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Sample records for brain perfusion abnormalities

  1. Cerebral abnormalities in cocaine abusers: Demonstration by SPECT perfusion brain scintigraphy. Work in progress

    SciTech Connect

    Tumeh, S.S.; Nagel, J.S.; English, R.J.; Moore, M.; Holman, B.L. )

    1990-09-01

    Single photon emission computed tomography (SPECT) perfusion brain scans with iodine-123 isopropyl iodoamphetamine (IMP) were obtained in 12 subjects who acknowledged using cocaine on a sporadic to a daily basis. The route of cocaine administration varied from nasal to intravenous. Concurrent abuse of other drugs was also reported. None of the patients were positive for human immunodeficiency virus. Brain scans demonstrated focal defects in 11 subjects, including seven who were asymptomatic, and no abnormality in one. Among the findings were scattered focal cortical deficits, which were seen in several patients and which ranged in severity from small and few to multiple and large, with a special predilection for the frontal and temporal lobes. No perfusion deficits were seen on I-123 SPECT images in five healthy volunteers. Focal alterations in cerebral perfusion are seen commonly in asymptomatic drug users, and these focal deficits are readily depicted by I-123 IMP SPECT.

  2. Simulation of realistic abnormal SPECT brain perfusion images: application in semi-quantitative analysis

    NASA Astrophysics Data System (ADS)

    Ward, T.; Fleming, J. S.; Hoffmann, S. M. A.; Kemp, P. M.

    2005-11-01

    Simulation is useful in the validation of functional image analysis methods, particularly when considering the number of analysis techniques currently available lacking thorough validation. Problems exist with current simulation methods due to long run times or unrealistic results making it problematic to generate complete datasets. A method is presented for simulating known abnormalities within normal brain SPECT images using a measured point spread function (PSF), and incorporating a stereotactic atlas of the brain for anatomical positioning. This allows for the simulation of realistic images through the use of prior information regarding disease progression. SPECT images of cerebral perfusion have been generated consisting of a control database and a group of simulated abnormal subjects that are to be used in a UK audit of analysis methods. The abnormality is defined in the stereotactic space, then transformed to the individual subject space, convolved with a measured PSF and removed from the normal subject image. The dataset was analysed using SPM99 (Wellcome Department of Imaging Neuroscience, University College, London) and the MarsBaR volume of interest (VOI) analysis toolbox. The results were evaluated by comparison with the known ground truth. The analysis showed improvement when using a smoothing kernel equal to system resolution over the slightly larger kernel used routinely. Significant correlation was found between effective volume of a simulated abnormality and the detected size using SPM99. Improvements in VOI analysis sensitivity were found when using the region median over the region mean. The method and dataset provide an efficient methodology for use in the comparison and cross validation of semi-quantitative analysis methods in brain SPECT, and allow the optimization of analysis parameters.

  3. Structural and Perfusion Abnormalities of Brain on MRI and Technetium-99m-ECD SPECT in Children With Cerebral Palsy: A Comparative Study.

    PubMed

    Rana, Kamer Singh; Narwal, Varun; Chauhan, Lokesh; Singh, Giriraj; Sharma, Monica; Chauhan, Suneel

    2016-04-01

    Cerebral palsy has traditionally been associated with hypoxic ischemic brain damage. This study was undertaken to demonstrate structural and perfusion brain abnormalities. Fifty-six children diagnosed clinically as having cerebral palsy were studied between 1 to 14 years of age and were subjected to 3 Tesla magnetic resonance imaging (MRI). Brain and Technetium-99m-ECD brain single-photon emission computed tomography (SPECT) scan. Male to female ratio was 1.8:1 with a mean age of 4.16 ± 2.274 years. Spastic cerebral palsy was the most common type, observed in 91%. Birth asphyxia was the most common etiology (69.6%). White matter changes (73.2%) such as periventricular leukomalacia and corpus callosal thinning were the most common findings on MRI. On SPECT all cases except one revealed perfusion impairments in different regions of brain. MRI is more sensitive in detecting white matter changes, whereas SPECT is better in detecting cortical and subcortical gray matter abnormalities of perfusion.

  4. Structural and Perfusion Abnormalities of Brain on MRI and Technetium-99m-ECD SPECT in Children With Cerebral Palsy: A Comparative Study.

    PubMed

    Rana, Kamer Singh; Narwal, Varun; Chauhan, Lokesh; Singh, Giriraj; Sharma, Monica; Chauhan, Suneel

    2016-04-01

    Cerebral palsy has traditionally been associated with hypoxic ischemic brain damage. This study was undertaken to demonstrate structural and perfusion brain abnormalities. Fifty-six children diagnosed clinically as having cerebral palsy were studied between 1 to 14 years of age and were subjected to 3 Tesla magnetic resonance imaging (MRI). Brain and Technetium-99m-ECD brain single-photon emission computed tomography (SPECT) scan. Male to female ratio was 1.8:1 with a mean age of 4.16 ± 2.274 years. Spastic cerebral palsy was the most common type, observed in 91%. Birth asphyxia was the most common etiology (69.6%). White matter changes (73.2%) such as periventricular leukomalacia and corpus callosal thinning were the most common findings on MRI. On SPECT all cases except one revealed perfusion impairments in different regions of brain. MRI is more sensitive in detecting white matter changes, whereas SPECT is better in detecting cortical and subcortical gray matter abnormalities of perfusion. PMID:26353878

  5. Hepatic perfusion abnormalities during CT angiography: Detection and interpretation

    SciTech Connect

    Freeny, P.C.; Marks, W.M.

    1986-06-01

    Twenty-seven perfusion abnormalities were detected in 17 of 50 patients who underwent computed tomographic angiography (CTA) of the liver. All but one of the perfusion abnormalities occurred in patients with primary or metastatic liver tumors. Perfusion abnormalities were lobar in nine cases, segmental in 11, and subsegmental in seven; 14 were hypoperfusion and 13 were hyperperfusion abnormalities. The causes for the abnormalities included nonperfusion of a replaced hepatic artery (n = 11), cirrhosis and nodular regeneration (n = 3), altered hepatic hemodynamics (e.g., siphoning, laminar flow) caused by tumor (n = 7), contrast media washout from a nonperfused vessel (n = 1), compression of adjacent hepatic parenchyma (n = 1), and unknown (n = 4). Differentiation of perfusion abnormalities from tumor usually can be made by comparing the morphology of the known tumor with the suspected perfusion abnormality, changes of each on delayed CTA scans, and review of initial angiograms and other imaging studies.

  6. Pattern of brain blood perfusion in tinnitus patients using technetium-99m SPECT imaging

    PubMed Central

    Mahmoudian, Saeid; Farhadi, Mohammad; Gholami, Saeid; Saddadi, Fariba; Karimian, Ali Reza; Mirzaei, Mohammad; Ghoreyshi, Esmaeel; Ahmadizadeh, Majid; Lenarz, Thomas

    2012-01-01

    Background and Purpose: Tinnitus is associated with an increased activity in central auditory system as demonstrated by neuroimaging studies. Brain perfusion scanning using single photon emission computed tomography (SPECT) was done to understand the pattern of brain blood perfusion of tinnitus subjects and find the areas which are mostly abnormal in these patients. Materials and Methods: A number of 122 patients with tinnitus were enrolled to this cross-sectional study. They underwent SPECT and magnetic resonance imaging (MRI) of brain, and the images were fused to find the regions with abnormal perfusion. Results: SPECT scan results were abnormal in 101 patients (83%). Most patients had bilateral abnormal perfusion (N = 65, 53.3%), and most subjects had abnormality in middle-temporal gyrus (N = 83, 68%) and temporoparietal cortex (N = 46, 37.7%). Patients with multifocal involvement had the least mean age than other 2 groups (patients with no abnormality and unifocal abnormality) (P value = 0.045). Conclusions: Brain blood perfusion pattern differs in patient with tinnitus than others. These patients have brain perfusion abnormality, mostly in auditory gyrus (middle temporal) and associative cortex (temporoparietal cortex). Multifocal abnormalities might be due to more cognitive and emotional brain centers involvement due to tinnitus or more stress and anxiety of tinnitus in the young patients. PMID:23267375

  7. {sup 99m}Tc radiopharmaceuticals for brain perfusion imaging

    SciTech Connect

    Deutsch, E.; Volkert, W.A.

    1991-12-31

    It is well established that small, neutral, lipophilic technetium complexes can diffuse into the brain and then be trapped intracellularly by a variety of mechanisms. A more detailed understanding of the structural and chemical parameters which promote efficient diffusion into the brain, and which underlie the trapping mechanisms, will be necessary to delineate the clinical relevance of current agents, and to design improved technetium 99 pharmaceuticals. Current technetium 99 brain-perfusion imaging agents do not show ideal characteristics of brain uptake and retention. Furthermore, significant fractions of the technetium 99 complexes are lost between site of injection and the brain. Thus, it is difficult to use these current agents to quantitate regional cerebral blood flow. Nevertheless, these agents are proving extremely valuable for the SPECT evaluation of abnormalities in brain perfusion patients with neurological disorders.

  8. Myocardial perfusion abnormalities in asymptomatic patients with systemic lupus erythematosus

    SciTech Connect

    Hosenpud, J.D.; Montanaro, A.; Hart, M.V.; Haines, J.E.; Specht, H.D.; Bennett, R.M.; Kloster, F.E.

    1984-08-01

    Accelerated coronary artery disease and myocardial infarction in young patients with systemic lupus erythematosus is well documented; however, the prevalence of coronary involvement is unknown. Accordingly, 26 patients with systemic lupus were selected irrespective of previous cardiac history to undergo exercise thallium-201 cardiac scintigraphy. Segmental perfusion abnormalities were present in 10 of the 26 studies (38.5 percent). Five patients had reversible defects suggesting ischemia, four patients had persistent defects consistent with scar, and one patient had both reversible and persistent defects in two areas. There was no correlation between positive thallium results and duration of disease, amount of corticosteroid treatment, major organ system involvement or age. Only a history of pericarditis appeared to be associated with positive thallium-201 results (p less than 0.05). It is concluded that segmental myocardial perfusion abnormalities are common in patients with systemic lupus erythematosus. Whether this reflects large-vessel coronary disease or small-vessel abnormalities remains to be determined.

  9. Perfusion harmonic imaging of the human brain

    NASA Astrophysics Data System (ADS)

    Metzler, Volker H.; Seidel, Guenter; Wiesmann, Martin; Meyer, Karsten; Aach, Til

    2003-05-01

    The fast visualisation of cerebral microcirculation supports diagnosis of acute cerebrovascular diseases. However, the commonly used CT/MRI-based methods are time consuming and, moreover, costly. Therefore we propose an alternative approach to brain perfusion imaging by means of ultrasonography. In spite of the low signal/noise-ratio of transcranial ultrasound and the high impedance of the skull, flow images of cerebral blood flow can be derived by capturing the kinetics of appropriate contrast agents by harmonic ultrasound image sequences. In this paper we propose three different methods for human brain perfusion imaging, each of which yielding flow images indicating the status of the patient's cerebral microcirculation by visualising local flow parameters. Bolus harmonic imaging (BHI) displays the flow kinetics of bolus injections, while replenishment (RHI) and diminution harmonic imaging (DHI) compute flow characteristics from contrast agent continuous infusions. RHI measures the contrast agents kinetics in the influx phase and DHI displays the diminution kinetics of the contrast agent acquired from the decay phase. In clinical studies, BHI- and RHI-parameter images were found to represent comprehensive and reproducible distributions of physiological cerebral blood flow. For DHI it is shown, that bubble destruction and hence perfusion phenomena principally can be displayed. Generally, perfusion harmonic imaging enables reliable and fast bedside imaging of human brain perfusion. Due to its cost efficiency it complements cerebrovascular diagnostics by established CT/MRI-based methods.

  10. Perfusion Neuroimaging Abnormalities Alone Distinguish National Football League Players from a Healthy Population

    PubMed Central

    Amen, Daniel G.; Willeumier, Kristen; Omalu, Bennet; Newberg, Andrew; Raghavendra, Cauligi; Raji, Cyrus A.

    2016-01-01

    Background: National Football League (NFL) players are exposed to multiple head collisions during their careers. Increasing awareness of the adverse long-term effects of repetitive head trauma has raised substantial concern among players, medical professionals, and the general public. Objective: To determine whether low perfusion in specific brain regions on neuroimaging can accurately separate professional football players from healthy controls. Method: A cohort of retired and current NFL players (n = 161) were recruited in a longitudinal study starting in 2009 with ongoing interval follow up. A healthy control group (n = 124) was separately recruited for comparison. Assessments included medical examinations, neuropsychological tests, and perfusion neuroimaging with single photon emission computed tomography (SPECT). Perfusion estimates of each scan were quantified using a standard atlas. We hypothesized that hypoperfusion particularly in the orbital frontal, anterior cingulate, anterior temporal, hippocampal, amygdala, insular, caudate, superior/mid occipital, and cerebellar sub-regions alone would reliably separate controls from NFL players. Cerebral perfusion differences were calculated using a one-way ANOVA and diagnostic separation was determined with discriminant and automatic linear regression predictive models. Results: NFL players showed lower cerebral perfusion on average (p < 0.01) in 36 brain regions. The discriminant analysis subsequently distinguished NFL players from controls with 90% sensitivity, 86% specificity, and 94% accuracy (95% CI 95-99). Automatic linear modeling achieved similar results. Inclusion of age and clinical co-morbidities did not improve diagnostic classification. Conclusion: Specific brain regions commonly damaged in traumatic brain injury show abnormally low perfusion on SPECT in professional NFL players. These same regions alone can distinguish this group from healthy subjects with high diagnostic accuracy. This

  11. Whole-Brain Computed Tomographic Perfusion Imaging in Acute Cerebral Venous Sinus Thrombosis

    PubMed Central

    Mokin, Maxim; Ciambella, Chelsey C.; Masud, Muhammad W.; Levy, Elad I.; Snyder, Kenneth V.; Siddiqui, Adnan H.

    2016-01-01

    Background Acute cerebral venous sinus thrombosis (VST) can be difficult to diagnose because of its diverse clinical presentation. The utility of perfusion imaging for diagnosing VST is not well understood. Summary We retrospectively reviewed cases of acute VST in patients who underwent whole-brain (320-detector-row) computed tomographic (CT) perfusion imaging in combination with craniocervical CT venography. Perfusion maps that were analyzed included cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time, and time to peak. Among the 10 patients with acute VST included in this study, 9 had perfusion abnormalities. All perfusion abnormalities were localized in areas adjacent to the occluded sinus and did not match typical anterior or posterior circulation arterial territories. Bilateral perfusion deficits were seen in 4 cases. In 2 cases, parenchymal hemorrhage was diagnosed on noncontrast CT imaging; in those cases, focal CBV and CBF were reduced. Key Messages Whole-brain CT perfusion imaging with 320-detector-row scanners can further assist in establishing the diagnosis of VST by detecting perfusion abnormalities corresponding to venous and not arterial territories. CT perfusion could assist in the differentiation between focal reversible changes, such as those caused by vasogenic edema, and irreversible changes due to infarction. PMID:27051406

  12. Injury and repair in perinatal brain injury: Insights from non-invasive MR perfusion imaging.

    PubMed

    Wintermark, Pia

    2015-03-01

    Injury to the developing brain remains an important complication in critically ill newborns, placing them at risk for future neurodevelopment impairments. Abnormal brain perfusion is often a key mechanism underlying neonatal brain injury. A better understanding of how alternations in brain perfusion can affect normal brain development will permit the development of therapeutic strategies that prevent and/or minimize brain injury and improve the neurodevelopmental outcome of these high-risk newborns. Recently, non-invasive MR perfusion imaging of the brain has been successfully applied to the neonatal brain, which is known to be smaller and have lower brain perfusion compared to older children and adults. This article will present an overview of the potential role of non-invasive perfusion imaging by MRI to study maturation, injury, and repair in perinatal brain injury and demonstrate why this perfusion sequence is an important addition to current neonatal imaging protocols, which already include different sequences to assess the anatomy and metabolism of the neonatal brain.

  13. Quantification of brain perfusion with tracers retained by the brain

    SciTech Connect

    Pupi, A.; Bacciottini, L.; De Cristofaro, M.T.R.; Formiconi, A.R.; Castagnoli, A.

    1991-12-31

    Almost a decade ago, tracers, labelled with {sup 123}I and {sup 99m}Tc, that are retained by the brain, started to be used for studies of regional brain perfusion (regional cerebral blood flow, rCBF). To date, these tracers have been used for brain perfusion imaging with SPECT in brain disorders as well as for physiological activation protocols. Only seldom, however, have they been used in protocols that quantitatively measure rCBF. Nevertheless, comparative studies with perfusion reference tracers have repeatedly demonstrated that the brain uptake of these brain-retained tracers is correlated to perfusion, the major determinant of the distribution of these tracers in the brain. The brain kinetics of {sup 99m}Tc HMPAO, which is the tracer most commonly used, was described with a two-compartment tissue model. The theoretical approach, which is, in itself, sufficient for modeling quantitative measurements with {sup 99m}Tc HMPAO, initially suggested the possibility of empirically narrowing the distance between the brain`s regional uptake of the tracer and rCBF with a linearization algorithm which uses the cerebellum as the reference region. The value of this empirical method is hampered by the fact that the cerebellum can be involved in cerebrovascular disease (i.e. cerebellar diaschisis) as well as in several other brain disorders (e.g. anxiety, and dementia of the Alzheimer type). It also was proposed that different reference regions (occipital, whole slice, or whole brain) should be selected in relation to the brain disorder under study. However, this approach does not solve the main problem because it does not equip us with a reliable tool to evaluate rCBF with a high predictive value, and, at the same time, to reduce intersubject variability. The solution would be to measure a quantitative parameter which directly reflects rCBF, such as the unidirectional influx constant of the freely diffusible flow-limited tracers. 45 refs., 3 figs., 1 tab.

  14. The pediatric template of brain perfusion.

    PubMed

    Avants, Brian B; Duda, Jeffrey T; Kilroy, Emily; Krasileva, Kate; Jann, Kay; Kandel, Benjamin T; Tustison, Nicholas J; Yan, Lirong; Jog, Mayank; Smith, Robert; Wang, Yi; Dapretto, Mirella; Wang, Danny J J

    2015-01-01

    Magnetic resonance imaging (MRI) captures the dynamics of brain development with multiple modalities that quantify both structure and function. These measurements may yield valuable insights into the neural patterns that mark healthy maturation or that identify early risk for psychiatric disorder. The Pediatric Template of Brain Perfusion (PTBP) is a free and public neuroimaging resource that will help accelerate the understanding of childhood brain development as seen through the lens of multiple modality neuroimaging and in relation to cognitive and environmental factors. The PTBP uses cross-sectional and longitudinal MRI to quantify cortex, white matter, resting state functional connectivity and brain perfusion, as measured by Arterial Spin Labeling (ASL), in 120 children 7-18 years of age. We describe the PTBP and show, as a demonstration of validity, that global summary measurements capture the trajectories that demarcate critical turning points in brain maturation. This novel resource will allow a more detailed understanding of the network-level, structural and functional landmarks that are obtained during normal adolescent brain development. PMID:25977810

  15. The pediatric template of brain perfusion

    PubMed Central

    Avants, Brian B; Duda, Jeffrey T; Kilroy, Emily; Krasileva, Kate; Jann, Kay; Kandel, Benjamin T; Tustison, Nicholas J; Yan, Lirong; Jog, Mayank; Smith, Robert; Wang, Yi; Dapretto, Mirella; Wang, Danny J J

    2015-01-01

    Magnetic resonance imaging (MRI) captures the dynamics of brain development with multiple modalities that quantify both structure and function. These measurements may yield valuable insights into the neural patterns that mark healthy maturation or that identify early risk for psychiatric disorder. The Pediatric Template of Brain Perfusion (PTBP) is a free and public neuroimaging resource that will help accelerate the understanding of childhood brain development as seen through the lens of multiple modality neuroimaging and in relation to cognitive and environmental factors. The PTBP uses cross-sectional and longitudinal MRI to quantify cortex, white matter, resting state functional connectivity and brain perfusion, as measured by Arterial Spin Labeling (ASL), in 120 children 7–18 years of age. We describe the PTBP and show, as a demonstration of validity, that global summary measurements capture the trajectories that demarcate critical turning points in brain maturation. This novel resource will allow a more detailed understanding of the network-level, structural and functional landmarks that are obtained during normal adolescent brain development. PMID:25977810

  16. Brain perfusion in polysubstance users: Relationship to substance and tobacco use, cognition, and self-regulation*

    PubMed Central

    Murray, Donna E.; Durazzo, Timothy C.; Mon, Anderson; Schmidt, Thomas P.; Meyerhoff, Dieter J.

