brain regions. As the volumes of both these regions also correlated with brain volume (BV) in our models, we tested whether they show the same pattern of evolution in response to changes in BV and found that the do. Therefore, we show that the primary brain nuclei underlying reproductive behaviour in vertebrates can evolve in a mosaic fashion, differently between males and females, likely in response to sexual selection, and that these same regions are simultaneously evolving in concert in relation to overall brain size. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

Mindfulness Meditation Training and Self-Referential Processing in Social Anxiety Disorder: Behavioral and Neural Effects

PubMed Central

Goldin, Philippe; Ramel, Wiveka; Gross, James

2014-01-01

This study examined the effects of mindfulness-based stress reduction (MBSR) on the brain-behavior mechanisms of self-referential processing in patients with social anxiety disorder (SAD). Sixteen patients underwent functional magnetic resonance imaging while encoding self-referential, valence, and orthographic features of social trait adjectives. Post-MBSR, 14 patients completed neuroimaging. Compared to baseline, MBSR completers showed (a) increased self-esteem and decreased anxiety, (b) increased positive and decreased negative self-endorsement, (c) increased activity in a brain network related to attention regulation, and (d) reduced activity in brain systems implicated in conceptual-linguistic self-view. MBSR-related changes in maladaptive or distorted social self-view in adults diagnosed with SAD may be related to modulation of conceptual self-processing and attention regulation. Self-referential processing may serve as a functional biobehavioral target to measure the effects of mindfulness training. PMID:25568592

Emotion regulation ability varies in relation to intrinsic functional brain architecture

PubMed Central

Uchida, Mai; Biederman, Joseph; Gabrieli, John D. E.; Micco, Jamie; de Los Angeles, Carlo; Brown, Ariel; Kenworthy, Tara; Kagan, Elana

2015-01-01

This study investigated the neural basis of individual variation in emotion regulation, specifically the ability to reappraise negative stimuli so as to down-regulate negative affect. Brain functions in young adults were measured with functional Magnetic Resonance Imaging during three conditions: (i) attending to neutral pictures; (ii) attending to negative pictures and (iii) reappraising negative pictures. Resting-state functional connectivity was measured with amygdala and dorsolateral prefrontal cortical (DLPFC) seed regions frequently associated with emotion regulation. Participants reported more negative affect after attending to negative than neutral pictures, and less negative affect following reappraisal. Both attending to negative vs neutral pictures and reappraising vs attending to negative pictures yielded widespread activations that were significantly right-lateralized for attending to negative pictures and left-lateralized for reappraising negative pictures. Across participants, more successful reappraisal correlated with less trait anxiety and more positive daily emotion, greater activation in medial and lateral prefrontal regions, and lesser resting-state functional connectivity between (a) right amygdala and both medial prefrontal and posterior cingulate cortices, and (b) bilateral DLPFC and posterior visual cortices. The ability to regulate emotion, a source of resilience or of risk for distress, appears to vary in relation to differences in intrinsic functional brain architecture. PMID:25999363

Emotion regulation ability varies in relation to intrinsic functional brain architecture.

PubMed

Uchida, Mai; Biederman, Joseph; Gabrieli, John D E; Micco, Jamie; de Los Angeles, Carlo; Brown, Ariel; Kenworthy, Tara; Kagan, Elana; Whitfield-Gabrieli, Susan

2015-12-01

This study investigated the neural basis of individual variation in emotion regulation, specifically the ability to reappraise negative stimuli so as to down-regulate negative affect. Brain functions in young adults were measured with functional Magnetic Resonance Imaging during three conditions: (i) attending to neutral pictures; (ii) attending to negative pictures and (iii) reappraising negative pictures. Resting-state functional connectivity was measured with amygdala and dorsolateral prefrontal cortical (DLPFC) seed regions frequently associated with emotion regulation. Participants reported more negative affect after attending to negative than neutral pictures, and less negative affect following reappraisal. Both attending to negative vs neutral pictures and reappraising vs attending to negative pictures yielded widespread activations that were significantly right-lateralized for attending to negative pictures and left-lateralized for reappraising negative pictures. Across participants, more successful reappraisal correlated with less trait anxiety and more positive daily emotion, greater activation in medial and lateral prefrontal regions, and lesser resting-state functional connectivity between (a) right amygdala and both medial prefrontal and posterior cingulate cortices, and (b) bilateral DLPFC and posterior visual cortices. The ability to regulate emotion, a source of resilience or of risk for distress, appears to vary in relation to differences in intrinsic functional brain architecture. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

A strategy to measure electrophysiological changes with photoacoustic imaging (Conference Presentation)

NASA Astrophysics Data System (ADS)

Sepela, Rebecka J.; Sherlock, Benjamin E.; Tian, Lin; Marcu, Laura; Sack, Jon

2017-03-01

Photoacoustic imaging is an emerging technology capable of both functional and structural biological imaging. Absorption and scattering in tissue limit the penetration depth of conventional microscopy techniques to <1mm. Photoacoustic imaging however, can offer high-resolution and contrast at depths of several centimeters. Though functional imaging of endogenous contrast agents, such as hemoglobin, is widely implemented, currently photoacoustic imaging is unable to functionally report electrophysiological changes within cells. We aim to develop photoacoustic contrast agents to fulfill this need. Cells throughout the brain and body create electrical signals using ion channel proteins. These proteins undergo structural changes to regulate the flux of salt ions into the cell. We have recently developed ion channel activity tracers that dissociate from ion channels after the protein changes structure. By conjugating the tracer to dyes that are sensitive to changes in their chemical environment, we can detect tracer dissociation and therefore ion channel activity. We are exploring whether a similar mechanism can create photoacoustic signal intensity changes. To test if the environmental sensitivity of the dye is photoacoustically distinguishable, we imaged the dye in different solvent backgrounds. We report that manipulation of the chemical environment of the contrast dye results in robust changes in photoacoustic properties. We are working to capture photoacoustic signal changes that occur when ion channel proteins activate using live cell imaging. This technology could permit photoacoustic imaging of electrophysiological dynamics in deep tissue, such as the brain. Further optimization of this technology could lead to concurrent imaging of neural activity and hemodynamic responses, a crucial step towards understanding neurovascular coupling in the brain.

Abnormalities in emotion processing within cortical and subcortical regions in criminal psychopaths: evidence from a functional magnetic resonance imaging study using pictures with emotional content.

PubMed

Müller, Jürgen L; Sommer, Monika; Wagner, Verena; Lange, Kirsten; Taschler, Heidrun; Röder, Christian H; Schuierer, Gerhardt; Klein, Helmfried E; Hajak, Göran

2003-07-15

Neurobiology of psychopathy is important for our understanding of current neuropsychiatric questions. Despite a growing interest in biological research in psychopathy, its neural underpinning remains obscure. We used functional magnetic resonance imaging to study the influence of affective contents on brain activation in psychopaths. Series containing positive and negative pictures from the International Affective Picture System were shown to six male psychopaths and six male control subjects while 100 whole-brain echo-planar-imaging measurements were acquired. Differences in brain activation were evaluated using BrainVoyager software 4.6. In psychopaths, increased activation through negative contents was found right-sided in prefrontal regions and amygdala. Activation was reduced right-sided in the subgenual cingulate and the temporal gyrus, and left-sided in the dorsal cingulate and the parahippocampal gyrus. Increased activation through positive contents was found left-sided in the orbitofrontal regions. Activation was reduced in right medial frontal and medial temporal regions. These findings underline the hypotheses that psychopathy is neurobiologically reflected by dysregulation and disturbed functional connectivity of emotion-related brain regions. These findings may be interpreted within a framework including prefrontal regions that provide top-down control to and regulate bottom-up signals from limbic areas. Because of the small sample size, the results of this study have to be regarded as preliminary.

Detecting occlusion inside a ventricular catheter using photoacoustic imaging through skull

NASA Astrophysics Data System (ADS)

Tavakoli, Behnoosh; Guo, Xiaoyu; Taylor, Russell H.; Kang, Jin U.; Boctor, Emad M.

2014-03-01

Ventricular catheters are used to treat hydrocephalus by diverting the excess of the cerebrospinal fluid (CSF) to the reabsorption site so as to regulate the intracranial pressure. The failure rate of these shunts is extremely high due to the ingrown tissue that blocks the CSF flow. We have studied a method to image the occlusion inside the shunt through the skull. In this approach the pulsed laser light coupled to the optical fiber illuminate the occluding tissue inside the catheter and an external ultrasound transducer is applied to detect the generated photoacoustic signal. The feasibility of this method is investigated using a phantom made of ovis aries brain tissue and adult human skull. We were able to image the target inside the shunt located 20mm deep inside the brain through about 4mm thick skull bone. This study could lead to the development of a simple, safe and non-invasive device for percutaneous restoration of patency to occluded shunts. This will eliminate the need of the surgical replacement of the occluded catheters which expose the patients to risks including hemorrhage and brain injury.

Regulatory brain development: balancing emotion and cognition.

PubMed

Perlman, Susan B; Pelphrey, Kevin A

2010-01-01

Emotion regulation is a critical aspect of children's social development, yet few studies have examined the brain mechanisms involved in its development. Theoretical accounts have conceptualized emotion regulation as relying on prefrontal control of limbic regions, specifying the anterior cingulate cortex (ACC) as a key brain region. Functional magnetic resonance imaging in 5- to 11-year-olds during emotion regulation and processing of emotionally expressive faces revealed that older children preferentially recruited the more dorsal “cognitive” areas of the ACC, while younger children preferentially engaged the more ventral “emotional” areas. Additionally, children with more fearful temperaments exhibited more ventral ACC activity while less fearful children exhibited increased activity in the dorsal ACC. These findings provide insight into a potential neurobiological mechanism underlying well-documented behavioral and cognitive changes from more emotional to more cognitive regulatory strategies with increasing age, as well as individual differences in this developmental process as a function of temperament. Our results hold important implications for our understanding of normal development and should also help to inform our understanding and management of emotional disorders. © 2010 Psychology Press

New insights into coupling and uncoupling of cerebral blood flow and metabolism in the brain

PubMed Central

Venkat, Poornima; Chopp, Michael; Chen, Jieli

2016-01-01

The brain has high metabolic and energy needs and requires continuous cerebral blood flow (CBF), which is facilitated by a tight coupling between neuronal activity, CBF, and metabolism. Upon neuronal activation, there is an increase in energy demand, which is then met by a hemodynamic response that increases CBF. Such regional CBF increase in response to neuronal activation is observed using neuroimaging techniques such as functional magnetic resonance imaging and positron emission tomography. The mechanisms and mediators (eg, nitric oxide, astrocytes, and ion channels) that regulate CBF-metabolism coupling have been extensively studied. The neurovascular unit is a conceptual model encompassing the anatomical and metabolic interactions between the neurons, vascular components, and glial cells in the brain. It is compromised under disease states such as stroke, diabetes, hypertension, dementias, and with aging, all of which trigger a cascade of inflammatory responses that exacerbate brain damage. Hence, tight regulation and maintenance of neurovascular coupling is central for brain homeostasis. This review article also discusses the waste clearance pathways in the brain such as the glymphatic system. The glymphatic system is a functional waste clearance pathway that removes metabolic wastes and neurotoxins from the brain along paravascular channels. Disruption of the glymphatic system burdens the brain with accumulating waste and has been reported in aging as well as several neurological diseases. PMID:27374823

New insights into coupling and uncoupling of cerebral blood flow and metabolism in the brain.

PubMed

Venkat, Poornima; Chopp, Michael; Chen, Jieli

2016-06-30

The brain has high metabolic and energy needs and requires continuous cerebral blood flow (CBF), which is facilitated by a tight coupling between neuronal activity, CBF, and metabolism. Upon neuronal activation, there is an increase in energy demand, which is then met by a hemodynamic response that increases CBF. Such regional CBF increase in response to neuronal activation is observed using neuroimaging techniques such as functional magnetic resonance imaging and positron emission tomography. The mechanisms and mediators (eg, nitric oxide, astrocytes, and ion channels) that regulate CBF-metabolism coupling have been extensively studied. The neurovascular unit is a conceptual model encompassing the anatomical and metabolic interactions between the neurons, vascular components, and glial cells in the brain. It is compromised under disease states such as stroke, diabetes, hypertension, dementias, and with aging, all of which trigger a cascade of inflammatory responses that exacerbate brain damage. Hence, tight regulation and maintenance of neurovascular coupling is central for brain homeostasis. This review article also discusses the waste clearance pathways in the brain such as the glymphatic system. The glymphatic system is a functional waste clearance pathway that removes metabolic wastes and neurotoxins from the brain along paravascular channels. Disruption of the glymphatic system burdens the brain with accumulating waste and has been reported in aging as well as several neurological diseases.

Real-time functional magnetic resonance imaging neurofeedback in motor neurorehabilitation.

PubMed

Linden, David E J; Turner, Duncan L

2016-08-01

Recent developments in functional magnetic resonance imaging (fMRI) have catalyzed a new field of translational neuroscience. Using fMRI to monitor the aspects of task-related changes in neural activation or brain connectivity, investigators can offer feedback of simple or complex neural signals/patterns back to the participant on a quasireal-time basis [real-time-fMRI-based neurofeedback (rt-fMRI-NF)]. Here, we introduce some background methodology of the new developments in this field and give a perspective on how they may be used in neurorehabilitation in the future. The development of rt-fMRI-NF has been used to promote self-regulation of activity in several brain regions and networks. In addition, and unlike other noninvasive techniques, rt-fMRI-NF can access specific subcortical regions and in principle any region that can be monitored using fMRI including the cerebellum, brainstem and spinal cord. In Parkinson's disease and stroke, rt-fMRI-NF has been demonstrated to alter neural activity after the self-regulation training was completed and to modify specific behaviours. Future exploitation of rt-fMRI-NF could be used to induce neuroplasticity in brain networks that are involved in certain neurological conditions. However, currently, the use of rt-fMRI-NF in randomized, controlled clinical trials is in its infancy.

Mapping the brain correlates of borderline personality disorder: A functional neuroimaging meta-analysis of resting state studies.

PubMed

Visintin, Eleonora; De Panfilis, Chiara; Amore, Mario; Balestrieri, Matteo; Wolf, Robert Christian; Sambataro, Fabio

2016-11-01

Altered intrinsic function of the brain has been implicated in Borderline Personality Disorder (BPD). Nonetheless, imaging studies have yielded inconsistent alterations of brain function. To investigate the neural activity at rest in BPD, we conducted a set of meta-analyses of brain imaging studies performed at rest. A total of seven functional imaging studies (152 patients with BPD and 147 control subjects) were combined using whole-brain Signed Differential Mapping meta-analyses. Furthermore, two conjunction meta-analyses of neural activity at rest were also performed: with neural activity changes during emotional processing, and with structural differences, respectively. We found altered neural activity in the regions of the default mode network (DMN) in BPD. Within the regions of the midline core DMN, patients with BPD showed greater activity in the anterior as well as in the posterior midline hubs relative to controls. Conversely, in the regions of the dorsal DMN they showed reduced activity compared to controls in the right lateral temporal complex and bilaterally in the orbitofrontal cortex. Increased activity in the precuneus was observed both at rest and during emotional processing. Reduced neural activity at rest in lateral temporal complex was associated with smaller volume of this area. Heterogeneity across imaging studies. Altered activity in the regions of the midline core as well as of the dorsal subsystem of the DMN may reflect difficulties with interpersonal and affective regulation in BPD. These findings suggest that changes in spontaneous neural activity could underlie core symptoms in BPD. Copyright © 2016 Elsevier B.V. All rights reserved.

Brain regions implicated in inhibitory control and appetite regulation are activated in response to food portion size and energy density in children.

PubMed

English, L K; Fearnbach, S N; Lasschuijt, M; Schlegel, A; Anderson, K; Harris, S; Wilson, S J; Fisher, J O; Savage, J S; Rolls, B J; Keller, K L

2016-10-01

Large portions of energy-dense foods drive energy intake but the brain mechanisms underlying this effect are not clear. Our main objective was to investigate brain function in response to food images varied by portion size (PS) and energy density (ED) in children using functional magnetic resonance imaging (fMRI). Blood-oxygen-level-dependent (BOLD) fMRI was completed in 36 children (ages 7-10 years) after a 2-h fast while viewing food images at two levels of PS (Large PS, Small PS) and two levels of ED (High ED, Low ED). Children rated perceived fullness pre- and post-fMRI, as well as liking of images on visual analog scales post-fMRI. Anthropometrics were completed 4 weeks before the fMRI. Large PS vs Small PS and High ED vs Low ED were compared with region-of-interest analyses using Brain Voyager v 2.8. Region-of-interest analyses revealed that activation in the right inferior frontal gyrus (P=0.03) was greater for Large PS vs Small PS. Activation was reduced for High ED vs Low ED in the left hypothalamus (P=0.03). Main effects were no longer significant after adjustment for pre-fMRI fullness and liking ratings (PS, P=0.92; ED, P=0.58). This is the first fMRI study to report increased activation to large portions in a brain region that is involved in inhibitory control. These findings may contribute to understanding why some children overeat when presented with large portions of palatable food.

Salience network integrity predicts default mode network function after traumatic brain injury

PubMed Central

Bonnelle, Valerie; Ham, Timothy E.; Leech, Robert; Kinnunen, Kirsi M.; Mehta, Mitul A.; Greenwood, Richard J.; Sharp, David J.

2012-01-01

Efficient behavior involves the coordinated activity of large-scale brain networks, but the way in which these networks interact is uncertain. One theory is that the salience network (SN)—which includes the anterior cingulate cortex, presupplementary motor area, and anterior insulae—regulates dynamic changes in other networks. If this is the case, then damage to the structural connectivity of the SN should disrupt the regulation of associated networks. To investigate this hypothesis, we studied a group of 57 patients with cognitive impairments following traumatic brain injury (TBI) and 25 control subjects using the stop-signal task. The pattern of brain activity associated with stop-signal task performance was studied by using functional MRI, and the structural integrity of network connections was quantified by using diffusion tensor imaging. Efficient inhibitory control was associated with rapid deactivation within parts of the default mode network (DMN), including the precuneus and posterior cingulate cortex. TBI patients showed a failure of DMN deactivation, which was associated with an impairment of inhibitory control. TBI frequently results in traumatic axonal injury, which can disconnect brain networks by damaging white matter tracts. The abnormality of DMN function was specifically predicted by the amount of white matter damage in the SN tract connecting the right anterior insulae to the presupplementary motor area and dorsal anterior cingulate cortex. The results provide evidence that structural integrity of the SN is necessary for the efficient regulation of activity in the DMN, and that a failure of this regulation leads to inefficient cognitive control. PMID:22393019

Neurofeedback with fMRI: A critical systematic review.

PubMed

Thibault, Robert T; MacPherson, Amanda; Lifshitz, Michael; Roth, Raquel R; Raz, Amir

2018-05-15

Neurofeedback relying on functional magnetic resonance imaging (fMRI-nf) heralds new prospects for self-regulating brain and behavior. Here we provide the first comprehensive review of the fMRI-nf literature and the first systematic database of fMRI-nf findings. We synthesize information from 99 fMRI-nf experiments-the bulk of currently available data. The vast majority of fMRI-nf findings suggest that self-regulation of specific brain signatures seems viable; however, replication of concomitant behavioral outcomes remains sparse. To disentangle placebo influences and establish the specific effects of neurofeedback, we highlight the need for double-blind placebo-controlled studies alongside rigorous and standardized statistical analyses. Before fMRI-nf can join the clinical armamentarium, research must first confirm the sustainability, transferability, and feasibility of fMRI-nf in patients as well as in healthy individuals. Whereas modulating specific brain activity promises to mold cognition, emotion, thought, and action, reducing complex mental health issues to circumscribed brain regions may represent a tenuous goal. We can certainly change brain activity with fMRI-nf. However, it remains unclear whether such changes translate into meaningful behavioral improvements in the clinical domain. Copyright © 2017 Elsevier Inc. All rights reserved.

Aging reduces the stimulating effect of blue light on cognitive brain functions.

PubMed

Daneault, Véronique; Hébert, Marc; Albouy, Geneviève; Doyon, Julien; Dumont, Marie; Carrier, Julie; Vandewalle, Gilles

2014-01-01

Light exposure, particularly blue light, is being recognized as a potent mean to stimulate alertness and cognition in young individuals. Aging is associated with changes in alertness regulation and cognition. Whether the effect of light on cognitive brain function changes with aging is unknown, however. Cross-sectional study. Functional Neuroimaging Unit, University of Montreal Geriatric Institute. Sixteen younger (23 ± 4.1 y) and 14 older (61 ± 4.5 y) healthy participants were recruited in the current study. Blue light administration. We used functional magnetic resonance imaging to record brain responses to an auditory working memory task in young and older healthy individuals, alternatively maintained in darkness or exposed to blue light. Results show that the older brain remains capable of showing sustained responses to light in several brain areas. However, compared to young individuals, the effect of blue light is decreased in the pulvinar, amygdala, and tegmentum as well as in the insular, prefrontal, and occipital cortices in elderly individuals. The effect of blue light on brain responses diminishes with aging in areas typically involved in visual functions and in key regions for alertness regulation and higher executive processes. Our findings provide the first indications that the effect of light on cognition may be reduced in healthy aging.

Functional divisions for visual processing in the central brain of flying Drosophila

PubMed Central

Weir, Peter T.; Dickinson, Michael H.

2015-01-01

Although anatomy is often the first step in assigning functions to neural structures, it is not always clear whether architecturally distinct regions of the brain correspond to operational units. Whereas neuroarchitecture remains relatively static, functional connectivity may change almost instantaneously according to behavioral context. We imaged panneuronal responses to visual stimuli in a highly conserved central brain region in the fruit fly, Drosophila, during flight. In one substructure, the fan-shaped body, automated analysis revealed three layers that were unresponsive in quiescent flies but became responsive to visual stimuli when the animal was flying. The responses of these regions to a broad suite of visual stimuli suggest that they are involved in the regulation of flight heading. To identify the cell types that underlie these responses, we imaged activity in sets of genetically defined neurons with arborizations in the targeted layers. The responses of this collection during flight also segregated into three sets, confirming the existence of three layers, and they collectively accounted for the panneuronal activity. Our results provide an atlas of flight-gated visual responses in a central brain circuit. PMID:26324910

Functional divisions for visual processing in the central brain of flying Drosophila.

PubMed

Weir, Peter T; Dickinson, Michael H

2015-10-06

Although anatomy is often the first step in assigning functions to neural structures, it is not always clear whether architecturally distinct regions of the brain correspond to operational units. Whereas neuroarchitecture remains relatively static, functional connectivity may change almost instantaneously according to behavioral context. We imaged panneuronal responses to visual stimuli in a highly conserved central brain region in the fruit fly, Drosophila, during flight. In one substructure, the fan-shaped body, automated analysis revealed three layers that were unresponsive in quiescent flies but became responsive to visual stimuli when the animal was flying. The responses of these regions to a broad suite of visual stimuli suggest that they are involved in the regulation of flight heading. To identify the cell types that underlie these responses, we imaged activity in sets of genetically defined neurons with arborizations in the targeted layers. The responses of this collection during flight also segregated into three sets, confirming the existence of three layers, and they collectively accounted for the panneuronal activity. Our results provide an atlas of flight-gated visual responses in a central brain circuit.

The hippocampal response to psychosocial stress varies with salivary uric acid level

PubMed Central

Goodman, Adam M.; Wheelock, Muriah D.; Harnett, Nathaniel G.; Mrug, Sylvie; Granger, Douglas A.; Knight, David C.

2016-01-01

Uric acid is a naturally occurring, endogenous compound that impacts mental health. In particular, uric acid levels are associated with emotion-related psychopathology (e.g., anxiety and depression). Therefore, understanding uric acid’s impact on the brain would provide valuable new knowledge regarding neural mechanisms that mediate the relationship between uric acid and mental health. Brain regions including the prefrontal cortex, amygdala, and hippocampus underlie stress reactivity and emotion regulation. Thus, uric acid may impact emotion by modifying the function of these brain regions. The present study used functional magnetic resonance imaging (fMRI) during a psychosocial stress task to investigate the relationship between baseline uric acid levels (in saliva) and brain function. Results demonstrate that activity within the bilateral hippocampal complex varied with uric acid concentrations. Specifically, activity within the hippocampus and surrounding cortex increased as a function of uric acid level. The current findings suggest that uric acid levels modulate stress-related hippocampal activity. Given that the hippocampus has been implicated in emotion regulation during psychosocial stress, the present findings offer a potential mechanism by which uric acid impacts mental health. PMID:27725214

Brain CT image similarity retrieval method based on uncertain location graph.

PubMed

Pan, Haiwei; Li, Pengyuan; Li, Qing; Han, Qilong; Feng, Xiaoning; Gao, Linlin

2014-03-01

A number of brain computed tomography (CT) images stored in hospitals that contain valuable information should be shared to support computer-aided diagnosis systems. Finding the similar brain CT images from the brain CT image database can effectively help doctors diagnose based on the earlier cases. However, the similarity retrieval for brain CT images requires much higher accuracy than the general images. In this paper, a new model of uncertain location graph (ULG) is presented for brain CT image modeling and similarity retrieval. According to the characteristics of brain CT image, we propose a novel method to model brain CT image to ULG based on brain CT image texture. Then, a scheme for ULG similarity retrieval is introduced. Furthermore, an effective index structure is applied to reduce the searching time. Experimental results reveal that our method functions well on brain CT images similarity retrieval with higher accuracy and efficiency.

Imaging characteristics of hemophagocytic lymphohistiocytosis.

PubMed

Fitzgerald, Nancy E; MacClain, Kenneth L

2003-06-01

Hemophagocytic lymphohistiocytosis (HLH) is a nonmalignant disorder of immune regulation, with overproduction of cytokines and diminished immune surveillance. Symptoms are nonspecific and may affect multiple organs, including the central nervous system. Neuroimaging findings have been described in case reports and small series; body imaging findings have not been described extensively. OBJECTIVE. To summarize findings of the most frequently performed imaging studies of the brain, chest and abdomen in patients with HLH. Retrospective review of chest radiographs and CT, abdominal ultrasound and CT, brain CT and MRI, skeletal surveys, and autopsy data. Twenty-five patients were diagnosed and treated for HLH at our institution over an 11-year period; 15 patients (60%) died. Common chest radiograph findings included alveolar-interstitial opacities with pleural effusions, often with rapid evolution and resolution. Hepatosplenomegaly, gallbladder wall thickening, hyperechoic kidneys and ascites were common abdominal findings, which resolved after therapy in some cases. Brain-imaging studies revealed nonspecific periventricular white-matter abnormalities, brain-volume loss and enlargement of extra-axial fluid spaces. Three infant cases, one with intracranial hemorrhage, one with multiple pathologic rib fractures and one with diaphyseal periosteal reaction involving multiple long bones on skeletal survey, raised suspicion of child abuse at presentation. Abuse was not substantiated in any case. Clinicians and radiologists should be aware of the radiographic manifestations of HLH, which are nonspecific and overlap with infectious, inflammatory and neoplastic disorders. Findings in the chest (similar to acute respiratory distress syndrome) and abdomen may progress rapidly and then regress with institution of appropriate anti-HLH therapy. CNS findings may be progressive. In some infants, initial imaging findings may mimic nonaccidental trauma.

Brain imaging and behavioral outcome in traumatic brain injury.

PubMed

Bigler, E D

1996-09-01

Brain imaging studies have become an essential diagnostic assessment procedure in evaluating the effects of traumatic brain injury (TBI). Such imaging studies provide a wealth of information about structural and functional deficits following TBI. But how pathologic changes identified by brain imaging methods relate to neurobehavioral outcome is not as well known. Thus, the focus of this article is on brain imaging findings and outcome following TBI. The article starts with an overview of current research dealing with the cellular pathology associated with TBI. Understanding the cellular elements of pathology permits extrapolation to what is observed with brain imaging. Next, this article reviews the relationship of brain imaging findings to underlying pathology and how that pathology relates to neurobehavioral outcome. The brain imaging techniques of magnetic resonance imaging, computerized tomography, and single photon emission computed tomography are reviewed. Various image analysis procedures, and how such findings relate to neuropsychological testing, are discussed. The importance of brain imaging in evaluating neurobehavioral deficits following brain injury is stressed.

Maintenance of Voluntary Self-regulation Learned through Real-Time fMRI Neurofeedback

PubMed Central

Robineau, Fabien; Meskaldji, Djalel E.; Koush, Yury; Rieger, Sebastian W.; Mermoud, Christophe; Morgenthaler, Stephan; Van De Ville, Dimitri; Vuilleumier, Patrik; Scharnowski, Frank

2017-01-01

Neurofeedback based on real-time functional magnetic resonance imaging (fMRI) is an emerging technique that allows for learning voluntary control over brain activity. Such brain training has been shown to cause specific behavioral or cognitive enhancements, and even therapeutic effects in neurological and psychiatric patient populations. However, for clinical applications it is important to know if learned self-regulation can be maintained over longer periods of time and whether it transfers to situations without neurofeedback. Here, we present preliminary results from five healthy participants who successfully learned to control their visual cortex activity and who we re-scanned 6 and 14 months after the initial neurofeedback training to perform learned self-regulation. We found that participants achieved levels of self-regulation that were similar to those achieved at the end of the successful initial training, and this without further neurofeedback information. Our results demonstrate that learned self-regulation can be maintained over longer periods of time and causes lasting transfer effects. They thus support the notion that neurofeedback is a promising therapeutic approach whose effects can last far beyond the actual training period. PMID:28386224

Developing a clinical translational neuroscience taxonomy for anxiety and mood disorder: protocol for the baseline-follow up Research domain criteria Anxiety and Depression ("RAD") project.

PubMed

Williams, Leanne M; Goldstein-Piekarski, Andrea N; Chowdhry, Nowreen; Grisanzio, Katherine A; Haug, Nancy A; Samara, Zoe; Etkin, Amit; O'Hara, Ruth; Schatzberg, Alan F; Suppes, Trisha; Yesavage, Jerome

2016-03-15

Understanding how brain circuit dysfunctions relate to specific symptoms offers promise for developing a brain-based taxonomy for classifying psychopathology, identifying targets for mechanistic studies and ultimately for guiding treatment choice. The goal of the Research Domain Criteria (RDoC) initiative of the National Institute of Mental Health is to accelerate the development of such neurobiological models of mental disorder independent of traditional diagnostic criteria. In our RDoC Anxiety and Depression ("RAD") project we focus trans-diagnostically on the spectrum of depression and anxiety psychopathology. Our aims are a) to use brain imaging to define cohesive dimensions defined by dysfunction of circuits involved in reactivity to and regulation of negatively valenced emotional stimulation and in cognitive control, b) to assess the relationships between these dimension and specific symptoms, behavioral performance and the real world capacity to function socially and at work and c) to assess the stability of brain-symptom-behavior-function relationships over time. Here we present the protocol for the "RAD" project, one of the first RDoC studies to use brain circuit functioning to define new dimensions of psychopathology. The RAD project follows baseline-follow up design. In line with RDoC principles we use a strategy for recruiting all clients who "walk through the door" of a large community mental health clinic as well as the surrounding community. The clinic attends to a broad spectrum of anxiety and mood-related symptoms. Participants are unmedicated and studied at baseline using a standardized battery of functional brain imaging, structural brain imaging and behavioral probes that assay constructs of threat reactivity, threat regulation and cognitive control. The battery also includes self-report measures of anxiety and mood symptoms, and social and occupational functioning. After baseline assessments, therapists in the clinic apply treatment planning as usual. Follow-up assessments are undertaken at 3 months, to establish the reliability of brain-based subgroups over time and to assess whether these subgroups predict real-world functional capacity over time. First enrollment was August 2013, and is ongoing. This project is designed to advance knowledge toward a neural circuit taxonomy for mental disorder. Data will be shared via the RDoC database for dissemination to the scientific community. The clinical translational neuroscience goals of the project are to develop brain-behavior profile reports for each individual participant and to refine these reports with therapist feedback. Reporting of results is expected from December 2016 onward. ClinicalTrials.gov Identifier: NCT02220309 . Registered: August 13, 2014.

Rapid Postnatal Expansion of Neural Networks Occurs in an Environment of Altered Neurovascular and Neurometabolic Coupling.

PubMed

Kozberg, Mariel G; Ma, Ying; Shaik, Mohammed A; Kim, Sharon H; Hillman, Elizabeth M C

2016-06-22

In the adult brain, increases in neural activity lead to increases in local blood flow. However, many prior measurements of functional hemodynamics in the neonatal brain, including functional magnetic resonance imaging (fMRI) in human infants, have noted altered and even inverted hemodynamic responses to stimuli. Here, we demonstrate that localized neural activity in early postnatal mice does not evoke blood flow increases as in the adult brain, and elucidate the neural and metabolic correlates of these altered functional hemodynamics as a function of developmental age. Using wide-field GCaMP imaging, the development of neural responses to somatosensory stimulus is visualized over the entire bilaterally exposed cortex. Neural responses are observed to progress from tightly localized, unilateral maps to bilateral responses as interhemispheric connectivity becomes established. Simultaneous hemodynamic imaging confirms that spatiotemporally coupled functional hyperemia is not present during these early stages of postnatal brain development, and develops gradually as cortical connectivity is established. Exploring the consequences of this lack of functional hyperemia, measurements of oxidative metabolism via flavoprotein fluorescence suggest that neural activity depletes local oxygen to below baseline levels at early developmental stages. Analysis of hemoglobin oxygenation dynamics at the same age confirms oxygen depletion for both stimulus-evoked and resting-state neural activity. This state of unmet metabolic demand during neural network development poses new questions about the mechanisms of neurovascular development and its role in both normal and abnormal brain development. These results also provide important insights for the interpretation of fMRI studies of the developing brain. This work demonstrates that the postnatal development of neuronal connectivity is accompanied by development of the mechanisms that regulate local blood flow in response to neural activity. Novel in vivo imaging reveals that, in the developing mouse brain, strong and localized GCaMP neural responses to stimulus fail to evoke local blood flow increases, leading to a state in which oxygen levels become locally depleted. These results demonstrate that the development of cortical connectivity occurs in an environment of altered energy availability that itself may play a role in shaping normal brain development. These findings have important implications for understanding the pathophysiology of abnormal developmental trajectories, and for the interpretation of functional magnetic resonance imaging data acquired in the developing brain. Copyright © 2016 the authors 0270-6474/16/366704-14$15.00/0.

Brain medical image diagnosis based on corners with importance-values.

PubMed

Gao, Linlin; Pan, Haiwei; Li, Qing; Xie, Xiaoqin; Zhang, Zhiqiang; Han, Jinming; Zhai, Xiao

2017-11-21

Brain disorders are one of the top causes of human death. Generally, neurologists analyze brain medical images for diagnosis. In the image analysis field, corners are one of the most important features, which makes corner detection and matching studies essential. However, existing corner detection studies do not consider the domain information of brain. This leads to many useless corners and the loss of significant information. Regarding corner matching, the uncertainty and structure of brain are not employed in existing methods. Moreover, most corner matching studies are used for 3D image registration. They are inapplicable for 2D brain image diagnosis because of the different mechanisms. To address these problems, we propose a novel corner-based brain medical image classification method. Specifically, we automatically extract multilayer texture images (MTIs) which embody diagnostic information from neurologists. Moreover, we present a corner matching method utilizing the uncertainty and structure of brain medical images and a bipartite graph model. Finally, we propose a similarity calculation method for diagnosis. Brain CT and MRI image sets are utilized to evaluate the proposed method. First, classifiers are trained in N-fold cross-validation analysis to produce the best θ and K. Then independent brain image sets are tested to evaluate the classifiers. Moreover, the classifiers are also compared with advanced brain image classification studies. For the brain CT image set, the proposed classifier outperforms the comparison methods by at least 8% on accuracy and 2.4% on F1-score. Regarding the brain MRI image set, the proposed classifier is superior to the comparison methods by more than 7.3% on accuracy and 4.9% on F1-score. Results also demonstrate that the proposed method is robust to different intensity ranges of brain medical image. In this study, we develop a robust corner-based brain medical image classifier. Specifically, we propose a corner detection method utilizing the diagnostic information from neurologists and a corner matching method based on the uncertainty and structure of brain medical images. Additionally, we present a similarity calculation method for brain image classification. Experimental results on two brain image sets show the proposed corner-based brain medical image classifier outperforms the state-of-the-art studies.

[Three-dimensional reconstruction of functional brain images].

PubMed

Inoue, M; Shoji, K; Kojima, H; Hirano, S; Naito, Y; Honjo, I

1999-08-01

We consider PET (positron emission tomography) measurement with SPM (Statistical Parametric Mapping) analysis to be one of the most useful methods to identify activated areas of the brain involved in language processing. SPM is an effective analytical method that detects markedly activated areas over the whole brain. However, with the conventional presentations of these functional brain images, such as horizontal slices, three directional projection, or brain surface coloring, makes understanding and interpreting the positional relationships among various brain areas difficult. Therefore, we developed three-dimensionally reconstructed images from these functional brain images to improve the interpretation. The subjects were 12 normal volunteers. The following three types of images were constructed: 1) routine images by SPM, 2) three-dimensional static images, and 3) three-dimensional dynamic images, after PET images were analyzed by SPM during daily dialog listening. The creation of images of both the three-dimensional static and dynamic types employed the volume rendering method by VTK (The Visualization Toolkit). Since the functional brain images did not include original brain images, we synthesized SPM and MRI brain images by self-made C++ programs. The three-dimensional dynamic images were made by sequencing static images with available software. Images of both the three-dimensional static and dynamic types were processed by a personal computer system. Our newly created images showed clearer positional relationships among activated brain areas compared to the conventional method. To date, functional brain images have been employed in fields such as neurology or neurosurgery, however, these images may be useful even in the field of otorhinolaryngology, to assess hearing and speech. Exact three-dimensional images based on functional brain images are important for exact and intuitive interpretation, and may lead to new developments in brain science. Currently, the surface model is the most common method of three-dimensional display. However, the volume rendering method may be more effective for imaging regions such as the brain.

Brain basis of early parent–infant interactions: psychology, physiology, and in vivo functional neuroimaging studies

PubMed Central

Swain, James E.; Lorberbaum, Jeffrey P.; Kose, Samet; Strathearn, Lane

2015-01-01

Parenting behavior critically shapes human infants’ current and future behavior. The parent–infant relationship provides infants with their first social experiences, forming templates of what they can expect from others and how to best meet others’ expectations. In this review, we focus on the neurobiology of parenting behavior, including our own functional magnetic resonance imaging (fMRI) brain imaging experiments of parents. We begin with a discussion of background, perspectives and caveats for considering the neurobiology of parent–infant relationships. Then, we discuss aspects of the psychology of parenting that are significantly motivating some of the more basic neuroscience research. Following that, we discuss some of the neurohormones that are important for the regulation of social bonding, and the dysregulation of parenting with cocaine abuse. Then, we review the brain circuitry underlying parenting, proceeding from relevant rodent and nonhuman primate research to human work. Finally, we focus on a study-by-study review of functional neuroimaging studies in humans. Taken together, this research suggests that networks of highly conserved hypothalamic–midbrain–limbic–paralimbic–cortical circuits act in concert to support aspects of parent response to infants, including the emotion, attention, motivation, empathy, decision-making and other thinking that are required to navigate the complexities of parenting. Specifically, infant stimuli activate basal forebrain regions, which regulate brain circuits that handle specific nurturing and caregiving responses and activate the brain’s more general circuitry for handling emotions, motivation, attention, and empathy – all of which are crucial for effective parenting. We argue that an integrated understanding of the brain basis of parenting has profound implications for mental health. PMID:17355399

MALDI Imaging Analysis of Neuropeptides in Africanized Honeybee (Apis mellifera) Brain: Effect of Aggressiveness.

PubMed

Pratavieira, Marcel; Menegasso, Anally Ribeiro da Silva; Esteves, Franciele Grego; Sato, Kenny Umino; Malaspina, Osmar; Palma, Mario Sérgio

2018-05-18

The aggressiveness in honeybees seems to be regulated by multiple genes, under the influence of different factors, such as polyethism of workers, environmental factors, and response to alarm pheromones, creating a series of behavioral responses. It is suspected that neuropeptides seem to be involved with the regulation of the aggressive behavior. The role of allatostatin and tachykinin-related neuropeptides in honeybee brain during the aggressive behavior is unknown; thus, worker honeybees were stimulated to attack and to sting leather targets hanged in front of the colonies. The aggressive individuals were collected and immediately frozen in liquid nitrogen; the heads were removed, and sliced at sagittal plan. The brain slices were submitted to MALDI-Spectral-Imaging analysis, and the results of the present study reported the processing of the precursors proteins into mature forms of the neuropeptides AmAST A (59-76) (AYTYVSEYKRLPVYNFGL-NH2), AmAST A (69-76) (LPVYNFGL-NH2), AmTRP (88 - 96) (APMGFQGMR-NH2), and AmTRP (254 - 262) (ARMGFHGMR-NH2), which apparently acted in different neuropils of honeybee brain, during the aggressive behavior, possibly playing the neuromodulation of different aspects of this complex behavior. These results were biologically validated performing aggressiveness-related behavioral assays, using young honeybee workers that received 1 ng of AmAST A (69-76) or AmTRP (88 - 96) via hemocele. The young workers that were not expected to be aggressive individuals, presented a complete series of the aggressive behaviors, in presence of the neuropeptides, corroborating the hypothesis that correlates the presence of mature AmASTs A and AmTRPs in honeybee brain with the aggressiveness of this insect.

A Multifaceted Mass Spectrometric Method to Probe Feeding Related Neuropeptide Changes in Callinectes sapidus and Carcinus maenas

NASA Astrophysics Data System (ADS)

Zhang, Yuzhuo; DeLaney, Kellen; Hui, Limei; Wang, Junhua; Sturm, Robert M.; Li, Lingjun

2018-02-01

Food intake is regulated by various neuromodulators, including numerous neuropeptides. However, it remains elusive at the molecular and cellular level as to how these important chemicals regulate internal processes and which regions of the neuronal organs are responsible for regulating the behavior. Here we report a comparative neuropeptidomic analysis of the brain and pericardial organ (PO) in response to feeding in two well-studied crustacean physiology model organisms, Callinectes sapidus and Carcinus maenas, using mass spectrometry (MS) techniques. A multifaceted MS-based approach has been developed to obtain complementary information on the expression changes of a large array of neuropeptides in the brain and PO. The method employs stable isotope labeling of brain and PO extracts for relative MS quantitation, capillary electrophoresis (CE)-MS for fractionation and high-specificity analysis, and mass spectrometric imaging (MSI) for in-situ molecular mapping of peptides. A number of neuropeptides, including RFamides, B-type allatostatins (AST-B), RYamides, and orcokinins exhibit significant changes in abundance after feeding in this investigation. Peptides from the AST-B family found in PO tissue were shown to have both altered expression and localization changes after feeding, indicating that they may be a class of vital neuropeptide regulators involved in feeding behavior. [Figure not available: see fulltext.

A Multifaceted Mass Spectrometric Method to Probe Feeding Related Neuropeptide Changes in Callinectes sapidus and Carcinus maenas

NASA Astrophysics Data System (ADS)

Zhang, Yuzhuo; DeLaney, Kellen; Hui, Limei; Wang, Junhua; Sturm, Robert M.; Li, Lingjun

2018-05-01

Food intake is regulated by various neuromodulators, including numerous neuropeptides. However, it remains elusive at the molecular and cellular level as to how these important chemicals regulate internal processes and which regions of the neuronal organs are responsible for regulating the behavior. Here we report a comparative neuropeptidomic analysis of the brain and pericardial organ (PO) in response to feeding in two well-studied crustacean physiology model organisms, Callinectes sapidus and Carcinus maenas, using mass spectrometry (MS) techniques. A multifaceted MS-based approach has been developed to obtain complementary information on the expression changes of a large array of neuropeptides in the brain and PO. The method employs stable isotope labeling of brain and PO extracts for relative MS quantitation, capillary electrophoresis (CE)-MS for fractionation and high-specificity analysis, and mass spectrometric imaging (MSI) for in-situ molecular mapping of peptides. A number of neuropeptides, including RFamides, B-type allatostatins (AST-B), RYamides, and orcokinins exhibit significant changes in abundance after feeding in this investigation. Peptides from the AST-B family found in PO tissue were shown to have both altered expression and localization changes after feeding, indicating that they may be a class of vital neuropeptide regulators involved in feeding behavior. [Figure not available: see fulltext.

A Multifaceted Mass Spectrometric Method to Probe Feeding Related Neuropeptide Changes in Callinectes sapidus and Carcinus maenas.

PubMed

Zhang, Yuzhuo; DeLaney, Kellen; Hui, Limei; Wang, Junhua; Sturm, Robert M; Li, Lingjun

2018-05-01

Food intake is regulated by various neuromodulators, including numerous neuropeptides. However, it remains elusive at the molecular and cellular level as to how these important chemicals regulate internal processes and which regions of the neuronal organs are responsible for regulating the behavior. Here we report a comparative neuropeptidomic analysis of the brain and pericardial organ (PO) in response to feeding in two well-studied crustacean physiology model organisms, Callinectes sapidus and Carcinus maenas, using mass spectrometry (MS) techniques. A multifaceted MS-based approach has been developed to obtain complementary information on the expression changes of a large array of neuropeptides in the brain and PO. The method employs stable isotope labeling of brain and PO extracts for relative MS quantitation, capillary electrophoresis (CE)-MS for fractionation and high-specificity analysis, and mass spectrometric imaging (MSI) for in-situ molecular mapping of peptides. A number of neuropeptides, including RFamides, B-type allatostatins (AST-B), RYamides, and orcokinins exhibit significant changes in abundance after feeding in this investigation. Peptides from the AST-B family found in PO tissue were shown to have both altered expression and localization changes after feeding, indicating that they may be a class of vital neuropeptide regulators involved in feeding behavior. Graphical Abstract ᅟ.

Brain response to images of food varying in energy density is associated with body composition in 7- to 10-year-old children: Results of an exploratory study.

PubMed

Fearnbach, S Nicole; English, Laural K; Lasschuijt, Marlou; Wilson, Stephen J; Savage, Jennifer S; Fisher, Jennifer O; Rolls, Barbara J; Keller, Kathleen L

2016-08-01

Energy balance is regulated by a multifaceted system of physiological signals that influence energy intake and expenditure. Therefore, variability in the brain's response to food may be partially explained by differences in levels of metabolically active tissues throughout the body, including fat-free mass (FFM) and fat mass (FM). The purpose of this study was to test the hypothesis that children's body composition would be related to their brain response to food images varying in energy density (ED), a measure of energy content per weight of food. Functional magnetic resonance imaging (fMRI) was used to measure brain response to High (>1.5kcal/g) and Low (<1.5kcal/g) ED food images, and Control images, in 36 children ages 7-10years. Body composition was measured using bioelectrical impedance analysis. Multi-subject random effects general linear model (GLM) and two-factor repeated measures analysis of variance (ANOVA) were used to test for main effects of ED (High ED vs. Low ED) in a priori defined brain regions of interest previously implicated in energy homeostasis and reward processing. Pearson's correlations were then calculated between activation in these regions for various contrasts (High ED-Low ED, High ED-Control, Low ED-Control) and child body composition (FFM index, FM index, % body fat). Relative to Low ED foods, High ED foods elicited greater BOLD activation in the left thalamus. In the right substantia nigra, BOLD activation for the contrast of High ED-Low ED foods was positively associated with child FFM. There were no significant results for the High ED-Control or Low ED-Control contrasts. Our findings support literature on FFM as an appetitive driver, such that greater amounts of lean mass were associated with greater activation for High ED foods in an area of the brain associated with dopamine signaling and reward (substantia nigra). These results confirm our hypothesis that brain response to foods varying in energy content is related to measures of child body composition. Copyright © 2016 Elsevier Inc. All rights reserved.

Activation of prefrontal cortex and anterior thalamus in alcoholic subjects on exposure to alcohol-specific cues.

PubMed

George, M S; Anton, R F; Bloomer, C; Teneback, C; Drobes, D J; Lorberbaum, J P; Nahas, Z; Vincent, D J

2001-04-01

Functional imaging studies have recently demonstrated that specific brain regions become active in cocaine addicts when they are exposed to cocaine stimuli. To test whether there are regional brain activity differences during alcohol cue exposure between alcoholic subjects and social drinkers, we designed a functional magnetic resonance imaging (fMRI) protocol involving alcohol-specific cues. Ten non-treatment-seeking adult alcoholic subjects (2 women) (mean [SD] age, 29.9 [9.9] years) as well as 10 healthy social drinking controls of similar age (2 women) (mean [SD] age, 29.4 [8.9] years) were recruited, screened, and scanned. In the 1.5-T magnetic resonance imaging scanner, subjects were serially rated for alcohol craving before and after a sip of alcohol, and after a 9-minute randomized presentation of pictures of alcoholic beverages, control nonalcoholic beverages, and 2 different visual control tasks. During picture presentation, changes in regional brain activity were measured with the blood oxygen level-dependent technique. Alcoholic subjects, compared with the social drinking subjects, reported higher overall craving ratings for alcohol. After a sip of alcohol, while viewing alcohol cues compared with viewing other beverage cues, only the alcoholic subjects had increased activity in the left dorsolateral prefrontal cortex and the anterior thalamus. The social drinkers exhibited specific activation only while viewing the control beverage pictures. When exposed to alcohol cues, alcoholic subjects have increased brain activity in the prefrontal cortex and anterior thalamus-brain regions associated with emotion regulation, attention, and appetitive behavior.

Discovery of a highly selective glycogen synthase kinase-3 inhibitor (PF-04802367) that modulates tau phosphorylation in brain: Translation for PET neuroimaging

PubMed Central

Liang, Steven H.; Chen, Jinshan Michael; Normandin, Marc D.; Chang, Jeanne S.; Chang, George C.; Taylor, Christine K.; Trapa, Patrick; Plummer, Mark S.; Para, Kimberly S.; Conn, Edward L.; Lopresti-Morrow, Lori; Lanyon, Lorraine F.; Cook, James M.; Richter, Karl E. G.; Nolan, Charlie E.; Schachter, Joel B.; Janat, Fouad; Che, Ye; Shanmugasundaram, Veerabahu; Lefker, Bruce A.; Enerson, Bradley E.; Livni, Elijahu; Wang, Lu; Guehl, Nicolas; Patnaik, Debasis; Wagner, Florence F.; Perlis, Roy; Holson, Edward B.; Haggarty, Stephen J.; Fakhri, Georges El

2016-01-01

Glycogen synthase kinase-3 (GSK-3) regulates multiple cellular processes in diabetes, oncology and neurology. We have identified N-(3-(1H-1,2,4-triazol-1-yl)propyl)-5-(3-chloro-4-methoxyphenyl)oxazole-4-carboxamide (PF-04802367 or PF-367) as a highly potent inhibitor, which is among the most selective antagonists of GSK-3 to date. We demonstrated its efficacy in modulation of tau phosphorylation in vitro and in vivo. Whereas the kinetics of PF-367 binding in brain tissues are too fast for an effective therapeutic agent, the pharmacokinetic profile of PF-367 is ideal for discovery of radiopharmaceuticals for GSK-3 in the central nervous system. A 11C-isotopologue of PF-367 was synthesized and preliminary PET imaging studies in non-human primates confirmed that we have overcome the two major obstacles for imaging GSK-3, namely, reasonable brain permeability and displaceable binding. PMID:27355874

[11C]PF-3274167 as a PET radiotracer of oxytocin receptors: Radiosynthesis and evaluation in rat brain.

PubMed

Vidal, Benjamin; Karpenko, Iuliia A; Liger, François; Fieux, Sylvain; Bouillot, Caroline; Billard, Thierry; Hibert, Marcel; Zimmer, Luc

2017-12-01

Oxytocin plays a major role in the regulation of social interactions in mammals by interacting with the oxytocin receptor (OTR) expressed in the brain. Furthermore, the oxytocin system appears as a possible therapeutic target in autism spectrum disorders and other psychiatric troubles, justifying current pharmacological researches. Since no specific PET radioligand is currently available to image OTR in the brain, the aim of this study was to radiolabel the specific OTR antagonist PF-3274167 and to evaluate [ 11 C]PF-3274167 as a potential PET tracer for OTR in rat brains. [ 11 C]PF-3274167 was prepared via the O-methylation of its desmethyl precursor with [ 11 C]methyl iodide. The lipophilicity of the radioactive compound was evaluated by measuring the n-octanol-buffer partition coefficient (logD). Autoradiography experiments were performed on rat brain tissue to evaluate the in vitro distribution of the [ 11 C]PF-3274167. MicroPET experiments were conducted with and without pre-injection of ciclosporin in order to evaluate the influence of the P-glycoprotein (P-gp) on the brain uptake. [ 11 C]PF-3274167 was synthesized with high radiochemical and chemical purities (>95%) and good specific activity. The measured logD was 1.93. In vitro, [ 11 C]PF-3274167 did not show any evidence of specific binding to OTR. PET imaging showed that [ 11 C]PF-3274167 uptake in rat brain was very low in basal conditions but increased significantly after the administration of ciclosporin, suggesting that it is a substrate of the P-gp. In the ciclosporin-pre-injected rat, however, [ 11 C]PF-3274167 distribution did not match with the known distribution of OTR in rats. [ 11 C]PF-3274167 is not a suitable tracer for imaging of OTR in rat brain, probably because of a too low affinity for this receptor in addition to a poor brain penetration. Copyright © 2017 Elsevier Inc. All rights reserved.

Prediction of standard-dose brain PET image by using MRI and low-dose brain [18F]FDG PET images.

PubMed

Kang, Jiayin; Gao, Yaozong; Shi, Feng; Lalush, David S; Lin, Weili; Shen, Dinggang

2015-09-01

Positron emission tomography (PET) is a nuclear medical imaging technology that produces 3D images reflecting tissue metabolic activity in human body. PET has been widely used in various clinical applications, such as in diagnosis of brain disorders. High-quality PET images play an essential role in diagnosing brain diseases/disorders. In practice, in order to obtain high-quality PET images, a standard-dose radionuclide (tracer) needs to be used and injected into a living body. As a result, it will inevitably increase the patient's exposure to radiation. One solution to solve this problem is predicting standard-dose PET images using low-dose PET images. As yet, no previous studies with this approach have been reported. Accordingly, in this paper, the authors propose a regression forest based framework for predicting a standard-dose brain [(18)F]FDG PET image by using a low-dose brain [(18)F]FDG PET image and its corresponding magnetic resonance imaging (MRI) image. The authors employ a regression forest for predicting the standard-dose brain [(18)F]FDG PET image by low-dose brain [(18)F]FDG PET and MRI images. Specifically, the proposed method consists of two main steps. First, based on the segmented brain tissues (i.e., cerebrospinal fluid, gray matter, and white matter) in the MRI image, the authors extract features for each patch in the brain image from both low-dose PET and MRI images to build tissue-specific models that can be used to initially predict standard-dose brain [(18)F]FDG PET images. Second, an iterative refinement strategy, via estimating the predicted image difference, is used to further improve the prediction accuracy. The authors evaluated their algorithm on a brain dataset, consisting of 11 subjects with MRI, low-dose PET, and standard-dose PET images, using leave-one-out cross-validations. The proposed algorithm gives promising results with well-estimated standard-dose brain [(18)F]FDG PET image and substantially enhanced image quality of low-dose brain [(18)F]FDG PET image. In this paper, the authors propose a framework to generate standard-dose brain [(18)F]FDG PET image using low-dose brain [(18)F]FDG PET and MRI images. Both the visual and quantitative results indicate that the standard-dose brain [(18)F]FDG PET can be well-predicted using MRI and low-dose brain [(18)F]FDG PET.

Prediction of standard-dose brain PET image by using MRI and low-dose brain [18F]FDG PET images

PubMed Central

Kang, Jiayin; Gao, Yaozong; Shi, Feng; Lalush, David S.; Lin, Weili; Shen, Dinggang

2015-01-01

Purpose: Positron emission tomography (PET) is a nuclear medical imaging technology that produces 3D images reflecting tissue metabolic activity in human body. PET has been widely used in various clinical applications, such as in diagnosis of brain disorders. High-quality PET images play an essential role in diagnosing brain diseases/disorders. In practice, in order to obtain high-quality PET images, a standard-dose radionuclide (tracer) needs to be used and injected into a living body. As a result, it will inevitably increase the patient’s exposure to radiation. One solution to solve this problem is predicting standard-dose PET images using low-dose PET images. As yet, no previous studies with this approach have been reported. Accordingly, in this paper, the authors propose a regression forest based framework for predicting a standard-dose brain [18F]FDG PET image by using a low-dose brain [18F]FDG PET image and its corresponding magnetic resonance imaging (MRI) image. Methods: The authors employ a regression forest for predicting the standard-dose brain [18F]FDG PET image by low-dose brain [18F]FDG PET and MRI images. Specifically, the proposed method consists of two main steps. First, based on the segmented brain tissues (i.e., cerebrospinal fluid, gray matter, and white matter) in the MRI image, the authors extract features for each patch in the brain image from both low-dose PET and MRI images to build tissue-specific models that can be used to initially predict standard-dose brain [18F]FDG PET images. Second, an iterative refinement strategy, via estimating the predicted image difference, is used to further improve the prediction accuracy. Results: The authors evaluated their algorithm on a brain dataset, consisting of 11 subjects with MRI, low-dose PET, and standard-dose PET images, using leave-one-out cross-validations. The proposed algorithm gives promising results with well-estimated standard-dose brain [18F]FDG PET image and substantially enhanced image quality of low-dose brain [18F]FDG PET image. Conclusions: In this paper, the authors propose a framework to generate standard-dose brain [18F]FDG PET image using low-dose brain [18F]FDG PET and MRI images. Both the visual and quantitative results indicate that the standard-dose brain [18F]FDG PET can be well-predicted using MRI and low-dose brain [18F]FDG PET. PMID:26328979

Prediction of standard-dose brain PET image by using MRI and low-dose brain [{sup 18}F]FDG PET images

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kang, Jiayin; Gao, Yaozong; Shi, Feng

Purpose: Positron emission tomography (PET) is a nuclear medical imaging technology that produces 3D images reflecting tissue metabolic activity in human body. PET has been widely used in various clinical applications, such as in diagnosis of brain disorders. High-quality PET images play an essential role in diagnosing brain diseases/disorders. In practice, in order to obtain high-quality PET images, a standard-dose radionuclide (tracer) needs to be used and injected into a living body. As a result, it will inevitably increase the patient’s exposure to radiation. One solution to solve this problem is predicting standard-dose PET images using low-dose PET images. Asmore » yet, no previous studies with this approach have been reported. Accordingly, in this paper, the authors propose a regression forest based framework for predicting a standard-dose brain [{sup 18}F]FDG PET image by using a low-dose brain [{sup 18}F]FDG PET image and its corresponding magnetic resonance imaging (MRI) image. Methods: The authors employ a regression forest for predicting the standard-dose brain [{sup 18}F]FDG PET image by low-dose brain [{sup 18}F]FDG PET and MRI images. Specifically, the proposed method consists of two main steps. First, based on the segmented brain tissues (i.e., cerebrospinal fluid, gray matter, and white matter) in the MRI image, the authors extract features for each patch in the brain image from both low-dose PET and MRI images to build tissue-specific models that can be used to initially predict standard-dose brain [{sup 18}F]FDG PET images. Second, an iterative refinement strategy, via estimating the predicted image difference, is used to further improve the prediction accuracy. Results: The authors evaluated their algorithm on a brain dataset, consisting of 11 subjects with MRI, low-dose PET, and standard-dose PET images, using leave-one-out cross-validations. The proposed algorithm gives promising results with well-estimated standard-dose brain [{sup 18}F]FDG PET image and substantially enhanced image quality of low-dose brain [{sup 18}F]FDG PET image. Conclusions: In this paper, the authors propose a framework to generate standard-dose brain [{sup 18}F]FDG PET image using low-dose brain [{sup 18}F]FDG PET and MRI images. Both the visual and quantitative results indicate that the standard-dose brain [{sup 18}F]FDG PET can be well-predicted using MRI and low-dose brain [{sup 18}F]FDG PET.« less

Functional Magnetic Resonance Imaging with Concurrent Urodynamic Testing Identifies Brain Structures Involved in Micturition Cycle in Patients with Multiple Sclerosis.

PubMed

Khavari, Rose; Karmonik, Christof; Shy, Michael; Fletcher, Sophie; Boone, Timothy

2017-02-01

Neurogenic lower urinary tract dysfunction, which is common in patients with multiple sclerosis, has a significant impact on quality of life. In this study we sought to determine brain activity processes during the micturition cycle in female patients with multiple sclerosis and neurogenic lower urinary tract dysfunction. We report brain activity on functional magnetic resonance imaging and simultaneous urodynamic testing in 23 ambulatory female patients with multiple sclerosis. Individual functional magnetic resonance imaging activation maps at strong desire to void and at initiation of voiding were calculated and averaged at Montreal Neuroimaging Institute. Areas of significant activation were identified in these average maps. Subgroup analysis was performed in patients with elicitable neurogenic detrusor overactivity or detrusor-sphincter dyssynergia. Group analysis of all patients at strong desire to void yielded areas of activation in regions associated with executive function (frontal gyrus), emotional regulation (cingulate gyrus) and motor control (putamen, cerebellum and precuneus). Comparison of the average change in activation between previously reported healthy controls and patients with multiple sclerosis showed predominantly stronger, more focal activation in the former and lower, more diffused activation in the latter. Patients with multiple sclerosis who had demonstrable neurogenic detrusor overactivity and detrusor-sphincter dyssynergia showed a trend toward distinct brain activation at full urge and at initiation of voiding respectively. We successfully studied brain activation during the entire micturition cycle in female patients with neurogenic lower urinary tract dysfunction and multiple sclerosis using a concurrent functional magnetic resonance imaging/urodynamic testing platform. Understanding the central neural processes involved in specific parts of micturition in patients with neurogenic lower urinary tract dysfunction may identify areas of interest for future intervention. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Cognitive and neural contributors to emotion regulation in aging

PubMed Central

Winecoff, Amy; LaBar, Kevin S.; Madden, David J.; Cabeza, Roberto

2011-01-01

Older adults, compared to younger adults, focus on emotional well-being. While the lifespan trajectory of emotional processing and its regulation has been characterized behaviorally, few studies have investigated the underlying neural mechanisms. Here, older adults (range: 59–73 years) and younger adults (range: 19–33 years) participated in a cognitive reappraisal task during functional magnetic resonance imaging (fMRI) scanning. On each trial, participants viewed positive, negative or neutral pictures and either naturally experienced the image (‘Experience’ condition) or attempted to detach themselves from the image (‘Reappraise’ condition). Across both age groups, cognitive reappraisal activated prefrontal regions similar to those reported in prior studies of emotion regulation, while emotional experience activated the bilateral amygdala. Psychophysiological interaction analyses revealed that the left inferior frontal gyrus (IFG) and amygdala demonstrated greater inverse connectivity during the ‘Reappraise’ condition relative to the ‘Experience’ condition. The only regions exhibiting significant age differences were the left IFG and the left superior temporal gyrus, for which greater regulation-related activation was observed in younger adults. Controlling for age, increased performance on measures of cognition predicted greater regulation-related decreases in amygdala activation. Thus, while older and younger adults use similar brain structures for emotion regulation and experience, the functional efficacy of those structures depends on underlying cognitive ability. PMID:20385663

Targeting neurotransmitter receptors with nanoparticles in vivo allows single-molecule tracking in acute brain slices

NASA Astrophysics Data System (ADS)

Varela, Juan A.; Dupuis, Julien P.; Etchepare, Laetitia; Espana, Agnès; Cognet, Laurent; Groc, Laurent

2016-03-01

Single-molecule imaging has changed the way we understand many biological mechanisms, particularly in neurobiology, by shedding light on intricate molecular events down to the nanoscale. However, current single-molecule studies in neuroscience have been limited to cultured neurons or organotypic slices, leaving as an open question the existence of fast receptor diffusion in intact brain tissue. Here, for the first time, we targeted dopamine receptors in vivo with functionalized quantum dots and were able to perform single-molecule tracking in acute rat brain slices. We propose a novel delocalized and non-inflammatory way of delivering nanoparticles (NPs) in vivo to the brain, which allowed us to label and track genetically engineered surface dopamine receptors in neocortical neurons, revealing inherent behaviour and receptor activity regulations. We thus propose a NP-based platform for single-molecule studies in the living brain, opening new avenues of research in physiological and pathological animal models.

In vivo metabolic labeling of sialoglycans in the mouse brain by using a liposome-assisted bioorthogonal reporter strategy

PubMed Central

Xie, Ran; Dong, Lu; Du, Yifei; Zhu, Yuntao; Hua, Rui; Zhang, Chen; Chen, Xing

2016-01-01

Mammalian brains are highly enriched with sialoglycans, which have been implicated in brain development and disease progression. However, in vivo labeling and visualization of sialoglycans in the mouse brain remain a challenge because of the blood−brain barrier. Here we introduce a liposome-assisted bioorthogonal reporter (LABOR) strategy for shuttling 9-azido sialic acid (9AzSia), a sialic acid reporter, into the brain to metabolically label sialoglycoconjugates, including sialylated glycoproteins and glycolipids. Subsequent bioorthogonal conjugation of the incorporated 9AzSia with fluorescent probes via click chemistry enabled fluorescence imaging of brain sialoglycans in living animals and in brain sections. Newly synthesized sialoglycans were found to widely distribute on neuronal cell surfaces, in particular at synaptic sites. Furthermore, large-scale proteomic profiling identified 140 brain sialylated glycoproteins, including a wealth of synapse-associated proteins. Finally, by performing a pulse−chase experiment, we showed that dynamic sialylation is spatially regulated, and that turnover of sialoglycans in the hippocampus is significantly slower than that in other brain regions. The LABOR strategy provides a means to directly visualize and monitor the sialoglycan biosynthesis in the mouse brain and will facilitate elucidating the functional role of brain sialylation. PMID:27125855

Visual assessment of brain magnetic resonance imaging detects injury to cognitive regulatory sites in patients with heart failure.

PubMed

Pan, Alan; Kumar, Rajesh; Macey, Paul M; Fonarow, Gregg C; Harper, Ronald M; Woo, Mary A

2013-02-01

Heart failure (HF) patients exhibit depression and executive function impairments that contribute to HF mortality. Using specialized magnetic resonance imaging (MRI) analysis procedures, brain changes appear in areas regulating these functions (mammillary bodies, hippocampi, and frontal cortex). However, specialized MRI procedures are not part of standard clinical assessment for HF (which is usually a visual evaluation), and it is unclear whether visual MRI examination can detect changes in these structures. Using brain MRI, we visually examined the mammillary bodies and frontal cortex for global and hippocampi for global and regional tissue changes in 17 HF and 50 control subjects. Significantly global changes emerged in the right mammillary body (HF 1.18 ± 1.13 vs control 0.52 ± 0.74; P = .024), right hippocampus (HF 1.53 ± 0.94 vs control 0.80 ± 0.86; P = .005), and left frontal cortex (HF 1.76 ± 1.03 vs control 1.24 ± 0.77; P = .034). Comparison of the visual method with specialized MRI techniques corroborates right hippocampal and left frontal cortical, but not mammillary body, tissue changes. Visual examination of brain MRI can detect damage in HF in areas regulating depression and executive function, including the right hippocampus and left frontal cortex. Visual MRI assessment in HF may facilitate evaluation of injury to these structures and the assessment of the impact of potential treatments for this damage. Copyright © 2013 Elsevier Inc. All rights reserved.

Pain anticipation: an activation likelihood estimation meta-analysis of brain imaging studies.

PubMed

Palermo, Sara; Benedetti, Fabrizio; Costa, Tommaso; Amanzio, Martina

2015-05-01

The anticipation of pain has been investigated in a variety of brain imaging studies. Importantly, today there is no clear overall picture of the areas that are involved in different studies and the exact role of these regions in pain expectation remains especially unexploited. To address this issue, we used activation likelihood estimation meta-analysis to analyze pain anticipation in several neuroimaging studies. A total of 19 functional magnetic resonance imaging were included in the analysis to search for the cortical areas involved in pain anticipation in human experimental models. During anticipation, activated foci were found in the dorsolateral prefrontal, midcingulate and anterior insula cortices, medial and inferior frontal gyri, inferior parietal lobule, middle and superior temporal gyrus, thalamus, and caudate. Deactivated foci were found in the anterior cingulate, superior frontal gyrus, parahippocampal gyrus and in the claustrum. The results of the meta-analytic connectivity analysis provide an overall view of the brain responses triggered by the anticipation of a noxious stimulus. Such a highly distributed perceptual set of self-regulation may prime brain regions to process information where emotion, action and perception as well as their related subcategories play a central role. Not only do these findings provide important information on the neural events when anticipating pain, but also they may give a perspective into nocebo responses, whereby negative expectations may lead to pain worsening. © 2014 Wiley Periodicals, Inc.

Brain Imaging and Behavioral Outcome in Traumatic Brain Injury.

ERIC Educational Resources Information Center

Bigler, Erin D.

1996-01-01

This review explores the cellular pathology associated with traumatic brain injury (TBI) and its relation to neurobehavioral outcomes, the relationship of brain imaging findings to underlying pathology, brain imaging techniques, various image analysis procedures and how they relate to neuropsychological testing, and the importance of brain imaging…

Multiple faces of pain: effects of chronic pain on the brain regulation of facial expression

PubMed Central

Vachon-Presseau, Etienne; Roy, Mathieu; Woo, Choong-Wan; Kunz, Miriam; Martel, Marc-Olivier; Sullivan, Michael J.; Jackson, Philip L.; Wager, Tor D.; Rainville, Pierre

2018-01-01

Pain behaviors are shaped by social demands and learning processes, and chronic pain has been previously suggested to affect their meaning. In this study, we combined functional magnetic resonance imaging with in-scanner video recording during thermal pain stimulations and use multilevel mediation analyses to study the brain mediators of pain facial expressions and the perception of pain intensity (self-reports) in healthy individuals and patients with chronic back pain (CBP). Behavioral data showed that the relation between pain expression and pain report was disrupted in CBP. In both patients with CBP and healthy controls, brain activity varying on a trial-by-trial basis with pain facial expressions was mainly located in the primary motor cortex and completely dissociated from the pattern of brain activity varying with pain intensity ratings. Stronger activity was observed in CBP specifically during pain facial expressions in several nonmotor brain regions such as the medial prefrontal cortex, the precuneus, and the medial temporal lobe. In sharp contrast, no moderating effect of chronic pain was observed on brain activity associated with pain intensity ratings. Our results demonstrate that pain facial expressions and pain intensity ratings reflect different aspects of pain processing and support psychosocial models of pain suggesting that distinctive mechanisms are involved in the regulation of pain behaviors in chronic pain. PMID:27411160

Amygdala Response and Functional Connectivity During Emotion Regulation: A Study of 14 Depressed Adolescents

PubMed Central

Perlman, Greg; Simmons, Alan N.; Wu, Jing; Hahn, Kevin S.; Tapert, Susan F.; Max, Jeffrey E.; Paulus, Martin P.; Brown, Gregory G.; Frank, Guido K.; Campbell-Sills, Laura; Yang, Tony T.

2012-01-01

Background Ineffective emotion regulation and abnormal amygdala activation have each been found in adolescent-onset major depressive disorder. However, amygdala activation during emotion regulation has not been studied in adolescent-onset major depressive disorder. Method Fourteen unmedicated adolescents diagnosed with current depression without comorbid psychiatric disorders and fourteen well-matched controls ages 13 to 17 years underwent an emotional regulation task during functional magnetic resonance imaging. During this task, participants viewed negatively-valence images and were asked to notice how they were feeling without trying to change it and maintain their emotional reaction (“Maintain”) or to interpret the image in such a way as minimize their emotional response (“Reduce”). Results Imaging analyses demonstrated that adolescents with depression showed: (1) greater right amygdala activation during the maintain condition relative to controls, (2) less connectivity during the maintain condition between the amygdala and both the insula and medial prefrontal cortex than controls, and (3) a significant positive correlation between amygdala-seeded connectivity during maintenance of emotion and psychosocial functioning. Limitations The current study is cross-sectional comparison and longitudinal investigations with larger sample sizes are needed to examine the association between amygdala reactivity and emotion regulation over time in adolescent MDD. Conclusions During the maintain condition, adolescents with depression showed a heightened amygdala response and less reciprocal activation in brain regions that may modulate the amygdala. A poorly modulated, overreactive amygdala may contribute to poor emotion regulation. PMID:22401827

On the nature and evolution of the neural bases of human language

NASA Technical Reports Server (NTRS)

Lieberman, Philip

2002-01-01

The traditional theory equating the brain bases of language with Broca's and Wernicke's neocortical areas is wrong. Neural circuits linking activity in anatomically segregated populations of neurons in subcortical structures and the neocortex throughout the human brain regulate complex behaviors such as walking, talking, and comprehending the meaning of sentences. When we hear or read a word, neural structures involved in the perception or real-world associations of the word are activated as well as posterior cortical regions adjacent to Wernicke's area. Many areas of the neocortex and subcortical structures support the cortical-striatal-cortical circuits that confer complex syntactic ability, speech production, and a large vocabulary. However, many of these structures also form part of the neural circuits regulating other aspects of behavior. For example, the basal ganglia, which regulate motor control, are also crucial elements in the circuits that confer human linguistic ability and abstract reasoning. The cerebellum, traditionally associated with motor control, is active in motor learning. The basal ganglia are also key elements in reward-based learning. Data from studies of Broca's aphasia, Parkinson's disease, hypoxia, focal brain damage, and a genetically transmitted brain anomaly (the putative "language gene," family KE), and from comparative studies of the brains and behavior of other species, demonstrate that the basal ganglia sequence the discrete elements that constitute a complete motor act, syntactic process, or thought process. Imaging studies of intact human subjects and electrophysiologic and tracer studies of the brains and behavior of other species confirm these findings. As Dobzansky put it, "Nothing in biology makes sense except in the light of evolution" (cited in Mayr, 1982). That applies with as much force to the human brain and the neural bases of language as it does to the human foot or jaw. The converse follows: the mark of evolution on the brains of human beings and other species provides insight into the evolution of the brain bases of human language. The neural substrate that regulated motor control in the common ancestor of apes and humans most likely was modified to enhance cognitive and linguistic ability. Speech communication played a central role in this process. However, the process that ultimately resulted in the human brain may have started when our earliest hominid ancestors began to walk.

Neuroendocrinology and brain imaging of reward in eating disorders: A possible key to the treatment of anorexia nervosa and bulimia nervosa.

PubMed

Monteleone, Alessio Maria; Castellini, Giovanni; Volpe, Umberto; Ricca, Valdo; Lelli, Lorenzo; Monteleone, Palmiero; Maj, Mario

2018-01-03

Anorexia nervosa and bulimia nervosa are severe eating disorders whose etiopathogenesis is still unknown. Clinical features suggest that eating disorders may develop as reward-dependent syndromes, since eating less food is perceived as rewarding in anorexia nervosa while consumption of large amounts of food during binge episodes in bulimia nervosa aims at reducing the patient's negative emotional states. Therefore, brain reward mechanisms have been a major focus of research in the attempt to contribute to the comprehension of the pathophysiology of these disorders. Structural brain imaging data provided the evidence that brain reward circuits may be altered in patients with anorexia or bulimia nervosa. Similarly, functional brain imaging studies exploring the activation of brain reward circuits by food stimuli as well as by stimuli recognized to be potentially rewarding for eating disordered patients, such as body image cues or stimuli related to food deprivation and physical hyperactivity, showed several dysfunctions in ED patients. Moreover, very recently, it has been demonstrated that some of the biochemical homeostatic modulators of eating behavior are also implicated in the regulation of food-related and non-food-related reward, representing a possible link between the aberrant behaviors of ED subjects and their hypothesized deranged reward processes. In particular, changes in leptin and ghrelin occur in patients with anorexia or bulimia nervosa and have been suggested to represent not only homeostatic adaptations to an altered energy balance but to contribute also to the acquisition and/or maintenance of persistent starvation, binge eating and physical hyperactivity, which are potentially rewarding for ED patients. On the basis of such findings new pathogenetic models of EDs have been proposed, and these models may provide new theoretical basis for the development of innovative treatment strategies, either psychological and pharmacological, with the aim to improve the outcomes of so severe disabling disorders. Copyright © 2017 Elsevier Inc. All rights reserved.

BDNF and BMI effects on brain structures of bipolar offspring: results from the global mood and brain science initiative.

PubMed

Mansur, R B; Brietzke, E; McIntyre, R S; Cao, B; Lee, Y; Japiassú, L; Chen, K; Lu, R; Lu, W; Li, T; Xu, G; Lin, K

2017-12-01

To compare brain-derived neurotrophic factor (BDNF) levels between offspring of individuals with bipolar disorders (BD) and healthy controls (HCs) and investigate the effects of BDNF levels and body mass index (BMI) on brain structures. Sixty-seven bipolar offspring and 45 HCs were included (ages 8-28). Structural images were acquired using 3.0 Tesla magnetic resonance imaging. Serum BDNF levels were measured using enzyme-linked immunosorbent assay. Multivariate and univariate analyses of covariance were conducted. Significantly higher BDNF levels were observed among bipolar offspring, relative to HCs (P > 0.025). Offspring status moderated the association between BDNF and BMI (F 1 =4.636, P = 0.034). After adjustment for relevant covariates, there was a trend for a significant interaction of group and BDNF on neuroimaging parameters (Wilks'λ F 56,94 =1.463, P = 0.052), with significant effects on cerebellar white matter and superior and middle frontal regions. Brain volume and BDNF were positively correlated among HCs and negatively correlated among bipolar offspring. Interactions between BDNF and BMI on brain volumes were non-significant among HCs (Wilks'λ F 28,2 =2.229, P = 0.357), but significant among bipolar offspring (Wilks'λ F 28,12 =2.899, P = 0.028). Offspring status and BMI moderate the association between BDNF levels and brain structures among bipolar offspring, underscoring BDNF regulation and overweight/obesity as key moderators of BD pathogenesis. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Emotion introspection and regulation in depression.

PubMed

Herwig, Uwe; Opialla, Sarah; Cattapan, Katja; Wetter, Thomas C; Jäncke, Lutz; Brühl, Annette B

2018-07-30

Depressed patients suffer from an impairment to voluntarily influence and regulate their unpleasant emotional state. Strengthening the mental ability to interfere with dysfunctional emotion processing may be beneficial in treating depression. According to models of emotion processing this may be done by successful down-regulation of enhanced amygdala activity. We investigated short periods of intentional emotion-introspection compared with cognitive self-reflection as two domains of self-awareness in terms of effects on emotion regulation. Thirty depressed patients performed twelve second periods of emotion-introspection, self-reflection and a neutral condition during functional magnetic resonance imaging. We analyzed brain activation in the patients with depression by means of whole brain, region of interest and connectivity analyses. Amygdala activity decreased during emotion-introspection relative to self-reflection and to the neutral condition, whereby left amygdala was inversely activated relative to the left insula. Insula activity itself was correlated with medial and dorsolateral prefrontal cortex (PFC) activation. In conclusion, depressed patients are able to down-regulate amygdala activity by emotion-introspection. This may be interpreted as well-working emotion regulation supposedly induced by PFC connections mediated via insula. The finding supports the application of emotion-introspection, a mindfulness-related process, in a clinical setting as an element of psychotherapy to train and improve emotion regulation. Copyright © 2018 Elsevier B.V. All rights reserved.

In vivo Postnatal Electroporation and Time-lapse Imaging of Neuroblast Migration in Mouse Acute Brain Slices

PubMed Central

Oudin, Madeleine Julie; Doherty, Patrick; Lalli, Giovanna

2013-01-01

The subventricular zone (SVZ) is one of the main neurogenic niches in the postnatal brain. Here, neural progenitors proliferate and give rise to neuroblasts able to move along the rostral migratory stream (RMS) towards the olfactory bulb (OB). This long-distance migration is required for the subsequent maturation of newborn neurons in the OB, but the molecular mechanisms regulating this process are still unclear. Investigating the signaling pathways controlling neuroblast motility may not only help understand a fundamental step in neurogenesis, but also have therapeutic regenerative potential, given the ability of these neuroblasts to target brain sites affected by injury, stroke, or degeneration. In this manuscript we describe a detailed protocol for in vivo postnatal electroporation and subsequent time-lapse imaging of neuroblast migration in the mouse RMS. Postnatal electroporation can efficiently transfect SVZ progenitor cells, which in turn generate neuroblasts migrating along the RMS. Using confocal spinning disk time-lapse microscopy on acute brain slice cultures, neuroblast migration can be monitored in an environment closely resembling the in vivo condition. Moreover, neuroblast motility can be tracked and quantitatively analyzed. As an example, we describe how to use in vivo postnatal electroporation of a GFP-expressing plasmid to label and visualize neuroblasts migrating along the RMS. Electroporation of shRNA or CRE recombinase-expressing plasmids in conditional knockout mice employing the LoxP system can also be used to target genes of interest. Pharmacological manipulation of acute brain slice cultures can be performed to investigate the role of different signaling molecules in neuroblast migration. By coupling in vivo electroporation with time-lapse imaging, we hope to understand the molecular mechanisms controlling neuroblast motility and contribute to the development of novel approaches to promote brain repair. PMID:24326479

MRI measurements of Blood-Brain Barrier function in dementia: A review of recent studies.

PubMed

Raja, Rajikha; Rosenberg, Gary A; Caprihan, Arvind

2018-05-15

Blood-brain barrier (BBB) separates the systemic circulation and the brain, regulating transport of most molecules to protect the brain microenvironment. Multiple structural and functional components preserve the integrity of the BBB. Several imaging modalities are available to study disruption of the BBB. However, the subtle changes in BBB leakage that occurs in vascular cognitive impairment and Alzheimer's disease have been less well studied. Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) is the most widely adopted non-invasive imaging technique for evaluating BBB breakdown. It is used as a significant marker for a wide variety of diseases with large permeability leaks, such as brain tumors and multiple sclerosis, to more subtle disruption in chronic vascular disease and dementia. DCE-MRI analysis of BBB includes both model-free parameters and quantitative parameters using pharmacokinetic modelling. We review MRI studies of BBB breakdown in dementia. The challenges in measuring subtle BBB changes and the state of the art techniques are initially examined. Subsequently, a systematic review comparing methodologies from recent in-vivo MRI studies is presented. Various factors related to subtle BBB permeability measurement such as DCE-MRI acquisition parameters, arterial input assessment, T 1 mapping and data analysis methods are reviewed with the focus on finding the optimal technique. Finally, the reported BBB permeability values in dementia are compared across different studies and across various brain regions. We conclude that reliable measurement of low-level BBB permeability across sites remains a difficult problem and a standardization of the methodology for both data acquisition and quantitative analysis is required. This article is part of the Special Issue entitled 'Cerebral Ischemia'. Copyright © 2017 Elsevier Ltd. All rights reserved.

Methods of the pharmacological imaging of the cannabinoid system (PhICS) study: towards understanding the role of the brain endocannabinoid system in human cognition.

PubMed

van Hell, Hendrika H; Bossong, Matthijs G; Jager, Gerry; Kahn, René S; Ramsey, Nick F

2011-03-01

Various lines of (pre)clinical research indicate that cannabinoid agents carry the potential for therapeutic application to reduce symptoms in several psychiatric disorders. However, direct testing of the involvement of cannabinoid brain systems in psychiatric syndromes is essential for further development. In the Pharmacological Imaging of the Cannabinoid System (PhICS) study, the involvement of the endocannabinoid system in cognitive brain function is assessed by comparing acute effects of the cannabinoid agonist Δ9-tetrahydrocannabinol (THC) on brain function between healthy controls and groups of psychiatric patients showing cognitive dysfunction. This article describes the objectives and methods of the PhICS study and presents preliminary results of the administration procedure on subjective and neurophysiological parameters. Core elements in the methodology of PhICS are the administration method (THC is administered by inhalation using a vaporizing device) and a comprehensive use of pharmacological magnetic resonance imaging (phMRI) combining several types of MRI scans including functional MRI (fMRI), Arterial Spin Labeling (ASL) to measure brain perfusion, and resting-state fMRI. Additional methods like neuropsychological testing further specify the exact role of the endocannabinoid system in regulating cognition. Preliminary results presented in this paper indicate robust behavioral and subjective effects of THC. In addition, fMRI paradigms demonstrate activation of expected networks of brain regions in the cognitive domains of interest. The presented administration and assessment protocol provides a basis for further research on the involvement of the endocannabionoid systems in behavior and in psychopathology, which in turn may lead to development of therapeutic opportunities of cannabinoid ligands. Copyright © 2011 John Wiley & Sons, Ltd.

Brain serotonergic circuitries

PubMed Central

Charnay, Yves; Leger, Lucienne

2010-01-01

Brain serotonergic circuitries interact with other neurotransmitter systems on a multitude of different molecular levels. In humans, as in other mammalian species, serotonin (5-HT) plays a modulatory role in almost every physiological function. Furthermore, serotonergic dysfunction is thought to be implicated in several psychiatric and neurodegenerative disorders. We describe the neuroanatomy and neurochemistry of brain serotonergic circuitries. The contribution of emergent in vivo imaging methods to the regional localization of binding site receptors and certain aspects of their functional connectivity in correlation to behavior is also discussed. 5-HT cell bodies, mainly localized in the raphe nuclei, send axons to almost every brain region. It is argued that the specificity of the local chemocommunication between 5-HT and other neuronal elements mainly depends on mechanisms regulating the extracellular concentration of 5-HT, the diversity of high-affinity membrane receptors, and their specific transduction modalities. PMID:21319493

Genotype and Ancestry Modulate Brain's DAT Availability in Healthy Humans

PubMed Central

Shumay, Elena; Chen, John; Fowler, Joanna S.; Volkow, Nora D.

2011-01-01

The dopamine transporter (DAT) is a principal regulator of dopaminergic neurotransmission and its gene (the SLC6A3) is a strong biological candidate gene for various behavioral- and neurological disorders. Intense investigation of the link between the SLC6A3 polymorphisms and behavioral phenotypes yielded inconsistent and even contradictory results. Reliance on objective brain phenotype measures, for example, those afforded by brain imaging, might critically improve detection of DAT genotype-phenotype association. Here, we tested the relationship between the DAT brain availability and the SLC6A3 genotypes using an aggregate sample of 95 healthy participants of several imaging studies. These studies employed positron emission tomography (PET) with [11C]cocaine wherein the DAT availability was estimated as Bmax/Kd; while the genotype values were obtained on two repeat polymorphisms - 3-UTR- and intron 8- VNTRs. The main findings are the following: 1) both polymorphisms analyzed as single genetic markers and in combination (haplotype) modulate DAT density in midbrain; 2) ethnic background and age influence the strength of these associations; and 3) age-related changes in DAT availability differ in the 3-UTR and intron8 – genotype groups. PMID:21826203

Genotype and ancestry modulate brain's DAT availability in healthy humans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shumay, E.; Shumay, E.; Chen, J.

2011-08-01

The dopamine transporter (DAT) is a principal regulator of dopaminergic neurotransmission and its gene (the SLC6A3) is a strong biological candidate gene for various behavioral- and neurological disorders. Intense investigation of the link between the SLC6A3 polymorphisms and behavioral phenotypes yielded inconsistent and even contradictory results. Reliance on objective brain phenotype measures, for example, those afforded by brain imaging, might critically improve detection of DAT genotype-phenotype association. Here, we tested the relationship between the DAT brain availability and the SLC6A3 genotypes using an aggregate sample of 95 healthy participants of several imaging studies. These studies employed positron emission tomography (PET)more » with [{sup 11}C] cocaine wherein the DAT availability was estimated as Bmax/Kd; while the genotype values were obtained on two repeat polymorphisms - 3-UTR- and intron 8- VNTRs. The main findings are the following: (1) both polymorphisms analyzed as single genetic markers and in combination (haplotype) modulate DAT density in midbrain; (2) ethnic background and age influence the strength of these associations; and (3) age-related changes in DAT availability differ in the 3-UTR and intron8 - genotype groups.« less

[Brain activitivation of euthymic patients with Type I bipolar disorder in resting state Default Mode Network].

PubMed

Vargas, Cristian; Pineda, Julián; Calvo, Víctor; López-Jaramillo, Carlos

2014-01-01

As there are still doubts about brain connectivity in type I bipolar disorder (BID), resting-state functional magnetic resonance imaging (RS-fMRI) studies are necessary during euthymia for a better control of confounding factors. To evaluate the differences in brain activation between euthymic BID patients and control subjects using resting state- functional-magnetic resonance imaging (RS-fMRI), and to identify the lithium effect in these activations. A cross-sectional study was conducted on 21 BID patients (10 receiving lithium only, and 11 non-medicated) and 12 healthy control subjects, using RS fMRI and independent component analysis (ICA). Increased activation was found in the right hippocampus (P=.049) and posterior cingulate (P=.040) within the Default Mode Network (DMN) when BID and control group were compared. No statistically significant differences were identified between BID on lithium only therapy and non-medicated BID patients. The results suggest that there are changes in brain activation and connectivity in BID even during euthymic phase and mainly within the DMN network, which could be relevant in affect regulation. Copyright © 2013 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

TAM receptors regulate multiple features of microglial physiology.

PubMed

Fourgeaud, Lawrence; Través, Paqui G; Tufail, Yusuf; Leal-Bailey, Humberto; Lew, Erin D; Burrola, Patrick G; Callaway, Perri; Zagórska, Anna; Rothlin, Carla V; Nimmerjahn, Axel; Lemke, Greg

2016-04-14

Microglia are damage sensors for the central nervous system (CNS), and the phagocytes responsible for routine non-inflammatory clearance of dead brain cells. Here we show that the TAM receptor tyrosine kinases Mer and Axl regulate these microglial functions. We find that adult mice deficient in microglial Mer and Axl exhibit a marked accumulation of apoptotic cells specifically in neurogenic regions of the CNS, and that microglial phagocytosis of the apoptotic cells generated during adult neurogenesis is normally driven by both TAM receptor ligands Gas6 and protein S. Using live two-photon imaging, we demonstrate that the microglial response to brain damage is also TAM-regulated, as TAM-deficient microglia display reduced process motility and delayed convergence to sites of injury. Finally, we show that microglial expression of Axl is prominently upregulated in the inflammatory environment that develops in a mouse model of Parkinson's disease. Together, these results establish TAM receptors as both controllers of microglial physiology and potential targets for therapeutic intervention in CNS disease.

vlPFC-vmPFC-Amygdala Interactions Underlie Age-Related Differences in Cognitive Regulation of Emotion.

PubMed

Silvers, Jennifer A; Insel, Catherine; Powers, Alisa; Franz, Peter; Helion, Chelsea; Martin, Rebecca E; Weber, Jochen; Mischel, Walter; Casey, B J; Ochsner, Kevin N

2017-07-01

Emotion regulation is a critical life skill that develops throughout childhood and adolescence. Despite this development in emotional processes, little is known about how the underlying brain systems develop with age. This study examined emotion regulation in 112 individuals (aged 6-23 years) as they viewed aversive and neutral images using a reappraisal task. On "reappraisal" trials, participants were instructed to view the images as distant, a strategy that has been previously shown to reduce negative affect. On "reactivity" trials, participants were instructed to view the images without regulating emotions to assess baseline emotional responding. During reappraisal, age predicted less negative affect, reduced amygdala responses and inverse coupling between the ventromedial prefrontal cortex (vmPFC) and amygdala. Moreover, left ventrolateral prefrontal (vlPFC) recruitment mediated the relationship between increasing age and diminishing amygdala responses. This negative vlPFC-amygdala association was stronger for individuals with inverse coupling between the amygdala and vmPFC. These data provide evidence that vmPFC-amygdala connectivity facilitates vlPFC-related amygdala modulation across development. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Hypoxic stress up-regulates Kir2.1 expression and facilitates cell proliferation in brain capillary endothelial cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yamamura, Hideto; Suzuki, Yoshiaki; Yamamura, Hisao

The blood-brain barrier (BBB) is mainly composed of brain capillary endothelial cells (BCECs), astrocytes and pericytes. Brain ischemia causes hypoxic encephalopathy and damages BBB. However, it remains still unclear how hypoxia affects BCECs. In the present study, t-BBEC117 cells, an immortalized bovine brain endothelial cell line, were cultured under hypoxic conditions at 4–5% oxygen for 72 h. This hypoxic stress caused hyperpolarization of resting membrane potential. Patch-clamp recordings revealed a marked increase in Ba{sup 2+}-sensitive inward rectifier K{sup +} current in t-BBEC117 cells after hypoxic culture. Western blot and real-time PCR analyses showed that Kir2.1 expression was significantly up-regulated at protein level butmore » not at mRNA level after the hypoxic culture. Ca{sup 2+} imaging study revealed that the hypoxic stress enhanced store-operated Ca{sup 2+} (SOC) entry, which was significantly reduced in the presence of 100 μM Ba{sup 2+}. On the other hand, the expression of SOC channels such as Orai1, Orai2, and transient receptor potential channels was not affected by hypoxic stress. MTT assay showed that the hypoxic stress significantly enhanced t-BBEC117 cell proliferation, which was inhibited by approximately 60% in the presence of 100 μM Ba{sup 2+}. We first show here that moderate cellular stress by cultivation under hypoxic conditions hyperpolarizes membrane potential via the up-regulation of functional Kir2.1 expression and presumably enhances Ca{sup 2+} entry, resulting in the facilitation of BCEC proliferation. These findings suggest potential roles of Kir2.1 expression in functional changes of BCECs in BBB following ischemia. -- Highlights: •Hypoxic culture of brain endothelial cells (BEC) caused membrane hyperpolarization. •This hyperpolarization was due to the increased expression of Kir2.1 channels. •Hypoxia enhanced store-operated Ca{sup 2+} (SOC) entry via Kir2.1 up-regulation. •Expression levels of putative SOC channels were not affected by hypoxia. •Kir2.1 up-regulation is responsible for hypoxia-enhanced BEC proliferation.« less

Image formation of brain function in patients suffering from knee osteoarthritis treated with moxibustion.

PubMed

Xie, Hongwu; Xu, Fangming; Chen, Rixin; Luo, Tianyou; Chen, Mingren; Fang, Weidong; Lü, Fajin; Wu, Fei; Song, Yune; Xiong, Jun

2013-04-01

Functional magnetic resonance imaging (fMRI) technology was used to study changes to the resting state blood flow in the brains of patients with knee osteoarthritis (KOA) before and after treatment with moxibustion at the acupoint of the left Dubi (ST 35) and to probe the cerebral mechanism underlying the effect of moxibustion. The resting state brain function of 30 patients with left KOA was scanned with fMRI before and after treatment with moxibustion. The analytic methods of fractional amplitude of low frequency fluctuation (fALFF) and regional homogeneity (ReHo) were used to observe changes in resting state brain function. The fALFF values of the right cerebrum, extra-nucleus, left cerebellum, left cerebrum and white matter of patients after moxibustion treatment were higher than before treatment, and the fALFF values of the precentral gyrus, frontal lobe and occipital lobe were lower than before treatment (P < 0.05, K > or = 85). The ReHo values of the thalamus, extra-nucleus and parietal lobe of patients were much higher than those before moxibustion treatment, and the ReHo values of the right cerebrum, left cerebrum and frontal lobe were lower than before treatment (P < 0.05, K > or = 85). The influence of moxibustion on obvious changes in brain regions basically conforms to the way that pain and warmth is transmitted in the body, and the activation of sensitive systems in the body may be objective evidence of channel transmission. The regulation of brain function by moxibustion is not in a single brain region but rather in a network of many brain regions.

Fueling and imaging brain activation

PubMed Central

Dienel, Gerald A

2012-01-01

Metabolic signals are used for imaging and spectroscopic studies of brain function and disease and to elucidate the cellular basis of neuroenergetics. The major fuel for activated neurons and the models for neuron–astrocyte interactions have been controversial because discordant results are obtained in different experimental systems, some of which do not correspond to adult brain. In rats, the infrastructure to support the high energetic demands of adult brain is acquired during postnatal development and matures after weaning. The brain's capacity to supply and metabolize glucose and oxygen exceeds demand over a wide range of rates, and the hyperaemic response to functional activation is rapid. Oxidative metabolism provides most ATP, but glycolysis is frequently preferentially up-regulated during activation. Underestimation of glucose utilization rates with labelled glucose arises from increased lactate production, lactate diffusion via transporters and astrocytic gap junctions, and lactate release to blood and perivascular drainage. Increased pentose shunt pathway flux also causes label loss from C1 of glucose. Glucose analogues are used to assay cellular activities, but interpretation of results is uncertain due to insufficient characterization of transport and phosphorylation kinetics. Brain activation in subjects with low blood-lactate levels causes a brain-to-blood lactate gradient, with rapid lactate release. In contrast, lactate flooding of brain during physical activity or infusion provides an opportunistic, supplemental fuel. Available evidence indicates that lactate shuttling coupled to its local oxidation during activation is a small fraction of glucose oxidation. Developmental, experimental, and physiological context is critical for interpretation of metabolic studies in terms of theoretical models. PMID:22612861

Depression-like behaviour in mice is associated with disrupted circadian rhythms in nucleus accumbens and periaqueductal grey.

PubMed

Landgraf, Dominic; Long, Jaimie E; Welsh, David K

2016-05-01

An association between circadian rhythms and mood regulation is well established, and disturbed circadian clocks are believed to contribute to the development of mood disorders, including major depressive disorder. The circadian system is coordinated by the suprachiasmatic nucleus (SCN), the master pacemaker in the hypothalamus that receives light input from the retina and synchronizes circadian oscillators in other brain regions and peripheral tissues. Lacking the tight neuronal network that couples single-cell oscillators in the SCN, circadian clocks outside the SCN may be less stable and more susceptible to disturbances, for example by clock gene mutations or uncontrollable stress. However, non-SCN circadian clocks have not been studied extensively in rodent models of mood disorders. In the present study, it was hypothesized that disturbances of local circadian clocks in mood-regulating brain areas are associated with depression-like behaviour in mice. Using the learned helplessness procedure, depression-like behaviour was evoked in mice bearing the PER2::LUC circadian reporter, and then circadian rhythms of PER2 expression were examined in brain slices from these mice using luminometry and bioluminescence imaging. It was found that helplessness is associated with absence of circadian rhythms in the nucleus accumbens and the periaqueductal grey, two of the most critical brain regions within the reward circuit. The current study provides evidence that susceptibility of mice to depression-like behaviour is associated with disturbed local circadian clocks in a subset of mood-regulating brain areas, but the direction of causality remains to be determined. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

An automatic rat brain extraction method based on a deformable surface model.

PubMed

Li, Jiehua; Liu, Xiaofeng; Zhuo, Jiachen; Gullapalli, Rao P; Zara, Jason M

2013-08-15

The extraction of the brain from the skull in medical images is a necessary first step before image registration or segmentation. While pre-clinical MR imaging studies on small animals, such as rats, are increasing, fully automatic imaging processing techniques specific to small animal studies remain lacking. In this paper, we present an automatic rat brain extraction method, the Rat Brain Deformable model method (RBD), which adapts the popular human brain extraction tool (BET) through the incorporation of information on the brain geometry and MR image characteristics of the rat brain. The robustness of the method was demonstrated on T2-weighted MR images of 64 rats and compared with other brain extraction methods (BET, PCNN, PCNN-3D). The results demonstrate that RBD reliably extracts the rat brain with high accuracy (>92% volume overlap) and is robust against signal inhomogeneity in the images. Copyright © 2013 Elsevier B.V. All rights reserved.

Effects of hunger state on the brain responses to food cues across the life span.

PubMed

Charbonnier, L; van Meer, F; Johnstone, A M; Crabtree, D; Buosi, W; Manios, Y; Androutsos, O; Giannopoulou, A; Viergever, M A; Smeets, P A M

2018-05-01

The abundant exposure to food cues in our environment is one of the main drivers of overconsumption. Food evaluation is important for the regulation of food intake by the brain and it's interaction with hunger state. Children are especially susceptible to food cues. Understanding the mechanisms behind this regulation in healthy individuals across the life span can help to elucidate the mechanisms underlying overconsumption and aid the development of future obesity prevention strategies. Few functional neuroimaging studies have been done in children and elderly. Furthermore, it is unknown how hunger state affects neural food cue reactivity in these groups, since this has not been examined consistently. We examined the effects of hunger state and age on the brain responses to low- and high calorie foods. On two mornings, 122 participants (17 children; 38 teens; 36 adults; 31 elderly) performed a food image viewing task while being scanned using fMRI, either fasted or sated. Hunger induced greater activation during high versus low calorie food image viewing than satiety in the bilateral dorsomedial (dmPFC) and in the right dorsolateral prefrontal cortex (dlPFC) across all age groups. There was no significant main effect of age group on high versus low calorie food image viewing and no interaction between age group and hunger state. The greater activation of the dlPFC across all age groups during high calorie food image viewing in a fasted state might reflect increased inhibitory control in response to these foods. This may underlie the ability to resist overconsumption of high calorie foods. Furthermore, increased medial prefrontal cortex activation during hunger might reflect increased reward value of high calorie foods, which declines with satiation. Further studies are needed to better understand these results. Notably, overweight and obese individuals should be included to examine whether these responses are altered by weight status across the life span. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

NgR1: A Tunable Sensor Regulating Memory Formation, Synaptic, and Dendritic Plasticity.

PubMed

Karlsson, Tobias E; Smedfors, Gabriella; Brodin, Alvin T S; Åberg, Elin; Mattsson, Anna; Högbeck, Isabelle; Wellfelt, Katrin; Josephson, Anna; Brené, Stefan; Olson, Lars

2016-04-01

Nogo receptor 1 (NgR1) is expressed in forebrain neurons and mediates nerve growth inhibition in response to Nogo and other ligands. Neuronal activity downregulates NgR1 and the inability to downregulate NgR1 impairs long-term memory. We investigated behavior in a serial behavioral paradigm in mice that overexpress or lack NgR1, finding impaired locomotor behavior and recognition memory in mice lacking NgR1 and impaired sequential spatial learning in NgR1 overexpressing mice. We also investigated a role for NgR1 in drug-mediated sensitization and found that repeated cocaine exposure caused stronger locomotor responses but limited development of stereotypies in NgR1 overexpressing mice. This suggests that NgR1-regulated synaptic plasticity is needed to develop stereotypies. Ex vivo magnetic resonance imaging and diffusion tensor imaging analyses of NgR1 overexpressing brains did not reveal any major alterations. NgR1 overexpression resulted in significantly reduced density of mature spines and dendritic complexity. NgR1 overexpression also altered cocaine-induced effects on spine plasticity. Our results show that NgR1 is a negative regulator of both structural synaptic plasticity and dendritic complexity in a brain region-specific manner, and highlight anterior cingulate cortex as a key area for memory-related plasticity. © The Author 2016. Published by Oxford University Press.

NgR1: A Tunable Sensor Regulating Memory Formation, Synaptic, and Dendritic Plasticity

PubMed Central

Karlsson, Tobias E.; Smedfors, Gabriella; Brodin, Alvin T. S.; Åberg, Elin; Mattsson, Anna; Högbeck, Isabelle; Wellfelt, Katrin; Josephson, Anna; Brené, Stefan; Olson, Lars

2016-01-01

Nogo receptor 1 (NgR1) is expressed in forebrain neurons and mediates nerve growth inhibition in response to Nogo and other ligands. Neuronal activity downregulates NgR1 and the inability to downregulate NgR1 impairs long-term memory. We investigated behavior in a serial behavioral paradigm in mice that overexpress or lack NgR1, finding impaired locomotor behavior and recognition memory in mice lacking NgR1 and impaired sequential spatial learning in NgR1 overexpressing mice. We also investigated a role for NgR1 in drug-mediated sensitization and found that repeated cocaine exposure caused stronger locomotor responses but limited development of stereotypies in NgR1 overexpressing mice. This suggests that NgR1-regulated synaptic plasticity is needed to develop stereotypies. Ex vivo magnetic resonance imaging and diffusion tensor imaging analyses of NgR1 overexpressing brains did not reveal any major alterations. NgR1 overexpression resulted in significantly reduced density of mature spines and dendritic complexity. NgR1 overexpression also altered cocaine-induced effects on spine plasticity. Our results show that NgR1 is a negative regulator of both structural synaptic plasticity and dendritic complexity in a brain region-specific manner, and highlight anterior cingulate cortex as a key area for memory-related plasticity. PMID:26838771

Brain morphology in children with nevoid basal cell carcinoma syndrome.

PubMed

Shiohama, Tadashi; Fujii, Katsunori; Miyashita, Toshiyuki; Mizuochi, Hiromi; Uchikawa, Hideki; Shimojo, Naoki

2017-04-01

Brain morphology is tightly regulated by diverse signaling pathways. Hedgehog signaling is a candidate pathway considered responsible for regulating brain morphology. Nevoid basal cell carcinoma syndrome (NBCCS), caused by a PTCH1 mutation in the hedgehog signaling pathway, occasionally exhibits macrocephaly and medulloblastoma. Although cerebellar enlargement occurs in ptch1 heterozygous-deficient mice, its impact on human brain development remains unknown. We investigated the brain morphological characteristics of children with NBCCS. We evaluated brain T1-weighted images from nine children with NBCCS and 15 age-matched normal control (NC) children (mean [standard deviation], 12.2 [2.8] vs. 11.6 [2.3] years old). The diameters of the cerebrum, corpus callosum, and brain stem and the cerebellar volume were compared using two-tailed t-tests with Welch's correction. The transverse diameters (150.4 [9.9] vs. 136.0 [5.5] mm, P = 0.002) and longitudinal diameters (165.4 [8.0] vs. 151.3 [8.7] mm, P = 0.0007) of the cerebrum, cross-sectional area of the cerebellar vermis (18.7 [2.6] vs. 11.8 [1.7] cm 2 , P = 0.0001), and total volume of the cerebellar hemispheres (185.1 [13.0] vs. 131.9 [10.4] cm 3 , P = 0.0001) were significantly larger in the children with NBCCS than in NC children. Thinning of the corpus callosum and ventricular enlargement were also confirmed in children with NBCCS. We demonstrate that, on examination of the brain morphology, an increase in the size of the cerebrum, cerebellum, and cerebral ventricles is revealed in children with NBCCS compared to NC children. This suggests that constitutively active hedgehog signaling affects human brain morphology and the PI3K/AKT and RAS/MAPK pathways. © 2017 Wiley Periodicals, Inc.

Comparing three-dimensional serial optical coherence tomography histology to MRI imaging in the entire mouse brain

NASA Astrophysics Data System (ADS)

Castonguay, Alexandre; Lefebvre, Joël; Pouliot, Philippe; Lesage, Frédéric

2018-01-01

An automated serial histology setup combining optical coherence tomography (OCT) imaging with vibratome sectioning was used to image eight wild type mouse brains. The datasets resulted in thousands of volumetric tiles resolved at a voxel size of (4.9×4.9×6.5) μm3 stitched back together to give a three-dimensional map of the brain from which a template OCT brain was obtained. To assess deformation caused by tissue sectioning, reconstruction algorithms, and fixation, OCT datasets were compared to both in vivo and ex vivo magnetic resonance imaging (MRI) imaging. The OCT brain template yielded a highly detailed map of the brain structure, with a high contrast in white matter fiber bundles and was highly resemblant to the in vivo MRI template. Brain labeling using the Allen brain framework showed little variation in regional brain volume among imaging modalities with no statistical differences. The high correspondence between the OCT template brain and its in vivo counterpart demonstrates the potential of whole brain histology to validate in vivo imaging.

Brain Injury in Neonates with Complex Congenital Heart Disease: What Is the Predictive Value of MRI in the Fetal Period?

PubMed

Brossard-Racine, M; du Plessis, A; Vezina, G; Robertson, R; Donofrio, M; Tworetzky, W; Limperopoulos, C

2016-07-01

Brain injury in neonates with congenital heart disease is an important predictor of adverse neurodevelopmental outcome. Impaired brain development in congenital heart disease may have a prenatal origin, but the sensitivity and specificity of fetal brain MR imaging for predicting neonatal brain lesions are currently unknown. We sought to determine the value of conventional fetal MR imaging for predicting abnormal findings on neonatal preoperative MR imaging in neonates with complex congenital heart disease. MR imaging studies were performed in 103 fetuses with confirmed congenital heart disease (mean gestational age, 31.57 ± 3.86 weeks) and were repeated postnatally before cardiac surgery (mean age, 6.8 ± 12.2 days). Each MR imaging study was read by a pediatric neuroradiologist. Brain abnormalities were detected in 17/103 (16%) fetuses by fetal MR imaging and in 33/103 (32%) neonates by neonatal MR imaging. Only 9/33 studies with abnormal neonatal findings were preceded by abnormal findings on fetal MR imaging. The sensitivity and specificity of conventional fetal brain MR imaging for predicting neonatal brain abnormalities were 27% and 89%, respectively. Brain abnormalities detected by in utero MR imaging in fetuses with congenital heart disease are associated with higher risk of postnatal preoperative brain injury. However, a substantial proportion of anomalies on postnatal MR imaging were not present on fetal MR imaging; this result is likely due to the limitations of conventional fetal MR imaging and the emergence of new lesions that occurred after the fetal studies. Postnatal brain MR imaging studies are needed to confirm the presence of injury before open heart surgery. © 2016 by American Journal of Neuroradiology.

Compact and mobile high resolution PET brain imager

DOEpatents

Majewski, Stanislaw [Yorktown, VA; Proffitt, James [Newport News, VA

2011-02-08

A brain imager includes a compact ring-like static PET imager mounted in a helmet-like structure. When attached to a patient's head, the helmet-like brain imager maintains the relative head-to-imager geometry fixed through the whole imaging procedure. The brain imaging helmet contains radiation sensors and minimal front-end electronics. A flexible mechanical suspension/harness system supports the weight of the helmet thereby allowing for patient to have limited movements of the head during imaging scans. The compact ring-like PET imager enables very high resolution imaging of neurological brain functions, cancer, and effects of trauma using a rather simple mobile scanner with limited space needs for use and storage.

Loss of pons-to-hypothalamic white matter tracks in brainstem obesity.

PubMed

Purnell, J Q; Lahna, D L; Samuels, M H; Rooney, W D; Hoffman, W F

2014-12-01

Hyperphagia and obesity have been reported following damage to the hypothalamus in humans. Other brain sites are also postulated to be involved in the control of food intake and body weight regulation, such as the amygdala and brainstem. The brainstem, however, is thought to primarily integrate short-term meal-related signals but not affect long-term alterations in body weight, which is controlled by higher centers. The objective of this study was to identify structural pathways damaged in a patient with a brainstem cavernoma who experienced sudden onset of hyperphagia and >50 kg weight gain in <1 year following surgical drainage via a midline suboccipital craniotomy. Diffusion tensor imaging revealed loss of nerve fiber connections between her brainstem, hypothalamus and higher brain centers with preservation of motor tracks. Imaging and endocrine testing confirmed normal hypothalamic structure and function. Gastric bypass surgery restored normal appetite and body weight to baseline. This is the first report of 'brainstem obesity' and adds to the brain regions that can determine the long-term body weight set point in humans.

In Vivo Analysis of the Neurovascular Niche in the Developing Xenopus Brain

PubMed Central

Li, Jianli

2017-01-01

Abstract The neurovascular niche is a specialized microenvironment formed by the interactions between neural progenitor cells (NPCs) and the vasculature. While it is thought to regulate adult neurogenesis by signaling through vascular-derived soluble cues or contacted-mediated cues, less is known about the neurovascular niche during development. In Xenopus laevis tadpole brain, NPCs line the ventricle and extend radial processes tipped with endfeet to the vascularized pial surface. Using in vivo labeling and time-lapse imaging in tadpoles, we find that intracardial injection of fluorescent tracers rapidly labels Sox2/3-expressing NPCs and that vascular-circulating molecules are endocytosed by NPC endfeet. Confocal imaging indicates that about half of the endfeet appear to appose the vasculature, and time-lapse analysis of NPC proliferation and endfeet-vascular interactions suggest that proliferative activity does not correlate with stable vascular apposition. Together, these findings characterize the neurovascular niche in the developing brain and suggest that, while signaling to NPCs may occur through vascular-derived soluble cues, stable contact between NPC endfeet and the vasculature is not required for developmental neurogenesis. PMID:28795134

The Self-Liking Brain: A VBM Study on the Structural Substrate of Self-Esteem

PubMed Central

Agroskin, Dmitrij; Klackl, Johannes; Jonas, Eva

2014-01-01

Abundant evidence suggests that self-esteem is an important personality resource for emotion regulation in response to stressful experiences. It was thus hypothesized that the relative grey matter volume of brain regions involved in responding to and coping with stress is related to individual differences in trait self-esteem. Using structural magnetic resonance imaging of 48 healthy adults in conjunction with voxel-based morphometry and diffeomorphic anatomical registration using exponentiated lie algebra (VBM-DARTEL), positive associations between self-esteem and regional grey matter volume were indeed found in the anterior cingulate cortex (ACC), right lateral prefrontal cortex (LPFC), right hippocampus, and left hypothalamus. In addition, self-esteem positively covaried with grey matter volume in the right temporo-parietal junction (TPJ), which has been implicated in pride and theory of mind. The results suggest that persons with low self-esteem have reduced grey matter volume in brain regions that contribute to emotion/stress regulation, pride, and theory of mind. The findings provide novel neuroanatomical evidence for the view that self-esteem constitutes a vital coping resource. PMID:24489727

The self-liking brain: a VBM study on the structural substrate of self-esteem.

PubMed

Agroskin, Dmitrij; Klackl, Johannes; Jonas, Eva

2014-01-01

Abundant evidence suggests that self-esteem is an important personality resource for emotion regulation in response to stressful experiences. It was thus hypothesized that the relative grey matter volume of brain regions involved in responding to and coping with stress is related to individual differences in trait self-esteem. Using structural magnetic resonance imaging of 48 healthy adults in conjunction with voxel-based morphometry and diffeomorphic anatomical registration using exponentiated lie algebra (VBM-DARTEL), positive associations between self-esteem and regional grey matter volume were indeed found in the anterior cingulate cortex (ACC), right lateral prefrontal cortex (LPFC), right hippocampus, and left hypothalamus. In addition, self-esteem positively covaried with grey matter volume in the right temporo-parietal junction (TPJ), which has been implicated in pride and theory of mind. The results suggest that persons with low self-esteem have reduced grey matter volume in brain regions that contribute to emotion/stress regulation, pride, and theory of mind. The findings provide novel neuroanatomical evidence for the view that self-esteem constitutes a vital coping resource.

Neural Control of the Lower Urinary Tract

PubMed Central

de Groat, William C.; Griffiths, Derek; Yoshimura, Naoki

2015-01-01

This article summarizes anatomical, neurophysiological, pharmacological, and brain imaging studies in humans and animals that have provided insights into the neural circuitry and neurotransmitter mechanisms controlling the lower urinary tract. The functions of the lower urinary tract to store and periodically eliminate urine are regulated by a complex neural control system in the brain, spinal cord, and peripheral autonomic ganglia that coordinates the activity of smooth and striated muscles of the bladder and urethral outlet. The neural control of micturition is organized as a hierarchical system in which spinal storage mechanisms are in turn regulated by circuitry in the rostral brain stem that initiates reflex voiding. Input from the forebrain triggers voluntary voiding by modulating the brain stem circuitry. Many neural circuits controlling the lower urinary tract exhibit switch-like patterns of activity that turn on and off in an all-or-none manner. The major component of the micturition switching circuit is a spinobulbospinal parasympathetic reflex pathway that has essential connections in the periaqueductal gray and pontine micturition center. A computer model of this circuit that mimics the switching functions of the bladder and urethra at the onset of micturition is described. Micturition occurs involuntarily in infants and young children until the age of 3 to 5 years, after which it is regulated voluntarily. Diseases or injuries of the nervous system in adults can cause the re-emergence of involuntary micturition, leading to urinary incontinence. Neuroplasticity underlying these developmental and pathological changes in voiding function is discussed. PMID:25589273

Pulse Coupled Neural Networks for the Segmentation of Magnetic Resonance Brain Images.

DTIC Science & Technology

1996-12-01

PULSE COUPLED NEURAL NETWORKS FOR THE SEGMENTATION OF MAGNETIC RESONANCE BRAIN IMAGES THESIS Shane Lee Abrahamson First Lieutenant, USAF AFIT/GCS/ENG...COUPLED NEURAL NETWORKS FOR THE SEGMENTATION OF MAGNETIC RESONANCE BRAIN IMAGES THESIS Shane Lee Abrahamson First Lieutenant, USAF AFIT/GCS/ENG/96D-01...research develops an automated method for segmenting Magnetic Resonance (MR) brain images based on Pulse Coupled Neural Networks (PCNN). MR brain image

Irrelevant stimulus processing in ADHD: catecholamine dynamics and attentional networks.

PubMed

Aboitiz, Francisco; Ossandón, Tomás; Zamorano, Francisco; Palma, Bárbara; Carrasco, Ximena

2014-01-01

A cardinal symptom of attention deficit and hyperactivity disorder (ADHD) is a general distractibility where children and adults shift their attentional focus to stimuli that are irrelevant to the ongoing behavior. This has been attributed to a deficit in dopaminergic signaling in cortico-striatal networks that regulate goal-directed behavior. Furthermore, recent imaging evidence points to an impairment of large scale, antagonistic brain networks that normally contribute to attentional engagement and disengagement, such as the task-positive networks and the default mode network (DMN). Related networks are the ventral attentional network (VAN) involved in attentional shifting, and the salience network (SN) related to task expectancy. Here we discuss the tonic-phasic dynamics of catecholaminergic signaling in the brain, and attempt to provide a link between this and the activities of the large-scale cortical networks that regulate behavior. More specifically, we propose that a disbalance of tonic catecholamine levels during task performance produces an emphasis of phasic signaling and increased excitability of the VAN, yielding distractibility symptoms. Likewise, immaturity of the SN may relate to abnormal tonic signaling and an incapacity to build up a proper executive system during task performance. We discuss different lines of evidence including pharmacology, brain imaging and electrophysiology, that are consistent with our proposal. Finally, restoring the pharmacodynamics of catecholaminergic signaling seems crucial to alleviate ADHD symptoms; however, the possibility is open to explore cognitive rehabilitation strategies to top-down modulate network dynamics compensating the pharmacological deficits.

Mapping Alterations to the Endogenous Elemental Distribution within the Lateral Ventricles and Choroid Plexus in Brain Disorders Using X-Ray Fluorescence Imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lins, Brittney R.; Pushie, Jake M.; Jones, Michael

The choroid plexus and cerebral ventricles are critical structures for the production of cerebral spinal fluid (CSF) and play an important role in regulating ion and metal transport in the brain, however many aspects of its roles in normal physiology and disease states, such as psychiatric illness, remain unknown. The choroid plexus is difficult to examine in vivo, and in situ ex vivo, and as such has typically been examined indirectly with radiolabeled tracers or ex vivo stains, making measurements of the endogenous K +, Cl -, and Ca + distributions unreliable. In the present study, we directly examined themore » distribution of endogenous ions and biologically relevant transition metals in the choroid plexus and regions surrounding the ventricles (ventricle wall, cortex, corpus callosum, striatum) using X-ray fluorescence imaging (XFI). We find that the choroid plexus was rich in Cl - and Fe while K + levels increase further from the ventricle as Cl - levels decrease, consistent with the known role of ion transporters in the choroid plexus CSF production. A polyI:C offspring displayed enlarged ventricles, elevated Cl - surrounding the ventricles, and intraventricular calcifications. These observations fit with clinical findings in patients with schizophrenia and suggest maternal treatment with polyI:C may lead to dysfunctional ion regulation in offspring. Furthermore, this study demonstrates the power of XFI for examining the endogenous elemental distributions of the ventricular system in healthy brain tissue as well as disease models.« less

Mapping Alterations to the Endogenous Elemental Distribution within the Lateral Ventricles and Choroid Plexus in Brain Disorders Using X-Ray Fluorescence Imaging

PubMed Central

Lins, Brittney R.; Pushie, Jake M.; Jones, Michael; Howard, Daryl L.; Howland, John G.; Hackett, Mark J.

2016-01-01

The choroid plexus and cerebral ventricles are critical structures for the production of cerebral spinal fluid (CSF) and play an important role in regulating ion and metal transport in the brain, however many aspects of its roles in normal physiology and disease states, such as psychiatric illness, remain unknown. The choroid plexus is difficult to examine in vivo, and in situ ex vivo, and as such has typically been examined indirectly with radiolabeled tracers or ex vivo stains, making measurements of the endogenous K+, Cl−, and Ca+ distributions unreliable. In the present study, we directly examined the distribution of endogenous ions and biologically relevant transition metals in the choroid plexus and regions surrounding the ventricles (ventricle wall, cortex, corpus callosum, striatum) using X-ray fluorescence imaging (XFI). We find that the choroid plexus was rich in Cl− and Fe while K+ levels increase further from the ventricle as Cl− levels decrease, consistent with the known role of ion transporters in the choroid plexus CSF production. A polyI:C offspring displayed enlarged ventricles, elevated Cl− surrounding the ventricles, and intraventricular calcifications. These observations fit with clinical findings in patients with schizophrenia and suggest maternal treatment with polyI:C may lead to dysfunctional ion regulation in offspring. This study demonstrates the power of XFI for examining the endogenous elemental distributions of the ventricular system in healthy brain tissue as well as disease models. PMID:27351594

Irrelevant stimulus processing in ADHD: catecholamine dynamics and attentional networks

PubMed Central

Aboitiz, Francisco; Ossandón, Tomás; Zamorano, Francisco; Palma, Bárbara; Carrasco, Ximena

2014-01-01

A cardinal symptom of attention deficit and hyperactivity disorder (ADHD) is a general distractibility where children and adults shift their attentional focus to stimuli that are irrelevant to the ongoing behavior. This has been attributed to a deficit in dopaminergic signaling in cortico-striatal networks that regulate goal-directed behavior. Furthermore, recent imaging evidence points to an impairment of large scale, antagonistic brain networks that normally contribute to attentional engagement and disengagement, such as the task-positive networks and the default mode network (DMN). Related networks are the ventral attentional network (VAN) involved in attentional shifting, and the salience network (SN) related to task expectancy. Here we discuss the tonic–phasic dynamics of catecholaminergic signaling in the brain, and attempt to provide a link between this and the activities of the large-scale cortical networks that regulate behavior. More specifically, we propose that a disbalance of tonic catecholamine levels during task performance produces an emphasis of phasic signaling and increased excitability of the VAN, yielding distractibility symptoms. Likewise, immaturity of the SN may relate to abnormal tonic signaling and an incapacity to build up a proper executive system during task performance. We discuss different lines of evidence including pharmacology, brain imaging and electrophysiology, that are consistent with our proposal. Finally, restoring the pharmacodynamics of catecholaminergic signaling seems crucial to alleviate ADHD symptoms; however, the possibility is open to explore cognitive rehabilitation strategies to top-down modulate network dynamics compensating the pharmacological deficits. PMID:24723897

Mapping Alterations to the Endogenous Elemental Distribution within the Lateral Ventricles and Choroid Plexus in Brain Disorders Using X-Ray Fluorescence Imaging

DOE PAGES

Lins, Brittney R.; Pushie, Jake M.; Jones, Michael; ...

2016-06-28

The choroid plexus and cerebral ventricles are critical structures for the production of cerebral spinal fluid (CSF) and play an important role in regulating ion and metal transport in the brain, however many aspects of its roles in normal physiology and disease states, such as psychiatric illness, remain unknown. The choroid plexus is difficult to examine in vivo, and in situ ex vivo, and as such has typically been examined indirectly with radiolabeled tracers or ex vivo stains, making measurements of the endogenous K +, Cl -, and Ca + distributions unreliable. In the present study, we directly examined themore » distribution of endogenous ions and biologically relevant transition metals in the choroid plexus and regions surrounding the ventricles (ventricle wall, cortex, corpus callosum, striatum) using X-ray fluorescence imaging (XFI). We find that the choroid plexus was rich in Cl - and Fe while K + levels increase further from the ventricle as Cl - levels decrease, consistent with the known role of ion transporters in the choroid plexus CSF production. A polyI:C offspring displayed enlarged ventricles, elevated Cl - surrounding the ventricles, and intraventricular calcifications. These observations fit with clinical findings in patients with schizophrenia and suggest maternal treatment with polyI:C may lead to dysfunctional ion regulation in offspring. Furthermore, this study demonstrates the power of XFI for examining the endogenous elemental distributions of the ventricular system in healthy brain tissue as well as disease models.« less

Demeclocycline as a contrast agent for detecting brain neoplasms using confocal microscopy

NASA Astrophysics Data System (ADS)

Wirth, Dennis; Smith, Thomas W.; Moser, Richard; Yaroslavsky, Anna N.

2015-04-01

Complete resection of brain tumors improves life expectancy and quality. Thus, there is a strong need for high-resolution detection and microscopically controlled removal of brain neoplasms. The goal of this study was to test demeclocycline as a contrast enhancer for the intraoperative detection of brain tumors. We have imaged benign and cancerous brain tumors using multimodal confocal microscopy. The tumors investigated included pituitary adenoma, meningiomas, glioblastomas, and metastatic brain cancers. Freshly excised brain tissues were stained in 0.75 mg ml-1 aqueous solution of demeclocyline. Reflectance images were acquired at 402 nm. Fluorescence signals were excited at 402 nm and registered between 500 and 540 nm. After imaging, histological sections were processed from the imaged specimens and compared to the optical images. Fluorescence images highlighted normal and cancerous brain cells, while reflectance images emphasized the morphology of connective tissue. The optical and histological images were in accordance with each other for all types of tumors investigated. Demeclocyline shows promise as a contrast agent for intraoperative detection of brain tumors.

Functional connectivity analysis of the neural bases of emotion regulation: A comparison of independent component method with density-based k-means clustering method.

PubMed

Zou, Ling; Guo, Qian; Xu, Yi; Yang, Biao; Jiao, Zhuqing; Xiang, Jianbo

2016-04-29

Functional magnetic resonance imaging (fMRI) is an important tool in neuroscience for assessing connectivity and interactions between distant areas of the brain. To find and characterize the coherent patterns of brain activity as a means of identifying brain systems for the cognitive reappraisal of the emotion task, both density-based k-means clustering and independent component analysis (ICA) methods can be applied to characterize the interactions between brain regions involved in cognitive reappraisal of emotion. Our results reveal that compared with the ICA method, the density-based k-means clustering method provides a higher sensitivity of polymerization. In addition, it is more sensitive to those relatively weak functional connection regions. Thus, the study concludes that in the process of receiving emotional stimuli, the relatively obvious activation areas are mainly distributed in the frontal lobe, cingulum and near the hypothalamus. Furthermore, density-based k-means clustering method creates a more reliable method for follow-up studies of brain functional connectivity.

Functional expression of SGLTs in rat brain.

PubMed

Yu, Amy S; Hirayama, Bruce A; Timbol, Gerald; Liu, Jie; Basarah, Ernest; Kepe, Vladimir; Satyamurthy, Nagichettiar; Huang, Sung-Cheng; Wright, Ernest M; Barrio, Jorge R

2010-12-01

This work provides evidence of previously unrecognized uptake of glucose via sodium-coupled glucose transporters (SGLTs) in specific regions of the brain. The current understanding of functional glucose utilization in brain is largely based on studies using positron emission tomography (PET) with the glucose tracer 2-deoxy-2-[F-18]fluoro-D-glucose (2-FDG). However, 2-FDG is only a good substrate for facilitated-glucose transporters (GLUTs), not for SGLTs. Thus, glucose accumulation measured by 2-FDG omits the role of SGLTs. We designed and synthesized two high-affinity tracers: one, α-methyl-4-[F-18]fluoro-4-deoxy-D-glucopyranoside (Me-4FDG), is a highly specific SGLT substrate and not transported by GLUTs; the other one, 4-[F-18]fluoro-4-deoxy-D-glucose (4-FDG), is transported by both SGLTs and GLUTs and will pass through the blood brain barrier (BBB). In vitro Me-4FDG autoradiography was used to map the distribution of uptake by functional SGLTs in brain slices with a comparable result from in vitro 4-FDG autoradiography. Immunohistochemical assays showed that uptake was consistent with the distribution of SGLT protein. Ex vivo 4-FDG autoradiography showed that SGLTs in these areas are functionally active in the normal in vivo brain. The results establish that SGLTs are a normal part of the physiology of specific areas of the brain, including hippocampus, amygdala, hypothalamus, and cerebral cortices. 4-FDG PET imaging also established that this BBB-permeable SGLT tracer now offers a functional imaging approach in humans to assess regulation of SGLT activity in health and disease.

Changes in brain activation during working memory and facial recognition tasks in patients with bipolar disorder with Lamotrigine monotherapy.

PubMed

Haldane, Morgan; Jogia, Jigar; Cobb, Annabel; Kozuch, Eliza; Kumari, Veena; Frangou, Sophia

2008-01-01

Verbal working memory and emotional self-regulation are impaired in Bipolar Disorder (BD). Our aim was to investigate the effect of Lamotrigine (LTG), which is effective in the clinical management of BD, on the neural circuits subserving working memory and emotional processing. Functional Magnetic Resonance Imaging data from 12 stable BD patients was used to detect LTG-induced changes as the differences in brain activity between drug-free and post-LTG monotherapy conditions during a verbal working memory (N-back sequential letter task) and an angry facial affect recognition task. For both tasks, LGT monotherapy compared to baseline was associated with increased activation mostly within the prefrontal cortex and cingulate gyrus, in regions normally engaged in verbal working memory and emotional processing. Therefore, LTG monotherapy in BD patients may enhance cortical function within neural circuits involved in memory and emotional self-regulation.

Thyroid Hormone Acts Locally to Increase Neurogenesis, Neuronal Differentiation, and Dendritic Arbor Elaboration in the Tadpole Visual System

PubMed Central

Thompson, Christopher K.

2016-01-01

Thyroid hormone (TH) regulates many cellular events underlying perinatal brain development in vertebrates. Whether and how TH regulates brain development when neural circuits are first forming is less clear. Furthermore, although the molecular mechanisms that impose spatiotemporal constraints on TH action in the brain have been described, the effects of local TH signaling are poorly understood. We determined the effects of manipulating TH signaling on development of the optic tectum in stage 46–49 Xenopus laevis tadpoles. Global TH treatment caused large-scale morphological effects in tadpoles, including changes in brain morphology and increased tectal cell proliferation. Either increasing or decreasing endogenous TH signaling in tectum, by combining targeted DIO3 knockdown and methimazole, led to corresponding changes in tectal cell proliferation. Local increases in TH, accomplished by injecting suspensions of tri-iodothyronine (T3) in coconut oil into the midbrain ventricle or into the eye, selectively increased tectal or retinal cell proliferation, respectively. In vivo time-lapse imaging demonstrated that local TH first increased tectal progenitor cell proliferation, expanding the progenitor pool, and subsequently increased neuronal differentiation. Local T3 also dramatically increased dendritic arbor growth in neurons that had already reached a growth plateau. The time-lapse data indicate that the same cells are differentially sensitive to T3 at different time points. Finally, TH increased expression of genes pertaining to proliferation and neuronal differentiation. These experiments indicate that endogenous TH locally regulates neurogenesis at developmental stages relevant to circuit assembly by affecting cell proliferation and differentiation and by acting on neurons to increase dendritic arbor elaboration. SIGNIFICANCE STATEMENT Thyroid hormone (TH) is a critical regulator of perinatal brain development in vertebrates. Abnormal TH signaling in early pregnancy is associated with significant cognitive deficits in humans; however, it is difficult to probe the function of TH in early brain development in mammals because of the inaccessibility of the fetal brain in the uterine environment and the challenge of disambiguating maternal versus fetal contributions of TH. The external development of tadpoles allows manipulation and direct observation of the molecular and cellular mechanisms underlying TH's effects on brain development in ways not possible in mammals. We find that endogenous TH locally regulates neurogenesis at developmental stages relevant to circuit assembly by affecting neural progenitor cell proliferation and differentiation and by acting on neurons to enhance dendritic arbor elaboration. PMID:27707971

Novel active contour model based on multi-variate local Gaussian distribution for local segmentation of MR brain images

NASA Astrophysics Data System (ADS)

Zheng, Qiang; Li, Honglun; Fan, Baode; Wu, Shuanhu; Xu, Jindong

2017-12-01

Active contour model (ACM) has been one of the most widely utilized methods in magnetic resonance (MR) brain image segmentation because of its ability of capturing topology changes. However, most of the existing ACMs only consider single-slice information in MR brain image data, i.e., the information used in ACMs based segmentation method is extracted only from one slice of MR brain image, which cannot take full advantage of the adjacent slice images' information, and cannot satisfy the local segmentation of MR brain images. In this paper, a novel ACM is proposed to solve the problem discussed above, which is based on multi-variate local Gaussian distribution and combines the adjacent slice images' information in MR brain image data to satisfy segmentation. The segmentation is finally achieved through maximizing the likelihood estimation. Experiments demonstrate the advantages of the proposed ACM over the single-slice ACM in local segmentation of MR brain image series.

Identification of elevated urea as a severe, ubiquitous metabolic defect in the brain of patients with Huntington's disease.

PubMed

Patassini, Stefano; Begley, Paul; Reid, Suzanne J; Xu, Jingshu; Church, Stephanie J; Curtis, Maurice; Dragunow, Mike; Waldvogel, Henry J; Unwin, Richard D; Snell, Russell G; Faull, Richard L M; Cooper, Garth J S

Huntington's disease (HD) is a neurodegenerative disorder wherein the aetiological defect is a mutation in the Huntington's gene (HTT), which alters the structure of the huntingtin protein through the lengthening of a polyglutamine tract and initiates a cascade that ultimately leads to dementia and premature death. However, neurodegeneration typically manifests in HD only in middle age, and processes linking the causative mutation to brain disease are poorly understood. Here, our objective was to elucidate further the processes that cause neurodegeneration in HD, by measuring levels of metabolites in brain regions known to undergo varying degrees of damage. We applied gas-chromatography/mass spectrometry-based metabolomics in a case-control study of eleven brain regions in short post-mortem-delay human tissue from nine well-characterized HD patients and nine controls. Unexpectedly, a single major abnormality was evident in all eleven brain regions studied across the forebrain, midbrain and hindbrain, namely marked elevation of urea, a metabolite formed in the urea cycle by arginase-mediated cleavage of arginine. Urea cycle activity localizes primarily in the liver, where it functions to incorporate protein-derived amine-nitrogen into urea for recycling or urinary excretion. It also occurs in other cell-types, but systemic over-production of urea is not known in HD. These findings are consistent with impaired local urea regulation in brain, by up-regulation of synthesis and/or defective clearance. We hypothesize that defective brain urea metabolism could play a substantive role in the pathogenesis of neurodegeneration, perhaps via defects in osmoregulation or nitrogen metabolism. Brain urea metabolism is therefore a target for generating novel monitoring/imaging strategies and/or therapeutic interventions aimed at ameliorating the impact of HD in patients. Copyright © 2015 Elsevier Inc. All rights reserved.

Alteration of functional connectivity during real-time fMRI regulation of PCC

NASA Astrophysics Data System (ADS)

Zhang, Gaoyan; Yao, Li; Long, Zhiying

2012-03-01

Real-time functional magnetic resonance imaging (rtfMRI) can be used to train the subjects to selectively control activity of specific brain area so as to affect the activation in the target region and even to improve cognition and behavior. So far, whether brain activity in posterior cingulate cortex (PCC) can be regulated by rtfMRI has not been reported. In the present study, we aimed at investigating whether real-time regulation of activity in PCC can change the functional connectivity between PCC and other brain regions. A total of 12 subjects underwent two training runs, each lasts 782s. During the training, subjects were instructed to down regulate activity in PCC by imagining right hand finger movement with the sequence of 4-2-3-1-3-4-2 during task and relax as possible as they can during rest. To control for any effects induced by repeated practice, another 12 subjects in the control group received the same experiment procedure and instruction except with no feedback during training. Experiment results show that increased functional connectivity of PCC with medial frontal cortex (MFC) was observed in both groups during the two training runs. However, PCC of the experimental group is correlated with larger areas in MFC than the control group. Because the positive correlation between task performance and MFC to PCC connectivity has been demonstrated previously, we infer that the stronger connectivity between PCC and MFC in the experimental group may suggest that the experimental group with neurofeedback can more efficiently regulate PCC than the control group without neurofeedback.

The Nutrient-Responsive Hormone CCHamide-2 Controls Growth by Regulating Insulin-like Peptides in the Brain of Drosophila melanogaster.

PubMed

Sano, Hiroko; Nakamura, Akira; Texada, Michael J; Truman, James W; Ishimoto, Hiroshi; Kamikouchi, Azusa; Nibu, Yutaka; Kume, Kazuhiko; Ida, Takanori; Kojima, Masayasu

2015-05-01

The coordination of growth with nutritional status is essential for proper development and physiology. Nutritional information is mostly perceived by peripheral organs before being relayed to the brain, which modulates physiological responses. Hormonal signaling ensures this organ-to-organ communication, and the failure of endocrine regulation in humans can cause diseases including obesity and diabetes. In Drosophila melanogaster, the fat body (adipose tissue) has been suggested to play an important role in coupling growth with nutritional status. Here, we show that the peripheral tissue-derived peptide hormone CCHamide-2 (CCHa2) acts as a nutrient-dependent regulator of Drosophila insulin-like peptides (Dilps). A BAC-based transgenic reporter revealed strong expression of CCHa2 receptor (CCHa2-R) in insulin-producing cells (IPCs) in the brain. Calcium imaging of brain explants and IPC-specific CCHa2-R knockdown demonstrated that peripheral-tissue derived CCHa2 directly activates IPCs. Interestingly, genetic disruption of either CCHa2 or CCHa2-R caused almost identical defects in larval growth and developmental timing. Consistent with these phenotypes, the expression of dilp5, and the release of both Dilp2 and Dilp5, were severely reduced. Furthermore, transcription of CCHa2 is altered in response to nutritional levels, particularly of glucose. These findings demonstrate that CCHa2 and CCHa2-R form a direct link between peripheral tissues and the brain, and that this pathway is essential for the coordination of systemic growth with nutritional availability. A mammalian homologue of CCHa2-R, Bombesin receptor subtype-3 (Brs3), is an orphan receptor that is expressed in the islet β-cells; however, the role of Brs3 in insulin regulation remains elusive. Our genetic approach in Drosophila melanogaster provides the first evidence, to our knowledge, that bombesin receptor signaling with its endogenous ligand promotes insulin production.

Automated segmentation of three-dimensional MR brain images

NASA Astrophysics Data System (ADS)

Park, Jonggeun; Baek, Byungjun; Ahn, Choong-Il; Ku, Kyo Bum; Jeong, Dong Kyun; Lee, Chulhee

2006-03-01

Brain segmentation is a challenging problem due to the complexity of the brain. In this paper, we propose an automated brain segmentation method for 3D magnetic resonance (MR) brain images which are represented as a sequence of 2D brain images. The proposed method consists of three steps: pre-processing, removal of non-brain regions (e.g., the skull, meninges, other organs, etc), and spinal cord restoration. In pre-processing, we perform adaptive thresholding which takes into account variable intensities of MR brain images corresponding to various image acquisition conditions. In segmentation process, we iteratively apply 2D morphological operations and masking for the sequences of 2D sagittal, coronal, and axial planes in order to remove non-brain tissues. Next, final 3D brain regions are obtained by applying OR operation for segmentation results of three planes. Finally we reconstruct the spinal cord truncated during the previous processes. Experiments are performed with fifteen 3D MR brain image sets with 8-bit gray-scale. Experiment results show the proposed algorithm is fast, and provides robust and satisfactory results.

Hypoxic stress up-regulates Kir2.1 expression and facilitates cell proliferation in brain capillary endothelial cells.

PubMed

Yamamura, Hideto; Suzuki, Yoshiaki; Yamamura, Hisao; Asai, Kiyofumi; Imaizumi, Yuji

2016-08-05

The blood-brain barrier (BBB) is mainly composed of brain capillary endothelial cells (BCECs), astrocytes and pericytes. Brain ischemia causes hypoxic encephalopathy and damages BBB. However, it remains still unclear how hypoxia affects BCECs. In the present study, t-BBEC117 cells, an immortalized bovine brain endothelial cell line, were cultured under hypoxic conditions at 4-5% oxygen for 72 h. This hypoxic stress caused hyperpolarization of resting membrane potential. Patch-clamp recordings revealed a marked increase in Ba(2+)-sensitive inward rectifier K(+) current in t-BBEC117 cells after hypoxic culture. Western blot and real-time PCR analyses showed that Kir2.1 expression was significantly up-regulated at protein level but not at mRNA level after the hypoxic culture. Ca(2+) imaging study revealed that the hypoxic stress enhanced store-operated Ca(2+) (SOC) entry, which was significantly reduced in the presence of 100 μM Ba(2+). On the other hand, the expression of SOC channels such as Orai1, Orai2, and transient receptor potential channels was not affected by hypoxic stress. MTT assay showed that the hypoxic stress significantly enhanced t-BBEC117 cell proliferation, which was inhibited by approximately 60% in the presence of 100 μM Ba(2+). We first show here that moderate cellular stress by cultivation under hypoxic conditions hyperpolarizes membrane potential via the up-regulation of functional Kir2.1 expression and presumably enhances Ca(2+) entry, resulting in the facilitation of BCEC proliferation. These findings suggest potential roles of Kir2.1 expression in functional changes of BCECs in BBB following ischemia. Copyright © 2016 Elsevier Inc. All rights reserved.

Brain connectivity aberrations in anabolic-androgenic steroid users.

PubMed

Westlye, Lars T; Kaufmann, Tobias; Alnæs, Dag; Hullstein, Ingunn R; Bjørnebekk, Astrid

2017-01-01

Sustained anabolic-androgenic steroid (AAS) use has adverse behavioral consequences, including aggression, violence and impulsivity. Candidate mechanisms include disruptions of brain networks with high concentrations of androgen receptors and critically involved in emotional and cognitive regulation. Here, we tested the effects of AAS on resting-state functional brain connectivity in the largest sample of AAS-users to date. We collected resting-state functional magnetic resonance imaging (fMRI) data from 151 males engaged in heavy resistance strength training. 50 users tested positive for AAS based on the testosterone to epitestosterone (T/E) ratio and doping substances in urine. 16 previous users and 59 controls tested negative. We estimated brain network nodes and their time-series using ICA and dual regression and defined connectivity matrices as the between-node partial correlations. In line with the emotional and behavioral consequences of AAS, current users exhibited reduced functional connectivity between key nodes involved in emotional and cognitive regulation, in particular reduced connectivity between the amygdala and default-mode network (DMN) and between the dorsal attention network (DAN) and a frontal node encompassing the superior and inferior frontal gyri (SFG/IFG) and the anterior cingulate cortex (ACC), with further reductions as a function of dependency, lifetime exposure, and cycle state (on/off).

Exploration and Modulation of Brain Network Interactions with Noninvasive Brain Stimulation in Combination with Neuroimaging

PubMed Central

Shafi, Mouhsin M.; Westover, M. Brandon; Fox, Michael D.; Pascual-Leone, Alvaro

2012-01-01

Much recent work in systems neuroscience has focused on how dynamic interactions between different cortical regions underlie complex brain functions such as motor coordination, language, and emotional regulation. Various studies using neuroimaging and neurophysiologic techniques have suggested that in many neuropsychiatric disorders, these dynamic brain networks are dysregulated. Here we review the utility of combined noninvasive brain stimulation and neuroimaging approaches towards greater understanding of dynamic brain networks in health and disease. Brain stimulation techniques, such as transcranial magnetic stimulation and transcranial direct current stimulation, use electromagnetic principles to noninvasively alter brain activity, and induce focal but also network effects beyond the stimulation site. When combined with brain imaging techniques such as functional MRI, PET and EEG, these brain stimulation techniques enable a causal assessment of the interaction between different network components, and their respective functional roles. The same techniques can also be applied to explore hypotheses regarding the changes in functional connectivity that occur during task performance and in various disease states such as stroke, depression and schizophrenia. Finally, in diseases characterized by pathologic alterations in either the excitability within a single region or in the activity of distributed networks, such techniques provide a potential mechanism to alter cortical network function and architectures in a beneficial manner. PMID:22429242

Selective Audiovisual Semantic Integration Enabled by Feature-Selective Attention.

PubMed

Li, Yuanqing; Long, Jinyi; Huang, Biao; Yu, Tianyou; Wu, Wei; Li, Peijun; Fang, Fang; Sun, Pei

2016-01-13

An audiovisual object may contain multiple semantic features, such as the gender and emotional features of the speaker. Feature-selective attention and audiovisual semantic integration are two brain functions involved in the recognition of audiovisual objects. Humans often selectively attend to one or several features while ignoring the other features of an audiovisual object. Meanwhile, the human brain integrates semantic information from the visual and auditory modalities. However, how these two brain functions correlate with each other remains to be elucidated. In this functional magnetic resonance imaging (fMRI) study, we explored the neural mechanism by which feature-selective attention modulates audiovisual semantic integration. During the fMRI experiment, the subjects were presented with visual-only, auditory-only, or audiovisual dynamical facial stimuli and performed several feature-selective attention tasks. Our results revealed that a distribution of areas, including heteromodal areas and brain areas encoding attended features, may be involved in audiovisual semantic integration. Through feature-selective attention, the human brain may selectively integrate audiovisual semantic information from attended features by enhancing functional connectivity and thus regulating information flows from heteromodal areas to brain areas encoding the attended features.

Improving the convergence rate in affine registration of PET and SPECT brain images using histogram equalization.

PubMed

Salas-Gonzalez, D; Górriz, J M; Ramírez, J; Padilla, P; Illán, I A

2013-01-01

A procedure to improve the convergence rate for affine registration methods of medical brain images when the images differ greatly from the template is presented. The methodology is based on a histogram matching of the source images with respect to the reference brain template before proceeding with the affine registration. The preprocessed source brain images are spatially normalized to a template using a general affine model with 12 parameters. A sum of squared differences between the source images and the template is considered as objective function, and a Gauss-Newton optimization algorithm is used to find the minimum of the cost function. Using histogram equalization as a preprocessing step improves the convergence rate in the affine registration algorithm of brain images as we show in this work using SPECT and PET brain images.

Volitional regulation of brain responses to food stimuli in overweight and obese subjects: A real-time fMRI feedback study.

PubMed

Spetter, Maartje S; Malekshahi, Rahim; Birbaumer, Niels; Lührs, Michael; van der Veer, Albert H; Scheffler, Klaus; Spuckti, Sophia; Preissl, Hubert; Veit, Ralf; Hallschmid, Manfred

2017-05-01

Obese subjects who achieve weight loss show increased functional connectivity between dorsolateral prefrontal cortex (dlPFC) and ventromedial prefrontal cortex (vmPFC), key areas of executive control and reward processing. We investigated the potential of real-time functional magnetic resonance imaging (rt-fMRI) neurofeedback training to achieve healthier food choices by enhancing self-control of the interplay between these brain areas. We trained eight male individuals with overweight or obesity (age: 31.8 ± 4.4 years, BMI: 29.4 ± 1.4 kg/m 2 ) to up-regulate functional connectivity between the dlPFC and the vmPFC by means of a four-day rt-fMRI neurofeedback protocol including, on each day, three training runs comprised of six up-regulation and six passive viewing trials. During the up-regulation runs of the four training days, participants successfully learned to increase functional connectivity between dlPFC and vmPFC. In addition, a trend towards less high-calorie food choices emerged from before to after training, which however was associated with a trend towards increased covertly assessed snack intake. Findings of this proof-of-concept study indicate that overweight and obese participants can increase functional connectivity between brain areas that orchestrate the top-down control of appetite for high-calorie foods. Neurofeedback training might therefore be a useful tool in achieving and maintaining weight loss. Copyright © 2017 Elsevier Ltd. All rights reserved.

A Primer on Brain Imaging in Developmental Psychopathology: What Is It Good For?

ERIC Educational Resources Information Center

Pine, Daniel S.

2006-01-01

This primer introduces a Special Section on brain imaging, which includes a commentary and 10 data papers presenting applications of brain imaging to questions on developmental psychopathology. This primer serves two purposes. First, the article summarizes the strength and weaknesses of various brain-imaging techniques typically employed in…

Brain MR image segmentation using NAMS in pseudo-color.

PubMed

Li, Hua; Chen, Chuanbo; Fang, Shaohong; Zhao, Shengrong

2017-12-01

Image segmentation plays a crucial role in various biomedical applications. In general, the segmentation of brain Magnetic Resonance (MR) images is mainly used to represent the image with several homogeneous regions instead of pixels for surgical analyzing and planning. This paper proposes a new approach for segmenting MR brain images by using pseudo-color based segmentation with Non-symmetry and Anti-packing Model with Squares (NAMS). First of all, the NAMS model is presented. The model can represent the image with sub-patterns to keep the image content and largely reduce the data redundancy. Second, the key idea is proposed that convert the original gray-scale brain MR image into a pseudo-colored image and then segment the pseudo-colored image with NAMS model. The pseudo-colored image can enhance the color contrast in different tissues in brain MR images, which can improve the precision of segmentation as well as directly visual perceptional distinction. Experimental results indicate that compared with other brain MR image segmentation methods, the proposed NAMS based pseudo-color segmentation method performs more excellent in not only segmenting precisely but also saving storage.

Structural Image Analysis of the Brain in Neuropsychology Using Magnetic Resonance Imaging (MRI) Techniques.

PubMed

Bigler, Erin D

2015-09-01

Magnetic resonance imaging (MRI) of the brain provides exceptional image quality for visualization and neuroanatomical classification of brain structure. A variety of image analysis techniques provide both qualitative as well as quantitative methods to relate brain structure with neuropsychological outcome and are reviewed herein. Of particular importance are more automated methods that permit analysis of a broad spectrum of anatomical measures including volume, thickness and shape. The challenge for neuropsychology is which metric to use, for which disorder and the timing of when image analysis methods are applied to assess brain structure and pathology. A basic overview is provided as to the anatomical and pathoanatomical relations of different MRI sequences in assessing normal and abnormal findings. Some interpretive guidelines are offered including factors related to similarity and symmetry of typical brain development along with size-normalcy features of brain anatomy related to function. The review concludes with a detailed example of various quantitative techniques applied to analyzing brain structure for neuropsychological outcome studies in traumatic brain injury.

High-Speed and Scalable Whole-Brain Imaging in Rodents and Primates.

PubMed

Seiriki, Kaoru; Kasai, Atsushi; Hashimoto, Takeshi; Schulze, Wiebke; Niu, Misaki; Yamaguchi, Shun; Nakazawa, Takanobu; Inoue, Ken-Ichi; Uezono, Shiori; Takada, Masahiko; Naka, Yuichiro; Igarashi, Hisato; Tanuma, Masato; Waschek, James A; Ago, Yukio; Tanaka, Kenji F; Hayata-Takano, Atsuko; Nagayasu, Kazuki; Shintani, Norihito; Hashimoto, Ryota; Kunii, Yasuto; Hino, Mizuki; Matsumoto, Junya; Yabe, Hirooki; Nagai, Takeharu; Fujita, Katsumasa; Matsuda, Toshio; Takuma, Kazuhiro; Baba, Akemichi; Hashimoto, Hitoshi

2017-06-21

Subcellular resolution imaging of the whole brain and subsequent image analysis are prerequisites for understanding anatomical and functional brain networks. Here, we have developed a very high-speed serial-sectioning imaging system named FAST (block-face serial microscopy tomography), which acquires high-resolution images of a whole mouse brain in a speed range comparable to that of light-sheet fluorescence microscopy. FAST enables complete visualization of the brain at a resolution sufficient to resolve all cells and their subcellular structures. FAST renders unbiased quantitative group comparisons of normal and disease model brain cells for the whole brain at a high spatial resolution. Furthermore, FAST is highly scalable to non-human primate brains and human postmortem brain tissues, and can visualize neuronal projections in a whole adult marmoset brain. Thus, FAST provides new opportunities for global approaches that will allow for a better understanding of brain systems in multiple animal models and in human diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

Antecedent descriptions change brain reactivity to emotional stimuli: a functional magnetic resonance imaging study of an extrinsic and incidental reappraisal strategy.

PubMed

Mocaiber, I; Sanchez, T A; Pereira, M G; Erthal, F S; Joffily, M; Araujo, D B; Volchan, E; de Oliveira, L

2011-10-13

In the present study we investigated whether individuals would take advantage of an extrinsic and incidental reappraisal strategy by giving them precedent descriptions to attenuate the emotional impact of unpleasant pictures. In fact, precedent descriptions have successfully promoted down-regulation of electrocortical activity and physiological responses to unpleasant pictures. However, the neuronal substrate underlying this effect remains unclear. Particularly, we investigated whether amygdala and insula responses, brain regions consistently implicated in emotional processing, would be modulated by this strategy. To achieve this, highly unpleasant pictures were shown in two contexts in which a prior description presented them as taken from movie scenes (fictitious) or real scenes. Results showed that the fictitious condition was characterized by down-regulation of amygdala and insula responses. Thus, the present study provides new evidence on reappraisal strategies to down-regulate emotional reactions and suggest that amygdala and insula responses to emotional stimuli are adaptive and highly flexible. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

Deformably registering and annotating whole CLARITY brains to an atlas via masked LDDMM

NASA Astrophysics Data System (ADS)

Kutten, Kwame S.; Vogelstein, Joshua T.; Charon, Nicolas; Ye, Li; Deisseroth, Karl; Miller, Michael I.

2016-04-01

The CLARITY method renders brains optically transparent to enable high-resolution imaging in the structurally intact brain. Anatomically annotating CLARITY brains is necessary for discovering which regions contain signals of interest. Manually annotating whole-brain, terabyte CLARITY images is difficult, time-consuming, subjective, and error-prone. Automatically registering CLARITY images to a pre-annotated brain atlas offers a solution, but is difficult for several reasons. Removal of the brain from the skull and subsequent storage and processing cause variable non-rigid deformations, thus compounding inter-subject anatomical variability. Additionally, the signal in CLARITY images arises from various biochemical contrast agents which only sparsely label brain structures. This sparse labeling challenges the most commonly used registration algorithms that need to match image histogram statistics to the more densely labeled histological brain atlases. The standard method is a multiscale Mutual Information B-spline algorithm that dynamically generates an average template as an intermediate registration target. We determined that this method performs poorly when registering CLARITY brains to the Allen Institute's Mouse Reference Atlas (ARA), because the image histogram statistics are poorly matched. Therefore, we developed a method (Mask-LDDMM) for registering CLARITY images, that automatically finds the brain boundary and learns the optimal deformation between the brain and atlas masks. Using Mask-LDDMM without an average template provided better results than the standard approach when registering CLARITY brains to the ARA. The LDDMM pipelines developed here provide a fast automated way to anatomically annotate CLARITY images; our code is available as open source software at http://NeuroData.io.