    2015-01-01

    Background Brain perfusion is altered in both alcohol dependence and stimulant dependence. Although most substance users also abuse/depend on alcohol concurrently (polysubstance users; PSU), rigorous perfusion research in PSU is limited. Also, the relationships of perfusion abnormalities with cognition, impulsivity or decision making are not well known. Methods Arterial spin labeling MRI and neuropsychological measures assessed perfusion levels and neurocognition in 20 alcohol dependent individuals with comorbid stimulant dependence (PSU), 26 individuals dependent on alcohol only (ALC), and 31 light/non-drinking controls (LD). The patient groups included smokers and non-smokers. Results ALC had lower perfusion than LD in subcortical and cortical brain regions including the brain reward/executive oversight system (BREOS). Contrary to our hypothesis, regional perfusion was generally not lower in PSU than ALC. However, smoking PSU had lower perfusion than smoking ALC in several regions, including BREOS. Lower BREOS perfusion related to greater drinking severity in smoking substance users and to greater smoking severity in smoking ALC. Lower regional perfusion in ALC and PSU correlated with worse performance in different cognitive domains; smoking status affected perfusion-cognition relationships in ALC only. Lower BREOS perfusion in both substance using groups related to higher impulsivity. Conclusion Although regional perfusion was not decreased in PSU as a group, the combination of cigarette smoking and polysubstance use is strongly related to hypoperfusion in important cortical and subcortical regions. As lower perfusion relates to greater smoking severity, worse cognition and higher impulsivity, smoking cessation is warranted for treatment-seeking PSU and ALC. PMID:25772434

  17. Schizophrenia and abnormal brain network hubs

    PubMed Central

    Rubinov, Mikail; Bullmore, Ed.

    2013-01-01

    Schizophrenia is a heterogeneous psychiatric disorder of unknown cause or characteristic pathology. Clinical neuroscientists increasingly postulate that schizophrenia is a disorder of brain network organization. In this article we discuss the conceptual framework of this dysconnection hypothesis, describe the predominant methodological paradigm for testing this hypothesis, and review recent evidence for disruption of central/hub brain regions, as a promising example of this hypothesis. We summarize studies of brain hubs in large-scale structural and functional brain networks and find strong evidence for network abnormalities of prefrontal hubs, and moderate evidence for network abnormalities of limbic, temporal, and parietal hubs. Future studies are needed to differentiate network dysfunction from previously observed gray- and white-matter abnormalities of these hubs, and to link endogenous network dysfunction phenotypes with perceptual, behavioral, and cognitive clinical phenotypes of schizophrenia. PMID:24174905

  18. Schizophrenia and abnormal brain network hubs.

    PubMed

    Rubinov, Mikail; Bullmore, Ed

    2013-09-01

    Schizophrenia is a heterogeneous psychiatric disorder of unknown cause or characteristic pathology. Clinical neuroscientists increasingly postulate that schizophrenia is a disorder of brain network organization. In this article we discuss the conceptual framework of this dysconnection hypothesis, describe the predominant methodological paradigm for testing this hypothesis, and review recent evidence for disruption of central/hub brain regions, as a promising example of this hypothesis. We summarize studies of brain hubs in large-scale structural and functional brain networks and find strong evidence for network abnormalities of prefrontal hubs, and moderate evidence for network abnormalities of limbic, temporal, and parietal hubs. Future studies are needed to differentiate network dysfunction from previously observed gray- and white-matter abnormalities of these hubs, and to link endogenous network dysfunction phenotypes with perceptual, behavioral, and cognitive clinical phenotypes of schizophrenia.

  19. Brain perfusion: computed tomography and magnetic resonance techniques.

    PubMed

    Copen, William A; Lev, Michael H; Rapalino, Otto

    2016-01-01

    Cerebral perfusion imaging provides assessment of regional microvascular hemodynamics in the living brain, enabling in vivo measurement of a variety of different hemodynamic parameters. Perfusion imaging techniques that are used in the clinical setting usually rely upon X-ray computed tomography (CT) or magnetic resonance imaging (MRI). This chapter reviews CT- and MRI-based perfusion imaging techniques, with attention to image acquisition, clinically relevant aspects of image postprocessing, and fundamental differences between CT- and MRI-based techniques. Correlations with cerebrovascular physiology and potential clinical applications of perfusion imaging are reviewed, focusing upon the two major classes of neurologic disease in which perfusion imaging is most often performed: primary perfusion disorders (including ischemic stroke, transient ischemic attack, and reperfusion syndrome), and brain tumors.

  20. Comparison of Regional Brain Perfusion Levels in Chronically Smoking and Non-Smoking Adults

    PubMed Central

    Durazzo, Timothy C.; Meyerhoff, Dieter J.; Murray, Donna E.

    2015-01-01

    Chronic cigarette smoking is associated with numerous abnormalities in brain neurobiology, but few studies specifically investigated the chronic effects of smoking (compared to the acute effects of smoking, nicotine administration, or nicotine withdrawal) on cerebral perfusion (i.e., blood flow). Predominately middle-aged male (47 ± 11 years of age) smokers (n = 34) and non-smokers (n = 27) were compared on regional cortical perfusion measured by continuous arterial spin labeling magnetic resonance studies at 4 Tesla. Smokers showed significantly lower perfusion than non-smokers in the bilateral medial and lateral orbitofrontal cortices, bilateral inferior parietal lobules, bilateral superior temporal gyri, left posterior cingulate, right isthmus of cingulate, and right supramarginal gyrus. Greater lifetime duration of smoking (adjusted for age) was related to lower perfusion in multiple brain regions. The results indicated smokers showed significant perfusion deficits in anterior cortical regions implicated in the development, progression, and maintenance of all addictive disorders. Smokers concurrently demonstrated reduced blood flow in posterior brain regions that show morphological and metabolic aberrations as well as elevated beta amyloid deposition demonstrated by those with early stage Alzheimer disease. The findings provide additional novel evidence of the adverse effects of cigarette smoking on the human brain. PMID:26193290

  1. Comparison of Regional Brain Perfusion Levels in Chronically Smoking and Non-Smoking Adults.

    PubMed

    Durazzo, Timothy C; Meyerhoff, Dieter J; Murray, Donna E

    2015-07-16

    Chronic cigarette smoking is associated with numerous abnormalities in brain neurobiology, but few studies specifically investigated the chronic effects of smoking (compared to the acute effects of smoking, nicotine administration, or nicotine withdrawal) on cerebral perfusion (i.e., blood flow). Predominately middle-aged male (47 ± 11 years of age) smokers (n = 34) and non-smokers (n = 27) were compared on regional cortical perfusion measured by continuous arterial spin labeling magnetic resonance studies at 4 Tesla. Smokers showed significantly lower perfusion than non-smokers in the bilateral medial and lateral orbitofrontal cortices, bilateral inferior parietal lobules, bilateral superior temporal gyri, left posterior cingulate, right isthmus of cingulate, and right supramarginal gyrus. Greater lifetime duration of smoking (adjusted for age) was related to lower perfusion in multiple brain regions. The results indicated smokers showed significant perfusion deficits in anterior cortical regions implicated in the development, progression, and maintenance of all addictive disorders. Smokers concurrently demonstrated reduced blood flow in posterior brain regions that show morphological and metabolic aberrations as well as elevated beta amyloid deposition demonstrated by those with early stage Alzheimer disease. The findings provide additional novel evidence of the adverse effects of cigarette smoking on the human brain.

  2. Schizophrenia, abnormal connection, and brain evolution.

    PubMed

    Randall, P L

    1983-03-01

    Abnormalities of functional connection between specialized areas in the human brain may underlie the symptoms which constitute the schizophrenia syndrome. Callosal and intrahemispheric fibres may be equally involved. The clinical emergence of symptoms in the later stages of brain maturation may be dependent on myelination of these fibre groups, both of which have extended myelination cycles. Ontogenetically earlier variants of the same mechanism could theoretically result in dyslexia and the syndromes of Kanner and Gilles de la Tourette. As new and unique extensions of specialized function emerge within the evolving brain, biological trial and error of connection both within and between them may produce individuals possessing phylogenetically advanced abilities, or equally, others possessing a wide range of abnormalities including those which comprise the schizophrenia syndrome. A dormant phenotypic potential for schizophrenia may exist in individuals who never develop symptoms during the course of a lifetime though some of these may become clinically apparent under the influence of various precipitating factors. It is concluded that abnormal functional connection and its normal and "supernormal" counterparts may be natural, essential, and inevitable consequences of brain evolution, and that this may have been so throughout the history of vertebrate brain evolution.

  3. Voxel-by-voxel analysis of brain SPECT perfusion in Fibromyalgia

    NASA Astrophysics Data System (ADS)

    Guedj, Eric; Taïeb, David; Cammilleri, Serge; Lussato, David; de Laforte, Catherine; Niboyet, Jean; Mundler, Olivier

    2007-02-01

    We evaluated brain perfusion SPECT at rest, without noxious stiumuli, in a homogeneous group of hyperalgesic FM patients. We performed a voxel-based analysis in comparison to a control group, matched for age and gender. Under such conditions, we made the assumption that significant cerebral perfusion abnormalities could be demonstrated, evidencing altered cerebral processing associated with spontaneous pain in FM patients. The secondary objective was to study the reversibility and the prognostic value of such possible perfusion abnormalities under specific treatment. Eighteen hyperalgesic FM women (mean age 48 yr; range 25-63 yr; ACR criteria) and 10 healthy women matched for age were enrolled in the study. A voxel-by-voxel group analysis was performed using SPM2 ( p<0.05, corrected for multiple comparisons). All brain SPECT were performed before any change was made in therapy in the pain care unit. A second SPECT was performed a month later after specific treatment by Ketamine. Compared to control subjects, we observed individual brain SPECT abnormalities in FM patients, confirmed by SPM2 analysis with hyperperfusion of the somatosensory cortex and hypoperfusion of the frontal, cingulate, medial temporal and cerebellar cortices. We also found that a medial frontal and anterior cingulate hypoperfusions were highly predictive (PPV=83%; NPV=91%) of non-response on Ketamine, and that only responders showed significant modification of brain perfusion, after treatment. In the present study performed without noxious stimuli in hyperalgesic FM patients, we found significant hyperperfusion in regions of the brain known to be involved in sensory dimension of pain processing and significant hypoperfusion in areas assumed to be associated with the affective dimension. As current pharmacological and non-pharmacological therapies act differently on both components of pain, we hypothesize that SPECT could be a valuable and readily available tool to guide individual therapeutic

  4. Tissue-specific sparse deconvolution for brain CT perfusion.

    PubMed

    Fang, Ruogu; Jiang, Haodi; Huang, Junzhou

    2015-12-01

    Enhancing perfusion maps in low-dose computed tomography perfusion (CTP) for cerebrovascular disease diagnosis is a challenging task, especially for low-contrast tissue categories where infarct core and ischemic penumbra usually occur. Sparse perfusion deconvolution has been recently proposed to effectively improve the image quality and diagnostic accuracy of low-dose perfusion CT by extracting the complementary information from the high-dose perfusion maps to restore the low-dose using a joint spatio-temporal model. However the low-contrast tissue classes where infarct core and ischemic penumbra are likely to occur in cerebral perfusion CT tend to be over-smoothed, leading to loss of essential biomarkers. In this paper, we propose a tissue-specific sparse deconvolution approach to preserve the subtle perfusion information in the low-contrast tissue classes. We first build tissue-specific dictionaries from segmentations of high-dose perfusion maps using online dictionary learning, and then perform deconvolution-based hemodynamic parameters estimation for block-wise tissue segments on the low-dose CTP data. Extensive validation on clinical datasets of patients with cerebrovascular disease demonstrates the superior performance of our proposed method compared to state-of-art, and potentially improve diagnostic accuracy by increasing the differentiation between normal and ischemic tissues in the brain. PMID:26055434

  5. Tissue-specific sparse deconvolution for brain CT perfusion.

    PubMed

    Fang, Ruogu; Jiang, Haodi; Huang, Junzhou

    2015-12-01

    Enhancing perfusion maps in low-dose computed tomography perfusion (CTP) for cerebrovascular disease diagnosis is a challenging task, especially for low-contrast tissue categories where infarct core and ischemic penumbra usually occur. Sparse perfusion deconvolution has been recently proposed to effectively improve the image quality and diagnostic accuracy of low-dose perfusion CT by extracting the complementary information from the high-dose perfusion maps to restore the low-dose using a joint spatio-temporal model. However the low-contrast tissue classes where infarct core and ischemic penumbra are likely to occur in cerebral perfusion CT tend to be over-smoothed, leading to loss of essential biomarkers. In this paper, we propose a tissue-specific sparse deconvolution approach to preserve the subtle perfusion information in the low-contrast tissue classes. We first build tissue-specific dictionaries from segmentations of high-dose perfusion maps using online dictionary learning, and then perform deconvolution-based hemodynamic parameters estimation for block-wise tissue segments on the low-dose CTP data. Extensive validation on clinical datasets of patients with cerebrovascular disease demonstrates the superior performance of our proposed method compared to state-of-art, and potentially improve diagnostic accuracy by increasing the differentiation between normal and ischemic tissues in the brain.

  6. Abnormal Asymmetry of Brain Connectivity in Schizophrenia

    PubMed Central

    Ribolsi, Michele; Daskalakis, Zafiris J.; Siracusano, Alberto; Koch, Giacomo

    2014-01-01

    Recently, a growing body of data has revealed that beyond a dysfunction of connectivity among different brain areas in schizophrenia patients (SCZ), there is also an abnormal asymmetry of functional connectivity compared with healthy subjects. The loss of the cerebral torque and the abnormalities of gyrification, with an increased or more complex cortical folding in the right hemisphere may provide an anatomical basis for such aberrant connectivity in SCZ. Furthermore, diffusion tensor imaging studies have shown a significant reduction of leftward asymmetry in some key white-matter tracts in SCZ. In this paper, we review the studies that investigated both structural brain asymmetry and asymmetry of functional connectivity in healthy subjects and SCZ. From an analysis of the existing literature on this topic, we can hypothesize an overall generally attenuated asymmetry of functional connectivity in SCZ compared to healthy controls. Such attenuated asymmetry increases with the duration of the disease and correlates with psychotic symptoms. Finally, we hypothesize that structural deficits across the corpus callosum may contribute to the abnormal asymmetry of intra-hemispheric connectivity in schizophrenia. PMID:25566030

  7. Multislice CT brain image registration for perfusion studies

    NASA Astrophysics Data System (ADS)

    Lin, Zhong Min; Pohlman, Scott; Chandra, Shalabh

    2002-04-01

    During the last several years perfusion CT techniques have been developed as an effective technique for clinically evaluating cerebral hemodynamics. Perfusion CT techniques are capable of measurings functional parameters such as tissue perfusion, blood flow, blood volume, and mean transit time and are commonly used to evaluate stroke patients. However, the quality of functional images of the brain frequently suffers from patient head motion. Because the time window for an effective treatment of stroke patient is narrow, a fast motion correction is required. The purpose of the paper is to present a fast and accurate registration technique for motion correction of multi-slice CT and to demonstrate the effects of the registration on perfusion calculation.

  8. A General Approach to the Evaluation of Ventilation-Perfusion Ratios in Normal and Abnormal Lungs

    ERIC Educational Resources Information Center

    Wagner, Peter D.

    1977-01-01

    Outlines methods for manipulating multiple gas data so as to gain the greatest amount of insight into the properties of ventilation-perfusion distributions. Refers to data corresponding to normal and abnormal lungs. Uses a two-dimensional framework with the respiratory gases of oxygen and carbon dioxide. (CS)

  9. Modelling Brain Temperature and Perfusion for Cerebral Cooling

    NASA Astrophysics Data System (ADS)

    Blowers, Stephen; Valluri, Prashant; Marshall, Ian; Andrews, Peter; Harris, Bridget; Thrippleton, Michael

    2015-11-01

    Brain temperature relies heavily on two aspects: i) blood perfusion and porous heat transport through tissue and ii) blood flow and heat transfer through embedded arterial and venous vasculature. Moreover brain temperature cannot be measured directly unless highly invasive surgical procedures are used. A 3D two-phase fluid-porous model for mapping flow and temperature in brain is presented with arterial and venous vessels extracted from MRI scans. Heat generation through metabolism is also included. The model is robust and reveals flow and temperature maps in unprecedented 3D detail. However, the Karmen-Kozeny parameters of the porous (tissue) phase need to be optimised for expected perfusion profiles. In order to optimise the K-K parameters a reduced order two-phase model is developed where 1D vessels are created with a tree generation algorithm embedded inside a 3D porous domain. Results reveal that blood perfusion is a strong function of the porosity distribution in the tissue. We present a qualitative comparison between the simulated perfusion maps and those obtained clinically. We also present results studying the effect of scalp cooling on core brain temperature and preliminary results agree with those observed clinically.

  10. Brain perfusion in acute and chronic hyperglycemia in rats

    SciTech Connect

    Kikano, G.E.; LaManna, J.C.; Harik, S.I. )

    1989-08-01

    Recent studies show that acute and chronic hyperglycemia cause a diffuse decrease in regional cerebral blood flow and that chronic hyperglycemia decreases the brain L-glucose space. Since these changes can be caused by a decreased density of perfused brain capillaries, we used 30 adult male Wistar rats to study the effect of acute and chronic hyperglycemia on (1) the brain intravascular space using radioiodinated albumin, (2) the anatomic density of brain capillaries using alkaline phosphatase histochemistry, and (3) the fraction of brain capillaries that are perfused using the fluorescein isothiocyanate-dextran method. Our results indicate that acute and chronic hyperglycemia do not affect the brain intravascular space nor the anatomic density of brain capillaries. Also, there were no differences in capillary recruitment among normoglycemic, acutely hyperglycemic, and chronically hyperglycemic rats. These results suggest that the shrinkage of the brain L-glucose space in chronic hyperglycemia is more likely due to changes in the blood-brain barrier permeability to L-glucose.

  11. Simulation model for contrast agent dynamics in brain perfusion scans.

    PubMed

    Bredno, Jörg; Olszewski, Mark E; Wintermark, Max

    2010-07-01

    Standardization efforts are currently under way to reduce the heterogeneity of quantitative brain perfusion methods. A brain perfusion simulation model is proposed to generate test data for an unbiased comparison of these methods. This model provides realistic simulated patient data and is independent of and different from any computational method. The flow of contrast agent solute and blood through cerebral vasculature with disease-specific configurations is simulated. Blood and contrast agent dynamics are modeled as a combination of convection and diffusion in tubular networks. A combination of a cerebral arterial model and a microvascular model provides arterial-input and time-concentration curves for a wide range of flow and perfusion statuses. The model is configured to represent an embolic stroke in one middle cerebral artery territory and provides physiologically plausible vascular dispersion operators for major arteries and tissue contrast agent retention functions. These curves are fit to simpler template curves to allow the use of the simulation results in multiple validation studies. A gamma-variate function with fit parameters is proposed as the vascular dispersion operator, and a combination of a boxcar and exponential decay function is proposed as the retention function. Such physiologically plausible operators should be used to create test data that better assess the strengths and the weaknesses of various analysis methods.

  12. Clinical Correlation between Perverted Nystagmus and Brain MRI Abnormal Findings

    PubMed Central

    Han, Won-Gue; Yoon, Hee-Chul; Kim, Tae-Min; Rah, Yoon Chan

    2016-01-01

    Background and Objectives To analyze the clinical correlation between perverted nystagmus and brain magnetic resonance imaging (MRI) abnormal findings and to evaluate whether perverted nystagmus is clinically significant results of brain abnormal lesions or not. Subjects and Methods We performed medical charts review from January 2008 to July 2014, retrospectively. Patients who were suspected central originated vertigo at Frenzel goggles test were included among patients who visited our hospital. To investigate the correlation with nystagmus suspected central originated vertigo and brain MRI abnormal findings, we confirmed whether performing brain MRI or not. Then we exclude that patients not performed brain MRI. Results The number of patients with perverted nystagmus was 15, upbeating was 1 and down-beating was 14. Among these patients, 5 patients have brain MRI abnormal findings. However, 2 patients with MRI abnormal findings were not associated correctly with perverted nystagmus and only 3 patients with perverted nystagmus were considered central originated vertigo and further evaluation and treatment was performed by the department of neurology. Conclusions Perverted nystagmus was considered to the abnormalities at brain lesions, especially cerebellum, but neurologic symptoms and further evaluation were needed for exact diagnosis of central originated vertigo.

  13. Clinical Correlation between Perverted Nystagmus and Brain MRI Abnormal Findings

    PubMed Central

    Han, Won-Gue; Yoon, Hee-Chul; Kim, Tae-Min; Rah, Yoon Chan

    2016-01-01

    Background and Objectives To analyze the clinical correlation between perverted nystagmus and brain magnetic resonance imaging (MRI) abnormal findings and to evaluate whether perverted nystagmus is clinically significant results of brain abnormal lesions or not. Subjects and Methods We performed medical charts review from January 2008 to July 2014, retrospectively. Patients who were suspected central originated vertigo at Frenzel goggles test were included among patients who visited our hospital. To investigate the correlation with nystagmus suspected central originated vertigo and brain MRI abnormal findings, we confirmed whether performing brain MRI or not. Then we exclude that patients not performed brain MRI. Results The number of patients with perverted nystagmus was 15, upbeating was 1 and down-beating was 14. Among these patients, 5 patients have brain MRI abnormal findings. However, 2 patients with MRI abnormal findings were not associated correctly with perverted nystagmus and only 3 patients with perverted nystagmus were considered central originated vertigo and further evaluation and treatment was performed by the department of neurology. Conclusions Perverted nystagmus was considered to the abnormalities at brain lesions, especially cerebellum, but neurologic symptoms and further evaluation were needed for exact diagnosis of central originated vertigo. PMID:27626081

  14. Do thallium myocardial perfusion scan abnormalities predict survival in sarcoid patients without cardiac symptoms

    SciTech Connect

    Kinney, E.L.; Caldwell, J.W. )

    1990-07-01

    Whereas the total mortality rate for sarcoidosis is 0.2 per 100,000, the prognosis, when the heart is involved, is very much worse. The authors used the difference in mortality rate to infer whether thallium 201 myocardial perfusion scan abnormalities correspond to myocardial sarcoid by making the simplifying assumption that if they do, then patients with abnormal scans will be found to have a death rate similar to patients with sarcoid heart disease. The authors therefore analyzed complete survival data on 52 sarcoid patients without cardiac symptoms an average of eighty-nine months after they had been scanned as part of a protocol. By use of survival analysis (the Cox proportional hazards model), the only variable that was significantly associated with survival was age. The patients' scan pattern, treatment status, gender, and race were not significantly related to survival. The authors conclude that thallium myocardial perfusion scans cannot reliably be used to diagnose sarcoid heart disease in sarcoid patients without cardiac symptoms.

  15. Baseline brain perfusion and brain structure in patients with major depression: a multimodal magnetic resonance imaging study

    PubMed Central

    Vasic, Nenad; Wolf, Nadine D.; Grön, Georg; Sosic-Vasic, Zrinka; Connemann, Bernhard J.; Sambataro, Fabio; von Strombeck, Anna; Lang, Dirk; Otte, Stefanie; Dudek, Manuela; Wolf, Robert C.

    2015-01-01

    Background Abnormal regional cerebral blood flow (rCBF) and grey matter volume have been frequently reported in patients with major depressive disorder (MDD). However, it is unclear to what extent structural and functional change co-occurs in patients with MDD and whether markers of neural activity, such as rCBF, can be predicted by structural change. Methods Using MRI, we investigated resting-state rCBF and brain structure in patients with MDD and healthy controls between July 2008 and January 2013. We acquired perfusion images obtained with continuous arterial spin labelling, used voxel-based morphometry to assess grey matter volume and integrated biological parametric mapping analyses to investigate the impact of brain atrophy on rCBF. Results We included 43 patients and 29 controls in our study. Frontotemporal grey matter volume was reduced in patients compared with controls. In patients, rCBF was reduced in the anterior cingulate and bilateral parahippocampal areas and increased in frontoparietal and striatal regions. These abnormalities were confirmed by analyses with brain volume as a covariate. In patients with MDD there were significant negative correlations between the extent of depressive symptoms and bilateral parahippocampal rCBF. We found a positive correlation between depressive symptoms and rCBF for right middle frontal cortical blood flow. Limitations Medication use in patients has to be considered as a limitation of our study. Conclusion Our data suggest that while changes of cerebral blood flow and brain volume co-occur in patients with MDD, structural change is not sufficient to explain altered neural activity in patients at rest. Abnormal brain structure and function in patients with MDD appear to reflect distinct levels of neuropathology. PMID:26125119

  16. [Antegrade unilateral perfusion of the brain through the brachiocephalic trunk in operations on the aortic arch].

    PubMed

    Kozlov, B N; Panfilov, D S; Kuznetsov, M S; Ponomarenko, I V; Nasrashvili, G G; Shipulin, V M

    2016-01-01

    Presented herein is a technique of unilateral antegrade perfusion of the brain in operations on the aortic arch. The method makes it possible to perform both systemic artificial circulation and adequate physiological perfusion of the brain, promoting minimization of the number of neurological complications. PMID:27100557

  17. Arterial Spin Labeling Perfusion Study in the Patients with Subacute Mild Traumatic Brain Injury

    PubMed Central

    Lin, Che-Ming; Tseng, Ying-Chi; Hsu, Hui-Ling; Chen, Chi-Jen; Chen, David Yen-Ting; Yan, Feng-Xian; Chiu, Wen-Ta

    2016-01-01

    Background This study uses a MRI technique, three-dimension pulse continuous arterial spin labeling (3D-PCASL), to measure the patient’s cerebral blood flow (CBF) at the subacute stage of mild traumatic brain injury (MTBI) in order to analyze the relationship between cerebral blood flow and neurocognitive deficits. Objective To provide the relationship between cortical CBF and neuropsychological dysfunction for the subacute MTBI patients. Methods After MTBI, perfusion MR imaging technique (3D-PCASL) measures the CBF of MTBI patients (n = 23) within 1 month and that of normal controls (n = 22) to determine the quantity and location of perfusion defect. The correlation between CBF abnormalities and cognitive deficits was elucidated by combining the results of the neuropsychological tests of the patients. Result We observed a substantial reduction in CBF in the bilateral frontal and left occipital cortex as compared with the normal persons. In addition, there were correlation between post concussive symptoms (including dizziness and simulator sickness) and CBF in the hypoperfused areas. The more severe symptom was correlated with higher CBF in bilateral frontal and left occipital lobes. Conclusion First, this study determined that despite no significant abnormality detected on conventional CT and MRI studies, hypoperfusion was observed in MTBI group using 3D-PCASL technique in subacute stage, which suggested that this approach may increase sensitivity to MTBI. Second, the correlation between CBF and the severity of post concussive symptoms suggested that changes in cerebral hemodynamics may play a role in pathophysiology underlies the symptoms. PMID:26871696

  18. Brief Report: Brain Mechanisms in Autism: Functional and Structural Abnormalities.

    ERIC Educational Resources Information Center

    Minshew, Nancy J.

    1996-01-01

    This paper summarizes results of research on functional and structural abnormalities of the brain in autism. The current concept of causation is seen to involve multiple biologic levels. A consistent profile of brain function and dysfunction across methods has been found and specific neuropathologic findings have been found; but some research…

  19. Regional Cerebral Blood-Flow with 99mTc-ECD Brain Perfusion SPECT in Landau-Kleffner Syndrome: Report of Two Cases.

    PubMed

    Nemati, Reza; Nabipour, Iraj; Javadi, Hamid; Chabi, Negar; Assadi, Majid

    2014-01-01

    Landau-Kleffner syndrome (LKS) is a rare childhood disorder characterized by acquired aphasia and epilepsy. 99mTc-ECD SPECT imaging was performed in two right-handed children with LKS. A relative decrease in perfusion was found in the left frontal-temporal cortices of both patients as well as in the left and right parietal cortices of one patient with aphasia, without clinical epilepsy. The degree of regional cerebral perfusion impairment did not correlate with the severity of the clinical and EEG abnormalities, but the area of hypoperfusion was compatible with the speech area of the brain. Overall, although asymmetrical temporoparietal perfusion appears as a common finding in LKS, SPECT findings in LKS alone cannot elucidate the pathogenic features of the disorder in the brain. Here, we present two cases of LKS in which we investigated SPECT perfusion scans.

  20. The ageing brain: normal and abnormal memory.

    PubMed Central

    Albert, M S

    1997-01-01

    With advancing age, the majority of individuals experience declines in their ability to learn and remember. An examination of brain structure and function in healthy older persons across the age range indicates that there are substantial changes in the brain that appear to be related to alterations in memory. The nature of the cognitive and neurobiological alterations associated with age-related change is substantially different from that seen in the early stages of a dementing illness, such as Alzheimer's disease. These differences have implications for potential intervention strategies. PMID:9415922

  1. Quantitative iodine-123 IMP imaging of brain perfusion in schizophrenia

    SciTech Connect

    Cohen, M.B.; Lake, R.R.; Graham, L.S.; King, M.A.; Kling, A.S.; Fitten, L.J.; O'Rear, J.; Bronca, G.A.; Gan, M.; Servrin, R. )

    1989-10-01

    Decreased perfusion in the frontal lobes of patients with chronic schizophrenia has been reported by multiple observes using a variety of techniques. Other observers have been unable to confirm this finding using similar techniques. In this study quantitative single photon emission computed tomography brain imaging was performed using p,5n ({sup 123}I)IMP in five normal subjects and ten chronically medicated patients with schizophrenia. The acquisition data were preprocessed with an image dependent Metz filter and reconstructed using a ramp filtered back projection technique. The uptake in each of 50 regions of interest in each subject was normalized to the uptake in the cerebellum. There were no significant confirmed differences in the comparable ratios of normal subjects and patients with schizophrenia even at the p = 0.15 level. Hypofrontality was not observed.

  2. NeuroGam Software Analysis in Epilepsy Diagnosis Using 99mTc-ECD Brain Perfusion SPECT Imaging.

    PubMed

    Fu, Peng; Zhang, Fang; Gao, Jianqing; Jing, Jianmin; Pan, Liping; Li, Dongxue; Wei, Lingge

    2015-09-20

    BACKGROUND The aim of this study was to explore the value of NeuroGam software in diagnosis of epilepsy by 99Tcm-ethyl cysteinate dimer (ECD) brain imaging. MATERIAL AND METHODS NeuroGam was used to analyze 52 cases of clinically proven epilepsy by 99Tcm-ECD brain imaging. The results were compared with EEG and MRI, and the positive rates and localization to epileptic foci were analyzed. RESULTS NeuroGam analysis showed that 42 of 52 epilepsy cases were abnormal. 99Tcm-ECD brain imaging revealed a positive rate of 80.8% (42/52), with 36 out of 42 patients (85.7%) clearly showing an abnormal area. Both were higher than that of brain perfusion SPECT, with a consistency of 64.5% (34/52) using these 2 methods. Decreased regional cerebral blood flow (rCBF) was observed in frontal (18), temporal (20), and parietal lobes (2). Decreased rCBF was seen in frontal and temporal lobes in 4 out of 36 patients, and in temporal and parietal lobes of 2 out of 36 patients. NeuroGam further showed that the abnormal area was located in a different functional area of the brain. EEG abnormalities were detected in 29 out of 52 patients (55.8%) with 16 cases (55.2%) clearly showing an abnormal area. MRI abnormalities were detected in 17 out of 43 cases (39.5%), including 9 cases (52.9%) clearly showing an abnormal area. The consistency of NeuroGam software analysis, and EEG and MRI were 48.1% (25/52) and 34.9% (15/43), respectively. CONCLUSIONS NeuroGam software analysis offers a higher sensitivity in detecting epilepsy than EEG or MRI. It is a powerful tool in 99Tcm-ECD brain imaging.

  3. Associated brain abnormalities in patients with corpus callosum anomalies.

    PubMed

    Tekgül, H; Dizdarer, G; Yalman, O; Sener, N; Yünten, N; Tütüncüoğlu, S

    1999-01-01

    Forty-nine patients with corpus callosum (CC) anomalies were evaluated in terms of the clinical features and magnetic resonance imaging (MRI) findings. CC anomalies were classified as CC agenesis: 6 (12%), CC hypogenesis: 5 (10%), and CC hypoplasia: 38 (78%). In the CC hypoplasia group the mean value of the genu thickness of the CC was 0.29 +/- 0.1 cm, which was less than the normal value of the age-matched normal children (normal range: 0.6-1.2 cm). The associated brain abnormalities were in five distinct groups: gray matter abnormalities, white matter abnormalities, midline brain structure defects, cortical atrophy, and encephalomalacia. There was no uniformity for the clinical spectrum of CC anomalies. Microcephaly, developmental delay and seizures were the prominent findings in patients. The clinical features were more severe in cases with associated brain anomalies.

  4. Reconciling abnormalities of brain network structure and function in schizophrenia.

    PubMed

    Fornito, Alex; Bullmore, Edward T

    2015-02-01

    Schizophrenia is widely regarded as a disorder of abnormal brain connectivity. Magnetic resonance imaging (MRI) suggests that patients show robust reductions of structural connectivity. However, corresponding changes in functional connectivity do not always follow, with increased functional connectivity being reported in many cases. Here, we consider different methodological and mechanistic accounts that might reconcile these apparently contradictory findings and argue that increased functional connectivity in schizophrenia likely represents a pathophysiological dysregulation of brain activity arising from abnormal neurodevelopmental wiring of structural connections linking putative hub regions of association cortex to other brain areas. Elucidating the pathophysiological significance of connectivity abnormalities in schizophrenia will be contingent on better understanding how network structure shapes and constrains function.

  5. An observer study methodology for evaluating detection of motion abnormalities in gated myocardial perfusion SPECT.

    PubMed

    Lalush, David S; Jatko, Megan K; Segars, W Paul

    2005-03-01

    To address the task of detecting nonischemic motion abnormalities from animated displays of gated myocardial perfusion single photon emission computed tomography data, we performed an observer study to evaluate the difference in detection performance between gating to 8 and 16 frames. Images were created from the NCAT mathematical phantom with a realistic heart simulating hypokinetic motion in the left lateral wall. Realistic noise-free projection data were simulated for both normal and defective hearts to obtain 16 frames for the cardiac cycle. Poisson noise was then simulated for each frame to create 50 realizations of each heart, All datasets were processed in two ways: reconstructed as a 16-frame set, and collapsed to 8 frames and reconstructed. Ten observers viewed the cardiac images animated with a realistic real-time frame rate. Observers trained on 100 images and tested on 100 images, rating their confidence on the presence of a motion defect on a continuous scale. None of the observers showed a significant difference in performance between the two gating methods. The 95% confidence interval on the difference in areas under the ROC curve (Az8 - Az16) was -0.029-0.085. Our test did not find a significant difference in detection performance between 8-frame gating and 16-frame gating. We conclude that, for the task of detecting abnormal motion, increasing the number of gated frames from 8 to 16 offers no apparent advantage.

  6. Brain abnormalities in murderers indicated by positron emission tomography.

    PubMed

    Raine, A; Buchsbaum, M; LaCasse, L

    1997-09-15

    Murderers pleading not guilty by reason of insanity (NGRI) are thought to have brain dysfunction, but there have been no previous studies reporting direct measures of both cortical and subcortical brain functioning in this specific group. Positron emission tomography brain imaging using a continuous performance challenge task was conducted on 41 murderers pleading not guilty by reason of insanity and 41 age- and sex-matched controls. Murderers were characterized by reduced glucose metabolism in the prefrontal cortex, superior parietal gyrus, left angular gyrus, and the corpus callosum, while abnormal asymmetries of activity (left hemisphere lower than right) were also found in the amygdala, thalamus, and medial temporal lobe. These preliminary findings provide initial indications of a network of abnormal cortical and subcortical brain processes that may predispose to violence in murderers pleading NGRI.

  7. Mapping brain volumetric abnormalities in never-treated pathological gamblers.

    PubMed

    Fuentes, Daniel; Rzezak, Patricia; Pereira, Fabricio R; Malloy-Diniz, Leandro F; Santos, Luciana C; Duran, Fábio L S; Barreiros, Maria A; Castro, Cláudio C; Busatto, Geraldo F; Tavares, Hermano; Gorenstein, Clarice

    2015-06-30

    Several magnetic resonance imaging (MRI) studies to date have investigated brain abnormalities in association with the diagnosis of pathological gambling (PG), but very few of these have specifically searched for brain volume differences between PG patients and healthy volunteers (HV). To investigate brain volume differences between PG patients and HV, 30 male never-treated PG patients (DSM-IV-TR criteria) and 30 closely matched HV without history of psychiatric disorders in the past 2 years underwent structural magnetic resonance imaging with a 1.5-T instrument. Using Freesurfer software, we performed an exploratory whole-brain voxelwise volume comparison between the PG group and the HV group, with false-discovery rate correction for multiple comparisons (p < 0.05). Using a more flexible statistical threshold (p < 0.01, uncorrected for multiple comparisons), we also measured absolute and regional volumes of several brain structures separately. The voxelwise analysis showed no clusters of significant regional differences between the PG and HV groups. The additional analyses of absolute and regional brain volumes showed increased absolute global gray matter volumes in PG patients relative to the HV group, as well as relatively decreased volumes specifically in the left putamen, right thalamus and right hippocampus (corrected for total gray matter). Our findings indicate that structural brain abnormalities may contribute to the functional changes associated with the symptoms of PG, and they highlight the relevance of the brain reward system to the pathophysiology of this disorder.

  8. Fetal Brain during a Binge Drinking Episode: A dynamic susceptibility contrast MRI fetal brain perfusion study

    PubMed Central

    Kochunov, Peter; Castro, Carlos; Davis, Duff M; Dudley, Donald; Wey, Hsiao-Ying; Purdy, David; Fox, Peter T; Simerly, Calvin; Schatten, Gerald

    2010-01-01

    We assessed the effects of a single episode of maternal alcohol intoxication on fetal brain blood perfusion in three pregnant dam (baboons) at the 24th week of pregnancy, using dynamic susceptibility contrast MRI. Following the oral administration of alcohol there was a four-fold increase in the peak contrast concentrations in the fetal brain. Additionally, we observed a two-to-three fold increase in the contrast uptake and washout rates in fetal brain. The underlying mechanisms of these changes are unknown but we hypothesized these could include the alcohol-mediated changes in placental permeability and fetal cerebral blood flow. Our findings indicate that alcohol intoxication produced profound changes, which may detrimentally influence neurodevelopmental processes in the brain. PMID:20505549

  9. Brain perfusion SPECT and MRI in foetal alcohol syndrome.

    PubMed

    Riikonen, R; Salonen, I; Partanen, K; Verho, S

    1999-10-01

    Six boys and five girls with a mean age of 8.6 (range 3 to 13) years with foetal alcohol syndrome (FAS) were studied by MRI and single photon emission computed tomography (SPECT) to find specific areas of vulnerability. Morphological anomalies shown in six of 11 patients by MRI were situated both cortically and subcortically: cortical atrophy (N = 2), dilated ventricle (N = 1), corpus callosum hypoplasia (N = 1), cerebellar atrophy (N = 2), one of the latter with Arnold-Chiari malformation (N = 1). Delayed myelination of the white matter was seen in two patients. Volumetric studies of the hippocampus showed morphological left-right asymmetry in five of eight patients. However, SPECT showed mild hypoperfusion of the left hemisphere in all 10 subjects. The negative left-right index was located especially in the left parietooccipital region, i.e. in the brain areas implicated in arithmetical and logical-grammatical functions, which are known to be affected in FAS. Normal left-right dominance was also lacking in the frontal area, i.e. the brain area affected in attention-deficit-hyperactivity disorder (ADHD). Detection of these abnormalities, although they are not unique to FAS, may be helpful in the diagnosis and any attempts at rehabilitation. Diverse morphological and functional abnormalities are more frequent than has usually been believed even in less impaired children with FAS.

  10. Genetic abnormality predicts benefit for a rare brain tumor

    Cancer.gov

    A clinical trial has shown that addition of chemotherapy to radiation therapy leads to a near doubling of median survival time in patients with a form of brain tumor (oligodendroglioma) that carries a chromosomal abnormality called the 1p19q co-deletion.