Multicolor Fluorescence Imaging of Traumatic Brain Injury in a Cryolesion Mouse Model

PubMed Central

2012-01-01

Traumatic brain injury is characterized by initial tissue damage, which then can lead to secondary processes such as cell death and blood-brain-barrier disruption. Clinical and preclinical studies of traumatic brain injury typically employ anatomical imaging techniques and there is a need for new molecular imaging methods that provide complementary biochemical information. Here, we assess the ability of a targeted, near-infrared fluorescent probe, named PSS-794, to detect cell death in a brain cryolesion mouse model that replicates certain features of traumatic brain injury. In short, the model involves brief contact of a cold rod to the head of a living, anesthetized mouse. Using noninvasive whole-body fluorescence imaging, PSS-794 permitted visualization of the cryolesion in the living animal. Ex vivo imaging and histological analysis confirmed PSS-794 localization to site of brain cell death. The nontargeted, deep-red Tracer-653 was validated as a tracer dye for monitoring blood-brain-barrier disruption, and a binary mixture of PSS-794 and Tracer-653 was employed for multicolor imaging of cell death and blood-brain-barrier permeability in a single animal. The imaging data indicates that at 3 days after brain cryoinjury the amount of cell death had decreased significantly, but the integrity of the blood-brain-barrier was still impaired; at 7 days, the blood-brain-barrier was still three times more permeable than before cryoinjury. PMID:22860222

OPTICAL AND PHARMACOLOGICAL TOOLS TO INVESTIGATE THE ROLE OF MITOCHONDRIA DURING OXIDATIVE STRESS AND NEURODEGENERATION

PubMed Central

Foster, Kelley A.; Galeffi, Francesca; Gerich, Florian J.; Turner, Dennis A.; Müller, Michael

2007-01-01

Mitochondria are critical for cellular ATP production; however, recent studies suggest that these organelles fulfill a much broader range of tasks. For example, they are involved in the regulation of cytosolic Ca2+ levels, intracellular pH and apoptosis, and are the major source of reactive oxygen species (ROS). Various reactive molecules that originate from mitochondria, such as ROS, are critical in pathological events, such as ischemia, as well as in physiological events such as long-term potentiation, neuronal-vascular coupling and neuronal-glial interactions. Due to their key roles in the regulation of several cellular functions, the dysfunction of mitochondria may be critical in various brain disorders. There has been increasing interest in the development of tools that modulate mitochondrial function, and the refinement of techniques that allow for real time monitoring of mitochondria, particularly within their intact cellular environment. Innovative imaging techniques are especially powerful since they allow for mitochondrial visualization at high resolution, tracking of mitochondrial structures and optical real time monitoring of parameters of mitochondrial function. Among the techniques discussed are the uses of classic imaging techniques such as rhodamine-123, the highly advanced semi-conductor nanoparticles (quantum dots), and wide field microscopy as well as high-resolution multi-photon imaging. We have highlighted the use of these techniques to study mitochondrial function in brain tissue and have included studies from our laboratories in which these techniques have been successfully applied. PMID:16920246

A study of the standard brain in Japanese children: morphological comparison with the MNI template.

PubMed

Uchiyama, Hitoshi T; Seki, Ayumi; Tanaka, Daisuke; Koeda, Tatsuya; Jcs Group

2013-03-01

Functional magnetic resonance imaging (MRI) studies involve normalization so that the brains of different subjects can be described using the same coordinate system. However, standard brain templates, including the Montreal Neurological Institute (MNI) template that is most frequently used at present, were created based on the brains of Western adults. Because morphological characteristics of the brain differ by race and ethnicity and between adults and children, errors are likely to occur when data from the brains of non-Western individuals are processed using these templates. Therefore, this study was conducted to collect basic data for the creation of a Japanese pediatric standard brain. Participants in this study were 45 healthy children (contributing 65 brain images) between the ages of 6 and 9 years, who had nothing notable in their perinatal and other histories and neurological findings, had normal physical findings and cognitive function, exhibited no behavioral abnormalities, and provided analyzable MR images. 3D-T1-weighted images were obtained using a 1.5-T MRI device, and images from each child were adjusted to the reference image by affine transformation using SPM8. The lengths were measured and compared with those of the MNI template. The Western adult standard brain and the Japanese pediatric standard brain obtained in this study differed greatly in size, particularly along the anteroposterior diameter and in height, suggesting that the correction rates are high, and that errors are likely to occur in the normalization of pediatric brain images. We propose that the use of the Japanese pediatric standard brain created in this study will improve the accuracy of identification of brain regions in functional brain imaging studies involving children. Copyright © 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Virtual Reality Therapy for the Treatment of Alcohol Dependence: A Preliminary Investigation With Positron Emission Tomography/Computerized Tomography.

PubMed

Son, Ji Hyun; Lee, Sang Hoon; Seok, Ju Won; Kee, Baik Seok; Lee, Hyun Woong; Kim, Hyung Joon; Lee, Tae Kyung; Han, Doug Hyun

2015-07-01

Virtual reality therapy (VRT) uses multimodal stimulation that includes visual, auditory, olfactory, and gustatory stimuli. The aim of this study was to assess the effectiveness of VRT in treating subjects with alcohol dependence (AD) by evaluating changes in brain metabolism. The VRT protocol consisted of three steps: relaxation, presentation of a high-risk situation, and presentation of an aversive situation. Twelve alcohol-dependent subjects underwent 10 sessions of VRT. The alcohol-dependent subjects were assessed with 18F-fluorodeoxyglucose positron emission tomography images before and after VRT, whereas the control group underwent imaging according to the same protocol only at baseline. Compared with the healthy control group, AD subjects showed higher metabolism in the right lentiform nucleus and right temporal lobe (BA20) at baseline (P(FDR < .05) = .026). In addition, the metabolism in the left anterior cingulate was lower in subjects with AD (P(uncorr) = .001). After VRT, alcohol-dependent subjects showed decreased brain metabolism in the right lentiform nucleus (P(FDR < .05) = .026) and right temporal lobe (BA38, P(FDR < .05) = .032) relative to that at baseline. Our results suggest a neurobiological imbalance, notably, a high sensitivity to stimuli, in the limbic system in subjects with AD. Furthermore, we determined that metabolism decreased in the basal ganglia after VRT, which may explain the limbic-regulated responses of reward and regulation. Therefore, we tentatively recommend VRT to treat AD through its regulating effect on limbic circuits.

Aberrant brain stem morphometry associated with sleep disturbance in drug-naïve subjects with Alzheimer's disease.

PubMed

Lee, Ji Han; Jung, Won Sang; Choi, Woo Hee; Lim, Hyun Kook

2016-01-01

Among patients with Alzheimer's disease (AD), sleep disturbances are common and serious noncognitive symptoms. Previous studies of AD patients have identified deformations in the brain stem, which may play an important role in the regulation of sleep. The aim of this study was to further investigate the relationship between sleep disturbances and alterations in brain stem morphology in AD. In 44 patients with AD and 40 healthy elderly controls, sleep disturbances were measured using the Neuropsychiatry Inventory sleep subscale. We employed magnetic resonance imaging-based automated segmentation tools to examine the relationship between sleep disturbances and changes in brain stem morphology. Analyses of the data from AD subjects revealed significant correlations between the Neuropsychiatry Inventory sleep-subscale scores and structural alterations in the left posterior lateral region of the brain stem, as well as normalized brain stem volumes. In addition, significant group differences in posterior brain stem morphology were observed between the AD group and the control group. This study is the first to analyze an association between sleep disturbances and brain stem morphology in AD. In line with previous findings, this study lends support to the possibility that brain stem structural abnormalities might be important neurobiological mechanisms underlying sleep disturbances associated with AD. Further longitudinal research is needed to confirm these findings.

Enhanced visualization of MR angiogram with modified MIP and 3D image fusion

NASA Astrophysics Data System (ADS)

Kim, JongHyo; Yeon, Kyoung M.; Han, Man Chung; Lee, Dong Hyuk; Cho, Han I.

1997-05-01

We have developed a 3D image processing and display technique that include image resampling, modification of MIP, volume rendering, and fusion of MIP image with volumetric rendered image. This technique facilitates the visualization of the 3D spatial relationship between vasculature and surrounding organs by overlapping the MIP image on the volumetric rendered image of the organ. We applied this technique to a MR brain image data to produce an MRI angiogram that is overlapped with 3D volume rendered image of brain. MIP technique was used to visualize the vasculature of brain, and volume rendering was used to visualize the other structures of brain. The two images are fused after adjustment of contrast and brightness levels of each image in such a way that both the vasculature and brain structure are well visualized either by selecting the maximum value of each image or by assigning different color table to each image. The resultant image with this technique visualizes both the brain structure and vasculature simultaneously, allowing the physicians to inspect their relationship more easily. The presented technique will be useful for surgical planning for neurosurgery.

Semiautomated volumetry of the cerebrum, cerebellum-brain stem, and temporal lobe on brain magnetic resonance images.

PubMed

Hayashi, Norio; Sanada, Shigeru; Suzuki, Masayuki; Matsuura, Yukihiro; Kawahara, Kazuhiro; Tsujii, Hideo; Yamamoto, Tomoyuki; Matsui, Osamu

2008-02-01

The aim of this study was to develop an automated method of segmenting the cerebrum, cerebellum-brain stem, and temporal lobe simultaneously on magnetic resonance (MR) images. We obtained T1-weighted MR images from 10 normal subjects and 19 patients with brain atrophy. To perform automated volumetry from MR images, we performed the following three steps: (1) segmentation of the brain region; (2) separation between the cerebrum and the cerebellum-brain stem; and (3) segmentation of the temporal lobe. Evaluation was based on the correctly recognized region (CRR) (i.e., the region recognized by both the automated and manual methods). The mean CRRs of the normal and atrophic brains were 98.2% and 97.9% for the cerebrum, 87.9% and 88.5% for the cerebellum-brain stem, and 76.9% and 85.8% for the temporal lobe, respectively. We introduce an automated volumetric method for the cerebrum, cerebellum-brain stem, and temporal lobe on brain MR images. Our method can be applied to not only the normal brain but also the atrophic brain.

ViRPET--combination of virtual reality and PET brain imaging

DOEpatents

Majewski, Stanislaw; Brefczynski-Lewis, Julie

2017-05-23

Various methods, systems and apparatus are provided for brain imaging during virtual reality stimulation. In one example, among others, a system for virtual ambulatory environment brain imaging includes a mobile brain imager configured to obtain positron emission tomography (PET) scans of a subject in motion, and a virtual reality (VR) system configured to provide one or more stimuli to the subject during the PET scans. In another example, a method for virtual ambulatory environment brain imaging includes providing stimulation to a subject through a virtual reality (VR) system; and obtaining a positron emission tomography (PET) scan of the subject while moving in response to the stimulation from the VR system. The mobile brain imager can be positioned on the subject with an array of imaging photodetector modules distributed about the head of the subject.

Pain measurement and brain activity: will neuroimages replace pain ratings?

PubMed

Robinson, Michael E; Staud, Roland; Price, Donald D

2013-04-01

Arguments made for the advantages of replacing pain ratings with brain-imaging data include assumptions that pain ratings are less reliable and objective and that brain image data would greatly benefit the measurement of treatment efficacy. None of these assumptions are supported by available evidence. Self-report of pain is predictable and does not necessarily reflect unreliability or error. Because pain is defined as an experience, magnitudes of its dimensions can be estimated by well-established methods, including those used to validate brain imaging of pain. Brain imaging helps to study pain mechanisms and might be used as proxy measures of pain in persons unable to provide verbal reports. Yet eliminating pain ratings or replacing them with neuroimaging data is misguided because brain images only help explain pain if they are used in conjunction with self-report. There is no objective readout mechanism of pain (pain thermometer) that is unaffected by psychological factors. Benefits from including neuroimaging data might include increased understanding of underlying neural mechanisms of treatment efficacy, discovery of new treatment vectors, and support of conclusions derived from self-report. However, neither brain imaging nor self-report data are privileged over the other. The assumption that treatment efficacy is hampered by self-report has not been shown; there is a plethora of treatment studies showing that self-report is sensitive to treatment. Dismissal of patients' self-reports (pain ratings) by brain-imaging data is potentially harmful. The aim of replacing self-report with brain-imaging data is misguided and has no scientific or philosophical foundation. Although brain imaging may offer considerable insight into the neural mechanisms of pain, including relevant causes and correlations, brain images cannot and should not replace self-report. Only the latter assesses the experience of pain, which is not identical to neural activity. Brain imaging may help to explain pain, but replacing self-report with brain-imaging data would be philosophically and scientifically misguided and potentially harmful to pain patients. Copyright © 2013 American Pain Society. Published by Elsevier Inc. All rights reserved.

The study on increasing the equivalent SNR in the certain DOI by adjusting the SD separation in near-infrared brain imaging application

NASA Astrophysics Data System (ADS)

Wang, Jinhai; Liu, Dongyuan; Sun, Jinggong; Zhang, Yanjun; Sun, Qiuming; Ma, Jun; Zheng, Yu; Wang, Huiquan

2016-10-01

Near-infrared (NIR) brain imaging is one of the most promising techniques for brain research in recent years. As a significant supplement to the clinical imaging technique, such as CT and MRI, the NIR technique can achieve a fast, non-invasive, and low cost imaging of the brain, which is widely used for the brain functional imaging and hematoma detection. NIR imaging can achieve an imaging depth up to only several centimeters due to the reduced optical attenuation. The structure of the human brain is so particularly complex, from the perspective of optical detection, the measurement light needs go through the skin, skull, cerebrospinal fluid (CSF), grey matter, and white matter, and then reverses the order reflected by the detector. The more photons from the Depth of Interest (DOI) in brain the detector capture, the better detection accuracy and stability can be obtained. In this study, the Equivalent Signal to Noise Ratio (ESNR) was defined as the proportion of the photons from the DOI to the total photons the detector evaluated the best Source and Detector (SD) separation. The Monte-Carlo (MC) simulation was used to establish a multi brain layer model to analyze the distribution of the ESNR along the radial direction for different DOIs and several basic brain optical and structure parameters. A map between the best detection SD separation, in which distance the ESNR was the highest, and the brain parameters was established for choosing the best detection point in the NIR brain imaging application. The results showed that the ESNR was very sensitivity to the SD separation. So choosing the best SD separation based on the ESNR is very significant for NIR brain imaging application. It provides an important reference and new thinking for the brain imaging in the near infrared.

The role of image registration in brain mapping

PubMed Central

Toga, A.W.; Thompson, P.M.

2008-01-01

Image registration is a key step in a great variety of biomedical imaging applications. It provides the ability to geometrically align one dataset with another, and is a prerequisite for all imaging applications that compare datasets across subjects, imaging modalities, or across time. Registration algorithms also enable the pooling and comparison of experimental findings across laboratories, the construction of population-based brain atlases, and the creation of systems to detect group patterns in structural and functional imaging data. We review the major types of registration approaches used in brain imaging today. We focus on their conceptual basis, the underlying mathematics, and their strengths and weaknesses in different contexts. We describe the major goals of registration, including data fusion, quantification of change, automated image segmentation and labeling, shape measurement, and pathology detection. We indicate that registration algorithms have great potential when used in conjunction with a digital brain atlas, which acts as a reference system in which brain images can be compared for statistical analysis. The resulting armory of registration approaches is fundamental to medical image analysis, and in a brain mapping context provides a means to elucidate clinical, demographic, or functional trends in the anatomy or physiology of the brain. PMID:19890483

Dye-enhanced multimodal confocal imaging as a novel approach to intraoperative diagnosis of brain tumors.

PubMed

Snuderl, Matija; Wirth, Dennis; Sheth, Sameer A; Bourne, Sarah K; Kwon, Churl-Su; Ancukiewicz, Marek; Curry, William T; Frosch, Matthew P; Yaroslavsky, Anna N

2013-01-01

Intraoperative diagnosis plays an important role in accurate sampling of brain tumors, limiting the number of biopsies required and improving the distinction between brain and tumor. The goal of this study was to evaluate dye-enhanced multimodal confocal imaging for discriminating gliomas from nonglial brain tumors and from normal brain tissue for diagnostic use. We investigated a total of 37 samples including glioma (13), meningioma (7), metastatic tumors (9) and normal brain removed for nontumoral indications (8). Tissue was stained in 0.05 mg/mL aqueous solution of methylene blue (MB) for 2-5 minutes and multimodal confocal images were acquired using a custom-built microscope. After imaging, tissue was formalin fixed and paraffin embedded for standard neuropathologic evaluation. Thirteen pathologists provided diagnoses based on the multimodal confocal images. The investigated tumor types exhibited distinctive and complimentary characteristics in both the reflectance and fluorescence responses. Images showed distinct morphological features similar to standard histology. Pathologists were able to distinguish gliomas from normal brain tissue and nonglial brain tumors, and to render diagnoses from the images in a manner comparable to haematoxylin and eosin (H&E) slides. These results confirm the feasibility of multimodal confocal imaging for intravital intraoperative diagnosis. © 2012 The Authors; Brain Pathology © 2012 International Society of Neuropathology.

Neuroanatomical phenotyping of the mouse brain with three-dimensional autofluorescence imaging

PubMed Central

Wong, Michael D.; Dazai, Jun; Altaf, Maliha; Mark Henkelman, R.; Lerch, Jason P.; Nieman, Brian J.

2012-01-01

The structural organization of the brain is important for normal brain function and is critical to understand in order to evaluate changes that occur during disease processes. Three-dimensional (3D) imaging of the mouse brain is necessary to appreciate the spatial context of structures within the brain. In addition, the small scale of many brain structures necessitates resolution at the ∼10 μm scale. 3D optical imaging techniques, such as optical projection tomography (OPT), have the ability to image intact large specimens (1 cm3) with ∼5 μm resolution. In this work we assessed the potential of autofluorescence optical imaging methods, and specifically OPT, for phenotyping the mouse brain. We found that both specimen size and fixation methods affected the quality of the OPT image. Based on these findings we developed a specimen preparation method to improve the images. Using this method we assessed the potential of optical imaging for phenotyping. Phenotypic differences between wild-type male and female mice were quantified using computer-automated methods. We found that optical imaging of the endogenous autofluorescence in the mouse brain allows for 3D characterization of neuroanatomy and detailed analysis of brain phenotypes. This will be a powerful tool for understanding mouse models of disease and development and is a technology that fits easily within the workflow of biology and neuroscience labs. PMID:22718750

Advanced Pediatric Brain Imaging Research and Training Program

DTIC Science & Technology

2013-10-01

diffusion tensor imaging and perfusion ( arterial spin labeling) MRI data and to relate measures of global and regional brain microstructural organization...AD_________________ Award Number: W81XWH-11-2-0198 TITLE: Advanced Pediatric Brain Imaging...September 2013 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Advanced Pediatric Brain Imaging Research and Training Program 5b. GRANT NUMBER W81XWH

MRI Segmentation of the Human Brain: Challenges, Methods, and Applications

PubMed Central

Despotović, Ivana

2015-01-01

Image segmentation is one of the most important tasks in medical image analysis and is often the first and the most critical step in many clinical applications. In brain MRI analysis, image segmentation is commonly used for measuring and visualizing the brain's anatomical structures, for analyzing brain changes, for delineating pathological regions, and for surgical planning and image-guided interventions. In the last few decades, various segmentation techniques of different accuracy and degree of complexity have been developed and reported in the literature. In this paper we review the most popular methods commonly used for brain MRI segmentation. We highlight differences between them and discuss their capabilities, advantages, and limitations. To address the complexity and challenges of the brain MRI segmentation problem, we first introduce the basic concepts of image segmentation. Then, we explain different MRI preprocessing steps including image registration, bias field correction, and removal of nonbrain tissue. Finally, after reviewing different brain MRI segmentation methods, we discuss the validation problem in brain MRI segmentation. PMID:25945121

Driving the brain towards creativity and intelligence: A network control theory analysis.

PubMed

Kenett, Yoed N; Medaglia, John D; Beaty, Roger E; Chen, Qunlin; Betzel, Richard F; Thompson-Schill, Sharon L; Qiu, Jiang

2018-01-04

High-level cognitive constructs, such as creativity and intelligence, entail complex and multiple processes, including cognitive control processes. Recent neurocognitive research on these constructs highlight the importance of dynamic interaction across neural network systems and the role of cognitive control processes in guiding such a dynamic interaction. How can we quantitatively examine the extent and ways in which cognitive control contributes to creativity and intelligence? To address this question, we apply a computational network control theory (NCT) approach to structural brain imaging data acquired via diffusion tensor imaging in a large sample of participants, to examine how NCT relates to individual differences in distinct measures of creative ability and intelligence. Recent application of this theory at the neural level is built on a model of brain dynamics, which mathematically models patterns of inter-region activity propagated along the structure of an underlying network. The strength of this approach is its ability to characterize the potential role of each brain region in regulating whole-brain network function based on its anatomical fingerprint and a simplified model of node dynamics. We find that intelligence is related to the ability to "drive" the brain system into easy to reach neural states by the right inferior parietal lobe and lower integration abilities in the left retrosplenial cortex. We also find that creativity is related to the ability to "drive" the brain system into difficult to reach states by the right dorsolateral prefrontal cortex (inferior frontal junction) and higher integration abilities in sensorimotor areas. Furthermore, we found that different facets of creativity-fluency, flexibility, and originality-relate to generally similar but not identical network controllability processes. We relate our findings to general theories on intelligence and creativity. Copyright © 2018 Elsevier Ltd. All rights reserved.

Prefrontal and amygdala engagement during emotional reactivity and regulation in generalized anxiety disorder.

PubMed

Fitzgerald, Jacklynn M; Phan, K Luan; Kennedy, Amy E; Shankman, Stewart A; Langenecker, Scott A; Klumpp, Heide

2017-08-15

Emotion dysregulation is prominent in generalized anxiety disorder (GAD), characterized clinically by exaggerated reactivity to negative stimuli and difficulty in down-regulating this response. Although limited research implicates frontolimbic disturbances in GAD, whether neural aberrations occur during emotional reactivity, regulation, or both is not well understood. During functional magnetic resonance imaging (fMRI), 30 individuals with GAD and 30 healthy controls (HC) completed a well-validated explicit emotion regulation task designed to measure emotional reactivity and regulation of reactivity. During the task, participants viewed negative images ('Look-Negative' condition) and, on some trials, used a cognitive strategy to reduce negative affective response ('Reappraise' condition). Results from an Analysis of Variance corrected for whole brain multiple comparisons showed a significant group x condition interaction in the left amygdala and left inferior frontal gyrus (IFG). Results from post-hoc analyses showed that the GAD group engaged these regions to a greater extent than HCs during Look-Negative but not Reappraise. Behaviorally, the GAD group reported feeling more negative than the HC group in each condition, although both groups reported reduced negative affect following regulation. As comorbidity was permitted, the presence of concurrent disorders, like other anxiety disorders and depression, detracts our ability to classify neural engagement particular to GAD alone. Individuals with GAD exhibited over-engagement of amygdala and frontal regions during the viewing of negative images, compared to HCs. Together, these aberrations may indicate that deficits in emotional reactivity rather than regulation contribute to emotion dysregulation in those with GAD. Copyright © 2017. Published by Elsevier B.V.

Emotion Regulation Training for Treating Warfighters with Combat-Related PTSD Using Real-Time fMRI and EEG-Assisted Neurofeedback

DTIC Science & Technology

2014-10-01

Real-Time fMRI and EEG -Assisted Neurofeedback . PRINCIPAL INVESTIGATOR: Jerzy Bodurka RECIPIENT: Laureate Institute for Brain Research REPORT...imaging neurofeedback (rtfMRI-nf) training with concurrent electroencephalography ( EEG ) recordings to directly target and modulate the emotion...the project and are actively enrolling veterans to complete rtfMRI-nf neurofeedback training with simultaneous EEG recordings, and a pre-, post

The social life of laughter

PubMed Central

Scott, Sophie; Lavan, Nadine; Chen, Sinead; McGettigan, Carolyn

2014-01-01

Laughter is often considered to be the product of humour. However laughter is a social emotion, occurring most often in interactions, where it is associated with bonding, agreement, affection and emotional regulation. Laughter is underpinned by complex neural systems, allowing it to be used flexibly: in humans and chimpanzees, social (voluntary) laughter is distinctly different from evoked (involuntary) laughter, a distinction which is also seen in brain imaging studies of laughter. PMID:25439499

Proteomic analysis and comparison of the biopsy and autopsy specimen of human brain temporal lobe.

PubMed

He, Sizhi; Wang, Qingsong; He, Jintang; Pu, Hai; Yang, Wei; Ji, Jianguo

2006-09-01

The proteomic study on human temporal lobe can help us to understand the physiological function of CNS in normal as well as in pathological state. Proteomic tools are potent for the assessment of protein stability post mortem. In this pilot study, the human temporal lobe biopsy specimen with chronic pharmacoresistant temporal lobe epilepsy (TLE) and autopsy specimen in control were separated by 2-DE. Using MALDI-TOF-MS and MS/MS, 375 protein spots were identified which were the products of 267 genes. Six down-regulated and 23 up-regulated protein spots in the autopsy specimen were ascertained after the gel image analysis with the ImageMaster software. A number of proteins that include neurotransmitter metabolic and glycolytic enzymes, cytoprotective proteins and cytoskeleton were found decreased while the precursor of apolipoprotein A-I increased in the TLE brain. We tried several methods to prepare the protein samples and found that DNase and RNase treatment, ultracentrifugation and Amersham clean-up kit purification can improve gel separation quality. This work optimized the sample preparation method and constructed a primary protein database of human temporal lobe and found some proteins with remarkable level change probably involved in the post-mortem process and chronic pharmacoresistant TLE pathogenesis.

Improving data availability for brain image biobanking in healthy subjects: Practice-based suggestions from an international multidisciplinary working group

PubMed Central

Shenkin, Susan D.; Pernet, Cyril; Nichols, Thomas E.; Poline, Jean-Baptiste; Matthews, Paul M.; van der Lugt, Aad; Mackay, Clare; Lanyon, Linda; Mazoyer, Bernard; Boardman, James P.; Thompson, Paul M.; Fox, Nick; Marcus, Daniel S.; Sheikh, Aziz; Cox, Simon R.; Anblagan, Devasuda; Job, Dominic E.; Dickie, David Alexander; Rodriguez, David; Wardlaw, Joanna M.

2017-01-01

Brain imaging is now ubiquitous in clinical practice and research. The case for bringing together large amounts of image data from well-characterised healthy subjects and those with a range of common brain diseases across the life course is now compelling. This report follows a meeting of international experts from multiple disciplines, all interested in brain image biobanking. The meeting included neuroimaging experts (clinical and non-clinical), computer scientists, epidemiologists, clinicians, ethicists, and lawyers involved in creating brain image banks. The meeting followed a structured format to discuss current and emerging brain image banks; applications such as atlases; conceptual and statistical problems (e.g. defining ‘normality’); legal, ethical and technological issues (e.g. consents, potential for data linkage, data security, harmonisation, data storage and enabling of research data sharing). We summarise the lessons learned from the experiences of a wide range of individual image banks, and provide practical recommendations to enhance creation, use and reuse of neuroimaging data. Our aim is to maximise the benefit of the image data, provided voluntarily by research participants and funded by many organisations, for human health. Our ultimate vision is of a federated network of brain image biobanks accessible for large studies of brain structure and function. PMID:28232121

Improving data availability for brain image biobanking in healthy subjects: Practice-based suggestions from an international multidisciplinary working group.

PubMed

Shenkin, Susan D; Pernet, Cyril; Nichols, Thomas E; Poline, Jean-Baptiste; Matthews, Paul M; van der Lugt, Aad; Mackay, Clare; Lanyon, Linda; Mazoyer, Bernard; Boardman, James P; Thompson, Paul M; Fox, Nick; Marcus, Daniel S; Sheikh, Aziz; Cox, Simon R; Anblagan, Devasuda; Job, Dominic E; Dickie, David Alexander; Rodriguez, David; Wardlaw, Joanna M

2017-06-01

Brain imaging is now ubiquitous in clinical practice and research. The case for bringing together large amounts of image data from well-characterised healthy subjects and those with a range of common brain diseases across the life course is now compelling. This report follows a meeting of international experts from multiple disciplines, all interested in brain image biobanking. The meeting included neuroimaging experts (clinical and non-clinical), computer scientists, epidemiologists, clinicians, ethicists, and lawyers involved in creating brain image banks. The meeting followed a structured format to discuss current and emerging brain image banks; applications such as atlases; conceptual and statistical problems (e.g. defining 'normality'); legal, ethical and technological issues (e.g. consents, potential for data linkage, data security, harmonisation, data storage and enabling of research data sharing). We summarise the lessons learned from the experiences of a wide range of individual image banks, and provide practical recommendations to enhance creation, use and reuse of neuroimaging data. Our aim is to maximise the benefit of the image data, provided voluntarily by research participants and funded by many organisations, for human health. Our ultimate vision is of a federated network of brain image biobanks accessible for large studies of brain structure and function. Copyright © 2017 Elsevier Inc. All rights reserved.

Dedicated mobile volumetric cone-beam computed tomography for human brain imaging: A phantom study.

PubMed

Ryu, Jong-Hyun; Kim, Tae-Hoon; Jeong, Chang-Won; Jun, Hong-Young; Heo, Dong-Woon; Lee, Jinseok; Kim, Kyong-Woo; Yoon, Kwon-Ha

2015-01-01

Mobile computed tomography (CT) with a cone-beam source is increasingly used in the clinical field. Mobile cone-beam CT (CBCT) has great merits; however, its clinical utility for brain imaging has been limited due to problems including scan time and image quality. The aim of this study was to develop a dedicated mobile volumetric CBCT for obtaining brain images, and to optimize the imaging protocol using a brain phantom. The mobile volumetric CBCT system was evaluated with regards to scan time and image quality, measured as signal-to-noise-ratio (SNR), contrast-to-noise-ratio (CNR), spatial resolution (10% MTF), and effective dose. Brain images were obtained using a CT phantom. The CT scan took 5.14 s at 360 projection views. SNR and CNR were 5.67 and 14.5 at 120 kV/10 mA. SNR and CNR values showed slight improvement as the x-ray voltage and current increased (p < 0.001). Effective dose and 10% MTF were 0.92 mSv and 360 μ m at 120 kV/10 mA. Various intracranial structures were clearly visible in the brain phantom images. Using this CBCT under optimal imaging acquisition conditions, it is possible to obtain human brain images with low radiation dose, reproducible image quality, and fast scan time.

Opposite brain emotion-regulation patterns in identity states of dissociative identity disorder: a PET study and neurobiological model.

PubMed

Reinders, Antje A T S; Willemsen, Antoon T M; den Boer, Johan A; Vos, Herry P J; Veltman, Dick J; Loewenstein, Richard J

2014-09-30

Imaging studies in posttraumatic stress disorder (PTSD) have shown differing neural network patterns between hypo-aroused/dissociative and hyper-aroused subtypes. Since dissociative identity disorder (DID) involves different emotional states, this study tests whether DID fits aspects of the differing brain-activation patterns in PTSD. While brain activation was monitored using positron emission tomography, DID individuals (n=11) and matched DID-simulating healthy controls (n=16) underwent an autobiographic script-driven imagery paradigm in a hypo-aroused and a hyper-aroused identity state. Results were consistent with those previously found in the two PTSD subtypes for the rostral/dorsal anterior cingulate, the prefrontal cortex, and the amygdala and insula, respectively. Furthermore, the dissociative identity state uniquely activated the posterior association areas and the parahippocampal gyri, whereas the hyper-aroused identity state uniquely activated the caudate nucleus. Therefore, we proposed an extended PTSD-based neurobiological model for emotion modulation in DID: the hypo-aroused identity state activates the prefrontal cortex, cingulate, posterior association areas and parahippocampal gyri, thereby overmodulating emotion regulation; the hyper-aroused identity state activates the amygdala and insula as well as the dorsal striatum, thereby undermodulating emotion regulation. This confirms the notion that DID is related to PTSD as hypo-aroused and hyper-arousal states in DID and PTSD are similar. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

The iconographic brain. A critical philosophical inquiry into (the resistance of) the image

PubMed Central

De Vos, Jan

2014-01-01

The brain image plays a central role in contemporary image culture and, in turn, (co)constructs contemporary forms of subjectivity. The central aim of this paper is to probe the unmistakably potent interpellative power of brain images by delving into the power of imaging and the power of the image itself. This is not without relevance for the neurosciences, inasmuch as these do not take place in a vacuum; hence the importance of inquiring into the status of the image within scientific culture and science itself. I will mount a critical philosophical investigation of the brain qua image, focusing on the issue of mapping the mental onto the brain and how, in turn, the brain image plays a pivotal role in processes of subjectivation. Hereto, I draw upon Science & Technology Studies, juxtaposed with culture and ideology critique and theories of image culture. The first section sets out from Althusser's concept of interpellation, linking ideology to subjectivity. Doing so allows to spell out the central question of the paper: what could serve as the basis for a critical approach, or, where can a locus of resistance be found? In the second section, drawing predominantly on Baudrillard, I delve into the dimension of virtuality as this is opened up by brain image culture. This leads to the question of whether the digital brain must be opposed to old analog psychology: is it the psyche which resists? This issue is taken up in the third section which, ultimately, concludes that the psychological is not the requisite locus of resistance. The fourth section proceeds to delineate how the brain image is constructed from what I call the data-gaze (the claim that brain data are always already visual). In the final section, I discuss how an engagement with theories of iconology affords a critical understanding of the interpellative force of the brain image, which culminates in the somewhat unexpected claim that the sought after resistance lies in the very status of the image itself. PMID:24860480

Electrophysiological Source Imaging: A Noninvasive Window to Brain Dynamics.

PubMed

He, Bin; Sohrabpour, Abbas; Brown, Emery; Liu, Zhongming

2018-06-04

Brain activity and connectivity are distributed in the three-dimensional space and evolve in time. It is important to image brain dynamics with high spatial and temporal resolution. Electroencephalography (EEG) and magnetoencephalography (MEG) are noninvasive measurements associated with complex neural activations and interactions that encode brain functions. Electrophysiological source imaging estimates the underlying brain electrical sources from EEG and MEG measurements. It offers increasingly improved spatial resolution and intrinsically high temporal resolution for imaging large-scale brain activity and connectivity on a wide range of timescales. Integration of electrophysiological source imaging and functional magnetic resonance imaging could further enhance spatiotemporal resolution and specificity to an extent that is not attainable with either technique alone. We review methodological developments in electrophysiological source imaging over the past three decades and envision its future advancement into a powerful functional neuroimaging technology for basic and clinical neuroscience applications.

High-sensitivity terahertz imaging of traumatic brain injury in a rat model

NASA Astrophysics Data System (ADS)

Zhao, Hengli; Wang, Yuye; Chen, Linyu; Shi, Jia; Ma, Kang; Tang, Longhuang; Xu, Degang; Yao, Jianquan; Feng, Hua; Chen, Tunan

2018-03-01

We demonstrated that different degrees of experimental traumatic brain injury (TBI) can be differentiated clearly in fresh slices of rat brain tissues using transmission-type terahertz (THz) imaging system. The high absorption region in THz images corresponded well with the injured area in visible images and magnetic resonance imaging results. The THz image and absorption characteristics of dehydrated paraffin-embedded brain slices and the hematoxylin and eosin (H&E)-stained microscopic images were investigated to account for the intrinsic differences in the THz images for the brain tissues suffered from different degrees of TBI and normal tissue aside from water. The THz absorption coefficients of rat brain tissues showed an increase in the aggravation of brain damage, particularly in the high-frequency range, whereas the cell density decreased as the order of mild, moderate, and severe TBI tissues compared with the normal tissue. Our results indicated that the different degrees of TBI were distinguishable owing to the different water contents and probable hematoma components distribution rather than intrinsic cell intensity. These promising results suggest that THz imaging has great potential as an alternative method for the fast diagnosis of TBI.

Brain extraction from normal and pathological images: A joint PCA/Image-Reconstruction approach.

PubMed

Han, Xu; Kwitt, Roland; Aylward, Stephen; Bakas, Spyridon; Menze, Bjoern; Asturias, Alexander; Vespa, Paul; Van Horn, John; Niethammer, Marc

2018-08-01

Brain extraction from 3D medical images is a common pre-processing step. A variety of approaches exist, but they are frequently only designed to perform brain extraction from images without strong pathologies. Extracting the brain from images exhibiting strong pathologies, for example, the presence of a brain tumor or of a traumatic brain injury (TBI), is challenging. In such cases, tissue appearance may substantially deviate from normal tissue appearance and hence violates algorithmic assumptions for standard approaches to brain extraction; consequently, the brain may not be correctly extracted. This paper proposes a brain extraction approach which can explicitly account for pathologies by jointly modeling normal tissue appearance and pathologies. Specifically, our model uses a three-part image decomposition: (1) normal tissue appearance is captured by principal component analysis (PCA), (2) pathologies are captured via a total variation term, and (3) the skull and surrounding tissue is captured by a sparsity term. Due to its convexity, the resulting decomposition model allows for efficient optimization. Decomposition and image registration steps are alternated to allow statistical modeling of normal tissue appearance in a fixed atlas coordinate system. As a beneficial side effect, the decomposition model allows for the identification of potentially pathological areas and the reconstruction of a quasi-normal image in atlas space. We demonstrate the effectiveness of our approach on four datasets: the publicly available IBSR and LPBA40 datasets which show normal image appearance, the BRATS dataset containing images with brain tumors, and a dataset containing clinical TBI images. We compare the performance with other popular brain extraction models: ROBEX, BEaST, MASS, BET, BSE and a recently proposed deep learning approach. Our model performs better than these competing approaches on all four datasets. Specifically, our model achieves the best median (97.11) and mean (96.88) Dice scores over all datasets. The two best performing competitors, ROBEX and MASS, achieve scores of 96.23/95.62 and 96.67/94.25 respectively. Hence, our approach is an effective method for high quality brain extraction for a wide variety of images. Copyright © 2018 Elsevier Inc. All rights reserved.

Medical Imaging for Understanding Sleep Regulation

NASA Astrophysics Data System (ADS)

Wong, Kenneth

2011-10-01

Sleep is essential for the health of the nervous system. Lack of sleep has a profound negative effect on cognitive ability and task performance. During sustained military operations, soldiers often suffer from decreased quality and quantity of sleep, increasing their susceptibility to neurological problems and limiting their ability to perform the challenging mental tasks that their missions require. In the civilian sector, inadequate sleep and overt sleep pathology are becoming more common, with many detrimental impacts. There is a strong need for new, in vivo studies of human brains during sleep, particularly the initial descent from wakefulness. Our research team is investigating sleep using a combination of magnetic resonance imaging (MRI), positron emission tomography (PET), and electroencephalography (EEG). High resolution MRI combined with PET enables localization of biochemical processes (e.g., metabolism) to anatomical structures. MRI methods can also be used to examine functional connectivity among brain regions. Neural networks are dynamically reordered during different sleep stages, reflecting the disconnect with the waking world and the essential yet unconscious brain activity that occurs during sleep.[4pt] In collaboration with Linda Larson-Prior, Washington University; Alpay Ozcan, Virginia Tech; Seong Mun, Virginia Tech; and Zang-Hee Cho, Gachon University.

Structured Illumination Diffuse Optical Tomography for Mouse Brain Imaging

NASA Astrophysics Data System (ADS)

Reisman, Matthew David

As advances in functional magnetic resonance imaging (fMRI) have transformed the study of human brain function, they have also widened the divide between standard research techniques used in humans and those used in mice, where high quality images are difficult to obtain using fMRI given the small volume of the mouse brain. Optical imaging techniques have been developed to study mouse brain networks, which are highly valuable given the ability to study brain disease treatments or development in a controlled environment. A planar imaging technique known as optical intrinsic signal (OIS) imaging has been a powerful tool for capturing functional brain hemodynamics in rodents. Recent wide field-of-view implementations of OIS have provided efficient maps of functional connectivity from spontaneous brain activity in mice. However, OIS requires scalp retraction and is limited to imaging a 2-dimensional view of superficial cortical tissues. Diffuse optical tomography (DOT) is a non-invasive, volumetric neuroimaging technique that has been valuable for bedside imaging of patients in the clinic, but previous DOT systems for rodent neuroimaging have been limited by either sparse spatial sampling or by slow speed. My research has been to develop diffuse optical tomography for whole brain mouse neuroimaging by expanding previous techniques to achieve high spatial sampling using multiple camera views for detection and high speed using structured illumination sources. I have shown the feasibility of this method to perform non-invasive functional neuroimaging in mice and its capabilities of imaging the entire volume of the brain. Additionally, the system has been built with a custom, flexible framework to accommodate the expansion to imaging multiple dynamic contrasts in the brain and populations that were previously difficult or impossible to image, such as infant mice and awake mice. I have contributed to preliminary feasibility studies of these more advanced techniques using OIS, which can now be carried out using the structured illumination diffuse optical tomography technique to perform longitudinal, non-invasive studies of the whole volume of the mouse brain.

Look again: effects of brain images and mind-brain dualism on lay evaluations of research.

PubMed

Hook, Cayce J; Farah, Martha J

2013-09-01

Brain scans have frequently been credited with uniquely seductive and persuasive qualities, leading to claims that fMRI research receives a disproportionate share of public attention and funding. It has been suggested that functional brain images are fascinating because they contradict dualist beliefs regarding the relationship between the body and the mind. Although previous research has indicated that brain images can increase judgments of an article's scientific reasoning, the hypotheses that brain scans make research appear more interesting, surprising, or worthy of funding have not been tested. Neither has the relation between the allure of brain imaging and dualism. In the following three studies, laypersons rated both fictional research descriptions and real science news articles accompanied by brain scans, bar charts, or photographs. Across 988 participants, we found little evidence of neuroimaging's seductive allure or of its relation to self-professed dualistic beliefs. These results, taken together with other recent null findings, suggest that brain images are less powerful than has been argued.

Combined multi-kernel head computed tomography images optimized for depicting both brain parenchyma and bone.

PubMed

Takagi, Satoshi; Nagase, Hiroyuki; Hayashi, Tatsuya; Kita, Tamotsu; Hayashi, Katsumi; Sanada, Shigeru; Koike, Masayuki

2014-01-01

The hybrid convolution kernel technique for computed tomography (CT) is known to enable the depiction of an image set using different window settings. Our purpose was to decrease the number of artifacts in the hybrid convolution kernel technique for head CT and to determine whether our improved combined multi-kernel head CT images enabled diagnosis as a substitute for both brain (low-pass kernel-reconstructed) and bone (high-pass kernel-reconstructed) images. Forty-four patients with nondisplaced skull fractures were included. Our improved multi-kernel images were generated so that pixels of >100 Hounsfield unit in both brain and bone images were composed of CT values of bone images and other pixels were composed of CT values of brain images. Three radiologists compared the improved multi-kernel images with bone images. The improved multi-kernel images and brain images were identically displayed on the brain window settings. All three radiologists agreed that the improved multi-kernel images on the bone window settings were sufficient for diagnosing skull fractures in all patients. This improved multi-kernel technique has a simple algorithm and is practical for clinical use. Thus, simplified head CT examinations and fewer images that need to be stored can be expected.

Reliability evaluation of I-123 ADAM SPECT imaging using SPM software and AAL ROI methods

NASA Astrophysics Data System (ADS)

Yang, Bang-Hung; Tsai, Sung-Yi; Wang, Shyh-Jen; Su, Tung-Ping; Chou, Yuan-Hwa; Chen, Chia-Chieh; Chen, Jyh-Cheng

2011-08-01

The level of serotonin was regulated by serotonin transporter (SERT), which is a decisive protein in regulation of serotonin neurotransmission system. Many psychiatric disorders and therapies were also related to concentration of cerebral serotonin. I-123 ADAM was the novel radiopharmaceutical to image SERT in brain. The aim of this study was to measure reliability of SERT densities of healthy volunteers by automated anatomical labeling (AAL) method. Furthermore, we also used statistic parametric mapping (SPM) on a voxel by voxel analysis to find difference of cortex between test and retest of I-123 ADAM single photon emission computed tomography (SPECT) images.Twenty-one healthy volunteers were scanned twice with SPECT at 4 h after intravenous administration of 185 MBq of 123I-ADAM. The image matrix size was 128×128 and pixel size was 3.9 mm. All images were obtained through filtered back-projection (FBP) reconstruction algorithm. Region of interest (ROI) definition was performed based on the AAL brain template in PMOD version 2.95 software package. ROI demarcations were placed on midbrain, pons, striatum, and cerebellum. All images were spatially normalized to the SPECT MNI (Montreal Neurological Institute) templates supplied with SPM2. And each image was transformed into standard stereotactic space, which was matched to the Talairach and Tournoux atlas. Then differences across scans were statistically estimated on a voxel by voxel analysis using paired t-test (population main effect: 2 cond's, 1 scan/cond.), which was applied to compare concentration of SERT between the test and retest cerebral scans.The average of specific uptake ratio (SUR: target/cerebellum-1) of 123I-ADAM binding to SERT in midbrain was 1.78±0.27, pons was 1.21±0.53, and striatum was 0.79±0.13. The cronbach's α of intra-class correlation coefficient (ICC) was 0.92. Besides, there was also no significant statistical finding in cerebral area using SPM2 analysis. This finding might help us to understand reliability of I-123 ADAM SPECT imaging and further develop new strategy for the treatment of psychiatric disorders.

Habitual emotion regulation strategies and depressive symptoms in healthy subjects predict fMRI brain activation patterns related to major depression.

PubMed

Abler, Birgit; Hofer, Christian; Walter, Henrik; Erk, Susanne; Hoffmann, Holger; Traue, Harald C; Kessler, Henrik

2010-08-30

The response-focused emotion regulation style 'Expressive suppression' has been associated with symptoms of lower psychological well-being and increased function magnetic resonance imaging (fMRI) activation of the sublenticular extended amygdala (SLEA) in patients with major depression. Extending prior studies on active emotion regulation, we were interested in effects of habitual emotion regulation on neurobiology. Thirty subjects with either relatively high or low suppression scores as assessed with the Emotion Regulation Questionnaire without symptoms of clinical depression participated in the study. They were instructed to expect and then perceive emotionally unpleasant, pleasant or neutral stimuli selected from the International Affective Picture System that were announced by a congruent cue during fMRI. In the subjects with high suppression scores, decreased activation of the orbital medial prefrontal cortex (oMFC) when expecting negative pictures and increased activation of the SLEA upon presentation of neutral stimuli were found. Subclinical depression ratings independently of suppression scores in the healthy subjects were positively correlated with brain activation in the SLEA when expecting negative pictures. SLEA hyperactivity may represent an emotional responsivity that involves less successful habitual emotion regulation and a tendency to depressed mood in healthy subjects, as shown in patients with major depression. Decreased anticipatory oMFC activation may parallel a lack of antecedent emotion regulation in subjects with high suppression scores, representing another neurobiological predictor of lower mental well-being. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

The neural correlates of regulating another person's emotions: an exploratory fMRI study

PubMed Central

Hallam, Glyn P.; Webb, Thomas L.; Sheeran, Paschal; Miles, Eleanor; Niven, Karen; Wilkinson, Iain D.; Hunter, Michael D.; Woodruff, Peter W. R.; Totterdell, Peter; Farrow, Tom F. D.

2014-01-01

Studies investigating the neurophysiological basis of intrapersonal emotion regulation (control of one's own emotional experience) report that the frontal cortex exerts a modulatory effect on limbic structures such as the amygdala and insula. However, no imaging study to date has examined the neurophysiological processes involved in interpersonal emotion regulation, where the goal is explicitly to regulate another person's emotion. Twenty healthy participants (10 males) underwent fMRI while regulating their own or another person's emotions. Intrapersonal and interpersonal emotion regulation tasks recruited an overlapping network of brain regions including bilateral lateral frontal cortex, pre-supplementary motor area, and left temporo-parietal junction. Activations unique to the interpersonal condition suggest that both affective (emotional simulation) and cognitive (mentalizing) aspects of empathy may be involved in the process of interpersonal emotion regulation. These findings provide an initial insight into the neural correlates of regulating another person's emotions and may be relevant to understanding mental health issues that involve problems with social interaction. PMID:24936178

The effects of high-intensity exercise on neural responses to images of food.

PubMed

Crabtree, Daniel R; Chambers, Edward S; Hardwick, Robert M; Blannin, Andrew K

2014-02-01

Acute bouts of high-intensity exercise modulate peripheral appetite regulating hormones to transiently suppress hunger. However, the effects of physical activity on central appetite regulation have yet to be fully investigated. We used functional magnetic resonance imaging (fMRI) to compare neural responses to visual food stimuli after intense exercise and rest. Fifteen lean healthy men [mean ± SD age: 22.5 ± 3.1 y; mean ± SD body mass index (in kg/m(2)): 24.2 ± 2.4] completed two 60-min trials-exercise (EX; running at ∼70% maximum aerobic capacity) and a resting control trial (REST)-in a counterbalanced order. After each trial, an fMRI assessment was completed in which images of high- and low-calorie foods were viewed. EX significantly suppressed subjective appetite responses while increasing thirst and core-body temperature. Furthermore, EX significantly suppressed ghrelin concentrations and significantly enhanced peptide YY release. Neural responses to images of high-calorie foods significantly increased dorsolateral prefrontal cortex activation and suppressed orbitofrontal cortex (OFC) and hippocampus activation after EX compared with REST. After EX, low-calorie food images increased insula and putamen activation and reduced OFC activation compared with REST. Furthermore, left pallidum activity was significantly elevated after EX when low-calorie images were viewed and was suppressed when high-calorie images were viewed, and these responses correlated significantly with thirst. Exercise increases neural responses in reward-related regions of the brain in response to images of low-calorie foods and suppresses activation during the viewing of high-calorie foods. These central responses are associated with exercise-induced changes in peripheral signals related to appetite-regulation and hydration status. This trial was registered at www.clinicaltrials.gov as NCT01926431.

D-serine signalling as a prominent determinant of neuronal-glial dialogue in the healthy and diseased brain.

PubMed

Billard, J-M

2008-10-01

Rather different from their initial image as passive supportive cells of the CNS, the astrocytes are now considered as active partners at synapses, able to release a set of gliotransmitter-like substances to modulate synaptic communication within neuronal networks. Whereas glutamate and ATP were first regarded as main determinants of gliotransmission, growing evidence indicates now that the amino acid D-serine is another important player in the neuronal-glial dialogue. Through the regulation of glutamatergic neurotransmission through both N-methyl-D-aspartate (NMDA-R) and non-NMDA-R, D-serine is helping in modelling the appropriate connections in the developing brain and influencing the functional plasticity within neuronal networks throughout lifespan. The understanding of D-serine signalling, which has increased linearly in the last few years, gives new insights into the critical role of impaired neuronal-glial communication in the diseased brain, and offers new opportunities for developing relevant strategies to treat cognitive deficits associated to brain disorders.

Variability in Reward Responsivity and Obesity: Evidence from Brain Imaging Studies

PubMed Central

Burger, Kyle S.; Stice, Eric

2012-01-01

Advances in neuroimaging techniques have provided insight into the role of the brain in the regulation of food intake and weight. Growing evidence demonstrate that energy dense, palatable foods elicit similar responses in reward-related brain regions that mimic those of addictive substances. Currently, various models of obesity’s relation to reward from food have been theorized. There is evidence to support a theory of hypo-responsivity of reward regions to food, where individuals consume excess amounts to overcome this reward deficit. There is also data to support a theory of hyper-responsivity of reward regions, where individuals who experience greater reward from food intake are at risk for overeating. However, these seemingly discordant theories are static in nature and do not account for the possible effects of repeated overeating on brain responsivity to food and initial vulnerability factors. Here we review data that support these theories and propose a dynamic vulnerability model of obesity that appears to offer a parsimonious theory that accommodates extant findings. PMID:21999692

D-serine signalling as a prominent determinant of neuronal-glial dialogue in the healthy and diseased brain

PubMed Central

Billard, J-M

2008-01-01

Rather different from their initial image as passive supportive cells of the CNS, the astrocytes are now considered as active partners at synapses, able to release a set of gliotransmitter-like substances to modulate synaptic communication within neuronal networks. Whereas glutamate and ATP were first regarded as main determinants of gliotransmission, growing evidence indicates now that the amino acid D-serine is another important player in the neuronal-glial dialogue. Through the regulation of glutamatergic neurotransmission through both N-methyl-D-aspartate (NMDA-R) and non-NMDA-R, D-serine is helping in modelling the appropriate connections in the developing brain and influencing the functional plasticity within neuronal networks throughout lifespan. The understanding of D-serine signalling, which has increased linearly in the last few years, gives new insights into the critical role of impaired neuronal-glial communication in the diseased brain, and offers new opportunities for developing relevant strategies to treat cognitive deficits associated to brain disorders. PMID:18363840

Brain lesions in septic shock: a magnetic resonance imaging study.

PubMed

Sharshar, Tarek; Carlier, Robert; Bernard, Francis; Guidoux, Céline; Brouland, Jean-Philippe; Nardi, Olivier; de la Grandmaison, Geoffroy Lorin; Aboab, Jérôme; Gray, Françoise; Menon, David; Annane, Djillali

2007-05-01

Understanding of sepsis-induced brain dysfunction remains poor, and relies mainly on data from animals or post-mortem studies in patients. The current study provided findings from magnetic resonance imaging of the brain in septic shock. Nine patients with septic shock and brain dysfunction [7 women, median age 63 years (interquartile range 61-79 years), SAPS II: 48 (44-56), SOFA: 8 (6-10)] underwent brain magnetic resonance imaging including gradient echo T1-weighted, fluid-attenuated inversion recovery (FLAIR), T2-weighted and diffusion isotropic images, and mapping of apparent diffusion coefficient. Brain imaging was normal in two patients, showed multiple ischaemic strokes in two patients, and in the remaining patients showed white matter lesions at the level of the centrum semiovale, predominating around Virchow-Robin spaces, ranging from small multiple areas to diffuse lesions, and characterised by hyperintensity on FLAIR images. The main lesions were also characterised by reduced signal on diffusion isotropic images and increased apparent diffusion coefficient. The lesions of the white matter worsened with increasing duration of shock and were correlated with Glasgow Outcome Score. This preliminary study showed that sepsis-induced brain lesions can be documented by magnetic resonance imaging. These lesions predominated in the white matter, suggesting increased blood-brain barrier permeability, and were associated with poor outcome.

Dorsal brain stem syndrome: MR imaging location of brain stem tegmental lesions in neonates with oral motor dysfunction.

PubMed

Quattrocchi, C C; Longo, D; Delfino, L N; Cilio, M R; Piersigilli, F; Capua, M D; Seganti, G; Danhaive, O; Fariello, G

2010-09-01

The anatomic extent of brain stem damage may provide information about clinical outcome and prognosis in children with hypoxic-ischemic encephalopathy and oral motor dysfunction. The aim of this study was to retrospectively characterize the location and extent of brain stem lesions in children with oral motor dysfunction. From January 2005 to August 2009, 43 infants hospitalized at our institution were included in the study because of a history of hypoxic-ischemic events. Of this group, 14 patients showed oral motor dysfunction and brain stem tegmental lesions detected at MR imaging. MR imaging showed hypoxic-ischemic lesions in supra- and infratentorial areas. Six of 14 patients revealed only infratentorial lesions. Focal symmetric lesions of the tegmental brain stem were always present. The lesions appeared hyperintense on T2-weighted images and hypointense on IR images. We found a strong association (P < .0001) between oral motor dysfunction and infratentorial lesions on MR imaging. Oral motor dysfunction was associated with brain stem tegmental lesions in posthypoxic-ischemic infants. The MR imaging examination should be directed to the brain stem, especially when a condition of prolonged gavage feeding is necessary in infants.

Quantitative comparison of 3D third harmonic generation and fluorescence microscopy images.

PubMed

Zhang, Zhiqing; Kuzmin, Nikolay V; Groot, Marie Louise; de Munck, Jan C

2018-01-01

Third harmonic generation (THG) microscopy is a label-free imaging technique that shows great potential for rapid pathology of brain tissue during brain tumor surgery. However, the interpretation of THG brain images should be quantitatively linked to images of more standard imaging techniques, which so far has been done qualitatively only. We establish here such a quantitative link between THG images of mouse brain tissue and all-nuclei-highlighted fluorescence images, acquired simultaneously from the same tissue area. For quantitative comparison of a substantial pair of images, we present here a segmentation workflow that is applicable for both THG and fluorescence images, with a precision of 91.3 % and 95.8 % achieved respectively. We find that the correspondence between the main features of the two imaging modalities amounts to 88.9 %, providing quantitative evidence of the interpretation of dark holes as brain cells. Moreover, 80 % bright objects in THG images overlap with nuclei highlighted in the fluorescence images, and they are 2 times smaller than the dark holes, showing that cells of different morphologies can be recognized in THG images. We expect that the described quantitative comparison is applicable to other types of brain tissue and with more specific staining experiments for cell type identification. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

3-D in vivo brain tumor geometry study by scaling analysis

NASA Astrophysics Data System (ADS)

Torres Hoyos, F.; Martín-Landrove, M.

2012-02-01

A new method, based on scaling analysis, is used to calculate fractal dimension and local roughness exponents to characterize in vivo 3-D tumor growth in the brain. Image acquisition was made according to the standard protocol used for brain radiotherapy and radiosurgery, i.e., axial, coronal and sagittal magnetic resonance T1-weighted images, and comprising the brain volume for image registration. Image segmentation was performed by the application of the k-means procedure upon contrasted images. We analyzed glioblastomas, astrocytomas, metastases and benign brain tumors. The results show significant variations of the parameters depending on the tumor stage and histological origin.

Some Problems for Representations of Brain Organization Based on Activation in Functional Imaging

ERIC Educational Resources Information Center

Sidtis, John J.

2007-01-01

Functional brain imaging has overshadowed traditional lesion studies in becoming the dominant approach to the study of brain-behavior relationships. The proponents of functional imaging studies frequently argue that this approach provides an advantage over lesion studies by observing normal brain activity in vivo without the disruptive effects of…

Transcriptional regulation of brain gene expression in response to a territorial intrusion

PubMed Central

Sanogo, Yibayiri O.; Band, Mark; Blatti, Charles; Sinha, Saurabh; Bell, Alison M.

2012-01-01

Aggressive behaviour associated with territorial defence is widespread and has fitness consequences. However, excess aggression can interfere with other important biological functions such as immunity and energy homeostasis. How the expression of complex behaviours such as aggression is regulated in the brain has long intrigued ethologists, but has only recently become amenable for molecular dissection in non-model organisms. We investigated the transcriptomic response to territorial intrusion in four brain regions in breeding male threespined sticklebacks using expression microarrays and quantitative polymerase chain reaction (qPCR). Each region of the brain had a distinct genomic response to a territorial challenge. We identified a set of genes that were upregulated in the diencephalon and downregulated in the cerebellum and the brain stem. Cis-regulatory network analysis suggested transcription factors that regulated or co-regulated genes that were consistently regulated in all brain regions and others that regulated gene expression in opposing directions across brain regions. Our results support the hypothesis that territorial animals respond to social challenges via transcriptional regulation of genes in different brain regions. Finally, we found a remarkably close association between gene expression and aggressive behaviour at the individual level. This study sheds light on the molecular mechanisms in the brain that underlie the response to social challenges. PMID:23097509

The FTD-like syndrome causing TREM2 T66M mutation impairs microglia function, brain perfusion, and glucose metabolism.

PubMed

Kleinberger, Gernot; Brendel, Matthias; Mracsko, Eva; Wefers, Benedikt; Groeneweg, Linda; Xiang, Xianyuan; Focke, Carola; Deußing, Maximilian; Suárez-Calvet, Marc; Mazaheri, Fargol; Parhizkar, Samira; Pettkus, Nadine; Wurst, Wolfgang; Feederle, Regina; Bartenstein, Peter; Mueggler, Thomas; Arzberger, Thomas; Knuesel, Irene; Rominger, Axel; Haass, Christian

2017-07-03

Genetic variants in the triggering receptor expressed on myeloid cells 2 (TREM2) increase the risk for several neurodegenerative diseases including Alzheimer's disease and frontotemporal dementia (FTD). Homozygous TREM2 missense mutations, such as p.T66M, lead to the FTD-like syndrome, but how they cause pathology is unknown. Using CRISPR/Cas9 genome editing, we generated a knock-in mouse model for the disease-associated Trem2 p.T66M mutation. Consistent with a loss-of-function mutation, we observe an intracellular accumulation of immature mutant Trem2 and reduced generation of soluble Trem2 similar to patients with the homozygous p.T66M mutation. Trem2 p.T66M knock-in mice show delayed resolution of inflammation upon in vivo lipopolysaccharide stimulation and cultured macrophages display significantly reduced phagocytic activity. Immunohistochemistry together with in vivo TSPO small animal positron emission tomography (μPET) demonstrates an age-dependent reduction in microglial activity. Surprisingly, perfusion magnetic resonance imaging and FDG-μPET imaging reveal a significant reduction in cerebral blood flow and brain glucose metabolism. Thus, we demonstrate that a TREM2 loss-of-function mutation causes brain-wide metabolic alterations pointing toward a possible function of microglia in regulating brain glucose metabolism. © 2017 The Authors.

Robust generative asymmetric GMM for brain MR image segmentation.

PubMed

Ji, Zexuan; Xia, Yong; Zheng, Yuhui

2017-11-01

Accurate segmentation of brain tissues from magnetic resonance (MR) images based on the unsupervised statistical models such as Gaussian mixture model (GMM) has been widely studied during last decades. However, most GMM based segmentation methods suffer from limited accuracy due to the influences of noise and intensity inhomogeneity in brain MR images. To further improve the accuracy for brain MR image segmentation, this paper presents a Robust Generative Asymmetric GMM (RGAGMM) for simultaneous brain MR image segmentation and intensity inhomogeneity correction. First, we develop an asymmetric distribution to fit the data shapes, and thus construct a spatial constrained asymmetric model. Then, we incorporate two pseudo-likelihood quantities and bias field estimation into the model's log-likelihood, aiming to exploit the neighboring priors of within-cluster and between-cluster and to alleviate the impact of intensity inhomogeneity, respectively. Finally, an expectation maximization algorithm is derived to iteratively maximize the approximation of the data log-likelihood function to overcome the intensity inhomogeneity in the image and segment the brain MR images simultaneously. To demonstrate the performances of the proposed algorithm, we first applied the proposed algorithm to a synthetic brain MR image to show the intermediate illustrations and the estimated distribution of the proposed algorithm. The next group of experiments is carried out in clinical 3T-weighted brain MR images which contain quite serious intensity inhomogeneity and noise. Then we quantitatively compare our algorithm to state-of-the-art segmentation approaches by using Dice coefficient (DC) on benchmark images obtained from IBSR and BrainWeb with different level of noise and intensity inhomogeneity. The comparison results on various brain MR images demonstrate the superior performances of the proposed algorithm in dealing with the noise and intensity inhomogeneity. In this paper, the RGAGMM algorithm is proposed which can simply and efficiently incorporate spatial constraints into an EM framework to simultaneously segment brain MR images and estimate the intensity inhomogeneity. The proposed algorithm is flexible to fit the data shapes, and can simultaneously overcome the influence of noise and intensity inhomogeneity, and hence is capable of improving over 5% segmentation accuracy comparing with several state-of-the-art algorithms. Copyright © 2017 Elsevier B.V. All rights reserved.

Non-invasive imaging of the levels and effects of glutathione on the redox status of mouse brain using electron paramagnetic resonance imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Emoto, Miho C.; Department of Neurology, Sapporo Medical University School of Medicine, Sapporo, Hokkaido 060-8556; Matsuoka, Yuta

Glutathione (GSH) is the most abundant non-protein thiol that buffers reactive oxygen species in the brain. GSH does not reduce nitroxides directly, but in the presence of ascorbates, addition of GSH increases ascorbate-induced reduction of nitroxides. In this study, we used electron paramagnetic resonance (EPR) imaging and the nitroxide imaging probe, 3-methoxycarbonyl-2,2,5,5-tetramethyl-piperidine-1-oxyl (MCP), to non-invasively obtain spatially resolved redox data from mouse brains depleted of GSH with diethyl maleate compared to control. Based on the pharmacokinetics of the reduction reaction of MCP in the mouse heads, the pixel-based rate constant of its reduction reaction was calculated as an index ofmore » the redox status in vivo and mapped as a “redox map”. The obtained redox maps from control and GSH-depleted mouse brains showed a clear change in the brain redox status, which was due to the decreased levels of GSH in brains as measured by a biochemical assay. We observed a linear relationship between the reduction rate constant of MCP and the level of GSH for both control and GSH-depleted mouse brains. Using this relationship, the GSH level in the brain can be estimated from the redox map obtained with EPR imaging. - Highlights: • Redox status of glutathione-depleted mouse brain was examined with EPR imaging. • Redox status of mouse brain changed depending on glutathione (GSH) levels in brains. • Linear relationship between GSH levels and redox status in brains was found. • Using this relation, estimation of GSH levels in brains is possible from EPR images.« less

Selective Audiovisual Semantic Integration Enabled by Feature-Selective Attention

PubMed Central

Li, Yuanqing; Long, Jinyi; Huang, Biao; Yu, Tianyou; Wu, Wei; Li, Peijun; Fang, Fang; Sun, Pei

2016-01-01

An audiovisual object may contain multiple semantic features, such as the gender and emotional features of the speaker. Feature-selective attention and audiovisual semantic integration are two brain functions involved in the recognition of audiovisual objects. Humans often selectively attend to one or several features while ignoring the other features of an audiovisual object. Meanwhile, the human brain integrates semantic information from the visual and auditory modalities. However, how these two brain functions correlate with each other remains to be elucidated. In this functional magnetic resonance imaging (fMRI) study, we explored the neural mechanism by which feature-selective attention modulates audiovisual semantic integration. During the fMRI experiment, the subjects were presented with visual-only, auditory-only, or audiovisual dynamical facial stimuli and performed several feature-selective attention tasks. Our results revealed that a distribution of areas, including heteromodal areas and brain areas encoding attended features, may be involved in audiovisual semantic integration. Through feature-selective attention, the human brain may selectively integrate audiovisual semantic information from attended features by enhancing functional connectivity and thus regulating information flows from heteromodal areas to brain areas encoding the attended features. PMID:26759193

On the growth and form of cortical convolutions

NASA Astrophysics Data System (ADS)

Tallinen, Tuomas; Chung, Jun Young; Rousseau, François; Girard, Nadine; Lefèvre, Julien; Mahadevan, L.

2016-06-01

The rapid growth of the human cortex during development is accompanied by the folding of the brain into a highly convoluted structure. Recent studies have focused on the genetic and cellular regulation of cortical growth, but understanding the formation of the gyral and sulcal convolutions also requires consideration of the geometry and physical shaping of the growing brain. To study this, we use magnetic resonance images to build a 3D-printed layered gel mimic of the developing smooth fetal brain; when immersed in a solvent, the outer layer swells relative to the core, mimicking cortical growth. This relative growth puts the outer layer into mechanical compression and leads to sulci and gyri similar to those in fetal brains. Starting with the same initial geometry, we also build numerical simulations of the brain modelled as a soft tissue with a growing cortex, and show that this also produces the characteristic patterns of convolutions over a realistic developmental course. All together, our results show that although many molecular determinants control the tangential expansion of the cortex, the size, shape, placement and orientation of the folds arise through iterations and variations of an elementary mechanical instability modulated by early fetal brain geometry.

Imaging of brain metastases.

PubMed

Fink, Kathleen R; Fink, James R

2013-01-01

Imaging plays a key role in the diagnosis of central nervous system (CNS) metastasis. Imaging is used to detect metastases in patients with known malignancies and new neurological signs or symptoms, as well as to screen for CNS involvement in patients with known cancer. Computed tomography (CT) and magnetic resonance imaging (MRI) are the key imaging modalities used in the diagnosis of brain metastases. In difficult cases, such as newly diagnosed solitary enhancing brain lesions in patients without known malignancy, advanced imaging techniques including proton magnetic resonance spectroscopy (MRS), contrast enhanced magnetic resonance perfusion (MRP), diffusion weighted imaging (DWI), and diffusion tensor imaging (DTI) may aid in arriving at the correct diagnosis. This image-rich review discusses the imaging evaluation of patients with suspected intracranial involvement and malignancy, describes typical imaging findings of parenchymal brain metastasis on CT and MRI, and provides clues to specific histological diagnoses such as the presence of hemorrhage. Additionally, the role of advanced imaging techniques is reviewed, specifically in the context of differentiating metastasis from high-grade glioma and other solitary enhancing brain lesions. Extra-axial CNS involvement by metastases, including pachymeningeal and leptomeningeal metastases is also briefly reviewed.

In vivo rat deep brain imaging using photoacoustic computed tomography (Conference Presentation)

NASA Astrophysics Data System (ADS)

Lin, Li; Li, Lei; Zhu, Liren; Hu, Peng; Wang, Lihong V.

2017-03-01

The brain has been likened to a great stretch of unknown territory consisting of a number of unexplored continents. Small animal brain imaging plays an important role charting that territory. By using 1064 nm illumination from the side, we imaged the full coronal depth of rat brains in vivo. The experiment was performed using a real-time full-ring-array photoacoustic computed tomography (PACT) imaging system, which achieved an imaging depth of 11 mm and a 100 μm radial resolution. Because of the fast imaging speed of the full-ring-array PACT system, no animal motion artifact was induced. The frame rate of the system was limited by the laser repetition rate (50 Hz). In addition to anatomical imaging of the blood vessels in the brain, we continuously monitored correlations between the two brain hemispheres in one of the coronal planes. The resting states in the coronal plane were measured before and after stroke ligation surgery at a neck artery.

Registration of 3D fetal neurosonography and MRI☆

PubMed Central

Kuklisova-Murgasova, Maria; Cifor, Amalia; Napolitano, Raffaele; Papageorghiou, Aris; Quaghebeur, Gerardine; Rutherford, Mary A.; Hajnal, Joseph V.; Noble, J. Alison; Schnabel, Julia A.

2013-01-01

We propose a method for registration of 3D fetal brain ultrasound with a reconstructed magnetic resonance fetal brain volume. This method, for the first time, allows the alignment of models of the fetal brain built from magnetic resonance images with 3D fetal brain ultrasound, opening possibilities to develop new, prior information based image analysis methods for 3D fetal neurosonography. The reconstructed magnetic resonance volume is first segmented using a probabilistic atlas and a pseudo ultrasound image volume is simulated from the segmentation. This pseudo ultrasound image is then affinely aligned with clinical ultrasound fetal brain volumes using a robust block-matching approach that can deal with intensity artefacts and missing features in the ultrasound images. A qualitative and quantitative evaluation demonstrates good performance of the method for our application, in comparison with other tested approaches. The intensity average of 27 ultrasound images co-aligned with the pseudo ultrasound template shows good correlation with anatomy of the fetal brain as seen in the reconstructed magnetic resonance image. PMID:23969169

Advantages in functional imaging of the brain.

PubMed

Mier, Walter; Mier, Daniela

2015-01-01

As neuronal pathologies cause only minor morphological alterations, molecular imaging techniques are a prerequisite for the study of diseases of the brain. The development of molecular probes that specifically bind biochemical markers and the advances of instrumentation have revolutionized the possibilities to gain insight into the human brain organization and beyond this-visualize structure-function and brain-behavior relationships. The review describes the development and current applications of functional brain imaging techniques with a focus on applications in psychiatry. A historical overview of the development of functional imaging is followed by the portrayal of the principles and applications of positron emission tomography (PET) and functional magnetic resonance imaging (fMRI), two key molecular imaging techniques that have revolutionized the ability to image molecular processes in the brain. We conclude that the juxtaposition of PET and fMRI in hybrid PET/MRI scanners enhances the significance of both modalities for research in neurology and psychiatry and might pave the way for a new area of personalized medicine.

A validation framework for brain tumor segmentation.

PubMed

Archip, Neculai; Jolesz, Ferenc A; Warfield, Simon K

2007-10-01

We introduce a validation framework for the segmentation of brain tumors from magnetic resonance (MR) images. A novel unsupervised semiautomatic brain tumor segmentation algorithm is also presented. The proposed framework consists of 1) T1-weighted MR images of patients with brain tumors, 2) segmentation of brain tumors performed by four independent experts, 3) segmentation of brain tumors generated by a semiautomatic algorithm, and 4) a software tool that estimates the performance of segmentation algorithms. We demonstrate the validation of the novel segmentation algorithm within the proposed framework. We show its performance and compare it with existent segmentation. The image datasets and software are available at http://www.brain-tumor-repository.org/. We present an Internet resource that provides access to MR brain tumor image data and segmentation that can be openly used by the research community. Its purpose is to encourage the development and evaluation of segmentation methods by providing raw test and image data, human expert segmentation results, and methods for comparing segmentation results.

[Neurofeedback for the treatment of chronic tinnitus : Review and future perspectives].

PubMed

Kleinjung, T; Thüring, C; Güntensperger, D; Neff, P; Meyer, M

2018-03-01

Neurofeedback is a noninvasive neuromodulation technique employing real-time display of brain activity in terms of electroencephalography (EEG) signals to teach self-regulation of distinct patterns of brain activity or influence brain activity in a targeted manner. The benefit of this approach for control of symptoms in attention deficit disorders, hyperactivity, depression, and migraine has been proven. Studies in recent years have also repeatedly shown this treatment to improve tinnitus symptoms, although it has not become established as routine therapy. The primary focus of this review is the rational of EEG neurofeedback for tinnitus treatment and the currently available data from published studies. Furthermore, alternative neurofeedback protocols using real-time functional magnetic resonance imaging (fMRI) measurements for tinnitus control are considered. Finally, this article highlights how modern EEG analysis (source localization, connectivity) and the improving understanding of tinnitus pathology can contribute to development of more focused neurofeedback protocols for more sustainable control of tinnitus.

Vasodilation by in vivo activation of astrocyte endfeet via two-photon calcium uncaging as a strategy to prevent brain ischemia

NASA Astrophysics Data System (ADS)

Chen, Yuanxin; Mancuso, James; Zhao, Zhen; Li, Xuping; Cheng, Jie; Roman, Gustavo; Wong, Stephen T. C.

2013-12-01

Decreased cerebral blood flow causes brain ischemia and plays an important role in the pathophysiology of many neurodegenerative diseases, including Alzheimer's disease and vascular dementia. In this study, we photomodulated astrocytes in the live animal by a combination of two-photon calcium uncaging in the astrocyte endfoot and in vivo imaging of neurovasculature and astrocytes by intravital two-photon microscopy after labeling with cell type specific fluorescent dyes. Our study demonstrates that photomodulation at the endfoot of a single astrocyte led to a 25% increase in the diameter of a neighboring arteriole, which is a crucial factor regulating cerebral microcirculation in downstream capillaries. Two-photon uncaging in the astrocyte soma or endfoot near veins does not show the same effect on microcirculation. These experimental results suggest that infrared photomodulation on astrocyte endfeet may be a strategy to increase cerebral local microcirculation and thus prevent brain ischemia.

Automated deep-phenotyping of the vertebrate brain

PubMed Central

Allalou, Amin; Wu, Yuelong; Ghannad-Rezaie, Mostafa; Eimon, Peter M; Yanik, Mehmet Fatih

2017-01-01

Here, we describe an automated platform suitable for large-scale deep-phenotyping of zebrafish mutant lines, which uses optical projection tomography to rapidly image brain-specific gene expression patterns in 3D at cellular resolution. Registration algorithms and correlation analysis are then used to compare 3D expression patterns, to automatically detect all statistically significant alterations in mutants, and to map them onto a brain atlas. Automated deep-phenotyping of a mutation in the master transcriptional regulator fezf2 not only detects all known phenotypes but also uncovers important novel neural deficits that were overlooked in previous studies. In the telencephalon, we show for the first time that fezf2 mutant zebrafish have significant patterning deficits, particularly in glutamatergic populations. Our findings reveal unexpected parallels between fezf2 function in zebrafish and mice, where mutations cause deficits in glutamatergic neurons of the telencephalon-derived neocortex. DOI: http://dx.doi.org/10.7554/eLife.23379.001 PMID:28406399

In-vivo imaging of the morphology and blood perfusion of brain tumours in rats with UHR-OCT (Conference Presentation)

NASA Astrophysics Data System (ADS)

Bizheva, Kostadinka; Tan, Bingyao; Fisher, Carl J.; Mason, Erik; Lilge, Lothar D.

2017-02-01

Brain tumors are characterized with morphological changes at cellular level such as enlarged, non-spherical nuclei, microcalcifications, cysts, etc., and are highly vascularized. In this study, two research-grade optical coherence tomography (OCT) systems operating at 800 nm and 1060 nm with axial resolution of 0.95 µm and 3.5 µm in biological tissue respectively, were used to image in vivo and ex vivo the structure of brain tumours in rats. Female Fischer 344 rats were used for this study, which has received ethics clearance by the Animal Research Ethics Committees of the University of Waterloo and the University Health Network, Toronto. Brain tumours were induced by injection of rat brain cancer cell line (RG2 glioma) through a small craniotomy. Presence of brain tumours was verified by MRI imaging on day 7 post tumour cells injection. The in vivo OCT imaging session was conducted on day 14 of the study with the 1060 nm OCT system and both morphological OCT, Doppler OCT and OMAG images were acquired from the brain tumour and the surrounding healthy brain tissue. After completion of the imaging procedure, the brains were harvested, fixed in formalin and reimaged after 2 weeks with the 800 nm OCT system. The in vivo and ex vivo OCT morphological images were correlated with H and E histology. Results from this study demonstrate that UHR-OCT can distinguish between healthy and cancerous brain tissue based on differences in structural and vascular pattern.

Advancing multiscale structural mapping of the brain through fluorescence imaging and analysis across length scales

PubMed Central

Hogstrom, L. J.; Guo, S. M.; Murugadoss, K.; Bathe, M.

2016-01-01

Brain function emerges from hierarchical neuronal structure that spans orders of magnitude in length scale, from the nanometre-scale organization of synaptic proteins to the macroscopic wiring of neuronal circuits. Because the synaptic electrochemical signal transmission that drives brain function ultimately relies on the organization of neuronal circuits, understanding brain function requires an understanding of the principles that determine hierarchical neuronal structure in living or intact organisms. Recent advances in fluorescence imaging now enable quantitative characterization of neuronal structure across length scales, ranging from single-molecule localization using super-resolution imaging to whole-brain imaging using light-sheet microscopy on cleared samples. These tools, together with correlative electron microscopy and magnetic resonance imaging at the nanoscopic and macroscopic scales, respectively, now facilitate our ability to probe brain structure across its full range of length scales with cellular and molecular specificity. As these imaging datasets become increasingly accessible to researchers, novel statistical and computational frameworks will play an increasing role in efforts to relate hierarchical brain structure to its function. In this perspective, we discuss several prominent experimental advances that are ushering in a new era of quantitative fluorescence-based imaging in neuroscience along with novel computational and statistical strategies that are helping to distil our understanding of complex brain structure. PMID:26855758

Automated Morphological Analysis of Microglia After Stroke.

PubMed

Heindl, Steffanie; Gesierich, Benno; Benakis, Corinne; Llovera, Gemma; Duering, Marco; Liesz, Arthur

2018-01-01

Microglia are the resident immune cells of the brain and react quickly to changes in their environment with transcriptional regulation and morphological changes. Brain tissue injury such as ischemic stroke induces a local inflammatory response encompassing microglial activation. The change in activation status of a microglia is reflected in its gradual morphological transformation from a highly ramified into a less ramified or amoeboid cell shape. For this reason, the morphological changes of microglia are widely utilized to quantify microglial activation and studying their involvement in virtually all brain diseases. However, the currently available methods, which are mainly based on manual rating of immunofluorescent microscopic images, are often inaccurate, rater biased, and highly time consuming. To address these issues, we created a fully automated image analysis tool, which enables the analysis of microglia morphology from a confocal Z-stack and providing up to 59 morphological features. We developed the algorithm on an exploratory dataset of microglial cells from a stroke mouse model and validated the findings on an independent data set. In both datasets, we could demonstrate the ability of the algorithm to sensitively discriminate between the microglia morphology in the peri-infarct and the contralateral, unaffected cortex. Dimensionality reduction by principal component analysis allowed to generate a highly sensitive compound score for microglial shape analysis. Finally, we tested for concordance of results between the novel automated analysis tool and the conventional manual analysis and found a high degree of correlation. In conclusion, our novel method for the fully automatized analysis of microglia morphology shows excellent accuracy and time efficacy compared to traditional analysis methods. This tool, which we make openly available, could find application to study microglia morphology using fluorescence imaging in a wide range of brain disease models.

Brain volumetric abnormalities in patients with anorexia and bulimia nervosa: a voxel-based morphometry study.

PubMed

Amianto, Federico; Caroppo, Paola; D'Agata, Federico; Spalatro, Angela; Lavagnino, Luca; Caglio, Marcella; Righi, Dorico; Bergui, Mauro; Abbate-Daga, Giovanni; Rigardetto, Roberto; Mortara, Paolo; Fassino, Secondo

2013-09-30

Recent studies focussing on neuroimaging features of eating disorders have observed that anorexia nervosa (AN) is characterized by significant grey matter (GM) atrophy in many brain regions, especially in the cerebellum and anterior cingulate cortex. To date, no studies have found GM atrophy in bulimia nervosa (BN) or have directly compared patients with AN and BN. We used voxel-based morphometry (VBM) to characterize brain abnormalities in AN and BN patients, comparing them with each other and with a control group, and correlating brain volume with clinical features. We recruited 17 AN, 13 BN and 14 healthy controls. All subjects underwent high-resolution magnetic resonance imaging (MRI) with a T1-weighted 3D image. VBM analysis was carried out with the FSL-VBM 4.1 tool. We found no global atrophy, but regional GM reduction in AN with respect to controls and BN in the cerebellum, fusiform area, supplementary motor area, and occipital cortex, and in the caudate in BN compared to AN and controls. Both groups of patients had a volumetric increase bilaterally in somatosensory regions with respect to controls, in areas that are typically involved in the sensory-motor integration of body stimuli and in mental representation of the body image. Our VBM study documented, for the first time in BN patients, the presence of volumetric alterations and replicated previous findings in AN patients. We evidenced morphological differences between AN and BN, demonstrating in the latter atrophy of the caudate nucleus, a region involved in reward mechanisms and processes of self-regulation, perhaps involved in the genesis of the binge-eating behaviors of this disorder. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Common genetic variants influence human subcortical brain structures.

PubMed

Hibar, Derrek P; Stein, Jason L; Renteria, Miguel E; Arias-Vasquez, Alejandro; Desrivières, Sylvane; Jahanshad, Neda; Toro, Roberto; Wittfeld, Katharina; Abramovic, Lucija; Andersson, Micael; Aribisala, Benjamin S; Armstrong, Nicola J; Bernard, Manon; Bohlken, Marc M; Boks, Marco P; Bralten, Janita; Brown, Andrew A; Chakravarty, M Mallar; Chen, Qiang; Ching, Christopher R K; Cuellar-Partida, Gabriel; den Braber, Anouk; Giddaluru, Sudheer; Goldman, Aaron L; Grimm, Oliver; Guadalupe, Tulio; Hass, Johanna; Woldehawariat, Girma; Holmes, Avram J; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H; Olde Loohuis, Loes M; Luciano, Michelle; Macare, Christine; Mather, Karen A; Mattheisen, Manuel; Milaneschi, Yuri; Nho, Kwangsik; Papmeyer, Martina; Ramasamy, Adaikalavan; Risacher, Shannon L; Roiz-Santiañez, Roberto; Rose, Emma J; Salami, Alireza; Sämann, Philipp G; Schmaal, Lianne; Schork, Andrew J; Shin, Jean; Strike, Lachlan T; Teumer, Alexander; van Donkelaar, Marjolein M J; van Eijk, Kristel R; Walters, Raymond K; Westlye, Lars T; Whelan, Christopher D; Winkler, Anderson M; Zwiers, Marcel P; Alhusaini, Saud; Athanasiu, Lavinia; Ehrlich, Stefan; Hakobjan, Marina M H; Hartberg, Cecilie B; Haukvik, Unn K; Heister, Angelien J G A M; Hoehn, David; Kasperaviciute, Dalia; Liewald, David C M; Lopez, Lorna M; Makkinje, Remco R R; Matarin, Mar; Naber, Marlies A M; McKay, D Reese; Needham, Margaret; Nugent, Allison C; Pütz, Benno; Royle, Natalie A; Shen, Li; Sprooten, Emma; Trabzuni, Daniah; van der Marel, Saskia S L; van Hulzen, Kimm J E; Walton, Esther; Wolf, Christiane; Almasy, Laura; Ames, David; Arepalli, Sampath; Assareh, Amelia A; Bastin, Mark E; Brodaty, Henry; Bulayeva, Kazima B; Carless, Melanie A; Cichon, Sven; Corvin, Aiden; Curran, Joanne E; Czisch, Michael; de Zubicaray, Greig I; Dillman, Allissa; Duggirala, Ravi; Dyer, Thomas D; Erk, Susanne; Fedko, Iryna O; Ferrucci, Luigi; Foroud, Tatiana M; Fox, Peter T; Fukunaga, Masaki; Gibbs, J Raphael; Göring, Harald H H; Green, Robert C; Guelfi, Sebastian; Hansell, Narelle K; Hartman, Catharina A; Hegenscheid, Katrin; Heinz, Andreas; Hernandez, Dena G; Heslenfeld, Dirk J; Hoekstra, Pieter J; Holsboer, Florian; Homuth, Georg; Hottenga, Jouke-Jan; Ikeda, Masashi; Jack, Clifford R; Jenkinson, Mark; Johnson, Robert; Kanai, Ryota; Keil, Maria; Kent, Jack W; Kochunov, Peter; Kwok, John B; Lawrie, Stephen M; Liu, Xinmin; Longo, Dan L; McMahon, Katie L; Meisenzahl, Eva; Melle, Ingrid; Mohnke, Sebastian; Montgomery, Grant W; Mostert, Jeanette C; Mühleisen, Thomas W; Nalls, Michael A; Nichols, Thomas E; Nilsson, Lars G; Nöthen, Markus M; Ohi, Kazutaka; Olvera, Rene L; Perez-Iglesias, Rocio; Pike, G Bruce; Potkin, Steven G; Reinvang, Ivar; Reppermund, Simone; Rietschel, Marcella; Romanczuk-Seiferth, Nina; Rosen, Glenn D; Rujescu, Dan; Schnell, Knut; Schofield, Peter R; Smith, Colin; Steen, Vidar M; Sussmann, Jessika E; Thalamuthu, Anbupalam; Toga, Arthur W; Traynor, Bryan J; Troncoso, Juan; Turner, Jessica A; Valdés Hernández, Maria C; van 't Ent, Dennis; van der Brug, Marcel; van der Wee, Nic J A; van Tol, Marie-Jose; Veltman, Dick J; Wassink, Thomas H; Westman, Eric; Zielke, Ronald H; Zonderman, Alan B; Ashbrook, David G; Hager, Reinmar; Lu, Lu; McMahon, Francis J; Morris, Derek W; Williams, Robert W; Brunner, Han G; Buckner, Randy L; Buitelaar, Jan K; Cahn, Wiepke; Calhoun, Vince D; Cavalleri, Gianpiero L; Crespo-Facorro, Benedicto; Dale, Anders M; Davies, Gareth E; Delanty, Norman; Depondt, Chantal; Djurovic, Srdjan; Drevets, Wayne C; Espeseth, Thomas; Gollub, Randy L; Ho, Beng-Choon; Hoffmann, Wolfgang; Hosten, Norbert; Kahn, René S; Le Hellard, Stephanie; Meyer-Lindenberg, Andreas; Müller-Myhsok, Bertram; Nauck, Matthias; Nyberg, Lars; Pandolfo, Massimo; Penninx, Brenda W J H; Roffman, Joshua L; Sisodiya, Sanjay M; Smoller, Jordan W; van Bokhoven, Hans; van Haren, Neeltje E M; Völzke, Henry; Walter, Henrik; Weiner, Michael W; Wen, Wei; White, Tonya; Agartz, Ingrid; Andreassen, Ole A; Blangero, John; Boomsma, Dorret I; Brouwer, Rachel M; Cannon, Dara M; Cookson, Mark R; de Geus, Eco J C; Deary, Ian J; Donohoe, Gary; Fernández, Guillén; Fisher, Simon E; Francks, Clyde; Glahn, David C; Grabe, Hans J; Gruber, Oliver; Hardy, John; Hashimoto, Ryota; Hulshoff Pol, Hilleke E; Jönsson, Erik G; Kloszewska, Iwona; Lovestone, Simon; Mattay, Venkata S; Mecocci, Patrizia; McDonald, Colm; McIntosh, Andrew M; Ophoff, Roel A; Paus, Tomas; Pausova, Zdenka; Ryten, Mina; Sachdev, Perminder S; Saykin, Andrew J; Simmons, Andy; Singleton, Andrew; Soininen, Hilkka; Wardlaw, Joanna M; Weale, Michael E; Weinberger, Daniel R; Adams, Hieab H H; Launer, Lenore J; Seiler, Stephan; Schmidt, Reinhold; Chauhan, Ganesh; Satizabal, Claudia L; Becker, James T; Yanek, Lisa; van der Lee, Sven J; Ebling, Maritza; Fischl, Bruce; Longstreth, W T; Greve, Douglas; Schmidt, Helena; Nyquist, Paul; Vinke, Louis N; van Duijn, Cornelia M; Xue, Luting; Mazoyer, Bernard; Bis, Joshua C; Gudnason, Vilmundur; Seshadri, Sudha; Ikram, M Arfan; Martin, Nicholas G; Wright, Margaret J; Schumann, Gunter; Franke, Barbara; Thompson, Paul M; Medland, Sarah E

2015-04-09

The highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume and intracranial volume. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 × 10(-33); 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction.

Detecting stripe artifacts in ultrasound images.

PubMed

Maciak, Adam; Kier, Christian; Seidel, Günter; Meyer-Wiethe, Karsten; Hofmann, Ulrich G

2009-10-01

Brain perfusion diseases such as acute ischemic stroke are detectable through computed tomography (CT)-/magnetic resonance imaging (MRI)-based methods. An alternative approach makes use of ultrasound imaging. In this low-cost bedside method, noise and artifacts degrade the imaging process. Especially stripe artifacts show a similar signal behavior compared to acute stroke or brain perfusion diseases. This document describes how stripe artifacts can be detected and eliminated in ultrasound images obtained through harmonic imaging (HI). On the basis of this new method, both proper identification of areas with critically reduced brain tissue perfusion and classification between brain perfusion defects and ultrasound stripe artifacts are made possible.

Novel Nanotechnologies for Brain Cancer Therapeutics and Imaging.

PubMed

Ferroni, Letizia; Gardin, Chiara; Della Puppa, Alessandro; Sivolella, Stefano; Brunello, Giulia; Scienza, Renato; Bressan, Eriberto; D'Avella, Domenico; Zavan, Barbara

2015-11-01

Despite progress in surgery, radiotherapy, and in chemotherapy, an effective curative treatment of brain cancer, specifically malignant gliomas, does not yet exist. The efficacy of current anti-cancer strategies in brain tumors is limited by the lack of specific therapies against malignant cells. Besides, the delivery of the drugs to brain tumors is limited by the presence of the blood-brain barrier. Nanotechnology today offers a unique opportunity to develop more effective brain cancer imaging and therapeutics. In particular, the development of nanocarriers that can be conjugated with several functional molecules including tumor-specific ligands, anticancer drugs, and imaging probes, can provide new devices which are able to overcome the difficulties of the classical strategies. Nanotechnology-based approaches hold great promise for revolutionizing brain cancer medical treatments, imaging, and diagnosis.

Simultaneous two-photon imaging of intracellular chloride concentration and pH in mouse pyramidal neurons in vivo

PubMed Central

Sulis Sato, Sebastian; Artoni, Pietro; Landi, Silvia; Cozzolino, Olga; Parra, Riccardo; Pracucci, Enrico; Trovato, Francesco; Szczurkowska, Joanna; Arosio, Daniele; Beltram, Fabio; Cancedda, Laura; Kaila, Kai

2017-01-01

Intracellular chloride ([Cl−]i) and pH (pHi) are fundamental regulators of neuronal excitability. They exert wide-ranging effects on synaptic signaling and plasticity and on development and disorders of the brain. The ideal technique to elucidate the underlying ionic mechanisms is quantitative and combined two-photon imaging of [Cl−]i and pHi, but this has never been performed at the cellular level in vivo. Here, by using a genetically encoded fluorescent sensor that includes a spectroscopic reference (an element insensitive to Cl− and pH), we show that ratiometric imaging is strongly affected by the optical properties of the brain. We have designed a method that fully corrects for this source of error. Parallel measurements of [Cl−]i and pHi at the single-cell level in the mouse cortex showed the in vivo presence of the widely discussed developmental fall in [Cl−]i and the role of the K-Cl cotransporter KCC2 in this process. Then, we introduce a dynamic two-photon excitation protocol to simultaneously determine the changes of pHi and [Cl−]i in response to hypercapnia and seizure activity. PMID:28973889

Performance analysis of unsupervised optimal fuzzy clustering algorithm for MRI brain tumor segmentation.

PubMed

Blessy, S A Praylin Selva; Sulochana, C Helen

2015-01-01

Segmentation of brain tumor from Magnetic Resonance Imaging (MRI) becomes very complicated due to the structural complexities of human brain and the presence of intensity inhomogeneities. To propose a method that effectively segments brain tumor from MR images and to evaluate the performance of unsupervised optimal fuzzy clustering (UOFC) algorithm for segmentation of brain tumor from MR images. Segmentation is done by preprocessing the MR image to standardize intensity inhomogeneities followed by feature extraction, feature fusion and clustering. Different validation measures are used to evaluate the performance of the proposed method using different clustering algorithms. The proposed method using UOFC algorithm produces high sensitivity (96%) and low specificity (4%) compared to other clustering methods. Validation results clearly show that the proposed method with UOFC algorithm effectively segments brain tumor from MR images.

Prenatal Brain MR Imaging: Reference Linear Biometric Centiles between 20 and 24 Gestational Weeks.

PubMed

Conte, G; Milani, S; Palumbo, G; Talenti, G; Boito, S; Rustico, M; Triulzi, F; Righini, A; Izzo, G; Doneda, C; Zolin, A; Parazzini, C

2018-05-01

Evaluation of biometry is a fundamental step in prenatal brain MR imaging. While different studies have reported reference centiles for MR imaging biometric data of fetuses in the late second and third trimesters of gestation, no one has reported them in fetuses in the early second trimester. We report centiles of normal MR imaging linear biometric data of a large cohort of fetal brains within 24 weeks of gestation. From the data bases of 2 referral centers of fetal medicine, accounting for 3850 examinations, we retrospectively collected 169 prenatal brain MR imaging examinations of singleton pregnancies, between 20 and 24 weeks of gestational age, with normal brain anatomy at MR imaging and normal postnatal neurologic development. To trace the reference centiles, we used the CG-LMS method. Reference biometric centiles for the developing structures of the cerebrum, cerebellum, brain stem, and theca were obtained. The overall interassessor agreement was adequate for all measurements. Reference biometric centiles of the brain structures in fetuses between 20 and 24 weeks of gestational age may be a reliable tool in assessing fetal brain development. © 2018 by American Journal of Neuroradiology.

The macrophage marker translocator protein (TSPO) is down-regulated on pro-inflammatory 'M1' human macrophages.

PubMed

Narayan, Nehal; Mandhair, Harpreet; Smyth, Erica; Dakin, Stephanie Georgina; Kiriakidis, Serafim; Wells, Lisa; Owen, David; Sabokbar, Afsie; Taylor, Peter

2017-01-01

The translocator protein (TSPO) is a mitochondrial membrane protein, of as yet uncertain function. Its purported high expression on activated macrophages, has lent utility to TSPO targeted molecular imaging in the form of positron emission tomography (PET), as a means to detect and quantify inflammation in vivo. However, existing literature regarding TSPO expression on human activated macrophages is lacking, mostly deriving from brain tissue studies, including studies of brain malignancy, and inflammatory diseases such as multiple sclerosis. Here, we utilized three human sources of monocyte derived macrophages (MDM), from THP-1 monocytes, healthy peripheral blood monocytes and synovial fluid monocytes from patients with rheumatoid arthritis, to undertake a detailed investigation of TSPO expression in activated macrophages. In this work, we demonstrate a consistent down-regulation of TSPO mRNA and protein in macrophages activated to a pro-inflammatory, or 'M1' phenotype. Conversely, stimulation of macrophages to an M2 phenotype with IL-4, dexamethasone or TGF-β1 did not alter TSPO expression, regardless of MDM source. The reasons for this are uncertain, but our study findings add some supporting evidence for recent investigations concluding that TSPO may be involved in negative regulation of inflammatory responses in macrophages.

Genetic variant for behavioral regulation factor of executive function and its possible brain mechanism in attention deficit hyperactivity disorder.

PubMed

Sun, Xiao; Wu, Zhaomin; Cao, Qingjiu; Qian, Ying; Liu, Yong; Yang, Binrang; Chang, Suhua; Yang, Li; Wang, Yufeng

2018-05-16

As a childhood-onset psychiatric disorder, attention deficit hyperactivity disorder (ADHD) is complicated by phenotypic and genetic heterogeneity. Lifelong executive function deficits in ADHD are described in many literatures and have been proposed as endophenotypes of ADHD. However, its genetic basis is still elusive. In this study, we performed a genome-wide association study of executive function, rated with Behavioral Rating Inventory of Executive Function (BRIEF), in ADHD children. We identified one significant variant (rs852004, P = 2.51e-08) for the overall score of BRIEF. The association analyses for each component of executive function found this locus was more associated with inhibit and monitor components. Further principle component analysis and confirmatory factor analysis provided an ADHD-specific executive function pattern including inhibit and monitor factors. SNP rs852004 was mainly associated with the Behavioral Regulation factor. Meanwhile, we found the significant locus was associated with ADHD symptom. The Behavioral Regulation factor mediated its effect on ADHD symptom. Functional magnetic resonance imaging (fMRI) analyses further showed evidence that this variant affected the activity of inhibition control related brain regions. It provided new insights for the genetic basis of executive function in ADHD.

Imaging Human Brain Perfusion with Inhaled Hyperpolarized 129Xe MR Imaging.

PubMed

Rao, Madhwesha R; Stewart, Neil J; Griffiths, Paul D; Norquay, Graham; Wild, Jim M

2018-02-01

Purpose To evaluate the feasibility of directly imaging perfusion of human brain tissue by using magnetic resonance (MR) imaging with inhaled hyperpolarized xenon 129 ( 129 Xe). Materials and Methods In vivo imaging with 129 Xe was performed in three healthy participants. The combination of a high-yield spin-exchange optical pumping 129 Xe polarizer, custom-built radiofrequency coils, and an optimized gradient-echo MR imaging protocol was used to achieve signal sensitivity sufficient to directly image hyperpolarized 129 Xe dissolved in the human brain. Conventional T1-weighted proton (hydrogen 1 [ 1 H]) images and perfusion images by using arterial spin labeling were obtained for comparison. Results Images of 129 Xe uptake were obtained with a signal-to-noise ratio of 31 ± 9 and demonstrated structural similarities to the gray matter distribution on conventional T1-weighted 1 H images and to perfusion images from arterial spin labeling. Conclusion Hyperpolarized 129 Xe MR imaging is an injection-free means of imaging the perfusion of cerebral tissue. The proposed method images the uptake of inhaled xenon gas to the extravascular brain tissue compartment across the intact blood-brain barrier. This level of sensitivity is not readily available with contemporary MR imaging methods. © RSNA, 2017.

Computer-aided diagnosis with radiogenomics: analysis of the relationship between genotype and morphological changes of the brain magnetic resonance images.

PubMed

Kai, Chiharu; Uchiyama, Yoshikazu; Shiraishi, Junji; Fujita, Hiroshi; Doi, Kunio

2018-05-10

In the post-genome era, a novel research field, 'radiomics' has been developed to offer a new viewpoint for the use of genotypes in radiology and medicine research which have traditionally focused on the analysis of imaging phenotypes. The present study analyzed brain morphological changes related to the individual's genotype. Our data consisted of magnetic resonance (MR) images of patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD), as well as their apolipoprotein E (APOE) genotypes. First, statistical parametric mapping (SPM) 12 was used for three-dimensional anatomical standardization of the brain MR images. A total of 30 normal images were used to create a standard normal brain image. Z-score maps were generated to identify the differences between an abnormal image and the standard normal brain. Our experimental results revealed that cerebral atrophies, depending on genotypes, can occur in different locations and that morphological changes may differ between MCI and AD. Using a classifier to characterize cerebral atrophies related to an individual's genotype, we developed a computer-aided diagnosis (CAD) scheme to identify the disease. For the early detection of cerebral diseases, a screening system using MR images, called Brain Check-up, is widely performed in Japan. Therefore, our proposed CAD scheme would be used in Brain Check-up.

Minocycline Effects on Intracerebral Hemorrhage-Induced Iron Overload in Aged Rats: Brain Iron Quantification With Magnetic Resonance Imaging.

PubMed

Cao, Shenglong; Hua, Ya; Keep, Richard F; Chaudhary, Neeraj; Xi, Guohua

2018-04-01

Brain iron overload is a key factor causing brain injury after intracerebral hemorrhage (ICH). This study quantified brain iron levels after ICH with magnetic resonance imaging R2* mapping. The effect of minocycline on iron overload and ICH-induced brain injury in aged rats was also determined. Aged (18 months old) male Fischer 344 rats had an intracerebral injection of autologous blood or saline, and brain iron levels were measured by magnetic resonance imaging R2* mapping. Some ICH rats were treated with minocycline or vehicle. The rats were euthanized at days 7 and 28 after ICH, and brains were used for immunohistochemistry and Western blot analyses. Magnetic resonance imaging (T2-weighted, T2* gradient-echo, and R2* mapping) sequences were performed at different time points. ICH-induced brain iron overload in the perihematomal area could be quantified by R2* mapping. Minocycline treatment reduced brain iron accumulation, T2* lesion volume, iron-handling protein upregulation, neuronal cell death, and neurological deficits ( P <0.05). Magnetic resonance imaging R2* mapping is a reliable and noninvasive method, which can quantitatively measure brain iron levels after ICH. Minocycline reduced ICH-related perihematomal iron accumulation and brain injury in aged rats. © 2018 American Heart Association, Inc.

Groupwise registration of MR brain images with tumors.

PubMed

Tang, Zhenyu; Wu, Yihong; Fan, Yong

2017-08-04

A novel groupwise image registration framework is developed for registering MR brain images with tumors. Our method iteratively estimates a normal-appearance counterpart for each tumor image to be registered and constructs a directed graph (digraph) of normal-appearance images to guide the groupwise image registration. Particularly, our method maps each tumor image to its normal appearance counterpart by identifying and inpainting brain tumor regions with intensity information estimated using a low-rank plus sparse matrix decomposition based image representation technique. The estimated normal-appearance images are groupwisely registered to a group center image guided by a digraph of images so that the total length of 'image registration paths' to be the minimum, and then the original tumor images are warped to the group center image using the resulting deformation fields. We have evaluated our method based on both simulated and real MR brain tumor images. The registration results were evaluated with overlap measures of corresponding brain regions and average entropy of image intensity information, and Wilcoxon signed rank tests were adopted to compare different methods with respect to their regional overlap measures. Compared with a groupwise image registration method that is applied to normal-appearance images estimated using the traditional low-rank plus sparse matrix decomposition based image inpainting, our method achieved higher image registration accuracy with statistical significance (p  =  7.02  ×  10 -9 ).

Photoacoustic imaging for transvascular drug delivery to the rat brain

NASA Astrophysics Data System (ADS)

Watanabe, Ryota; Sato, Shunichi; Tsunoi, Yasuyuki; Kawauchi, Satoko; Takemura, Toshiya; Terakawa, Mitsuhiro

2015-03-01

Transvascular drug delivery to the brain is difficult due to the blood-brain barrier (BBB). Thus, various methods for safely opening the BBB have been investigated, for which real-time imaging methods are desired both for the blood vessels and distribution of a drug. Photoacoustic (PA) imaging, which enables depth-resolved visualization of chromophores in tissue, would be useful for this purpose. In this study, we performed in vivo PA imaging of the blood vessels and distribution of a drug in the rat brain by using an originally developed compact PA imaging system with fiber-based illumination. As a test drug, Evans blue (EB) was injected to the tail vein, and a photomechanical wave was applied to the targeted brain tissue to increase the permeability of the blood vessel walls. For PA imaging of blood vessels and EB distribution, nanosecond pulses at 532 nm and 670 nm were used, respectively. We clearly visualized blood vessels with diameters larger than 50 μm and the distribution of EB in the brain, showing spatiotemporal characteristics of EB that was transvascularly delivered to the target tissue in the brain.

Embedding and Chemical Reactivation of Green Fluorescent Protein in the Whole Mouse Brain for Optical Micro-Imaging

PubMed Central

Gang, Yadong; Zhou, Hongfu; Jia, Yao; Liu, Ling; Liu, Xiuli; Rao, Gong; Li, Longhui; Wang, Xiaojun; Lv, Xiaohua; Xiong, Hanqing; Yang, Zhongqin; Luo, Qingming; Gong, Hui; Zeng, Shaoqun

2017-01-01

Resin embedding has been widely applied to fixing biological tissues for sectioning and imaging, but has long been regarded as incompatible with green fluorescent protein (GFP) labeled sample because it reduces fluorescence. Recently, it has been reported that resin-embedded GFP-labeled brain tissue can be imaged with high resolution. In this protocol, we describe an optimized protocol for resin embedding and chemical reactivation of fluorescent protein labeled mouse brain, we have used mice as experiment model, but the protocol should be applied to other species. This method involves whole brain embedding and chemical reactivation of the fluorescent signal in resin-embedded tissue. The whole brain embedding process takes a total of 7 days. The duration of chemical reactivation is ~2 min for penetrating 4 μm below the surface in the resin-embedded brain. This protocol provides an efficient way to prepare fluorescent protein labeled sample for high-resolution optical imaging. This kind of sample was demonstrated to be imaged by various optical micro-imaging methods. Fine structures labeled with GFP across a whole brain can be detected. PMID:28352214

Correspondence of the brain's functional architecture during activation and rest.

PubMed

Smith, Stephen M; Fox, Peter T; Miller, Karla L; Glahn, David C; Fox, P Mickle; Mackay, Clare E; Filippini, Nicola; Watkins, Kate E; Toro, Roberto; Laird, Angela R; Beckmann, Christian F

2009-08-04

Neural connections, providing the substrate for functional networks, exist whether or not they are functionally active at any given moment. However, it is not known to what extent brain regions are continuously interacting when the brain is "at rest." In this work, we identify the major explicit activation networks by carrying out an image-based activation network analysis of thousands of separate activation maps derived from the BrainMap database of functional imaging studies, involving nearly 30,000 human subjects. Independently, we extract the major covarying networks in the resting brain, as imaged with functional magnetic resonance imaging in 36 subjects at rest. The sets of major brain networks, and their decompositions into subnetworks, show close correspondence between the independent analyses of resting and activation brain dynamics. We conclude that the full repertoire of functional networks utilized by the brain in action is continuously and dynamically "active" even when at "rest."

Retractor-induced brain shift compensation in image-guided neurosurgery

NASA Astrophysics Data System (ADS)

Fan, Xiaoyao; Ji, Songbai; Hartov, Alex; Roberts, David; Paulsen, Keith

2013-03-01

In image-guided neurosurgery, intraoperative brain shift significantly degrades the accuracy of neuronavigation that is solely based on preoperative magnetic resonance images (pMR). To compensate for brain deformation and to maintain the accuracy in image guidance achieved at the start of surgery, biomechanical models have been developed to simulate brain deformation and to produce model-updated MR images (uMR) to compensate for brain shift. To-date, most studies have focused on shift compensation at early stages of surgery (i.e., updated images are only produced after craniotomy and durotomy). Simulating surgical events at later stages such as retraction and tissue resection are, perhaps, clinically more relevant because of the typically much larger magnitudes of brain deformation. However, these surgical events are substantially more complex in nature, thereby posing significant challenges in model-based brain shift compensation strategies. In this study, we present results from an initial investigation to simulate retractor-induced brain deformation through a biomechanical finite element (FE) model where whole-brain deformation assimilated from intraoperative data was used produce uMR for improved accuracy in image guidance. Specifically, intensity-encoded 3D surface profiles at the exposed cortical area were reconstructed from intraoperative stereovision (iSV) images before and after tissue retraction. Retractor-induced surface displacements were then derived by coregistering the surfaces and served as sparse displacement data to drive the FE model. With one patient case, we show that our technique is able to produce uMR that agrees well with the reconstructed iSV surface after retraction. The computational cost to simulate retractor-induced brain deformation was approximately 10 min. In addition, our approach introduces minimal interruption to the surgical workflow, suggesting the potential for its clinical application.

Hemorrhage detection in MRI brain images using images features

NASA Astrophysics Data System (ADS)

Moraru, Luminita; Moldovanu, Simona; Bibicu, Dorin; Stratulat (Visan), Mirela

2013-11-01

The abnormalities appear frequently on Magnetic Resonance Images (MRI) of brain in elderly patients presenting either stroke or cognitive impairment. Detection of brain hemorrhage lesions in MRI is an important but very time-consuming task. This research aims to develop a method to extract brain tissue features from T2-weighted MR images of the brain using a selection of the most valuable texture features in order to discriminate between normal and affected areas of the brain. Due to textural similarity between normal and affected areas in brain MR images these operation are very challenging. A trauma may cause microstructural changes, which are not necessarily perceptible by visual inspection, but they could be detected by using a texture analysis. The proposed analysis is developed in five steps: i) in the pre-processing step: the de-noising operation is performed using the Daubechies wavelets; ii) the original images were transformed in image features using the first order descriptors; iii) the regions of interest (ROIs) were cropped from images feature following up the axial symmetry properties with respect to the mid - sagittal plan; iv) the variation in the measurement of features was quantified using the two descriptors of the co-occurrence matrix, namely energy and homogeneity; v) finally, the meaningful of the image features is analyzed by using the t-test method. P-value has been applied to the pair of features in order to measure they efficacy.

When the Brain Takes 'BOLD' Steps: Real-Time fMRI Neurofeedback Can Further Enhance the Ability to Gradually Self-regulate Regional Brain Activation.

PubMed

Sorger, Bettina; Kamp, Tabea; Weiskopf, Nikolaus; Peters, Judith Caroline; Goebel, Rainer

2018-05-15

Brain-computer interfaces (BCIs) based on real-time functional magnetic resonance imaging (rtfMRI) are currently explored in the context of developing alternative (motor-independent) communication and control means for the severely disabled. In such BCI systems, the user encodes a particular intention (e.g., an answer to a question or an intended action) by evoking specific mental activity resulting in a distinct brain state that can be decoded from fMRI activation. One goal in this context is to increase the degrees of freedom in encoding different intentions, i.e., to allow the BCI user to choose from as many options as possible. Recently, the ability to voluntarily modulate spatial and/or temporal blood oxygenation level-dependent (BOLD)-signal features has been explored implementing different mental tasks and/or different encoding time intervals, respectively. Our two-session fMRI feasibility study systematically investigated for the first time the possibility of using magnitudinal BOLD-signal features for intention encoding. Particularly, in our novel paradigm, participants (n=10) were asked to alternately self-regulate their regional brain-activation level to 30%, 60% or 90% of their maximal capacity by applying a selected activation strategy (i.e., performing a mental task, e.g., inner speech) and modulation strategies (e.g., using different speech rates) suggested by the experimenters. In a second step, we tested the hypothesis that the additional availability of feedback information on the current BOLD-signal level within a region of interest improves the gradual-self regulation performance. Therefore, participants were provided with neurofeedback in one of the two fMRI sessions. Our results show that the majority of the participants were able to gradually self-regulate regional brain activation to at least two different target levels even in the absence of neurofeedback. When provided with continuous feedback on their current BOLD-signal level, most participants further enhanced their gradual self-regulation ability. Our findings were observed across a wide variety of mental tasks and across clinical MR field strengths (i.e., at 1.5T and 3T), indicating that these findings are robust and can be generalized across mental tasks and scanner types. The suggested novel parametric activation paradigm enriches the spectrum of current rtfMRI-neurofeedback and BCI methodology and has considerable potential for fundamental and clinical neuroscience applications. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Brain Tumor Image Segmentation in MRI Image

NASA Astrophysics Data System (ADS)

Peni Agustin Tjahyaningtijas, Hapsari

2018-04-01

Brain tumor segmentation plays an important role in medical image processing. Treatment of patients with brain tumors is highly dependent on early detection of these tumors. Early detection of brain tumors will improve the patient’s life chances. Diagnosis of brain tumors by experts usually use a manual segmentation that is difficult and time consuming because of the necessary automatic segmentation. Nowadays automatic segmentation is very populer and can be a solution to the problem of tumor brain segmentation with better performance. The purpose of this paper is to provide a review of MRI-based brain tumor segmentation methods. There are number of existing review papers, focusing on traditional methods for MRI-based brain tumor image segmentation. this paper, we focus on the recent trend of automatic segmentation in this field. First, an introduction to brain tumors and methods for brain tumor segmentation is given. Then, the state-of-the-art algorithms with a focus on recent trend of full automatic segmentaion are discussed. Finally, an assessment of the current state is presented and future developments to standardize MRI-based brain tumor segmentation methods into daily clinical routine are addressed.

Abnormalities in the zinc-metalloprotease-BDNF axis may contribute to megalencephaly and cortical hyperconnectivity in young autism spectrum disorder patients.

PubMed

Koh, Jae-Young; Lim, Joon Seo; Byun, Hyae-Ran; Yoo, Min-Heui

2014-09-03

Whereas aberrant brain connectivity is likely the core pathology of autism-spectrum disorder (ASD), studies do not agree as to whether hypo- or hyper-connectivity is the main underlying problem. Recent functional imaging studies have shown that, in most young ASD patients, cerebral cortical regions appear hyperconnected, and cortical thickness/brain size is increased. Collectively, these findings indicate that developing ASD brains may exist in an altered neurotrophic milieu. Consistently, some ASD patients, as well as some animal models of ASD, show increased levels of brain-derived neurotrophic factor (BDNF). However, how BDNF is upregulated in ASD is unknown. To address this question, we propose the novel hypothesis that a putative zinc-metalloprotease-BDNF (ZMB) axis in the forebrain plays a pivotal role in the development of hyperconnectivity and megalencephaly in ASD. We have previously demonstrated that extracellular zinc at micromolar concentrations can rapidly increase BDNF levels and phosphorylate the receptor tyrosine kinase TrkB via the activation of metalloproteases. The role of metalloproteases in ASD is still uncertain, but in fragile X syndrome, a monogenic disease with an autistic phenotype, the levels of MMP are increased. Early exposure to lipopolysaccharides (LPS) and other MMP activators such as organic mercurials also have been implicated in ASD pathogenesis. The resultant increases in BDNF levels at synapses, especially those involved in the zinc-containing, associative glutamatergic system may produce abnormal brain circuit development. Various genetic mutations that lead to ASD are also known to affect BDNF signaling: some down-regulate, and others up-regulate it. We hypothesize that, although both up- and down-regulation of BDNF may induce autism symptoms, only BDNF up-regulation is associated with the hyperconnectivity and large brain size observed in most young idiopathic ASD patients. To test this hypothesis, we propose to examine the ZMB axis in animal models of ASD. Synaptic zinc can be examined by fluorescence zinc staining. MMP activation can be measured by in situ zymography and Western blot analysis. Finally, regional levels of BDNF can be measured. Validating this hypothesis may shed light on the central pathogenic mechanism of ASD and aid in the identification of useful biomarkers and the development of preventive/therapeutic strategies.

Abnormalities in the zinc-metalloprotease-BDNF axis may contribute to megalencephaly and cortical hyperconnectivity in young autism spectrum disorder patients

PubMed Central

2014-01-01

Whereas aberrant brain connectivity is likely the core pathology of autism-spectrum disorder (ASD), studies do not agree as to whether hypo- or hyper-connectivity is the main underlying problem. Recent functional imaging studies have shown that, in most young ASD patients, cerebral cortical regions appear hyperconnected, and cortical thickness/brain size is increased. Collectively, these findings indicate that developing ASD brains may exist in an altered neurotrophic milieu. Consistently, some ASD patients, as well as some animal models of ASD, show increased levels of brain-derived neurotrophic factor (BDNF). However, how BDNF is upregulated in ASD is unknown. To address this question, we propose the novel hypothesis that a putative zinc-metalloprotease-BDNF (ZMB) axis in the forebrain plays a pivotal role in the development of hyperconnectivity and megalencephaly in ASD. We have previously demonstrated that extracellular zinc at micromolar concentrations can rapidly increase BDNF levels and phosphorylate the receptor tyrosine kinase TrkB via the activation of metalloproteases. The role of metalloproteases in ASD is still uncertain, but in fragile X syndrome, a monogenic disease with an autistic phenotype, the levels of MMP are increased. Early exposure to lipopolysaccharides (LPS) and other MMP activators such as organic mercurials also have been implicated in ASD pathogenesis. The resultant increases in BDNF levels at synapses, especially those involved in the zinc-containing, associative glutamatergic system may produce abnormal brain circuit development. Various genetic mutations that lead to ASD are also known to affect BDNF signaling: some down-regulate, and others up-regulate it. We hypothesize that, although both up- and down-regulation of BDNF may induce autism symptoms, only BDNF up-regulation is associated with the hyperconnectivity and large brain size observed in most young idiopathic ASD patients. To test this hypothesis, we propose to examine the ZMB axis in animal models of ASD. Synaptic zinc can be examined by fluorescence zinc staining. MMP activation can be measured by in situ zymography and Western blot analysis. Finally, regional levels of BDNF can be measured. Validating this hypothesis may shed light on the central pathogenic mechanism of ASD and aid in the identification of useful biomarkers and the development of preventive/therapeutic strategies. PMID:25182223

Progressive neurostructural changes in adolescent and adult patients with bipolar disorder.

PubMed

Lisy, Megan E; Jarvis, Kelly B; DelBello, Melissa P; Mills, Neil P; Weber, Wade A; Fleck, David; Strakowski, Stephen M; Adler, Caleb M

2011-06-01

Several lines of evidence suggest that bipolar disorder is associated with progressive changes in gray matter volume (GMV), particularly in brain structures involved in emotional regulation and expression. The majority of these studies however, have been cross-sectional in nature. In this study we compared baseline and follow-up scans in groups of bipolar disorder and healthy subjects. We hypothesized bipolar disorder subjects would demonstrate significant GMV changes over time. A total of 58 bipolar disorder and 48 healthy subjects participated in structural magnetic resonance imaging (MRI). Subjects were rescanned 3-34 months after their baseline MRI. MRI images were segmented, normalized to standard stereotactic space, and compared voxel-by-voxel using statistical parametrical mapping software (SPM2). A model was developed to investigate differences in GMV at baseline, and associated with time and episodes, as well as in comparison to healthy subjects. We observed increases in GMV in bipolar disorder subjects across several brain regions at baseline and over time, including portions of the prefrontal cortex as well as limbic and subcortical structures. Time-related changes differed to some degree between adolescent and adult bipolar disorder subjects. The interval between scans positively correlated with GMV increases in bipolar disorder subjects in portions of the prefrontal cortex, and both illness duration and number of depressive episodes were associated with increased GMV in subcortical and limbic structures. Our findings support suggestions that widely observed progressive neurofunctional changes in bipolar disorder patients may be related to structural brain abnormalities in anterior limbic structures. Abnormalities largely involve regions previously noted to be integral to emotional expression and regulation, and appear to vary by age. © 2011 John Wiley and Sons A/S.

A simple rapid process for semi-automated brain extraction from magnetic resonance images of the whole mouse head.

PubMed

Delora, Adam; Gonzales, Aaron; Medina, Christopher S; Mitchell, Adam; Mohed, Abdul Faheem; Jacobs, Russell E; Bearer, Elaine L

2016-01-15

Magnetic resonance imaging (MRI) is a well-developed technique in neuroscience. Limitations in applying MRI to rodent models of neuropsychiatric disorders include the large number of animals required to achieve statistical significance, and the paucity of automation tools for the critical early step in processing, brain extraction, which prepares brain images for alignment and voxel-wise statistics. This novel timesaving automation of template-based brain extraction ("skull-stripping") is capable of quickly and reliably extracting the brain from large numbers of whole head images in a single step. The method is simple to install and requires minimal user interaction. This method is equally applicable to different types of MR images. Results were evaluated with Dice and Jacquard similarity indices and compared in 3D surface projections with other stripping approaches. Statistical comparisons demonstrate that individual variation of brain volumes are preserved. A downloadable software package not otherwise available for extraction of brains from whole head images is included here. This software tool increases speed, can be used with an atlas or a template from within the dataset, and produces masks that need little further refinement. Our new automation can be applied to any MR dataset, since the starting point is a template mask generated specifically for that dataset. The method reliably and rapidly extracts brain images from whole head images, rendering them useable for subsequent analytical processing. This software tool will accelerate the exploitation of mouse models for the investigation of human brain disorders by MRI. Copyright © 2015 Elsevier B.V. All rights reserved.

Sex Commonalities and Differences in Obesity-Related Alterations in Intrinsic Brain Activity and Connectivity.

PubMed

Gupta, Arpana; Mayer, Emeran A; Labus, Jennifer S; Bhatt, Ravi R; Ju, Tiffany; Love, Aubrey; Bal, Amanat; Tillisch, Kirsten; Naliboff, Bruce; Sanmiguel, Claudia P; Kilpatrick, Lisa A

2018-02-01

This study aimed to characterize obesity-related sex differences in the intrinsic activity and connectivity of the brain's reward networks. Eighty-six women (n = 43) and men (n = 43) completed a 10-minute resting functional magnetic resonance imaging scan. Sex differences and commonalities in BMI-related frequency power distribution and reward seed-based connectivity were investigated by using partial least squares analysis. For whole-brain activity in both men and women, increased BMI was associated with increased slow-5 activity in the left globus pallidus (GP) and substantia nigra. In women only, increased BMI was associated with increased slow-4 activity in the right GP and bilateral putamen. For seed-based connectivity in women, increased BMI was associated with reduced slow-5 connectivity between the left GP and putamen and the emotion and cortical regulation regions, but in men, increased BMI was associated with increased connectivity with the medial frontal cortex. In both men and women, increased BMI was associated with increased slow-4 connectivity between the right GP and bilateral putamen and the emotion regulation and sensorimotor-related regions. The stronger relationship between increased BMI and decreased connectivity of core reward network components with cortical and emotion regulation regions in women may be related to the greater prevalence of emotional eating. The present findings suggest the importance of personalized treatments for obesity that consider the sex of the affected individual. © 2017 The Obesity Society.

Age Differences in Brain Activity during Emotion Processing: Reflections of Age-Related Decline or Increased Emotion Regulation?

PubMed Central

Nashiro, Kaoru; Sakaki, Michiko; Mather, Mara

2012-01-01

Despite the fact that physical health and cognitive abilities decline with aging, the ability to regulate emotion remains stable and in some aspects improves across the adult life span. Older adults also show a positivity effect in their attention and memory, with diminished processing of negative stimuli relative to positive stimuli compared with younger adults. The current paper reviews functional magnetic resonance imaging studies investigating age-related differences in emotional processing and discusses how this evidence relates to two opposing theoretical accounts of older adults’ positivity effect. The aging-brain model [Cacioppo et al. in: Social Neuroscience: Toward Understanding the Underpinnings of the Social Mind. New York, Oxford University Press, 2011] proposes that older adults’ positivity effect is a consequence of age-related decline in the amygdala, whereas the cognitive control hypothesis [Kryla-Lighthall and Mather in: Handbook of Theories of Aging, ed 2. New York, Springer, 2009; Mather and Carstensen: Trends Cogn Sci 2005;9:496–502; Mather and Knight: Psychol Aging 2005;20:554–570] argues that the positivity effect is a result of older adults’ greater focus on regulating emotion. Based on evidence for structural and functional preservation of the amygdala in older adults and findings that older adults show greater prefrontal cortex activity than younger adults while engaging in emotion-processing tasks, we argue that the cognitive control hypothesis is a more likely explanation for older adults’ positivity effect than the aging-brain model. PMID:21691052

Age differences in brain activity during emotion processing: reflections of age-related decline or increased emotion regulation?

PubMed

Nashiro, Kaoru; Sakaki, Michiko; Mather, Mara

2012-01-01

Despite the fact that physical health and cognitive abilities decline with aging, the ability to regulate emotion remains stable and in some aspects improves across the adult life span. Older adults also show a positivity effect in their attention and memory, with diminished processing of negative stimuli relative to positive stimuli compared with younger adults. The current paper reviews functional magnetic resonance imaging studies investigating age-related differences in emotional processing and discusses how this evidence relates to two opposing theoretical accounts of older adults' positivity effect. The aging-brain model [Cacioppo et al. in: Social Neuroscience: Toward Understanding the Underpinnings of the Social Mind. New York, Oxford University Press, 2011] proposes that older adults' positivity effect is a consequence of age-related decline in the amygdala, whereas the cognitive control hypothesis [Kryla-Lighthall and Mather in: Handbook of Theories of Aging, ed 2. New York, Springer, 2009; Mather and Carstensen: Trends Cogn Sci 2005;9:496-502; Mather and Knight: Psychol Aging 2005;20:554-570] argues that the positivity effect is a result of older adults' greater focus on regulating emotion. Based on evidence for structural and functional preservation of the amygdala in older adults and findings that older adults show greater prefrontal cortex activity than younger adults while engaging in emotion-processing tasks, we argue that the cognitive control hypothesis is a more likely explanation for older adults' positivity effect than the aging-brain model. Copyright © 2011 S. Karger AG, Basel.

Synchrotron radiation imaging is a powerful tool to image brain microvasculature

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Mengqi; Sun, Danni; Xie, Yuanyuan

2014-03-15

Synchrotron radiation (SR) imaging is a powerful experimental tool for micrometer-scale imaging of microcirculation in vivo. This review discusses recent methodological advances and findings from morphological investigations of cerebral vascular networks during several neurovascular pathologies. In particular, it describes recent developments in SR microangiography for real-time assessment of the brain microvasculature under various pathological conditions in small animal models. It also covers studies that employed SR-based phase-contrast imaging to acquire 3D brain images and provide detailed maps of brain vasculature. In addition, a brief introduction of SR technology and current limitations of SR sources are described in this review. Inmore » the near future, SR imaging could transform into a common and informative imaging modality to resolve subtle details of cerebrovascular function.« less

Synchrotron radiation imaging is a powerful tool to image brain microvasculature.

PubMed

Zhang, Mengqi; Peng, Guanyun; Sun, Danni; Xie, Yuanyuan; Xia, Jian; Long, Hongyu; Hu, Kai; Xiao, Bo

2014-03-01

Synchrotron radiation (SR) imaging is a powerful experimental tool for micrometer-scale imaging of microcirculation in vivo. This review discusses recent methodological advances and findings from morphological investigations of cerebral vascular networks during several neurovascular pathologies. In particular, it describes recent developments in SR microangiography for real-time assessment of the brain microvasculature under various pathological conditions in small animal models. It also covers studies that employed SR-based phase-contrast imaging to acquire 3D brain images and provide detailed maps of brain vasculature. In addition, a brief introduction of SR technology and current limitations of SR sources are described in this review. In the near future, SR imaging could transform into a common and informative imaging modality to resolve subtle details of cerebrovascular function.

Label-free imaging of brain and brain tumor specimens with combined two-photon excited fluorescence and second harmonic generation microscopy

NASA Astrophysics Data System (ADS)

Jiang, Liwei; Wang, Xingfu; Wu, Zanyi; Du, Huiping; Wang, Shu; Li, Lianhuang; Fang, Na; Lin, Peihua; Chen, Jianxin; Kang, Dezhi; Zhuo, Shuangmu

2017-10-01

Label-free imaging techniques are gaining acceptance within the medical imaging field, including brain imaging, because they have the potential to be applied to intraoperative in situ identifications of pathological conditions. In this paper, we describe the use of two-photon excited fluorescence (TPEF) and second harmonic generation (SHG) microscopy in combination for the label-free detection of brain and brain tumor specimens; gliomas. Two independently detecting channels were chosen to subsequently collect TPEF/SHG signals from the specimen to increase TPEF/SHG image contrasts. Our results indicate that the combined TPEF/SHG microscopic techniques can provide similar rat brain structural information and produce a similar resolution like conventional H&E staining in neuropathology; including meninges, cerebral cortex, white-matter structure corpus callosum, choroid plexus, hippocampus, striatum, and cerebellar cortex. It can simultaneously detect infiltrating human brain tumor cells, the extracellular matrix collagen fiber of connective stroma within brain vessels and collagen depostion in tumor microenvironments. The nuclear-to-cytoplasmic ratio and collagen content can be extracted as quantitative indicators for differentiating brain gliomas from healthy brain tissues. With the development of two-photon fiberscopes and microendoscope probes and their clinical applications, the combined TPEF and SHG microcopy may become an important multimodal, nonlinear optical imaging approach for real-time intraoperative histological diagnostics of residual brain tumors. These occur in various brain regions during ongoing surgeries through the method of simultaneously identifying tumor cells, and the change of tumor microenvironments, without the need for the removal biopsies and without the need for tissue labelling or fluorescent markers.

[Brain imaging in autism spectrum disorders. A review].

PubMed

Dziobek, I; Köhne, S

2011-05-01

In the past two decades, an increasing number of functional and structural brain imaging studies has provided insights into the neurobiological basis of autism spectrum disorders (ASD). This article summarizes pertinent functional brain imaging studies addressing the neuronal underpinnings of ASD symptomatology (impairments in social interaction and communication, repetitive and restrictive behavior) and associated neuropsychological deficits (theory of mind, executive functions, central coherence), complemented by relevant structural imaging findings. The results of these studies show that although cognitive functions in ASD are generally mediated by the same brain regions as in typically developed individuals, the degree and especially the patterns of brain activation often differ. Therefore, a hypothesis of aberrant network connectivity has increasingly been favored over one of focal brain dysfunction.

Contrast enhancement in EIT imaging of the brain.

PubMed

Nissinen, A; Kaipio, J P; Vauhkonen, M; Kolehmainen, V

2016-01-01

We consider electrical impedance tomography (EIT) imaging of the brain. The brain is surrounded by the poorly conducting skull which has low conductivity compared to the brain. The skull layer causes a partial shielding effect which leads to weak sensitivity for the imaging of the brain tissue. In this paper we propose an approach based on the Bayesian approximation error approach, to enhance the contrast in brain imaging. With this approach, both the (uninteresting) geometry and the conductivity of the skull are embedded in the approximation error statistics, which leads to a computationally efficient algorithm that is able to detect features such as internal haemorrhage with significantly increased sensitivity and specificity. We evaluate the approach with simulations and phantom data.

A brain imaging repository of normal structural MRI across the life course: Brain Images of Normal Subjects (BRAINS).

PubMed

Job, Dominic E; Dickie, David Alexander; Rodriguez, David; Robson, Andrew; Danso, Sammy; Pernet, Cyril; Bastin, Mark E; Boardman, James P; Murray, Alison D; Ahearn, Trevor; Waiter, Gordon D; Staff, Roger T; Deary, Ian J; Shenkin, Susan D; Wardlaw, Joanna M

2017-01-01

The Brain Images of Normal Subjects (BRAINS) Imagebank (http://www.brainsimagebank.ac.uk) is an integrated repository project hosted by the University of Edinburgh and sponsored by the Scottish Imaging Network: A Platform for Scientific Excellence (SINAPSE) collaborators. BRAINS provide sharing and archiving of detailed normal human brain imaging and relevant phenotypic data already collected in studies of healthy volunteers across the life-course. It particularly focusses on the extremes of age (currently older age, and in future perinatal) where variability is largest, and which are under-represented in existing databanks. BRAINS is a living imagebank where new data will be added when available. Currently BRAINS contains data from 808 healthy volunteers, from 15 to 81years of age, from 7 projects in 3 centres. Additional completed and ongoing studies of normal individuals from 1st to 10th decades are in preparation and will be included as they become available. BRAINS holds several MRI structural sequences, including T1, T2, T2* and fluid attenuated inversion recovery (FLAIR), available in DICOM (http://dicom.nema.org/); in future Diffusion Tensor Imaging (DTI) will be added where available. Images are linked to a wide range of 'textual data', such as age, medical history, physiological measures (e.g. blood pressure), medication use, cognitive ability, and perinatal information for pre/post-natal subjects. The imagebank can be searched to include or exclude ranges of these variables to create better estimates of 'what is normal' at different ages. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Advances in fMRI Real-Time Neurofeedback.

PubMed

Watanabe, Takeo; Sasaki, Yuka; Shibata, Kazuhisa; Kawato, Mitsuo

2017-12-01

Functional magnetic resonance imaging (fMRI) neurofeedback is a type of biofeedback in which real-time online fMRI signals are used to self-regulate brain function. Since its advent in 2003 significant progress has been made in fMRI neurofeedback techniques. Specifically, the use of implicit protocols, external rewards, multivariate analysis, and connectivity analysis has allowed neuroscientists to explore a possible causal involvement of modified brain activity in modified behavior. These techniques have also been integrated into groundbreaking new neurofeedback technologies, specifically decoded neurofeedback (DecNef) and functional connectivity-based neurofeedback (FCNef). By modulating neural activity and behavior, DecNef and FCNef have substantially advanced both basic and clinical research. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Auto-Context Convolutional Neural Network (Auto-Net) for Brain Extraction in Magnetic Resonance Imaging.

PubMed

Mohseni Salehi, Seyed Sadegh; Erdogmus, Deniz; Gholipour, Ali

2017-11-01

Brain extraction or whole brain segmentation is an important first step in many of the neuroimage analysis pipelines. The accuracy and the robustness of brain extraction, therefore, are crucial for the accuracy of the entire brain analysis process. The state-of-the-art brain extraction techniques rely heavily on the accuracy of alignment or registration between brain atlases and query brain anatomy, and/or make assumptions about the image geometry, and therefore have limited success when these assumptions do not hold or image registration fails. With the aim of designing an accurate, learning-based, geometry-independent, and registration-free brain extraction tool, in this paper, we present a technique based on an auto-context convolutional neural network (CNN), in which intrinsic local and global image features are learned through 2-D patches of different window sizes. We consider two different architectures: 1) a voxelwise approach based on three parallel 2-D convolutional pathways for three different directions (axial, coronal, and sagittal) that implicitly learn 3-D image information without the need for computationally expensive 3-D convolutions and 2) a fully convolutional network based on the U-net architecture. Posterior probability maps generated by the networks are used iteratively as context information along with the original image patches to learn the local shape and connectedness of the brain to extract it from non-brain tissue. The brain extraction results we have obtained from our CNNs are superior to the recently reported results in the literature on two publicly available benchmark data sets, namely, LPBA40 and OASIS, in which we obtained the Dice overlap coefficients of 97.73% and 97.62%, respectively. Significant improvement was achieved via our auto-context algorithm. Furthermore, we evaluated the performance of our algorithm in the challenging problem of extracting arbitrarily oriented fetal brains in reconstructed fetal brain magnetic resonance imaging (MRI) data sets. In this application, our voxelwise auto-context CNN performed much better than the other methods (Dice coefficient: 95.97%), where the other methods performed poorly due to the non-standard orientation and geometry of the fetal brain in MRI. Through training, our method can provide accurate brain extraction in challenging applications. This, in turn, may reduce the problems associated with image registration in segmentation tasks.

Clinics in diagnostic imaging (153). Severe hypoxic ischaemic brain injury.

PubMed Central

Chua, Wynne; Lim, Boon Keat; Lim, Tchoyoson Choie Cheio

2014-01-01

A 58-year-old Indian woman presented with asystole after an episode of haemetemesis, with a patient downtime of 20 mins. After initial resuscitation efforts, computed tomography of the brain, obtained to evaluate neurological injury, demonstrated evidence of severe hypoxic ischaemic brain injury. The imaging features of hypoxic ischaemic brain injury and the potential pitfalls with regard to image interpretation are herein discussed. PMID:25091891

Real-time reconstruction of three-dimensional brain surface MR image using new volume-surface rendering technique

DOE Office of Scientific and Technical Information (OSTI.GOV)

Watanabe, T.; Momose, T.; Oku, S.

It is essential to obtain realistic brain surface images, in which sulci and gyri are easily recognized, when examining the correlation between functional (PET or SPECT) and anatomical (MRI) brain studies. The volume rendering technique (VRT) is commonly employed to make three-dimensional (3D) brain surface images. This technique, however, takes considerable time to make only one 3D image. Therefore it has not been practical to make the brain surface images in arbitrary directions on a real-time basis using ordinary work stations or personal computers. The surface rendering technique (SRT), on the other hand, is much less computationally demanding, but themore » quality of resulting images is not satisfactory for our purpose. A new computer algorithm has been developed to make 3D brain surface MR images very quickly using a volume-surface rendering technique (VSRT), in which the quality of resulting images is comparable to that of VRT and computation time to SRT. In VSRT the process of volume rendering is done only once to the direction of the normal vector of each surface point, rather than each time a new view point is determined as in VRT. Subsequent reconstruction of the 3D image uses a similar algorithm to that of SRT. Thus we can obtain brain surface MR images of sufficient quality viewed from any direction on a real-time basis using an easily available personal computer (Macintosh Quadra 800). The calculation time to make a 3D image is less than 1 sec. in VSRT, while that is more than 15 sec. in the conventional VRT. The difference of resulting image quality between VSRT and VRT is almost imperceptible. In conclusion, our new technique for real-time reconstruction of 3D brain surface MR image is very useful and practical in the functional and anatomical correlation study.« less

The social life of laughter.

PubMed

Scott, Sophie K; Lavan, Nadine; Chen, Sinead; McGettigan, Carolyn

2014-12-01

Laughter is often considered to be the product of humour. However, laughter is a social emotion, occurring most often in interactions, where it is associated with bonding, agreement, affection, and emotional regulation. Laughter is underpinned by complex neural systems, allowing it to be used flexibly. In humans and chimpanzees, social (voluntary) laughter is distinctly different from evoked (involuntary) laughter, a distinction which is also seen in brain imaging studies of laughter. Copyright © 2014 Elsevier Ltd. All rights reserved.

Stress and brain functional changes in patients with Crohn's disease: A functional magnetic resonance imaging study.

PubMed

Agostini, A; Ballotta, D; Righi, S; Moretti, M; Bertani, A; Scarcelli, A; Sartini, A; Ercolani, M; Nichelli, P; Campieri, M; Benuzzi, F

2017-10-01

In Crohn's disease (CD) patients, stress is believed to influence symptoms generation. Stress may act via central nervous system pathways to affect visceral sensitivity and motility thus exacerbating gastrointestinal symptoms. The neural substrate underpinning these mechanisms needs to be investigated in CD. We conducted an explorative functional magnetic resonance imaging (fMRI) study in order to investigate potential differences in the brain stress response in CD patients compared to controls. 17 CD patients and 17 healthy controls underwent a fMRI scan while performing a stressful task consisting in a Stroop color-word interference task designed to induce mental stress in the fMRI environment. Compared to controls, in CD patients the stress task elicited greater blood oxygen level dependent (BOLD) signals in the midcingulate cortex (MCC). The MCC integrate "high" emotional processes with afferent sensory information ascending from the gut. In light of these integrative functions, the stress-evoked MCC hyperactivity in CD patients might represent a plausible neural substrate for the association between stress and symptomatic disease. The MCC dysfunction might be involved in mechanisms of central disinhibition of nociceptive inputs leading to amplify the visceral sensitivity. Finally, the stress-evoked MCC hyperactivity might affect the regulation of intestinal motility resulting in exacerbation of disease symptoms and the autonomic and neuroendocrine regulation of inflammation resulting in enhanced inflammatory activity. © 2017 John Wiley & Sons Ltd.

The detectability of brain metastases using contrast-enhanced spin-echo or gradient-echo images: a systematic review and meta-analysis.

PubMed

Suh, Chong Hyun; Jung, Seung Chai; Kim, Kyung Won; Pyo, Junhee

2016-09-01

This study aimed to compare the detectability of brain metastases using contrast-enhanced spin-echo (SE) and gradient-echo (GRE) T1-weighted images. The Ovid-MEDLINE and EMBASE databases were searched for studies on the detectability of brain metastases using contrast-enhanced SE or GRE images. The pooled proportions for the detectability of brain metastases were assessed using random-effects modeling. Heterogeneity among studies was determined using χ (2) statistics for the pooled estimates and the inconsistency index, I (2) . To overcome heterogeneity, subgroup analyses according to slice thickness and lesion size were performed. A total of eight eligible studies, which included a sample size of 252 patients and 1413 brain metastases, were included. The detectability of brain metastases using SE images (89.2 %) was higher than using GRE images (81.6 %; adjusted 84.0 %), but this difference was not statistically significant (p = 0.2385). In subgroup analysis of studies with 1-mm-thick slices and small metastases (<5 mm in diameter), 3-dimensional (3D) SE images demonstrated a higher detectability in comparison to 3D GRE images (93.7 % vs 73.1 % in 1-mm-thick slices; 89.5 % vs 59.4 % for small metastases) (p < 0.0001). Although both SE or GRE images are acceptable for detecting brain metastases, contrast-enhanced 3D SE images using 1-mm-thick slices are preferred for detecting brain metastases, especially small lesions (<5 mm in diameter).

A Unified Framework for Brain Segmentation in MR Images

PubMed Central

Yazdani, S.; Yusof, R.; Karimian, A.; Riazi, A. H.; Bennamoun, M.

2015-01-01

Brain MRI segmentation is an important issue for discovering the brain structure and diagnosis of subtle anatomical changes in different brain diseases. However, due to several artifacts brain tissue segmentation remains a challenging task. The aim of this paper is to improve the automatic segmentation of brain into gray matter, white matter, and cerebrospinal fluid in magnetic resonance images (MRI). We proposed an automatic hybrid image segmentation method that integrates the modified statistical expectation-maximization (EM) method and the spatial information combined with support vector machine (SVM). The combined method has more accurate results than what can be achieved with its individual techniques that is demonstrated through experiments on both real data and simulated images. Experiments are carried out on both synthetic and real MRI. The results of proposed technique are evaluated against manual segmentation results and other methods based on real T1-weighted scans from Internet Brain Segmentation Repository (IBSR) and simulated images from BrainWeb. The Kappa index is calculated to assess the performance of the proposed framework relative to the ground truth and expert segmentations. The results demonstrate that the proposed combined method has satisfactory results on both simulated MRI and real brain datasets. PMID:26089978

Quantitative Imaging of Energy Expenditure in Human Brain

PubMed Central

Zhu, Xiao-Hong; Qiao, Hongyan; Du, Fei; Xiong, Qiang; Liu, Xiao; Zhang, Xiaoliang; Ugurbil, Kamil; Chen, Wei

2012-01-01

Despite the essential role of the brain energy generated from ATP hydrolysis in supporting cortical neuronal activity and brain function, it is challenging to noninvasively image and directly quantify the energy expenditure in the human brain. In this study, we applied an advanced in vivo 31P MRS imaging approach to obtain regional cerebral metabolic rates of high-energy phosphate reactions catalyzed by ATPase (CMRATPase) and creatine kinase (CMRCK), and to determine CMRATPase and CMRCK in pure grey mater (GM) and white mater (WM), respectively. It was found that both ATPase and CK rates are three times higher in GM than WM; and CMRCK is seven times higher than CMRATPase in GM and WM. Among the total brain ATP consumption in the human cortical GM and WM, 77% of them are used by GM in which approximately 96% is by neurons. A single cortical neuron utilizes approximately 4.7 billion ATPs per second in a resting human brain. This study demonstrates the unique utility of in vivo 31P MRS imaging modality for direct imaging of brain energy generated from ATP hydrolysis, and provides new insights into the human brain energetics and its role in supporting neuronal activity and brain function. PMID:22487547

Colorization and Automated Segmentation of Human T2 MR Brain Images for Characterization of Soft Tissues

PubMed Central

Attique, Muhammad; Gilanie, Ghulam; Hafeez-Ullah; Mehmood, Malik S.; Naweed, Muhammad S.; Ikram, Masroor; Kamran, Javed A.; Vitkin, Alex

2012-01-01

Characterization of tissues like brain by using magnetic resonance (MR) images and colorization of the gray scale image has been reported in the literature, along with the advantages and drawbacks. Here, we present two independent methods; (i) a novel colorization method to underscore the variability in brain MR images, indicative of the underlying physical density of bio tissue, (ii) a segmentation method (both hard and soft segmentation) to characterize gray brain MR images. The segmented images are then transformed into color using the above-mentioned colorization method, yielding promising results for manual tracing. Our color transformation incorporates the voxel classification by matching the luminance of voxels of the source MR image and provided color image by measuring the distance between them. The segmentation method is based on single-phase clustering for 2D and 3D image segmentation with a new auto centroid selection method, which divides the image into three distinct regions (gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) using prior anatomical knowledge). Results have been successfully validated on human T2-weighted (T2) brain MR images. The proposed method can be potentially applied to gray-scale images from other imaging modalities, in bringing out additional diagnostic tissue information contained in the colorized image processing approach as described. PMID:22479421

The Importance of Neurogenic Inflammation in Blast-Induced Neurotrauma

DTIC Science & Technology

2013-01-01

mild/moderate BINT are imaged by magnetic resonance imaging ( MRI ) to visualize potential macrophage infiltration; blood-brain barrier (BBB) disturbance...TERMS blast, traumatic brain injury, brain, inflammation, magnetic resonance imaging , mice 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF...monitoring the success of therapeutic interventions. In this annual report we have utilized current live imaging methods (i.e. magnetic resonance

Brain tumour classification and abnormality detection using neuro-fuzzy technique and Otsu thresholding.

PubMed

Renjith, Arokia; Manjula, P; Mohan Kumar, P

2015-01-01

Brain tumour is one of the main causes for an increase in transience among children and adults. This paper proposes an improved method based on Magnetic Resonance Imaging (MRI) brain image classification and image segmentation approach. Automated classification is encouraged by the need of high accuracy when dealing with a human life. The detection of the brain tumour is a challenging problem, due to high diversity in tumour appearance and ambiguous tumour boundaries. MRI images are chosen for detection of brain tumours, as they are used in soft tissue determinations. First of all, image pre-processing is used to enhance the image quality. Second, dual-tree complex wavelet transform multi-scale decomposition is used to analyse texture of an image. Feature extraction extracts features from an image using gray-level co-occurrence matrix (GLCM). Then, the Neuro-Fuzzy technique is used to classify the stages of brain tumour as benign, malignant or normal based on texture features. Finally, tumour location is detected using Otsu thresholding. The classifier performance is evaluated based on classification accuracies. The simulated results show that the proposed classifier provides better accuracy than previous method.

Multi-modal imaging of long-term recovery post-stroke by positron emission tomography and matrix-assisted laser desorption/ionisation mass spectrometry.

PubMed

Henderson, Fiona; Hart, Philippa J; Pradillo, Jesus M; Kassiou, Michael; Christie, Lidan; Williams, Kaye J; Boutin, Herve; McMahon, Adam

2018-05-15

Stroke is a leading cause of disability worldwide. Understanding the recovery process post-stroke is essential; however, longer-term recovery studies are lacking. In vivo positron emission tomography (PET) can image biological recovery processes, but is limited by spatial resolution and its targeted nature. Untargeted mass spectrometry imaging offers high spatial resolution, providing an ideal ex vivo tool for brain recovery imaging. Magnetic resonance imaging (MRI) was used to image a rat brain 48 h after ischaemic stroke to locate the infarcted regions of the brain. PET was carried out 3 months post-stroke using the tracers [ 18 F]DPA-714 for TSPO and [ 18 F]IAM6067 for sigma-1 receptors to image neuroinflammation and neurodegeneration, respectively. The rat brain was flash-frozen immediately after PET scanning, and sectioned for matrix-assisted laser desorption/ionisation mass spectrometry (MALDI-MS) imaging. Three months post-stroke, PET imaging shows minimal detection of neurodegeneration and neuroinflammation, indicating that the brain has stabilised. However, MALDI-MS images reveal distinct differences in lipid distributions (e.g. phosphatidylcholine and sphingomyelin) between the scar and the healthy brain, suggesting that recovery processes are still in play. It is currently not known if the altered lipids in the scar will change on a longer time scale, or if they are stabilised products of the brain post-stroke. The data demonstrates the ability to combine MALD-MS with in vivo PET to image different aspects of stroke recovery. Copyright © 2018 John Wiley & Sons, Ltd.

Targeting caspase-3 as dual therapeutic benefits by RNAi facilitating brain-targeted nanoparticles in a rat model of Parkinson's disease.

PubMed

Liu, Yang; Guo, Yubo; An, Sai; Kuang, Yuyang; He, Xi; Ma, Haojun; Li, Jianfeng; Lu, Jing; Lv, Jing; Zhang, Ning; Jiang, Chen

2013-01-01

The activation of caspase-3 is an important hallmark in Parkinson's disease. It could induce neuron death by apoptosis and microglia activation by inflammation. As a result, inhibition the activation of caspase-3 would exert synergistic dual effect in brain in order to prevent the progress of Parkinson's disease. Silencing caspase-3 genes by RNA interference could inhibit the activation of caspase-3. We developed a brain-targeted gene delivery system based on non-viral gene vector, dendrigraft poly-L-lysines. A rabies virus glycoprotein peptide with 29 amino-acid linked to dendrigraft poly-L-lysines could render gene vectors the ability to get across the blood brain barrier by specific receptor mediated transcytosis. The resultant brain-targeted vector was complexed with caspase-3 short hairpin RNA coding plasmid DNA, yielding nanoparticles. In vivo imaging analysis indicated the targeted nanoparticles could accumulate in brain more efficiently than non-targeted ones. A multiple dosing regimen by weekly intravenous administration of the nanoparticles could reduce activated casapse-3 levels, significantly improve locomotor activity and rescue dopaminergic neuronal loss and in Parkinson's disease rats' brain. These results indicated the rabies virus glycoprotein peptide modified brain-targeted nanoparticles were promising gene delivery system for RNA interference to achieve anti-apoptotic and anti-inflammation synergistic therapeutic effects by down-regulation the expression and activation of caspase-3.

Regulation of Drosophila Brain Wiring by Neuropil Interactions via a Slit-Robo-RPTP Signaling Complex.

PubMed

Oliva, Carlos; Soldano, Alessia; Mora, Natalia; De Geest, Natalie; Claeys, Annelies; Erfurth, Maria-Luise; Sierralta, Jimena; Ramaekers, Ariane; Dascenco, Dan; Ejsmont, Radoslaw K; Schmucker, Dietmar; Sanchez-Soriano, Natalia; Hassan, Bassem A

2016-10-24

The axonal wiring molecule Slit and its Round-About (Robo) receptors are conserved regulators of nerve cord patterning. Robo receptors also contribute to wiring brain circuits. Whether molecular mechanisms regulating these signals are modified to fit more complex brain wiring processes is unclear. We investigated the role of Slit and Robo receptors in wiring Drosophila higher-order brain circuits and identified differences in the cellular and molecular mechanisms of Robo/Slit function. First, we find that signaling by Robo receptors in the brain is regulated by the Receptor Protein Tyrosine Phosphatase RPTP69d. RPTP69d increases membrane availability of Robo3 without affecting its phosphorylation state. Second, we detect no midline localization of Slit during brain development. Instead, Slit is enriched in the mushroom body, a neuronal structure covering large areas of the brain. Thus, a divergent molecular mechanism regulates neuronal circuit wiring in the Drosophila brain, partly in response to signals from the mushroom body. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Learning implicit brain MRI manifolds with deep learning

NASA Astrophysics Data System (ADS)

Bermudez, Camilo; Plassard, Andrew J.; Davis, Larry T.; Newton, Allen T.; Resnick, Susan M.; Landman, Bennett A.

2018-03-01

An important task in image processing and neuroimaging is to extract quantitative information from the acquired images in order to make observations about the presence of disease or markers of development in populations. Having a low-dimensional manifold of an image allows for easier statistical comparisons between groups and the synthesis of group representatives. Previous studies have sought to identify the best mapping of brain MRI to a low-dimensional manifold, but have been limited by assumptions of explicit similarity measures. In this work, we use deep learning techniques to investigate implicit manifolds of normal brains and generate new, high-quality images. We explore implicit manifolds by addressing the problems of image synthesis and image denoising as important tools in manifold learning. First, we propose the unsupervised synthesis of T1-weighted brain MRI using a Generative Adversarial Network (GAN) by learning from 528 examples of 2D axial slices of brain MRI. Synthesized images were first shown to be unique by performing a cross-correlation with the training set. Real and synthesized images were then assessed in a blinded manner by two imaging experts providing an image quality score of 1-5. The quality score of the synthetic image showed substantial overlap with that of the real images. Moreover, we use an autoencoder with skip connections for image denoising, showing that the proposed method results in higher PSNR than FSL SUSAN after denoising. This work shows the power of artificial networks to synthesize realistic imaging data, which can be used to improve image processing techniques and provide a quantitative framework to structural changes in the brain.

Rough-Fuzzy Clustering and Unsupervised Feature Selection for Wavelet Based MR Image Segmentation

PubMed Central

Maji, Pradipta; Roy, Shaswati

2015-01-01

Image segmentation is an indispensable process in the visualization of human tissues, particularly during clinical analysis of brain magnetic resonance (MR) images. For many human experts, manual segmentation is a difficult and time consuming task, which makes an automated brain MR image segmentation method desirable. In this regard, this paper presents a new segmentation method for brain MR images, integrating judiciously the merits of rough-fuzzy computing and multiresolution image analysis technique. The proposed method assumes that the major brain tissues, namely, gray matter, white matter, and cerebrospinal fluid from the MR images are considered to have different textural properties. The dyadic wavelet analysis is used to extract the scale-space feature vector for each pixel, while the rough-fuzzy clustering is used to address the uncertainty problem of brain MR image segmentation. An unsupervised feature selection method is introduced, based on maximum relevance-maximum significance criterion, to select relevant and significant textural features for segmentation problem, while the mathematical morphology based skull stripping preprocessing step is proposed to remove the non-cerebral tissues like skull. The performance of the proposed method, along with a comparison with related approaches, is demonstrated on a set of synthetic and real brain MR images using standard validity indices. PMID:25848961

Analysis of dual tree M-band wavelet transform based features for brain image classification.

PubMed

Ayalapogu, Ratna Raju; Pabboju, Suresh; Ramisetty, Rajeswara Rao

2018-04-29

The most complex organ in the human body is the brain. The unrestrained growth of cells in the brain is called a brain tumor. The cause of a brain tumor is still unknown and the survival rate is lower than other types of cancers. Hence, early detection is very important for proper treatment. In this study, an efficient computer-aided diagnosis (CAD) system is presented for brain image classification by analyzing MRI of the brain. At first, the MRI brain images of normal and abnormal categories are modeled by using the statistical features of dual tree m-band wavelet transform (DTMBWT). A maximum margin classifier, support vector machine (SVM) is then used for the classification and validated with k-fold approach. Results show that the system provides promising results on a repository of molecular brain neoplasia data (REMBRANDT) with 97.5% accuracy using 4 th level statistical features of DTMBWT. Viewing the experimental results, we conclude that the system gives a satisfactory performance for the brain image classification. © 2018 International Society for Magnetic Resonance in Medicine.

Oxytocin curbs calorie intake via food-specific increases in the activity of brain areas that process reward and establish cognitive control.

PubMed

Spetter, Maartje S; Feld, Gordon B; Thienel, Matthias; Preissl, Hubert; Hege, Maike A; Hallschmid, Manfred

2018-02-09

The hypothalamic neurohormone oxytocin decreases food intake via largely unexplored mechanisms. We investigated the central nervous mediation of oxytocin's hypophagic effect in comparison to its impact on the processing of generalized rewards. Fifteen fasted normal-weight, young men received intranasal oxytocin (24 IU) or placebo before functional magnetic resonance imaging (fMRI) measurements of brain activity during exposure to food stimuli and a monetary incentive delay task (MID). Subsequently, ad-libitum breakfast intake was assessed. Oxytocin compared to placebo increased activity in the ventromedial prefrontal cortex, supplementary motor area, anterior cingulate, and ventrolateral prefrontal cortices in response to high- vs. low-calorie food images in the fasted state, and reduced calorie intake by 12%. During anticipation of monetary rewards, oxytocin compared to placebo augmented striatal, orbitofrontal and insular activity without altering MID performance. We conclude that during the anticipation of generalized rewards, oxytocin stimulates dopaminergic reward-processing circuits. In contrast, oxytocin restrains food intake by enhancing the activity of brain regions that exert cognitive control, while concomitantly increasing the activity of structures that process food reward value. This pattern points towards a specific role of oxytocin in the regulation of eating behaviour in humans that might be of relevance for potential clinical applications.