  11. Morphometric Brain Abnormalities in Boys with Conduct Disorder

    ERIC Educational Resources Information Center

    Huebner, Thomas; Vloet, Timo D.; Marx, Ivo; Konrad, Kerstin; Fink, Gereon R.; Herpertz, Sabine C.; Herpertz-Dahlmann, Beate

    2008-01-01

    Conduct disorder (CD) is associated with antisocial personality behavior that violates the basic rights of others. Results, on examining the structural brain aberrations in boys' CD, show that boys with CD and cormobid attention-deficit/hyperactivity disorder showed abnormalities in frontolimbic areas that could contribute to antisocial…

  12. Abnormal brain structure in adults with Van der Woude syndrome.

    PubMed

    Nopoulos, P; Richman, L; Andreasen, N C; Murray, J C; Schutte, B

    2007-06-01

    Van der Woude syndrome (VWS) is an autosomal dominant disorder manifested in cleft lip and/or palate and lip pits. Isolated clefts of the lip and/or palate (ICLP) have both genotype and phenotype overlap with VWS. Subjects with ICLP have abnormalities in brain structure and function. Given the similarities between VWS and ICLP, the current study was designed to evaluate the pattern of brain structure of adults with VWS. Fourteen adults with VWS were compared to age- and gender-matched healthy controls. Brain structure was evaluated using magnetic resonance imaging. All subjects with VWS had enlarged volumes of the anterior regions of the cerebrum. Men with VWS had reduced volumes of the posterior cerebrum. Anterior cerebrum volume was negatively correlated with intelligent quotient in the subjects with VWS indicating that the enlargement of this brain region was 'pathologic.' The pattern of brain structure in VWS is nearly identical to those seen in ICLP. In addition, men are affected more severely. Pathologic enlargement of the tissue and a gender effect with men affected more severely are common features of neurodevelopmental disorders supporting the notion that the brain structure of VWS and ICLP may be because of abnormal brain development. PMID:17539900

  13. Brain tumors and synchrotron radiation: Methodological developments in quantitative brain perfusion imaging and radiation therapy

    SciTech Connect

    Adam, Jean-Francois

    2005-04-01

    High-grade gliomas are the most frequent type of primary brain tumors in adults. Unfortunately, the management of glioblastomas is still mainly palliative and remains a difficult challenge, despite advances in brain tumor molecular biology and in some emerging therapies. Synchrotron radiation opens fields for medical imaging and radiation therapy by using monochromatic intense x-ray beams. It is now well known that angiogenesis plays a critical role in the tumor growth process and that brain perfusion is representative of the tumor mitotic activity. Synchrotron radiation quantitative computed tomography (SRCT) is one of the most accurate techniques for measuring in vivo contrast agent concentration and thus computing precise and accurate absolute values of the brain perfusion key parameters. The methodological developments of SRCT absolute brain perfusion measurements as well as their preclinical validation are detailed in this thesis. In particular, absolute cerebral volume and blood brain barrier permeability high-resolution (pixel size <50x50 {mu}m{sup 2}) parametric maps were reported. In conventional radiotherapy, the treatment of these tumors remains a delicate challenge, because the damages to the surrounding normal brain tissue limit the amount of radiation that can be delivered. One strategy to overcome this limitation is to infuse an iodinated contrast agent to the patient during the irradiation. The contrast agent accumulates in the tumor, through the broken blood brain barrier, and the irradiation is performed with kilovoltage x rays, in tomography mode, the tumor being located at the center of rotation and the beam size adjusted to the tumor dimensions. The dose enhancement results from the photoelectric effect on the heavy element and from the irradiation geometry. Synchrotron beams, providing high intensity, tunable monochromatic x rays, are ideal for this treatment. The beam properties allow the selection of monochromatic irradiation, at the optimal

  14. Connectivity and functional profiling of abnormal brain structures in pedophilia

    PubMed Central

    Poeppl, Timm B.; Eickhoff, Simon B.; Fox, Peter T.; Laird, Angela R.; Rupprecht, Rainer; Langguth, Berthold; Bzdok, Danilo

    2015-01-01

    Despite its 0.5–1% lifetime prevalence in men and its general societal relevance, neuroimaging investigations in pedophilia are scarce. Preliminary findings indicate abnormal brain structure and function. However, no study has yet linked structural alterations in pedophiles to both connectional and functional properties of the aberrant hotspots. The relationship between morphological alterations and brain function in pedophilia as well as their contribution to its psychopathology thus remain unclear. First, we assessed bimodal connectivity of structurally altered candidate regions using meta-analytic connectivity modeling (MACM) and resting-state correlations employing openly accessible data. We compared the ensuing connectivity maps to the activation likelihood estimation (ALE) maps of a recent quantitative meta-analysis of brain activity during processing of sexual stimuli. Second, we functionally characterized the structurally altered regions employing meta-data of a large-scale neuroimaging database. Candidate regions were functionally connected to key areas for processing of sexual stimuli. Moreover, we found that the functional role of structurally altered brain regions in pedophilia relates to nonsexual emotional as well as neurocognitive and executive functions, previously reported to be impaired in pedophiles. Our results suggest that structural brain alterations affect neural networks for sexual processing by way of disrupted functional connectivity, which may entail abnormal sexual arousal patterns. The findings moreover indicate that structural alterations account for common affective and neurocognitive impairments in pedophilia. The present multi-modal integration of brain structure and function analyses links sexual and nonsexual psychopathology in pedophilia. PMID:25733379

  15. Sleep Deprivation Reveals Altered Brain Perfusion Patterns in Somnambulism

    PubMed Central

    Dang-Vu, Thien Thanh; Zadra, Antonio; Labelle, Marc-Antoine; Petit, Dominique; Soucy, Jean-Paul; Montplaisir, Jacques

    2015-01-01

    Background Despite its high prevalence, relatively little is known about the pathophysiology of somnambulism. Increasing evidence indicates that somnambulism is associated with functional abnormalities during wakefulness and that sleep deprivation constitutes an important drive that facilitates sleepwalking in predisposed patients. Here, we studied the neural mechanisms associated with somnambulism using Single Photon Emission Computed Tomography (SPECT) with 99mTc-Ethylene Cysteinate Dimer (ECD), during wakefulness and after sleep deprivation. Methods Ten adult sleepwalkers and twelve controls with normal sleep were scanned using 99mTc-ECD SPECT in morning wakefulness after a full night of sleep. Eight of the sleepwalkers and nine of the controls were also scanned during wakefulness after a night of total sleep deprivation. Between-group comparisons of regional cerebral blood flow (rCBF) were performed to characterize brain activity patterns during wakefulness in sleepwalkers. Results During wakefulness following a night of total sleep deprivation, rCBF was decreased bilaterally in the inferior temporal gyrus in sleepwalkers compared to controls. Conclusions Functional neural abnormalities can be observed during wakefulness in somnambulism, particularly after sleep deprivation and in the inferior temporal cortex. Sleep deprivation thus not only facilitates the occurrence of sleepwalking episodes, but also uncovers patterns of neural dysfunction that characterize sleepwalkers during wakefulness. PMID:26241047

  16. Brain abnormality segmentation based on l1-norm minimization

    NASA Astrophysics Data System (ADS)

    Zeng, Ke; Erus, Guray; Tanwar, Manoj; Davatzikos, Christos

    2014-03-01

    We present a method that uses sparse representations to model the inter-individual variability of healthy anatomy from a limited number of normal medical images. Abnormalities in MR images are then defined as deviations from the normal variation. More precisely, we model an abnormal (pathological) signal y as the superposition of a normal part ~y that can be sparsely represented under an example-based dictionary, and an abnormal part r. Motivated by a dense error correction scheme recently proposed for sparse signal recovery, we use l1- norm minimization to separate ~y and r. We extend the existing framework, which was mainly used on robust face recognition in a discriminative setting, to address challenges of brain image analysis, particularly the high dimensionality and low sample size problem. The dictionary is constructed from local image patches extracted from training images aligned using smooth transformations, together with minor perturbations of those patches. A multi-scale sliding-window scheme is applied to capture anatomical variations ranging from fine and localized to coarser and more global. The statistical significance of the abnormality term r is obtained by comparison to its empirical distribution through cross-validation, and is used to assign an abnormality score to each voxel. In our validation experiments the method is applied for segmenting abnormalities on 2-D slices of FLAIR images, and we obtain segmentation results consistent with the expert-defined masks.

  17. Inborn errors of metabolism: a cause of abnormal brain development.

    PubMed

    Nissenkorn, A; Michelson, M; Ben-Zeev, B; Lerman-Sagie, T

    2001-05-22

    Brain malformations are caused by a disruption in the sequence of normal development by various environmental or genetic factors. By modifying the intrauterine milieu, inborn errors of metabolism may cause brain dysgenesis. However, this association is typically described in single case reports. The authors review the relationship between brain dysgenesis and specific inborn errors of metabolism. Peroxisomal disorders and fatty acid oxidation defects can produce migration defects. Pyruvate dehydrogenase deficiency, nonketotic hyperglycinemia, and maternal phenylketonuria preferentially cause a dysgenetic corpus callosum. Abnormal metabolism of folic acid causes neural tube defects, whereas defects in cholesterol metabolism may produce holoprosencephaly. Various mechanisms have been proposed to explain abnormal brain development in inborn errors of metabolism: production of a toxic or energy-deficient intrauterine milieu, modification of the content and function of membranes, or disturbance of the normal expression of intrauterine genes responsible for morphogenesis. The recognition of a metabolic disorder as the cause of the brain malformation has implications for both the care of the patient and for genetic counseling to prevent recurrence in subsequent pregnancies. PMID:11383558

  18. Gyrification brain abnormalities as predictors of outcome in anorexia nervosa.

    PubMed

    Favaro, Angela; Tenconi, Elena; Degortes, Daniela; Manara, Renzo; Santonastaso, Paolo

    2015-12-01

    Gyrification brain abnormalities are considered a marker of early deviations from normal developmental trajectories and a putative predictor of poor outcome in psychiatric disorders. The aim of this study was to explore cortical folding morphology in patients with anorexia nervosa (AN). A MRI brain study was conducted on 38 patients with AN, 20 fully recovered patients, and 38 healthy women. Local gyrification was measured with procedures implemented in FreeSurfer. Vertex-wise comparisons were carried out to compare: (1) AN patients and healthy women; (2) patients with a full remission at a 3-year longitudinal follow-up assessment and patients who did not recover. AN patients exhibited significantly lower gyrification when compared with healthy controls. Patients with a poor 3-year outcome had significantly lower baseline gyrification when compared to both healthy women and patients with full recovery at follow-up, even after controlling for the effects of duration of illness and gray matter volume. No significant correlation has been found between gyrification, body mass index, amount of weight loss, onset age, and duration of illness. Brain gyrification significantly predicted outcome at follow-up even after controlling for the effects of duration of illness and other clinical prognostic factors. Although the role of starvation in determining our findings cannot be excluded, our study showed that brain gyrification might be a predictor of outcome in AN. Further studies are needed to understand if brain gyrification abnormalities are indices of early neurodevelopmental alterations, the consequence of starvation, or the interaction between both factors.

  19. Volumetric brain abnormalities in polysubstance use disorder patients

    PubMed Central

    Noyan, Cemal Onur; Kose, Samet; Nurmedov, Serdar; Metin, Baris; Darcin, Aslı Enez; Dilbaz, Nesrin

    2016-01-01

    Aim Polysubstance users represent the largest group of patients seeking treatment at addiction and rehabilitation clinics in Turkey. There is little knowledge about the structural brain abnormalities seen in polysubstance users. This study was conducted to examine the structural brain differences between polysubstance use disorder patients and healthy control subjects using voxel-based morphometry. Methods Forty-six male polysubstance use disorder patients in the early abstinence period and 30 healthy male controls underwent structural magnetic resonance imaging scans. Voxel-based morphometry analysis was performed to examine gray matter (GM) abnormality differences. Results Polysubstance use disorder patients displayed significantly smaller GM volume in the thalamus, temporal pole, superior frontal gyrus, cerebellum, gyrus rectus, occipital lobe, anterior cingulate cortex, superior temporal gyrus, and postcentral gyrus. Conclusion A widespread and smaller GM volume has been found at different regions of the frontal, temporal, occipital, and parietal lobes, cerebellum, and anterior cingulate cortex in polysubstance users. PMID:27358566

  20. Cerebral blood flow is an earlier indicator of perfusion abnormalities than cerebral blood volume in Alzheimer's disease.

    PubMed

    Lacalle-Aurioles, María; Mateos-Pérez, José M; Guzmán-De-Villoria, Juan A; Olazarán, Javier; Cruz-Orduña, Isabel; Alemán-Gómez, Yasser; Martino, María-Elena; Desco, Manuel

    2014-04-01

    The purpose of this study was to elucidate whether cerebral blood flow (CBF) can better characterize perfusion abnormalities in predementia stages of Alzheimer's disease (AD) than cerebral blood volume (CBV) and whether cortical atrophy is more associated with decreased CBV or with decreased CBF. We compared measurements of CBV, CBF, and mean cortical thickness obtained from magnetic resonance images in a group of healthy controls, patients with mild cognitive impairment (MCI) who converted to AD after 2 years of clinical follow-up (MCI-c), and patients with mild AD. A significant decrease in perfusion was detected in the parietal lobes of the MCI-c patients with CBF parametric maps but not with CBV maps. In the MCI-c group, a negative correlation between CBF values and cortical thickness in the right parahippocampal gyrus suggests an increase in CBF that depends on cortical atrophy in predementia stages of AD. Our study also suggests that CBF deficits appear before CBV deficits in the progression of AD, as CBV abnormalities were only detected at the AD stage, whereas CBF changes were already detected in the MCI stage. These results confirm the hypothesis that CBF is a more sensitive parameter than CBV for perfusion abnormalities in MCI-c patients.

  1. Cerebral blood flow is an earlier indicator of perfusion abnormalities than cerebral blood volume in Alzheimer's disease

    PubMed Central

    Lacalle-Aurioles, María; Mateos-Pérez, José M; Guzmán-De-Villoria, Juan A; Olazarán, Javier; Cruz-Orduña, Isabel; Alemán-Gómez, Yasser; Martino, María-Elena; Desco, Manuel

    2014-01-01

    The purpose of this study was to elucidate whether cerebral blood flow (CBF) can better characterize perfusion abnormalities in predementia stages of Alzheimer's disease (AD) than cerebral blood volume (CBV) and whether cortical atrophy is more associated with decreased CBV or with decreased CBF. We compared measurements of CBV, CBF, and mean cortical thickness obtained from magnetic resonance images in a group of healthy controls, patients with mild cognitive impairment (MCI) who converted to AD after 2 years of clinical follow-up (MCI-c), and patients with mild AD. A significant decrease in perfusion was detected in the parietal lobes of the MCI-c patients with CBF parametric maps but not with CBV maps. In the MCI-c group, a negative correlation between CBF values and cortical thickness in the right parahippocampal gyrus suggests an increase in CBF that depends on cortical atrophy in predementia stages of AD. Our study also suggests that CBF deficits appear before CBV deficits in the progression of AD, as CBV abnormalities were only detected at the AD stage, whereas CBF changes were already detected in the MCI stage. These results confirm the hypothesis that CBF is a more sensitive parameter than CBV for perfusion abnormalities in MCI-c patients. PMID:24424381

  2. Correction for partial volume effects in brain perfusion ECT imaging

    NASA Astrophysics Data System (ADS)

    Koole, Michel; Staelens, Steven; Van de Walle, Rik; Lemahieu, Ignace L.

    2003-05-01

    The accurate quantification of brain perfusion for emission computed tomography data (PET-SPECT) is limited by partial volume effects (PVE). This study presents a new approach to estimate accurately the true tissue tracer activity within the grey matter tissue compartment. The methodology is based on the availability of additional anatomical side information and on the assumption that activity concentration within the white matter tissue compartment is constant. Starting from an initial estimate for the white matter grey matter activity, the true tracer activity within the grey matter tissue compartment is estimated by an alternating ML-EM-algorithm. During the updating step the constant activity concentration within the white matter compartment is modelled in the forward projection in order to reconstruct the true activity distribution within the grey matter tissue compartment, hence reducing partial volume averaging. Consequently the estimate for the constant activity in the white matter tissue compartment is updated based on the new estimated activity distribution in the grey matter tissue compartment. We have tested this methodology by means of computer simulations. A T1-weighted MR brainscan of a patient was segmented into white matter, grey matter and cerebrospinal fluid, using the segmentation package of the SPM-software (Statistical Parametric Mapping). The segmented grey and white matter were used to simulate a SPECT acquisition, modelling the noise and the distance dependant detector response. Scatter and attenuation were ignored. Following the above described strategy, simulations have shown it is possible to reconstruct the true activity distribution for the grey matter tissue compartment (activity/tissue volume), assuming constant activity in the white matter tissue compartment.

  3. Non Tumor Perfusion Changes Following Stereotactic Radiosurgery to Brain Metastases

    PubMed Central

    Jakubovic, Raphael; Sahgal, Arjun; Ruschin, Mark; Pejović-Milić, Ana; Milwid, Rachael; Aviv, Richard I.

    2015-01-01

    Purpose: To evaluate early perfusion changes in normal tissue following stereotactic radiosurgery (SRS). Methods: Nineteen patients harboring twenty-two brain metastases treated with SRS were imaged with dynamic susceptibility magnetic resonance imaging (DSC MRI) at baseline, 1 week and 1 month post SRS. Relative cerebral blood volume and flow (rCBV and rCBF) ratios were evaluated outside of tumor within a combined region of interest (ROI) and separately within gray matter (GM) and white matter (WM) ROIs. Three-dimensional dose distribution from each SRS plan was divided into six regions: (1) <2 Gy; (2) 2-5 Gy; (3) 5-10 Gy; (4) 10-12 Gy; (5) 12-16 Gy; and (6) >16 Gy. rCBV and rCBF ratio differences between baseline, 1 week and 1 month were compared. Best linear fit plots quantified normal tissue dose-dependency. Results: Significant rCBV ratio increases were present between baseline and 1 month for all ROIs and dose ranges except for WM ROI receiving <2 Gy. rCBV ratio for all ROIs was maximally increased from baseline to 1 month with the greatest changes occurring within the 5-10 Gy dose range (53.1%). rCBF ratio was maximally increased from baseline to 1 month for all ROIs within the 5-10 Gy dose range (33.9-45.0%). Both rCBV and rCBF ratios were most elevated within GM ROIs. A weak, positive but not significant association between dose, rCBV and rCBF ratio was demonstrated. Progressive rCBV and rCBF ratio increased with dose up to 10 Gy at 1 month. Conclusion: Normal tissue response following SRS can be characterized by dose, tissue, and time specific increases in rCBV and rCBF ratio. PMID:26269612

  4. Midline Brain Abnormalities Across Psychotic and Mood Disorders.

    PubMed

    Landin-Romero, Ramón; Amann, Benedikt L; Sarró, Salvador; Guerrero-Pedraza, Amalia; Vicens, Victor; Rodriguez-Cano, Elena; Vieta, Eduard; Salvador, Raymond; Pomarol-Clotet, Edith; Radua, Joaquim

    2016-01-01

    Patients with schizophrenia are known to have increased prevalence of abnormalities in midline brain structures, such as a failure of the septum pellucidum to fuse (cavum septum pellucidum) and the absence of the adhesio interthalamica. This is the first study to investigate the prevalence of these abnormalities across a large multidiagnostic sample. Presence of cavum septum pellucidum and absence of the adhesio interthalamica was assessed in 639 patients with chronic schizophrenia, delusional disorder, schizoaffective disorder, bipolar disorder, major depressive disorder, or a first episode of psychosis, mania or unipolar depression. This was compared with 223 healthy controls using logistic-regression-derived odds ratios (OR). Patients with psychotic or mood disorders showed an increased prevalence of both abnormalities (OR of cavum septum pellucidum = 2.1, OR of absence of the adhesio interthalamica = 2.6, OR of both cavum septum pellucidum and absence of the adhesio interthalamica = 3.8, all P < .001). This increased prevalence was separately observed in nearly all disorders as well as after controlling for potential confounding factors. This study supports a general increased prevalence of midline brain abnormalities across mood and psychotic disorders. This nonspecificity may suggest that these disorders share a common neurodevelopmental etiology.

  5. Physiological and psychological individual differences influence resting brain function measured by ASL perfusion.

    PubMed

    Kano, M; Coen, S J; Farmer, A D; Aziz, Q; Williams, S C R; Alsop, D C; Fukudo, S; O'Gorman, R L

    2014-09-01

    Effects of physiological and/or psychological inter-individual differences on the resting brain state have not been fully established. The present study investigated the effects of individual differences in basal autonomic tone and positive and negative personality dimensions on resting brain activity. Whole-brain resting cerebral perfusion images were acquired from 32 healthy subjects (16 males) using arterial spin labeling perfusion MRI. Neuroticism and extraversion were assessed with the Eysenck Personality Questionnaire-Revised. Resting autonomic activity was assessed using a validated measure of baseline cardiac vagal tone (CVT) in each individual. Potential associations between the perfusion data and individual CVT (27 subjects) and personality score (28 subjects) were tested at the level of voxel clusters by fitting a multiple regression model at each intracerebral voxel. Greater baseline perfusion in the dorsal anterior cingulate cortex (ACC) and cerebellum was associated with lower CVT. At a corrected significance threshold of p < 0.01, strong positive correlations were observed between extraversion and resting brain perfusion in the right caudate, brain stem, and cingulate gyrus. Significant negative correlations between neuroticism and regional cerebral perfusion were identified in the left amygdala, bilateral insula, ACC, and orbitofrontal cortex. These results suggest that individual autonomic tone and psychological variability influence resting brain activity in brain regions, previously shown to be associated with autonomic arousal (dorsal ACC) and personality traits (amygdala, caudate, etc.) during active task processing. The resting brain state may therefore need to be taken into account when interpreting the neurobiology of individual differences in structural and functional brain activity.

  6. Fast nonlinear regression method for CT brain perfusion analysis.

    PubMed

    Bennink, Edwin; Oosterbroek, Jaap; Kudo, Kohsuke; Viergever, Max A; Velthuis, Birgitta K; de Jong, Hugo W A M

    2016-04-01

    Although computed tomography (CT) perfusion (CTP) imaging enables rapid diagnosis and prognosis of ischemic stroke, current CTP analysis methods have several shortcomings. We propose a fast nonlinear regression method with a box-shaped model (boxNLR) that has important advantages over the current state-of-the-art method, block-circulant singular value decomposition (bSVD). These advantages include improved robustness to attenuation curve truncation, extensibility, and unified estimation of perfusion parameters. The method is compared with bSVD and with a commercial SVD-based method. The three methods were quantitatively evaluated by means of a digital perfusion phantom, described by Kudo et al. and qualitatively with the aid of 50 clinical CTP scans. All three methods yielded high Pearson correlation coefficients ([Formula: see text]) with the ground truth in the phantom. The boxNLR perfusion maps of the clinical scans showed higher correlation with bSVD than the perfusion maps from the commercial method. Furthermore, it was shown that boxNLR estimates are robust to noise, truncation, and tracer delay. The proposed method provides a fast and reliable way of estimating perfusion parameters from CTP scans. This suggests it could be a viable alternative to current commercial and academic methods. PMID:27413770

  7. Quantitative assessment of angiogenesis, perfused blood vessels and endothelial tip cells in the postnatal mouse brain.

    PubMed

    Wälchli, Thomas; Mateos, José María; Weinman, Oliver; Babic, Daniela; Regli, Luca; Hoerstrup, Simon P; Gerhardt, Holger; Schwab, Martin E; Vogel, Johannes

    2015-01-01

    During development and in various diseases of the CNS, new blood vessel formation starts with endothelial tip cell selection and vascular sprout migration, followed by the establishment of functional, perfused blood vessels. Here we describe a method that allows the assessment of these distinct angiogenic steps together with antibody-based protein detection in the postnatal mouse brain. Intravascular and perivascular markers such as Evans blue (EB), isolectin B4 (IB4) or laminin (LN) are used alongside simultaneous immunofluorescence on the same sections. By using confocal laser-scanning microscopy and stereological methods for analysis, detailed quantification of the 3D postnatal brain vasculature for perfused and nonperfused vessels (e.g., vascular volume fraction, vessel length and number, number of branch points and perfusion status of the newly formed vessels) and characterization of sprouting activity (e.g., endothelial tip cell density, filopodia number) can be obtained. The entire protocol, from mouse perfusion to vessel analysis, takes ∼10 d.

  8. Abnormal Brain Network Organization in Body Dysmorphic Disorder

    PubMed Central

    Arienzo, Donatello; Leow, Alex; Brown, Jesse A; Zhan, Liang; GadElkarim, Johnson; Hovav, Sarit; Feusner, Jamie D

    2013-01-01

    Body dysmorphic disorder (BDD) is characterized by preoccupation with misperceived defects of appearance, causing significant distress and disability. Previous studies suggest abnormalities in information processing characterized by greater local relative to global processing. The purpose of this study was to probe whole-brain and regional white matter network organization in BDD, and to relate this to specific metrics of symptomatology. We acquired diffusion-weighted 34-direction MR images from 14 unmedicated participants with DSM-IV BDD and 16 healthy controls, from which we conducted whole-brain deterministic diffusion tensor imaging tractography. We then constructed white matter structural connectivity matrices to derive whole-brain and regional graph theory metrics, which we compared between groups. Within the BDD group, we additionally correlated these metrics with scores on psychometric measures of BDD symptom severity as well as poor insight/delusionality. The BDD group showed higher whole-brain mean clustering coefficient than controls. Global efficiency negatively correlated with BDD symptom severity. The BDD group demonstrated greater edge betweenness centrality for connections between the anterior temporal lobe and the occipital cortex, and between bilateral occipital poles. This represents the first brain network analysis in BDD. Results suggest disturbances in whole brain structural topological organization in BDD, in addition to correlations between clinical symptoms and network organization. There is also evidence of abnormal connectivity between regions involved in lower-order visual processing and higher-order visual and emotional processing, as well as interhemispheric visual information transfer. These findings may relate to disturbances in information processing found in previous studies. PMID:23322186

  9. Drag-Reducing Polymer Enhances Microvascular Perfusion in the Traumatized Brain with Intracranial Hypertension.

    PubMed

    Bragin, Denis E; Thomson, Susan; Bragina, Olga; Statom, Gloria; Kameneva, Marina V; Nemoto, Edwin M

    2016-01-01

    Current treatments for traumatic brain injury (TBI) have not focused on improving microvascular perfusion. Drag-reducing polymers (DRP), linear, long-chain, blood-soluble, nontoxic macromolecules, may offer a new approach to improving cerebral perfusion by primary alteration of the fluid dynamic properties of blood. Nanomolar concentrations of DRP have been shown to improve hemodynamics in animal models of ischemic myocardium and ischemic limb, but have not yet been studied in the brain. We recently demonstrated that DRP improved microvascular perfusion and tissue oxygenation in a normal rat brain. We hypothesized that DRP could restore microvascular perfusion in hypertensive brain after TBI. Using in vivo two-photon laser scanning microscopy we examined the effect of DRP on microvascular blood flow and tissue oxygenation in hypertensive rat brains with and without TBI. DRP enhanced and restored capillary flow, decreased microvascular shunt flow, and, as a result, reduced tissue hypoxia in both nontraumatized and traumatized rat brains at high intracranial pressure. Our study suggests that DRP could constitute an effective treatment for improving microvascular flow in brain ischemia caused by high intracranial pressure after TBI. PMID:27165871

  10. Drag-Reducing Polymer Enhances Microvascular Perfusion in the Traumatized Brain with Intracranial Hypertension.

    PubMed

    Bragin, Denis E; Thomson, Susan; Bragina, Olga; Statom, Gloria; Kameneva, Marina V; Nemoto, Edwin M

    2016-01-01

    Current treatments for traumatic brain injury (TBI) have not focused on improving microvascular perfusion. Drag-reducing polymers (DRP), linear, long-chain, blood-soluble, nontoxic macromolecules, may offer a new approach to improving cerebral perfusion by primary alteration of the fluid dynamic properties of blood. Nanomolar concentrations of DRP have been shown to improve hemodynamics in animal models of ischemic myocardium and ischemic limb, but have not yet been studied in the brain. We recently demonstrated that DRP improved microvascular perfusion and tissue oxygenation in a normal rat brain. We hypothesized that DRP could restore microvascular perfusion in hypertensive brain after TBI. Using in vivo two-photon laser scanning microscopy we examined the effect of DRP on microvascular blood flow and tissue oxygenation in hypertensive rat brains with and without TBI. DRP enhanced and restored capillary flow, decreased microvascular shunt flow, and, as a result, reduced tissue hypoxia in both nontraumatized and traumatized rat brains at high intracranial pressure. Our study suggests that DRP could constitute an effective treatment for improving microvascular flow in brain ischemia caused by high intracranial pressure after TBI.

  11. Combining diffusion and perfusion differentiates tumor from bevacizumab-related imaging abnormality (bria).

    PubMed

    Farid, Nikdokht; Almeida-Freitas, Daniela B; White, Nathan S; McDonald, Carrie R; Kuperman, Joshua M; Almutairi, Abdulrahman A; Muller, Karra A; VandenBerg, Scott R; Kesari, Santosh; Dale, Anders M

    2014-12-01

    A subset of patients with high-grade glioma and brain metastases who are treated with bevacizumab develop regions of marked and persistent restricted diffusion that do not reflect recurrent tumor. Here, we quantify the degree of restricted diffusion and the relative cerebral blood volume (rCBV) within these regions of bevacizumab-related imaging abnormality (BRIA) in order to facilitate differentiation of these lesions from recurrent tumor. Six patients with high-grade glioma and two patients with brain metastases who developed regions of restricted diffusion after initiation of bevacizumab were included. Six pre-treatment GBM controls were also included. Restriction spectrum imaging (RSI) was used to create diffusion maps which were co-registered with rCBV maps. Within regions of restricted diffusion, mean RSI values and mean rCBV values were calculated for patients with BRIA and for the GBM controls. These values were also calculated for normal-appearing white matter (NAWM). RSI values in regions of restricted diffusion were higher for both BRIA and tumor when compared to NAWM; furthermore RSI values in BRIA were slightly higher than in tumor. Conversely, rCBV values were very low in BRIA-lower than both tumor and NAWM. However, there was only a trend for rCBV values to be higher in tumor than in NAWM. When evaluating areas of restricted diffusion in patients with high-grade glioma or brain metastases treated with bevacizumab, RSI is better able to detect the presence of pathology whereas rCBV is better able to differentiate BRIA from tumor. Thus, combining these tools may help to differentiate necrotic tissue related to bevacizumab treatment from recurrent tumor.

  12. Electrocardiographic abnormalities and cardiac arrhythmias in structural brain lesions.

    PubMed

    Katsanos, Aristeidis H; Korantzopoulos, Panagiotis; Tsivgoulis, Georgios; Kyritsis, Athanassios P; Kosmidou, Maria; Giannopoulos, Sotirios

    2013-07-31

    Cardiac arrhythmias and electrocardiographic abnormalities are frequently observed after acute cerebrovascular events. The precise mechanism that leads to the development of these arrhythmias is still uncertain, though increasing evidence suggests that it is mainly due to autonomic nervous system dysregulation. In massive brain lesions sympathetic predominance and parasympathetic withdrawal during the first 72 h are associated with the occurrence of severe secondary complications in the first week. Right insular cortex lesions are also related with sympathetic overactivation and with a higher incidence of electrocardiographic abnormalities, mostly QT prolongation, in patients with ischemic stroke. Additionally, female sex and hypokalemia are independent risk factors for severe prolongation of the QT interval which subsequently results in malignant arrhythmias and poor outcome. The prognostic value of repolarization changes commonly seen after aneurysmal subarachnoid hemorrhage, such as ST segment, T wave, and U wave abnormalities, still remains controversial. In patients with traumatic brain injury both intracranial hypertension and cerebral hypoperfusion correlate with low heart rate variability and increased mortality. Given that there are no firm guidelines for the prevention or treatment of the arrhythmias that appear after cerebral incidents this review aims to highlight important issues on this topic. Selected patients with the aforementioned risk factors could benefit from electrocardiographic monitoring, reassessment of the medications that prolong QTc interval, and administration of antiadrenergic agents. Further research is required in order to validate these assumptions and to establish specific therapeutic strategies.

  13. Structural Brain Abnormalities in Youth with Psychosis-Spectrum Symptoms

    PubMed Central

    Satterthwaite, Theodore D.; Wolf, Daniel H.; Calkins, Monica E.; Vandekar, Simon N.; Erus, Guray; Ruparel, Kosha; Roalf, David R.; Linn, Kristin A.; Elliott, Mark A.; Moore, Tyler M.; Hakonarson, Hakon; Shinohara, Russell T.; Davatzikos, Christos; Gur, Ruben C.; Gur, Raquel E.

    2016-01-01

    Importance Structural brain abnormalities are prominent in psychotic disorders including schizophrenia. However, it is unclear when aberrations emerge in the disease process, and if such deficits are present in association with less severe psychosis-spectrum (PS) symptoms in youth. Objective To investigate the presence of structural brain abnormalities in youth with PS symptoms. Design The Philadelphia Neurodevelopmental Cohort (PNC) is a prospectively accrued community-based sample of nearly 10,000 youths who received a structured psychiatric evaluation. A subsample of 1,601 subjects underwent neuroimaging including structural magnetic resonance imaging. Setting The PNC is a collaboration between The Children’s Hospital of Philadelphia and the Hospital of the University of Pennsylvania. Participants Youths ages 8–22 years identified through structured interview as having psychosis-spectrum features (PS, n=391), and typically developing comparison subjects without significant psychopathology (TD, n=400). Main Outcomes and Measures Measures of brain volume derived from T1-weighted structural neuroimaging at 3T. Analyses were conducted at global, regional, and voxelwise levels. Regional volumes were estimated with an advanced multi-atlas regional segmentation procedure; voxelwise volumetric analyses were conducted as well. Nonlinear developmental patterns were examined using penalized splines within a general additive model. PS symptom severity was summarized using factor analysis and evaluated dimensionally. Results Compared to the TD group, the PS group had diminished whole brain gray matter volume and expanded white matter volume. Voxelwise analyses revealed significantly lower gray matter volume in the medial temporal lobes as well as in frontal, temporal, and parietal cortex. Reduction of medial temporal lobe volume was correlated with PS symptom severity. Conclusions and Relevance Structural brain abnormalities that have been commonly reported in adults

  14. Cellular abnormalities in depression: evidence from postmortem brain tissue.

    PubMed

    Stockmeier, Craig A; Rajkowska, Grazyna

    2004-06-01

    During the past two decades, in vivo neuroimaging studies have permitted significant insights into the general location of dysfunctional brain regions in depression. In parallel and often intersecting ways, neuroanatomical, pharmacological, and biochemical studies of postmortem brain tissue are permitting new insights into the pathophysiology of depression. In addition to long-recognized neurochemical abnormalities in depression, novel studies at the microscopic level support the contention that mood disorders are associated with abnormalities in cell morphology and distribution. In the past 6 years, cell-counting studies have identified changes in the density and size of both neurons and glia in a number of frontolimbic brain regions, including dorsolateral prefrontal, orbitofrontal, and anterior cingulate cortex, and the amygdala and hippocampus. Convergence of cellular changes at the microscopic level with neuroimaging changes detected in vivo provides a compelling integration of clinical and basic research for disentangling the pathophysiology of depression. The ultimate integration of these two research approaches will occur with premortem longitudinal clinical studies on well-characterized patients linked to postmortem studies of the same subjects.

  15. Dopamine transporter SPECT/CT and perfusion brain SPECT imaging in idiopathic basal ganglia calcinosis.

    PubMed

    Paschali, Anna; Lakiotis, Velissarios; Messinis, Lambros; Markaki, Elli; Constantoyannis, Constantine; Ellul, John; Vassilakos, Pavlos

    2009-07-01

    A case of idiopathic basal ganglia calcification in a 56-year-old woman with parkinsonism and cognitive impairment is described. The nigrostriatal dopaminergic pathway and regional cerebral blood flow were evaluated using dopamine transporter (DAT) brain single photon emission tomography combined with a low-dose x-ray computerized tomography transmission (hybrid SPECT/CT) and Tc-99m HMPAO brain perfusion SPECT study, respectively. DAT SPECT/CT imaging revealed a reduction in DAT binding in both striatum regions coinciding with bilateral calcifications in the basal ganglia. Brain perfusion scan showed hypoperfusion in basal ganglia regions, posterior parietal cortex bilaterally, left frontopolar and dorsolateral prefrontal cortex, and left temporal lobe. These findings correlated well with the clinical condition of the patient. Mineralization may play a critical role in the pathogenesis of neuronal degeneration. Cortical perfusion changes in patients may better explain the patient's altered cognitive and motor functions.

  16. Influence of Thin Slice Reconstruction on CT Brain Perfusion Analysis

    PubMed Central

    Bennink, Edwin; Oosterbroek, Jaap; Horsch, Alexander D.; Dankbaar, Jan Willem; Velthuis, Birgitta K.; Viergever, Max A.; de Jong, Hugo W. A. M.

    2015-01-01

    Objectives Although CT scanners generally allow dynamic acquisition of thin slices (1 mm), thick slice (≥5 mm) reconstruction is commonly used for stroke imaging to reduce data, processing time, and noise level. Thin slice CT perfusion (CTP) reconstruction may suffer less from partial volume effects, and thus yield more accurate quantitative results with increased resolution. Before thin slice protocols are to be introduced clinically, it needs to be ensured that this does not affect overall CTP constancy. We studied the influence of thin slice reconstruction on average perfusion values by comparing it with standard thick slice reconstruction. Materials and Methods From 50 patient studies, absolute and relative hemisphere averaged estimates of cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT), and permeability-surface area product (PS) were analyzed using 0.8, 2.4, 4.8, and 9.6 mm slice reconstructions. Specifically, the influence of Gaussian and bilateral filtering, the arterial input function (AIF), and motion correction on the perfusion values was investigated. Results Bilateral filtering gave noise levels comparable to isotropic Gaussian filtering, with less partial volume effects. Absolute CBF, CBV and PS were 22%, 14% and 46% lower with 0.8 mm than with 4.8 mm slices. If the AIF and motion correction were based on thin slices prior to reconstruction of thicker slices, these differences reduced to 3%, 4% and 3%. The effect of slice thickness on relative values was very small. Conclusions This study shows that thin slice reconstruction for CTP with unaltered acquisition protocol gives relative perfusion values without clinically relevant bias. It does however affect absolute perfusion values, of which CBF and CBV are most sensitive. Partial volume effects in large arteries and veins lead to overestimation of these values. The effects of reconstruction slice thickness should be taken into account when absolute perfusion values are

  17. Multimodal functional cardiac MRI in creatine kinase-deficient mice reveals subtle abnormalities in myocardial perfusion and mechanics.

    PubMed

    Nahrendorf, Matthias; Streif, Jörg U; Hiller, Karl-Heinz; Hu, Kai; Nordbeck, Peter; Ritter, Oliver; Sosnovik, David; Bauer, Lisa; Neubauer, Stefan; Jakob, Peter M; Ertl, Georg; Spindler, Matthias; Bauer, Wolfgang R

    2006-06-01

    A decrease in the supply of ATP from the creatine kinase (CK) system is thought to contribute to the evolution of heart failure. However, previous studies on mice with a combined knockout of the mitochondrial and cytosolic CK (CK(-/-)) have not revealed overt left ventricular dysfunction. The aim of this study was to employ novel MRI techniques to measure maximal myocardial velocity (V(max)) and myocardial perfusion and thus determine whether abnormalities in the myocardial phenotype existed in CK(-/-) mice, both at baseline and 4 wk after myocardial infarction (MI). As a result, myocardial hypertrophy was seen in all CK(-/-) mice, but ejection fraction (EF) remained normal. V(max), however, was significantly reduced in the CK(-/-) mice [wild-type, 2.32 +/- 0.09 vs. CK(-/-), 1.43 +/- 0.16 cm/s, P < 0.05; and wild-type MI, 1.53 +/- 0.11 vs. CK(-/-) MI, 1.26 +/- 0.11 cm/s, P = not significant (NS), P < 0.05 vs. baseline]. Myocardial perfusion was also lower in the CK(-/-) mice (wild-type, 6.68 +/- 0.27 vs. CK(-/-), 4.12 +/- 0.63 ml/g.min, P < 0.05; and wild-type MI, 3.97 +/- 0.65 vs. CK(-/-) MI, 3.71 +/- 0.57 ml/g.min, P = NS, P < 0.05 vs. baseline), paralleled by a significantly reduced capillary density (histology). In conclusion, myocardial function in transgenic mice may appear normal when only gross indexes of performance such as EF are assessed. However, the use of a combination of novel MRI techniques to measure myocardial perfusion and mechanics allowed the abnormalities in the CK(-/-) phenotype to be detected. The myocardium in CK-deficient mice is characterized by reduced perfusion and reduced maximal contraction velocity, suggesting that the myocardial hypertrophy seen in these mice cannot fully compensate for the absence of the CK system.

  18. Brain perfusion correlates of visuoperceptual deficits in Mild Cognitive Impairment and mild Alzheimer’s disease

    PubMed Central

    Alegret, Montserrat; Vinyes-Junqué, Georgina; Boada, Mercè; Martínez-Lage, Pablo; Cuberas, Gemma; Espinosa, Ana; Roca, Isabel; Hernández, Isabel; Valero, Sergi; Rosende-Roca, Maitée; Mauleón, Ana; Becker, James T.; Tárraga, Lluís

    2012-01-01

    Background Visuoperceptual processing is impaired early in the clinical course of Alzheimer’s disease (AD). The 15-Objects Test (15-OT) detects such subtle performance deficits in Mild Cognitive Impairment (MCI) and mild AD. Reduced brain perfusion in the temporal, parietal and prefrontal regions have been found in early AD and MCI patients. Objectives To confirm the role of the 15-OT in the diagnosis of MCI and AD, and to investigate the brain perfusion correlates of visuoperceptual dysfunction (15-OT) in subjects with MCI, AD and normal aging. Methods Forty-two AD, 42 MCI and 42 healthy elderly control (EC) subjects underwent a brain Single Photon Emission Tomography (SPECT) and separately completed the 15-OT. An analysis of variance compared 15-OT scores between groups. SPM5 was used to analyse the SPECT data. Results 15-OT performace was impaired in the MCI and AD patients. In terms of the SPECT scans, AD patients showed reduced perfusion in temporal-parietal regions, while the MCI subjects had decreased perfusion in the middle and posterior cingulate. When MCI and AD groups were compared, a significant brain perfusion reduction was found in temporo-parietal regions. In the whole sample, 15-OT performance was significantly correlated with the clinical dementia rating scores, and with the perfusion in the bilateral posterior cingulate and the right temporal pole, with no significant correlation in each separate group. Conclusion Our findings suggest that the 15-OT performance provides a useful gradation of impairment from normal aging to AD, and it seems to be related to perfusion in the bilateral posterior cingulate and the right temporal pole. PMID:20555146

  19. Challenges for non-invasive brain perfusion quantification using arterial spin labeling.

    PubMed

    Sousa, I; Santos, N; Sanches, J; Figueiredo, P

    2011-03-29

    Arterial Spin Labeling (ASL) sequences for perfusion Magnetic Resonance Imaging (MRI) have recently become available to be used in the clinical practice, offering a completely non-invasive technique for the quantitative evaluation of brain perfusion. Despite its great potential, ASL perfusion imaging still presents important methodological challenges before its incorporation in routine protocols. Specifically, in some pathological conditions in which the cerebrovascular dynamics is altered, the standard application of ASL may lead to measurement errors. In these cases, it would be possible to estimate perfusion, as well as arterial transit times, by collecting images at multiple time points and then fitting a mathematical model to the data. This approach can be optimized by selecting a set of optimal imaging time points and incorporating knowledge about the physiological distributions of the parameters into the model estimation procedures. In this study, we address the challenges that arise in the measurement of brain perfusion using PASL, due to variations in the arterial transit times, by estimating the errors produced using different types of acquisitions and proposing methods for minimizing such errors. We show by simulation that multiple inversion time ASL acquisitions are expected to reduce measurement errors relative to standard approaches. In data collected from a group of subjects, we further observed reduced inter-subject variability in perfusion measurements when using a multiple versus single inversion time acquisitions. Both measurement errors and variability were further reduced if optimized acquisition and analysis techniques were employed.