High-resolution in vivo Wistar rodent brain atlas based on T1 weighted image

NASA Astrophysics Data System (ADS)

Huang, Su; Lu, Zhongkang; Huang, Weimin; Seramani, Sankar; Ramasamy, Boominathan; Sekar, Sakthivel; Guan, Cuntai; Bhakoo, Kishore

2016-03-01

Image based atlases for rats brain have a significant impact on pre-clinical research. In this project we acquired T1-weighted images from Wistar rodent brains with fine 59μm isotropical resolution for generation of the atlas template image. By applying post-process procedures using a semi-automatic brain extraction method, we delineated the brain tissues from source data. Furthermore, we applied a symmetric group-wise normalization method to generate an optimized template of T1 image of rodent brain, then aligned our template to the Waxholm Space. In addition, we defined several simple and explicit landmarks to corresponding our template with the well known Paxinos stereotaxic reference system. Anchoring at the origin of the Waxholm Space, we applied piece-wise linear transformation method to map the voxels of the template into the coordinates system in Paxinos' stereotoxic coordinates to facilitate the labelling task. We also cross-referenced our data with both published rodent brain atlas and image atlases available online, methodologically labelling the template to produce a Wistar brain atlas identifying more than 130 structures. Particular attention was paid to the cortex and cerebellum, as these areas encompass the most researched aspects of brain functions. Moreover, we adopted the structure hierarchy and naming nomenclature common to various atlases, so that the names and hierarchy structure presented in the atlas are readily recognised for easy use. It is believed the atlas will present a useful tool in rodent brain functional and pharmaceutical studies.

A combined solenoid-surface RF coil for high-resolution whole-brain rat imaging on a 3.0 Tesla clinical MR scanner.

PubMed

Underhill, Hunter R; Yuan, Chun; Hayes, Cecil E

2010-09-01

Rat brain models effectively simulate a multitude of human neurological disorders. Improvements in coil design have facilitated the wider utilization of rat brain models by enabling the utilization of clinical MR scanners for image acquisition. In this study, a novel coil design, subsequently referred to as the rat brain coil, is described that exploits and combines the strengths of both solenoids and surface coils into a simple, multichannel, receive-only coil dedicated to whole-brain rat imaging on a 3.0 T clinical MR scanner. Compared with a multiturn solenoid mouse body coil, a 3-cm surface coil, a modified Helmholtz coil, and a phased-array surface coil, the rat brain coil improved signal-to-noise ratio by approximately 72, 61, 78, and 242%, respectively. Effects of the rat brain coil on amplitudes of static field and radiofrequency field uniformity were similar to each of the other coils. In vivo, whole-brain images of an adult male rat were acquired with a T(2)-weighted spin-echo sequence using an isotropic acquisition resolution of 0.25 x 0.25 x 0.25 mm(3) in 60.6 min. Multiplanar images of the in vivo rat brain with identification of anatomic structures are presented. Improvement in signal-to-noise ratio afforded by the rat brain coil may broaden experiments that utilize clinical MR scanners for in vivo image acquisition. 2010 Wiley-Liss, Inc.

A framework for correcting brain retraction based on an eXtended Finite Element Method using a laser range scanner.

PubMed

Li, Ping; Wang, Weiwei; Song, Zhijian; An, Yong; Zhang, Chenxi

2014-07-01

Brain retraction causes great distortion that limits the accuracy of an image-guided neurosurgery system that uses preoperative images. Therefore, brain retraction correction is an important intraoperative clinical application. We used a linear elastic biomechanical model, which deforms based on the eXtended Finite Element Method (XFEM) within a framework for brain retraction correction. In particular, a laser range scanner was introduced to obtain a surface point cloud of the exposed surgical field including retractors inserted into the brain. A brain retraction surface tracking algorithm converted these point clouds into boundary conditions applied to XFEM modeling that drive brain deformation. To test the framework, we performed a brain phantom experiment involving the retraction of tissue. Pairs of the modified Hausdorff distance between Canny edges extracted from model-updated images, pre-retraction, and post-retraction CT images were compared to evaluate the morphological alignment of our framework. Furthermore, the measured displacements of beads embedded in the brain phantom and the predicted ones were compared to evaluate numerical performance. The modified Hausdorff distance of 19 pairs of images decreased from 1.10 to 0.76 mm. The forecast error of 23 stainless steel beads in the phantom was between 0 and 1.73 mm (mean 1.19 mm). The correction accuracy varied between 52.8 and 100 % (mean 81.4 %). The results demonstrate that the brain retraction compensation can be incorporated intraoperatively into the model-updating process in image-guided neurosurgery systems.

Physiological and brain activity after a combined cognitive behavioral treatment plus video game therapy for emotional regulation in bulimia nervosa: a case report.

PubMed

Fagundo, Ana Beatriz; Via, Esther; Sánchez, Isabel; Jiménez-Murcia, Susana; Forcano, Laura; Soriano-Mas, Carles; Giner-Bartolomé, Cristina; Santamaría, Juan J; Ben-Moussa, Maher; Konstantas, Dimitri; Lam, Tony; Lucas, Mikkel; Nielsen, Jeppe; Lems, Peter; Cardoner, Narcís; Menchón, Jose M; de la Torre, Rafael; Fernandez-Aranda, Fernando

2014-08-12

PlayMancer is a video game designed to increase emotional regulation and reduce general impulsive behaviors, by training to decrease arousal and improve decision-making and planning. We have previously demonstrated the usefulness of PlayMancer in reducing impulsivity and improving emotional regulation in bulimia nervosa (BN) patients. However, whether these improvements are actually translated into brain changes remains unclear. The aim of this case study was to report on a 28-year-old Spanish woman with BN, and to examine changes in physiological variables and brain activity after a combined treatment of video game therapy (VGT) and cognitive behavioral therapy (CBT). Ten VGT sessions were carried out on a weekly basis. Anxiety, physiological, and impulsivity measurements were recorded. The patient was scanned in a 1.5-T magnetic resonance scanner, prior to and after the 10-week VGT/CBT combined treatment, using two paradigms: (1) an emotional face-matching task, and (2) a multi-source interference task (MSIT). Upon completing the treatment, a decrease in average heart rate was observed. The functional magnetic resonance imaging (fMRI) results indicated a post-treatment reduction in reaction time along with high accuracy. The patient engaged areas typically active in healthy controls, although the cluster extension of the active areas decreased after the combined treatment. These results suggest a global improvement in emotional regulation and impulsivity control after the VGT therapy in BN, demonstrated by both physiological and neural changes. These promising results suggest that a combined treatment of CBT and VGT might lead to functional cerebral changes that ultimately translate into better cognitive and emotional performances.

Physiological and Brain Activity After a Combined Cognitive Behavioral Treatment Plus Video Game Therapy for Emotional Regulation in Bulimia Nervosa: A Case Report

PubMed Central

Fagundo, Ana Beatriz; Via, Esther; Sánchez, Isabel; Jiménez-Murcia, Susana; Forcano, Laura; Soriano-Mas, Carles; Giner-Bartolomé, Cristina; Santamaría, Juan J; Ben-Moussa, Maher; Konstantas, Dimitri; Lam, Tony; Lucas, Mikkel; Nielsen, Jeppe; Lems, Peter; Cardoner, Narcís; Menchón, Jose M; de la Torre, Rafael

2014-01-01

Background PlayMancer is a video game designed to increase emotional regulation and reduce general impulsive behaviors, by training to decrease arousal and improve decision-making and planning. We have previously demonstrated the usefulness of PlayMancer in reducing impulsivity and improving emotional regulation in bulimia nervosa (BN) patients. However, whether these improvements are actually translated into brain changes remains unclear. Objective The aim of this case study was to report on a 28-year-old Spanish woman with BN, and to examine changes in physiological variables and brain activity after a combined treatment of video game therapy (VGT) and cognitive behavioral therapy (CBT). Methods Ten VGT sessions were carried out on a weekly basis. Anxiety, physiological, and impulsivity measurements were recorded. The patient was scanned in a 1.5-T magnetic resonance scanner, prior to and after the 10-week VGT/CBT combined treatment, using two paradigms: (1) an emotional face-matching task, and (2) a multi-source interference task (MSIT). Results Upon completing the treatment, a decrease in average heart rate was observed. The functional magnetic resonance imaging (fMRI) results indicated a post-treatment reduction in reaction time along with high accuracy. The patient engaged areas typically active in healthy controls, although the cluster extension of the active areas decreased after the combined treatment. Conclusions These results suggest a global improvement in emotional regulation and impulsivity control after the VGT therapy in BN, demonstrated by both physiological and neural changes. These promising results suggest that a combined treatment of CBT and VGT might lead to functional cerebral changes that ultimately translate into better cognitive and emotional performances. PMID:25116416

Social reinforcement can regulate localized brain activity.

PubMed

Mathiak, Krystyna A; Koush, Yury; Dyck, Miriam; Gaber, Tilman J; Alawi, Eliza; Zepf, Florian D; Zvyagintsev, Mikhail; Mathiak, Klaus

2010-11-01

Social learning is essential for adaptive behavior in humans. Neurofeedback based on functional magnetic resonance imaging (fMRI) trains control over localized brain activity. It can disentangle learning processes at the neural level and thus investigate the mechanisms of operant conditioning with explicit social reinforcers. In a pilot study, a computer-generated face provided a positive feedback (smiling) when activity in the anterior cingulate cortex (ACC) increased and gradually returned to a neutral expression when the activity dropped. One female volunteer without previous experience in fMRI underwent training based on a social reinforcer. Directly before and after the neurofeedback runs, neural responses to a cognitive interference task (Simon task) were recorded. We observed a significant increase in activity within ACC during the neurofeedback blocks, correspondent with the a-priori defined anatomical region of interest. In the course of the neurofeedback training, the subject learned to regulate ACC activity and could maintain the control even without direct feedback. Moreover, ACC was activated significantly stronger during Simon task after the neurofeedback training when compared to before. Localized brain activity can be controlled by social reward. The increased ACC activity transferred to a cognitive task with the potential to reduce cognitive interference. Systematic studies are required to explore long-term effects on social behavior and clinical applications.

Altered resting-state amygdala functional connectivity in men with posttraumatic stress disorder

PubMed Central

Sripada, Rebecca K.; King, Anthony P.; Garfinkel, Sarah N.; Wang, Xin; Sripada, Chandra S.; Welsh, Robert C.; Liberzon, Israel

2012-01-01

Background Converging neuroimaging research suggests altered emotion neurocircuitry in individuals with posttraumatic stress disorder (PTSD). Emotion activation studies in these individuals have shown hyperactivation in emotion-related regions, including the amygdala and insula, and hypoactivation in emotion-regulation regions, including the medial prefrontal cortex (mPFC) and anterior cingulate cortex (ACC). However, few studies have examined patterns of connectivity at rest in individuals with PTSD, a potentially powerful method for illuminating brain network structure. Methods Using the amygdala as a seed region, we measured resting-state brain connectivity using 3 T functional magnetic resonance imaging in returning male veterans with PTSD and combat controls without PTSD. Results Fifteen veterans with PTSD and 14 combat controls enrolled in our study. Compared with controls, veterans with PTSD showed greater positive connectivity between the amygdala and insula, reduced positive connectivity between the amygdala and hippocampus, and reduced anticorrelation between the amygdala and dorsal ACC and rostral ACC. Limitations Only male veterans with combat exposure were tested, thus our findings cannot be generalized to women or to individuals with non–combat related PTSD. Conclusion These results demonstrate that studies of functional connectivity during resting state can discern aberrant patterns of coupling within emotion circuits and suggest a possible brain basis for emotion-processing and emotion-regulation deficits in individuals with PTSD. PMID:22313617

Conservative nature of oestradiol signalling pathways in the brain lobes of octopus vulgaris involved in reproduction, learning and motor coordination.

PubMed

De Lisa, E; Paolucci, M; Di Cosmo, A

2012-02-01

Oestradiol plays crucial roles in the mammalian brain by modulating reproductive behaviour, neural plasticity and pain perception. The cephalopod Octopus vulgaris is considered, along with its relatives, to be the most behaviourally advanced invertebrate, although the neurophysiological basis of its behaviours, including pain perception, remain largely unknown. In the present study, using a combination of molecular and imaging techniques, we found that oestradiol up-regulated O. vulgaris gonadotrophin-releasing hormone (Oct-GnRH) and O. vulgaris oestrogen receptor (Oct-ER) mRNA levels in the olfactory lobes; in turn, Oct-ER mRNA was regulated by NMDA in lobes involved in learning and motor coordination. Fluorescence resonance energy transfer analysis revealed that oestradiol binds Oct-ER causing conformational modifications and nuclear translocation consistent with the classical genomic mechanism of the oestrogen receptor. Moreover, oestradiol triggered a calcium influx and cyclic AMP response element binding protein phosphorylation via membrane receptors, providing evidence for a rapid nongenomic action of oestradiol in O. vulgaris. In the present study, we demonstrate, for the first time, the physiological role of oestradiol in the brain lobes of O. vulgaris involved in reproduction, learning and motor coordination. © 2011 The Authors. Journal of Neuroendocrinology © 2011 Blackwell Publishing Ltd.

Evaluation of five diffeomorphic image registration algorithms for mouse brain magnetic resonance microscopy.

PubMed

Fu, Zhenrong; Lin, Lan; Tian, Miao; Wang, Jingxuan; Zhang, Baiwen; Chu, Pingping; Li, Shaowu; Pathan, Muhammad Mohsin; Deng, Yulin; Wu, Shuicai

2017-11-01

The development of genetically engineered mouse models for neuronal diseases and behavioural disorders have generated a growing need for small animal imaging. High-resolution magnetic resonance microscopy (MRM) provides powerful capabilities for noninvasive studies of mouse brains, while avoiding some limits associated with the histological procedures. Quantitative comparison of structural images is a critical step in brain imaging analysis, which highly relies on the performance of image registration techniques. Nowadays, there is a mushrooming growth of human brain registration algorithms, while fine-tuning of those algorithms for mouse brain MRMs is rarely addressed. Because of their topology preservation property and outstanding performance in human studies, diffeomorphic transformations have become popular in computational anatomy. In this study, we specially tuned five diffeomorphic image registration algorithms [DARTEL, geodesic shooting, diffeo-demons, SyN (Greedy-SyN and geodesic-SyN)] for mouse brain MRMs and evaluated their performance using three measures [volume overlap percentage (VOP), residual intensity error (RIE) and surface concordance ratio (SCR)]. Geodesic-SyN performed significantly better than the other methods according to all three different measures. These findings are important for the studies on structural brain changes that may occur in wild-type and transgenic mouse brains. © 2017 The Authors Journal of Microscopy © 2017 Royal Microscopical Society.

Decoding brain responses to pixelized images in the primary visual cortex: implications for visual cortical prostheses

PubMed Central

Guo, Bing-bing; Zheng, Xiao-lin; Lu, Zhen-gang; Wang, Xing; Yin, Zheng-qin; Hou, Wen-sheng; Meng, Ming

2015-01-01

Visual cortical prostheses have the potential to restore partial vision. Still limited by the low-resolution visual percepts provided by visual cortical prostheses, implant wearers can currently only “see” pixelized images, and how to obtain the specific brain responses to different pixelized images in the primary visual cortex (the implant area) is still unknown. We conducted a functional magnetic resonance imaging experiment on normal human participants to investigate the brain activation patterns in response to 18 different pixelized images. There were 100 voxels in the brain activation pattern that were selected from the primary visual cortex, and voxel size was 4 mm × 4 mm × 4 mm. Multi-voxel pattern analysis was used to test if these 18 different brain activation patterns were specific. We chose a Linear Support Vector Machine (LSVM) as the classifier in this study. The results showed that the classification accuracies of different brain activation patterns were significantly above chance level, which suggests that the classifier can successfully distinguish the brain activation patterns. Our results suggest that the specific brain activation patterns to different pixelized images can be obtained in the primary visual cortex using a 4 mm × 4 mm × 4 mm voxel size and a 100-voxel pattern. PMID:26692860

Deformation Invariant Attribute Vector for Deformable Registration of Longitudinal Brain MR Images

PubMed Central

Li, Gang; Guo, Lei; Liu, Tianming

2009-01-01

This paper presents a novel approach to define deformation invariant attribute vector (DIAV) for each voxel in 3D brain image for the purpose of anatomic correspondence detection. The DIAV method is validated by using synthesized deformation in 3D brain MRI images. Both theoretic analysis and experimental studies demonstrate that the proposed DIAV is invariant to general nonlinear deformation. Moreover, our experimental results show that the DIAV is able to capture rich anatomic information around the voxels and exhibit strong discriminative ability. The DIAV has been integrated into a deformable registration algorithm for longitudinal brain MR images, and the results on both simulated and real brain images are provided to demonstrate the good performance of the proposed registration algorithm based on matching of DIAVs. PMID:19369031

Neuroimaging Feature Terminology: A Controlled Terminology for the Annotation of Brain Imaging Features.

PubMed

Iyappan, Anandhi; Younesi, Erfan; Redolfi, Alberto; Vrooman, Henri; Khanna, Shashank; Frisoni, Giovanni B; Hofmann-Apitius, Martin

2017-01-01

Ontologies and terminologies are used for interoperability of knowledge and data in a standard manner among interdisciplinary research groups. Existing imaging ontologies capture general aspects of the imaging domain as a whole such as methodological concepts or calibrations of imaging instruments. However, none of the existing ontologies covers the diagnostic features measured by imaging technologies in the context of neurodegenerative diseases. Therefore, the Neuro-Imaging Feature Terminology (NIFT) was developed to organize the knowledge domain of measured brain features in association with neurodegenerative diseases by imaging technologies. The purpose is to identify quantitative imaging biomarkers that can be extracted from multi-modal brain imaging data. This terminology attempts to cover measured features and parameters in brain scans relevant to disease progression. In this paper, we demonstrate the systematic retrieval of measured indices from literature and how the extracted knowledge can be further used for disease modeling that integrates neuroimaging features with molecular processes.

Fuzzy object models for newborn brain MR image segmentation

NASA Astrophysics Data System (ADS)

Kobashi, Syoji; Udupa, Jayaram K.

2013-03-01

Newborn brain MR image segmentation is a challenging problem because of variety of size, shape and MR signal although it is the fundamental study for quantitative radiology in brain MR images. Because of the large difference between the adult brain and the newborn brain, it is difficult to directly apply the conventional methods for the newborn brain. Inspired by the original fuzzy object model introduced by Udupa et al. at SPIE Medical Imaging 2011, called fuzzy shape object model (FSOM) here, this paper introduces fuzzy intensity object model (FIOM), and proposes a new image segmentation method which combines the FSOM and FIOM into fuzzy connected (FC) image segmentation. The fuzzy object models are built from training datasets in which the cerebral parenchyma is delineated by experts. After registering FSOM with the evaluating image, the proposed method roughly recognizes the cerebral parenchyma region based on a prior knowledge of location, shape, and the MR signal given by the registered FSOM and FIOM. Then, FC image segmentation delineates the cerebral parenchyma using the fuzzy object models. The proposed method has been evaluated using 9 newborn brain MR images using the leave-one-out strategy. The revised age was between -1 and 2 months. Quantitative evaluation using false positive volume fraction (FPVF) and false negative volume fraction (FNVF) has been conducted. Using the evaluation data, a FPVF of 0.75% and FNVF of 3.75% were achieved. More data collection and testing are underway.

Near-Infrared Confocal Laser Reflectance Cytoarchitectural Imaging of the Substantia Nigra and Cerebellum in the Fresh Human Cadaver.

PubMed

Cheyuo, Cletus; Grand, Walter; Balos, Lucia L

2017-01-01

Cytoarchitectural neuroimaging remains critical for diagnosis of many brain diseases. Fluorescent dye-enhanced, near-infrared confocal in situ cellular imaging of the brain has been reported. However, impermeability of the blood-brain barrier to most fluorescent dyes limits clinical utility of this modality. The differential degree of reflectance from brain tissue with unenhanced near-infrared imaging may represent an alternative technique for in situ cytoarchitectural neuroimaging. We assessed the utility of unenhanced near-infrared confocal laser reflectance imaging of the cytoarchitecture of the cerebellum and substantia nigra in 2 fresh human cadaver brains using a confocal near-infrared laser probe. Cellular images based on near-infrared differential reflectance were captured at depths of 20-180 μm from the brain surface. Parts of the cerebellum and substantia nigra imaged using the probe were subsequently excised and stained with hematoxylin and eosin for histologic correlation. Near-infrared reflectance imaging revealed the 3-layered cytoarchitecture of the cerebellum, with Purkinje cells appearing hyperreflectant. In the substantia nigra, neurons appeared hyporeflectant with hyperreflectant neuromelanin cytoplasmic inclusions. Cytoarchitecture of the cerebellum and substantia nigra revealed on near-infrared imaging closely correlated with the histology on hematoxylin-eosin staining. We showed that unenhanced near-infrared reflectance imaging of fresh human cadaver brain can reliably identify and distinguish neurons and detailed cytoarchitecture of the cerebellum and substantia nigra. Copyright © 2016 Elsevier Inc. All rights reserved.

Optical Brain Imaging: A Powerful Tool for Neuroscience.

PubMed

Zhu, Xinpei; Xia, Yanfang; Wang, Xuecen; Si, Ke; Gong, Wei

2017-02-01

As the control center of organisms, the brain remains little understood due to its complexity. Taking advantage of imaging methods, scientists have found an accessible approach to unraveling the mystery of neuroscience. Among these methods, optical imaging techniques are widely used due to their high molecular specificity and single-molecule sensitivity. Here, we overview several optical imaging techniques in neuroscience of recent years, including brain clearing, the micro-optical sectioning tomography system, and deep tissue imaging.

Automatic Brain Tumor Detection in T2-weighted Magnetic Resonance Images

NASA Astrophysics Data System (ADS)

Dvořák, P.; Kropatsch, W. G.; Bartušek, K.

2013-10-01

This work focuses on fully automatic detection of brain tumors. The first aim is to determine, whether the image contains a brain with a tumor, and if it does, localize it. The goal of this work is not the exact segmentation of tumors, but the localization of their approximate position. The test database contains 203 T2-weighted images of which 131 are images of healthy brain and the remaining 72 images contain brain with pathological area. The estimation, whether the image shows an afflicted brain and where a pathological area is, is done by multi resolution symmetry analysis. The first goal was tested by five-fold cross-validation technique with 100 repetitions to avoid the result dependency on sample order. This part of the proposed method reaches the true positive rate of 87.52% and the true negative rate of 93.14% for an afflicted brain detection. The evaluation of the second part of the algorithm was carried out by comparing the estimated location to the true tumor location. The detection of the tumor location reaches the rate of 95.83% of correct anomaly detection and the rate 87.5% of correct tumor location.

Spatial Mapping of Structural and Connectional Imaging Data for the Developing Human Brain with Diffusion Tensor Imaging

PubMed Central

Ouyang, Austin; Jeon, Tina; Sunkin, Susan M.; Pletikos, Mihovil; Sedmak, Goran; Sestan, Nenad; Lein, Ed S.; Huang, Hao

2014-01-01

During human brain development from fetal stage to adulthood, the white matter (WM) tracts undergo dramatic changes. Diffusion tensor imaging (DTI), a widely used magnetic resonance imaging (MRI) modality, offers insight into the dynamic changes of WM fibers as these fibers can be noninvasively traced and three-dimensionally (3D) reconstructed with DTI tractography. The DTI and conventional T1 weighted MRI images also provide sufficient cortical anatomical details for mapping the cortical regions of interests (ROIs). In this paper, we described basic concepts and methods of DTI techniques that can be used to trace major WM tracts noninvasively from fetal brain of 14 postconceptional weeks (pcw) to adult brain. We applied these techniques to acquire DTI data and trace, reconstruct and visualize major WM tracts during development. After categorizing major WM fiber bundles into five unique functional tract groups, namely limbic, brain stem, projection, commissural and association tracts, we revealed formation and maturation of these 3D reconstructed WM tracts of the developing human brain. The structural and connectional imaging data offered by DTI provides the anatomical backbone of transcriptional atlas of the developing human brain. PMID:25448302

Dissociations between behavioural and functional magnetic resonance imaging-based evaluations of cognitive function after brain injury

PubMed Central

Bardin, Jonathan C.; Fins, Joseph J.; Katz, Douglas I.; Hersh, Jennifer; Heier, Linda A.; Tabelow, Karsten; Dyke, Jonathan P.; Ballon, Douglas J.; Schiff, Nicholas D.

2011-01-01

Functional neuroimaging methods hold promise for the identification of cognitive function and communication capacity in some severely brain-injured patients who may not retain sufficient motor function to demonstrate their abilities. We studied seven severely brain-injured patients and a control group of 14 subjects using a novel hierarchical functional magnetic resonance imaging assessment utilizing mental imagery responses. Whereas the control group showed consistent and accurate (for communication) blood-oxygen-level-dependent responses without exception, the brain-injured subjects showed a wide variation in the correlation of blood-oxygen-level-dependent responses and overt behavioural responses. Specifically, the brain-injured subjects dissociated bedside and functional magnetic resonance imaging-based command following and communication capabilities. These observations reveal significant challenges in developing validated functional magnetic resonance imaging-based methods for clinical use and raise interesting questions about underlying brain function assayed using these methods in brain-injured subjects. PMID:21354974

Development of a High Angular Resolution Diffusion Imaging Human Brain Template

PubMed Central

Varentsova, Anna; Zhang, Shengwei; Arfanakis, Konstantinos

2014-01-01

Brain diffusion templates contain rich information about the microstructure of the brain, and are used as references in spatial normalization or in the development of brain atlases. The accuracy of diffusion templates constructed based on the diffusion tensor (DT) model is limited in regions with complex neuronal micro-architecture. High angular resolution diffusion imaging (HARDI) overcomes limitations of the DT model and is capable of resolving intravoxel heterogeneity. However, when HARDI is combined with multiple-shot sequences to minimize image artifacts, the scan time becomes inappropriate for human brain imaging. In this work, an artifact-free HARDI template of the human brain was developed from low angular resolution multiple-shot diffusion data. The resulting HARDI template was produced in ICBM-152 space based on Turboprop diffusion data, was shown to resolve complex neuronal micro-architecture in regions with intravoxel heterogeneity, and contained fiber orientation information consistent with known human brain anatomy. PMID:24440528

Anti-Inflammatory Effects of Omega-3 Fatty Acids in the Brain: Physiological Mechanisms and Relevance to Pharmacology.

PubMed

Layé, Sophie; Nadjar, Agnès; Joffre, Corinne; Bazinet, Richard P

2018-01-01

Classically, polyunsaturated fatty acids (PUFA) were largely thought to be relatively inert structural components of brain, largely important for the formation of cellular membranes. Over the past 10 years, a host of bioactive lipid mediators that are enzymatically derived from arachidonic acid, the main n-6 PUFA, and docosahexaenoic acid, the main n-3 PUFA in the brain, known to regulate peripheral immune function, have been detected in the brain and shown to regulate microglia activation. Recent advances have focused on how PUFA regulate the molecular signaling of microglia, especially in the context of neuroinflammation and behavior. Several active drugs regulate brain lipid signaling and provide proof of concept for targeting the brain. Because brain lipid metabolism relies on a complex integration of diet, peripheral metabolism, including the liver and blood, which supply the brain with PUFAs that can be altered by genetics, sex, and aging, there are many pathways that can be disrupted, leading to altered brain lipid homeostasis. Brain lipid signaling pathways are altered in neurologic disorders and may be viable targets for the development of novel therapeutics. In this study, we discuss in particular how n-3 PUFAs and their metabolites regulate microglia phenotype and function to exert their anti-inflammatory and proresolving activities in the brain. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

Positive effects of neurofeedback on autism symptoms correlate with brain activation during imitation and observation.

PubMed

Datko, Michael; Pineda, Jaime A; Müller, Ralph-Axel

2018-03-01

Autism has been characterized by atypical task-related brain activation and functional connections, coinciding with deficits in sociocommunicative abilities. However, evidence of the brain's experience-dependent plasticity suggests that abnormal activity patterns may be reversed with treatment. In particular, neurofeedback training (NFT), an intervention based on operant conditioning resulting in self-regulation of brain electrical oscillations, has shown increasing promise in addressing abnormalities in brain function and behavior. We examined the effects of ≥ 20 h of sensorimotor mu-rhythm-based NFT in children with high-functioning autism spectrum disorders (ASD) and a matched control group of typically developing children (ages 8-17). During a functional magnetic resonance imaging imitation and observation task, the ASD group showed increased activation in regions of the human mirror neuron system following the NFT, as part of a significant interaction between group (ASD vs. controls) and training (pre- vs. post-training). These changes were positively correlated with behavioral improvements in the ASD participants, indicating that mu-rhythm NFT may be beneficial to individuals with ASD. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Adolescent brain development in normality and psychopathology

PubMed Central

LUCIANA, MONICA

2014-01-01

Since this journal’s inception, the field of adolescent brain development has flourished, as researchers have investigated the underpinnings of adolescent risk-taking behaviors. Explanations based on translational models initially attributed such behaviors to executive control deficiencies and poor frontal lobe function. This conclusion was bolstered by evidence that the prefrontal cortex and its interconnections are among the last brain regions to structurally and functionally mature. As substantial heterogeneity of prefrontal function was revealed, applications of neuroeconomic theory to adolescent development led to dual systems models of behavior. Current epidemiological trends, behavioral observations, and functional magnetic resonance imaging based brain activity patterns suggest a quadratic increase in limbically mediated incentive motivation from childhood to adolescence and a decline thereafter. This elevation occurs in the context of immature prefrontal function, so motivational strivings may be difficult to regulate. Theoretical models explain this patterning through brain-based accounts of subcortical–cortical integration, puberty-based models of adolescent sensation seeking, and neurochemical dynamics. Empirically sound tests of these mechanisms, as well as investigations of biology–context interactions, represent the field’s most challenging future goals, so that applications to psychopathology can be refined and so that developmental cascades that incorporate neurobiological variables can be modeled. PMID:24342843

Adolescent brain development in normality and psychopathology.

PubMed

Luciana, Monica

2013-11-01

Since this journal's inception, the field of adolescent brain development has flourished, as researchers have investigated the underpinnings of adolescent risk-taking behaviors. Explanations based on translational models initially attributed such behaviors to executive control deficiencies and poor frontal lobe function. This conclusion was bolstered by evidence that the prefrontal cortex and its interconnections are among the last brain regions to structurally and functionally mature. As substantial heterogeneity of prefrontal function was revealed, applications of neuroeconomic theory to adolescent development led to dual systems models of behavior. Current epidemiological trends, behavioral observations, and functional magnetic resonance imaging based brain activity patterns suggest a quadratic increase in limbically mediated incentive motivation from childhood to adolescence and a decline thereafter. This elevation occurs in the context of immature prefrontal function, so motivational strivings may be difficult to regulate. Theoretical models explain this patterning through brain-based accounts of subcortical-cortical integration, puberty-based models of adolescent sensation seeking, and neurochemical dynamics. Empirically sound tests of these mechanisms, as well as investigations of biology-context interactions, represent the field's most challenging future goals, so that applications to psychopathology can be refined and so that developmental cascades that incorporate neurobiological variables can be modeled.

Involvement of specific macrophage-lineage cells surrounding arterioles in barrier and scavenger function in brain cortex.

PubMed Central

Mato, M; Ookawara, S; Sakamoto, A; Aikawa, E; Ogawa, T; Mitsuhashi, U; Masuzawa, T; Suzuki, H; Honda, M; Yazaki, Y; Watanabe, E; Luoma, J; Yla-Herttuala, S; Fraser, I; Gordon, S; Kodama, T

1996-01-01

The transport of solutes between blood and brain is regulated by a specific barrier. Capillary endothelial cells of brain are known to mediate barrier function and facilitate transport. Here we report that specific cells surrounding arterioles, known as Mato's fluorescent granular perithelial (FGP) cells or perivascular microglial cells, contribute to the barrier function. Immunohistochemical and in situ hybridization studies indicate that, in normal brain cortex, type I and type II macrophage scavenger receptors are expressed only in FGP/perivascular microglial cells, and surface markers of macrophage lineage are also detected on them. These cells mediate the uptake of macromolecules, including modified low density lipoprotein, horseradish peroxidase, and ferritin injected either into the blood or into the cerebral ventricles. Accumulation of scavenged materials with aging or after the administration of a high-fat diet results in the formation of honeycomb-like foam cells and the narrowing of the lumen of arterioles in the brain cortex. These results indicate involvement of FGP/perivascular microglial cells in the barrier and scavenger functions in the central nervous system. Images Fig. 1 Fig. 2 Fig. 4 Fig. 5 Fig. 6 PMID:8622926

Generating Text from Functional Brain Images

PubMed Central

Pereira, Francisco; Detre, Greg; Botvinick, Matthew

2011-01-01

Recent work has shown that it is possible to take brain images acquired during viewing of a scene and reconstruct an approximation of the scene from those images. Here we show that it is also possible to generate text about the mental content reflected in brain images. We began with images collected as participants read names of concrete items (e.g., “Apartment’’) while also seeing line drawings of the item named. We built a model of the mental semantic representation of concrete concepts from text data and learned to map aspects of such representation to patterns of activation in the corresponding brain image. In order to validate this mapping, without accessing information about the items viewed for left-out individual brain images, we were able to generate from each one a collection of semantically pertinent words (e.g., “door,” “window” for “Apartment’’). Furthermore, we show that the ability to generate such words allows us to perform a classification task and thus validate our method quantitatively. PMID:21927602

Mechanical stress regulates transport in a compliant 3D model of the blood-brain barrier.

PubMed

Partyka, Paul P; Godsey, George A; Galie, John R; Kosciuk, Mary C; Acharya, Nimish K; Nagele, Robert G; Galie, Peter A

2017-01-01

Transport of fluid and solutes is tightly controlled within the brain, where vasculature exhibits a blood-brain barrier and there is no organized lymphatic network facilitating waste transport from the interstitial space. Here, using a compliant, three-dimensional co-culture model of the blood-brain barrier, we show that mechanical stimuli exerted by blood flow mediate both the permeability of the endothelial barrier and waste transport along the basement membrane. Application of both shear stress and cyclic strain facilitates tight junction formation in the endothelial monolayer, with and without the presence of astrocyte endfeet in the surrounding matrix. We use both dextran perfusion and TEER measurements to assess the initiation and maintenance of the endothelial barrier, and microparticle image velocimetry to characterize the fluid dynamics within the in vitro vessels. Application of pulsatile flow to the in vitro vessels induces pulsatile strain to the vascular wall, providing an opportunity to investigate stretch-induced transport along the basement membrane. We find that a pulsatile wave speed of approximately 1 mm/s with Womersley number of 0.004 facilitates retrograde transport of high molecular weight dextran along the basement membrane between the basal endothelium and surrounding astrocytes. Together, these findings indicate that the mechanical stress exerted by blood flow is an important regulator of transport both across and along the walls of cerebral microvasculature. Copyright © 2016 Elsevier Ltd. All rights reserved.

Regional brain injury on conventional and diffusion weighted MRI is associated with outcome after pediatric cardiac arrest.

PubMed

Fink, Ericka L; Panigrahy, A; Clark, R S B; Fitz, C R; Landsittel, D; Kochanek, P M; Zuccoli, G

2013-08-01

To assess regional brain injury on magnetic resonance imaging (MRI) after pediatric cardiac arrest (CA) and to associate regional injury with patient outcome and effects of hypothermia therapy for neuroprotection. We performed a retrospective chart review with prospective imaging analysis. Children between 1 week and 17 years of age who had a brain MRI in the first 2 weeks after CA without other acute brain injury between 2002 and 2008 were included. Brain MRI (1.5 T General Electric, Milwaukee, WI, USA) images were analyzed by 2 blinded neuroradiologists with adjudication; images were visually graded. Brain lobes, basal ganglia, thalamus, brain stem, and cerebellum were analyzed using T1, T2, and diffusion-weighted images (DWI). We examined 28 subjects with median age 1.9 years (IQR 0.4-13.0) and 19 (68 %) males. Increased intensity on T2 in the basal ganglia and restricted diffusion in the brain lobes were associated with unfavorable outcome (all P < 0.05). Therapeutic hypothermia had no effect on regional brain injury. Repeat brain MRI was infrequently performed but demonstrated evolution of lesions. Children with lesions in the basal ganglia on conventional MRI and brain lobes on DWI within the first 2 weeks after CA represent a group with increased risk of poor outcome. These findings may be important for developing neuroprotective strategies based on regional brain injury and for evaluating response to therapy in interventional clinical trials.

Brain tumor segmentation using holistically nested neural networks in MRI images.

PubMed

Zhuge, Ying; Krauze, Andra V; Ning, Holly; Cheng, Jason Y; Arora, Barbara C; Camphausen, Kevin; Miller, Robert W

2017-10-01

Gliomas are rapidly progressive, neurologically devastating, largely fatal brain tumors. Magnetic resonance imaging (MRI) is a widely used technique employed in the diagnosis and management of gliomas in clinical practice. MRI is also the standard imaging modality used to delineate the brain tumor target as part of treatment planning for the administration of radiation therapy. Despite more than 20 yr of research and development, computational brain tumor segmentation in MRI images remains a challenging task. We are presenting a novel method of automatic image segmentation based on holistically nested neural networks that could be employed for brain tumor segmentation of MRI images. Two preprocessing techniques were applied to MRI images. The N4ITK method was employed for correction of bias field distortion. A novel landmark-based intensity normalization method was developed so that tissue types have a similar intensity scale in images of different subjects for the same MRI protocol. The holistically nested neural networks (HNN), which extend from the convolutional neural networks (CNN) with a deep supervision through an additional weighted-fusion output layer, was trained to learn the multiscale and multilevel hierarchical appearance representation of the brain tumor in MRI images and was subsequently applied to produce a prediction map of the brain tumor on test images. Finally, the brain tumor was obtained through an optimum thresholding on the prediction map. The proposed method was evaluated on both the Multimodal Brain Tumor Image Segmentation (BRATS) Benchmark 2013 training datasets, and clinical data from our institute. A dice similarity coefficient (DSC) and sensitivity of 0.78 and 0.81 were achieved on 20 BRATS 2013 training datasets with high-grade gliomas (HGG), based on a two-fold cross-validation. The HNN model built on the BRATS 2013 training data was applied to ten clinical datasets with HGG from a locally developed database. DSC and sensitivity of 0.83 and 0.85 were achieved. A quantitative comparison indicated that the proposed method outperforms the popular fully convolutional network (FCN) method. In terms of efficiency, the proposed method took around 10 h for training with 50,000 iterations, and approximately 30 s for testing of a typical MRI image in the BRATS 2013 dataset with a size of 160 × 216 × 176, using a DELL PRECISION workstation T7400, with an NVIDIA Tesla K20c GPU. An effective brain tumor segmentation method for MRI images based on a HNN has been developed. The high level of accuracy and efficiency make this method practical in brain tumor segmentation. It may play a crucial role in both brain tumor diagnostic analysis and in the treatment planning of radiation therapy. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

If the skull fits: magnetic resonance imaging and microcomputed tomography for combined analysis of brain and skull phenotypes in the mouse

PubMed Central

Blank, Marissa C.; Roman, Brian B.; Henkelman, R. Mark; Millen, Kathleen J.

2012-01-01

The mammalian brain and skull develop concurrently in a coordinated manner, consistently producing a brain and skull that fit tightly together. It is common that abnormalities in one are associated with related abnormalities in the other. However, this is not always the case. A complete characterization of the relationship between brain and skull phenotypes is necessary to understand the mechanisms that cause them to be coordinated or divergent and to provide perspective on the potential diagnostic or prognostic significance of brain and skull phenotypes. We demonstrate the combined use of magnetic resonance imaging and microcomputed tomography for analysis of brain and skull phenotypes in the mouse. Co-registration of brain and skull images allows comparison of the relationship between phenotypes in the brain and those in the skull. We observe a close fit between the brain and skull of two genetic mouse models that both show abnormal brain and skull phenotypes. Application of these three-dimensional image analyses in a broader range of mouse mutants will provide a map of the relationships between brain and skull phenotypes generally and allow characterization of patterns of similarities and differences. PMID:22947655

Scalable Joint Segmentation and Registration Framework for Infant Brain Images.

PubMed

Dong, Pei; Wang, Li; Lin, Weili; Shen, Dinggang; Wu, Guorong

2017-03-15

The first year of life is the most dynamic and perhaps the most critical phase of postnatal brain development. The ability to accurately measure structure changes is critical in early brain development study, which highly relies on the performances of image segmentation and registration techniques. However, either infant image segmentation or registration, if deployed independently, encounters much more challenges than segmentation/registration of adult brains due to dynamic appearance change with rapid brain development. In fact, image segmentation and registration of infant images can assists each other to overcome the above challenges by using the growth trajectories (i.e., temporal correspondences) learned from a large set of training subjects with complete longitudinal data. Specifically, a one-year-old image with ground-truth tissue segmentation can be first set as the reference domain. Then, to register the infant image of a new subject at earlier age, we can estimate its tissue probability maps, i.e., with sparse patch-based multi-atlas label fusion technique, where only the training images at the respective age are considered as atlases since they have similar image appearance. Next, these probability maps can be fused as a good initialization to guide the level set segmentation. Thus, image registration between the new infant image and the reference image is free of difficulty of appearance changes, by establishing correspondences upon the reasonably segmented images. Importantly, the segmentation of new infant image can be further enhanced by propagating the much more reliable label fusion heuristics at the reference domain to the corresponding location of the new infant image via the learned growth trajectories, which brings image segmentation and registration to assist each other. It is worth noting that our joint segmentation and registration framework is also flexible to handle the registration of any two infant images even with significant age gap in the first year of life, by linking their joint segmentation and registration through the reference domain. Thus, our proposed joint segmentation and registration method is scalable to various registration tasks in early brain development studies. Promising segmentation and registration results have been achieved for infant brain MR images aged from 2-week-old to 1-year-old, indicating the applicability of our method in early brain development study.

Correspondence of the brain's functional architecture during activation and rest

PubMed Central

Smith, Stephen M.; Fox, Peter T.; Miller, Karla L.; Glahn, David C.; Fox, P. Mickle; Mackay, Clare E.; Filippini, Nicola; Watkins, Kate E.; Toro, Roberto; Laird, Angela R.; Beckmann, Christian F.

2009-01-01

Neural connections, providing the substrate for functional networks, exist whether or not they are functionally active at any given moment. However, it is not known to what extent brain regions are continuously interacting when the brain is “at rest.” In this work, we identify the major explicit activation networks by carrying out an image-based activation network analysis of thousands of separate activation maps derived from the BrainMap database of functional imaging studies, involving nearly 30,000 human subjects. Independently, we extract the major covarying networks in the resting brain, as imaged with functional magnetic resonance imaging in 36 subjects at rest. The sets of major brain networks, and their decompositions into subnetworks, show close correspondence between the independent analyses of resting and activation brain dynamics. We conclude that the full repertoire of functional networks utilized by the brain in action is continuously and dynamically “active” even when at “rest.” PMID:19620724

Magnetic resonance imaging of the pediatric brain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Salamon, G.; Raynaud, C.; Regis, J.

1990-01-01

The atlas presents sequences of MRI sections parallel to the orbito-meatal plane in children from birth through the age of sixteen years. Each child was studied horizontally and sagitally and three-dimensional brain images were reconstructed to facilitate accurate identification of sulci and gyri. The images show crucial aspects of brain development such as the constancy of the brain stem and primitive brain from birth onward; the development of the telencephalon, characterized by deepening of sulci and growth of the cerebral cortex surface; and the different stages of white matter myelinization.

Estrogen: A master regulator of bioenergetic systems in the brain and body

PubMed Central

Rettberg, Jamaica R; Yao, Jia; Brinton, Roberta Diaz

2014-01-01

Estrogen is a fundamental regulator of the metabolic system of the female brain and body. Within the brain, estrogen regulates glucose transport, aerobic glycolysis, and mitochondrial function to generate ATP. In the body, estrogen protects against adiposity, insulin resistance, and type II diabetes, and regulates energy intake and expenditure. During menopause, decline in circulating estrogen is coincident with decline in brain bioenergetics and shift towards a metabolically compromised phenotype. Compensatory bioenergetic adaptations, or lack thereof, to estrogen loss could determine risk of late-onset Alzheimer’s disease. Estrogen coordinates brain and body metabolism, such that peripheral metabolic state can indicate bioenergetic status of the brain. By generating biomarker profiles that encompass peripheral metabolic changes occurring with menopause, individual risk profiles for decreased brain bioenergetics and cognitive decline can be created. Biomarker profiles could identify women at risk while also serving as indicators of efficacy of hormone therapy or other preventative interventions. PMID:23994581

Structural and synaptic plasticity in stress-related disorders

PubMed Central

Christoffel, Daniel J.; Golden, Sam A.; Russo, Scott J.

2011-01-01

Stress can have a lasting impact on the structure and function of brain circuitry that results in long-lasting changes in the behavior of an organism. Synaptic plasticity is the mechanism by which information is stored and maintained within individual synapses, neurons, and neuronal circuits to guide the behavior of an organism. Although these mechanisms allow the organism to adapt to its constantly evolving environment, not all of these adaptations are beneficial. Under prolonged bouts of physical or psychological stress, these mechanisms become dysregulated, and the connectivity between brain regions becomes unbalanced, resulting in pathological behaviors. In this review, we highlight the effects of stress on the structure and function of neurons within the mesocorticolimbic brain systems known to regulate mood and motivation. We then discuss the implications of these spine adaptations on neuronal activity and pathological behaviors implicated in mood disorders. Finally, we end by discussing recent brain imaging studies in human depression within the context of these basic findings to provide insight into the underlying mechanisms leading to neural dysfunction in depression. PMID:21967517

Intranasal insulin enhances brain functional connectivity mediating the relationship between adiposity and subjective feeling of hunger.

PubMed

Kullmann, Stephanie; Heni, Martin; Veit, Ralf; Scheffler, Klaus; Machann, Jürgen; Häring, Hans-Ulrich; Fritsche, Andreas; Preissl, Hubert

2017-05-09

Brain insulin sensitivity is an important link between metabolism and cognitive dysfunction. Intranasal insulin is a promising tool to investigate central insulin action in humans. We evaluated the acute effects of 160 U intranasal insulin on resting-state brain functional connectivity in healthy young adults. Twenty-five lean and twenty-two overweight and obese participants underwent functional magnetic resonance imaging, on two separate days, before and after intranasal insulin or placebo application. Insulin compared to placebo administration resulted in increased functional connectivity between the prefrontal regions of the default-mode network and the hippocampus as well as the hypothalamus. The change in hippocampal functional connectivity significantly correlated with visceral adipose tissue and the change in subjective feeling of hunger after intranasal insulin. Mediation analysis revealed that the intranasal insulin induced hippocampal functional connectivity increase served as a mediator, suppressing the relationship between visceral adipose tissue and hunger. The insulin-induced hypothalamic functional connectivity change showed a significant interaction with peripheral insulin sensitivity. Only participants with high peripheral insulin sensitivity showed a boost in hypothalamic functional connectivity. Hence, brain insulin action may regulate eating behavior and facilitate weight loss by modifying brain functional connectivity within and between cognitive and homeostatic brain regions.

Trojan Horse Transit Contributes to Blood-Brain Barrier Crossing of a Eukaryotic Pathogen

PubMed Central

Santiago-Tirado, Felipe H.; Onken, Michael D.; Cooper, John A.; Klein, Robyn S.

2017-01-01

ABSTRACT The blood-brain barrier (BBB) protects the central nervous system (CNS) by restricting the passage of molecules and microorganisms. Despite this barrier, however, the fungal pathogen Cryptococcus neoformans invades the brain, causing a meningoencephalitis that is estimated to kill over 600,000 people annually. Cryptococcal infection begins in the lung, and experimental evidence suggests that host phagocytes play a role in subsequent dissemination, although this role remains ill defined. Additionally, the disparate experimental approaches that have been used to probe various potential routes of BBB transit make it impossible to assess their relative contributions, confounding any integrated understanding of cryptococcal brain entry. Here we used an in vitro model BBB to show that a “Trojan horse” mechanism contributes significantly to fungal barrier crossing and that host factors regulate this process independently of free fungal transit. We also, for the first time, directly imaged C. neoformans-containing phagocytes crossing the BBB, showing that they do so via transendothelial pores. Finally, we found that Trojan horse crossing enables CNS entry of fungal mutants that cannot otherwise traverse the BBB, and we demonstrate additional intercellular interactions that may contribute to brain entry. Our work elucidates the mechanism of cryptococcal brain invasion and offers approaches to study other neuropathogens. PMID:28143979

Impact of Cognitive-Behavioral Therapy for Social Anxiety Disorder on the Neural Bases of Emotional Reactivity to and Regulation of Social Evaluation

PubMed Central

Goldin, Philippe R.; Ziv, Michal; Jazaieri, Hooria; Weeks, Justin; Heimberg, Richard G.; Gross, James J.

2014-01-01

We examined whether Cognitive-Behavioral Therapy (CBT) for social anxiety disorder (SAD) would modify self-reported negative emotion and functional magnetic resonance imaging brain responses when reacting to and reappraising social evaluation, and tested whether changes would predict treatment outcome in 59 patients with SAD who completed CBT or waitlist groups. For reactivity, compared to waitlist, CBT resulted in (a) increased brain responses in right superior frontal gyrus (SFG), inferior parietal lobule (IPL), and middle occipital gyrus (MOG) when reacting to social praise, and (b) increases in right SFG and IPL and decreases in left posterior superior temporal gyrus (pSTG) when reacting to social criticism. For reappraisal, compared to waitlist, CBT resulted in greater (c) reductions in self-reported negative emotion, and (d) increases in brain responses in right SFG and MOG, and decreases in left pSTG. A linear regression found that after controlling for CBT-induced changes in reactivity and reappraisal negative emotion ratings and brain changes in reactivity to praise and criticism, reappraisal of criticism brain response changes predicted 24% of the unique variance in CBT-related reductions in social anxiety. Thus, one mechanism underlying CBT for SAD may be changes in reappraisal-related brain responses to social criticism. PMID:25193002

Imaging of Traumatic Brain Injury.

PubMed

Bodanapally, Uttam K; Sours, Chandler; Zhuo, Jiachen; Shanmuganathan, Kathirkamanathan

2015-07-01

Imaging plays an important role in the management of patients with traumatic brain injury (TBI). Computed tomography (CT) is the first-line imaging technique allowing rapid detection of primary structural brain lesions that require surgical intervention. CT also detects various deleterious secondary insults allowing early medical and surgical management. Serial imaging is critical to identifying secondary injuries. MR imaging is indicated in patients with acute TBI when CT fails to explain neurologic findings. However, MR imaging is superior in patients with subacute and chronic TBI and also predicts neurocognitive outcome. Copyright © 2015 Elsevier Inc. All rights reserved.

Delivery of Nano-Tethered Therapies to Brain Metastases of Primary Breast Cancer Using a Cellular Trojan Horse

DTIC Science & Technology

2015-10-01

tomography images. The CT image densities in Hounsfield units (HU) of the brain were translated into corresponding optical properties (absorption...derived the Hounsfield units and optical properties of brain tissues such as white/gray matter. 13-15 The segmentation software generated an optical map...treatment protocol. Head CT image densities (in Hounsfield Units /HU) are segmented and translated into optical properties of the brain tissue

Stress and visceral pain: focusing on irritable bowel syndrome.

PubMed

Fukudo, Shin

2013-12-01

Recent advances in brain science have shown that the brain function encoding emotion depends on interoceptive signals such as visceral pain. Visceral pain arose early in our evolutionary history. Bottom-up processing from gut-to-brain and top-down autonomic/neuroendocrine mechanisms in brain-to-gut signaling constitute a circuit. Brain imaging techniques have enabled us to depict the visceral pain pathway as well as the related emotional circuit. Irritable bowel syndrome (IBS) is characterized by chronic recurrent abdominal pain or abdominal discomfort associated with bowel dysfunction. It is also thought to be a disorder of the brain-gut link associated with an exaggerated response to stress. Corticotropin-releasing hormone (CRH), a major mediator of the stress response in the brain-gut axis, is an obvious candidate in the pathophysiology of IBS. Indeed, administration of CRH has been shown to aggravate the visceral sensorimotor response in IBS patients, and the administration of peptidergic CRH antagonists seems to alleviate IBS pathophysiology. Serotonin (5-HT) is another likely candidate associated with brain-gut function in IBS, as 5-HT3 antagonists, 5-HT4 agonists, and antidepressants were demonstrated to regulate 5-HT neurotransmission in IBS patients. Autonomic nervous system function, the neuroimmune axis, and the brain-gut-microbiota axis show specific profiles in IBS patients. Further studies on stress and visceral pain neuropathways in IBS patients are warranted. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

A Pathological Brain Detection System based on Extreme Learning Machine Optimized by Bat Algorithm.

PubMed

Lu, Siyuan; Qiu, Xin; Shi, Jianping; Li, Na; Lu, Zhi-Hai; Chen, Peng; Yang, Meng-Meng; Liu, Fang-Yuan; Jia, Wen-Juan; Zhang, Yudong

2017-01-01

It is beneficial to classify brain images as healthy or pathological automatically, because 3D brain images can generate so much information which is time consuming and tedious for manual analysis. Among various 3D brain imaging techniques, magnetic resonance (MR) imaging is the most suitable for brain, and it is now widely applied in hospitals, because it is helpful in the four ways of diagnosis, prognosis, pre-surgical, and postsurgical procedures. There are automatic detection methods; however they suffer from low accuracy. Therefore, we proposed a novel approach which employed 2D discrete wavelet transform (DWT), and calculated the entropies of the subbands as features. Then, a bat algorithm optimized extreme learning machine (BA-ELM) was trained to identify pathological brains from healthy controls. A 10x10-fold cross validation was performed to evaluate the out-of-sample performance. The method achieved a sensitivity of 99.04%, a specificity of 93.89%, and an overall accuracy of 98.33% over 132 MR brain images. The experimental results suggest that the proposed approach is accurate and robust in pathological brain detection. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Mapping fetal brain development in utero using magnetic resonance imaging: the Big Bang of brain mapping.

PubMed

Studholme, Colin

2011-08-15

The development of tools to construct and investigate probabilistic maps of the adult human brain from magnetic resonance imaging (MRI) has led to advances in both basic neuroscience and clinical diagnosis. These tools are increasingly being applied to brain development in adolescence and childhood, and even to neonatal and premature neonatal imaging. Even earlier in development, parallel advances in clinical fetal MRI have led to its growing use as a tool in challenging medical conditions. This has motivated new engineering developments encompassing optimal fast MRI scans and techniques derived from computer vision, the combination of which allows full 3D imaging of the moving fetal brain in utero without sedation. These promise to provide a new and unprecedented window into early human brain growth. This article reviews the developments that have led us to this point, examines the current state of the art in the fields of fast fetal imaging and motion correction, and describes the tools to analyze dynamically changing fetal brain structure. New methods to deal with developmental tissue segmentation and the construction of spatiotemporal atlases are examined, together with techniques to map fetal brain growth patterns.

Advances in neuroimaging of traumatic brain injury and posttraumatic stress disorder

PubMed Central

Van Boven, Robert W.; Harrington, Greg S.; Hackney, David B.; Ebel, Andreas; Gauger, Grant; Bremner, J. Douglas; D’Esposito, Mark; Detre, John A.; Haacke, E. Mark; Jack, Clifford R.; Jagust, William J.; Le Bihan, Denis; Mathis, Chester A.; Mueller, Susanne; Mukherjee, Pratik; Schuff, Norbert; Chen, Anthony; Weiner, Michael W.

2011-01-01

Improved diagnosis and treatment of traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) are needed for our military and veterans, their families, and society at large. Advances in brain imaging offer important biomarkers of structural, functional, and metabolic information concerning the brain. This article reviews the application of various imaging techniques to the clinical problems of TBI and PTSD. For TBI, we focus on findings and advances in neuroimaging that hold promise for better detection, characterization, and monitoring of objective brain changes in symptomatic patients with combat-related, closed-head brain injuries not readily apparent by standard computed tomography or conventional magnetic resonance imaging techniques. PMID:20104401

Seeing Is Believing: The Effect of Brain Images on Judgments of Scientific Reasoning

ERIC Educational Resources Information Center

McCabe, David P.; Castel, Alan D.

2008-01-01

Brain images are believed to have a particularly persuasive influence on the public perception of research on cognition. Three experiments are reported showing that presenting brain images with articles summarizing cognitive neuroscience research resulted in higher ratings of scientific reasoning for arguments made in those articles, as compared…

TransOmic analysis of forebrain sections in Sp2 conditional knockout embryonic mice using IR-MALDESI imaging of lipids and LC-MS/MS label-free proteomics

PubMed Central

Loziuk, Philip; Meier, Florian; Johnson, Caroline

2016-01-01

Quantitative methods for detection of biological molecules are needed more than ever before in the emerging age of “omics” and “big data.” Here, we provide an integrated approach for systematic analysis of the “lipidome” in tissue. To test our approach in a biological context, we utilized brain tissue selectively deficient for the transcription factor Specificity Protein 2 (Sp2). Conditional deletion of Sp2 in the mouse cerebral cortex results in developmental deficiencies including disruption of lipid metabolism. Silver (Ag) cationization was implemented for infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) to enhance the ion abundances for olefinic lipids, as these have been linked to regulation by Sp2. Combining Ag-doped and conventional IR-MALDESI imaging, this approach was extended to IR-MALDESI imaging of embryonic mouse brains. Further, our imaging technique was combined with bottom-up shotgun proteomic LC-MS/MS analysis and western blot for comparing Sp2 conditional knockout (Sp2-cKO) and wild-type (WT) cortices of tissue sections. This provided an integrated omics dataset which revealed many specific changes to fundamental cellular processes and biosynthetic pathways. In particular, step-specific altered abundances of nucleotides, lipids, and associated proteins were observed in the cerebral cortices of Sp2-cKO embryos. PMID:26942738

Ex vivo micro-CT imaging of murine brain models using non-ionic iodinated contrast

NASA Astrophysics Data System (ADS)

Salas Bautista, N.; Martínez-Dávalos, A.; Rodríguez-Villafuerte, M.; Murrieta-Rodríguez, T.; Manjarrez-Marmolejo, J.; Franco-Pérez, J.; Calvillo-Velasco, M. E.

2014-11-01

Preclinical investigation of brain tumors is frequently carried out by means of intracranial implantation of brain tumor xenografts or allografts, with subsequent analysis of tumor growth using conventional histopathology. However, very little has been reported on the use contrast-enhanced techniques in micro-CT imaging for the study of malignant brain tumors in small animal models. The aim of this study has been to test a protocol for ex vivo imaging of murine brain models of glioblastoma multiforme (GBM) after treatment with non-ionic iodinated solution, using an in-house developed laboratory micro-CT. We have found that the best compromise between acquisition time and image quality is obtained using a 50 kVp, 0.5 mAs, 1° angular step on a 360 degree orbit acquisition protocol, with 70 μm reconstructed voxel size using the Feldkamp algorithm. With this parameters up to 4 murine brains can be scanned in tandem in less than 15 minutes. Image segmentation and analysis of three sample brains allowed identifying tumor volumes as small as 0.4 mm3.

Precursors to radiopharmaceutical agents for tissue imaging

DOEpatents

Srivastava, Prem C.; Knapp, Jr., Furn F.

1988-01-01

A class of radiolabeled compounds to be used in tissue imaging that exhibits rapid brain uptake, good brain:blood radioactivity ratios, and long retention times. The imaging agents are more specifically radioiodinated aromatic amines attached to dihydropyridine carriers, that exhibit heart as well as brain specificity. In addition to the radiolabeled compounds, classes of compounds are also described that are used as precursors and intermediates in the preparation of the imaging agents.

Patient-specific semi-supervised learning for postoperative brain tumor segmentation.

PubMed

Meier, Raphael; Bauer, Stefan; Slotboom, Johannes; Wiest, Roland; Reyes, Mauricio

2014-01-01

In contrast to preoperative brain tumor segmentation, the problem of postoperative brain tumor segmentation has been rarely approached so far. We present a fully-automatic segmentation method using multimodal magnetic resonance image data and patient-specific semi-supervised learning. The idea behind our semi-supervised approach is to effectively fuse information from both pre- and postoperative image data of the same patient to improve segmentation of the postoperative image. We pose image segmentation as a classification problem and solve it by adopting a semi-supervised decision forest. The method is evaluated on a cohort of 10 high-grade glioma patients, with segmentation performance and computation time comparable or superior to a state-of-the-art brain tumor segmentation method. Moreover, our results confirm that the inclusion of preoperative MR images lead to a better performance regarding postoperative brain tumor segmentation.

Hybrid Clustering And Boundary Value Refinement for Tumor Segmentation using Brain MRI

NASA Astrophysics Data System (ADS)

Gupta, Anjali; Pahuja, Gunjan

2017-08-01

The method of brain tumor segmentation is the separation of tumor area from Brain Magnetic Resonance (MR) images. There are number of methods already exist for segmentation of brain tumor efficiently. However it’s tedious task to identify the brain tumor from MR images. The segmentation process is extraction of different tumor tissues such as active, tumor, necrosis, and edema from the normal brain tissues such as gray matter (GM), white matter (WM), as well as cerebrospinal fluid (CSF). As per the survey study, most of time the brain tumors are detected easily from brain MR image using region based approach but required level of accuracy, abnormalities classification is not predictable. The segmentation of brain tumor consists of many stages. Manually segmenting the tumor from brain MR images is very time consuming hence there exist many challenges in manual segmentation. In this research paper, our main goal is to present the hybrid clustering which consists of Fuzzy C-Means Clustering (for accurate tumor detection) and level set method(for handling complex shapes) for the detection of exact shape of tumor in minimal computational time. using this approach we observe that for a certain set of images 0.9412 sec of time is taken to detect tumor which is very less in comparison to recent existing algorithm i.e. Hybrid clustering (Fuzzy C-Means and K Means clustering).

Imaging fast electrical activity in the brain with electrical impedance tomography

PubMed Central

Aristovich, Kirill Y.; Packham, Brett C.; Koo, Hwan; Santos, Gustavo Sato dos; McEvoy, Andy; Holder, David S.

2016-01-01

Imaging of neuronal depolarization in the brain is a major goal in neuroscience, but no technique currently exists that could image neural activity over milliseconds throughout the whole brain. Electrical impedance tomography (EIT) is an emerging medical imaging technique which can produce tomographic images of impedance changes with non-invasive surface electrodes. We report EIT imaging of impedance changes in rat somatosensory cerebral cortex with a resolution of 2 ms and < 200 μm during evoked potentials using epicortical arrays with 30 electrodes. Images were validated with local field potential recordings and current source-sink density analysis. Our results demonstrate that EIT can image neural activity in a volume 7 × 5 × 2 mm in somatosensory cerebral cortex with reduced invasiveness, greater resolution and imaging volume than other methods. Modeling indicates similar resolutions are feasible throughout the entire brain so this technique, uniquely, has the potential to image functional connectivity of cortical and subcortical structures. PMID:26348559

Brain's tumor image processing using shearlet transform

NASA Astrophysics Data System (ADS)

Cadena, Luis; Espinosa, Nikolai; Cadena, Franklin; Korneeva, Anna; Kruglyakov, Alexey; Legalov, Alexander; Romanenko, Alexey; Zotin, Alexander

2017-09-01

Brain tumor detection is well known research area for medical and computer scientists. In last decades there has been much research done on tumor detection, segmentation, and classification. Medical imaging plays a central role in the diagnosis of brain tumors and nowadays uses methods non-invasive, high-resolution techniques, especially magnetic resonance imaging and computed tomography scans. Edge detection is a fundamental tool in image processing, particularly in the areas of feature detection and feature extraction, which aim at identifying points in a digital image at which the image has discontinuities. Shearlets is the most successful frameworks for the efficient representation of multidimensional data, capturing edges and other anisotropic features which frequently dominate multidimensional phenomena. The paper proposes an improved brain tumor detection method by automatically detecting tumor location in MR images, its features are extracted by new shearlet transform.

INVITED REVIEW – NEUROIMAGING RESPONSE ASSESSMENT CRITERIA FOR BRAIN TUMORS IN VETERINARY PATIENTS

PubMed Central

Rossmeisl, John H.; Garcia, Paulo A.; Daniel, Gregory B.; Bourland, John Daniel; Debinski, Waldemar; Dervisis, Nikolaos; Klahn, Shawna

2013-01-01

The evaluation of therapeutic response using cross-sectional imaging techniques, particularly gadolinium-enhanced MRI, is an integral part of the clinical management of brain tumors in veterinary patients. Spontaneous canine brain tumors are increasingly recognized and utilized as a translational model for the study of human brain tumors. However, no standardized neuroimaging response assessment criteria have been formulated for use in veterinary clinical trials. Previous studies have found that the pathophysiologic features inherent to brain tumors and the surrounding brain complicate the use of the Response Evaluation Criteria in Solid Tumors (RECIST) assessment system. Objectives of this review are to describe strengths and limitations of published imaging-based brain tumor response criteria and propose a system for use in veterinary patients. The widely used human Macdonald and Response Assessment in Neuro-oncology (RANO) criteria are reviewed and described as to how they can be applied to veterinary brain tumors. Discussion points will include current challenges associated with the interpretation of brain tumor therapeutic responses such as imaging pseudophenomena and treatment-induced necrosis, and how advancements in perfusion imaging, positron emission tomography, and magnetic resonance spectroscopy have shown promise in differentiating tumor progression from therapy-induced changes. Finally, although objective endpoints such as MR-imaging and survival estimates will likely continue to comprise the foundations for outcome measures in veterinary brain tumor clinical trials, we propose that in order to provide a more relevant therapeutic response metric for veterinary patients, composite response systems should be formulated and validated that combine imaging and clinical assessment criteria. PMID:24219161

Chapter 18: the origins of functional brain imaging in humans.

PubMed

Raichle, Marcus E

2010-01-01

Functional brain imaging in humans as we presently know it began when the experimental strategies of cognitive psychology were combined with modern brain imaging techniques, first positron emission tomography (PET) and then functional magnetic resonance imaging (fMRI), to examine how brain function supports mental activities. This marriage of disciplines and techniques galvanized the field of cognitive neuroscience, which has rapidly expanded to include a broad range of the social sciences as well as basic scientists interested in the neurophysiology, cell biology and genetics of the imaging signals. While much of this work has transpired over the past couple of decades, its roots can be traced back more than a century.

Application of an enhanced fuzzy algorithm for MR brain tumor image segmentation

NASA Astrophysics Data System (ADS)

Hemanth, D. Jude; Vijila, C. Kezi Selva; Anitha, J.

2010-02-01

Image segmentation is one of the significant digital image processing techniques commonly used in the medical field. One of the specific applications is tumor detection in abnormal Magnetic Resonance (MR) brain images. Fuzzy approaches are widely preferred for tumor segmentation which generally yields superior results in terms of accuracy. But most of the fuzzy algorithms suffer from the drawback of slow convergence rate which makes the system practically non-feasible. In this work, the application of modified Fuzzy C-means (FCM) algorithm to tackle the convergence problem is explored in the context of brain image segmentation. This modified FCM algorithm employs the concept of quantization to improve the convergence rate besides yielding excellent segmentation efficiency. This algorithm is experimented on real time abnormal MR brain images collected from the radiologists. A comprehensive feature vector is extracted from these images and used for the segmentation technique. An extensive feature selection process is performed which reduces the convergence time period and improve the segmentation efficiency. After segmentation, the tumor portion is extracted from the segmented image. Comparative analysis in terms of segmentation efficiency and convergence rate is performed between the conventional FCM and the modified FCM. Experimental results show superior results for the modified FCM algorithm in terms of the performance measures. Thus, this work highlights the application of the modified algorithm for brain tumor detection in abnormal MR brain images.

Tissue Probability Map Constrained 4-D Clustering Algorithm for Increased Accuracy and Robustness in Serial MR Brain Image Segmentation

PubMed Central

Xue, Zhong; Shen, Dinggang; Li, Hai; Wong, Stephen

2010-01-01

The traditional fuzzy clustering algorithm and its extensions have been successfully applied in medical image segmentation. However, because of the variability of tissues and anatomical structures, the clustering results might be biased by the tissue population and intensity differences. For example, clustering-based algorithms tend to over-segment white matter tissues of MR brain images. To solve this problem, we introduce a tissue probability map constrained clustering algorithm and apply it to serial MR brain image segmentation, i.e., a series of 3-D MR brain images of the same subject at different time points. Using the new serial image segmentation algorithm in the framework of the CLASSIC framework, which iteratively segments the images and estimates the longitudinal deformations, we improved both accuracy and robustness for serial image computing, and at the mean time produced longitudinally consistent segmentation and stable measures. In the algorithm, the tissue probability maps consist of both the population-based and subject-specific segmentation priors. Experimental study using both simulated longitudinal MR brain data and the Alzheimer’s Disease Neuroimaging Initiative (ADNI) data confirmed that using both priors more accurate and robust segmentation results can be obtained. The proposed algorithm can be applied in longitudinal follow up studies of MR brain imaging with subtle morphological changes for neurological disorders. PMID:26566399

Noninvasive photoacoustic computed tomography of mouse brain metabolism in vivo

NASA Astrophysics Data System (ADS)

Yao, Junjie; Xia, Jun; Maslov, Konstantin; Avanaki, Mohammadreza R. N.; Tsytsarev, Vassiliy; Demchenko, Alexei V.; Wang, Lihong V.

2013-03-01

To control the overall action of the body, brain consumes a large amount of energy in proportion to its volume. In humans and many other species, the brain gets most of its energy from oxygen-dependent metabolism of glucose. An abnormal metabolic rate of glucose and/or oxygen usually reflects a diseased status of brain, such as cancer or Alzheimer's disease. We have demonstrated the feasibility of imaging mouse brain metabolism using photoacoustic computed tomography (PACT), a fast, noninvasive and functional imaging modality with optical contrast and acoustic resolution. Brain responses to forepaw stimulations were imaged transdermally and transcranially. 2-NBDG, which diffuses well across the blood-brain-barrier, provided exogenous contrast for photoacoustic imaging of glucose response. Concurrently, hemoglobin provided endogenous contrast for photoacoustic imaging of hemodynamic response. Glucose and hemodynamic responses were quantitatively unmixed by using two-wavelength measurements. We found that glucose uptake and blood perfusion around the somatosensory region of the contralateral hemisphere were both increased by stimulations, indicating elevated neuron activity. The glucose response amplitude was about half that of the hemodynamic response. While the glucose response area was more homogenous and confined within the somatosensory region, the hemodynamic response area showed a clear vascular pattern and spread about twice as wide as that of the glucose response. The PACT of mouse brain metabolism was validated by high-resolution open-scalp OR-PAM and fluorescence imaging. Our results demonstrate that 2-NBDG-enhanced PACT is a promising tool for noninvasive studies of brain metabolism.

A fast atlas-guided high density diffuse optical tomography system for brain imaging

NASA Astrophysics Data System (ADS)

Dai, Xianjin; Zhang, Tao; Yang, Hao; Jiang, Huabei

2017-02-01

Near infrared spectroscopy (NIRS) is an emerging functional brain imaging tool capable of assessing cerebral concentrations of oxygenated hemoglobin (HbO) and deoxygenated hemoglobin (HbR) during brain activation noninvasively. As an extension of NIRS, diffuse optical tomography (DOT) not only shares the merits of providing continuous readings of cerebral oxygenation, but also has the ability to provide spatial resolution in the millimeter scale. Based on the scattering and absorption properties of nonionizing near-infrared light in biological tissue, DOT has been successfully applied in the imaging of breast tumors, osteoarthritis and cortex activations. Here, we present a state-of-art fast high density DOT system suitable for brain imaging. It can achieve up to a 21 Hz sampling rate for a full set of two-wavelength data for 3-D DOT brain image reconstruction. The system was validated using tissue-mimicking brain-model phantom. Then, experiments on healthy subjects were conducted to demonstrate the capability of the system.

A system architecture for sharing de-identified, research-ready brain scans and health information across clinical imaging centers.

PubMed

Chervenak, Ann L; van Erp, Theo G M; Kesselman, Carl; D'Arcy, Mike; Sobell, Janet; Keator, David; Dahm, Lisa; Murry, Jim; Law, Meng; Hasso, Anton; Ames, Joseph; Macciardi, Fabio; Potkin, Steven G

2012-01-01

Progress in our understanding of brain disorders increasingly relies on the costly collection of large standardized brain magnetic resonance imaging (MRI) data sets. Moreover, the clinical interpretation of brain scans benefits from compare and contrast analyses of scans from patients with similar, and sometimes rare, demographic, diagnostic, and treatment status. A solution to both needs is to acquire standardized, research-ready clinical brain scans and to build the information technology infrastructure to share such scans, along with other pertinent information, across hospitals. This paper describes the design, deployment, and operation of a federated imaging system that captures and shares standardized, de-identified clinical brain images in a federation across multiple institutions. In addition to describing innovative aspects of the system architecture and our initial testing of the deployed infrastructure, we also describe the Standardized Imaging Protocol (SIP) developed for the project and our interactions with the Institutional Review Board (IRB) regarding handling patient data in the federated environment.

A System Architecture for Sharing De-Identified, Research-Ready Brain Scans and Health Information Across Clinical Imaging Centers

PubMed Central

Chervenak, Ann L.; van Erp, Theo G.M.; Kesselman, Carl; D’Arcy, Mike; Sobell, Janet; Keator, David; Dahm, Lisa; Murry, Jim; Law, Meng; Hasso, Anton; Ames, Joseph; Macciardi, Fabio; Potkin, Steven G.

2015-01-01

Progress in our understanding of brain disorders increasingly relies on the costly collection of large standardized brain magnetic resonance imaging (MRI) data sets. Moreover, the clinical interpretation of brain scans benefits from compare and contrast analyses of scans from patients with similar, and sometimes rare, demographic, diagnostic, and treatment status. A solution to both needs is to acquire standardized, research-ready clinical brain scans and to build the information technology infrastructure to share such scans, along with other pertinent information, across hospitals. This paper describes the design, deployment, and operation of a federated imaging system that captures and shares standardized, de-identified clinical brain images in a federation across multiple institutions. In addition to describing innovative aspects of the system architecture and our initial testing of the deployed infrastructure, we also describe the Standardized Imaging Protocol (SIP) developed for the project and our interactions with the Institutional Review Board (IRB) regarding handling patient data in the federated environment. PMID:22941984

A radiologic correlation with the basic functional neuroanatomy of the brain.

PubMed

Bilicka, Z; Liska, M; Bluska, P; Bilicky, J

2014-01-01

Primary cortical areas for motor, sensory and sensitive functions are localized in certain areas of the brain cortex. In clinical practice, cross sectional imaging (computer tomography and magnetic resonance) is wildy used for diagnostics purpose, treatment planning and follow up of the patients. Accurate orientation in brain structures is necessary for the evaluation of radiological images. There are numerable landmark signs, which can be used for precise identification of important brain structures. In this review article, the mostly used anatomical landmarks are described and shown on the cross sectional images (magnetic resonance imaging) (Fig. 14, Ref. 25).

STroke imAging pRevention and treatment (START): A longitudinal stroke cohort study: Clinical trials protocol.

PubMed

Carey, Leeanne M; Crewther, Sheila; Salvado, Olivier; Lindén, Thomas; Connelly, Alan; Wilson, William; Howells, David W; Churilov, Leonid; Ma, Henry; Tse, Tamara; Rose, Stephen; Palmer, Susan; Bougeat, Pierrick; Campbell, Bruce C V; Christensen, Soren; Macaulay, S Lance; Favaloro, Jenny; O' Collins, Victoria; McBride, Simon; Bates, Susan; Cowley, Elise; Dewey, Helen; Wijeratne, Tissa; Gerraty, Richard; Phan, Thanh G; Yan, Bernard; Parsons, Mark W; Bladin, Chris; Barber, P Alan; Read, Stephen; Wong, Andrew; Lee, Andrew; Kleinig, Tim; Hankey, Graeme J; Blacker, David; Markus, Romesh; Leyden, James; Krause, Martin; Grimley, Rohan; Mahant, Neil; Jannes, Jim; Sturm, Jonathan; Davis, Stephen M; Donnan, Geoffrey A

2015-06-01

Stroke and poststroke depression are common and have a profound and ongoing impact on an individual's quality of life. However, reliable biological correlates of poststroke depression and functional outcome have not been well established in humans. Our aim is to identify biological factors, molecular and imaging, associated with poststroke depression and recovery that may be used to guide more targeted interventions. In a longitudinal cohort study of 200 stroke survivors, the START-STroke imAging pRevention and Treatment cohort, we will examine the relationship between gene expression, regulator proteins, depression, and functional outcome. Stroke survivors will be investigated at baseline, 24 h, three-days, three-months, and 12 months poststroke for blood-based biological associates and at days 3-7, three-months, and 12 months for depression and functional outcomes. A sub-group (n = 100), the PrePARE: Prediction and Prevention to Achieve optimal Recovery Endpoints after stroke cohort, will also be investigated for functional and structural changes in putative depression-related brain networks and for additional cognition and activity participation outcomes. Stroke severity, diet, and lifestyle factors that may influence depression will be monitored. The impact of depression on stroke outcomes and participation in previous life activities will be quantified. Clinical significance lies in the identification of biological factors associated with functional outcome to guide prevention and inform personalized and targeted treatments. Evidence of associations between depression, gene expression and regulator proteins, functional and structural brain changes, lifestyle and functional outcome will provide new insights for mechanism-based models of poststroke depression. © 2013 The Authors. International Journal of Stroke © 2013 World Stroke Organization.

Linking brain, mind and behavior.