  20. Challenges for non-invasive brain perfusion quantification using arterial spin labeling.

    PubMed

    Sousa, I; Santos, N; Sanches, J; Figueiredo, P

    2011-03-29

    Arterial Spin Labeling (ASL) sequences for perfusion Magnetic Resonance Imaging (MRI) have recently become available to be used in the clinical practice, offering a completely non-invasive technique for the quantitative evaluation of brain perfusion. Despite its great potential, ASL perfusion imaging still presents important methodological challenges before its incorporation in routine protocols. Specifically, in some pathological conditions in which the cerebrovascular dynamics is altered, the standard application of ASL may lead to measurement errors. In these cases, it would be possible to estimate perfusion, as well as arterial transit times, by collecting images at multiple time points and then fitting a mathematical model to the data. This approach can be optimized by selecting a set of optimal imaging time points and incorporating knowledge about the physiological distributions of the parameters into the model estimation procedures. In this study, we address the challenges that arise in the measurement of brain perfusion using PASL, due to variations in the arterial transit times, by estimating the errors produced using different types of acquisitions and proposing methods for minimizing such errors. We show by simulation that multiple inversion time ASL acquisitions are expected to reduce measurement errors relative to standard approaches. In data collected from a group of subjects, we further observed reduced inter-subject variability in perfusion measurements when using a multiple versus single inversion time acquisitions. Both measurement errors and variability were further reduced if optimized acquisition and analysis techniques were employed. PMID:24059574

  1. Optimization of flow-sensitive alternating inversion recovery (FAIR) for perfusion functional MRI of rodent brain.

    PubMed

    Nasrallah, Fatima A; Lee, Eugene L Q; Chuang, Kai-Hsiang

    2012-11-01

    Arterial spin labeling (ASL) MRI provides a noninvasive method to image perfusion, and has been applied to map neural activation in the brain. Although pulsed labeling methods have been widely used in humans, continuous ASL with a dedicated neck labeling coil is still the preferred method in rodent brain functional MRI (fMRI) to maximize the sensitivity and allow multislice acquisition. However, the additional hardware is not readily available and hence its application is limited. In this study, flow-sensitive alternating inversion recovery (FAIR) pulsed ASL was optimized for fMRI of rat brain. A practical challenge of FAIR is the suboptimal global inversion by the transmit coil of limited dimensions, which results in low effective labeling. By using a large volume transmit coil and proper positioning to optimize the body coverage, the perfusion signal was increased by 38.3% compared with positioning the brain at the isocenter. An additional 53.3% gain in signal was achieved using optimized repetition and inversion times compared with a long TR. Under electrical stimulation to the forepaws, a perfusion activation signal change of 63.7 ± 6.3% can be reliably detected in the primary somatosensory cortices using single slice or multislice echo planar imaging at 9.4 T. This demonstrates the potential of using pulsed ASL for multislice perfusion fMRI in functional and pharmacological applications in rat brain.

  2. Verapamil prevents silent myocardial perfusion abnormalities during exercise in asymptomatic patients with hypertrophic cardiomyopathy

    SciTech Connect

    Udelson, J.E.; Bonow, R.O.; O'Gara, P.T.; Maron, B.J.; Van Lingen, A.; Bacharach, S.L.; Epstein, S.E.

    1989-05-01

    Recent studies indicate that reversible 201Tl perfusion defects, compatible with silent myocardial ischemia, commonly develop during exercise in asymptomatic or mildly symptomatic patients with hypertrophic cardiomyopathy (HCM). To determine whether this represents a dynamic process that may be modified favorably by medical therapy, we studied 29 asymptomatic or minimally symptomatic patients with HCM, aged 12-55 years (mean, 28), with exercise 201Tl emission computed tomography under control conditions and again after 1 week of oral verapamil (mean dosage, 453 mg/day). Treadmill time increased slightly during verapamil (21.0 +/- 3.6 to 21.9 +/- 2.7 minutes, p less than 0.005), but peak heart rate-blood pressure product was unchanged (26.3 +/- 6.0 X 10(3)) compared with 25.0 +/- 6.4 X 10(3). Two midventricular short-axis images per study were divided into five regions each, and each of these 10 regions was then analyzed on a 0-2 scale by three observers blinded with regard to the patients' therapy. Average regional scores of 1.5 or less were considered to represent perfusion defects, and a change in regional score of 0.5 or more was considered to constitute a significant change. During control studies, 15 patients (52%) developed perfusion defects with exercise (average, 3.7 regions per patient). In 14 of these patients, all perfusion defects completely reversed after 3 hours of rest; one patient had fixed defects. After administration of verapamil, exercise perfusion scores improved in 10 of the 14 patients (71%) with reversible defects; there was overall improvement in 34 of 50 (68%) regions with initially reversible perfusion defects.

  3. The course of neuropsychological impairment and brain structure abnormalities in psychotic disorders.

    PubMed

    Woodward, Neil D

    2016-01-01

    Neuropsychological impairment and abnormalities in brain structure are commonly observed in psychotic disorders, including schizophrenia and bipolar disorder. Shared deficits in neuropsychological functioning and abnormalities in brain structure suggest overlapping neuropathology between schizophrenia and bipolar disorder which has important implications for psychiatric nosology, treatment, and our understanding of the etiology of psychotic illnesses. However, the emergence and trajectory of brain dysfunction in psychotic disorders is less well understood. Differences in the course and progression of neuropsychological impairment and brain abnormalities among psychotic disorders may point to unique neuropathological processes. This article reviews the course of neuropsychological impairment and brain structure abnormalities in schizophrenia and bipolar disorder.

  4. Perfused drop microfluidic device for brain slice culture-based drug discovery.

    PubMed

    Liu, Jing; Pan, Liping; Cheng, Xuanhong; Berdichevsky, Yevgeny

    2016-06-01

    Living slices of brain tissue are widely used to model brain processes in vitro. In addition to basic neurophysiology studies, brain slices are also extensively used for pharmacology, toxicology, and drug discovery research. In these experiments, high parallelism and throughput are critical. Capability to conduct long-term electrical recording experiments may also be necessary to address disease processes that require protein synthesis and neural circuit rewiring. We developed a novel perfused drop microfluidic device for use with long term cultures of brain slices (organotypic cultures). Slices of hippocampus were placed into wells cut in polydimethylsiloxane (PDMS) film. Fluid level in the wells was hydrostatically controlled such that a drop was formed around each slice. The drops were continuously perfused with culture medium through microchannels. We found that viable organotypic hippocampal slice cultures could be maintained for at least 9 days in vitro. PDMS microfluidic network could be readily integrated with substrate-printed microelectrodes for parallel electrical recordings of multiple perfused organotypic cultures on a single MEA chip. We expect that this highly scalable perfused drop microfluidic device will facilitate high-throughput drug discovery and toxicology. PMID:27194028

  5. Whole-Brain CT Perfusion to Quantify Acute Ischemic Penumbra and Core.

    PubMed

    Lin, Longting; Bivard, Andrew; Krishnamurthy, Venkatesh; Levi, Christopher R; Parsons, Mark W

    2016-06-01

    Purpose To validate the use of perfusion computed tomography (CT) with whole-brain coverage to measure the ischemic penumbra and core and to compare its performance to that of limited-coverage perfusion CT. Materials and Methods Institutional ethics committee approval and informed consent were obtained. Patients (n = 296) who underwent 320-detector CT perfusion within 6 hours of the onset of ischemic stroke were studied. First, the ischemic volume at CT perfusion was compared with the penumbra and core reference values at magnetic resonance (MR) imaging to derive CT perfusion penumbra and core thresholds. Second, the thresholds were tested in a different group of patients to predict the final infarction at diffusion-weighted imaging 24 hours after CT perfusion. Third, the change in ischemic volume delineated by the optimal penumbra and core threshold was determined as the brain coverage was gradually reduced from 160 mm to 20 mm. The Wilcoxon signed-rank test, concordance correlation coefficient (CCC), and analysis of variance were used for the first, second, and third steps, respectively. Results CT perfusion at penumbra and core thresholds resulted in the least volumetric difference from MR imaging reference values with delay times greater than 3 seconds and delay-corrected cerebral blood flow of less than 30% (P = .34 and .33, respectively). When the thresholds were applied to the new group of patients, prediction of the final infarction was allowed with delay times greater than 3 seconds in patients with no recanalization of the occluded artery (CCC, 0.96 [95% confidence interval: 0.92, 0.98]) and with delay-corrected cerebral blood flow less than 30% in patients with complete recanalization (CCC, 0.91 [95% confidence interval: 0.83, 0.95]). However, the ischemic volume with a delay time greater than 3 seconds was underestimated when the brain coverage was reduced to 80 mm (P = .04) and the core volume measured as cerebral blood flow less than 30% was

  6. ASFNR recommendations for clinical performance of MR dynamic susceptibility contrast perfusion imaging of the brain.

    PubMed

    Welker, K; Boxerman, J; Kalnin, A; Kaufmann, T; Shiroishi, M; Wintermark, M

    2015-06-01

    MR perfusion imaging is becoming an increasingly common means of evaluating a variety of cerebral pathologies, including tumors and ischemia. In particular, there has been great interest in the use of MR perfusion imaging for both assessing brain tumor grade and for monitoring for tumor recurrence in previously treated patients. Of the various techniques devised for evaluating cerebral perfusion imaging, the dynamic susceptibility contrast method has been employed most widely among clinical MR imaging practitioners. However, when implementing DSC MR perfusion imaging in a contemporary radiology practice, a neuroradiologist is confronted with a large number of decisions. These include choices surrounding appropriate patient selection, scan-acquisition parameters, data-postprocessing methods, image interpretation, and reporting. Throughout the imaging literature, there is conflicting advice on these issues. In an effort to provide guidance to neuroradiologists struggling to implement DSC perfusion imaging in their MR imaging practice, the Clinical Practice Committee of the American Society of Functional Neuroradiology has provided the following recommendations. This guidance is based on review of the literature coupled with the practice experience of the authors. While the ASFNR acknowledges that alternate means of carrying out DSC perfusion imaging may yield clinically acceptable results, the following recommendations should provide a framework for achieving routine success in this complicated-but-rewarding aspect of neuroradiology MR imaging practice.

  7. Implementation of quantitative perfusion imaging techniques for functional brain mapping using pulsed arterial spin labeling.

    PubMed

    Wong, E C; Buxton, R B; Frank, L R

    1997-01-01

    We describe here experimental considerations in the implementation of quantitative perfusion imaging techniques for functional MRI using pulsed arterial spin labeling. Three tagging techniques: EPISTAR, PICORE, and FAIR are found to give very similar perfusion results despite large differences in static tissue contrast. Two major sources of systematic error in the perfusion measurement are identified: the transit delay from the tagging region to the imaging slice; and the inclusion of intravascular tagged signal. A modified technique called QUIPSS II is described that decreases sensitivity to these effects by explicitly controlling the time width of the tag bolus and imaging after the bolus is entirely deposited into the slice. With appropriate saturation pulses the pulse sequence can be arranged so as to allow for simultaneous collection of perfusion and BOLD data that can be cleanly separated. Such perfusion and BOLD signals reveal differences in spatial location and dynamics that may be useful both for functional brain mapping and for study of the BOLD contrast mechanism. The implementation of multislice perfusion imaging introduces additional complications, primarily in the elimination of signal from static tissue. In pulsed ASL, this appears to be related to the slice profile of the inversion tag pulse in the presence of relaxation, rather than magnetization transfer effects as in continuous arterial spin labeling, and can be alleviated with careful adjustment of inversion pulse parameters. PMID:9430354

  8. Neuroendocrine abnormalities in patients with traumatic brain injury

    NASA Technical Reports Server (NTRS)

    Yuan, X. Q.; Wade, C. E.

    1991-01-01

    This article provides an overview of hypothalamic and pituitary alterations in brain trauma, including the incidence of hypothalamic-pituitary damage, injury mechanisms, features of the hypothalamic-pituitary defects, and major hypothalamic-pituitary disturbances in brain trauma. While hypothalamic-pituitary lesions have been commonly described at postmortem examination, only a limited number of clinical cases of traumatic hypothalamic-pituitary dysfunction have been reported, probably because head injury of sufficient severity to cause hypothalamic and pituitary damage usually leads to early death. With the improvement in rescue measures, an increasing number of severely head-injured patients with hypothalamic-pituitary dysfunction will survive to be seen by clinicians. Patterns of endocrine abnormalities following brain trauma vary depending on whether the injury site is in the hypothalamus, the anterior or posterior pituitary, or the upper or lower portion of the pituitary stalk. Injury predominantly to the hypothalamus can produce dissociated ACTH-cortisol levels with no response to insulin-induced hypoglycemia and a limited or failed metopirone test, hypothyroxinemia with a preserved thyroid-stimulating hormone response to thyrotropin-releasing hormone, low gonadotropin levels with a normal response to gonadotropin-releasing hormone, a variable growth hormone (GH) level with a paradoxical rise in GH after glucose loading, hyperprolactinemia, the syndrome of inappropriate ADH secretion (SIADH), temporary or permanent diabetes insipidus (DI), disturbed glucose metabolism, and loss of body temperature control. Severe damage to the lower pituitary stalk or anterior lobe can cause low basal levels of all anterior pituitary hormones and eliminate responses to their releasing factors. Only a few cases showed typical features of hypothalamic or pituitary dysfunction. Most severe injuries are sufficient to damage both structures and produce a mixed endocrine picture

  9. Biochemical abnormalities and excitotoxicity in Huntington's disease brain.

    PubMed

    Tabrizi, S J; Cleeter, M W; Xuereb, J; Taanman, J W; Cooper, J M; Schapira, A H

    1999-01-01

    The physiological role of huntingtin and the mechanisms by which the expanded CAG repeat in ITI5 and its polyglutamine stretch in mutant huntingtin induce Huntington's disease (HD) are unknown. Several techniques have now demonstrated abnormal metabolism in HD brain; direct measurement of respiratory chain enzyme activities has shown severe deficiency of complex II/III and a milder defect of complex IV. We confirm that these abnormalities appear to be confined to the striatum within the HD brain. Analysis of complex II/III activity in HD fibroblasts was normal, despite expression of mutant huntingtin. Although glyceraldehyde 3-phosphate dehydrogenase (a huntingtin binding protein) activity was normal in all areas studied, aconitase activity was decreased to 8% in HD caudate, 27% in putamen, and 52% in cerebral cortex, but normal in HD cerebellum and fibroblasts. We have demonstrated that although complexes II and III are those parts of the respiratory chain most vulnerable to inhibition in the presence of a nitric oxide (NO*) generator, aconitase activity was even more sensitive to inhibition. The pattern of these enzyme deficiencies and their parallel to the anatomical distribution of HD pathology support an important role for NO* and excitotoxicity in HD pathogenesis. Furthermore, based on the biochemical defects we have described, we suggest that NO* generation produces a graded response, with aconitase inhibition followed by complex II/III inhibition and the initiation of a self-amplifying cycle of free radical generation and aconitase inhibition, which results in severe ATP depletion. We propose that these events are important in determining neuronal cell death and are critical steps in the pathogenesis of HD. PMID:9894873

  10. The cerebral imaging using vessel-around method in the perfusion CT of the human brain

    NASA Astrophysics Data System (ADS)

    Ahn, Choong-Il; Choi, Seung-Wook; Park, Seung-Chul; Shin, Yeong-Gil; Kim, Jae-Hyoung; Chong, Gi-Bong

    2005-04-01

    Perfusion CT has been successfully used as a functional imaging technique for diagnosis of patients with hyperacute stroke. However, the commonly used methods based on curve-fitting are time consuming. Numerous researchers have investigated to what extent Perfusion CT can be used for the quantitative assessment of cerebral ischemia and to rapidly obtain comprehensive information regarding the extent of ischemic damage in acute stroke patients. The aim of this study is to propose an alternative approach to rapidly obtain the brain perfusion mapping and to show the proposed cerebral flow imaging of the vessel and tissue in human brain be reliable and useful. Our main design concern was algorithmic speed, robustness and automation in order to allow its potential use in the emergency situation of acute stroke. To obtain a more effective mapping, we analyzed the signal characteristics of Perfusion CT and defined the vessel-around model which includes the vessel and tissue. We proposed a nonparametric vessel-around approach which automatically discriminates the vessel and tissue around vessel from non-interested brain matter stratifying the level of maximum enhancement of pixel-based TAC. The stratification of pixel-based TAC was executed using the mean and standard deviation of the signal intensity of each pixel and mapped to the cerebral flow imaging. The defined vessel-around model was used to show the cerebral flow imaging and to specify the area of markedly reduced perfusion with loss of function of still viable neurons. Perfusion CT is a fast and practical technique for routine clinical application. It provides substantial and important additional information for the selection of the optimal treatment strategy for patients with hyperacute stroke. The vessel-around approach reduces the computation time significantly when compared with the perfusion imaging using the GVF. The proposed cerebral imaging shows reliable results which are validated by physicians and

  11. Assessment of drug disposition in the perfused rat brain by statistical moment analysis

    SciTech Connect

    Sakane, T.; Nakatsu, M.; Yamamoto, A.; Hashida, M.; Sezaki, H.; Yamashita, S.; Nadai, T. )

    1991-06-01

    Drug disposition in the brain was investigated by statistical moment analysis using an improved in situ brain perfusion technique. The right cerebral hemisphere of the rat was perfused in situ. The drug and inulin were injected into the right internal carotid artery as a rapid bolus and the venous outflow curve at the posterior facial vein was obtained. The infusion rate was adjusted to minimize the flow of perfusion fluid into the left hemisphere. The obtained disposition parameters were characteristics and considered to reflect the physicochemical properties of each drug. Antipyrine showed a small degree of initial uptake. Therefore, its apparent distribution volume (Vi) and apparent intrinsic clearance (CLint,i) were small. Diazepam showed large degrees of both influx and efflux and, thus, a large Vi. Water showed parameters intermediate between those of antipyrine and those of diazepam. Imipramine, desipramine, and propranolol showed a large CLint,i compared with those of the other drugs. The extraction ratio of propranolol significantly decreased with increasing concentrations of unlabeled propranolol in the perfusion fluid. These findings may be explained partly by the tissue binding of these drugs. In conclusion, the present method is useful for studying drug disposition in the brain.

  12. Quantitative Perfusion and Permeability Biomarkers in Brain Cancer from Tomographic CT and MR Images

    PubMed Central

    Eilaghi, Armin; Yeung, Timothy; d’Esterre, Christopher; Bauman, Glenn; Yartsev, Slav; Easaw, Jay; Fainardi, Enrico; Lee, Ting-Yim; Frayne, Richard

    2016-01-01

    Dynamic contrast-enhanced perfusion and permeability imaging, using computed tomography and magnetic resonance systems, are important techniques for assessing the vascular supply and hemodynamics of healthy brain parenchyma and tumors. These techniques can measure blood flow, blood volume, and blood–brain barrier permeability surface area product and, thus, may provide information complementary to clinical and pathological assessments. These have been used as biomarkers to enhance the treatment planning process, to optimize treatment decision-making, and to enable monitoring of the treatment noninvasively. In this review, the principles of magnetic resonance and computed tomography dynamic contrast-enhanced perfusion and permeability imaging are described (with an emphasis on their commonalities), and the potential values of these techniques for differentiating high-grade gliomas from other brain lesions, distinguishing true progression from posttreatment effects, and predicting survival after radiotherapy, chemotherapy, and antiangiogenic treatments are presented. PMID:27398030

  13. Dependence of Brain Intravoxel Incoherent Motion Perfusion Parameters on the Cardiac Cycle

    PubMed Central

    Federau, Christian; Hagmann, Patric; Maeder, Philippe; Müller, Markus; Meuli, Reto; Stuber, Matthias; O’Brien, Kieran

    2013-01-01

    Measurement of microvascular perfusion with Intravoxel Incoherent Motion (IVIM) MRI is gaining interest. Yet, the physiological influences on the IVIM perfusion parameters (“pseudo-diffusion” coefficient D*, perfusion fraction f, and flow related parameter fD*) remain insufficiently characterized. In this article, we hypothesize that D* and fD*, which depend on blood speed, should vary during the cardiac cycle. We extended the IVIM model to include time dependence of D* = D*(t), and demonstrate in the healthy human brain that both parameters D* and fD* are significantly larger during systole than diastole, while the diffusion coefficient D and f do not vary significantly. The results non-invasively demonstrate the pulsatility of the brain’s microvasculature. PMID:24023649

  14. Microvascular perfusion during focal vasogenic brain edema: a scanning laser fluorescence microscopy study.

    PubMed

    Lindsberg, P J; Sirén, A L; Hallenbeck, J M

    1997-01-01

    Controversy exists about the effect of tissue edema on cerebral microcirculation. High spatial resolution is required for observation of extravasation and microcirculation during focal vasogenic edema formation. To study the relationship between tissue edema and perfusion, we developed a technique for simultaneous visualization of extravasation and microvessel perfusion in rats. Focal intracortical microvascular injury was generated with a 1-sec Nd-YAG laser pulse. Evans blue albumin (EBA) was infused 30 min before decapitation to study extravasation and FITC-dextran was injected 30 sec prior to decapitation to examine microvessel perfusion. Computerized scanning laser-excited fluorescence microscopy followed by high resolution image analysis permitted quantitative assessment of both parameters on single fresh-frozen brain sections. Studied at 30 min (3.66 +/- 0.15 mm), 2 hr (4.14 +/- 0.08 mm, P < .05), and 8 hr (4.69 +/- 0.18 mm, P < .01) after injury, the diameter of the circular, sharply demarcated zone of EBA-extravasation increased progressively. At 30 min, microvessels at a zone surrounding the area of EBA-extravasation contained 69 +/- 14% (P < .05) more fluorescent FITC-filling than in the control hemisphere, but the density of perfused microvessels was unchanged. At 2 hr, secondary tissue changes had already occurred in a zone surrounding the initial laser lesion. While severe reduction in the density (-76 +/- 13%, P < .05) of perfused microvessels was observed within 400 to 240 microm inside the border of EBA extravasation, perfusion indexes were normal despite the presence of extravasated plasma constituents within 0-80 microm from the border. In a narrow zone (80 microm) outside the border of extravasation, individual microvessels contained 34 +/- 9% (P < .01) less FITC-fluorescence than those in a homologous area of the uninjured contralateral hemisphere. This report demonstrates the feasibility of simultaneous measurement and high-resolution mapping

  15. Mapping abnormal subcortical brain morphometry in an elderly HIV+ cohort.

    PubMed

    Wade, Benjamin S C; Valcour, Victor G; Wendelken-Riegelhaupt, Lauren; Esmaeili-Firidouni, Pardis; Joshi, Shantanu H; Gutman, Boris A; Thompson, Paul M

    2015-01-01

    Over 50% of HIV + individuals exhibit neurocognitive impairment and subcortical atrophy, but the profile of brain abnormalities associated with HIV is still poorly understood. Using surface-based shape analyses, we mapped the 3D profile of subcortical morphometry in 63 elderly HIV + participants and 31 uninfected controls. The thalamus, caudate, putamen, pallidum, hippocampus, amygdala, brainstem, accumbens, callosum and ventricles were segmented from high-resolution MRIs. To investigate shape-based morphometry, we analyzed the Jacobian determinant (JD) and radial distances (RD) defined on each region's surfaces. We also investigated effects of nadir CD4 + T-cell counts, viral load, time since diagnosis (TSD) and cognition on subcortical morphology. Lastly, we explored whether HIV + participants were distinguishable from unaffected controls in a machine learning context. All shape and volume features were included in a random forest (RF) model. The model was validated with 2-fold cross-validation. Volumes of HIV + participants' bilateral thalamus, left pallidum, left putamen and callosum were significantly reduced while ventricular spaces were enlarged. Significant shape variation was associated with HIV status, TSD and the Wechsler adult intelligence scale. HIV + people had diffuse atrophy, particularly in the caudate, putamen, hippocampus and thalamus. Unexpectedly, extended TSD was associated with increased thickness of the anterior right pallidum. In the classification of HIV + participants vs. controls, our RF model attained an area under the curve of 72%.

  16. Mapping abnormal subcortical brain morphometry in an elderly HIV + cohort

    PubMed Central

    Wade, Benjamin S.C.; Valcour, Victor G.; Wendelken-Riegelhaupt, Lauren; Esmaeili-Firidouni, Pardis; Joshi, Shantanu H.; Gutman, Boris A.; Thompson, Paul M.

    2015-01-01

    Over 50% of HIV + individuals exhibit neurocognitive impairment and subcortical atrophy, but the profile of brain abnormalities associated with HIV is still poorly understood. Using surface-based shape analyses, we mapped the 3D profile of subcortical morphometry in 63 elderly HIV + participants and 31 uninfected controls. The thalamus, caudate, putamen, pallidum, hippocampus, amygdala, brainstem, accumbens, callosum and ventricles were segmented from high-resolution MRIs. To investigate shape-based morphometry, we analyzed the Jacobian determinant (JD) and radial distances (RD) defined on each region's surfaces. We also investigated effects of nadir CD4 + T-cell counts, viral load, time since diagnosis (TSD) and cognition on subcortical morphology. Lastly, we explored whether HIV + participants were distinguishable from unaffected controls in a machine learning context. All shape and volume features were included in a random forest (RF) model. The model was validated with 2-fold cross-validation. Volumes of HIV + participants' bilateral thalamus, left pallidum, left putamen and callosum were significantly reduced while ventricular spaces were enlarged. Significant shape variation was associated with HIV status, TSD and the Wechsler adult intelligence scale. HIV + people had diffuse atrophy, particularly in the caudate, putamen, hippocampus and thalamus. Unexpectedly, extended TSD was associated with increased thickness of the anterior right pallidum. In the classification of HIV + participants vs. controls, our RF model attained an area under the curve of 72%. PMID:26640768

  17. The influence of brain abnormalities on psychosocial development, criminal history and paraphilias in sexual murderers.

    PubMed

    Briken, Peer; Habermann, Niels; Berner, Wolfgang; Hill, Andreas

    2005-09-01

    The aim of this study was to investigate the number and type of brain abnormalities and their influence on psychosocial development, criminal history and paraphilias in sexual murderers. We analyzed psychiatric court reports of 166 sexual murderers and compared a group with notable signs of brain abnormalities (N = 50) with those without any signs (N = 116). Sexual murderers with brain abnormalities suffered more from early behavior problems. They were less likely to cohabitate with the victim at the time of the homicide and had more victims at the age of six years or younger. Psychiatric diagnoses revealed a higher total number of paraphilias: Transvestic fetishism and paraphilias not otherwise specified were more frequent in offenders with brain abnormalities. A binary logistic regression identified five predictors that accounted for 46.8% of the variance explaining the presence of brain abnormalities. Our results suggest the importance of a comprehensive neurological and psychological examination of this special offender group. PMID:16225232

  18. Cholinergic and perfusion brain networks in Parkinson disease dementia

    PubMed Central

    McKeith, Ian G.; Burn, David J.; Wyper, David J.; O'Brien, John T.; Taylor, John-Paul

    2016-01-01

    Objective: To investigate muscarinic M1/M4 cholinergic networks in Parkinson disease dementia (PDD) and their association with changes in Mini-Mental State Examination (MMSE) after 12 weeks of treatment with donepezil. Methods: Forty-nine participants (25 PDD and 24 elderly controls) underwent 123I-QNB and 99mTc-exametazime SPECT scanning. We implemented voxel principal components (PC) analysis, producing a series of PC images of patterns of interrelated voxels across individuals. Linear regression analyses derived specific M1/M4 and perfusion spatial covariance patterns (SCPs). Results: We found an M1/M4 SCP of relative decreased binding in basal forebrain, temporal, striatum, insula, and anterior cingulate (F1,47 = 31.9, p < 0.001) in cholinesterase inhibitor–naive patients with PDD, implicating limbic-paralimbic and salience cholinergic networks. The corresponding regional cerebral blood flow SCP showed relative decreased uptake in temporoparietal and prefrontal areas (F1,47 = 177.5, p < 0.001) and nodes of the frontoparietal and default mode networks (DMN). The M1/M4 pattern that correlated with an improvement in MMSE (r = 0.58, p = 0.005) revealed relatively preserved/increased pre/medial/orbitofrontal, parietal, and posterior cingulate areas coinciding with the DMN and frontoparietal networks. Conclusion: Dysfunctional limbic-paralimbic and salience cholinergic networks were associated with PDD. Established cholinergic maintenance of the DMN and frontoparietal networks may be prerequisite for cognitive remediation following cholinergic treatment in this condition. PMID:27306636

  19. Patterns of pulmonary perfusion scans in normal subjects. IV. The prevalence of abnormal scans in smokers 30 to 49 years of age

    SciTech Connect

    Fedullo, P.F.; Kapitan, K.S.; Brewer, N.S.; Ashburn, W.L.; Hartman, M.T.; Moser, K.M.

    1989-05-01

    The usefulness of ventilation-perfusion scans in the diagnosis of pulmonary embolism is limited by the wide range of pulmonary diseases that are associated with abnormal scans, and by the largely undetermined prevalence of abnormal scans in persons without cardiopulmonary disease. In prior studies, we found perfusion defects to be rarely present in young persons and in older nonsmokers. To determine if normal older smokers have a higher prevalence of abnormal ventilation and perfusion scans, we performed six-view /sup 99m/Tc perfusion (Q) scans and /sup 133/Xe ventilation (V) scans in 40 subjects 30 to 49 yr of age who had no known cardiopulmonary disease. Each subject had undergone a history, physical examination, electrocardiogram, spirometry, and posteroanterior chest roentgenogram prior to scanning. All V and Q scans were interpreted blindly and independently by two experienced readers. No subject demonstrated a lobar or segmental defect on two views. One subject had a matched subsegmental defect, and one subject had delayed washout from a subsegmental area of the right upper lobe during V scanning, with a normal Q scan. We conclude that abnormal V and Q scans are uncommon among normal smokers 30 to 49 yr of age.

  20. A Device for Long-Term Perfusion, Imaging, and Electrical Interfacing of Brain Tissue In vitro.

    PubMed

    Killian, Nathaniel J; Vernekar, Varadraj N; Potter, Steve M; Vukasinovic, Jelena

    2016-01-01

    Distributed microelectrode array (MEA) recordings from consistent, viable, ≥500 μm thick tissue preparations over time periods from days to weeks may aid in studying a wide range of problems in neurobiology that require in vivo-like organotypic morphology. Existing tools for electrically interfacing with organotypic slices do not address necrosis that inevitably occurs within thick slices with limited diffusion of nutrients and gas, and limited removal of waste. We developed an integrated device that enables long-term maintenance of thick, functionally active, brain tissue models using interstitial perfusion and distributed recordings from thick sections of explanted tissue on a perforated multi-electrode array. This novel device allows for automated culturing, in situ imaging, and extracellular multi-electrode interfacing with brain slices, 3-D cell cultures, and potentially other tissue culture models. The device is economical, easy to assemble, and integrable with standard electrophysiology tools. We found that convective perfusion through the culture thickness provided a functional benefit to the preparations as firing rates were generally higher in perfused cultures compared to their respective unperfused controls. This work is a step toward the development of integrated tools for days-long experiments with more consistent, healthier, thicker, and functionally more active tissue cultures with built-in distributed electrophysiological recording and stimulation functionality. The results may be useful for the study of normal processes, pathological conditions, and drug screening strategies currently hindered by the limitations of acute (a few hours long) brain slice preparations. PMID:27065793

  1. ESR imaging of the rat brain with a nitroxide radical perfused by in vivo microdialysis.

    PubMed

    Ueda, Y; Yokoyama, H; Ohya-Nishiguchi, H; Kamada, H

    1997-01-01

    We report here our investigation of the spatial distribution of free radicals using an electron spin resonance (ESR)-imaging system combined with an in vivo brain microdialysis method, which was performed in the resonator of the ESR-imaging system. A nonmagnetic cannula, newly developed in this study, was used for the perfusion of the exogenous free radicals agent. A nitroxide, 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (carbamoyl PROYXL), was used as the imaging agent in saline solution at a concentration of 0.3 M, which was perfused into the right caudate putamen of the rat at 2 microliters/min by a microinfusion pump. Two-dimensional ESR projection of the Z-X plane, which was clearly distinguished (about phi 10 mm) from the nonperfused brain area, was obtained 6 h after the beginning of perfusion of carbamoyl PROXYL. The present method is considered to be a useful tool to introduce stable free radicals into a specific area of the brain.

  2. A Device for Long-Term Perfusion, Imaging, and Electrical Interfacing of Brain Tissue In vitro

    PubMed Central

    Killian, Nathaniel J.; Vernekar, Varadraj N.; Potter, Steve M.; Vukasinovic, Jelena

    2016-01-01

    Distributed microelectrode array (MEA) recordings from consistent, viable, ≥500 μm thick tissue preparations over time periods from days to weeks may aid in studying a wide range of problems in neurobiology that require in vivo-like organotypic morphology. Existing tools for electrically interfacing with organotypic slices do not address necrosis that inevitably occurs within thick slices with limited diffusion of nutrients and gas, and limited removal of waste. We developed an integrated device that enables long-term maintenance of thick, functionally active, brain tissue models using interstitial perfusion and distributed recordings from thick sections of explanted tissue on a perforated multi-electrode array. This novel device allows for automated culturing, in situ imaging, and extracellular multi-electrode interfacing with brain slices, 3-D cell cultures, and potentially other tissue culture models. The device is economical, easy to assemble, and integrable with standard electrophysiology tools. We found that convective perfusion through the culture thickness provided a functional benefit to the preparations as firing rates were generally higher in perfused cultures compared to their respective unperfused controls. This work is a step toward the development of integrated tools for days-long experiments with more consistent, healthier, thicker, and functionally more active tissue cultures with built-in distributed electrophysiological recording and stimulation functionality. The results may be useful for the study of normal processes, pathological conditions, and drug screening strategies currently hindered by the limitations of acute (a few hours long) brain slice preparations. PMID:27065793

  3. [Electrophysiological features (EEG) of ethanol withdrawal syndromes on isolated perfused rat brain].

    PubMed

    Tezikov, E B; Litvicki, P F

    2015-01-01

    On isolated rat brains we studied native EEC and its derivates (mean EEC amplitude and power spectrums - Fourier transformation) during perfusion with ethanol (65 Mm/ L) and after its withdrawal. Previously rats were undergone ethanol burden for 6 days according to Majchrowicz procedures to get alcohol withdrawal syndrome. Duration perfusion without ethanol was 5, 10 and 20 min depending on the experimental schedule. Ethanol infusion between periods of withdrawal comprised 20 min. 55% of isolated brains shown epileptiform activity after 1-2 min of ethanol withdrawal but others manifested only increased mean amplitude and the power spectrums of EEC as well as an appearance of single or batch spikes. Differences between in vivo and in vitro conditions can be explained by the accelerated rate of ethanol elimination. The high positive correlation was obtained between EEC findings at the 5-th min of the first ethanol withdrawal and the same findings at the 5-th min of ethanol withdrawal in the second and the third episodes of ethanol withdrawal. Prolongation of withdrawal period more than 5th min caused brain death showing epileptiform activity. Isolated rat brain is the convenient subject to study pathogenesis of excitability of neurons and examination of drugs to treat alcohol withdrawal syndrome.

  4. Whole-brain perfusion imaging with balanced steady-state free precession arterial spin labeling.

    PubMed

    Han, Paul Kyu; Ye, Jong Chul; Kim, Eung Yeop; Choi, Seung Hong; Park, Sung-Hong

    2016-03-01

    Recently, balanced steady-state free precession (bSSFP) readout has been proposed for arterial spin labeling (ASL) perfusion imaging to reduce susceptibility artifacts at a relatively high spatial resolution and signal-to-noise ratio (SNR). However, the main limitation of bSSFP-ASL is the low spatial coverage. In this work, methods to increase the spatial coverage of bSSFP-ASL are proposed for distortion-free, high-resolution, whole-brain perfusion imaging. Three strategies of (i) segmentation, (ii) compressed sensing (CS) and (iii) a hybrid approach combining the two methods were tested to increase the spatial coverage of pseudo-continuous ASL (pCASL) with three-dimensional bSSFP readout. The spatial coverage was increased by factors of two, four and six using each of the three approaches, whilst maintaining the same total scan time (5.3 min). The number of segments and/or CS acceleration rate (R) correspondingly increased to maintain the same bSSFP readout time (1.2 s). The segmentation approach allowed whole-brain perfusion imaging for pCASL-bSSFP with no penalty in SNR and/or total scan time. The CS approach increased the spatial coverage of pCASL-bSSFP whilst maintaining the temporal resolution, with minimal impact on the image quality. The hybrid approach provided compromised effects between the two methods. Balanced SSFP-based ASL allows the acquisition of perfusion images with wide spatial coverage, high spatial resolution and SNR, and reduced susceptibility artifacts, and thus may become a good choice for clinical and neurological studies. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26676386

  5. Whole-brain perfusion imaging with balanced steady-state free precession arterial spin labeling.

    PubMed

    Han, Paul Kyu; Ye, Jong Chul; Kim, Eung Yeop; Choi, Seung Hong; Park, Sung-Hong

    2016-03-01

    Recently, balanced steady-state free precession (bSSFP) readout has been proposed for arterial spin labeling (ASL) perfusion imaging to reduce susceptibility artifacts at a relatively high spatial resolution and signal-to-noise ratio (SNR). However, the main limitation of bSSFP-ASL is the low spatial coverage. In this work, methods to increase the spatial coverage of bSSFP-ASL are proposed for distortion-free, high-resolution, whole-brain perfusion imaging. Three strategies of (i) segmentation, (ii) compressed sensing (CS) and (iii) a hybrid approach combining the two methods were tested to increase the spatial coverage of pseudo-continuous ASL (pCASL) with three-dimensional bSSFP readout. The spatial coverage was increased by factors of two, four and six using each of the three approaches, whilst maintaining the same total scan time (5.3 min). The number of segments and/or CS acceleration rate (R) correspondingly increased to maintain the same bSSFP readout time (1.2 s). The segmentation approach allowed whole-brain perfusion imaging for pCASL-bSSFP with no penalty in SNR and/or total scan time. The CS approach increased the spatial coverage of pCASL-bSSFP whilst maintaining the temporal resolution, with minimal impact on the image quality. The hybrid approach provided compromised effects between the two methods. Balanced SSFP-based ASL allows the acquisition of perfusion images with wide spatial coverage, high spatial resolution and SNR, and reduced susceptibility artifacts, and thus may become a good choice for clinical and neurological studies. Copyright © 2015 John Wiley & Sons, Ltd.

  6. Prevalence and pattern of abnormal myocardial perfusion in patients with isolated coronary artery ectasia: study by 99mTc-sestamibi radionuclide scintigraphy.

    PubMed

    Ismail, Ahmed M; Rayan, Mona; Adel, Amr; Demerdash, Salah; Atef, Mohamed; Abdallah, Mohamed; Nammas, Wail

    2014-02-01

    We explored the prevalence and pattern of abnormal myocardial perfusion in patients with isolated coronary artery ectasia (CAE), as demonstrated by (99m)Tc-sestamibi scintigraphy. Prospectively, we enrolled 35 patients with angiographically documented CAE and no significant coronary obstruction, who underwent elective coronary angiography. Patients underwent Stress-rest (99m)Tc-sestamibi scintigraphy within 4 days of coronary angiography. They were divided into 2 groups: group I: with normal perfusion scan; and group II: with reversible perfusion defects. The mean age was 49.6 ± 6.9 years; 34 (97.1 %) were males. Seventy-nine (75.2 %) arteries were affected by CAE. Among 79 arteries affected by CAE, affection was diffuse in 37 (46.8 %). Thirteen (37.1 %) patients had normal perfusion scan (group I), whereas 22 (62.9 %) had reversible perfusion defects (group II). Among 22 patients with reversible perfusion defects, 20 (90.9 %) had mild and 2 (9.1 %) had moderate ischemia. Among 49 myocardial segments with reversible perfusion defects, 22 (44.9 %) were basal, 18 (36.7 %) mid-, and 9 (18.4 %) apical segments. Diffuse CAE was significantly more prevalent in group II versus group I, in all 3 major coronary arteries (p < 0.05 for all). In patients with isolated CAE who underwent elective coronary angiography, reversible perfusion defects demonstrated by (99m)Tc-sestamibi scintigraphy were rather prevalent, mostly mild, more likely to affect the basal and mid-segments of the myocardium, and more frequently associated with diffuse ectasia.

  7. SPECT brain perfusion imaging with Tc-99m ECD: Semi-quantitative regional analysis and database mapping

    SciTech Connect

    Schiepers, C.; Hegge, J.; De Roo, M.

    1994-05-01

    Brain SPECT is a well accepted method for the assessment of brain perfusion in various disorders such as epilepsy, stroke, dementia. A program for handling the tomographic data was developed, using a commercial spreadsheet (Microsoft EXCEL) with a set of macro`s for analysis, graphic display and database management of the final results.

  8. Perfusion MR Imaging: Clinical Utility for the Differential Diagnosis of Various Brain Tumors

    PubMed Central

    Cho, Sung Ki; Na, Dong Gyu; Ryoo, Jae Wook; Roh, Hong Gee; Moon, Chan Hong; Kim, Jong Hyun

    2002-01-01

    Objective To determine the utility of perfusion MR imaging in the differential diagnosis of brain tumors. Materials and Methods Fifty-seven patients with pathologically proven brain tumors (21 high-grade gliomas, 8 low-grade gliomas, 8 lymphomas, 6 hemangioblastomas, 7 metastases, and 7 various other tumors) were included in this study. Relative cerebral blood volume (rCBV) and time-to-peak (TTP) ratios were quantitatively analyzed and the rCBV grade of each tumor was also visually assessed on an rCBV map. Results The highest rCBV ratios were seen in hemangioblastomas, followed by high-grade gliomas, metastases, low-grade gliomas, and lymphomas. There was no significant difference in TTP ratios between each tumor group (p>0.05). At visual assessment, rCBV was high in 17 (81%) of 21 high-grade gliomas and in 4 (50%) of 8 low-grade gliomas. Hemangioblastomas showed the highest rCBV and lymphomas the lowest. Conclusion Perfusion MR imaging may be helpful in the differentiation of thevarious solid tumors found in the brain, and in assessing the grade of the various glial tumors occurring there. PMID:12271162

  9. [Abnormal cerebral blood flow distributions during the post-ictal phase of febrile status epilepticus in three pediatric patients measured by arterial spin labeling perfusion MRI].