PubMed

Makeig, Scott; Gramann, Klaus; Jung, Tzyy-Ping; Sejnowski, Terrence J; Poizner, Howard

2009-08-01

Cortical brain areas and dynamics evolved to organize motor behavior in our three-dimensional environment also support more general human cognitive processes. Yet traditional brain imaging paradigms typically allow and record only minimal participant behavior, then reduce the recorded data to single map features of averaged responses. To more fully investigate the complex links between distributed brain dynamics and motivated natural behavior, we propose the development of wearable mobile brain/body imaging (MoBI) systems that continuously capture the wearer's high-density electrical brain and muscle signals, three-dimensional body movements, audiovisual scene and point of regard, plus new data-driven analysis methods to model their interrelationships. The new imaging modality should allow new insights into how spatially distributed brain dynamics support natural human cognition and agency.

Sex hormones regulate cerebral drug metabolism via brain miRNAs: down-regulation of brain CYP2D by androgens reduces the analgesic effects of tramadol

PubMed Central

Li, Jie; Xie, Mengmeng; Wang, Xiaoshuang; Ouyang, Xiufang; Wan, Yu; Dong, Guicheng; Yang, Zheqiong; Yang, Jing; Yue, Jiang

2015-01-01

Background and Purpose Brain cytochrome P450 2D (CYP2D) metabolises exogenous neurotoxins, endogenous substances and neurotransmitters. Brain CYP2D can be regulated in an organ-specific manner, but the possible regulatory mechanisms are poorly understood. We investigated the involvement of miRNAs in the selective regulation of brain CYP2D by testosterone and the corresponding alteration of the pharmacological profiles of tramadol by testosterone. Experimental Approach The regulation of CYP2D and brain-enriched miRNAs by testosterone was investigated using SH-SY5Y cells, U251 cells, and HepG2 cells as well as orchiectomized growth hormone receptor knockout (GHR-KO) mice and rats. Concentration–time curves of tramadol in rat brain were determined using a microdialysis technique. The analgesic action of tramadol was assessed by the tail-flick test in rats. Key Results miR-101 and miR-128-2 bound the 3′-untranslated region of the CYP2D6 mRNA and decreased its level. Testosterone decreased CYP2D6 catalytic function via the up-regulation of miR-101 and miR-128-2 in SH-SY5Y and U251 cells, but not in HepG2 cells. Orchiectomy decreased the levels of miR-101 and miR-128-2 in the hippocampus of male GHR-KO mice, indicating that androgens regulate miRNAs directly, not via the alteration of growth hormone secretion patterns. Changes in the pharmacokinetic and pharmacodynamic profiles of tramadol by orchiectomy was attenuated by either testosterone supplementation or a specific brain CYP2D inhibitor. Conclusions and Implications The selective regulation of brain CYP2D via brain-enriched miRNAs, following changes in androgen levels, such as in testosterone therapy, androgen deprivation therapy and/or ageing may alter the response to centrally active substances. PMID:26031356

Quantifying structural alterations in Alzheimer's disease brains using quantitative phase imaging (Conference Presentation)

NASA Astrophysics Data System (ADS)

Lee, Moosung; Lee, Eeksung; Jung, JaeHwang; Yu, Hyeonseung; Kim, Kyoohyun; Yoon, Jonghee; Lee, Shinhwa; Jeong, Yong; Park, YongKeun

2017-02-01

Imaging brain tissues is an essential part of neuroscience because understanding brain structure provides relevant information about brain functions and alterations associated with diseases. Magnetic resonance imaging and positron emission tomography exemplify conventional brain imaging tools, but these techniques suffer from low spatial resolution around 100 μm. As a complementary method, histopathology has been utilized with the development of optical microscopy. The traditional method provides the structural information about biological tissues to cellular scales, but relies on labor-intensive staining procedures. With the advances of illumination sources, label-free imaging techniques based on nonlinear interactions, such as multiphoton excitations and Raman scattering, have been applied to molecule-specific histopathology. Nevertheless, these techniques provide limited qualitative information and require a pulsed laser, which is difficult to use for pathologists with no laser training. Here, we present a label-free optical imaging of mouse brain tissues for addressing structural alteration in Alzheimer's disease. To achieve the mesoscopic, unlabeled tissue images with high contrast and sub-micrometer lateral resolution, we employed holographic microscopy and an automated scanning platform. From the acquired hologram of the brain tissues, we could retrieve scattering coefficients and anisotropies according to the modified scattering-phase theorem. This label-free imaging technique enabled direct access to structural information throughout the tissues with a sub-micrometer lateral resolution and presented a unique means to investigate the structural changes in the optical properties of biological tissues.

Numerical Models of Human Circulatory System under Altered Gravity: Brain Circulation

NASA Technical Reports Server (NTRS)

Kim, Chang Sung; Kiris, Cetin; Kwak, Dochan; David, Tim

2003-01-01

A computational fluid dynamics (CFD) approach is presented to model the blood flow through the human circulatory system under altered gravity conditions. Models required for CFD simulation relevant to major hemodynamic issues are introduced such as non-Newtonian flow models governed by red blood cells, a model for arterial wall motion due to fluid-wall interactions, a vascular bed model for outflow boundary conditions, and a model for auto-regulation mechanism. The three-dimensional unsteady incompressible Navier-Stokes equations coupled with these models are solved iteratively using the pseudocompressibility method and dual time stepping. Moving wall boundary conditions from the first-order fluid-wall interaction model are used to study the influence of arterial wall distensibility on flow patterns and wall shear stresses during the heart pulse. A vascular bed modeling utilizing the analogy with electric circuits is coupled with an auto-regulation algorithm for multiple outflow boundaries. For the treatment of complex geometry, a chimera overset grid technique is adopted to obtain connectivity between arterial branches. For code validation, computed results are compared with experimental data for steady and unsteady non-Newtonian flows. Good agreement is obtained for both cases. In sin-type Gravity Benchmark Problems, gravity source terms are added to the Navier-Stokes equations to study the effect of gravitational variation on the human circulatory system. This computational approach is then applied to localized blood flows through a realistic carotid bifurcation and two Circle of Willis models, one using an idealized geometry and the other model using an anatomical data set. A three- dimensional anatomical Circle of Willis configuration is reconstructed from human-specific magnetic resonance images using an image segmentation method. The blood flow through these Circle of Willis models is simulated to provide means for studying gravitational effects on the brain circulation under auto-regulation.

Neuronal human BACE1 knockin induces systemic diabetes in mice.

PubMed

Plucińska, Kaja; Dekeryte, Ruta; Koss, David; Shearer, Kirsty; Mody, Nimesh; Whitfield, Phillip D; Doherty, Mary K; Mingarelli, Marco; Welch, Andy; Riedel, Gernot; Delibegovic, Mirela; Platt, Bettina

2016-07-01

β-Secretase 1 (BACE1) is a key enzyme in Alzheimer's disease pathogenesis that catalyses the amyloidogenic cleavage of amyloid precursor protein (APP). Recently, global Bace1 deletion was shown to protect against diet-induced obesity and diabetes, suggesting that BACE1 is a potential regulator of glucose homeostasis. Here, we investigated whether increased neuronal BACE1 is sufficient to alter systemic glucose metabolism, using a neuron-specific human BACE1 knockin mouse model (PLB4). Glucose homeostasis and adiposity were determined by glucose tolerance tests and EchoMRI, lipid species were measured by quantitative lipidomics, and biochemical and molecular alterations were assessed by western blotting, quantitative PCR and ELISAs. Glucose uptake in the brain and upper body was measured via (18)FDG-PET imaging. Physiological and molecular analyses demonstrated that centrally expressed human BACE1 induced systemic glucose intolerance in mice from 4 months of age onward, alongside a fatty liver phenotype and impaired hepatic glycogen storage. This diabetic phenotype was associated with hypothalamic pathology, i.e. deregulation of the melanocortin system, and advanced endoplasmic reticulum (ER) stress indicated by elevated central C/EBP homologous protein (CHOP) signalling and hyperphosphorylation of its regulator eukaryotic translation initiation factor 2α (eIF2α). In vivo (18)FDG-PET imaging further confirmed brain glucose hypometabolism in these mice; this corresponded with altered neuronal insulin-related signalling, enhanced protein tyrosine phosphatase 1B (PTP1B) and retinol-binding protein 4 (RBP4) levels, along with upregulation of the ribosomal protein and lipid translation machinery. Increased forebrain and plasma lipid accumulation (i.e. ceramides, triacylglycerols, phospholipids) was identified via lipidomics analysis. Our data reveal that neuronal BACE1 is a key regulator of metabolic homeostasis and provide a potential mechanism for the high prevalence of metabolic disturbance in Alzheimer's disease.

Identification of autism spectrum disorder using deep learning and the ABIDE dataset.

PubMed

Heinsfeld, Anibal Sólon; Franco, Alexandre Rosa; Craddock, R Cameron; Buchweitz, Augusto; Meneguzzi, Felipe

2018-01-01

The goal of the present study was to apply deep learning algorithms to identify autism spectrum disorder (ASD) patients from large brain imaging dataset, based solely on the patients brain activation patterns. We investigated ASD patients brain imaging data from a world-wide multi-site database known as ABIDE (Autism Brain Imaging Data Exchange). ASD is a brain-based disorder characterized by social deficits and repetitive behaviors. According to recent Centers for Disease Control data, ASD affects one in 68 children in the United States. We investigated patterns of functional connectivity that objectively identify ASD participants from functional brain imaging data, and attempted to unveil the neural patterns that emerged from the classification. The results improved the state-of-the-art by achieving 70% accuracy in identification of ASD versus control patients in the dataset. The patterns that emerged from the classification show an anticorrelation of brain function between anterior and posterior areas of the brain; the anticorrelation corroborates current empirical evidence of anterior-posterior disruption in brain connectivity in ASD. We present the results and identify the areas of the brain that contributed most to differentiating ASD from typically developing controls as per our deep learning model.

Age-dependent changes at the blood-brain barrier. A Comparative structural and functional study in young adult and middle aged rats.

PubMed

Bors, Luca; Tóth, Kinga; Tóth, Estilla Zsófia; Bajza, Ágnes; Csorba, Attila; Szigeti, Krisztián; Máthé, Domokos; Perlaki, Gábor; Orsi, Gergely; Tóth, Gábor K; Erdő, Franciska

2018-05-01

Decreased beta-amyloid clearance in Alzheimer's disease and increased blood-brain barrier permeability in aged subjects have been reported in several articles. However, morphological and functional characterization of blood-brain barrier and its membrane transporter activity have not been described in physiological aging yet. The aim of our study was to explore the structural changes in the brain microvessels and possible functional alterations of P-glycoprotein at the blood-brain barrier with aging. Our approach included MR imaging for anatomical orientation in middle aged rats, electronmicroscopy and immunohistochemistry to analyse the alterations at cellular level, dual or triple-probe microdialysis and SPECT to test P-glycoprotein functionality in young and middle aged rats. Our results indicate that the thickness of basal lamina increases, the number of tight junctions decreases and the size of astrocyte endfeet extends with advanced age. On the basis of microdialysis and SPECT results the P-gp function is reduced in old rats. With our multiparametric approach a complex regulation can be suggested which includes elements leading to increased permeability of blood-brain barrier by enhanced paracellular and transcellular transport, and factors working against it. To verify the role of P-gp pumps in brain aging further studies are warranted. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Common genetic variants influence human subcortical brain structures

PubMed Central

Hibar, Derrek P.; Stein, Jason L.; Renteria, Miguel E.; Arias-Vasquez, Alejandro; Desrivières, Sylvane; Jahanshad, Neda; Toro, Roberto; Wittfeld, Katharina; Abramovic, Lucija; Andersson, Micael; Aribisala, Benjamin S.; Armstrong, Nicola J.; Bernard, Manon; Bohlken, Marc M.; Boks, Marco P.; Bralten, Janita; Brown, Andrew A.; Chakravarty, M. Mallar; Chen, Qiang; Ching, Christopher R. K.; Cuellar-Partida, Gabriel; den Braber, Anouk; Giddaluru, Sudheer; Goldman, Aaron L.; Grimm, Oliver; Guadalupe, Tulio; Hass, Johanna; Woldehawariat, Girma; Holmes, Avram J.; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H.; Olde Loohuis, Loes M.; Luciano, Michelle; Macare, Christine; Mather, Karen A.; Mattheisen, Manuel; Milaneschi, Yuri; Nho, Kwangsik; Papmeyer, Martina; Ramasamy, Adaikalavan; Risacher, Shannon L.; Roiz-Santiañez, Roberto; Rose, Emma J.; Salami, Alireza; Sämann, Philipp G.; Schmaal, Lianne; Schork, Andrew J.; Shin, Jean; Strike, Lachlan T.; Teumer, Alexander; van Donkelaar, Marjolein M. J.; van Eijk, Kristel R.; Walters, Raymond K.; Westlye, Lars T.; Whelan, Christopher D.; Winkler, Anderson M.; Zwiers, Marcel P.; Alhusaini, Saud; Athanasiu, Lavinia; Ehrlich, Stefan; Hakobjan, Marina M. H.; Hartberg, Cecilie B.; Haukvik, Unn K.; Heister, Angelien J. G. A. M.; Hoehn, David; Kasperaviciute, Dalia; Liewald, David C. M.; Lopez, Lorna M.; Makkinje, Remco R. R.; Matarin, Mar; Naber, Marlies A. M.; McKay, D. Reese; Needham, Margaret; Nugent, Allison C.; Pütz, Benno; Royle, Natalie A.; Shen, Li; Sprooten, Emma; Trabzuni, Daniah; van der Marel, Saskia S. L.; van Hulzen, Kimm J. E.; Walton, Esther; Wolf, Christiane; Almasy, Laura; Ames, David; Arepalli, Sampath; Assareh, Amelia A.; Bastin, Mark E.; Brodaty, Henry; Bulayeva, Kazima B.; Carless, Melanie A.; Cichon, Sven; Corvin, Aiden; Curran, Joanne E.; Czisch, Michael; de Zubicaray, Greig I.; Dillman, Allissa; Duggirala, Ravi; Dyer, Thomas D.; Erk, Susanne; Fedko, Iryna O.; Ferrucci, Luigi; Foroud, Tatiana M.; Fox, Peter T.; Fukunaga, Masaki; Gibbs, J. Raphael; Göring, Harald H. H.; Green, Robert C.; Guelfi, Sebastian; Hansell, Narelle K.; Hartman, Catharina A.; Hegenscheid, Katrin; Heinz, Andreas; Hernandez, Dena G.; Heslenfeld, Dirk J.; Hoekstra, Pieter J.; Holsboer, Florian; Homuth, Georg; Hottenga, Jouke-Jan; Ikeda, Masashi; Jack, Clifford R.; Jenkinson, Mark; Johnson, Robert; Kanai, Ryota; Keil, Maria; Kent, Jack W.; Kochunov, Peter; Kwok, John B.; Lawrie, Stephen M.; Liu, Xinmin; Longo, Dan L.; McMahon, Katie L.; Meisenzahl, Eva; Melle, Ingrid; Mohnke, Sebastian; Montgomery, Grant W.; Mostert, Jeanette C.; Mühleisen, Thomas W.; Nalls, Michael A.; Nichols, Thomas E.; Nilsson, Lars G.; Nöthen, Markus M.; Ohi, Kazutaka; Olvera, Rene L.; Perez-Iglesias, Rocio; Pike, G. Bruce; Potkin, Steven G.; Reinvang, Ivar; Reppermund, Simone; Rietschel, Marcella; Romanczuk-Seiferth, Nina; Rosen, Glenn D.; Rujescu, Dan; Schnell, Knut; Schofield, Peter R.; Smith, Colin; Steen, Vidar M.; Sussmann, Jessika E.; Thalamuthu, Anbupalam; Toga, Arthur W.; Traynor, Bryan J.; Troncoso, Juan; Turner, Jessica A.; Valdés Hernández, Maria C.; van ’t Ent, Dennis; van der Brug, Marcel; van der Wee, Nic J. A.; van Tol, Marie-Jose; Veltman, Dick J.; Wassink, Thomas H.; Westman, Eric; Zielke, Ronald H.; Zonderman, Alan B.; Ashbrook, David G.; Hager, Reinmar; Lu, Lu; McMahon, Francis J.; Morris, Derek W.; Williams, Robert W.; Brunner, Han G.; Buckner, Randy L.; Buitelaar, Jan K.; Cahn, Wiepke; Calhoun, Vince D.; Cavalleri, Gianpiero L.; Crespo-Facorro, Benedicto; Dale, Anders M.; Davies, Gareth E.; Delanty, Norman; Depondt, Chantal; Djurovic, Srdjan; Drevets, Wayne C.; Espeseth, Thomas; Gollub, Randy L.; Ho, Beng-Choon; Hoffmann, Wolfgang; Hosten, Norbert; Kahn, René S.; Le Hellard, Stephanie; Meyer-Lindenberg, Andreas; Müller-Myhsok, Bertram; Nauck, Matthias; Nyberg, Lars; Pandolfo, Massimo; Penninx, Brenda W. J. H.; Roffman, Joshua L.; Sisodiya, Sanjay M.; Smoller, Jordan W.; van Bokhoven, Hans; van Haren, Neeltje E. M.; Völzke, Henry; Walter, Henrik; Weiner, Michael W.; Wen, Wei; White, Tonya; Agartz, Ingrid; Andreassen, Ole A.; Blangero, John; Boomsma, Dorret I.; Brouwer, Rachel M.; Cannon, Dara M.; Cookson, Mark R.; de Geus, Eco J. C.; Deary, Ian J.; Donohoe, Gary; Fernández, Guillén; Fisher, Simon E.; Francks, Clyde; Glahn, David C.; Grabe, Hans J.; Gruber, Oliver; Hardy, John; Hashimoto, Ryota; Hulshoff Pol, Hilleke E.; Jönsson, Erik G.; Kloszewska, Iwona; Lovestone, Simon; Mattay, Venkata S.; Mecocci, Patrizia; McDonald, Colm; McIntosh, Andrew M.; Ophoff, Roel A.; Paus, Tomas; Pausova, Zdenka; Ryten, Mina; Sachdev, Perminder S.; Saykin, Andrew J.; Simmons, Andy; Singleton, Andrew; Soininen, Hilkka; Wardlaw, Joanna M.; Weale, Michael E.; Weinberger, Daniel R.; Adams, Hieab H. H.; Launer, Lenore J.; Seiler, Stephan; Schmidt, Reinhold; Chauhan, Ganesh; Satizabal, Claudia L.; Becker, James T.; Yanek, Lisa; van der Lee, Sven J.; Ebling, Maritza; Fischl, Bruce; Longstreth, W. T.; Greve, Douglas; Schmidt, Helena; Nyquist, Paul; Vinke, Louis N.; van Duijn, Cornelia M.; Xue, Luting; Mazoyer, Bernard; Bis, Joshua C.; Gudnason, Vilmundur; Seshadri, Sudha; Ikram, M. Arfan; Martin, Nicholas G.; Wright, Margaret J.; Schumann, Gunter; Franke, Barbara; Thompson, Paul M.; Medland, Sarah E.

2015-01-01

The highly complex structure of the human brain is strongly shaped by genetic influences1. Subcortical brain regions form circuits with cortical areas to coordinate movement2, learning, memory3 and motivation4, and altered circuits can lead to abnormal behaviour and disease2. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume5 and intracranial volume6. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 × 10−33; 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability inhuman brain development, and may help to determine mechanisms of neuropsychiatric dysfunction. PMID:25607358

Non-invasive Imaging based Detection and Mapping of Brain Oxidative Stress and its Correlation with Cognitive Functions

DTIC Science & Technology

2017-05-14

AFRL-AFOSR-JP-TR-2017-0052 Non-invasive Imaging based Detection and Mapping of Brain Oxidative Stress and its Correlation with Cognative Functions...invasive Imaging based Detection and Mapping of Brain Oxidative Stress and its Correlation with Cognative Functions 5a.  CONTRACT NUMBER 5b.  GRANT...SUPPLEMENTARY NOTES 14. ABSTRACT Brain stress level measurement (non-invasively) in quantitative term is very helpful to correlate with various

Non invasive Imaging based Detection and Mapping of Brain Oxidative Stress and its Correlation with Cognative Functions

DTIC Science & Technology

2017-05-14

AFRL-AFOSR-JP-TR-2017-0052 Non-invasive Imaging based Detection and Mapping of Brain Oxidative Stress and its Correlation with Cognative Functions...invasive Imaging based Detection and Mapping of Brain Oxidative Stress and its Correlation with Cognative Functions 5a.  CONTRACT NUMBER 5b.  GRANT...SUPPLEMENTARY NOTES 14. ABSTRACT Brain stress level measurement (non-invasively) in quantitative term is very helpful to correlate with various

Automatic CT Brain Image Segmentation Using Two Level Multiresolution Mixture Model of EM

NASA Astrophysics Data System (ADS)

Jiji, G. Wiselin; Dehmeshki, Jamshid

2014-04-01

Tissue classification in computed tomography (CT) brain images is an important issue in the analysis of several brain dementias. A combination of different approaches for the segmentation of brain images is presented in this paper. A multi resolution algorithm is proposed along with scaled versions using Gaussian filter and wavelet analysis that extends expectation maximization (EM) algorithm. It is found that it is less sensitive to noise and got more accurate image segmentation than traditional EM. Moreover the algorithm has been applied on 20 sets of CT of the human brain and compared with other works. The segmentation results show the advantages of the proposed work have achieved more promising results and the results have been tested with Doctors.

Improved tumor identification using dual tracer molecular imaging in fluorescence guided brain surgery

NASA Astrophysics Data System (ADS)

Xu, Xiaochun; Torres, Veronica; Straus, David; Brey, Eric M.; Byrne, Richard W.; Tichauer, Kenneth M.

2015-03-01

Brain tumors represent a leading cause of cancer death for people under the age of 40 and the probability complete surgical resection of brain tumors remains low owing to the invasive nature of these tumors and the consequences of damaging healthy brain tissue. Molecular imaging is an emerging approach that has the potential to improve the ability for surgeons to correctly discriminate between healthy and cancerous tissue; however, conventional molecular imaging approaches in brain suffer from significant background signal in healthy tissue or an inability target more invasive sections of the tumor. This work presents initial studies investigating the ability of novel dual-tracer molecular imaging strategies to be used to overcome the major limitations of conventional "single-tracer" molecular imaging. The approach is evaluated in simulations and in an in vivo mice study with animals inoculated orthotopically using fluorescent human glioma cells. An epidermal growth factor receptor (EGFR) targeted Affibody-fluorescent marker was employed as a targeted imaging agent, and the suitability of various FDA approved untargeted fluorescent tracers (e.g. fluorescein & indocyanine green) were evaluated in terms of their ability to account for nonspecific uptake and retention of the targeted imaging agent. Signal-to-background ratio was used to measure and compare the amount of reporter in the tissue between targeted and untargeted tracer. The initial findings suggest that FDA-approved fluorescent imaging agents are ill-suited to act as untargeted imaging agents for dual-tracer fluorescent guided brain surgery as they suffer from poor delivery to the healthy brain tissue and therefore cannot be used to identify nonspecific vs. specific uptake of the targeted imaging agent where current surgery is most limited.

Potential application of a handheld confocal endomicroscope imaging system using a variety of fluorophores in experimental gliomas and normal brain.

PubMed

Martirosyan, Nikolay L; Georges, Joseph; Eschbacher, Jennifer M; Cavalcanti, Daniel D; Elhadi, Ali M; Abdelwahab, Mohammed G; Scheck, Adrienne C; Nakaji, Peter; Spetzler, Robert F; Preul, Mark C

2014-02-01

The authors sought to assess the feasibility of a handheld visible-wavelength confocal endomicroscope imaging system (Optiscan 5.1, Optiscan Pty., Ltd.) using a variety of rapid-acting fluorophores to provide histological information on gliomas, tumor margins, and normal brain in animal models. Mice (n = 25) implanted with GL261 cells were used to image fluorescein sodium (FNa), 5-aminolevulinic acid (5-ALA), acridine orange (AO), acriflavine (AF), and cresyl violet (CV). A U251 glioma xenograft model in rats (n = 5) was used to image sulforhodamine 101 (SR101). A swine (n = 3) model with AO was used to identify confocal features of normal brain. Images of normal brain, obvious tumor, and peritumoral zones were collected using the handheld confocal endomicroscope. Histological samples were acquired through biopsies from matched imaging areas. Samples were visualized with a benchtop confocal microscope. Histopathological features in corresponding confocal images and photomicrographs of H & E-stained tissues were reviewed. Fluorescence induced by FNa, 5-ALA, AO, AF, CV, and SR101 and detected with the confocal endomicroscope allowed interpretation of histological features. Confocal endomicroscopy revealed satellite tumor cells within peritumoral tissue, a definitive tumor border, and striking fluorescent cellular and subcellular structures. Fluorescence in various tumor regions correlated with standard histology and known tissue architecture. Characteristic features of different areas of normal brain were identified as well. Confocal endomicroscopy provided rapid histological information precisely related to the site of microscopic imaging with imaging characteristics of cells related to the unique labeling features of the fluorophores. Although experimental with further clinical trial validation required, these data suggest that intraoperative confocal imaging can help to distinguish normal brain from tumor and tumor margin and may have application in improving intraoperative decisions during resection of brain tumors.

A deep learning model integrating FCNNs and CRFs for brain tumor segmentation.

PubMed

Zhao, Xiaomei; Wu, Yihong; Song, Guidong; Li, Zhenye; Zhang, Yazhuo; Fan, Yong

2018-01-01

Accurate and reliable brain tumor segmentation is a critical component in cancer diagnosis, treatment planning, and treatment outcome evaluation. Build upon successful deep learning techniques, a novel brain tumor segmentation method is developed by integrating fully convolutional neural networks (FCNNs) and Conditional Random Fields (CRFs) in a unified framework to obtain segmentation results with appearance and spatial consistency. We train a deep learning based segmentation model using 2D image patches and image slices in following steps: 1) training FCNNs using image patches; 2) training CRFs as Recurrent Neural Networks (CRF-RNN) using image slices with parameters of FCNNs fixed; and 3) fine-tuning the FCNNs and the CRF-RNN using image slices. Particularly, we train 3 segmentation models using 2D image patches and slices obtained in axial, coronal and sagittal views respectively, and combine them to segment brain tumors using a voting based fusion strategy. Our method could segment brain images slice-by-slice, much faster than those based on image patches. We have evaluated our method based on imaging data provided by the Multimodal Brain Tumor Image Segmentation Challenge (BRATS) 2013, BRATS 2015 and BRATS 2016. The experimental results have demonstrated that our method could build a segmentation model with Flair, T1c, and T2 scans and achieve competitive performance as those built with Flair, T1, T1c, and T2 scans. Copyright © 2017 Elsevier B.V. All rights reserved.

Glucose-induced inhibition of the appetitive brain response to visual food cues in polycystic ovary syndrome patients.

PubMed

Van Vugt, Dean A; Krzemien, Alicja; Alsaadi, Hanin; Frank, Tamar C; Reid, Robert L

2014-04-16

We postulate that insulin regulation of food intake is compromised when insulin resistance is present. In order to investigate the effect of insulin sensitivity on appetitive brain responses, we conducted functional magnetic resonance imaging studies in a group of women diagnosed with polycystic ovary syndrome (PCOS) in which insulin sensitivity ranged from normal to resistant. Subjects (n=19) were imaged while viewing pictures of high calorie (HC) foods and low calorie (LC) foods after ingesting either 75 g glucose or an equivalent volume of water. The insulin sensitive group showed reduced blood oxygen level dependent (BOLD) signal in response to food pictures following glucose ingestion in numerous corticolimbic brain regions, whereas the insulin resistant group did not. There was a significant interaction between insulin sensitivity (sensitive vs resistant) and condition (water vs glucose). The largest clusters identified included the left insula, bilateral limbic/parahippocampal gyrus/culmen/midbrain, bilateral limbic lobe/precuneus, and left superior/mid temporal gyrus/parietal for HC and LC stimuli combined, the left parahippocampal gyrus/fusiform/pulvinar/midbrain for HC pictures, and the left superior/mid temporal gyrus/parietal and middle/inferior frontal gyrus/orbitofrontal cortex for LC pictures. Furthermore, BOLD signal in the anterior cingulate, medial frontal gyrus, posterior cingulate/precuneus, and parietal cortex during a glucose challenge correlated negatively with insulin sensitivity. We conclude the PCOS women with insulin resistance have an impaired brain response to a glucose challenge. The inability of postprandial hyperinsulinemia to inhibit brain responsiveness to food cues in insulin resistant subjects may lead to greater non-homeostatic eating. Copyright © 2014 Elsevier B.V. All rights reserved.

An Update Overview on Brain Imaging Studies of Internet Gaming Disorder

PubMed Central

Weinstein, Aviv M.

2017-01-01

There are a growing number of studies on structural and functional brain mechanisms underlying Internet gaming disorder (IGD). Recent functional magnetic resonance imaging studies showed that IGD adolescents and adults had reduced gray matter volume in regions associated with attention motor coordination executive function and perception. Adolescents with IGD showed lower white matter (WM) integrity measures in several brain regions that are involved in decision-making, behavioral inhibition, and emotional regulation. IGD adolescents had also disruption in the functional connectivity in areas responsible for learning memory and executive function, processing of auditory, visual, and somatosensory stimuli and relay of sensory and motor signals. IGD adolescents also had decreased functional connectivity of PFC-striatal circuits, increased risk-taking choices, and impaired ability to control their impulses similar to other impulse control disorders. Recent studies indicated that altered executive control mechanisms in attention deficit hyperactivity disorder (ADHD) would be a predisposition for developing IGD. Finally, patients with IGD have also shown an increased functional connectivity of several executive control brain regions that may related to comorbidity with ADHD and depression. The behavioral addiction model argues that IGD shows the features of excessive use despite adverse consequences, withdrawal phenomena, and tolerance that characterize substance use disorders. The evidence supports the behavioral addiction model of IGD by showing structural and functional changes in the mechanisms of reward and craving (but not withdrawal) in IGD. Future studies need to investigate WM density and functional connectivity in IGD in order to validate these findings. Furthermore, more research is required about the similarity in neurochemical and neurocognitive brain circuits in IGD and comorbid conditions such as ADHD and depression. PMID:29033857

A role for sex and a common HFE gene variant in brain iron uptake.

PubMed

Duck, Kari A; Neely, Elizabeth B; Simpson, Ian A; Connor, James R

2018-03-01

HFE (high iron) is an essential protein for regulating iron transport into cells. Mutations of the HFE gene result in loss of this regulation causing accumulation of iron within the cell. The mutated protein has been found increasingly in numerous neurodegenerative disorders in which increased levels of iron in the brain are reported. Additionally, evidence that these mutations are associated with elevated brain iron challenges the paradigm that the brain is protected by the blood-brain barrier. While much has been studied regarding the role of HFE in cellular iron uptake, it has remained unclear what role the protein plays in the transport of iron into the brain. We investigated regulation of iron transport into the brain using a mouse model with a mutation in the HFE gene. We demonstrated that the rate of radiolabeled iron ( 59 Fe) uptake was similar between the two genotypes despite higher brain iron concentrations in the mutant. However, there were significant differences in iron uptake between males and females regardless of genotype. These data indicate that brain iron status is consistently maintained and tightly regulated at the level of the blood-brain barrier.

The Potential of Using Brain Images for Authentication

PubMed Central

Zhou, Zongtan; Shen, Hui; Hu, Dewen

2014-01-01

Biometric recognition (also known as biometrics) refers to the automated recognition of individuals based on their biological or behavioral traits. Examples of biometric traits include fingerprint, palmprint, iris, and face. The brain is the most important and complex organ in the human body. Can it be used as a biometric trait? In this study, we analyze the uniqueness of the brain and try to use the brain for identity authentication. The proposed brain-based verification system operates in two stages: gray matter extraction and gray matter matching. A modified brain segmentation algorithm is implemented for extracting gray matter from an input brain image. Then, an alignment-based matching algorithm is developed for brain matching. Experimental results on two data sets show that the proposed brain recognition system meets the high accuracy requirement of identity authentication. Though currently the acquisition of the brain is still time consuming and expensive, brain images are highly unique and have the potential possibility for authentication in view of pattern recognition. PMID:25126604

The potential of using brain images for authentication.

PubMed

Chen, Fanglin; Zhou, Zongtan; Shen, Hui; Hu, Dewen

2014-01-01

Biometric recognition (also known as biometrics) refers to the automated recognition of individuals based on their biological or behavioral traits. Examples of biometric traits include fingerprint, palmprint, iris, and face. The brain is the most important and complex organ in the human body. Can it be used as a biometric trait? In this study, we analyze the uniqueness of the brain and try to use the brain for identity authentication. The proposed brain-based verification system operates in two stages: gray matter extraction and gray matter matching. A modified brain segmentation algorithm is implemented for extracting gray matter from an input brain image. Then, an alignment-based matching algorithm is developed for brain matching. Experimental results on two data sets show that the proposed brain recognition system meets the high accuracy requirement of identity authentication. Though currently the acquisition of the brain is still time consuming and expensive, brain images are highly unique and have the potential possibility for authentication in view of pattern recognition.

Biosensor Technologies for Augmented Brain-Computer Interfaces in the Next Decades

DTIC Science & Technology

2012-05-13

Research Triangle Park, NC 27709-2211 Augmented brain–computer interface (ABCI);biosensor; cognitive-state monitoring; electroencephalogram( EEG ); human...biosensor; cognitive-state monitoring; electroencephalogram ( EEG ); human brain imaging Manuscript received November 28, 2011; accepted December 20...magnetic reso- nance imaging (fMRI) [1], positron emission tomography (PET) [2], electroencephalograms ( EEGs ) and optical brain imaging techniques (i.e

Diffusion Tensor Imaging: Application to the Study of the Developing Brain

ERIC Educational Resources Information Center

Cascio, Carissa J.; Gerig, Guido; Piven, Joseph

2007-01-01

Objective: To provide an overview of diffusion tensor imaging (DTI) and its application to the study of white matter in the developing brain in both healthy and clinical samples. Method: The development of DTI and its application to brain imaging of white matter tracts is discussed. Forty-eight studies using DTI to examine diffusion properties of…

Novel strategies of Raman imaging for brain tumor research.

PubMed

Anna, Imiela; Bartosz, Polis; Lech, Polis; Halina, Abramczyk

2017-10-17

Raman diagnostics and imaging have been shown to be an effective tool for the analysis and discrimination of human brain tumors from normal structures. Raman spectroscopic methods have potential to be applied in clinical practice as they allow for identification of tumor margins during surgery. In this study, we investigate medulloblastoma (grade IV WHO) (n= 5), low-grade astrocytoma (grades I-II WHO) (n =4), ependymoma (n=3) and metastatic brain tumors (n= 1) and the tissue from the negative margins used as normal controls. We compare a high grade medulloblastoma, low grade astrocytoma and non-tumor samples from human central nervous system (CNS) tissue. Based on the properties of the Raman vibrational features and Raman images we provide a real-time feedback method that is label-free to monitor tumor metabolism that reveals reprogramming of biosynthesis of lipids, proteins, DNA and RNA. Our results indicate marked metabolic differences between low and high grade brain tumors. We discuss molecular mechanisms causing these metabolic changes, particularly lipid alterations in malignant medulloblastoma and low grade gliomas that may shed light on the mechanisms driving tumor recurrence thereby revealing new approaches for the treatment of malignant glioma. We have found that the high-grade tumors of central nervous system (medulloblastoma) exhibit enhanced level of β-sheet conformation and down-regulated level of α-helix conformation when comparing against normal tissue. We have found that almost all tumors studied in the paper have increased Raman signals of nucleic acids. This increase can be interpreted as increased DNA/RNA turnover in brain tumors. We have shown that the ratio of Raman intensities I 2930 /I 2845 at 2930 and 2845 cm -1 is a good source of information on the ratio of lipid and protein contents. We have found that the ratio reflects the different lipid and protein contents of cancerous brain tissue compared to the non-tumor tissue. We found that levels of the saturated fatty acids were significantly reduced in the high grade medulloblastoma samples compared with non-tumor brain samples and low grade astrocytoma. Differences were also noted in the n-6/n-3 polyunsaturated fatty acids (PUFA) content between medulloblastoma and non-tumor brain samples. The content of the oleic acid (OA) was significantly smaller in almost all brain high grade brain tumors than that observed in the control samples. It indicates that the fatty acid composition of human brain tumors differs from that found in non-tumor brain tissue. The iodine number N I for the normal brain tissue is 60. For comparison OA has 87, docosahexaenoic acid (DHA) 464, α-linolenic acid (ALA) 274. The high grade tumors have the iodine numbers between that for palmitic acid, stearic acid, arachidic acid (N I =0) and oleic acid (N I =87). Most low grade tumors have N I similar to that of OA. The iodine number for arachidonic acid (AA) (N I =334) is much higher than those observed for all studied samples.

Novel strategies of Raman imaging for brain tumor research

PubMed Central

Anna, Imiela; Bartosz, Polis; Lech, Polis; Halina, Abramczyk

2017-01-01

Raman diagnostics and imaging have been shown to be an effective tool for the analysis and discrimination of human brain tumors from normal structures. Raman spectroscopic methods have potential to be applied in clinical practice as they allow for identification of tumor margins during surgery. In this study, we investigate medulloblastoma (grade IV WHO) (n= 5), low-grade astrocytoma (grades I-II WHO) (n =4), ependymoma (n=3) and metastatic brain tumors (n= 1) and the tissue from the negative margins used as normal controls. We compare a high grade medulloblastoma, low grade astrocytoma and non-tumor samples from human central nervous system (CNS) tissue. Based on the properties of the Raman vibrational features and Raman images we provide a real–time feedback method that is label-free to monitor tumor metabolism that reveals reprogramming of biosynthesis of lipids, proteins, DNA and RNA. Our results indicate marked metabolic differences between low and high grade brain tumors. We discuss molecular mechanisms causing these metabolic changes, particularly lipid alterations in malignant medulloblastoma and low grade gliomas that may shed light on the mechanisms driving tumor recurrence thereby revealing new approaches for the treatment of malignant glioma. We have found that the high-grade tumors of central nervous system (medulloblastoma) exhibit enhanced level of β-sheet conformation and down-regulated level of α-helix conformation when comparing against normal tissue. We have found that almost all tumors studied in the paper have increased Raman signals of nucleic acids. This increase can be interpreted as increased DNA/RNA turnover in brain tumors. We have shown that the ratio of Raman intensities I2930/I2845 at 2930 and 2845 cm-1 is a good source of information on the ratio of lipid and protein contents. We have found that the ratio reflects the different lipid and protein contents of cancerous brain tissue compared to the non-tumor tissue. We found that levels of the saturated fatty acids were significantly reduced in the high grade medulloblastoma samples compared with non-tumor brain samples and low grade astrocytoma. Differences were also noted in the n-6/n-3 polyunsaturated fatty acids (PUFA) content between medulloblastoma and non-tumor brain samples. The content of the oleic acid (OA) was significantly smaller in almost all brain high grade brain tumors than that observed in the control samples. It indicates that the fatty acid composition of human brain tumors differs from that found in non-tumor brain tissue. The iodine number NI for the normal brain tissue is 60. For comparison OA has 87, docosahexaenoic acid (DHA) 464, α-linolenic acid (ALA) 274. The high grade tumors have the iodine numbers between that for palmitic acid, stearic acid, arachidic acid (NI=0) and oleic acid (NI=87). Most low grade tumors have NI similar to that of OA. The iodine number for arachidonic acid (AA) (NI=334) is much higher than those observed for all studied samples. PMID:29156720

Morphology of subcortical brain nuclei is associated with autonomic function in healthy humans.

PubMed

Ruffle, James K; Coen, Steven J; Giampietro, Vincent; Williams, Steven C R; Apkarian, A Vania; Farmer, Adam D; Aziz, Qasim

2018-01-01

The autonomic nervous system (ANS) is a brain body interface which serves to maintain homeostasis by influencing a plethora of physiological processes, including metabolism, cardiorespiratory regulation and nociception. Accumulating evidence suggests that ANS function is disturbed in numerous prevalent clinical disorders, including irritable bowel syndrome and fibromyalgia. While the brain is a central hub for regulating autonomic function, the association between resting autonomic activity and subcortical morphology has not been comprehensively studied and thus was our aim. In 27 healthy subjects [14 male and 13 female; mean age 30 years (range 22-53 years)], we quantified resting ANS function using validated indices of cardiac sympathetic index (CSI) and parasympathetic cardiac vagal tone (CVT). High resolution structural magnetic resonance imaging scans were acquired, and differences in subcortical nuclei shape, that is, 'deformation', contingent on resting ANS activity were investigated. CSI positively correlated with outward deformation of the brainstem, right nucleus accumbens, right amygdala and bilateral pallidum (all thresholded to corrected P < 0.05). In contrast, parasympathetic CVT negatively correlated with inward deformation of the right amygdala and pallidum (all thresholded to corrected P < 0.05). Left and right putamen volume positively correlated with CVT (r = 0.62, P = 0.0047 and r = 0.59, P = 0.008, respectively), as did the brainstem (r = 0.46, P = 0.049). These data provide novel evidence that resting autonomic state is associated with differences in the shape and volume of subcortical nuclei. Thus, subcortical morphological brain differences in various disorders may partly be attributable to perturbation in autonomic function. Further work is warranted to investigate these findings in clinical populations. Hum Brain Mapp 39:381-392, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Effects of Intranasal Oxytocin on the Blood Oxygenation Level-Dependent Signal in Food Motivation and Cognitive Control Pathways in Overweight and Obese Men.

PubMed

Plessow, Franziska; Marengi, Dean A; Perry, Sylvia K; Felicione, Julia M; Franklin, Rachel; Holmes, Tara M; Holsen, Laura M; Makris, Nikolaos; Deckersbach, Thilo; Lawson, Elizabeth A

2018-02-01

Recent research indicates that the hypothalamic neuropeptide hormone oxytocin is a key central nervous system factor in the regulation of food intake and weight. However, the mechanisms underlying the anorexigenic effects of oxytocin in humans are unknown and critical to study to consider oxytocin as a neurohormonal weight loss treatment. We performed a randomized, double-blind, placebo-controlled crossover study with single-dose intranasal oxytocin (24 IU) in ten overweight or obese, otherwise healthy men. Following oxytocin/placebo administration, participants completed an established functional magnetic resonance imaging food motivation paradigm. We hypothesized that oxytocin would reduce the blood oxygenation level-dependent (BOLD) signal to high-calorie food vs non-food visual stimuli in the ventral tegmental area (VTA), the origin of the mesolimbic dopaminergic reward system. Following oxytocin administration, compared to placebo, participants showed bilateral VTA hypoactivation to high-calorie food stimuli. A secondary exploratory whole-brain analysis revealed hypoactivation in additional hedonic (orbitofrontal cortex, insula, globus pallidus, putamen, hippocampus, and amygdala) and homeostatic (hypothalamus) food motivation and hyperactivation in cognitive control (anterior cingulate and frontopolar cortex) brain regions following oxytocin administration vs placebo. Oxytocin administration reduces the BOLD signal in reward-related food motivation brain regions, providing a potential neurobiological mechanism for the anorexigenic oxytocin effects in humans. Furthermore, our data indicate that oxytocin administration reduces activation in homeostatic and increases activation in cognitive control brain regions critically involved in regulating food intake and resolving affective conflict, respectively. Future studies are required to link these changes in brain activation to oxytocin effects on food intake and weight.

Altered brain morphology and functional connectivity reflect a vulnerable affective state after cumulative multigenerational stress in rats.

PubMed

McCreary, J Keiko; Truica, L Sorina; Friesen, Becky; Yao, Youli; Olson, David M; Kovalchuk, Igor; Cross, Albert R; Metz, Gerlinde A S

2016-08-25

Prenatal stress is a risk factor for abnormal neuroanatomical, cognitive, behavioral and mental health outcomes with potentially transgenerational consequences. Females in general seem more resilient to the effects of prenatal stress than males. Here, we examined if repeated stress across generations may diminish stress resiliency and cumulatively enhance the susceptibility for adverse health outcomes in females. Pregnant female rats of three successive generations were exposed to stress from gestational days 12-18 to generate multigenerational prenatal stress (MPS) in the maternal lineage. Stress response was measured by plasma corticosterone levels and open-field exploration in each generation. Neuromorphological consequences of MPS were investigated in the F3 generation using in vivo manganese-enhanced magnetic resonance imaging (MEMRI), T2-relaxometry, and cytoarchitectonics in relation to candidate gene expression involved in brain plasticity and mental health. Each additional generation of prenatal stress incrementally elevated hypothalamic-pituitary-adrenal axis activation, anxiety-like and aversive behaviors in adult female offspring. Elevated stress responses in the MPS F3 generation were accompanied by reduced neural density in prefrontal cortex, hippocampus and whole brain along with altered brain activation patterns in in vivo MEMRI. MPS increased ephrin receptor A5 (Epha5), neuronal growth regulator (Negr1) and synaptosomal-associated protein 25 (Snap25) gene expression and reduced fibroblast growth factor 12 (Fgf12) in prefrontal cortex. These genes regulate neuronal maturation, arborization and synaptic plasticity and may explain altered brain cytoarchitectonics and connectivity. These findings emphasize that recurrent stress across generations may cumulatively increase stress vulnerability and the risk of adverse health outcomes through perinatal programing in females. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Sex differences in associations of arginine vasopressin and oxytocin with resting-state functional brain connectivity.

PubMed

Rubin, Leah H; Yao, Li; Keedy, Sarah K; Reilly, James L; Bishop, Jeffrey R; Carter, C Sue; Pournajafi-Nazarloo, Hossein; Drogos, Lauren L; Tamminga, Carol A; Pearlson, Godfrey D; Keshavan, Matcheri S; Clementz, Brett A; Hill, Scot K; Liao, Wei; Ji, Gong-Jun; Lui, Su; Sweeney, John A

2017-01-02

Oxytocin (OT) and arginine vasopressin (AVP) exert robust and sexually dimorphic influences on cognition and emotion. How these hormones regulate relevant functional brain systems is not well understood. OT and AVP serum concentrations were assayed in 60 healthy individuals (36 women). Brain functional networks assessed with resting-state functional magnetic resonance imaging (rs-fMRI) were constructed with graph theory-based approaches that characterize brain networks as connected nodes. Sex differences were demonstrated in rs-fMRI. Men showed higher nodal degree (connectedness) and efficiency (information propagation capacity) in left inferior frontal gyrus (IFG) and bilateral superior temporal gyrus (STG) and higher nodal degree in left rolandic operculum. Women showed higher nodal betweenness (being part of paths between nodes) in right putamen and left inferior parietal gyrus (IPG). Higher hormone levels were associated with less intrinsic connectivity. In men, higher AVP was associated with lower nodal degree and efficiency in left IFG (pars orbitalis) and left STG and less efficiency in left IFG (pars triangularis). In women, higher AVP was associated with lower betweenness in left IPG, and higher OT was associated with lower nodal degree in left IFG (pars orbitalis). Hormones differentially correlate with brain networks that are important for emotion processing and cognition in men and women. AVP in men and OT in women may regulate orbital frontal cortex connectivity, which is important in emotion processing. Hormone associations with STG and pars triangularis in men and parietal cortex in women may account for well-established sex differences in verbal and visuospatial abilities, respectively. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Cocaine users with comorbid Cluster B personality disorders show dysfunctional brain activation and connectivity in the emotional regulation networks during negative emotion maintenance and reappraisal.

PubMed

Albein-Urios, Natalia; Verdejo-Román, Juan; Soriano-Mas, Carles; Asensio, Samuel; Martínez-González, José Miguel; Verdejo-García, Antonio

2013-12-01

Cocaine dependence often co-occurs with Cluster B personality disorders. Since both disorders are characterized by emotion regulation deficits, we predicted that cocaine comorbid patients would exhibit dysfunctional patterns of brain activation and connectivity during reappraisal of negative emotions. We recruited 18 cocaine users with comorbid Cluster B personality disorders, 17 cocaine users without comorbidities and 21 controls to be scanned using functional magnetic resonance imaging (fMRI) during performance on a reappraisal task in which they had to maintain or suppress the emotions induced by negative affective stimuli. We followed region of interest (ROI) and whole-brain approaches to investigate brain activations and connectivity associated with negative emotion experience and reappraisal. Results showed that cocaine users with comorbid personality disorders had reduced activation of the subgenual anterior cingulate cortex during negative emotion maintenance and increased activation of the lateral orbitofrontal cortex and the amygdala during reappraisal. Amygdala activation correlated with impulsivity and antisocial beliefs in the comorbid group. Connectivity analyses showed that in the cocaine comorbid group the subgenual cingulate was less efficiently connected with the amygdala and the fusiform gyri and more efficiently connected with the anterior insula during maintenance, whereas during reappraisal the left orbitofrontal cortex was more efficiently connected with the amygdala and the right orbitofrontal cortex was less efficiently connected with the dorsal striatum. We conclude that cocaine users with comorbid Cluster B personality disorders have distinctive patterns of brain activation and connectivity during maintenance and reappraisal of negative emotions, which correlate with impulsivity and dysfunctional beliefs. Copyright © 2013 Elsevier B.V. and ECNP. All rights reserved.

Cerebral ketone body metabolism.

PubMed

Morris, A A M

2005-01-01

Ketone bodies (KBs) are an important source of energy for the brain. During the neonatal period, they are also precursors for the synthesis of lipids (especially cholesterol) and amino acids. The rate of cerebral KB metabolism depends primarily on the concentration in blood; high concentrations occur during fasting and on a high-fat diet. Cerebral KB metabolism is also regulated by the permeability of the blood-brain barrier (BBB), which depends on the abundance of monocarboxylic acid transporters (MCT1). The BBB's permeability to KBs increases with fasting in humans. In rats, permeability increases during the suckling period, but human neonates have not been studied. Monocarboxylic acid transporters are also present in the plasma membranes of neurons and glia but their role in regulating KB metabolism is uncertain. Finally, the rate of cerebral KB metabolism depends on the activities of the relevant enzymes in brain. The activities vary with age in rats, but reliable results are not available for humans. Cerebral KB metabolism in humans differs from that in the rat in several respects. During fasting, for example, KBs supply more of the brain's energy in humans than in the rat. Conversely, KBs are probably used more extensively in the brain of suckling rats than in human neonates. These differences complicate the interpretation of rodent studies. Most patients with inborn errors of ketogenesis develop normally, suggesting that the only essential role for KBs is as an alternative fuel during illness or prolonged fasting. On the other hand, in HMG-CoA lyase deficiency, imaging generally shows asymptomatic white-matter abnormalities. The ability of KBs to act as an alternative fuel explains the effectiveness of the ketogenic diet in GLUT1 deficiency, but its effectiveness in epilepsy remains unexplained.

Quantifying Mesoscale Neuroanatomy Using X-Ray Microtomography

PubMed Central

Gray Roncal, William; Prasad, Judy A.; Fernandes, Hugo L.; Gürsoy, Doga; De Andrade, Vincent; Fezzaa, Kamel; Xiao, Xianghui; Vogelstein, Joshua T.; Jacobsen, Chris; Körding, Konrad P.

2017-01-01

Methods for resolving the three-dimensional (3D) microstructure of the brain typically start by thinly slicing and staining the brain, followed by imaging numerous individual sections with visible light photons or electrons. In contrast, X-rays can be used to image thick samples, providing a rapid approach for producing large 3D brain maps without sectioning. Here we demonstrate the use of synchrotron X-ray microtomography (µCT) for producing mesoscale (∼1 µm 3 resolution) brain maps from millimeter-scale volumes of mouse brain. We introduce a pipeline for µCT-based brain mapping that develops and integrates methods for sample preparation, imaging, and automated segmentation of cells, blood vessels, and myelinated axons, in addition to statistical analyses of these brain structures. Our results demonstrate that X-ray tomography achieves rapid quantification of large brain volumes, complementing other brain mapping and connectomics efforts. PMID:29085899

Fetal magnetic resonance imaging (MRI): a tool for a better understanding of normal and abnormal brain development.

PubMed

Saleem, Sahar N

2013-07-01

Knowledge of the anatomy of the developing fetal brain is essential to detect abnormalities and understand their pathogenesis. Capability of magnetic resonance imaging (MRI) to visualize the brain in utero and to differentiate between its various tissues makes fetal MRI a potential diagnostic and research tool for the developing brain. This article provides an approach to understand the normal and abnormal brain development through schematic interpretation of fetal brain MR images. MRI is a potential screening tool in the second trimester of pregnancies in fetuses at risk for brain anomalies and helps in describing new brain syndromes with in utero presentation. Accurate interpretation of fetal MRI can provide valuable information that helps genetic counseling, facilitates management decisions, and guides therapy. Fetal MRI can help in better understanding the pathogenesis of fetal brain malformations and can support research that could lead to disease-specific interventions.

Fiber tracking of brain white matter based on graph theory.

PubMed

Lu, Meng

2015-01-01

Brain white matter tractography is reconstructed via diffusion-weighted magnetic resonance images. Due to the complex structure of brain white matter fiber bundles, fiber crossing and fiber branching are abundant in human brain. And regular methods with diffusion tensor imaging (DTI) can't accurately handle this problem. the biggest problems of the brain tractography. Therefore, this paper presented a novel brain white matter tractography method based on graph theory, so the fiber tracking between two voxels is transformed into locating the shortest path in a graph. Besides, the presented method uses Q-ball imaging (QBI) as the source data instead of DTI, because QBI can provide accurate information about multiple fiber crossing and branching in one voxel using orientation distribution function (ODF). Experiments showed that the presented method can accurately handle the problem of brain white matter fiber crossing and branching, and reconstruct brain tractograhpy both in phantom data and real brain data.

Serotonin transporter genotype modulates cognitive reappraisal of negative emotions: a functional magnetic resonance imaging study

PubMed Central

Siep, Nicolette; Markus, C. Rob

2013-01-01

A functional polymorphism within the serotonin transporter gene (5-HTTLPR) has been reported to modulate emotionality and risk for affective disorders. The short (S) allele has less functional efficacy than the long (L) allele and has been associated with enhanced emotional reactivity. One possible contributing factor to the high emotionality in S carriers may be inefficient use of cognitive strategies such as reappraisal to regulate emotional responses. The aim of the present study was to test whether the 5-HTTLPR genotype modulates the neural correlates of emotion regulation. To determine neural differences between S and L allele carriers during reappraisal of negative emotions, 15 homozygous S (S′/S′) and 15 homozygous L (L′/L′) carriers underwent functional magnetic resonance imaging (fMRI), while performing an instructed emotion regulation task including downregulation, upregulation and passive viewing of negative emotional pictures. Compared to L′/L′ allele carriers, subjects who carry the S′/S′ allele responded with lower posterior insula and prefrontal brain activation during passive perception of negative emotional information but showed greater prefrontal activation and anterior insula activation during down- and upregulation of negative emotional responses. The current results support and extend previous findings of enhanced emotionality in S carriers by providing additional evidence of 5-HTTLPR modulation of volitional emotion regulation. PMID:22345383

Regulation of branching dynamics by axon-intrinsic asymmetries in Tyrosine Kinase Receptor signaling

PubMed Central

Zschätzsch, Marlen; Oliva, Carlos; Langen, Marion; De Geest, Natalie; Özel, Mehmet Neset; Williamson, W Ryan; Lemon, William C; Soldano, Alessia; Munck, Sebastian; Hiesinger, P Robin; Sanchez-Soriano, Natalia; Hassan, Bassem A

2014-01-01

Axonal branching allows a neuron to connect to several targets, increasing neuronal circuit complexity. While axonal branching is well described, the mechanisms that control it remain largely unknown. We find that in the Drosophila CNS branches develop through a process of excessive growth followed by pruning. In vivo high-resolution live imaging of developing brains as well as loss and gain of function experiments show that activation of Epidermal Growth Factor Receptor (EGFR) is necessary for branch dynamics and the final branching pattern. Live imaging also reveals that intrinsic asymmetry in EGFR localization regulates the balance between dynamic and static filopodia. Elimination of signaling asymmetry by either loss or gain of EGFR function results in reduced dynamics leading to excessive branch formation. In summary, we propose that the dynamic process of axon branch development is mediated by differential local distribution of signaling receptors. DOI: http://dx.doi.org/10.7554/eLife.01699.001 PMID:24755286

Incorporating virtual reality graphics with brain imaging for assessment of sport-related concussions.

PubMed

Slobounov, Semyon; Sebastianelli, Wayne; Newell, Karl M

2011-01-01

There is a growing concern that traditional neuropsychological (NP) testing tools are not sensitive to detecting residual brain dysfunctions in subjects suffering from mild traumatic brain injuries (MTBI). Moreover, most MTBI patients are asymptomatic based on anatomical brain imaging (CT, MRI), neurological examinations and patients' subjective reports within 10 days post-injury. Our ongoing research has documented that residual balance and visual-kinesthetic dysfunctions along with its underlying alterations of neural substrates may be detected in "asymptomatic subjects" by means of Virtual Reality (VR) graphics incorporated with brain imaging (EEG) techniques.

Hollow Polypropylene Yarns as a Biomimetic Brain Phantom for the Validation of High-Definition Fiber Tractography Imaging.

PubMed

Guise, Catarina; Fernandes, Margarida M; Nóbrega, João M; Pathak, Sudhir; Schneider, Walter; Fangueiro, Raul

2016-11-09

Current brain imaging methods largely fail to provide detailed information about the location and severity of axonal injuries and do not anticipate recovery of the patients with traumatic brain injury. High-definition fiber tractography appears as a novel imaging modality based on water motion in the brain that allows for direct visualization and quantification of the degree of axons damage, thus predicting the functional deficits due to traumatic axonal injury and loss of cortical projections. This neuroimaging modality still faces major challenges because it lacks a "gold standard" for the technique validation and respective quality control. The present work aims to study the potential of hollow polypropylene yarns to mimic human white matter axons and construct a brain phantom for the calibration and validation of brain diffusion techniques based on magnetic resonance imaging, including high-definition fiber tractography imaging. Hollow multifilament polypropylene yarns were produced by melt-spinning process and characterized in terms of their physicochemical properties. Scanning electronic microscopy images of the filaments cross section has shown an inner diameter of approximately 12 μm, confirming their appropriateness to mimic the brain axons. The chemical purity of polypropylene yarns as well as the interaction between the water and the filament surface, important properties for predicting water behavior and diffusion inside the yarns, were also evaluated. Restricted and hindered water diffusion was confirmed by fluorescence microscopy. Finally, the yarns were magnetic resonance imaging scanned and analyzed using high-definition fiber tractography, revealing an excellent choice of these hollow polypropylene structures for simulation of the white matter brain axons and their suitability for constructing an accurate brain phantom.

Brain imaging in methamphetamine-treated mice using a nitroxide contrast agent for EPR imaging of the redox status and a gadolinium contrast agent for MRI observation of blood-brain barrier function.

PubMed

Emoto, M C; Yamato, M; Sato-Akaba, H; Yamada, K; Matsuoka, Y; Fujii, H G

2015-01-01

Methamphetamine (METH)-induced neurotoxicity is associated with mitochondrial dysfunction and enhanced oxidative stress. The aims of the present study conducted in the mouse brain repetitively treated with METH were to (1) examine the redox status using the redox-sensitive imaging probe 3-methoxycarbonyl-2,2,5,5-tetramethylpiperidine-1-oxyl (MCP) and (2) non-invasively visualize the brain redox status with electron paramagnetic resonance (EPR) imaging. The rate of reduction of MCP was measured from a series of temporal EPR images of mouse heads, and this rate was used to construct a two-dimensional map of rate constants called a "redox map." The obtained redox map clearly illustrated the change in redox balance in the METH-treated mouse brain that is a known result of oxidative damage. Biochemical assays also showed that the level of thiobarbituric acid-reactive substance, an index of lipid peroxidation, was increased in mouse brains by METH. The enhanced reduction in MCP observed in mouse brains was remarkably suppressed by treatment with the dopamine synthase inhibitor, α-methyl-p-tyrosine, suggesting that enhancement of the reduction reaction of MCP resulted from enzymatic reduction in the mitochondrial respiratory chain. Furthermore, magnetic resonance imaging (MRI) of METH-treated mice using a blood-brain barrier (BBB)-impermeable paramagnetic contrast agent revealed BBB dysfunction after treatment with METH for 7 days. MRI also indicated that the impaired BBB recovered after withdrawal of METH. EPR imaging and MRI are useful tools not only for following changes in the redox status and BBB dysfunction in mouse brains repeatedly administered METH, but also for tracing the drug effect after withdrawal of METH.

Brain Lesions

MedlinePlus

... seen on a brain-imaging test, such as magnetic resonance imaging (MRI) or computerized tomography (CT). On ... A cohort study. PLOS One. 2013;8:e71467. Magnetic resonance imaging (MRI). National Multiple Sclerosis Society. http:// ...

Emerging Directions in Emotional Episodic Memory.

PubMed

Dolcos, Florin; Katsumi, Yuta; Weymar, Mathias; Moore, Matthew; Tsukiura, Takashi; Dolcos, Sanda

2017-01-01

Building upon the existing literature on emotional memory, the present review examines emerging evidence from brain imaging investigations regarding four research directions: (1) Social Emotional Memory , (2) The Role of Emotion Regulation in the Impact of Emotion on Memory , (3) The Impact of Emotion on Associative or Relational Memory , and (4) The Role of Individual Differences in Emotional Memory . Across these four domains, available evidence demonstrates that emotion- and memory-related medial temporal lobe brain regions (amygdala and hippocampus, respectively), together with prefrontal cortical regions, play a pivotal role during both encoding and retrieval of emotional episodic memories. This evidence sheds light on the neural mechanisms of emotional memories in healthy functioning, and has important implications for understanding clinical conditions that are associated with negative affective biases in encoding and retrieving emotional memories.

Emerging Directions in Emotional Episodic Memory

PubMed Central

Dolcos, Florin; Katsumi, Yuta; Weymar, Mathias; Moore, Matthew; Tsukiura, Takashi; Dolcos, Sanda

2017-01-01

Building upon the existing literature on emotional memory, the present review examines emerging evidence from brain imaging investigations regarding four research directions: (1) Social Emotional Memory, (2) The Role of Emotion Regulation in the Impact of Emotion on Memory, (3) The Impact of Emotion on Associative or Relational Memory, and (4) The Role of Individual Differences in Emotional Memory. Across these four domains, available evidence demonstrates that emotion- and memory-related medial temporal lobe brain regions (amygdala and hippocampus, respectively), together with prefrontal cortical regions, play a pivotal role during both encoding and retrieval of emotional episodic memories. This evidence sheds light on the neural mechanisms of emotional memories in healthy functioning, and has important implications for understanding clinical conditions that are associated with negative affective biases in encoding and retrieving emotional memories. PMID:29255432

Individual differences in nucleus accumbens activity to food and sexual images predict weight gain and sexual behavior.

PubMed

Demos, Kathryn E; Heatherton, Todd F; Kelley, William M

2012-04-18

Failures of self-regulation are common, leading to many of the most vexing problems facing contemporary society, from overeating and obesity to impulsive sexual behavior and STDs. One reason that people may be prone to engaging in unwanted behaviors is heightened sensitivity to cues related to those behaviors; people may overeat because of hyperresponsiveness to food cues, addicts may relapse following exposure to their drug of choice, and some people might engage in impulsive sexual activity because they are easily aroused by erotic stimuli. An open question is the extent to which individual differences in neural cue reactivity relate to actual behavioral outcomes. Here we show that individual differences in human reward-related brain activity in the nucleus accumbens to food and sexual images predict subsequent weight gain and sexual activity 6 months later. These findings suggest that heightened reward responsivity in the brain to food and sexual cues is associated with indulgence in overeating and sexual activity, respectively, and provide evidence for a common neural mechanism associated with appetitive behaviors.

Neuroimaging Feature Terminology: A Controlled Terminology for the Annotation of Brain Imaging Features

PubMed Central

Iyappan, Anandhi; Younesi, Erfan; Redolfi, Alberto; Vrooman, Henri; Khanna, Shashank; Frisoni, Giovanni B.; Hofmann-Apitius, Martin

2017-01-01

Ontologies and terminologies are used for interoperability of knowledge and data in a standard manner among interdisciplinary research groups. Existing imaging ontologies capture general aspects of the imaging domain as a whole such as methodological concepts or calibrations of imaging instruments. However, none of the existing ontologies covers the diagnostic features measured by imaging technologies in the context of neurodegenerative diseases. Therefore, the Neuro-Imaging Feature Terminology (NIFT) was developed to organize the knowledge domain of measured brain features in association with neurodegenerative diseases by imaging technologies. The purpose is to identify quantitative imaging biomarkers that can be extracted from multi-modal brain imaging data. This terminology attempts to cover measured features and parameters in brain scans relevant to disease progression. In this paper, we demonstrate the systematic retrieval of measured indices from literature and how the extracted knowledge can be further used for disease modeling that integrates neuroimaging features with molecular processes. PMID:28731430

Clinical applications of modern imaging technology: stereo image formation and location of brain cancer

NASA Astrophysics Data System (ADS)

Wang, Dezong; Wang, Jinxiang

1994-05-01

It is very important to locate the tumor for a patient, who has cancer in his brain. If he only gets X-CT or MRI pictures, the doctor does not know the size, shape location of the tumor and the relation between the tumor and other organs. This paper presents the formation of stereo images of cancer. On the basis of color code and color 3D reconstruction. The stereo images of tumor, brain and encephalic truncus are formed. The stereo image of cancer can be round on X, Y, Z-coordinates to show the shape from different directions. In order to show the location of tumor, stereo image of tumor and encephalic truncus are provided on different angles. The cross section pictures are also offered to indicate the relation of brain, tumor and encephalic truncus on cross sections. In this paper the calculating of areas, volume and the space between cancer and the side of the brain are also described.

Pulsed laser diode photoacoustic tomography (PLD-PAT) system for fast in vivo imaging of small animal brain

NASA Astrophysics Data System (ADS)

Upputuri, Paul Kumar; Kalva, Sandeep Kumar; Moothanchery, Mohesh; Pramanik, Manojit

2017-03-01

In recent years, high-repetition rate pulsed laser diode (PLD) was used as an alternative to the Nd:YAG lasers for photoacoustic tomography (PAT). The use of PLD makes the overall PAT system, a low-cost, portable, and high frame rate imaging tool for preclinical applications. In this work, we will present a portable in vivo pulsed laser diode based photoacoustic tomography (PLD-PAT) system. The PLD is integrated inside a circular scanning geometry. The PLD can provide near-infrared ( 803 nm) pulses with pulse duration 136 ns, and pulse energy 1.4 mJ / pulse at 7 kHz repetition rate. The system will be demonstrated for in vivo fast imaging of small animal brain. To enhance the contrast of brain imaging, experiments will be carried out using contrast agents which have strong absorption around laser excitation wavelength. This low-cost, portable small animal brain imaging system could be very useful for brain tumor imaging and therapy.

CT Perfusion in Acute Stroke: "Black Holes" on Time-to-Peak Image Maps Indicate Unsalvageable Brain.

PubMed

Meagher, Ruairi; Shankar, Jai Jai Shiva

2016-11-01

CT perfusion is becoming important in acute stroke imaging to determine optimal patient-management strategies. The purpose of this study was to examine the predictive value of time-to-peak image maps and, specifically, a phenomenon coined a "black hole" for assessing infarcted brain tissue at the time of scan. Acute stroke patients were screened for the presence of black holes and their follow-up imaging (noncontrast CT or MR) was reviewed to assess for infarcted brain tissue. Of the 23 patients with signs of acute ischemia on CT perfusion, all had black holes. The black holes corresponded with areas of infarcted brain on follow-up imaging (specificity 100%). Black holes demonstrated significantly lower cerebral blood volumes (P < .001) and cerebral blood flow (P < .001) compared to immediately adjacent tissue. Black holes on time-to-peak image maps represent areas of unsalvageable brain. Copyright © 2016 by the American Society of Neuroimaging.

Optical Coherence Tomography for Brain Imaging and Developmental Biology

PubMed Central

Men, Jing; Huang, Yongyang; Solanki, Jitendra; Zeng, Xianxu; Alex, Aneesh; Jerwick, Jason; Zhang, Zhan; Tanzi, Rudolph E.; Li, Airong; Zhou, Chao

2016-01-01

Optical coherence tomography (OCT) is a promising research tool for brain imaging and developmental biology. Serving as a three-dimensional optical biopsy technique, OCT provides volumetric reconstruction of brain tissues and embryonic structures with micrometer resolution and video rate imaging speed. Functional OCT enables label-free monitoring of hemodynamic and metabolic changes in the brain in vitro and in vivo in animal models. Due to its non-invasiveness nature, OCT enables longitudinal imaging of developing specimens in vivo without potential damage from surgical operation, tissue fixation and processing, and staining with exogenous contrast agents. In this paper, various OCT applications in brain imaging and developmental biology are reviewed, with a particular focus on imaging heart development. In addition, we report findings on the effects of a circadian gene (Clock) and high-fat-diet on heart development in Drosophila melanogaster. These findings contribute to our understanding of the fundamental mechanisms connecting circadian genes and obesity to heart development and cardiac diseases. PMID:27721647

MR image denoising method for brain surface 3D modeling

NASA Astrophysics Data System (ADS)

Zhao, De-xin; Liu, Peng-jie; Zhang, De-gan

2014-11-01

Three-dimensional (3D) modeling of medical images is a critical part of surgical simulation. In this paper, we focus on the magnetic resonance (MR) images denoising for brain modeling reconstruction, and exploit a practical solution. We attempt to remove the noise existing in the MR imaging signal and preserve the image characteristics. A wavelet-based adaptive curve shrinkage function is presented in spherical coordinates system. The comparative experiments show that the denoising method can preserve better image details and enhance the coefficients of contours. Using these denoised images, the brain 3D visualization is given through surface triangle mesh model, which demonstrates the effectiveness of the proposed method.

Revised Recommendations of the Consortium of MS Centers Task Force for a Standardized MRI Protocol and Clinical Guidelines for the Diagnosis and Follow-Up of Multiple Sclerosis

PubMed Central

Traboulsee, A.; Simon, J.H.; Stone, L.; Fisher, E.; Jones, D.E.; Malhotra, A.; Newsome, S.D.; Oh, J.; Reich, D.S.; Richert, N.; Rammohan, K.; Khan, O.; Radue, E.-W.; Ford, C.; Halper, J.; Li, D.

2016-01-01

SUMMARY An international group of neurologists and radiologists developed revised guidelines for standardized brain and spinal cord MR imaging for the diagnosis and follow-up of MS. A brain MR imaging with gadolinium is recommended for the diagnosis of MS. A spinal cord MR imaging is recommended if the brain MR imaging is nondiagnostic or if the presenting symptoms are at the level of the spinal cord. A follow-up brain MR imaging with gadolinium is recommended to demonstrate dissemination in time and ongoing clinically silent disease activity while on treatment, to evaluate unexpected clinical worsening, to re-assess the original diagnosis, and as a new baseline before starting or modifying therapy. A routine brain MR imaging should be considered every 6 months to 2 years for all patients with relapsing MS. The brain MR imaging protocol includes 3D T1-weighted, 3D T2-FLAIR, 3D T2-weighted, post-single-dose gadolinium-enhanced T1-weighted sequences, and a DWI sequence. The progressive multifocal leukoencephalopathy surveillance protocol includes FLAIR and DWI sequences only. The spinal cord MR imaging protocol includes sagittal T1-weighted and proton attenuation, STIR or phase-sensitive inversion recovery, axial T2- or T2*-weighted imaging through suspicious lesions, and, in some cases, postcontrast gadolinium-enhanced T1-weighted imaging. The clinical question being addressed should be provided in the requisition for the MR imaging. The radiology report should be descriptive, with results referenced to previous studies. MR imaging studies should be permanently retained and available. The current revision incorporates new clinical information and imaging techniques that have become more available. PMID:26564433

Neurons on the couch.

PubMed

Marić, Nadja P; Jašović-Gašić, Miroslava

2010-12-01

A hundred years after psychoanalysis was introduced, neuroscience has taken a giant step forward. It seems nowadays that effects of psychotherapy could be monitored and measured by state-of-the art brain imaging techniques. Today, the psychotherapy is considered as a strategic and purposeful environmental influence intended to enhance learning. Since gene expression is regulated by environmental influences throughout life and these processes create brain architecture and influence the strength of synaptic connections, psychotherapy (as a kind of learning) should be explored in the context of aforementioned paradigm. In other words, when placing a client on the couch, therapist actually placed client's neuronal network; while listening and talking, expressing and analyzing, experiencing transference and counter transference, therapist tends to stabilize synaptic connections and influence dendritic growth by regulating gene-transcriptional activity. Therefore, we strongly believe that, in the near future, an increasing knowledge on cellular and molecular interactions and mechanisms of action of different psycho- and pharmaco-therapeutic procedures will enable us to tailor a sophisticated therapeutic approach toward a person, by combining major therapeutic strategies in psychiatry on the basis of rational goals and evidence-based therapeutic expectations.

Application of optical coherence tomography based microangiography for cerebral imaging

NASA Astrophysics Data System (ADS)

Baran, Utku; Wang, Ruikang K.

2016-03-01

Requirements of in vivo rodent brain imaging are hard to satisfy using traditional technologies such as magnetic resonance imaging and two-photon microscopy. Optical coherence tomography (OCT) is an emerging tool that can easily reach at high speeds and provide high resolution volumetric images with a relatively large field of view for rodent brain imaging. Here, we provide the overview of recent developments of functional OCT based imaging techniques for neuroscience applications on rodents. Moreover, a summary of OCT-based microangiography (OMAG) studies for stroke and traumatic brain injury cases on rodents are provided.

Accurate and robust brain image alignment using boundary-based registration.

PubMed

Greve, Douglas N; Fischl, Bruce

2009-10-15

The fine spatial scales of the structures in the human brain represent an enormous challenge to the successful integration of information from different images for both within- and between-subject analysis. While many algorithms to register image pairs from the same subject exist, visual inspection shows that their accuracy and robustness to be suspect, particularly when there are strong intensity gradients and/or only part of the brain is imaged. This paper introduces a new algorithm called Boundary-Based Registration, or BBR. The novelty of BBR is that it treats the two images very differently. The reference image must be of sufficient resolution and quality to extract surfaces that separate tissue types. The input image is then aligned to the reference by maximizing the intensity gradient across tissue boundaries. Several lower quality images can be aligned through their alignment with the reference. Visual inspection and fMRI results show that BBR is more accurate than correlation ratio or normalized mutual information and is considerably more robust to even strong intensity inhomogeneities. BBR also excels at aligning partial-brain images to whole-brain images, a domain in which existing registration algorithms frequently fail. Even in the limit of registering a single slice, we show the BBR results to be robust and accurate.

MR Imaging Applications in Mild Traumatic Brain Injury: An Imaging Update

PubMed Central

Wu, Xin; Kirov, Ivan I.; Gonen, Oded; Ge, Yulin; Grossman, Robert I.

2016-01-01

Mild traumatic brain injury (mTBI), also commonly referred to as concussion, affects millions of Americans annually. Although computed tomography is the first-line imaging technique for all traumatic brain injury, it is incapable of providing long-term prognostic information in mTBI. In the past decade, the amount of research related to magnetic resonance (MR) imaging of mTBI has grown exponentially, partly due to development of novel analytical methods, which are applied to a variety of MR techniques. Here, evidence of subtle brain changes in mTBI as revealed by these techniques, which are not demonstrable by conventional imaging, will be reviewed. These changes can be considered in three main categories of brain structure, function, and metabolism. Macrostructural and microstructural changes have been revealed with three-dimensional MR imaging, susceptibility-weighted imaging, diffusion-weighted imaging, and higher order diffusion imaging. Functional abnormalities have been described with both task-mediated and resting-state blood oxygen level–dependent functional MR imaging. Metabolic changes suggesting neuronal injury have been demonstrated with MR spectroscopy. These findings improve understanding of the true impact of mTBI and its pathogenesis. Further investigation may eventually lead to improved diagnosis, prognosis, and management of this common and costly condition. © RSNA, 2016 PMID:27183405

Quantitative assessment of Cerenkov luminescence for radioguided brain tumor resection surgery

NASA Astrophysics Data System (ADS)

Klein, Justin S.; Mitchell, Gregory S.; Cherry, Simon R.

2017-05-01

Cerenkov luminescence imaging (CLI) is a developing imaging modality that detects radiolabeled molecules via visible light emitted during the radioactive decay process. We used a Monte Carlo based computer simulation to quantitatively investigate CLI compared to direct detection of the ionizing radiation itself as an intraoperative imaging tool for assessment of brain tumor margins. Our brain tumor model consisted of a 1 mm spherical tumor remnant embedded up to 5 mm in depth below the surface of normal brain tissue. Tumor to background contrast ranging from 2:1 to 10:1 were considered. We quantified all decay signals (e±, gamma photon, Cerenkov photons) reaching the brain volume surface. CLI proved to be the most sensitive method for detecting the tumor volume in both imaging and non-imaging strategies as assessed by contrast-to-noise ratio and by receiver operating characteristic output of a channelized Hotelling observer.

Brain abnormalities in antisocial individuals: implications for the law.

PubMed

Yang, Yaling; Glenn, Andrea L; Raine, Adrian

2008-01-01

With the increasing popularity in the use of brain imaging on antisocial individuals, an increasing number of brain imaging studies have revealed structural and functional impairments in antisocial, psychopathic, and violent individuals. This review summarizes key findings from brain imaging studies on antisocial/aggressive behavior. Key regions commonly found to be impaired in antisocial populations include the prefrontal cortex (particularly orbitofrontal and dorsolateral prefrontal cortex), superior temporal gyrus, amygdala-hippocampal complex, and anterior cingulate cortex. Key functions of these regions are reviewed to provide a better understanding on how deficits in these regions may predispose to antisocial behavior. Objections to the use of imaging findings in a legal context are outlined, and alternative perspectives raised. It is argued that brain dysfunction is a risk factor for antisocial behavior and that it is likely that imaging will play an increasing (albeit limited) role in legal decision-making. (c) 2008 John Wiley & Sons, Ltd.

Effects of leptin deficiency and replacement on cerebellar response to food-related cues

PubMed Central

Berman, Steven M.; Paz-Filho, Gilberto; Wong, Ma-Li; Kohno, Milky; Licinio, Julio; London, Edythe D.

2013-01-01

Leptin affects eating behavior partly by altering the response of the brain to food-related stimuli. Effects of leptin on brain structure have been observed in the cerebellum, where leptin receptors are most densely expressed, but the function of leptin in the cerebellum remains unclear. We performed a nonrandomized, prospective interventional study of three adults with genetically-mediated leptin deficiency. FMRI was recorded three times each year during years 5 and 6 of leptin replacement treatment. Session one of each year occurred after 10 months of continuous daily replacement, session two after 33–37 days without leptin, and session three 14–23 days after daily replacement was restored. Statistical parametric mapping software (SPM5) was employed to contrast the fMRI blood-oxygenation level-dependent response to images of high-calorie foods versus images of brick walls. Covariate analyses quantified the effects of the duration of leptin replacement and concomitant changes in body mass on the cerebral responses. Longer duration of replacement was associated with more activation by food images in a ventral portion of the posterior lobe of the cerebellum, while simultaneous decreases in body mass were associated with decreased activation in a more dorsal portion of the same lobe. These findings indicate that leptin replacement reversibly alters neural function within the posterior cerebellum, and modulates plasticity-dependent brain physiology in response to food cues. The results suggest an underexplored role for the posterior cerebellum in the regulation of leptin-mediated processes related to food intake. PMID:22576622

Automatic segmentation of multimodal brain tumor images based on classification of super-voxels.

PubMed

Kadkhodaei, M; Samavi, S; Karimi, N; Mohaghegh, H; Soroushmehr, S M R; Ward, K; All, A; Najarian, K

2016-08-01

Despite the rapid growth in brain tumor segmentation approaches, there are still many challenges in this field. Automatic segmentation of brain images has a critical role in decreasing the burden of manual labeling and increasing robustness of brain tumor diagnosis. We consider segmentation of glioma tumors, which have a wide variation in size, shape and appearance properties. In this paper images are enhanced and normalized to same scale in a preprocessing step. The enhanced images are then segmented based on their intensities using 3D super-voxels. Usually in images a tumor region can be regarded as a salient object. Inspired by this observation, we propose a new feature which uses a saliency detection algorithm. An edge-aware filtering technique is employed to align edges of the original image to the saliency map which enhances the boundaries of the tumor. Then, for classification of tumors in brain images, a set of robust texture features are extracted from super-voxels. Experimental results indicate that our proposed method outperforms a comparable state-of-the-art algorithm in term of dice score.

Deformable templates guided discriminative models for robust 3D brain MRI segmentation.

PubMed

Liu, Cheng-Yi; Iglesias, Juan Eugenio; Tu, Zhuowen

2013-10-01

Automatically segmenting anatomical structures from 3D brain MRI images is an important task in neuroimaging. One major challenge is to design and learn effective image models accounting for the large variability in anatomy and data acquisition protocols. A deformable template is a type of generative model that attempts to explicitly match an input image with a template (atlas), and thus, they are robust against global intensity changes. On the other hand, discriminative models combine local image features to capture complex image patterns. In this paper, we propose a robust brain image segmentation algorithm that fuses together deformable templates and informative features. It takes advantage of the adaptation capability of the generative model and the classification power of the discriminative models. The proposed algorithm achieves both robustness and efficiency, and can be used to segment brain MRI images with large anatomical variations. We perform an extensive experimental study on four datasets of T1-weighted brain MRI data from different sources (1,082 MRI scans in total) and observe consistent improvement over the state-of-the-art systems.

Connectome imaging for mapping human brain pathways

PubMed Central

Shi, Y; Toga, A W

2017-01-01

With the fast advance of connectome imaging techniques, we have the opportunity of mapping the human brain pathways in vivo at unprecedented resolution. In this article we review the current developments of diffusion magnetic resonance imaging (MRI) for the reconstruction of anatomical pathways in connectome studies. We first introduce the background of diffusion MRI with an emphasis on the technical advances and challenges in state-of-the-art multi-shell acquisition schemes used in the Human Connectome Project. Characterization of the microstructural environment in the human brain is discussed from the tensor model to the general fiber orientation distribution (FOD) models that can resolve crossing fibers in each voxel of the image. Using FOD-based tractography, we describe novel methods for fiber bundle reconstruction and graph-based connectivity analysis. Building upon these novel developments, there have already been successful applications of connectome imaging techniques in reconstructing challenging brain pathways. Examples including retinofugal and brainstem pathways will be reviewed. Finally, we discuss future directions in connectome imaging and its interaction with other aspects of brain imaging research. PMID:28461700

Phosphatidylserine-Targeted Nanotheranostics for Brain Tumor Imaging and Therapeutic Potential

PubMed Central

Wang, Lulu; Habib, Amyn A.; Mintz, Akiva; Li, King C.; Zhao, Dawen

2017-01-01

Phosphatidylserine (PS), the most abundant anionic phospholipid in cell membrane, is strictly confined to the inner leaflet in normal cells. However, this PS asymmetry is found disruptive in many tumor vascular endothelial cells. We discuss the underlying mechanisms for PS asymmetry maintenance in normal cells and its loss in tumor cells. The specificity of PS exposure in tumor vasculature but not normal blood vessels may establish it a useful biomarker for cancer molecular imaging. Indeed, utilizing PS-targeting antibodies, multiple imaging probes have been developed and multimodal imaging data have shown their high tumor-selective targeting in various cancers. There is a critical need for improved diagnosis and therapy for brain tumors. We have recently established PS-targeted nanoplatforms, aiming to enhance delivery of imaging contrast agents across the blood–brain barrier to facilitate imaging of brain tumors. Advantages of using the nanodelivery system, in particular, lipid-based nanocarriers, are discussed here. We also describe our recent research interest in developing PS-targeted nanotheranostics for potential image-guided drug delivery to treat brain tumors. PMID:28654387

Phosphatidylserine-Targeted Nanotheranostics for Brain Tumor Imaging and Therapeutic Potential.

PubMed

Wang, Lulu; Habib, Amyn A; Mintz, Akiva; Li, King C; Zhao, Dawen

2017-01-01

Phosphatidylserine (PS), the most abundant anionic phospholipid in cell membrane, is strictly confined to the inner leaflet in normal cells. However, this PS asymmetry is found disruptive in many tumor vascular endothelial cells. We discuss the underlying mechanisms for PS asymmetry maintenance in normal cells and its loss in tumor cells. The specificity of PS exposure in tumor vasculature but not normal blood vessels may establish it a useful biomarker for cancer molecular imaging. Indeed, utilizing PS-targeting antibodies, multiple imaging probes have been developed and multimodal imaging data have shown their high tumor-selective targeting in various cancers. There is a critical need for improved diagnosis and therapy for brain tumors. We have recently established PS-targeted nanoplatforms, aiming to enhance delivery of imaging contrast agents across the blood-brain barrier to facilitate imaging of brain tumors. Advantages of using the nanodelivery system, in particular, lipid-based nanocarriers, are discussed here. We also describe our recent research interest in developing PS-targeted nanotheranostics for potential image-guided drug delivery to treat brain tumors.

Transmission in near-infrared optical windows for deep brain imaging.

PubMed

Shi, Lingyan; Sordillo, Laura A; Rodríguez-Contreras, Adrián; Alfano, Robert

2016-01-01

Near-infrared (NIR) radiation has been employed using one- and two-photon excitation of fluorescence imaging at wavelengths 650-950 nm (optical window I) for deep brain imaging; however, longer wavelengths in NIR have been overlooked due to a lack of suitable NIR-low band gap semiconductor imaging detectors and/or femtosecond laser sources. This research introduces three new optical windows in NIR and demonstrates their potential for deep brain tissue imaging. The transmittances are measured in rat brain tissue in the second (II, 1,100-1,350 nm), third (III, 1,600-1,870 nm), and fourth (IV, centered at 2,200 nm) NIR optical tissue windows. The relationship between transmission and tissue thickness is measured and compared with the theory. Due to a reduction in scattering and minimal absorption, window III is shown to be the best for deep brain imaging, and windows II and IV show similar but better potential for deep imaging than window I. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Rough Sets and Stomped Normal Distribution for Simultaneous Segmentation and Bias Field Correction in Brain MR Images.

PubMed

Banerjee, Abhirup; Maji, Pradipta

2015-12-01

The segmentation of brain MR images into different tissue classes is an important task for automatic image analysis technique, particularly due to the presence of intensity inhomogeneity artifact in MR images. In this regard, this paper presents a novel approach for simultaneous segmentation and bias field correction in brain MR images. It integrates judiciously the concept of rough sets and the merit of a novel probability distribution, called stomped normal (SN) distribution. The intensity distribution of a tissue class is represented by SN distribution, where each tissue class consists of a crisp lower approximation and a probabilistic boundary region. The intensity distribution of brain MR image is modeled as a mixture of finite number of SN distributions and one uniform distribution. The proposed method incorporates both the expectation-maximization and hidden Markov random field frameworks to provide an accurate and robust segmentation. The performance of the proposed approach, along with a comparison with related methods, is demonstrated on a set of synthetic and real brain MR images for different bias fields and noise levels.

Expression of thyroid hormone transporters and deiodinases at the brain barriers in the embryonic chicken: Insights into the regulation of thyroid hormone availability during neurodevelopment.

PubMed

Van Herck, Stijn L J; Delbaere, Joke; Bourgeois, Nele M A; McAllan, Bronwyn M; Richardson, Samantha J; Darras, Veerle M

2015-04-01

Thyroid hormones (THs) are key regulators in the development of the vertebrate brain. Therefore, TH access to the developing brain needs to be strictly regulated. The brain barriers separate the central nervous system from the rest of the body and impose specific transport mechanisms on the exchange of molecules between the general circulation and the nervous system. As such they form ideal structures for regulating TH exchange between the blood and the brain. To investigate the mechanism by which the developing brain regulates TH availability, we investigated the ontogenetic expression profiles of TH transporters, deiodinases and the TH distributor protein transthyretin (TTR) at the brain barriers during embryonic and early postnatal development using the chicken as a model. In situ hybridisation revealed expression of the TH transporters monocarboxylate transporter 8 (MCT8) and 10 (MCT10), organic anion transporting polypeptide 1C1 (OATP1C1) and L-type amino acid transporter 1 (LAT1) and the inactivating type 3 deiodinase (D3) in the choroid plexus which forms the blood-cerebrospinal fluid barrier. This was confirmed by quantitative PCR which additionally indicated strongly increasing expression of TTR as well as detectable expression of the activating type 2 deiodinase (D2) and the (in)activating type 1 deiodinase (D1). In the brain capillaries forming the blood-brain barrier in situ hybridisation showed exclusive expression of LAT1 and D2. The combined presence of LAT1 and D2 in brain capillaries suggests that the blood-brain barrier forms the main route for receptor-active T3 uptake into the embryonic chicken brain. Expression of multiple transporters, deiodinases and TTR in the choroid plexus indicates that the blood-cerebrospinal fluid barrier is also important in regulating early TH availability. The impact of these barrier systems can be deduced from the clear difference in T3 and T4 levels as well as the T3/T4 ratio between the developing brain and the general circulation. We conclude that the tight regulation of TH exchange at the brain barriers from early embryonic stages is one of the factors needed to allow the brain to develop within a relative microenvironment. Copyright © 2015 Elsevier Inc. All rights reserved.

Impaired Recognition and Regulation of Disgust Is Associated with Distinct but Partially Overlapping Patterns of Decreased Gray Matter Volume in the Ventroanterior Insula.

PubMed

Woolley, Josh D; Strobl, Eric V; Sturm, Virginia E; Shany-Ur, Tal; Poorzand, Pardis; Grossman, Scott; Nguyen, Lauren; Eckart, Janet A; Levenson, Robert W; Seeley, William W; Miller, Bruce L; Rankin, Katherine P

2015-10-01

The ventroanterior insula is implicated in the experience, expression, and recognition of disgust; however, whether this brain region is required for recognizing disgust or regulating disgusting behaviors remains unknown. We examined the brain correlates of the presence of disgusting behavior and impaired recognition of disgust using voxel-based morphometry in a sample of 305 patients with heterogeneous patterns of neurodegeneration. Permutation-based analyses were used to determine regions of decreased gray matter volume at a significance level p <= .05 corrected for family-wise error across the whole brain and within the insula. Patients with behavioral variant frontotemporal dementia and semantic variant primary progressive aphasia were most likely to exhibit disgusting behaviors and were, on average, the most impaired at recognizing disgust in others. Imaging analysis revealed that patients who exhibited disgusting behaviors had significantly less gray matter volume bilaterally in the ventral anterior insula. A region of interest analysis restricted to behavioral variant frontotemporal dementia and semantic variant primary progressive aphasia patients alone confirmed this result. Moreover, impaired recognition of disgust was associated with decreased gray matter volume in the bilateral ventroanterior and ventral middle regions of the insula. There was an area of overlap in the bilateral anterior insula where decreased gray matter volume was associated with both the presence of disgusting behavior and impairments in recognizing disgust. These findings suggest that regulating disgusting behaviors and recognizing disgust in others involve two partially overlapping neural systems within the insula. Moreover, the ventral anterior insula is required for both processes. Published by Elsevier Inc.

Impaired recognition and regulation of disgust is associated with distinct but partially overlapping patterns of decreased gray matter volume in the ventroanterior insula

PubMed Central

Woolley, Joshua; Strobl, Eric V; Sturm, Virginia E; Shany-Ur, Tal; Poorzand, Pardis; Grossman, Scott; Nguyen, Lauren; Eckart, Janet A; Levenson, Robert W; Seeley, William W; Miller, Bruce L; Rankin, Katherine P

2015-01-01

Background The ventroanterior insula is implicated in the experience, expression, and recognition of disgust; however, whether this brain region is required for recognizing disgust or regulating disgusting behaviors remains unknown. Methods We examined the brain correlates of the presence of disgusting behavior and impaired recognition of disgust using voxel-based morphometry in a sample of 305 patients with heterogeneous patterns of neurodegeneration. Permutation-based analyses were used to determine regions of decreased grey matter volume at a significance level p<0.05 corrected for family-wise error across the whole brain and within the insula. Results Patients with behavioral variant frontotemporal dementia (bvFTD) and semantic variant primary progressive aphasia (svPPA) were most likely to exhibit disgusting behaviors and were, on average, the most impaired at recognizing disgust in others. Imaging analysis revealed that patients who exhibited disgusting behaviors had significantly less grey matter volume bilaterally in the ventral anterior insula. A region of interest analysis restricted to bvFTD and svPPA patients alone confirmed this result. Moreover, impaired recognition of disgust was associated with decreased grey matter volume in the bilateral ventroanterior and ventral middle regions of the insula. There was an area of overlap in the bilateral anterior insula where decreased grey matter volume was associated with both the presence of disgusting behavior and impairments in recognizing disgust. Conclusion These findings suggest that regulating disgusting behaviors and recognizing disgust in others involve two partially overlapping neural systems within the insula. Moreover, the ventral anterior insula is required for both processes. PMID:25890642

A mass spectrometry imaging approach for investigating how drug-drug interactions influence drug blood-brain barrier permeability.

PubMed

Vallianatou, Theodosia; Strittmatter, Nicole; Nilsson, Anna; Shariatgorji, Mohammadreza; Hamm, Gregory; Pereira, Marcela; Källback, Patrik; Svenningsson, Per; Karlgren, Maria; Goodwin, Richard J A; Andrén, Per E

2018-05-15

There is a high need to develop quantitative imaging methods capable of providing detailed brain localization information of several molecular species simultaneously. In addition, extensive information on the effect of the blood-brain barrier on the penetration, distribution and efficacy of neuroactive compounds is required. Thus, we have developed a mass spectrometry imaging method to visualize and quantify the brain distribution of drugs with varying blood-brain barrier permeability. With this approach, we were able to determine blood-brain barrier transport of different drugs and define the drug distribution in very small brain structures (e.g., choroid plexus) due to the high spatial resolution provided. Simultaneously, we investigated the effect of drug-drug interactions by inhibiting the membrane transporter multidrug resistance 1 protein. We propose that the described approach can serve as a valuable analytical tool during the development of neuroactive drugs, as it can provide physiologically relevant information often neglected by traditional imaging technologies. Copyright © 2018. Published by Elsevier Inc.

Development of a high angular resolution diffusion imaging human brain template.

PubMed

Varentsova, Anna; Zhang, Shengwei; Arfanakis, Konstantinos

2014-05-01

Brain diffusion templates contain rich information about the microstructure of the brain, and are used as references in spatial normalization or in the development of brain atlases. The accuracy of diffusion templates constructed based on the diffusion tensor (DT) model is limited in regions with complex neuronal micro-architecture. High angular resolution diffusion imaging (HARDI) overcomes limitations of the DT model and is capable of resolving intravoxel heterogeneity. However, when HARDI is combined with multiple-shot sequences to minimize image artifacts, the scan time becomes inappropriate for human brain imaging. In this work, an artifact-free HARDI template of the human brain was developed from low angular resolution multiple-shot diffusion data. The resulting HARDI template was produced in ICBM-152 space based on Turboprop diffusion data, was shown to resolve complex neuronal micro-architecture in regions with intravoxel heterogeneity, and contained fiber orientation information consistent with known human brain anatomy. Copyright © 2014 Elsevier Inc. All rights reserved.

Magnetic resonance characteristics and susceptibility weighted imaging of the brain in gadolinium encephalopathy.

PubMed

Samardzic, Dejan; Thamburaj, Krishnamoorthy

2015-01-01

To report the brain imaging features on magnetic resonance imaging (MRI) in inadvertent intrathecal gadolinium administration. A 67-year-old female with gadolinium encephalopathy from inadvertent high dose intrathecal gadolinium administration during an epidural steroid injection was studied with multisequence 3T MRI. T1-weighted imaging shows pseudo-T2 appearance with diffusion of gadolinium into the brain parenchyma, olivary bodies, and membranous labyrinth. Nulling of cerebrospinal fluid (CSF) signal is absent on fluid attenuation recovery (FLAIR). Susceptibility-weighted imaging (SWI) demonstrates features similar to subarachnoid hemorrhage. CT may demonstrate a pseudo-cerebral edema pattern given the high attenuation characteristics of gadolinium. Intrathecal gadolinium demonstrates characteristic imaging features on MRI of the brain and may mimic subarachnoid hemorrhage on susceptibility-weighted imaging. Identifying high dose gadolinium within the CSF spaces on MRI is essential to avoid diagnostic and therapeutic errors. Copyright © 2013 by the American Society of Neuroimaging.

Hierarchical and symmetric infant image registration by robust longitudinal-example-guided correspondence detection

PubMed Central

Wu, Yao; Wu, Guorong; Wang, Li; Munsell, Brent C.; Wang, Qian; Lin, Weili; Feng, Qianjin; Chen, Wufan; Shen, Dinggang

2015-01-01

Purpose: To investigate anatomical differences across individual subjects, or longitudinal changes in early brain development, it is important to perform accurate image registration. However, due to fast brain development and dynamic tissue appearance changes, it is very difficult to align infant brain images acquired from birth to 1-yr-old. Methods: To solve this challenging problem, a novel image registration method is proposed to align two infant brain images, regardless of age at acquisition. The main idea is to utilize the growth trajectories, or spatial-temporal correspondences, learned from a set of longitudinal training images, for guiding the registration of two different time-point images with different image appearances. Specifically, in the training stage, an intrinsic growth trajectory is first estimated for each training subject using the longitudinal images. To register two new infant images with potentially a large age gap, the corresponding images patches between each new image and its respective training images with similar age are identified. Finally, the registration between the two new images can be assisted by the learned growth trajectories from one time point to another time point that have been established in the training stage. To further improve registration accuracy, the proposed method is combined with a hierarchical and symmetric registration framework that can iteratively add new key points in both images to steer the estimation of the deformation between the two infant brain images under registration. Results: To evaluate image registration accuracy, the proposed method is used to align 24 infant subjects at five different time points (2-week-old, 3-month-old, 6-month-old, 9-month-old, and 12-month-old). Compared to the state-of-the-art methods, the proposed method demonstrated superior registration performance. Conclusions: The proposed method addresses the difficulties in the infant brain registration and produces better results compared to existing state-of-the-art registration methods. PMID:26133617

Structural (CT) and functional imaging (PET/SPECT) for the investigation of dolphin bioacoustics

NASA Astrophysics Data System (ADS)

Houser, Dorian S.; Finneran, James J.; Mattrey, Robert; Hoh, Carl; Ridgway, Sam

2003-10-01

A combination of imaging modalities was used to address physiological and anatomical questions relevant to dolphin bioacoustics. Three dolphins (Tursiops truncatus) were scanned with CT to investigate in vivo dolphin cranial anatomy. One dolphin underwent SPECT and PET scanning to investigate blood flow and metabolic activity of the cranial tissues. Air spaces were mostly contiguous and covered the periotic bone and auditory bulla dorsally and medially. Cranial air was compartmentalized by the nasal plug and constriction of the palatopharyngeus muscle. Blood flow, determined from SPECT imaging of 99Tc-bicisate distribution, was greatest in the brain, melon, and posterior fats of the lower jaw. Metabolic activity of tissues, assessed by monitoring the uptake of 18F-deoxyglucose via PET, indicated that melon and jaw fats were metabolically inert compared to the brain. Nasal cavity and sinus air volume that is reduced during diving may be replenished with lung air via the palatopharyngeus and Eustachian tube. Air covering the bulla may protect the ears from outgoing echolocation pulses and contribute to spectral and time of arrival cues. Blood flow to the melon and lower jaw fats may serve to either regulate the temperature of acoustic lipids or act as a site of counter-current heat exchange.

Use of High Resolution 3D Diffusion Tensor Imaging to Study Brain White Matter Development in Live Neonatal Rats

PubMed Central

Cai, Yu; McMurray, Matthew S.; Oguz, Ipek; Yuan, Hong; Styner, Martin A.; Lin, Weili; Johns, Josephine M.; An, Hongyu

2011-01-01

High resolution diffusion tensor imaging (DTI) can provide important information on brain development, yet it is challenging in live neonatal rats due to the small size of neonatal brain and motion-sensitive nature of DTI. Imaging in live neonatal rats has clear advantages over fixed brain scans, as longitudinal and functional studies would be feasible to understand neuro-developmental abnormalities. In this study, we developed imaging strategies that can be used to obtain high resolution 3D DTI images in live neonatal rats at postnatal day 5 (PND5) and PND14, using only 3 h of imaging acquisition time. An optimized 3D DTI pulse sequence and appropriate animal setup to minimize physiological motion artifacts are the keys to successful high resolution 3D DTI imaging. Thus, a 3D rapid acquisition relaxation enhancement DTI sequence with twin navigator echoes was implemented to accelerate imaging acquisition time and minimize motion artifacts. It has been suggested that neonatal mammals possess a unique ability to tolerate mild-to-moderate hypothermia and hypoxia without long term impact. Thus, we additionally utilized this ability to minimize motion artifacts in magnetic resonance images by carefully suppressing the respiratory rate to around 15/min for PND5 and 30/min for PND14 using mild-to-moderate hypothermia. These imaging strategies have been successfully implemented to study how the effect of cocaine exposure in dams might affect brain development in their rat pups. Image quality resulting from this in vivo DTI study was comparable to ex vivo scans. fractional anisotropy values were also similar between the live and fixed brain scans. The capability of acquiring high quality in vivo DTI imaging offers a valuable opportunity to study many neurological disorders in brain development in an authentic living environment. PMID:22013426

Combining Segmented Grey and White Matter Images Improves Voxel-based Morphometry for the Case of Dilated Lateral Ventricles.

PubMed

Goto, Masami; Abe, Osamu; Aoki, Shigeki; Kamagata, Koji; Hori, Masaaki; Miyati, Tosiaki; Gomi, Tsutomu; Takeda, Tohoru

2018-01-18

To evaluate the error in segmented tissue images and to show the usefulness of the brain image in voxel-based morphometry (VBM) using Statistical Parametric Mapping (SPM) 12 software and 3D T 1 -weighted magnetic resonance images (3D-T 1 WIs) processed to simulate idiopathic normal pressure hydrocephalus (iNPH). VBM analysis was performed on sagittal 3D-T 1 WIs obtained in 22 healthy volunteers using a 1.5T MR scanner. Regions of interest for the lateral ventricles of all subjects were carefully outlined on the original 3D-T 1 WIs, and two types of simulated 3D-T 1 WI were also prepared (non-dilated 3D-T 1 WI as normal control and dilated 3D-T 1 WI to simulate iNPH). All simulated 3D-T 1 WIs were segmented into gray matter, white matter, and cerebrospinal fluid images, and normalized to standard space. A brain image was made by adding the gray and white matter images. After smoothing with a 6-mm isotropic Gaussian kernel, group comparisons (dilated vs non-dilated) were made for gray and white matter, cerebrospinal fluid, and brain images using a paired t-test. In evaluation of tissue volume, estimation error was larger using gray or white matter images than using the brain image, and estimation errors in gray and white matter volume change were found for the brain surface. To our knowledge, this is the first VBM study to show the possibility that VBM of gray and white matter volume on the brain surface may be more affected by individual differences in the level of dilation of the lateral ventricles than by individual differences in gray and white matter volumes. We recommend that VBM evaluation in patients with iNPH should be performed using the brain image rather than the gray and white matter images.

Anatomical Brain Magnetic Resonance Imaging of Typically Developing Children and Adolescents

ERIC Educational Resources Information Center

Giedd, Jay N.; Lalonde, Francois M.; Celano, Mark J.; White, Samantha L.; Wallace, Gregory L.; Lee, Nancy R.; Lenroot, Rhoshel K.

2009-01-01

Methodological issues relevant to magnetic resonance imaging studies of brain anatomy are discussed along with the findings on the neuroanatomic changes during childhood and adolescence. The development of the brain is also discussed.

Brain white matter fiber estimation and tractography using Q-ball imaging and Bayesian MODEL.

PubMed

Lu, Meng

2015-01-01

Diffusion tensor imaging allows for the non-invasive in vivo mapping of the brain tractography. However, fiber bundles have complex structures such as fiber crossings, fiber branchings and fibers with large curvatures that tensor imaging (DTI) cannot accurately handle. This study presents a novel brain white matter tractography method using Q-ball imaging as the data source instead of DTI, because QBI can provide accurate information about multiple fiber crossings and branchings in a single voxel using an orientation distribution function (ODF). The presented method also uses graph theory to construct the Bayesian model-based graph, so that the fiber tracking between two voxels can be represented as the shortest path in a graph. Our experiment showed that our new method can accurately handle brain white matter fiber crossings and branchings, and reconstruct brain tractograhpy both in phantom data and real brain data.

Brain structure predicts risk for obesity ☆

PubMed Central

Smucny, Jason; Cornier, Marc-Andre; Eichman, Lindsay C.; Thomas, Elizabeth A.; Bechtell, Jamie L.; Tregellas, Jason R.

2014-01-01

The neurobiology of obesity is poorly understood. Here we report findings of a study designed to examine the differences in brain regional gray matter volume in adults recruited as either Obese Prone or Obese Resistant based on self-identification, body mass index, and personal/family weight history. Magnetic resonance imaging was performed in 28 Obese Prone (14 male, 14 female) and 25 Obese Resistant (13 male, 12 female) healthy adults. Voxel-based morphometry was used to identify gray matter volume differences between groups. Gray matter volume was found to be lower in the insula, medial orbitofrontal cortex and cerebellum in Obese Prone, as compared to Obese Resistant individuals. Adjusting for body fat mass did not impact these results. Insula gray matter volume was negatively correlated with leptin concentration and measures of hunger. These findings suggest that individuals at risk for weight gain have structural differences in brain regions known to be important in energy intake regulation, and that these differences, particularly in the insula, may be related to leptin. PMID:22963736

Background norepinephrine primes astrocytic calcium responses to subsequent norepinephrine stimuli in the cerebral cortex.

PubMed

Nuriya, Mutsuo; Takeuchi, Miyabi; Yasui, Masato

2017-01-29

Norepinephrine (NE) levels in the cerebral cortex are regulated in two modes; the brain state is correlated with slow changes in background NE concentration, while salient stimuli induce transient NE spikes. Previous studies have revealed their diverse neuromodulatory actions; however, the modulatory role of NE on astrocytic activity has been poorly characterized thus far. In this study, we evaluated the modulatory action of background NE on astrocytic responses to subsequent stimuli, using two-photon calcium imaging of acute murine cortical brain slices. We find that subthreshold background NE significantly augments calcium responses to subsequent pulsed NE stimulation in astrocytes. This priming effect is independent of neuronal activity and is mediated by the activation of β-adrenoceptors and the downstream cAMP pathway. These results indicate that background NE primes astrocytes for subsequent calcium responses to NE stimulation and suggest a novel gliomodulatory role for brain state-dependent background NE in the cerebral cortex. Copyright © 2016 Elsevier Inc. All rights reserved.

BAD and KATP channels regulate neuron excitability and epileptiform activity

PubMed Central

Fernández-Agüera, María Carmen; Nathwani, Nidhi; Lahmann, Carolina; Burnham, Veronica L

2018-01-01

Brain metabolism can profoundly influence neuronal excitability. Mice with genetic deletion or alteration of Bad (BCL-2 agonist of cell death) exhibit altered brain-cell fuel metabolism, accompanied by resistance to acutely induced epileptic seizures; this seizure protection is mediated by ATP-sensitive potassium (KATP) channels. Here we investigated the effect of BAD manipulation on KATP channel activity and excitability in acute brain slices. We found that BAD’s influence on neuronal KATP channels was cell-autonomous and directly affected dentate granule neuron (DGN) excitability. To investigate the role of neuronal KATP channels in the anticonvulsant effects of BAD, we imaged calcium during picrotoxin-induced epileptiform activity in entorhinal-hippocampal slices. BAD knockout reduced epileptiform activity, and this effect was lost upon knockout or pharmacological inhibition of KATP channels. Targeted BAD knockout in DGNs alone was sufficient for the antiseizure effect in slices, consistent with a ‘dentate gate’ function that is reinforced by increased KATP channel activity. PMID:29368690

The macrophage marker translocator protein (TSPO) is down-regulated on pro-inflammatory ‘M1’ human macrophages

PubMed Central

Mandhair, Harpreet; Smyth, Erica; Dakin, Stephanie Georgina; Kiriakidis, Serafim; Wells, Lisa; Owen, David; Sabokbar, Afsie; Taylor, Peter

2017-01-01

The translocator protein (TSPO) is a mitochondrial membrane protein, of as yet uncertain function. Its purported high expression on activated macrophages, has lent utility to TSPO targeted molecular imaging in the form of positron emission tomography (PET), as a means to detect and quantify inflammation in vivo. However, existing literature regarding TSPO expression on human activated macrophages is lacking, mostly deriving from brain tissue studies, including studies of brain malignancy, and inflammatory diseases such as multiple sclerosis. Here, we utilized three human sources of monocyte derived macrophages (MDM), from THP-1 monocytes, healthy peripheral blood monocytes and synovial fluid monocytes from patients with rheumatoid arthritis, to undertake a detailed investigation of TSPO expression in activated macrophages. In this work, we demonstrate a consistent down-regulation of TSPO mRNA and protein in macrophages activated to a pro-inflammatory, or ‘M1’ phenotype. Conversely, stimulation of macrophages to an M2 phenotype with IL-4, dexamethasone or TGF-β1 did not alter TSPO expression, regardless of MDM source. The reasons for this are uncertain, but our study findings add some supporting evidence for recent investigations concluding that TSPO may be involved in negative regulation of inflammatory responses in macrophages. PMID:28968465

Digital atlas of fetal brain MRI.

PubMed

Chapman, Teresa; Matesan, Manuela; Weinberger, Ed; Bulas, Dorothy I

2010-02-01

Fetal MRI can be performed in the second and third trimesters. During this time, the fetal brain undergoes profound structural changes. Interpretation of appropriate development might require comparison with normal age-based models. Consultation of a hard-copy atlas is limited by the inability to compare multiple ages simultaneously. To provide images of normal fetal brains from weeks 18 through 37 in a digital format that can be reviewed interactively. This will facilitate recognition of abnormal brain development. T2-W images for the atlas were obtained from fetal MR studies of normal brains scanned for other indications from 2005 to 2007. Images were oriented in standard axial, coronal and sagittal projections, with laterality established by situs. Gestational age was determined by last menstrual period, earliest US measurements and sonogram performed on the same day as the MR. The software program used for viewing the atlas, written in C#, permits linked scrolling and resizing the images. Simultaneous comparison of varying gestational ages is permissible. Fetal brain images across gestational ages 18 to 37 weeks are provided as an interactive digital atlas and are available for free download from http://radiology.seattlechildrens.org/teaching/fetal_brain . Improved interpretation of fetal brain abnormalities can be facilitated by the use of digital atlas cataloging of the normal changes throughout fetal development. Here we provide a description of the atlas and a discussion of normal fetal brain development.

Thyroid hormone and cerebellar development.

PubMed

Anderson, Grant W

2008-01-01

Thyroid hormone (TH) plays a key role in mammalian brain development. The developing brain is sensitive to both TH deficiency and excess. Brain development in the absence of TH results in motor skill deficiencies and reduced intellectual development. These functional abnormalities can be attributed to maldevelopment of specific cell types and regions of the brain including the cerebellum. TH functions at the molecular level by regulating gene transcription. Therefore, understanding how TH regulates cerebellar development requires identification of TH-regulated gene targets and the cells expressing these genes. Additionally, the process of TH-dependent regulation of gene expression is tightly controlled by mechanisms including regulation of TH transport, TH metabolism, toxicologic inhibition of TH signaling, and control of the nuclear TH response apparatus. This review will describe the functional, cellular, and molecular effects of TH deficit in the developing cerebellum and emphasize the most recent findings regarding TH action in this important brain region.

Brain self-regulation in criminal psychopaths.

PubMed

Konicar, Lilian; Veit, Ralf; Eisenbarth, Hedwig; Barth, Beatrix; Tonin, Paolo; Strehl, Ute; Birbaumer, Niels

2015-03-24

Psychopathic individuals are characterized by impaired affective processing, impulsivity, sensation-seeking, poor planning skills and heightened aggressiveness with poor self-regulation. Based on brain self-regulation studies using neurofeedback of Slow Cortical Potentials (SCPs) in disorders associated with a dysregulation of cortical activity thresholds and evidence of deficient cortical functioning in psychopathy, a neurobiological approach seems to be promising in the treatment of psychopathy. The results of our intensive brain regulation intervention demonstrate, that psychopathic offenders are able to gain control of their brain excitability over fronto-central brain areas. After SCP self-regulation training, we observed reduced aggression, impulsivity and behavioral approach tendencies, as well as improvements in behavioral-inhibition and increased cortical sensitivity for error-processing. This study demonstrates improvements on the neurophysiological, behavioral and subjective level in severe psychopathic offenders after SCP-neurofeedback training and could constitute a novel neurobiologically-based treatment for a seemingly change-resistant group of criminal psychopaths.

Adolescent Cannabis Use: What is the Evidence for Functional Brain Alteration?

PubMed

Lorenzetti, Valentina; Alonso-Lana, Silvia; Youssef, George J; Verdejo-Garcia, Antonio; Suo, Chao; Cousijn, Janna; Takagi, Michael; Yücel, Murat; Solowij, Nadia

2016-01-01

Cannabis use typically commences during adolescence, a period during which the brain undergoes profound remodeling in areas that are high in cannabinoid receptors and that mediate cognitive control and emotion regulation. It is therefore important to determine the impact of adolescent cannabis use on brain function. We investigate the impact of adolescent cannabis use on brain function by reviewing the functional magnetic resonance imaging studies in adolescent samples. We systematically reviewed the literature and identified 13 functional neuroimaging studies in adolescent cannabis users (aged 13 to 18 years) performing working memory, inhibition and reward processing tasks. The majority of the studies found altered brain function, but intact behavioural task performance in adolescent cannabis users versus controls. The most consistently reported differences were in the frontal-parietal network, which mediates cognitive control. Heavier use was associated with abnormal brain function in most samples. A minority of studies controlled for the influence of confounders that can also undermine brain function, such as tobacco and alcohol use, psychopathology symptoms, family history of psychiatric disorders and substance use. Emerging evidence shows abnormal frontal-parietal network activity in adolescent cannabis users, particularly in heavier users. Brain functional alterations may reflect a compensatory neural mechanism that enables normal behavioural performance. It remains unclear if cannabis exposure drives these alterations, as substance use and mental health confounders have not been systematically examined. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Semiautomatic Segmentation of Glioma on Mobile Devices.

PubMed

Wu, Ya-Ping; Lin, Yu-Song; Wu, Wei-Guo; Yang, Cong; Gu, Jian-Qin; Bai, Yan; Wang, Mei-Yun

2017-01-01

Brain tumor segmentation is the first and the most critical step in clinical applications of radiomics. However, segmenting brain images by radiologists is labor intense and prone to inter- and intraobserver variability. Stable and reproducible brain image segmentation algorithms are thus important for successful tumor detection in radiomics. In this paper, we propose a supervised brain image segmentation method, especially for magnetic resonance (MR) brain images with glioma. This paper uses hard edge multiplicative intrinsic component optimization to preprocess glioma medical image on the server side, and then, the doctors could supervise the segmentation process on mobile devices in their convenient time. Since the preprocessed images have the same brightness for the same tissue voxels, they have small data size (typically 1/10 of the original image size) and simple structure of 4 types of intensity value. This observation thus allows follow-up steps to be processed on mobile devices with low bandwidth and limited computing performance. Experiments conducted on 1935 brain slices from 129 patients show that more than 30% of the sample can reach 90% similarity; over 60% of the samples can reach 85% similarity, and more than 80% of the sample could reach 75% similarity. The comparisons with other segmentation methods also demonstrate both efficiency and stability of the proposed approach.

Preprocessing film-copied MRI for studying morphological brain changes.

PubMed

Pham, Tuan D; Eisenblätter, Uwe; Baune, Bernhard T; Berger, Klaus

2009-06-15

The magnetic resonance imaging (MRI) of the brain is one of the important data items for studying memory and morbidity in elderly as these images can provide useful information through the quantitative measures of various regions of interest of the brain. As an effort to fully automate the biomedical analysis of the brain that can be combined with the genetic data of the same human population and where the records of the original MRI data are missing, this paper presents two effective methods for addressing this imaging problem. The first method handles the restoration of the film-copied MRI. The second method involves the segmentation of the image data. Experimental results and comparisons with other methods suggest the usefulness of the proposed image analysis methodology.

Neonatal brain resting-state functional connectivity imaging modalities.

PubMed

Mohammadi-Nejad, Ali-Reza; Mahmoudzadeh, Mahdi; Hassanpour, Mahlegha S; Wallois, Fabrice; Muzik, Otto; Papadelis, Christos; Hansen, Anne; Soltanian-Zadeh, Hamid; Gelovani, Juri; Nasiriavanaki, Mohammadreza

2018-06-01

Infancy is the most critical period in human brain development. Studies demonstrate that subtle brain abnormalities during this state of life may greatly affect the developmental processes of the newborn infants. One of the rapidly developing methods for early characterization of abnormal brain development is functional connectivity of the brain at rest. While the majority of resting-state studies have been conducted using magnetic resonance imaging (MRI), there is clear evidence that resting-state functional connectivity (rs-FC) can also be evaluated using other imaging modalities. The aim of this review is to compare the advantages and limitations of different modalities used for the mapping of infants' brain functional connectivity at rest. In addition, we introduce photoacoustic tomography, a novel functional neuroimaging modality, as a complementary modality for functional mapping of infants' brain.

3D surface rendered MR images of the brain and its vasculature.

PubMed

Cline, H E; Lorensen, W E; Souza, S P; Jolesz, F A; Kikinis, R; Gerig, G; Kennedy, T E

1991-01-01

Both time-of-flight and phase contrast magnetic resonance angiography images are combined with stationary tissue images to provide data depicting two contrast relationships yielding intrinsic discrimination of brain matter and flowing blood. A computer analysis is based on nearest neighbor segmentation and the connection between anatomical structures to partition the images into different tissue categories: from which, high resolution brain parenchymal and vascular surfaces are constructed and rendered in juxtaposition, aiding in surgical planning.

Estrogen: a master regulator of bioenergetic systems in the brain and body.

PubMed

Rettberg, Jamaica R; Yao, Jia; Brinton, Roberta Diaz

2014-01-01

Estrogen is a fundamental regulator of the metabolic system of the female brain and body. Within the brain, estrogen regulates glucose transport, aerobic glycolysis, and mitochondrial function to generate ATP. In the body, estrogen protects against adiposity, insulin resistance, and type II diabetes, and regulates energy intake and expenditure. During menopause, decline in circulating estrogen is coincident with decline in brain bioenergetics and shift towards a metabolically compromised phenotype. Compensatory bioenergetic adaptations, or lack thereof, to estrogen loss could determine risk of late-onset Alzheimer's disease. Estrogen coordinates brain and body metabolism, such that peripheral metabolic state can indicate bioenergetic status of the brain. By generating biomarker profiles that encompass peripheral metabolic changes occurring with menopause, individual risk profiles for decreased brain bioenergetics and cognitive decline can be created. Biomarker profiles could identify women at risk while also serving as indicators of efficacy of hormone therapy or other preventative interventions. Copyright © 2013 Elsevier Inc. All rights reserved.

A combination of lipidomics, MS imaging, and PET scan imaging reveals differences in cerebral activity in rat pups according to the lipid quality of infant formulas.

PubMed

Aidoud, Nacima; Delplanque, Bernadette; Baudry, Charlotte; Garcia, Cyrielle; Moyon, Anais; Balasse, Laure; Guillet, Benjamin; Antona, Claudine; Darmaun, Dominique; Fraser, Karl; Ndiaye, Sega; Leruyet, Pascale; Martin, Jean-Charles

2018-03-22

We evaluated the effect of adding docosahexaenoic:arachidonic acids (3:2) (DHA+ARA) to 2 representative commercial infant formulas on brain activity and brain and eye lipids in an artificially reared rat pup model. The formula lipid background was either a pure plant oil blend, or dairy fat with a plant oil blend (1:1). Results at weaning were compared to breast milk-fed pups. Brain functional activity was determined by positron emission tomography scan imaging, the brain and eye fatty acid and lipid composition by targeted and untargeted lipidomics, and DHA brain regional location by mass-spectrometry imaging. The brain functional activity was normalized to controls with DHA+ARA added to the formulas. DHA in both brain and eyes was influenced by formula intake, but more than two-thirds of tissue DHA-glycerolipids remained insensitive to the dietary challenge. However, the DHA lipidome correlated better with brain function than sole DHA content ( r = 0.70 vs. r = 0.48; P < 0.05). Brain DHA regional distribution was more affected by the formula lipid background than the provision of PUFAs. Adding DHA+ARA to formulas alters the DHA content and lipidome of nervous tissue in the neonate, making it closer to dam milk-fed controls, and normalizes brain functional activity.-Aidoud, N., Delplanque, B., Baudry, C., Garcia, C., Moyon, A., Balasse, L., Guillet, B., Antona, C., Darmaun, D., Fraser, K., Ndiaye, S., Leruyet, P., Martin, J.-C. A combination of lipidomics, MS imaging, and PET scan imaging reveals differences in cerebral activity in rat pups according to the lipid quality of infant formulas.

Added Value of Including Entire Brain on Body Imaging With FDG PET/MRI.

PubMed

Franceschi, Ana M; Matthews, Robert; Bangiyev, Lev; Relan, Nand; Chaudhry, Ammar; Franceschi, Dinko

2018-05-24

FDG PET/MRI examination of the body is routinely performed from the skull base to the mid thigh. Many types of brain abnormalities potentially could be detected on PET/MRI if the head was included. The objective of this study was therefore to identify and characterize brain findings incidentally detected on PET/MRI of the body with the head included. We retrospectively identified 269 patients with FDG PET/MRI whole-body scans that included the head. PET/MR images of the brain were reviewed by a nuclear medicine physician and neuroradiologist, first individually and then concurrently. Both PET and MRI findings were identified, including abnormal FDG uptake, standardized uptake value, lesion size, and MRI signal characteristics. For each patient, relevant medical history and prior imaging were reviewed. Of the 269 subjects, 173 were women and 96 were men (mean age, 57.4 years). Only the initial PET/MR image of each patient was reviewed. A total of 37 of the 269 patients (13.8%) had abnormal brain findings noted on the PET/MRI whole-body scan. Sixteen patients (5.9%) had vascular disease, nine patients (3.3%) had posttherapy changes, and two (0.7%) had benign cystic lesions in the brain. Twelve patients (4.5%) had serious nonvascular brain abnormalities, including cerebral metastasis in five patients and pituitary adenomas in two patients. Only nine subjects (3.3%) had a new neurologic or cognitive symptom suggestive of a brain abnormality. Routine body imaging with FDG PET/MRI of the area from the skull base to the mid thigh may miss important brain abnormalities when the head is not included. The additional brain abnormalities identified on whole-body imaging may provide added clinical value to the management of oncology patients.

18F-FNDP for PET Imaging of Soluble Epoxide Hydrolase.

PubMed

Horti, Andrew G; Wang, Yuchuan; Minn, Il; Lan, Xi; Wang, Jian; Koehler, Raymond C; Alkayed, Nabil J; Dannals, Robert F; Pomper, Martin G

2016-11-01

Soluble epoxide hydrolase (sEH) is a bifunctional enzyme located within cytosol and peroxisomes that converts epoxides to the corresponding diols and hydrolyzes phosphate monoesters. It serves to inactivate epoxyeicosatrienoic acids (EETs), which are generated in the brain to couple neuronal activity and cerebral blood flow in normal and pathologic states. Altered regulation of sEH was observed previously in various neuropathologic disorders including vascular dementia and stroke. Inhibitors of sEH are pursued as agents to mitigate neuronal damage after stroke. We developed N-(3,3-diphenylpropyl)-6- 18 F-fluoronicotinamide ( 18 F-FNDP), which proved highly specific for imaging of sEH in the mouse and nonhuman primate brain with PET. 18 F-FNDP was synthesized from the corresponding bromo precursor. sEH inhibitory activity of 18 F-FNDP was measured using an sEH inhibitor screening assay kit. Biodistribution was undertaken in CD-1 mice. Binding specificity was assayed in CD-1 and sEH knock-out mice and Papio anubis (baboon) through pretreatment with an sEH inhibitor to block sEH binding. Dynamic PET imaging with arterial blood sampling was performed in 3 baboons, with regional tracer binding quantified using distribution volume. The metabolism of 18 F-FNDP in baboons was assessed using high-performance liquid chromatography. 18 F-FNDP (inhibition binding affinity constant, 1.73 nM) was prepared in 1 step in a radiochemical yield of 14% ± 7%, specific radioactivity in the range of 888-3,774 GBq/μmol, and a radiochemical purity greater than 99% using an automatic radiosynthesis module. The time of preparation was about 75 min. In CD-1 mice, regional uptake followed the pattern of striatum > cortex > hippocampus > cerebellum, consistent with the known brain distribution of sEH, with 5.2% injected dose per gram of tissue at peak uptake. Blockade of 80%-90% was demonstrated in all brain regions. Minimal radiotracer uptake was present in sEH knock-out mice. PET baboon brain distribution paralleled that seen in mouse, with a marked blockade (95%) noted in all regions indicating sEH-mediated uptake of 18 F-FNDP. Two hydrophilic metabolites were identified, with 20% parent compound present at 90 min after injection in baboon plasma. 18 F-FNDP can be synthesized in suitable radiochemical yield and high specific radioactivity and purity. In vivo imaging experiments demonstrated that 18 F-FNDP targeted sEH in murine and nonhuman primate brain specifically. 18 F-FNDP is a promising PET radiotracer likely to be useful for understanding the role of sEH in a variety of conditions affecting the central nervous system. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Segmenting Brain Tissues from Chinese Visible Human Dataset by Deep-Learned Features with Stacked Autoencoder

PubMed Central

Zhao, Guangjun; Wang, Xuchu; Niu, Yanmin; Tan, Liwen; Zhang, Shao-Xiang

2016-01-01

Cryosection brain images in Chinese Visible Human (CVH) dataset contain rich anatomical structure information of tissues because of its high resolution (e.g., 0.167 mm per pixel). Fast and accurate segmentation of these images into white matter, gray matter, and cerebrospinal fluid plays a critical role in analyzing and measuring the anatomical structures of human brain. However, most existing automated segmentation methods are designed for computed tomography or magnetic resonance imaging data, and they may not be applicable for cryosection images due to the imaging difference. In this paper, we propose a supervised learning-based CVH brain tissues segmentation method that uses stacked autoencoder (SAE) to automatically learn the deep feature representations. Specifically, our model includes two successive parts where two three-layer SAEs take image patches as input to learn the complex anatomical feature representation, and then these features are sent to Softmax classifier for inferring the labels. Experimental results validated the effectiveness of our method and showed that it outperformed four other classical brain tissue detection strategies. Furthermore, we reconstructed three-dimensional surfaces of these tissues, which show their potential in exploring the high-resolution anatomical structures of human brain. PMID:27057543

A survey of MRI-based medical image analysis for brain tumor studies

NASA Astrophysics Data System (ADS)

Bauer, Stefan; Wiest, Roland; Nolte, Lutz-P.; Reyes, Mauricio

2013-07-01

MRI-based medical image analysis for brain tumor studies is gaining attention in recent times due to an increased need for efficient and objective evaluation of large amounts of data. While the pioneering approaches applying automated methods for the analysis of brain tumor images date back almost two decades, the current methods are becoming more mature and coming closer to routine clinical application. This review aims to provide a comprehensive overview by giving a brief introduction to brain tumors and imaging of brain tumors first. Then, we review the state of the art in segmentation, registration and modeling related to tumor-bearing brain images with a focus on gliomas. The objective in the segmentation is outlining the tumor including its sub-compartments and surrounding tissues, while the main challenge in registration and modeling is the handling of morphological changes caused by the tumor. The qualities of different approaches are discussed with a focus on methods that can be applied on standard clinical imaging protocols. Finally, a critical assessment of the current state is performed and future developments and trends are addressed, giving special attention to recent developments in radiological tumor assessment guidelines.

Real-time simulation and visualization of volumetric brain deformation for image-guided neurosurgery

NASA Astrophysics Data System (ADS)

Ferrant, Matthieu; Nabavi, Arya; Macq, Benoit M. M.; Kikinis, Ron; Warfield, Simon K.

2001-05-01

During neurosurgery, the challenge for the neurosurgeon is to remove as much as possible of a tumor without destroying healthy tissue. This can be difficult because healthy and diseased tissue can have the same visual appearance. To this aim, and because the surgeon cannot see underneath the brain surface, image-guided neurosurgery systems are being increasingly used. However, during surgery, deformation of the brain occurs (due to brain shift and tumor resection), therefore causing errors in the surgical planning with respect to preoperative imaging. In our previous work, we developed software for capturing the deformation of the brain during neurosurgery. The software also allows preoperative data to be updated according to the intraoperative imaging so as to reflect the shape changes of the brain during surgery. Our goal in this paper was to rapidly visualize and characterize this deformation over the course of surgery with appropriate tools. Therefore, we developed tools allowing the doctor to visualize (in 2D and 3D) deformations, as well as the stress tensors characterizing the deformation along with the updated preoperative and intraoperative imaging during the course of surgery. Such tools significantly add to the value of intraoperative imaging and hence could improve surgical outcomes.

Segmenting Brain Tissues from Chinese Visible Human Dataset by Deep-Learned Features with Stacked Autoencoder.

PubMed

Zhao, Guangjun; Wang, Xuchu; Niu, Yanmin; Tan, Liwen; Zhang, Shao-Xiang

2016-01-01

Cryosection brain images in Chinese Visible Human (CVH) dataset contain rich anatomical structure information of tissues because of its high resolution (e.g., 0.167 mm per pixel). Fast and accurate segmentation of these images into white matter, gray matter, and cerebrospinal fluid plays a critical role in analyzing and measuring the anatomical structures of human brain. However, most existing automated segmentation methods are designed for computed tomography or magnetic resonance imaging data, and they may not be applicable for cryosection images due to the imaging difference. In this paper, we propose a supervised learning-based CVH brain tissues segmentation method that uses stacked autoencoder (SAE) to automatically learn the deep feature representations. Specifically, our model includes two successive parts where two three-layer SAEs take image patches as input to learn the complex anatomical feature representation, and then these features are sent to Softmax classifier for inferring the labels. Experimental results validated the effectiveness of our method and showed that it outperformed four other classical brain tissue detection strategies. Furthermore, we reconstructed three-dimensional surfaces of these tissues, which show their potential in exploring the high-resolution anatomical structures of human brain.

Mesoscale brain explorer, a flexible python-based image analysis and visualization tool.

PubMed

Haupt, Dirk; Vanni, Matthieu P; Bolanos, Federico; Mitelut, Catalin; LeDue, Jeffrey M; Murphy, Tim H

2017-07-01

Imaging of mesoscale brain activity is used to map interactions between brain regions. This work has benefited from the pioneering studies of Grinvald et al., who employed optical methods to image brain function by exploiting the properties of intrinsic optical signals and small molecule voltage-sensitive dyes. Mesoscale interareal brain imaging techniques have been advanced by cell targeted and selective recombinant indicators of neuronal activity. Spontaneous resting state activity is often collected during mesoscale imaging to provide the basis for mapping of connectivity relationships using correlation. However, the information content of mesoscale datasets is vast and is only superficially presented in manuscripts given the need to constrain measurements to a fixed set of frequencies, regions of interest, and other parameters. We describe a new open source tool written in python, termed mesoscale brain explorer (MBE), which provides an interface to process and explore these large datasets. The platform supports automated image processing pipelines with the ability to assess multiple trials and combine data from different animals. The tool provides functions for temporal filtering, averaging, and visualization of functional connectivity relations using time-dependent correlation. Here, we describe the tool and show applications, where previously published datasets were reanalyzed using MBE.

Functional connectivity in the mouse brain imaged by B-mode photoacoustic microscopy

NASA Astrophysics Data System (ADS)

Nasiriavanaki, Mohammadreza; Xing, Wenxin; Xia, Jun; Wang, Lihong V.

2014-03-01

The increasing use of mouse models for human brain disease studies, coupled with the fact that existing functional imaging modalities cannot be easily applied to mice, presents an emerging need for a new functional imaging modality. Utilizing acoustic-resolution photoacoustic microscopy (AR-PAM), we imaged spontaneous cerebral hemodynamic fluctuations and their associated functional connections in the mouse brain. The images were acquired noninvasively in B-scan mode with a fast frame rate, a large field of view, and a high spatial resolution. At a location relative to the bregma 0, correlations were investigated inter-hemispherically between bilaterally homologous regions, as well as intra-hemispherically within the same functional regions. The functional connectivity in different functional regions was studied. The locations of these regions agreed well with the Paxinos mouse brain atlas. The functional connectivity map obtained in this study can then be used in the investigation of brain disorders such as stroke, Alzheimer's, schizophrenia, multiple sclerosis, autism, and epilepsy. Our experiments show that photoacoustic microscopy is capable to detect connectivities between different functional regions in B-scan mode, promising a powerful functional imaging modality for future brain research.

Functional Imaging and Migraine: New Connections?

PubMed Central

Schwedt, Todd J.; Chong, Catherine D.

2015-01-01

Purpose of Review Over the last several years, a growing number of brain functional imaging studies have provided insights into mechanisms underlying migraine. This manuscript reviews the recent migraine functional neuroimaging literature and provides recommendations for future studies that will help fill knowledge gaps. Recent Findings Positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) studies have identified brain regions that might be responsible for mediating the onset of a migraine attack and those associated with migraine symptoms. Enhanced activation of brain regions that facilitate processing of sensory stimuli suggests a mechanism by which migraineurs are hypersensitive to visual, olfactory, and cutaneous stimuli. Resting state functional connectivity MRI studies have identified numerous brain regions and functional networks with atypical functional connectivity in migraineurs, suggesting that migraine is associated with aberrant brain functional organization. Summary fMRI and PET studies that have identified brain regions and brain networks that are atypical in migraine have helped to describe the neurofunctional basis for migraine symptoms. Future studies should compare functional imaging findings in migraine to other headache and pain disorders and should explore the utility of functional imaging data as biomarkers for diagnostic and treatment purposes. PMID:25887764

Non-imaged based method for matching brains in a common anatomical space for cellular imagery.

PubMed

Midroit, Maëllie; Thevenet, Marc; Fournel, Arnaud; Sacquet, Joelle; Bensafi, Moustafa; Breton, Marine; Chalençon, Laura; Cavelius, Matthias; Didier, Anne; Mandairon, Nathalie

2018-04-22

Cellular imagery using histology sections is one of the most common techniques used in Neuroscience. However, this inescapable technique has severe limitations due to the need to delineate regions of interest on each brain, which is time consuming and variable across experimenters. We developed algorithms based on a vectors field elastic registration allowing fast, automatic realignment of experimental brain sections and associated labeling in a brain atlas with high accuracy and in a streamlined way. Thereby, brain areas of interest can be finely identified without outlining them and different experimental groups can be easily analyzed using conventional tools. This method directly readjusts labeling in the brain atlas without any intermediate manipulation of images. We mapped the expression of cFos, in the mouse brain (C57Bl/6J) after olfactory stimulation or a non-stimulated control condition and found an increased density of cFos-positive cells in the primary olfactory cortex but not in non-olfactory areas of the odor-stimulated animals compared to the controls. Existing methods of matching are based on image registration which often requires expensive material (two-photon tomography mapping or imaging with iDISCO) or are less accurate since they are based on mutual information contained in the images. Our new method is non-imaged based and relies only on the positions of detected labeling and the external contours of sections. We thus provide a new method that permits automated matching of histology sections of experimental brains with a brain reference atlas. Copyright © 2018 Elsevier B.V. All rights reserved.

Image guided constitutive modeling of the silicone brain phantom

NASA Astrophysics Data System (ADS)

Puzrin, Alexander; Skrinjar, Oskar; Ozan, Cem; Kim, Sihyun; Mukundan, Srinivasan

2005-04-01

The goal of this work is to develop reliable constitutive models of the mechanical behavior of the in-vivo human brain tissue for applications in neurosurgery. We propose to define the mechanical properties of the brain tissue in-vivo, by taking the global MR or CT images of a brain response to ventriculostomy - the relief of the elevated intracranial pressure. 3D image analysis translates these images into displacement fields, which by using inverse analysis allow for the constitutive models of the brain tissue to be developed. We term this approach Image Guided Constitutive Modeling (IGCM). The presented paper demonstrates performance of the IGCM in the controlled environment: on the silicone brain phantoms closely simulating the in-vivo brain geometry, mechanical properties and boundary conditions. The phantom of the left hemisphere of human brain was cast using silicon gel. An inflatable rubber membrane was placed inside the phantom to model the lateral ventricle. The experiments were carried out in a specially designed setup in a CT scanner with submillimeter isotropic voxels. The non-communicative hydrocephalus and ventriculostomy were simulated by consequently inflating and deflating the internal rubber membrane. The obtained images were analyzed to derive displacement fields, meshed, and incorporated into ABAQUS. The subsequent Inverse Finite Element Analysis (based on Levenberg-Marquardt algorithm) allowed for optimization of the parameters of the Mooney-Rivlin non-linear elastic model for the phantom material. The calculated mechanical properties were consistent with those obtained from the element tests, providing justification for the future application of the IGCM to in-vivo brain tissue.

Reformatted images improve the detection rate of acute traumatic subdural hematomas on brain CT compared with axial images alone.

PubMed

Amrhein, Timothy J; Mostertz, William; Matheus, Maria Gisele; Maass-Bolles, Genevieve; Sharma, Komal; Collins, Heather R; Kranz, Peter G

2017-02-01

Subdural hematomas (SDHs) comprise a significant percentage of missed intracranial hemorrhage on axial brain CT. SDH detection rates could be improved with the addition of reformatted images. Though performed at some centers, the potential additional diagnostic sensitivity of reformatted images has not yet been investigated. The purpose of our study is to determine if the addition of coronal and sagittal reformatted images to an axial brain CT increases the sensitivity and specificity for detection of acute traumatic SDH. We retrospectively reviewed consecutive brain CTs acquired for acute trauma that contained new SDHs. An equivalent number of normal brain CTs served as control. Paired sets of images were created for each case: (1) axial images only ("axial only") and (2) axial, coronal, sagittal images ("reformat added"). Three readers interpreted both the axial only and companion reformat added for each case, separated by 1 month. Reading times and SDH detection rates were compared. One hundred SDH and 100 negative examinations were collected. Sensitivity and specificity for the axial-only scans were 75.7 and 94.3 %, respectively, compared with 88.3 and 98.3 % for reformat added. There was a 24.3 % false negative (missed SDH) rate with axial-only scans versus 11.7 % with reformat added (p = <0.001). Median reader interpretation times were longer with the addition of reformatted images (125 versus 89 s), but this difference was not significant (p = 0.23). The addition of coronal and sagittal images in trauma brain CT resulted in improved sensitivity and specificity as well as a reduction in SDH false negatives by greater than 50 %. Reformatted images substantially reduce the number of missed SDHs compared with axial images alone.

Image Statistics and the Representation of Material Properties in the Visual Cortex

PubMed Central

Baumgartner, Elisabeth; Gegenfurtner, Karl R.

2016-01-01

We explored perceived material properties (roughness, texturedness, and hardness) with a novel approach that compares perception, image statistics and brain activation, as measured with fMRI. We initially asked participants to rate 84 material images with respect to the above mentioned properties, and then scanned 15 of the participants with fMRI while they viewed the material images. The images were analyzed with a set of image statistics capturing their spatial frequency and texture properties. Linear classifiers were then applied to the image statistics as well as the voxel patterns of visually responsive voxels and early visual areas to discriminate between images with high and low perceptual ratings. Roughness and texturedness could be classified above chance level based on image statistics. Roughness and texturedness could also be classified based on the brain activation patterns in visual cortex, whereas hardness could not. Importantly, the agreement in classification based on image statistics and brain activation was also above chance level. Our results show that information about visual material properties is to a large degree contained in low-level image statistics, and that these image statistics are also partially reflected in brain activity patterns induced by the perception of material images. PMID:27582714

Image Statistics and the Representation of Material Properties in the Visual Cortex.

PubMed

Baumgartner, Elisabeth; Gegenfurtner, Karl R

2016-01-01

We explored perceived material properties (roughness, texturedness, and hardness) with a novel approach that compares perception, image statistics and brain activation, as measured with fMRI. We initially asked participants to rate 84 material images with respect to the above mentioned properties, and then scanned 15 of the participants with fMRI while they viewed the material images. The images were analyzed with a set of image statistics capturing their spatial frequency and texture properties. Linear classifiers were then applied to the image statistics as well as the voxel patterns of visually responsive voxels and early visual areas to discriminate between images with high and low perceptual ratings. Roughness and texturedness could be classified above chance level based on image statistics. Roughness and texturedness could also be classified based on the brain activation patterns in visual cortex, whereas hardness could not. Importantly, the agreement in classification based on image statistics and brain activation was also above chance level. Our results show that information about visual material properties is to a large degree contained in low-level image statistics, and that these image statistics are also partially reflected in brain activity patterns induced by the perception of material images.

Implantable self-reset CMOS image sensor and its application to hemodynamic response detection in living mouse brain

NASA Astrophysics Data System (ADS)

Yamaguchi, Takahiro; Takehara, Hiroaki; Sunaga, Yoshinori; Haruta, Makito; Motoyama, Mayumi; Ohta, Yasumi; Noda, Toshihiko; Sasagawa, Kiyotaka; Tokuda, Takashi; Ohta, Jun

2016-04-01

A self-reset pixel of 15 × 15 µm2 with high signal-to-noise ratio (effective peak SNR ≃64 dB) for an implantable image sensor has been developed for intrinsic signal detection arising from hemodynamic responses in a living mouse brain. For detecting local conversion between oxyhemoglobin (HbO) and deoxyhemoglobin (HbR) in brain tissues, an implantable imaging device was fabricated with our newly designed self-reset image sensor and orange light-emitting diodes (LEDs; λ = 605 nm). We demonstrated imaging of hemodynamic responses in the sensory cortical area accompanied by forelimb stimulation of a living mouse. The implantable imaging device for intrinsic signal detection is expected to be a powerful tool to measure brain activities in living animals used in behavioral analysis.

Fiber optic in vivo imaging in the mammalian nervous system

PubMed Central

Mehta, Amit D; Jung, Juergen C; Flusberg, Benjamin A; Schnitzer, Mark J

2010-01-01

The compact size, mechanical flexibility, and growing functionality of optical fiber and fiber optic devices are enabling several new modalities for imaging the mammalian nervous system in vivo. Fluorescence microendoscopy is a minimally invasive fiber modality that provides cellular resolution in deep brain areas. Diffuse optical tomography is a non-invasive modality that uses assemblies of fiber optic emitters and detectors on the cranium for volumetric imaging of brain activation. Optical coherence tomography is a sensitive interferometric imaging technique that can be implemented in a variety of fiber based formats and that might allow intrinsic optical detection of brain activity at a high resolution. Miniaturized fiber optic microscopy permits cellular level imaging in the brains of behaving animals. Together, these modalities will enable new uses of imaging in the intact nervous system for both research and clinical applications. PMID:15464896

Diagnostic Value of 68Ga PSMA-11 PET/CT Imaging of Brain Tumors-Preliminary Analysis.

PubMed

Sasikumar, Arun; Joy, Ajith; Pillai, M R A; Nanabala, Raviteja; Anees K, Muhammed; Jayaprakash, P G; Madhavan, Jayaprakash; Nair, Suresh

2017-01-01

To evaluate the feasibility of using Ga PSMA-11 PET/CT for imaging brain lesions and its comparison with F-FDG. Ten patients with brain lesions were included in the study. Five patients were treated cases of glioblastoma with suspected recurrence. F-FDG and Ga PSMA-11 brain scans were done for these patients. Five patients were sent for assessing the nature (primary lesion/metastasis) of space occupying lesion in brain. They underwent whole body F-FDG PET/CT scan and a primary site elsewhere in the body was ruled out. Subsequently they underwent Ga PSMA-11 brain PET/CT imaging. Target to background ratios (TBR) for the brain lesions were calculated using contralateral cerebellar uptake as background. In five treated cases of glioblastoma with suspected recurrence the findings of Ga PSMA-11 PET/CT showed good correlation with that of F-FDG PET/CT scan. Compared to the F-FDG, Ga PSMA-11 PET/CT showed better visualization of the recurrent lesion (presence/absence) owing to its significantly high TBR. Among the five cases evaluated for lesion characterization glioma and atypical meningioma patients showed higher SUVmax in the lesion with Ga PSMA-11 than with F-FDG and converse in cases of lymphoma. TBR was better with Ga PSMA PET/CT in all cases. Ga PSMA-11 PET/CT brain imaging is a potentially useful imaging tool in the evaluation of brain lesions. Absence of physiological uptake of Ga PSMA-11 in the normal brain parenchyma results in high TBR values and consequently better visualization of metabolically active disease in brain.

Dynamic subcellular imaging of cancer cell mitosis in the brain of live mice.

PubMed

Momiyama, Masashi; Suetsugu, Atsushi; Kimura, Hiroaki; Chishima, Takashi; Bouvet, Michael; Endo, Itaru; Hoffman, Robert M

2013-04-01

The ability to visualize cancer cell mitosis and apoptosis in the brain in real time would be of great utility in testing novel therapies. In order to achieve this goal, the cancer cells were labeled with green fluorescent protein (GFP) in the nucleus and red fluorescent protein (RFP) in the cytoplasm, such that mitosis and apoptosis could be clearly imaged. A craniotomy open window was made in athymic nude mice for real-time fluorescence imaging of implanted cancer cells growing in the brain. The craniotomy window was reversibly closed with a skin flap. Mitosis of the individual cancer cells were imaged dynamically in real time through the craniotomy-open window. This model can be used to evaluate brain metastasis and brain cancer at the subcellular level.

Transcriptomic characterization of MRI contrast with focus on the T1-w/T2-w ratio in the cerebral cortex.

PubMed

Ritchie, Jacob; Pantazatos, Spiro P; French, Leon

2018-07-01

Magnetic resonance (MR) images of the brain are of immense clinical and research utility. At the atomic and subatomic levels, the sources of MR signals are well understood. However, we lack a comprehensive understanding of the macromolecular correlates of MR signal contrast. To address this gap, we used genome-wide measurements to correlate gene expression with MR signal intensity across the cerebral cortex in the Allen Human Brain Atlas (AHBA). We focused on the ratio of T1-weighted and T2-weighted intensities (T1-w/T2-w ratio image), which is considered to be a useful proxy for myelin content. As expected, we found enrichment of positive correlations between myelin-associated genes and the ratio image, supporting its use as a myelin marker. Genome-wide, there was an association with protein mass, with genes coding for heavier proteins expressed in regions with high T1-w/T2-w values. Oligodendrocyte gene markers were strongly correlated with the T1-w/T2-w ratio, but this was not driven by myelin-associated genes. Mitochondrial genes exhibit the strongest relationship, showing higher expression in regions with low T1-w/T2-w ratio. This may be due to the pH gradient in mitochondria as genes up-regulated by pH in the brain were also highly correlated with the ratio. While we corroborate associations with myelin and synaptic plasticity, differences in the T1-w/T2-w ratio across the cortex are more strongly linked to molecule size, oligodendrocyte markers, mitochondria, and pH. We evaluate correlations between AHBA transcriptomic measurements and a group averaged T1-w/T2-w ratio image, showing agreement with in-sample results. Expanding our analysis to the whole brain results in strong positive T1-w/T2-w correlations for immune system, inflammatory disease, and microglia marker genes. Genes with negative correlations were enriched for neuron markers and synaptic plasticity genes. Lastly, our findings are similar when performed on T1-w or inverted T2-w intensities alone. These results provide a molecular characterization of MR contrast that will aid interpretation of future MR studies of the brain. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Improving Brain Magnetic Resonance Image (MRI) Segmentation via a Novel Algorithm based on Genetic and Regional Growth

PubMed Central

A., Javadpour; A., Mohammadi

2016-01-01

Background Regarding the importance of right diagnosis in medical applications, various methods have been exploited for processing medical images solar. The method of segmentation is used to analyze anal to miscall structures in medical imaging. Objective This study describes a new method for brain Magnetic Resonance Image (MRI) segmentation via a novel algorithm based on genetic and regional growth. Methods Among medical imaging methods, brains MRI segmentation is important due to high contrast of non-intrusive soft tissue and high spatial resolution. Size variations of brain tissues are often accompanied by various diseases such as Alzheimer’s disease. As our knowledge about the relation between various brain diseases and deviation of brain anatomy increases, MRI segmentation is exploited as the first step in early diagnosis. In this paper, regional growth method and auto-mate selection of initial points by genetic algorithm is used to introduce a new method for MRI segmentation. Primary pixels and similarity criterion are automatically by genetic algorithms to maximize the accuracy and validity in image segmentation. Results By using genetic algorithms and defining the fixed function of image segmentation, the initial points for the algorithm were found. The proposed algorithms are applied to the images and results are manually selected by regional growth in which the initial points were compared. The results showed that the proposed algorithm could reduce segmentation error effectively. Conclusion The study concluded that the proposed algorithm could reduce segmentation error effectively and help us to diagnose brain diseases. PMID:27672629

Mapping whole-brain activity with cellular resolution by light-sheet microscopy and high-throughput image analysis (Conference Presentation)

NASA Astrophysics Data System (ADS)

Silvestri, Ludovico; Rudinskiy, Nikita; Paciscopi, Marco; Müllenbroich, Marie Caroline; Costantini, Irene; Sacconi, Leonardo; Frasconi, Paolo; Hyman, Bradley T.; Pavone, Francesco S.

2016-03-01

Mapping neuronal activity patterns across the whole brain with cellular resolution is a challenging task for state-of-the-art imaging methods. Indeed, despite a number of technological efforts, quantitative cellular-resolution activation maps of the whole brain have not yet been obtained. Many techniques are limited by coarse resolution or by a narrow field of view. High-throughput imaging methods, such as light sheet microscopy, can be used to image large specimens with high resolution and in reasonable times. However, the bottleneck is then moved from image acquisition to image analysis, since many TeraBytes of data have to be processed to extract meaningful information. Here, we present a full experimental pipeline to quantify neuronal activity in the entire mouse brain with cellular resolution, based on a combination of genetics, optics and computer science. We used a transgenic mouse strain (Arc-dVenus mouse) in which neurons which have been active in the last hours before brain fixation are fluorescently labelled. Samples were cleared with CLARITY and imaged with a custom-made confocal light sheet microscope. To perform an automatic localization of fluorescent cells on the large images produced, we used a novel computational approach called semantic deconvolution. The combined approach presented here allows quantifying the amount of Arc-expressing neurons throughout the whole mouse brain. When applied to cohorts of mice subject to different stimuli and/or environmental conditions, this method helps finding correlations in activity between different neuronal populations, opening the possibility to infer a sort of brain-wide 'functional connectivity' with cellular resolution.

Using normalization 3D model for automatic clinical brain quantative analysis and evaluation

NASA Astrophysics Data System (ADS)

Lin, Hong-Dun; Yao, Wei-Jen; Hwang, Wen-Ju; Chung, Being-Tau; Lin, Kang-Ping

2003-05-01

Functional medical imaging, such as PET or SPECT, is capable of revealing physiological functions of the brain, and has been broadly used in diagnosing brain disorders by clinically quantitative analysis for many years. In routine procedures, physicians manually select desired ROIs from structural MR images and then obtain physiological information from correspondent functional PET or SPECT images. The accuracy of quantitative analysis thus relies on that of the subjectively selected ROIs. Therefore, standardizing the analysis procedure is fundamental and important in improving the analysis outcome. In this paper, we propose and evaluate a normalization procedure with a standard 3D-brain model to achieve precise quantitative analysis. In the normalization process, the mutual information registration technique was applied for realigning functional medical images to standard structural medical images. Then, the standard 3D-brain model that shows well-defined brain regions was used, replacing the manual ROIs in the objective clinical analysis. To validate the performance, twenty cases of I-123 IBZM SPECT images were used in practical clinical evaluation. The results show that the quantitative analysis outcomes obtained from this automated method are in agreement with the clinical diagnosis evaluation score with less than 3% error in average. To sum up, the method takes advantage of obtaining precise VOIs, information automatically by well-defined standard 3-D brain model, sparing manually drawn ROIs slice by slice from structural medical images in traditional procedure. That is, the method not only can provide precise analysis results, but also improve the process rate for mass medical images in clinical.

Whole brain myelin mapping using T1- and T2-weighted MR imaging data

PubMed Central

Ganzetti, Marco; Wenderoth, Nicole; Mantini, Dante

2014-01-01

Despite recent advancements in MR imaging, non-invasive mapping of myelin in the brain still remains an open issue. Here we attempted to provide a potential solution. Specifically, we developed a processing workflow based on T1-w and T2-w MR data to generate an optimized myelin enhanced contrast image. The workflow allows whole brain mapping using the T1-w/T2-w technique, which was originally introduced as a non-invasive method for assessing cortical myelin content. The hallmark of our approach is a retrospective calibration algorithm, applied to bias-corrected T1-w and T2-w images, that relies on image intensities outside the brain. This permits standardizing the intensity histogram of the ratio image, thereby allowing for across-subject statistical analyses. Quantitative comparisons of image histograms within and across different datasets confirmed the effectiveness of our normalization procedure. Not only did the calibrated T1-w/T2-w images exhibit a comparable intensity range, but also the shape of the intensity histograms was largely corresponding. We also assessed the reliability and specificity of the ratio image compared to other MR-based techniques, such as magnetization transfer ratio (MTR), fractional anisotropy (FA), and fluid-attenuated inversion recovery (FLAIR). With respect to these other techniques, T1-w/T2-w had consistently high values, as well as low inter-subject variability, in brain structures where myelin is most abundant. Overall, our results suggested that the T1-w/T2-w technique may be a valid tool supporting the non-invasive mapping of myelin in the brain. Therefore, it might find important applications in the study of brain development, aging and disease. PMID:25228871

Antisense imaging of gene expression in the brain in vivo

NASA Astrophysics Data System (ADS)

Shi, Ningya; Boado, Ruben J.; Pardridge, William M.

2000-12-01

Antisense radiopharmaceuticals could be used to image gene expression in the brain in vivo, should these polar molecules be made transportable through the blood-brain barrier. The present studies describe an antisense imaging agent comprised of an iodinated peptide nucleic acid (PNA) conjugated to a monoclonal antibody to the rat transferrin receptor by using avidin-biotin technology. The PNA was a 16-mer antisense to the sequence around the methionine initiation codon of the luciferase mRNA. C6 rat glioma cells were permanently transfected with a luciferase expression plasmid, and C6 experimental brain tumors were developed in adult rats. The expression of the luciferase transgene in the tumors in vivo was confirmed by measurement of luciferase enzyme activity in the tumor extract. The [125I]PNA conjugate was injected intravenously in anesthetized animals with brain tumors and killed 2 h later for frozen sectioning of brain and film autoradiography. No image of the luciferase gene expression was obtained after the administration of either the unconjugated antiluciferase PNA or a PNA conjugate that was antisense to the mRNA of a viral transcript. In contrast, tumors were imaged in all rats administered the [125I]PNA that was antisense to the luciferase sequence and was conjugated to the targeting antibody. In conclusion, these studies demonstrate gene expression in the brain in vivo can be imaged with antisense radiopharmaceuticals that are conjugated to a brain drug-targeting system.

Quantitative Machine Learning Analysis of Brain MRI Morphology throughout Aging.

PubMed

Shamir, Lior; Long, Joe

2016-01-01

While cognition is clearly affected by aging, it is unclear whether the process of brain aging is driven solely by accumulation of environmental damage, or involves biological pathways. We applied quantitative image analysis to profile the alteration of brain tissues during aging. A dataset of 463 brain MRI images taken from a cohort of 416 subjects was analyzed using a large set of low-level numerical image content descriptors computed from the entire brain MRI images. The correlation between the numerical image content descriptors and the age was computed, and the alterations of the brain tissues during aging were quantified and profiled using machine learning. The comprehensive set of global image content descriptors provides high Pearson correlation of ~0.9822 with the chronological age, indicating that the machine learning analysis of global features is sensitive to the age of the subjects. Profiling of the predicted age shows several periods of mild changes, separated by shorter periods of more rapid alterations. The periods with the most rapid changes were around the age of 55, and around the age of 65. The results show that the process of brain aging of is not linear, and exhibit short periods of rapid aging separated by periods of milder change. These results are in agreement with patterns observed in cognitive decline, mental health status, and general human aging, suggesting that brain aging might not be driven solely by accumulation of environmental damage. Code and data used in the experiments are publicly available.

In Vivo Follow-up of Brain Tumor Growth via Bioluminescence Imaging and Fluorescence Tomography

PubMed Central

Genevois, Coralie; Loiseau, Hugues; Couillaud, Franck

2016-01-01

Reporter gene-based strategies are widely used in experimental oncology. Bioluminescence imaging (BLI) using the firefly luciferase (Fluc) as a reporter gene and d-luciferin as a substrate is currently the most widely employed technique. The present paper compares the performances of BLI imaging with fluorescence imaging using the near infrared fluorescent protein (iRFP) to monitor brain tumor growth in mice. Fluorescence imaging includes fluorescence reflectance imaging (FRI), fluorescence diffuse optical tomography (fDOT), and fluorescence molecular Imaging (FMT®). A U87 cell line was genetically modified for constitutive expression of both the encoding Fluc and iRFP reporter genes and assayed for cell, subcutaneous tumor and brain tumor imaging. On cultured cells, BLI was more sensitive than FRI; in vivo, tumors were first detected by BLI. Fluorescence of iRFP provided convenient tools such as flux cytometry, direct detection of the fluorescent protein on histological slices, and fluorescent tomography that allowed for 3D localization and absolute quantification of the fluorescent signal in brain tumors. PMID:27809256

In Vivo Follow-up of Brain Tumor Growth via Bioluminescence Imaging and Fluorescence Tomography.

PubMed

Genevois, Coralie; Loiseau, Hugues; Couillaud, Franck

2016-10-31

Reporter gene-based strategies are widely used in experimental oncology. Bioluminescence imaging (BLI) using the firefly luciferase (Fluc) as a reporter gene and d-luciferin as a substrate is currently the most widely employed technique. The present paper compares the performances of BLI imaging with fluorescence imaging using the near infrared fluorescent protein (iRFP) to monitor brain tumor growth in mice. Fluorescence imaging includes fluorescence reflectance imaging (FRI), fluorescence diffuse optical tomography (fDOT), and fluorescence molecular Imaging (FMT ® ). A U87 cell line was genetically modified for constitutive expression of both the encoding Fluc and iRFP reporter genes and assayed for cell, subcutaneous tumor and brain tumor imaging. On cultured cells, BLI was more sensitive than FRI; in vivo, tumors were first detected by BLI. Fluorescence of iRFP provided convenient tools such as flux cytometry, direct detection of the fluorescent protein on histological slices, and fluorescent tomography that allowed for 3D localization and absolute quantification of the fluorescent signal in brain tumors.

Volumetric spiral chemical shift imaging of hyperpolarized [2-(13) c]pyruvate in a rat c6 glioma model.

PubMed

Park, Jae Mo; Josan, Sonal; Jang, Taichang; Merchant, Milton; Watkins, Ron; Hurd, Ralph E; Recht, Lawrence D; Mayer, Dirk; Spielman, Daniel M

2016-03-01

MRS of hyperpolarized [2-(13)C]pyruvate can be used to assess multiple metabolic pathways within mitochondria as the (13)C label is not lost with the conversion of pyruvate to acetyl-CoA. This study presents the first MR spectroscopic imaging of hyperpolarized [2-(13)C]pyruvate in glioma-bearing brain. Spiral chemical shift imaging with spectrally undersampling scheme (1042 Hz) and a hard-pulse excitation was exploited to simultaneously image [2-(13)C]pyruvate, [2-(13)C]lactate, and [5-(13)C]glutamate, the metabolites known to be produced in brain after an injection of hyperpolarized [2-(13)C]pyruvate, without chemical shift displacement artifacts. A separate undersampling scheme (890 Hz) was also used to image [1-(13)C]acetyl-carnitine. Healthy and C6 glioma-implanted rat brains were imaged at baseline and after dichloroacetate administration, a drug that modulates pyruvate dehydrogenase kinase activity. The baseline metabolite maps showed higher lactate and lower glutamate in tumor as compared to normal-appearing brain. Dichloroacetate led to an increase in glutamate in both tumor and normal-appearing brain. Dichloroacetate-induced %-decrease of lactate/glutamate was comparable to the lactate/bicarbonate decrease from hyperpolarized [1-(13)C]pyruvate studies. Acetyl-carnitine was observed in the muscle/fat tissue surrounding the brain. Robust volumetric imaging with hyperpolarized [2-(13)C]pyruvate and downstream products was performed in glioma-bearing rat brains, demonstrating changes in mitochondrial metabolism with dichloroacetate. © 2015 Wiley Periodicals, Inc.

Novel region of interest interrogation technique for diffusion tensor imaging analysis in the canine brain.

PubMed

Li, Jonathan Y; Middleton, Dana M; Chen, Steven; White, Leonard; Ellinwood, N Matthew; Dickson, Patricia; Vite, Charles; Bradbury, Allison; Provenzale, James M

2017-08-01

Purpose We describe a novel technique for measuring diffusion tensor imaging metrics in the canine brain. We hypothesized that a standard method for region of interest placement could be developed that is highly reproducible, with less than 10% difference in measurements between raters. Methods Two sets of canine brains (three seven-week-old full-brains and two 17-week-old single hemispheres) were scanned ex-vivo on a 7T small-animal magnetic resonance imaging system. Strict region of interest placement criteria were developed and then used by two raters to independently measure diffusion tensor imaging metrics within four different white-matter regions within each specimen. Average values of fractional anisotropy, radial diffusivity, and the three eigenvalues (λ1, λ2, and λ3) within each region in each specimen overall and within each individual image slice were compared between raters by calculating the percentage difference between raters for each metric. Results The mean percentage difference between raters for all diffusion tensor imaging metrics when pooled by each region and specimen was 1.44% (range: 0.01-5.17%). The mean percentage difference between raters for all diffusion tensor imaging metrics when compared by individual image slice was 2.23% (range: 0.75-4.58%) per hemisphere. Conclusion Our results indicate that the technique described is highly reproducible, even when applied to canine specimens of differing age, morphology, and image resolution. We propose this technique for future studies of diffusion tensor imaging analysis in canine brains and for cross-sectional and longitudinal studies of canine brain models of human central nervous system disease.

Multiscale Imaging of the Mouse Cortex Using Two-Photon Microscopy and Wide-Field Illumination

NASA Astrophysics Data System (ADS)

Bumstead, Jonathan R.

The mouse brain can be studied over vast spatial scales ranging from microscopic imaging of single neurons to macroscopic measurements of hemodynamics acquired over the majority of the mouse cortex. However, most neuroimaging modalities are limited by a fundamental trade-off between the spatial resolution and the field-of-view (FOV) over which the brain can be imaged, making it difficult to fully understand the functional and structural architecture of the healthy mouse brain and its disruption in disease. My dissertation has focused on developing multiscale optical systems capable of imaging the mouse brain at both microscopic and mesoscopic spatial scales, specifically addressing the difference in spatial scales imaged with two-photon microscopy (TPM) and optical intrinsic signal imaging (OISI). Central to this work has been the formulation of a principled design strategy for extending the FOV of the two-photon microscope. Using this design approach, we constructed a TPM system with subcellular resolution and a FOV area 100 times greater than a conventional two-photon microscope. To image the ellipsoidal shape of the mouse cortex, we also developed the microscope to image arbitrary surfaces within a single frame using an electrically tunable lens. Finally, to address the speed limitations of the TPM systems developed during my dissertation, I also conducted research in large-scale neural phenomena occurring in the mouse brain imaged with high-speed OISI. The work conducted during my dissertation addresses some of the fundamental principles in designing and applying optical systems for multiscale imaging of the mouse brain.

Deep Convolutional Neural Networks for Multi-Modality Isointense Infant Brain Image Segmentation

PubMed Central

Zhang, Wenlu; Li, Rongjian; Deng, Houtao; Wang, Li; Lin, Weili; Ji, Shuiwang; Shen, Dinggang

2015-01-01

The segmentation of infant brain tissue images into white matter (WM), gray matter (GM), and cerebrospinal fluid (CSF) plays an important role in studying early brain development in health and disease. In the isointense stage (approximately 6–8 months of age), WM and GM exhibit similar levels of intensity in both T1 and T2 MR images, making the tissue segmentation very challenging. Only a small number of existing methods have been designed for tissue segmentation in this isointense stage; however, they only used a single T1 or T2 images, or the combination of T1 and T2 images. In this paper, we propose to use deep convolutional neural networks (CNNs) for segmenting isointense stage brain tissues using multi-modality MR images. CNNs are a type of deep models in which trainable filters and local neighborhood pooling operations are applied alternatingly on the raw input images, resulting in a hierarchy of increasingly complex features. Specifically, we used multimodality information from T1, T2, and fractional anisotropy (FA) images as inputs and then generated the segmentation maps as outputs. The multiple intermediate layers applied convolution, pooling, normalization, and other operations to capture the highly nonlinear mappings between inputs and outputs. We compared the performance of our approach with that of the commonly used segmentation methods on a set of manually segmented isointense stage brain images. Results showed that our proposed model significantly outperformed prior methods on infant brain tissue segmentation. In addition, our results indicated that integration of multi-modality images led to significant performance improvement. PMID:25562829

The biochemical, nanomechanical and chemometric signatures of brain cancer

NASA Astrophysics Data System (ADS)

Abramczyk, Halina; Imiela, Anna

2018-01-01

Raman spectroscopy and imaging combined with AFM topography and mechanical indentation by AFM have been shown to be an effective tool for analysis and discrimination of human brain tumors from normal structures. Raman methods have potential to be applied in clinical practice as they allow for identification of tumor margins during surgery. In this study, we investigate medulloblastoma (grade IV WHO) (n = 5) and the tissue from the negative margins used as normal controls. We compare a high grade medulloblastoma (IV grade), and non-tumor samples from human central nervous system (CNS) tissue. Based on the properties of the Raman vibrational spectra and Raman images we provide a real-time feedback that is label-free method to monitor tumor metabolism that reveals reprogramming of biosynthesis of lipids, and proteins. We have found that the high-grade tumors of central nervous system (medulloblastoma) exhibit enhanced level of β-sheet conformation and down-regulated level of α-helix conformation when comparing against normal tissue. We have shown that the ratio of Raman intensities I2930/I2845 at 2930 and 2845 cm- 1 is a good source of information on the ratio of lipid and protein contents. We have found that the ratio reflects the lipid and protein contents of tumorous brain tissue compared to the non-tumor tissue. Almost all brain tumors have the Raman intensity ratios significantly higher (1.99 ± 0.026) than that found in non-tumor brain tissue, which is 1.456 ± 0.02, and indicates that the relative amount of lipids compared to proteins is significantly higher in the normal brain tissue. Mechanical indentation using AFM on sliced human brain tissues (medulloblastoma, grade IV) revealed that the mechanical properties of this tissue are strongly heterogeneous, between 1.8 and 75.7 kPa, and the mean of 27.16 kPa. The sensitivity and specificity obtained directly from PLSDA and cross validation gives a sensitivity and specificity of 98.5% and 96% and 96.3% and 92% for cross-validation, respectively. The high sensitivity and specificity demonstrates usefulness for a proper decision for a Raman diagnostic test on biochemical alterations monitored by Raman spectroscopy related to brain cancer development.

Na+/H+ Exchanger 9 Regulates Iron Mobilization at the Blood-Brain Barrier in Response to Iron Starvation.

PubMed

Beydoun, Rami; Hamood, Mohamed A; Gomez Zubieta, Daniela M; Kondapalli, Kalyan C

2017-03-10

Iron is essential for brain function, with loss of iron homeostasis in the brain linked to neurological diseases ranging from rare syndromes to more common disorders, such as Parkinson's and Alzheimer's diseases. Iron entry into the brain is regulated by the blood-brain barrier (BBB). Molecular mechanisms regulating this transport are poorly understood. Using an in vitro model of the BBB, we identify NHE9, an endosomal cation/proton exchanger, as a novel regulator of this system. Human brain microvascular endothelial cells (hBMVECs) that constitute the BBB receive brain iron status information via paracrine signals from ensheathing astrocytes. In hBMVECs, we show that NHE9 expression is up-regulated very early in a physiological response invoked by paracrine signals from iron-starved astrocytes. Ectopic expression of NHE9 in hBMVECs without external cues induced up-regulation of the transferrin receptor (TfR) and down-regulation of ferritin, leading to an increase in iron uptake. Mechanistically, we demonstrate that NHE9 localizes to recycling endosomes in hBMVECs where it raises the endosomal pH. The ensuing alkalization of the endosomal lumen increased translocation of TfRs to the hBMVEC membrane. TfRs on the membrane were previously shown to facilitate both recycling-dependent and -independent iron uptake. We propose that NHE9 regulates TfR-dependent, recycling-independent iron uptake in hBMVECs by fine-tuning the endosomal pH in response to paracrine signals and is therefore an important regulator in iron mobilization pathway at the BBB. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

[(18)F]-fluorodeoxyglucose positron emission tomography of the cat brain: A feasibility study to investigate osteoarthritis-associated pain.

PubMed

Guillot, Martin; Chartrand, Gabriel; Chav, Ramnada; Rousseau, Jacques; Beaudoin, Jean-François; Martel-Pelletier, Johanne; Pelletier, Jean-Pierre; Lecomte, Roger; de Guise, Jacques A; Troncy, Eric

2015-06-01

The objective of this pilot study was to investigate central nervous system (CNS) changes related to osteoarthritis (OA)-associated chronic pain in cats using [(18)F]-fluorodeoxyglucose ((18)FDG) positron emission tomography (PET) imaging. The brains of five normal, healthy (non-OA) cats and seven cats with pain associated with naturally occurring OA were imaged using (18)FDG-PET during a standardized mild anesthesia protocol. The PET images were co-registered over a magnetic resonance image of a cat brain segmented into several regions of interest. Brain metabolism was assessed in these regions using standardized uptake values. The brain metabolism in the secondary somatosensory cortex, thalamus and periaqueductal gray matter was increased significantly (P ≤ 0.005) in OA cats compared with non-OA cats. This study indicates that (18)FDG-PET brain imaging in cats is feasible to investigate CNS changes related to chronic pain. The results also suggest that OA is associated with sustained nociceptive inputs and increased activity of the descending modulatory pathways. Copyright © 2015 Elsevier Ltd. All rights reserved.

Fluorescence laminar optical tomography for brain imaging: system implementation and performance evaluation.

PubMed

Azimipour, Mehdi; Sheikhzadeh, Mahya; Baumgartner, Ryan; Cullen, Patrick K; Helmstetter, Fred J; Chang, Woo-Jin; Pashaie, Ramin

2017-01-01

We present our effort in implementing a fluorescence laminar optical tomography scanner which is specifically designed for noninvasive three-dimensional imaging of fluorescence proteins in the brains of small rodents. A laser beam, after passing through a cylindrical lens, scans the brain tissue from the surface while the emission signal is captured by the epi-fluorescence optics and is recorded using an electron multiplication CCD sensor. Image reconstruction algorithms are developed based on Monte Carlo simulation to model light–tissue interaction and generate the sensitivity matrices. To solve the inverse problem, we used the iterative simultaneous algebraic reconstruction technique. The performance of the developed system was evaluated by imaging microfabricated silicon microchannels embedded inside a substrate with optical properties close to the brain as a tissue phantom and ultimately by scanning brain tissue in vivo. Details of the hardware design and reconstruction algorithms are discussed and several experimental results are presented. The developed system can specifically facilitate neuroscience experiments where fluorescence imaging and molecular genetic methods are used to study the dynamics of the brain circuitries.

Brain Structure and Executive Functions in Children with Cerebral Palsy: A Systematic Review

ERIC Educational Resources Information Center

Weierink, Lonneke; Vermeulen, R. Jeroen; Boyd, Roslyn N.

2013-01-01

This systematic review aimed to establish the current knowledge about brain structure and executive function (EF) in children with cerebral palsy (CP). Five databases were searched (up till July 2012). Six articles met the inclusion criteria, all included structural brain imaging though no functional brain imaging. Study quality was assessed using…

Diagnostic imaging of traumatic brain injury.

PubMed

Furlow, Bryant

2006-01-01

In this Directed Reading, the history and epidemiology of traumatic brain injury (TBI) will be briefly introduced, the physical and physiological nature of TBI reviewed and the role of imaging in the assessment of TBI patients described. New imaging techniques and recent findings about the neurological correlates of TBI symptoms and outcomes from studies using different imaging modalities and techniques will also be discussed. This directed reading will focus on closed-head TBI; penetrating missile brain injuries, such as those caused by bullet wounds, will not be reviewed.

AUTOMATED CELL SEGMENTATION WITH 3D FLUORESCENCE MICROSCOPY IMAGES.

PubMed

Kong, Jun; Wang, Fusheng; Teodoro, George; Liang, Yanhui; Zhu, Yangyang; Tucker-Burden, Carol; Brat, Daniel J

2015-04-01

A large number of cell-oriented cancer investigations require an effective and reliable cell segmentation method on three dimensional (3D) fluorescence microscopic images for quantitative analysis of cell biological properties. In this paper, we present a fully automated cell segmentation method that can detect cells from 3D fluorescence microscopic images. Enlightened by fluorescence imaging techniques, we regulated the image gradient field by gradient vector flow (GVF) with interpolated and smoothed data volume, and grouped voxels based on gradient modes identified by tracking GVF field. Adaptive thresholding was then applied to voxels associated with the same gradient mode where voxel intensities were enhanced by a multiscale cell filter. We applied the method to a large volume of 3D fluorescence imaging data of human brain tumor cells with (1) small cell false detection and missing rates for individual cells; and (2) trivial over and under segmentation incidences for clustered cells. Additionally, the concordance of cell morphometry structure between automated and manual segmentation was encouraging. These results suggest a promising 3D cell segmentation method applicable to cancer studies.

Financial Incentives Differentially Regulate Neural Processing of Positive and Negative Emotions during Value-Based Decision-Making

PubMed Central

Farrell, Anne M.; Goh, Joshua O. S.; White, Brian J.

2018-01-01

Emotional and economic incentives often conflict in decision environments. To make economically desirable decisions then, deliberative neural processes must be engaged to regulate automatic emotional reactions. In this functional magnetic resonance imaging (fMRI) study, we evaluated how fixed wage (FW) incentives and performance-based (PB) financial incentives, in which pay is proportional to outcome, differentially regulate positive and negative emotional reactions to hypothetical colleagues that conflicted with the economics of available alternatives. Neural activity from FW to PB incentive contexts decreased for positive emotional stimuli but increased for negative stimuli in middle temporal, insula, and medial prefrontal regions. In addition, PB incentives further induced greater responses to negative than positive emotional decisions in the frontal and anterior cingulate regions involved in emotion regulation. Greater response to positive than negative emotional features in these regions also correlated with lower frequencies of economically desirable choices. Our findings suggest that whereas positive emotion regulation involves a reduction of responses in valence representation regions, negative emotion regulation additionally engages brain regions for deliberative processing and signaling of incongruous events. PMID:29487519

Financial Incentives Differentially Regulate Neural Processing of Positive and Negative Emotions during Value-Based Decision-Making.

PubMed

Farrell, Anne M; Goh, Joshua O S; White, Brian J

2018-01-01

Emotional and economic incentives often conflict in decision environments. To make economically desirable decisions then, deliberative neural processes must be engaged to regulate automatic emotional reactions. In this functional magnetic resonance imaging (fMRI) study, we evaluated how fixed wage (FW) incentives and performance-based (PB) financial incentives, in which pay is proportional to outcome, differentially regulate positive and negative emotional reactions to hypothetical colleagues that conflicted with the economics of available alternatives. Neural activity from FW to PB incentive contexts decreased for positive emotional stimuli but increased for negative stimuli in middle temporal, insula, and medial prefrontal regions. In addition, PB incentives further induced greater responses to negative than positive emotional decisions in the frontal and anterior cingulate regions involved in emotion regulation. Greater response to positive than negative emotional features in these regions also correlated with lower frequencies of economically desirable choices. Our findings suggest that whereas positive emotion regulation involves a reduction of responses in valence representation regions, negative emotion regulation additionally engages brain regions for deliberative processing and signaling of incongruous events.

Positron emission tomography assessment of 8-OH-DPAT-mediated changes in an index of cerebral glucose metabolism in female marmosets

PubMed Central

Converse, Alexander K.; Aubert, Yves; Farhoud, Mohammed; Weichert, Jamey P.; Rowland, Ian J.; Ingrisano, Nicole M.; Allers, Kelly A.; Sommer, Bernd; Abbott, David H.

2013-01-01

As part of a larger experiment investigating serotonergic regulation of female marmoset sexual behavior, this study was designed to (1) advance methods for PET imaging of common marmoset monkey brain, (2) measure normalized FDG uptake as an index of local cerebral metabolic rates for glucose, and (3) study changes induced in this index of cerebral glucose metabolism by chronic treatment of female marmosets with a serotonin 1A receptor (5-HT1A) agonist. We hypothesized that chronic treatment with the 5-HT1A agonist 8-OH-DPAT would alter the glucose metabolism index in dorsal raphe (DR), medial prefrontal cortex (mPFC), medial preoptic area of hypothalamus (mPOA), ventromedial nucleus of hypothalamus (VMH), and field CA1 of hippocampus. Eight adult ovariectomized female common marmosets (Callithrix jacchus) were studied with and without estradiol replacement. In a crossover design, each subject was treated daily with 8-OH-DPAT (0.1 mg/kg SC daily) or saline. After 42–49 days of treatment, the glucose metabolism radiotracer FDG was administered to each female immediately prior to 30 min of interaction with her male pairmate, after which the subject was anesthetized and imaged by PET. Whole brain normalized PET images were analyzed with anatomically defined regions of interest (ROI). Whole brain voxelwise mapping was also used to explore treatment effects and correlations between alterations in the glucose metabolism index and pairmate interactions. The rank order of normalized FDG uptake was VMH/mPOA>DR>mPFC/CA1 in both conditions. 8-OH-DPAT did not induce alterations in the glucose metabolism index in ROIs. Voxelwise mapping showed a significant reduction in normalized FDG uptake in response to 8-OH-DPAT in a cluster in medial occipital cortex as well as a significant correlation between increased rejection of mount attempts and reduced normalized FDG uptake in an overlapping cluster. In conclusion, PET imaging has been used to measure FDG uptake relative to whole brain in marmoset monkeys. Voxelwise mapping shows that 8-OH-DPAT reduces this index of glucose metabolism in medial occipital cortex, consistent with alterations in female sexual behavior. PMID:22233732

Magnetic resonance imaging of blood-brain barrier permeability in ischemic stroke using diffusion-weighted arterial spin labeling in rats.

PubMed

Tiwari, Yash V; Lu, Jianfei; Shen, Qiang; Cerqueira, Bianca; Duong, Timothy Q

2017-08-01

Diffusion-weighted arterial spin labeling magnetic resonance imaging has recently been proposed to quantify the rate of water exchange (K w ) across the blood-brain barrier in humans. This study aimed to evaluate the blood-brain barrier disruption in transient (60 min) ischemic stroke using K w magnetic resonance imaging with cross-validation by dynamic contrast-enhanced magnetic resonance imaging and Evans blue histology in the same rats. The major findings were: (i) at 90 min after stroke (30 min after reperfusion), group K w magnetic resonance imaging data showed no significant blood-brain barrier permeability changes, although a few animals showed slightly abnormal K w . Dynamic contrast-enhanced magnetic resonance imaging confirmed this finding in the same animals. (ii) At two days after stroke, K w magnetic resonance imaging revealed significant blood-brain barrier disruption. Regions with abnormal K w showed substantial overlap with regions of hyperintense T 2 (vasogenic edema) and hyperperfusion. Dynamic contrast-enhanced magnetic resonance imaging and Evans blue histology confirmed these findings in the same animals. The K w values in the normal contralesional hemisphere and the ipsilesional ischemic core two days after stroke were: 363 ± 17 and 261 ± 18 min -1 , respectively (P < 0.05, n = 9). K w magnetic resonance imaging is sensitive to blood-brain barrier permeability changes in stroke, consistent with dynamic contrast-enhanced magnetic resonance imaging and Evans blue extravasation. K w magnetic resonance imaging offers advantages over existing techniques because contrast agent is not needed and repeated measurements can be made for longitudinal monitoring or averaging.

First demonstration of in vivo mapping for regional brain monoacylglycerol lipase using PET with [11C]SAR127303.

PubMed

Yamasaki, Tomoteru; Mori, Wakana; Zhang, Yiding; Hatori, Akiko; Fujinaga, Masayuki; Wakizaka, Hidekatsu; Kurihara, Yusuke; Wang, Lu; Nengaki, Nobuki; Ohya, Tomoyuki; Liang, Steven H; Zhang, Ming-Rong

2018-08-01

Monoacylglycerol lipase (MAGL) is a main regulator of the endocannabinoid system within the central nervous system (CNS). Recently, [ 11 C]SAR127303 was developed as a promising radioligand for MAGL imaging. In this study, we aimed to quantify regional MAGL concentrations in the rat brain using positron emission tomography (PET) with [ 11 C]SAR127303. An irreversible two-tissue compartment model (2-TCMi, k 4  = 0) analysis was conducted to estimate quantitative parameters (k 3 , K i 2-TCMi , and λk 3 ). These parameters were successfully obtained with high identifiability (<10 %COV) for the following regions ranked in order from highest to lowest: cingulate cortex > striatum > hippocampus > thalamus > cerebellum > hypothalamus ≈ pons. In vitro autoradiographs using [ 11 C]SAR127303 showed a heterogeneous distribution of radioactivity, as seen in the PET images. The K i 2-TCMi and λk 3 values correlated relatively highly with in vitro binding (r > 0.4, P < 0.005). The K i 2-TCMi values showed high correlation and low underestimation (<10%) compared with the slope of a Patlak plot analysis with linear regression (K i Patlak ). In conclusion, we successfully estimated regional net uptake value of [ 11 C]SAR127303 reflecting MAGL concentrations in rat brain regions for the first time. Copyright © 2018 Elsevier Inc. All rights reserved.

Differences between endogenous and exogenous emotion inhibition in the human brain.

PubMed

Kühn, Simone; Haggard, Patrick; Brass, Marcel

2014-05-01

The regulation of emotions is an integral part of our mental health. It has only recently been investigated using brain imaging techniques. In most studies, participants are instructed by a cue to inhibit a specific emotional reaction. The aim of the present study was to investigate the alternative situation where a person decides to inhibit an emotion as an act of endogenous self-control. Healthy participants viewed highly arousing pictures with negative valence. In the endogenous condition, participants could freely choose on each trial to inhibit or feel the emotions elicited by the picture. In an exogenous condition, a visual cue instructed them to either feel or inhibit the emotion elicited by the picture. Participants' subjective ratings of intensity of experienced emotion showed an interaction effect between source of control (endogenous/exogenous) and feel/inhibit based on a stronger modulation between feel and inhibition for the endogenous compared to the exogenous condition. Endogenous inhibition of emotions was associated with dorso-medial prefrontal cortex activation, whereas exogenous inhibition was found associated with lateral prefrontal cortex activation. Thus, the brain regions for both endogenous and exogenous inhibition of emotion are highly similar to those for inhibition of motor actions in Brass and Haggard (J Neurosci 27:9141-9145, 2007), Kühn et al. (Hum Brain Mapp 30:2834-2843, 2009). Functional connectivity analyses showed that dorsofrontomedial cortex exerts greater control onto pre-supplementary motor area during endogenous inhibition compared to endogenous feel. This functional dissociation between an endogenous, fronto-medial and an exogenous, fronto-lateral inhibition centre has important implications for our understanding of emotion regulation in health and psychopathology.

Empathic control through coordinated interaction of amygdala, theory of mind and extended pain matrix brain regions.

PubMed

Bruneau, Emile G; Jacoby, Nir; Saxe, Rebecca

2015-07-01

Brain regions in the "pain matrix", can be activated by observing or reading about others in physical pain. In previous research, we found that reading stories about others' emotional suffering, by contrast, recruits a different group of brain regions mostly associated with thinking about others' minds. In the current study, we examined the neural circuits responsible for deliberately regulating empathic responses to others' pain and suffering. In Study 1, a sample of college-aged participants (n=18) read stories about physically painful and emotionally distressing events during functional magnetic resonance imaging (fMRI), while either actively empathizing with the main character or trying to remain objective. In Study 2, the same experiment was performed with professional social workers, who are chronically exposed to human suffering (n=21). Across both studies activity in the amygdala was associated with empathic regulation towards others' emotional pain, but not their physical pain. In addition, psychophysiological interaction (PPI) analysis and Granger causal modeling (GCM) showed that amygdala activity while reading about others' emotional pain was preceded by and positively coupled with activity in the theory of mind brain regions, and followed by and negatively coupled with activity in regions associated with physical pain and bodily sensations. Previous work has shown that the amygdala is critically involved in the deliberate control of self-focused distress - the current results extend the central importance of amygdala activity to the control of other-focused empathy, but only when considering others' emotional pain. Copyright © 2015 Elsevier Inc. All rights reserved.

Effects of Insulin Detemir and NPH Insulin on Body Weight and Appetite-Regulating Brain Regions in Human Type 1 Diabetes: A Randomized Controlled Trial

PubMed Central

van Golen, Larissa W.; Veltman, Dick J.; IJzerman, Richard G.; Deijen, Jan Berend; Heijboer, Annemieke C.; Barkhof, Frederik; Drent, Madeleine L.; Diamant, Michaela

2014-01-01

Studies in rodents have demonstrated that insulin in the central nervous system induces satiety. In humans, these effects are less well established. Insulin detemir is a basal insulin analog that causes less weight gain than other basal insulin formulations, including the current standard intermediate-long acting Neutral Protamine Hagedorn (NPH) insulin. Due to its structural modifications, which render the molecule more lipophilic, it was proposed that insulin detemir enters the brain more readily than other insulins. The aim of this study was to investigate whether insulin detemir treatment differentially modifies brain activation in response to food stimuli as compared to NPH insulin. In addition, cerebral spinal fluid (CSF) insulin levels were measured after both treatments. Brain responses to viewing food and non-food pictures were measured using functional Magnetic Resonance Imaging in 32 type 1 diabetic patients, after each of two 12-week treatment periods with insulin detemir and NPH insulin, respectively, both combined with prandial insulin aspart. CSF insulin levels were determined in a subgroup. Insulin detemir decreased body weight by 0.8 kg and NPH insulin increased weight by 0.5 kg (p = 0.02 for difference), while both treatments resulted in similar glycemic control. After treatment with insulin detemir, as compared to NPH insulin, brain activation was significantly lower in bilateral insula in response to visual food stimuli, compared to NPH (p = 0.02 for right and p = 0.05 for left insula). Also, CSF insulin levels were higher compared to those with NPH insulin treatment (p = 0.003). Our findings support the hypothesis that in type 1 diabetic patients, the weight sparing effect of insulin detemir may be mediated by its enhanced action on the central nervous system, resulting in blunted activation in bilateral insula, an appetite-regulating brain region, in response to food stimuli. Trial Registration ClinicalTrials.gov NCT00626080. PMID:24739875

Effects of insulin detemir and NPH insulin on body weight and appetite-regulating brain regions in human type 1 diabetes: a randomized controlled trial.

PubMed

van Golen, Larissa W; Veltman, Dick J; IJzerman, Richard G; Deijen, Jan Berend; Heijboer, Annemieke C; Barkhof, Frederik; Drent, Madeleine L; Diamant, Michaela

2014-01-01

Studies in rodents have demonstrated that insulin in the central nervous system induces satiety. In humans, these effects are less well established. Insulin detemir is a basal insulin analog that causes less weight gain than other basal insulin formulations, including the current standard intermediate-long acting Neutral Protamine Hagedorn (NPH) insulin. Due to its structural modifications, which render the molecule more lipophilic, it was proposed that insulin detemir enters the brain more readily than other insulins. The aim of this study was to investigate whether insulin detemir treatment differentially modifies brain activation in response to food stimuli as compared to NPH insulin. In addition, cerebral spinal fluid (CSF) insulin levels were measured after both treatments. Brain responses to viewing food and non-food pictures were measured using functional Magnetic Resonance Imaging in 32 type 1 diabetic patients, after each of two 12-week treatment periods with insulin detemir and NPH insulin, respectively, both combined with prandial insulin aspart. CSF insulin levels were determined in a subgroup. Insulin detemir decreased body weight by 0.8 kg and NPH insulin increased weight by 0.5 kg (p = 0.02 for difference), while both treatments resulted in similar glycemic control. After treatment with insulin detemir, as compared to NPH insulin, brain activation was significantly lower in bilateral insula in response to visual food stimuli, compared to NPH (p = 0.02 for right and p = 0.05 for left insula). Also, CSF insulin levels were higher compared to those with NPH insulin treatment (p = 0.003). Our findings support the hypothesis that in type 1 diabetic patients, the weight sparing effect of insulin detemir may be mediated by its enhanced action on the central nervous system, resulting in blunted activation in bilateral insula, an appetite-regulating brain region, in response to food stimuli. ClinicalTrials.gov NCT00626080.

STAMPS: Software Tool for Automated MRI Post-processing on a supercomputer.

PubMed

Bigler, Don C; Aksu, Yaman; Miller, David J; Yang, Qing X

2009-08-01

This paper describes a Software Tool for Automated MRI Post-processing (STAMP) of multiple types of brain MRIs on a workstation and for parallel processing on a supercomputer (STAMPS). This software tool enables the automation of nonlinear registration for a large image set and for multiple MR image types. The tool uses standard brain MRI post-processing tools (such as SPM, FSL, and HAMMER) for multiple MR image types in a pipeline fashion. It also contains novel MRI post-processing features. The STAMP image outputs can be used to perform brain analysis using Statistical Parametric Mapping (SPM) or single-/multi-image modality brain analysis using Support Vector Machines (SVMs). Since STAMPS is PBS-based, the supercomputer may be a multi-node computer cluster or one of the latest multi-core computers.

Wireless image-data transmission from an implanted image sensor through a living mouse brain by intra body communication

NASA Astrophysics Data System (ADS)

Hayami, Hajime; Takehara, Hiroaki; Nagata, Kengo; Haruta, Makito; Noda, Toshihiko; Sasagawa, Kiyotaka; Tokuda, Takashi; Ohta, Jun

2016-04-01

Intra body communication technology allows the fabrication of compact implantable biomedical sensors compared with RF wireless technology. In this paper, we report the fabrication of an implantable image sensor of 625 µm width and 830 µm length and the demonstration of wireless image-data transmission through a brain tissue of a living mouse. The sensor was designed to transmit output signals of pixel values by pulse width modulation (PWM). The PWM signals from the sensor transmitted through a brain tissue were detected by a receiver electrode. Wireless data transmission of a two-dimensional image was successfully demonstrated in a living mouse brain. The technique reported here is expected to provide useful methods of data transmission using micro sized implantable biomedical sensors.

Witnessing hateful people in pain modulates brain activity in regions associated with physical pain and reward

PubMed Central

Fox, Glenn R.; Sobhani, Mona; Aziz-Zadeh, Lisa

2013-01-01

How does witnessing a hateful person in pain compare to witnessing a likable person in pain? The current study compared the brain bases for how we perceive likable people in pain with those of viewing hateful people in pain. While social bonds are built through sharing the plight and pain of others in the name of empathy, viewing a hateful person in pain also has many potential ramifications. In this functional Magnetic Resonance Imaging (fMRI) study, Caucasian Jewish male participants viewed videos of (1) disliked, hateful, anti-Semitic individuals, and (2) liked, non-hateful, tolerant individuals in pain. The results showed that, compared with viewing liked people, viewing hateful people in pain elicited increased responses in regions associated with observation of physical pain (the insular cortex, the anterior cingulate cortex (ACC), and the somatosensory cortex), reward processing (the striatum), and frontal regions associated with emotion regulation. Functional connectivity analyses revealed connections between seed regions in the left ACC and right insular cortex with reward regions, the amygdala, and frontal regions associated with emotion regulation. These data indicate that regions of the brain active while viewing someone in pain may be more active in response to the danger or threat posed by witnessing the pain of a hateful individual more so than the desire to empathize with a likable person's pain. PMID:24167496

Goreisan Inhibits Upregulation of Aquaporin 4 and Formation of Cerebral Edema in the Rat Model of Juvenile Hypoxic-Ischemic Encephalopathy

PubMed Central

Yano, Hajime; Takahashi, Hisaaki; Yoshimoto, Kouhei; Tsuda, Shinji; Fujiyama, Kenta; Izumo-Shimizu, Yusuke; Motoie, Ryota; Ito, Masanori; Tanaka, Junya; Ishii, Eiichi

2017-01-01

Secondary cerebral edema regulation is of prognostic significance in hypoxic-ischemic encephalopathy (HIE), and aquaporin 4 (AQP4) plays an important role in the pathogenesis of cerebral edema. The traditional Japanese herbal medicine Goreisan relieves brain edema in adults; however, its effect and pharmacological mechanism in children are unknown. We investigated the effects of Goreisan on HIE-associated brain edema and AQP4 expression in a juvenile rat model, established by combined occlusion of middle cerebral and common carotid arteries. Magnetic resonance imaging showed that the lesion areas were significantly smaller in the Goreisan- (2 g/kg) treated group than in the nontreated (saline) group at 24 and 48 h postoperatively. AQP4 mRNA levels in the lesion and nonlesion sides were significantly suppressed in the Goreisan group compared with the nontreated group 36 h postoperatively. Western blotting revealed that levels of AQP4 protein were significantly decreased in the Goreisan group compared with the nontreated group in the lesion side 72 h postoperatively, but not at 12 or 36 h. After 14 days, the Goreisan group had a significantly better survival rate. These findings suggest that Goreisan suppresses brain edema in HIE and improves survival in juvenile rats, possibly via regulation of AQP4 expression and function. PMID:29234383

Environmental effects on molecular biomarkers expression in pancreatic and brain cancer

NASA Astrophysics Data System (ADS)

Mensah, Lawrence; Mallidi, Srivalleesha; Massodi, Iqbal; Anbil, Sriram; Mai, Zhiming; Hasan, Tayyaba

2013-03-01

A complete understanding of the biological mechanisms regulating devastating disease such as cancer remains elusive. Pancreatic and brain cancers are primary among the cancer types with poor prognosis. Molecular biomarkers have emerged as group of proteins that are preferentially overexpressed in cancers and with a key role in driving disease progression and resistance to chemotherapy. The epidermal growth factor receptor (EGFR), a cell proliferative biomarker is particularly highly expressed in most cancers including brain and pancreatic cancers. The ability of EGFR to sustain prolong cell proliferation is augmented by biomarkers such as Bax, Bcl-XL and Bcl-2, proteins regulating the apoptotic process. To better understand the role and effect of the microenvironment on these biomarkers in pancreatic cancer (PaCa); we analysed two pancreatic tumor lines (AsPc-1 and MiaPaCa-2) in 2D, 3D in-vitro cultures and in orthotopic tumors at different growth stages. We also investigated in patient derived glioblastoma (GBM) tumor cultures, the ability to utilize the EGFR expression to specifically deliver photosensitizer to the cells for photodynamic therapy. Overall, our results suggest that (1) microenvironment changes affect biomarker expression; thereby it is critical to understand these effects prior to designing combination therapies and (2) EGFR expression in tumor cells indeed could serve as a reliable and a robust biomarker that could be used to design targeted and image-guided photodynamic therapy.

A link between FTO, ghrelin, and impaired brain food-cue responsivity

PubMed Central

Karra, Efthimia; O’Daly, Owen G.; Choudhury, Agharul I.; Yousseif, Ahmed; Millership, Steven; Neary, Marianne T.; Scott, William R.; Chandarana, Keval; Manning, Sean; Hess, Martin E.; Iwakura, Hiroshi; Akamizu, Takashi; Millet, Queensta; Gelegen, Cigdem; Drew, Megan E.; Rahman, Sofia; Emmanuel, Julian J.; Williams, Steven C.R.; Rüther, Ulrich U.; Brüning, Jens C.; Withers, Dominic J.; Zelaya, Fernando O.; Batterham, Rachel L.

2013-01-01

Polymorphisms in the fat mass and obesity-associated gene (FTO) are associated with human obesity and obesity-prone behaviors, including increased food intake and a preference for energy-dense foods. FTO demethylates N6-methyladenosine, a potential regulatory RNA modification, but the mechanisms by which FTO predisposes humans to obesity remain unclear. In adiposity-matched, normal-weight humans, we showed that subjects homozygous for the FTO “obesity-risk” rs9939609 A allele have dysregulated circulating levels of the orexigenic hormone acyl-ghrelin and attenuated postprandial appetite reduction. Using functional MRI (fMRI) in normal-weight AA and TT humans, we found that the FTO genotype modulates the neural responses to food images in homeostatic and brain reward regions. Furthermore, AA and TT subjects exhibited divergent neural responsiveness to circulating acyl-ghrelin within brain regions that regulate appetite, reward processing, and incentive motivation. In cell models, FTO overexpression reduced ghrelin mRNA N6-methyladenosine methylation, concomitantly increasing ghrelin mRNA and peptide levels. Furthermore, peripheral blood cells from AA human subjects exhibited increased FTO mRNA, reduced ghrelin mRNA N6-methyladenosine methylation, and increased ghrelin mRNA abundance compared with TT subjects. Our findings show that FTO regulates ghrelin, a key mediator of ingestive behavior, and offer insight into how FTO obesity-risk alleles predispose to increased energy intake and obesity in humans. PMID:23867619

A link between FTO, ghrelin, and impaired brain food-cue responsivity.

PubMed

Karra, Efthimia; O'Daly, Owen G; Choudhury, Agharul I; Yousseif, Ahmed; Millership, Steven; Neary, Marianne T; Scott, William R; Chandarana, Keval; Manning, Sean; Hess, Martin E; Iwakura, Hiroshi; Akamizu, Takashi; Millet, Queensta; Gelegen, Cigdem; Drew, Megan E; Rahman, Sofia; Emmanuel, Julian J; Williams, Steven C R; Rüther, Ulrich U; Brüning, Jens C; Withers, Dominic J; Zelaya, Fernando O; Batterham, Rachel L

2013-08-01

Polymorphisms in the fat mass and obesity-associated gene (FTO) are associated with human obesity and obesity-prone behaviors, including increased food intake and a preference for energy-dense foods. FTO demethylates N6-methyladenosine, a potential regulatory RNA modification, but the mechanisms by which FTO predisposes humans to obesity remain unclear. In adiposity-matched, normal-weight humans, we showed that subjects homozygous for the FTO "obesity-risk" rs9939609 A allele have dysregulated circulating levels of the orexigenic hormone acyl-ghrelin and attenuated postprandial appetite reduction. Using functional MRI (fMRI) in normal-weight AA and TT humans, we found that the FTO genotype modulates the neural responses to food images in homeostatic and brain reward regions. Furthermore, AA and TT subjects exhibited divergent neural responsiveness to circulating acyl-ghrelin within brain regions that regulate appetite, reward processing, and incentive motivation. In cell models, FTO overexpression reduced ghrelin mRNA N6-methyladenosine methylation, concomitantly increasing ghrelin mRNA and peptide levels. Furthermore, peripheral blood cells from AA human subjects exhibited increased FTO mRNA, reduced ghrelin mRNA N6-methyladenosine methylation, and increased ghrelin mRNA abundance compared with TT subjects. Our findings show that FTO regulates ghrelin, a key mediator of ingestive behavior, and offer insight into how FTO obesity-risk alleles predispose to increased energy intake and obesity in humans.

DHEA Enhances Emotion Regulation Neurocircuits and Modulates Memory for Emotional Stimuli

PubMed Central

Sripada, Rebecca K; Marx, Christine E; King, Anthony P; Rajaram, Nirmala; Garfinkel, Sarah N; Abelson, James L; Liberzon, Israel

2013-01-01

Dehydroepiandrosterone (DHEA) is a neurosteroid with anxiolytic, antidepressant, and antiglucocorticoid properties. It is endogenously released in response to stress, and may reduce negative affect when administered exogenously. Although there have been multiple reports of DHEA's antidepressant and anxiolytic effects, no research to date has examined the neural pathways involved. In particular, brain imaging has not been used to link neurosteroid effects to emotion neurocircuitry. To investigate the brain basis of DHEA's impact on emotion modulation, patients were administered 400 mg of DHEA (N=14) or placebo (N=15) and underwent 3T fMRI while performing the shifted-attention emotion appraisal task (SEAT), a test of emotional processing and regulation. Compared with placebo, DHEA reduced activity in the amygdala and hippocampus, enhanced connectivity between the amygdala and hippocampus, and enhanced activity in the rACC. These activation changes were associated with reduced negative affect. DHEA reduced memory accuracy for emotional stimuli, and also reduced activity in regions associated with conjunctive memory encoding. These results demonstrate that DHEA reduces activity in regions associated with generation of negative emotion and enhances activity in regions linked to regulatory processes. Considering that activity in these regions is altered in mood and anxiety disorders, our results provide initial neuroimaging evidence that DHEA may be useful as a pharmacological intervention for these conditions and invite further investigation into the brain basis of neurosteroid emotion regulatory effects. PMID:23552182

New Clinically Feasible 3T MRI Protocol to Discriminate Internal Brain Stem Anatomy.

PubMed

Hoch, M J; Chung, S; Ben-Eliezer, N; Bruno, M T; Fatterpekar, G M; Shepherd, T M

2016-06-01

Two new 3T MR imaging contrast methods, track density imaging and echo modulation curve T2 mapping, were combined with simultaneous multisection acquisition to reveal exquisite anatomic detail at 7 canonical levels of the brain stem. Compared with conventional MR imaging contrasts, many individual brain stem tracts and nuclear groups were directly visualized for the first time at 3T. This new approach is clinically practical and feasible (total scan time = 20 minutes), allowing better brain stem anatomic localization and characterization. © 2016 by American Journal of Neuroradiology.

Region specific optimization of continuous linear attenuation coefficients based on UTE (RESOLUTE): application to PET/MR brain imaging

NASA Astrophysics Data System (ADS)

Ladefoged, Claes N.; Benoit, Didier; Law, Ian; Holm, Søren; Kjær, Andreas; Højgaard, Liselotte; Hansen, Adam E.; Andersen, Flemming L.

2015-10-01

The reconstruction of PET brain data in a PET/MR hybrid scanner is challenging in the absence of transmission sources, where MR images are used for MR-based attenuation correction (MR-AC). The main challenge of MR-AC is to separate bone and air, as neither have a signal in traditional MR images, and to assign the correct linear attenuation coefficient to bone. The ultra-short echo time (UTE) MR sequence was proposed as a basis for MR-AC as this sequence shows a small signal in bone. The purpose of this study was to develop a new clinically feasible MR-AC method with patient specific continuous-valued linear attenuation coefficients in bone that provides accurate reconstructed PET image data. A total of 164 [18F]FDG PET/MR patients were included in this study, of which 10 were used for training. MR-AC was based on either standard CT (reference), UTE or our method (RESOLUTE). The reconstructed PET images were evaluated in the whole brain, as well as regionally in the brain using a ROI-based analysis. Our method segments air, brain, cerebral spinal fluid, and soft tissue voxels on the unprocessed UTE TE images, and uses a mapping of R2* values to CT Hounsfield Units (HU) to measure the density in bone voxels. The average error of our method in the brain was 0.1% and less than 1.2% in any region of the brain. On average 95% of the brain was within  ±10% of PETCT, compared to 72% when using UTE. The proposed method is clinically feasible, reducing both the global and local errors on the reconstructed PET images, as well as limiting the number and extent of the outliers.

Ethanol fixed brain imaging by phase-contrast X-ray technique

NASA Astrophysics Data System (ADS)

Takeda, Tohoru; Thet-Thet-Lwin; Kunii, Takuya; Sirai, Ryota; Ohizumi, Takahito; Maruyama, Hiroko; Hyodo, Kazuyuki; Yoneyama, Akio; Ueda, Kazuhiro

2013-03-01

The two-crystal phase-contrast X-ray imaging technique using an X-ray crystal interferometer can depict the fine structures of rat's brain such as cerebral cortex, white matter, and basal ganglia. Image quality and contrast by ethanol fixed brain showed significantly better than those by usually used formalin fixation at 35 keV X-ray energy. Image contrast of cortex by ethanol fixation was more than 3-times higher than that by formalin fixation. Thus, the technique of ethanol fixation might be better suited to image cerebral structural detail at 35 keV X-ray energy.

Multimodal Imaging of Human Brain Activity: Rational, Biophysical Aspects and Modes of Integration

PubMed Central

Blinowska, Katarzyna; Müller-Putz, Gernot; Kaiser, Vera; Astolfi, Laura; Vanderperren, Katrien; Van Huffel, Sabine; Lemieux, Louis

2009-01-01

Until relatively recently the vast majority of imaging and electrophysiological studies of human brain activity have relied on single-modality measurements usually correlated with readily observable or experimentally modified behavioural or brain state patterns. Multi-modal imaging is the concept of bringing together observations or measurements from different instruments. We discuss the aims of multi-modal imaging and the ways in which it can be accomplished using representative applications. Given the importance of haemodynamic and electrophysiological signals in current multi-modal imaging applications, we also review some of the basic physiology relevant to understanding their relationship. PMID:19547657

Monoamine oxidase B is elevated in Alzheimer disease neurons, is associated with γ-secretase and regulates neuronal amyloid β-peptide levels.

PubMed

Schedin-Weiss, Sophia; Inoue, Mitsuhiro; Hromadkova, Lenka; Teranishi, Yasuhiro; Yamamoto, Natsuko Goto; Wiehager, Birgitta; Bogdanovic, Nenad; Winblad, Bengt; Sandebring-Matton, Anna; Frykman, Susanne; Tjernberg, Lars O

2017-08-01

Increased levels of the pathogenic amyloid β-peptide (Aβ), released from its precursor by the transmembrane protease γ-secretase, are found in Alzheimer disease (AD) brains. Interestingly, monoamine oxidase B (MAO-B) activity is also increased in AD brain, but its role in AD pathogenesis is not known. Recent neuroimaging studies have shown that the increased MAO-B expression in AD brain starts several years before the onset of the disease. Here, we show a potential connection between MAO-B, γ-secretase and Aβ in neurons. MAO-B immunohistochemistry was performed on postmortem human brain. Affinity purification of γ-secretase followed by mass spectrometry was used for unbiased identification of γ-secretase-associated proteins. The association of MAO-B with γ-secretase was studied by coimmunoprecipitation from brain homogenate, and by in-situ proximity ligation assay (PLA) in neurons as well as mouse and human brain sections. The effect of MAO-B on Aβ production and Notch processing in cell cultures was analyzed by siRNA silencing or overexpression experiments followed by ELISA, western blot or FRET analysis. Methodology for measuring relative intraneuronal MAO-B and Aβ42 levels in single cells was developed by combining immunocytochemistry and confocal microscopy with quantitative image analysis. Immunohistochemistry revealed MAO-B staining in neurons in the frontal cortex, hippocampus CA1 and entorhinal cortex in postmortem human brain. Interestingly, the neuronal staining intensity was higher in AD brain than in control brain in these regions. Mass spectrometric data from affinity purified γ-secretase suggested that MAO-B is a γ-secretase-associated protein, which was confirmed by immunoprecipitation and PLA, and a neuronal location of the interaction was shown. Strikingly, intraneuronal Aβ42 levels correlated with MAO-B levels, and siRNA silencing of MAO-B resulted in significantly reduced levels of intraneuronal Aβ42. Furthermore, overexpression of MAO-B enhanced Aβ production. This study shows that MAO-B levels are increased not only in astrocytes but also in pyramidal neurons in AD brain. The study also suggests that MAO-B regulates Aβ production in neurons via γ-secretase and thereby provides a key to understanding the relationship between MAO-B and AD pathogenesis. Potentially, the γ-secretase/MAO-B association may be a target for reducing Aβ levels using protein-protein interaction breakers.

Functional Magnetic Resonance Imaging and Spectroscopic Imaging of the Brain: Application of fMRI and fMRS to Reading Disabilities and Education.

ERIC Educational Resources Information Center

Richards, Todd L.

2001-01-01

This tutorial/review covers functional brain-imaging methods and results used to study language and reading disabilities. Although the emphasis is on magnetic resonance imaging and functional magnetic resonance spectroscopy, other imaging techniques are also discussed including positron emission tomography, electroencephalography,…

Transcranial fluorescence imaging of auditory cortical plasticity regulated by acoustic environments in mice.

PubMed

Takahashi, Kuniyuki; Hishida, Ryuichi; Kubota, Yamato; Kudoh, Masaharu; Takahashi, Sugata; Shibuki, Katsuei

2006-03-01

Functional brain imaging using endogenous fluorescence of mitochondrial flavoprotein is useful for investigating mouse cortical activities via the intact skull, which is thin and sufficiently transparent in mice. We applied this method to investigate auditory cortical plasticity regulated by acoustic environments. Normal mice of the C57BL/6 strain, reared in various acoustic environments for at least 4 weeks after birth, were anaesthetized with urethane (1.7 g/kg, i.p.). Auditory cortical images of endogenous green fluorescence in blue light were recorded by a cooled CCD camera via the intact skull. Cortical responses elicited by tonal stimuli (5, 10 and 20 kHz) exhibited mirror-symmetrical tonotopic maps in the primary auditory cortex (AI) and anterior auditory field (AAF). Depression of auditory cortical responses regarding response duration was observed in sound-deprived mice compared with naïve mice reared in a normal acoustic environment. When mice were exposed to an environmental tonal stimulus at 10 kHz for more than 4 weeks after birth, the cortical responses were potentiated in a frequency-specific manner in respect to peak amplitude of the responses in AI, but not for the size of the responsive areas. Changes in AAF were less clear than those in AI. To determine the modified synapses by acoustic environments, neural responses in cortical slices were investigated with endogenous fluorescence imaging. The vertical thickness of responsive areas after supragranular electrical stimulation was significantly reduced in the slices obtained from sound-deprived mice. These results suggest that acoustic environments regulate the development of vertical intracortical circuits in the mouse auditory cortex.

Magnetic resonance imaging spectrum of perinatal hypoxic-ischemic brain injury

PubMed Central

Varghese, Binoj; Xavier, Rose; Manoj, V C; Aneesh, M K; Priya, P S; Kumar, Ashok; Sreenivasan, V K

2016-01-01

Perinatal hypoxic–ischemic brain injury results in neonatal hypoxic–ischemic encephalopathy and serious long-term neurodevelopmental sequelae. Magnetic resonance imaging (MRI) of the brain is an ideal and safe imaging modality for suspected hypoxic–ischemic injury. The pattern of injury depends on brain maturity at the time of insult, severity of hypotension, and duration of insult. Time of imaging after the insult influences the imaging findings. Mild to moderate hypoperfusion results in germinal matrix hemorrhages and periventricular leukomalacia in preterm neonates and parasagittal watershed territory infarcts in full-term neonates. Severe insult preferentially damages the deep gray matter in both term and preterm infants. However, associated frequent perirolandic injury is seen in term neonates. MRI is useful in establishing the clinical diagnosis, assessing the severity of injury, and thereby prognosticating the outcome. Familiarity with imaging spectrum and insight into factors affecting the injury will enlighten the radiologist to provide an appropriate diagnosis. PMID:27857456

Level set method with automatic selective local statistics for brain tumor segmentation in MR images.

PubMed

Thapaliya, Kiran; Pyun, Jae-Young; Park, Chun-Su; Kwon, Goo-Rak

2013-01-01

The level set approach is a powerful tool for segmenting images. This paper proposes a method for segmenting brain tumor images from MR images. A new signed pressure function (SPF) that can efficiently stop the contours at weak or blurred edges is introduced. The local statistics of the different objects present in the MR images were calculated. Using local statistics, the tumor objects were identified among different objects. In this level set method, the calculation of the parameters is a challenging task. The calculations of different parameters for different types of images were automatic. The basic thresholding value was updated and adjusted automatically for different MR images. This thresholding value was used to calculate the different parameters in the proposed algorithm. The proposed algorithm was tested on the magnetic resonance images of the brain for tumor segmentation and its performance was evaluated visually and quantitatively. Numerical experiments on some brain tumor images highlighted the efficiency and robustness of this method. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

State-Dependent Differences in Emotion Regulation Between Unmedicated Bipolar Disorder and Major Depressive Disorder.

PubMed

Rive, Maria M; Mocking, Roel J T; Koeter, Maarten W J; van Wingen, Guido; de Wit, Stella J; van den Heuvel, Odile A; Veltman, Dick J; Ruhé, Henricus G; Schene, Aart H

2015-07-01

Major depressive disorder (MDD) and bipolar disorder (BD) are difficult to distinguish clinically during the depressed or remitted states. Both mood disorders are characterized by emotion regulation disturbances; however, little is known about emotion regulation differences between MDD and BD. Better insight into these differences would be helpful for differentiation based on disorder-specific underlying pathophysiological mechanisms. Previous studies comparing these disorders often allowed medication use, limiting generalizability and validity. Moreover, patients with MDD and BD were mostly compared during the depressed, but not the remitted, state, while state might potentially modulate differences between MDD and BD. To investigate positive and negative emotion regulation in medication-free patients with MDD and BD in 2 mood states: depressed or remitted. A cross-sectional study conducted from May 2009 to August 2013 comparing behavioral and functional magnetic resonance imaging emotion regulation data of 42 patients with MDD, 35 with BD, and 36 healthy control (HC) participants free of psychotropic medication recruited from several psychiatric institutions across the Netherlands. A voluntary emotion regulation functional magnetic resonance imaging task using positive and negative pictures. Behavioral and functional magnetic resonance imaging blood oxygen level-dependent responses during emotion regulation. In the remitted state, only patients with BD showed impaired emotion regulation (t = 3.39; P < .001; Cohen d = 0.70), irrespective of emotion type and associated with increased dorsolateral prefrontal cortex activity compared with those with MDD and healthy control participants (P = .008). In the depressed state, patients with MDD and BD differed with regard to happy vs sad emotion regulation (t = 4.19; P < .001; Cohen d = 1.66) associated with differences in rostral anterior cingulate activity (P < .001). Patients with MDD regulated sad and happy emotions poorly compared with those with BD and healthy control participants, while they demonstrated no rostral anterior cingulate difference between happy and sad emotion regulation. In contrast, patients with BD performed worse than those with MDD on sad emotion regulation but normal on happy emotion regulation, and they demonstrated significantly less rostral anterior cingulate activity while regulating happy compared with sad emotions. Medication-free patients with MDD vs BD appear to differ in brain activations during emotion regulation, both while depressed and in remission. These different neuropathophysiological mechanisms between MDD and BD may be useful for further development of additional diagnostic tools.

Resting functional imaging tools (MRS, SPECT, PET and PCT).

PubMed

Van Der Naalt, J

2015-01-01

Functional imaging includes imaging techniques that provide information about the metabolic and hemodynamic status of the brain. Most commonly applied functional imaging techniques in patients with traumatic brain injury (TBI) include magnetic resonance spectroscopy (MRS), single photon emission computed tomography (SPECT), positron emission tomography (PET) and perfusion CT (PCT). These imaging modalities are used to determine the extent of injury, to provide information for the prediction of outcome, and to assess evidence of cerebral ischemia. In TBI, secondary brain damage mainly comprises ischemia and is present in more than 80% of fatal cases with traumatic brain injury (Graham et al., 1989; Bouma et al., 1991; Coles et al., 2004). In particular, while SPECT measures cerebral perfusion and MRS determines metabolism, PET is able to assess both perfusion and cerebral metabolism. This chapter will describe the application of these techniques in traumatic brain injury separately for the major groups of severity comprising the mild and moderate to severe group. The application in TBI and potential difficulties of each technique is described. The use of imaging techniques in children will be separately outlined. © 2015 Elsevier B.V. All rights reserved.

CO2 induced pHi changes in the brain of polar fish: a TauCEST application.

PubMed

Wermter, Felizitas C; Maus, Bastian; Pörtner, Hans-O; Dreher, Wolfgang; Bock, Christian

2018-06-22

Chemical exchange saturation transfer (CEST) from taurine to water (TauCEST) can be used for in vivo mapping of taurine concentrations as well as for measurements of relative changes in intracellular pH (pH i ) at temperatures below 37°C. Therefore, TauCEST offers the opportunity to investigate acid-base regulation and neurological disturbances of ectothermic animals living at low temperatures, and in particular to study the impact of ocean acidification (OA) on neurophysiological changes of fish. Here, we report the first in vivo application of TauCEST imaging. Thus, the study aimed to investigate the TauCEST effect in a broad range of temperatures (1-37°C) and pH (5.5-8.0), motivated by the high taurine concentration measured in the brains of polar fish. The in vitro data show that the TauCEST effect is especially detectable in the low temperature range and strictly monotonic for the relevant pH range (6.8-7.5). To investigate the specificity of TauCEST imaging for the brain of polar cod (Boreogadus saida) at 1.5°C simulations were carried out, indicating a taurine contribution of about 65% to the in vivo expected CEST effect, if experimental parameters are optimized. B. saida was acutely exposed to three different CO 2 concentrations in the sea water (control normocapnia; comparatively moderate hypercapnia OA m  = 3300 μatm; high hypercapnia OA h  = 4900 μatm). TauCEST imaging of the brain showed a significant increase in the TauCEST effect under the different CO 2 concentrations of about 1.5-3% in comparison with control measurements, indicative of changes in pH i or metabolite concentration. Consecutive recordings of 1 H MR spectra gave no support for a concentration induced change of the in vivo observed TauCEST effect. Thus, the in vivo application of TauCEST offers the possibility of mapping relative changes in pH i in the brain of polar cod during exposure to CO 2 . © 2018 John Wiley & Sons, Ltd.

Comparison of In Vivo and Ex Vivo MRI for the Detection of Structural Abnormalities in a Mouse Model of Tauopathy

PubMed Central

Holmes, Holly E.; Powell, Nick M.; Ma, Da; Ismail, Ozama; Harrison, Ian F.; Wells, Jack A.; Colgan, Niall; O'Callaghan, James M.; Johnson, Ross A.; Murray, Tracey K.; Ahmed, Zeshan; Heggenes, Morten; Fisher, Alice; Cardoso, M. Jorge; Modat, Marc; O'Neill, Michael J.; Collins, Emily C.; Fisher, Elizabeth M. C.; Ourselin, Sébastien; Lythgoe, Mark F.

2017-01-01

With increasingly large numbers of mouse models of human disease dedicated to MRI studies, compromises between in vivo and ex vivo MRI must be fully understood in order to inform the choice of imaging methodology. We investigate the application of high resolution in vivo and ex vivo MRI, in combination with tensor-based morphometry (TBM), to uncover morphological differences in the rTg4510 mouse model of tauopathy. The rTg4510 mouse also offers a novel paradigm by which the overexpression of mutant tau can be regulated by the administration of doxycycline, providing us with a platform on which to investigate more subtle alterations in morphology with morphometry. Both in vivo and ex vivo MRI allowed the detection of widespread bilateral patterns of atrophy in the rTg4510 mouse brain relative to wild-type controls. Regions of volume loss aligned with neuronal loss and pathological tau accumulation demonstrated by immunohistochemistry. When we sought to investigate more subtle structural alterations in the rTg4510 mice relative to a subset of doxycycline-treated rTg4510 mice, ex vivo imaging enabled the detection of more regions of morphological brain changes. The disadvantages of ex vivo MRI may however mitigate this increase in sensitivity: we observed a 10% global shrinkage in brain volume of the post-mortem tissues due to formalin fixation, which was most notable in the cerebellum and olfactory bulbs. However, many central brain regions were not adversely affected by the fixation protocol, perhaps due to our “in-skull” preparation. The disparity between our TBM findings from in vivo and ex vivo MRI underlines the importance of appropriate study design, given the trade-off between these two imaging approaches. We support the utility of in vivo MRI for morphological phenotyping of mouse models of disease; however, for subtler phenotypes, ex vivo offers enhanced sensitivity to discrete morphological changes. PMID:28408879

Comparison of In Vivo and Ex Vivo MRI for the Detection of Structural Abnormalities in a Mouse Model of Tauopathy.

PubMed

Holmes, Holly E; Powell, Nick M; Ma, Da; Ismail, Ozama; Harrison, Ian F; Wells, Jack A; Colgan, Niall; O'Callaghan, James M; Johnson, Ross A; Murray, Tracey K; Ahmed, Zeshan; Heggenes, Morten; Fisher, Alice; Cardoso, M Jorge; Modat, Marc; O'Neill, Michael J; Collins, Emily C; Fisher, Elizabeth M C; Ourselin, Sébastien; Lythgoe, Mark F

2017-01-01

With increasingly large numbers of mouse models of human disease dedicated to MRI studies, compromises between in vivo and ex vivo MRI must be fully understood in order to inform the choice of imaging methodology. We investigate the application of high resolution in vivo and ex vivo MRI, in combination with tensor-based morphometry (TBM), to uncover morphological differences in the rTg4510 mouse model of tauopathy. The rTg4510 mouse also offers a novel paradigm by which the overexpression of mutant tau can be regulated by the administration of doxycycline, providing us with a platform on which to investigate more subtle alterations in morphology with morphometry. Both in vivo and ex vivo MRI allowed the detection of widespread bilateral patterns of atrophy in the rTg4510 mouse brain relative to wild-type controls. Regions of volume loss aligned with neuronal loss and pathological tau accumulation demonstrated by immunohistochemistry. When we sought to investigate more subtle structural alterations in the rTg4510 mice relative to a subset of doxycycline-treated rTg4510 mice, ex vivo imaging enabled the detection of more regions of morphological brain changes. The disadvantages of ex vivo MRI may however mitigate this increase in sensitivity: we observed a 10% global shrinkage in brain volume of the post-mortem tissues due to formalin fixation, which was most notable in the cerebellum and olfactory bulbs. However, many central brain regions were not adversely affected by the fixation protocol, perhaps due to our "in-skull" preparation. The disparity between our TBM findings from in vivo and ex vivo MRI underlines the importance of appropriate study design, given the trade-off between these two imaging approaches. We support the utility of in vivo MRI for morphological phenotyping of mouse models of disease; however, for subtler phenotypes, ex vivo offers enhanced sensitivity to discrete morphological changes.

Abnormal Neural Connectivity in Schizophrenia and fMRI-Brain-Computer Interface as a Potential Therapeutic Approach

PubMed Central

Ruiz, Sergio; Birbaumer, Niels; Sitaram, Ranganatha

2012-01-01

Considering that single locations of structural and functional abnormalities are insufficient to explain the diverse psychopathology of schizophrenia, new models have postulated that the impairments associated with the disease arise from a failure to integrate the activity of local and distributed neural circuits: the “abnormal neural connectivity hypothesis.” In the last years, new evidence coming from neuroimaging have supported and expanded this theory. However, despite the increasing evidence that schizophrenia is a disorder of neural connectivity, so far there are no treatments that have shown to produce a significant change in brain connectivity, or that have been specifically designed to alleviate this problem. Brain-Computer Interfaces based on real-time functional Magnetic Resonance Imaging (fMRI-BCI) are novel techniques that have allowed subjects to achieve self-regulation of circumscribed brain regions. In recent studies, experiments with this technology have resulted in new findings suggesting that this methodology could be used to train subjects to enhance brain connectivity, and therefore could potentially be used as a therapeutic tool in mental disorders including schizophrenia. The present article summarizes the findings coming from hemodynamics-based neuroimaging that support the abnormal connectivity hypothesis in schizophrenia, and discusses a new approach that could address this problem. PMID:23525496

Rapid transport within cerebral perivascular spaces underlies widespread tracer distribution in the brain after intranasal administration.

PubMed

Lochhead, Jeffrey J; Wolak, Daniel J; Pizzo, Michelle E; Thorne, Robert G

2015-03-01

The intranasal administration route is increasingly being used as a noninvasive method to bypass the blood-brain barrier because evidence suggests small fractions of nasally applied macromolecules may reach the brain directly via olfactory and trigeminal nerve components present in the nasal mucosa. Upon reaching the olfactory bulb (olfactory pathway) or brainstem (trigeminal pathway), intranasally delivered macromolecules appear to rapidly distribute within the brains of rodents and primates. The mechanisms responsible for this distribution have yet to be fully characterized. Here, we have used ex vivo fluorescence imaging to show that bulk flow within the perivascular space (PVS) of cerebral blood vessels contributes to the rapid central distribution of fluorescently labeled 3 and 10 kDa dextran tracers after intranasal administration in anesthetized adult rats. Comparison of tracer plasma levels and fluorescent signal distribution associated with the PVS of surface arteries and internal cerebral vessels showed that the intranasal route results in unique central access to the PVS not observed after matched intravascular dosing in separate animals. Intranasal targeting to the PVS was tracer size dependent and could be regulated by modifying nasal epithelial permeability. These results suggest cerebral perivascular convection likely has a key role in intranasal drug delivery to the brain.

Diattenuation of brain tissue and its impact on 3D polarized light imaging

PubMed Central

Menzel, Miriam; Reckfort, Julia; Weigand, Daniel; Köse, Hasan; Amunts, Katrin; Axer, Markus

2017-01-01

3D-polarized light imaging (3D-PLI) reconstructs nerve fibers in histological brain sections by measuring their birefringence. This study investigates another effect caused by the optical anisotropy of brain tissue – diattenuation. Based on numerical and experimental studies and a complete analytical description of the optical system, the diattenuation was determined to be below 4 % in rat brain tissue. It was demonstrated that the diattenuation effect has negligible impact on the fiber orientations derived by 3D-PLI. The diattenuation signal, however, was found to highlight different anatomical structures that cannot be distinguished with current imaging techniques, which makes Diattenuation Imaging a promising extension to 3D-PLI. PMID:28717561

Cortical Enhanced Tissue Segmentation of Neonatal Brain MR Images Acquired by a Dedicated Phased Array Coil

PubMed Central

Shi, Feng; Yap, Pew-Thian; Fan, Yong; Cheng, Jie-Zhi; Wald, Lawrence L.; Gerig, Guido; Lin, Weili; Shen, Dinggang

2010-01-01

The acquisition of high quality MR images of neonatal brains is largely hampered by their characteristically small head size and low tissue contrast. As a result, subsequent image processing and analysis, especially for brain tissue segmentation, are often hindered. To overcome this problem, a dedicated phased array neonatal head coil is utilized to improve MR image quality by effectively combing images obtained from 8 coil elements without lengthening data acquisition time. In addition, a subject-specific atlas based tissue segmentation algorithm is specifically developed for the delineation of fine structures in the acquired neonatal brain MR images. The proposed tissue segmentation method first enhances the sheet-like cortical gray matter (GM) structures in neonatal images with a Hessian filter for generation of cortical GM prior. Then, the prior is combined with our neonatal population atlas to form a cortical enhanced hybrid atlas, which we refer to as the subject-specific atlas. Various experiments are conducted to compare the proposed method with manual segmentation results, as well as with additional two population atlas based segmentation methods. Results show that the proposed method is capable of segmenting the neonatal brain with the highest accuracy, compared to other two methods. PMID:20862268

Study of the development of fetal baboon brain using magnetic resonance imaging at 3 Tesla

PubMed Central

Liu, Feng; Garland, Marianne; Duan, Yunsuo; Stark, Raymond I.; Xu, Dongrong; Dong, Zhengchao; Bansal, Ravi; Peterson, Bradley S.; Kangarlu, Alayar

2008-01-01

Direct observational data on the development of the brains of human and nonhuman primates is on remarkably scant, and most of our understanding of primate brain development is extrapolated from findings in rodent models. Magnetic resonance imaging (MRI) is a promising tool for the noninvasive, longitudinal study of the developing primate brain. We devised a protocol to scan pregnant baboons serially at 3 T for up to 3 h per session. Seven baboons were scanned 1–6 times, beginning as early as 56 days post-conceptional age, and as late as 185 days (term ~185 days). Successful scanning of the fetal baboon required careful animal preparation and anesthesia, in addition to optimization of the scanning protocol. We successfully acquired maps of relaxation times (T1 and T2) and high-resolution anatomical images of the brains of fetal baboons at multiple time points during the course of gestation. These images demonstrated the convergence of gray and white matter contrast near term, and furthermore demonstrated that the loss of contrast at that age is a consequence of the continuous change in relaxation times during fetal brain development. These data furthermore demonstrate that maps of relaxation times have clear advantages over the relaxation time weighted images for the tracking of the changes in brain structure during fetal development. This protocol for in utero MRI of fetal baboon brains will help to advance the use of nonhuman primate models to study fetal brain development longitudinally. PMID:18155925

Missouri University Multi-Plane Imager (MUMPI): A high sensitivity rapid dynamic ECT brain imager

DOE Office of Scientific and Technical Information (OSTI.GOV)

Logan, K.W.; Holmes, R.A.

1984-01-01

The authors have designed a unique ECT imaging device that can record rapid dynamic images of brain perfusion. The Missouri University Multi-Plane Imager (MUMPI) uses a single crystal detector that produces four orthogonal two-dimensional images simultaneously. Multiple slice images are reconstructed from counts recorded from stepwise or continuous collimator rotation. Four simultaneous 2-d image fields may also be recorded and reviewed. The cylindrical sodium iodide crystal and the rotating collimator concentrically surround the source volume being imaged with the collimator the only moving part. The design and function parameters of MUMPI have been compared to other competitive tomographic head imagingmore » devices. MUMPI's principal advantages are: 1) simultaneous direct acquisition of four two-dimensional images; 2) extremely rapid project set acquisition for ECT reconstruction; and 3) instrument practicality and economy due to single detector design and the absence of heavy mechanical moving components (only collimator rotation is required). MUMPI should be ideal for imaging neutral lipophilic chelates such as Tc-99m-PnAO which passively diffuses across the intact blood-brain-barrier and rapidly clears from brain tissue.« less

MRI-Based Measurement of Brain Stem Cross-Sectional Area in Relapsing-Remitting Multiple Sclerosis.

PubMed

Chivers, Tomos R; Constantinescu, Cris S; Tench, Christopher R

2015-01-01

To determine if patients with relapsing-remitting multiple sclerosis (RRMS) have a reduced brain stem cross-sectional area (CSA) compared to age- and sex-matched controls. The brain stem is a common site of involvement in MS. However, relatively few imaging studies have investigated brain stem atrophy. Brain magnetic resonance imaging (MRI) was performed on patients and controls using a 1.5T MRI scanner with a quadrature head coil. Three-dimensional magnetization-prepared rapid acquisition gradient-echo (MPRAGE) images with 128 contiguous slices, covering the whole brain and brain stem and a T2-weighted image with 3 mm transverse contiguous images were acquired. We measured the brain stem CSA at three sites, the midbrain, the pons, and the medulla oblongata in 35 RRMS patients and 35 controls using a semiautomated algorithm. CSA readings were normalized using the total external cranial volume to reduce normal population variance and increase statistical power. A significant CSA reduction was found in the midbrain (P ≤ .001), pons (P ≤ .001), and the medulla oblongata (P = .047) postnormalization. A CSA reduction of 9.3% was found in the midbrain, 8.7% in the pons, and 6.5% in the medulla oblongata. A significantly reduced, normalized brain stem CSA was detected in all areas of the brain stem of the RRMS patients, when compared to age- and gender-matched controls. Lack of detectable upper cervical cord atrophy in the same patients suggests some independence of the MS pathology in these regions. Copyright © 2015 by the American Society of Neuroimaging.

Fetal brain disruption sequence versus fetal brain arrest: A distinct autosomal recessive developmental brain malformation phenotype.

PubMed

Abdel-Salam, Ghada M H; Abdel-Hamid, Mohamed S; El-Khayat, Hamed A; Eid, Ola M; Saba, Soliman; Farag, Mona K; Saleem, Sahar N; Gaber, Khaled R

2015-05-01

The term fetal brain disruption sequence (FBDS) was coined to describe a number of sporadic conditions caused by numerous external disruptive events presenting with variable imaging findings. However, rare familial occurrences have been reported. We describe five patients (two sib pairs and one sporadic) with congenital severe microcephaly, seizures, and profound intellectual disability. Brain magnetic resonance imaging (MRI) revealed unique and uniform picture of underdeveloped cerebral hemispheres with increased extraxial CSF, abnormal gyral pattern (polymicrogyria-like lesions in two sibs and lissencephaly in the others), loss of white matter, dysplastic ventricles, hypogenesis of corpus callosum, and hypoplasia of the brainstem, but hypoplastic cerebellum in one. Fetal magnetic resonance imaging (FMRI) of two patients showed the same developmental brain malformations in utero. These imaging findings are in accordance with arrested brain development rather than disruption. Molecular analysis excluded mutations in potentially related genes such as NDE1, MKL2, OCLN, and JAM3. These unique clinical and imaging findings were described before among familial reports with FBDS. However, our patients represent a recognizable phenotype of developmental brain malformations, that is, apparently distinguishable from either familial microhydranencephaly or microlissencephaly that were collectively termed FBDS. Thus, the use of the umbrella term FBDS is no longer helpful. Accordingly, we propose the term fetal brain arrest to distinguish them from other familial patients diagnosed as FBDS. The presence of five affected patients from three unrelated consanguineous families suggests an autosomal-recessive mode of inheritance. The spectrum of fetal brain disruption sequence is reviewed. © 2015 Wiley Periodicals, Inc.