    PubMed

    Hirano, Keiko; Fukuda, Tokiko

    2016-05-01

    The ability to visualize brain perfusion is important for identifying epileptic foci. We present three pediatric cases showing asymmetrical cerebral blood flow (CBF) distributions during the post-ictal phase of febrile status epilepticus measured by arterial spin labeling (ASL) perfusion MRI. During the acute phase, regional CBF measurements in the areas considered including epileptic foci were higher than in the corresponding area of the contralateral hemisphere, though the exact quantitative value varied between cases. We could not identify the correct epileptogenic foci, because those ASL images were taken after the prolonged and extraordinary activation of neurons in the affected area. During the recovery phase, the differences reduced and the average regional CBF measurement was 54.6 ± 6.1 ml/100 g per minute, which was a little less than the number of previous ASL studies. ASL perfusion MRI imaging provides a method for evaluating regional CBF by using magnetically labeled arterial blood water as an endogenous tracer. With this technique, we can repeatedly evaluate both the brain structure and the level of perfusion at the same time. ASL is noninvasive and easily accessible, and therefore it could become a routine tool for assessment of perfusion in daily practice of pediatric neurology. PMID:27349086

  10. 99mTc-ECD brain perfusion SPECT imaging for the assessment of brain perfusion in cerebral palsy (CP) patients with evaluation of the effect of hyperbaric oxygen therapy

    PubMed Central

    Asl, Mina Taghizadeh; Yousefi, Farzaneh; Nemati, Reza; Assadi, Majid

    2015-01-01

    Objective: The present study was carried out to evaluate cerebral perfusion in different types of cerebral palsy (CP) patients. For those patients who underwent hyperbaric oxygen therapy, brain perfusion before and after the therapy was compared. Methods: A total of 11 CP patients were enrolled in this study, of which 4 patients underwent oxygen therapy. Before oxygen therapy and at the end of 40 sessions of oxygen treatment, 99mTc-ECD brain perfusion single photon emission computed tomography (SPECT) was performed , and the results were compared. Results: A total of 11 CP patients, 7 females and 4 males with an age range of 5-27 years participated in the study. In brain SPECT studies, all the patients showed perfusion impairments. The region most significantly involved was the frontal lobe (54.54%), followed by the temporal lobe (27.27%), the occipital lobe (18.18%), the visual cortex (18.18%), the basal ganglia (9.09%), the parietal lobe (9.09%), and the cerebellum (9.09%). Frontal-lobe hypoperfusion was seen in all types of cerebral palsy. Two out of 4 patients (2 males and 2 females) who underwent oxygen therapy revealed certain degree of brain perfusion improvement. Conclusion: This study demonstrated decreased cerebral perfusion in different types of CP patients. The study also showed that hyperbaric oxygen therapy improved cerebral perfusion in a few CP patients. However, it could keep the physiological discussion open and strenghten a link with other areas of neurology in which this approach may have some value. PMID:25785099

  11. Investigating individual differences in brain abnormalities in autism.

    PubMed Central

    Salmond, C H; de Haan, M; Friston, K J; Gadian, D G; Vargha-Khadem, F

    2003-01-01

    Autism is a psychiatric syndrome characterized by impairments in three domains: social interaction, communication, and restricted and repetitive behaviours and interests. Recent findings implicate the amygdala in the neurobiology of autism. In this paper, we report the results of a series of novel experimental investigations focusing on the structure and function of the amygdala in a group of children with autism. The first section attempts to determine if abnormality of the amygdala can be identified in an individual using magnetic resonance imaging in vivo. Using single-case voxel-based morphometric analyses, abnormality in the amygdala was detected in half the children with autism. Abnormalities in other regions were also found. In the second section, emotional modulation of the startle response was investigated in the group of autistic children. Surprisingly, there were no significant differences between the patterns of emotional modulation of the startle response in the autistic group compared with the controls. PMID:12639337

  12. A mismatch between the abnormalities in diffusion- and susceptibility-weighted magnetic resonance imaging may represent an acute ischemic penumbra with misery perfusion.

    PubMed

    Fujioka, Masayuki; Okuchi, Kazuo; Iwamura, Asami; Taoka, Toshiaki; Siesjö, Bo K

    2013-11-01

    Susceptibility-weighted imaging (SWI) has recently attracted attention for its ability to investigate acute stroke pathophysiology. SWI detects an increased ratio of deoxyhemoglobin to oxyhemoglobin in cerebral venous compartments, which can illustrate cerebral misery perfusion with a compensatory increase of oxygen extraction fraction in the hypoperfused brain. In this study we make the first case report of blunt cervical trauma leading to a stroke, demonstrating the disparity between diffusion-weighted imaging (DWI) and SWI changes, or DWI-SWI mismatch, in the acute ischemic brain. The area of mismatch between a smaller DWI cytotoxic edema and a larger SWI misery perfusion in our patient matured into a complete infarction with time. The DWI-SWI mismatch may signify the presence of an ischemic penumbra, and provide information about viability of the brain tissue at risk of potential infarction if without early reperfusion.

  13. Functional Brain Network Abnormalities during Verbal Working Memory Performance in Adolescents and Young Adults with Dyslexia

    ERIC Educational Resources Information Center

    Wolf, Robert Christian; Sambataro, Fabio; Lohr, Christina; Steinbrink, Claudia; Martin, Claudia; Vasic, Nenad

    2010-01-01

    Behavioral and functional neuroimaging studies indicate deficits in verbal working memory (WM) and frontoparietal dysfunction in individuals with dyslexia. Additionally, structural brain abnormalities in dyslexics suggest a dysconnectivity of brain regions associated with phonological processing. However, little is known about the functional…

  14. Developmental vitamin D deficiency causes abnormal brain development.

    PubMed

    Eyles, D W; Feron, F; Cui, X; Kesby, J P; Harms, L H; Ko, P; McGrath, J J; Burne, T H J

    2009-12-01

    There is now clear evidence that vitamin D is involved in brain development. Our group is interested in environmental factors that shape brain development and how this may be relevant to neuropsychiatric diseases including schizophrenia. The origins of schizophrenia are considered developmental. We hypothesised that developmental vitamin D (DVD) deficiency may be the plausible neurobiological explanation for several important epidemiological correlates of schizophrenia namely: (1) the excess winter/spring birth rate, (2) increased incidence of the disease in 2nd generation Afro-Caribbean migrants and (3) increased urban birth rate. Moreover we have published two pieces of direct epidemiological support for this hypothesis in patients. In order to establish the "Biological Plausibility" of this hypothesis we have developed an animal model to study the effect of DVD deficiency on brain development. We do this by removing vitamin D from the diet of female rats prior to breeding. At birth we return all dams to a vitamin D containing diet. Using this procedure we impose a transient, gestational vitamin D deficiency, while maintaining normal calcium levels throughout. The brains of offspring from DVD-deficient dams are characterised by (1) a mild distortion in brain shape, (2) increased lateral ventricle volumes, (3) reduced differentiation and (4) diminished expression of neurotrophic factors. As adults, the alterations in ventricular volume persist and alterations in brain gene and protein expression emerge. Adult DVD-deficient rats also display behavioural sensitivity to agents that induce psychosis (the NMDA antagonist MK-801) and have impairments in attentional processing. In this review we summarise the literature addressing the function of vitamin D on neuronal and non-neuronal cells as well as in vivo results from DVD-deficient animals. Our conclusions from these data are that vitamin D is a plausible biological risk factor for neuropsychiatric disorders and that

  15. Brain Structure Abnormalities in Adolescent Girls with Conduct Disorder

    ERIC Educational Resources Information Center

    Fairchild, Graeme; Hagan, Cindy C.; Walsh, Nicholas D.; Passamonti, Luca; Calder, Andrew J.; Goodyer, Ian M.

    2013-01-01

    Background: Conduct disorder (CD) in female adolescents is associated with a range of negative outcomes, including teenage pregnancy and antisocial personality disorder. Although recent studies have documented changes in brain structure and function in male adolescents with CD, there have been no neuroimaging studies of female adolescents with CD.…

  16. Childhood Onset Schizophrenia: Cortical Brain Abnormalities as Young Adults

    ERIC Educational Resources Information Center

    Greenstein, Deanna; Lerch, Jason; Shaw, Philip; Clasen, Liv; Giedd, Jay; Gochman, Peter; Rapoport, Judith; Gogtay, Nitin

    2006-01-01

    Background: Childhood onset schizophrenia (COS) is a rare but severe form of the adult onset disorder. While structural brain imaging studies show robust, widespread, and progressive gray matter loss in COS during adolescence, there have been no longitudinal studies of sufficient duration to examine comparability with the more common adult onset…

  17. Thrombotic thrombocytopenic purpura: MR demonstration of reversible brain abnormalities

    SciTech Connect

    D'Aprile, P.; Carella, A.; Pagliarulo, R. ); Farchi, G. )

    1994-01-01

    We report a case of thrombotic thrombocytopenic purpura evaluated by MR, Multiple hyperintense foci on the TS-weighted images, observed principally in the brain stem and in the region of the basal nuclei, and neurologic signs disappeared after 15 days of therapy. 6 refs., 2 figs.

  18. Structural and functional brain abnormalities place phenocopy frontotemporal dementia (FTD) in the FTD spectrum

    PubMed Central

    Steketee, Rebecca M.E.; Meijboom, Rozanna; Bron, Esther E.; Osse, Robert Jan; de Koning, Inge; Jiskoot, Lize C.; Klein, Stefan; de Jong, Frank Jan; van der Lugt, Aad; van Swieten, John C.; Smits, Marion

    2016-01-01

    Purpose ‘Phenocopy’ frontotemporal dementia (phFTD) patients may clinically mimic the behavioral variant of FTD (bvFTD), but do not show functional decline or abnormalities upon visual inspection of routine neuroimaging. We aimed to identify abnormalities in gray matter (GM) volume and perfusion in phFTD and to assess whether phFTD belongs to the FTD spectrum. We compared phFTD patients with both healthy controls and bvFTD patients. Materials & methods Seven phFTD and 11 bvFTD patients, and 20 age-matched controls underwent structural T1-weighted magnetic resonance imaging (MRI) and 3D pseudo-continuous arterial spin labeling (pCASL) at 3T. Normalized GM (nGM) volumes and perfusion, corrected for partial volume effects, were quantified regionally as well as in the entire supratentorial cortex, and compared between groups taking into account potential confounding effects of gender and scanner. Results PhFTD patients showed cortical atrophy, most prominently in the right temporal lobe. Apart from this regional atrophy, GM volume was generally not different from either controls or from bvFTD. BvFTD however showed extensive frontotemporal atrophy. Perfusion was increased in the left prefrontal cortex compared to bvFTD and to a lesser extent to controls. Conclusion PhFTD and bvFTD show overlapping cortical structural abnormalities indicating a continuum of changes especially in the frontotemporal regions. Together with functional changes suggestive of a compensatory response to incipient pathology in the left prefrontal regions, these findings are the first to support a possible neuropathological etiology of phFTD and suggest that phFTD may be a neurodegenerative disease on the FTD spectrum. PMID:27222795

  19. Neonatal brain abnormalities and memory and learning outcomes at 7 years in children born very preterm.

    PubMed

    Omizzolo, Cristina; Scratch, Shannon E; Stargatt, Robyn; Kidokoro, Hiroyuki; Thompson, Deanne K; Lee, Katherine J; Cheong, Jeanie; Neil, Jeffrey; Inder, Terrie E; Doyle, Lex W; Anderson, Peter J

    2014-01-01

    Using prospective longitudinal data from 198 very preterm and 70 full term children, this study characterised the memory and learning abilities of very preterm children at 7 years of age in both verbal and visual domains. The relationship between the extent of brain abnormalities on neonatal magnetic resonance imaging (MRI) and memory and learning outcomes at 7 years of age in very preterm children was also investigated. Neonatal MRI scans were qualitatively assessed for global, white-matter, cortical grey-matter, deep grey-matter, and cerebellar abnormalities. Very preterm children performed less well on measures of immediate memory, working memory, long-term memory, and learning compared with term-born controls. Neonatal brain abnormalities, and in particular deep grey-matter abnormality, were associated with poorer memory and learning performance at 7 years in very preterm children. Findings support the importance of cerebral neonatal pathology for predicting later memory and learning function.

  20. Human brain: reliability and reproducibility of pulsed arterial spin-labeling perfusion MR imaging.

    PubMed

    Jahng, Geon-Ho; Song, Enmin; Zhu, Xiao-Ping; Matson, Gerald B; Weiner, Michael W; Schuff, Norbert

    2005-03-01

    The Committee of Human Research of the University of California San Francisco approved this study, and all volunteers provided written informed consent. The goal of this study was to prospectively determine the global and regional reliability and reproducibility of noninvasive brain perfusion measurements obtained with different pulsed arterial spin-labeling (ASL) magnetic resonance (MR) imaging methods and to determine the extent to which within-subject variability and random noise limit reliability and reproducibility. Thirteen healthy volunteers were examined twice within 2 hours. The pulsed ASL methods compared in this study differ mainly with regard to magnetization transfer and eddy current effects. There were two main results: (a) Pulsed ASL MR imaging consistently had high measurement reliability (intraclass correlation coefficients greater than 0.75) and reproducibility (coefficients of variation less than 8.5%), and (b) random noise rather than within-subject variability limited reliability and reproducibility. It was concluded that low signal-to-noise ratios substantially limit the reliability and reproducibility of perfusion measurements.

  1. Brain potentials implicate temporal lobe abnormalities in criminal psychopaths.

    PubMed

    Kiehl, Kent A; Bates, Alan T; Laurens, Kristin R; Hare, Robert D; Liddle, Peter F

    2006-08-01

    Psychopathy is associated with abnormalities in attention and orienting. However, few studies have examined the neural systems underlying these processes. To address this issue, the authors recorded event-related potentials (ERPs) while 80 incarcerated men, classified as psychopathic or nonpsychopathic via the Hare Psychopathy Checklist--Revised (R. D. Hare, 1991, 2003), completed an auditory oddball task. Consistent with hypotheses, processing of targets elicited larger frontocentral negativities (N550) in psychopaths than in nonpsychopaths. Psychopaths also showed an enlarged N2 and reduced P3 during target detection. Similar ERP modulations have been reported in patients with amygdala and temporal lobe damage. The data are interpreted as supporting the hypothesis that psychopathy may be related to dysfunction of the paralimbic system--a system that includes parts of the temporal and frontal lobes. PMID:16866585

  2. Towards adapting a normal patient database for SPECT brain perfusion imaging

    NASA Astrophysics Data System (ADS)

    Smith, N. D.; Holmes, R. B.; Soleimani, M.; Evans, M. J.; Cade, S. C.; Mitchell, C. N.

    2012-06-01

    Single-photon emission computerized tomography (SPECT) is a tool which can be used to image perfusion in the brain. Clinicians can use such images to help diagnose dementias such as Alzheimer's disease. Due to the intrinsic stochasticity in the photon imaging system, some form of statistical comparison of an individual image with a 'normal' patient database gives a clinician additional confidence in interpreting the image. Due to the variations between SPECT camera systems, ideally a normal patient database is required for each individual system. However, cost or ethical considerations often prohibit the collection of such a database for each new camera system. Some method of adapting existing normal patient databases to new camera systems would be beneficial. This paper introduces a method which may be regarded as a 'first-pass' attempt based on 2-norm regularization and a codebook of discrete spatially stationary convolutional kernels. Some preliminary illustrative results are presented, together with discussion on limitations and possible improvements.

  3. [How can we determine the best cerebral perfusion pressure in pediatric traumatic brain injury?].

    PubMed

    Vuillaume, C; Mrozek, S; Fourcade, O; Geeraerts, T

    2013-12-01

    The management of cerebral perfusion pressure (CPP) is the one of the main preoccupation for the care of paediatric traumatic brain injury (TBI). The physiology of cerebral autoregulation, CO2 vasoreactivity, cerebral metabolism changes with age as well as the brain compliance. Low CPP leads to high morbidity and mortality in pediatric TBI. The recent guidelines for the management of CPP for the paediatric TBI indicate a CPP threshold 40-50 mmHg (infants for the lower and adolescent for the upper). But we must consider the importance of age-related differences in the arterial pressure and CPP. The best CPP is the one that allows to avoid cerebral ischaemia and oedema. In this way, the adaptation of optimal CPP must be individual. To assess this objective, interesting tools are available. Transcranial Doppler can be used to determine the best level of CPP. Other indicators can predict the impairment of autoregulation like pressure reactivity index (PRx) taking into consideration the respective changes in ICP and CPP. Measurement of brain tissue oxygen partial pressure is an other tool that can be used to determine the optimal CPP.

  4. Acute effects of alcohol on brain perfusion monitored with arterial spin labeling magnetic resonance imaging in young adults.

    PubMed

    Marxen, Michael; Gan, Gabriela; Schwarz, Daniel; Mennigen, Eva; Pilhatsch, Maximilian; Zimmermann, Ulrich S; Guenther, Matthias; Smolka, Michael N

    2014-03-01

    While a number of studies have established that moderate doses of alcohol increase brain perfusion, the time course of such an increase as a function of breath alcohol concentration (BrAC) has not yet been investigated, and studies differ about regional effects. Using arterial spin labeling (ASL) magnetic resonance imaging, we investigated (1) the time course of the perfusion increase during a 15-minute linear increase of BrAC up to 0.6 g/kg followed by a steady exposure of 100 minutes, (2) the regional distribution, (3) a potential gender effect, and (4) the temporal stability of perfusion effects. In 48 young adults who participated in the Dresden longitudinal study on alcohol effects in young adults, we observed (1) a 7% increase of global perfusion as compared with placebo and that perfusion and BrAC are tightly coupled in time, (2) that the increase reaches significance in most regions of the brain, (3) that the effect is stronger in women than in men, and (4) that an acute tolerance effect is not observable on the time scale of 2 hours. Larger studies are needed to investigate the origin and the consequences of the effect, as well as the correlates of inter-subject variations.

  5. Justification of administered dose level in brain perfusion imaging with 99mTc-HMPAO

    NASA Astrophysics Data System (ADS)

    Stefanoyiannis, A. P.; Gerogiannis, I.; Geronikola-Trapali, X.; Armeniakos, I.; Prentakis, A.; Soultanis, S.; Chatziioannou, S. N.

    2011-09-01

    Brain perfusion imaging by means of 99mTc-HMPAO is widely used in the diagnosis of Alzheimer's disease. The administered dose range recommended by the manufacturer and reported in bibliography is rather wide (~ 9.5 - 27 mCi), necessitating further quantitative analysis. In the framework of this study, a quantitative evaluation of the radiopharmaceutical performance for different values of administered dose was carried out, based on image quality indicators. Evaluation of image quality was based on wavelet-generated contrast, noise, and contrast-to-noise ratio indicators, denoted as CI, NI and CNR respectively. Subsequently, a generic image quality index was correlated with the administered dose, to produce an overall performance indicator (denoted as PI). Application of appropriate statistical tests (analysis of variance for normal and Kruskal-Wallis test for non-normal distributions) showed that there is a statistically significant difference in CI (p < 0.01), NI (p < 0.001) and CNR (p < 0.05), but not in PI (p > 0.05) values. Application of Tukey test for CI and NI normal distributions demonstrated that CI (10 mCi) = CI (20 mCi) < CI (15 mCi) and NI (10 mCi) > NI (20 mCi), while NI (15 mCi) could not be characterised. Finally, application of non-parametric multiple comparisons showed that CNR (20 mCi) < CNR (10 mCi), while CNR (15 mCi) could not be characterised. Consequently, brain perfusion imaging, by means of 99mTc-HMPAO utilising an administered dose of 20 mCi, results in improved image quality on the basis of the estimated indicators. Additionally, this image quality improvement is sufficient to justify the increased patient radiation burden.

  6. Abnormal brain structure in youth who commit homicide

    PubMed Central

    Cope, L.M.; Ermer, E.; Gaudet, L.M.; Steele, V.R.; Eckhardt, A.L.; Arbabshirani, M.R.; Caldwell, M.F.; Calhoun, V.D.; Kiehl, K.A.

    2014-01-01

    Background Violence that leads to homicide results in an extreme financial and emotional burden on society. Juveniles who commit homicide are often tried in adult court and typically spend the majority of their lives in prison. Despite the enormous costs associated with homicidal behavior, there have been no serious neuroscientific studies examining youth who commit homicide. Methods Here we use neuroimaging and voxel-based morphometry to examine brain gray matter in incarcerated male adolescents who committed homicide (n = 20) compared with incarcerated offenders who did not commit homicide (n = 135). Two additional control groups were used to understand further the nature of gray matter differences: incarcerated offenders who did not commit homicide matched on important demographic and psychometric variables (n = 20) and healthy participants from the community (n = 21). Results Compared with incarcerated adolescents who did not commit homicide (n = 135), incarcerated homicide offenders had reduced gray matter volumes in the medial and lateral temporal lobes, including the hippocampus and posterior insula. Feature selection and support vector machine learning classified offenders into the homicide and non-homicide groups with 81% overall accuracy. Conclusions Our results indicate that brain structural differences may help identify those at the highest risk for committing serious violent offenses. PMID:24936430

  7. Partial volume correction of brain perfusion estimates using the inherent signal data of time-resolved arterial spin labeling.

    PubMed

    Ahlgren, André; Wirestam, Ronnie; Petersen, Esben Thade; Ståhlberg, Freddy; Knutsson, Linda

    2014-09-01

    Quantitative perfusion MRI based on arterial spin labeling (ASL) is hampered by partial volume effects (PVEs), arising due to voxel signal cross-contamination between different compartments. To address this issue, several partial volume correction (PVC) methods have been presented. Most previous methods rely on segmentation of a high-resolution T1 -weighted morphological image volume that is coregistered to the low-resolution ASL data, making the result sensitive to errors in the segmentation and coregistration. In this work, we present a methodology for partial volume estimation and correction, using only low-resolution ASL data acquired with the QUASAR sequence. The methodology consists of a T1 -based segmentation method, with no spatial priors, and a modified PVC method based on linear regression. The presented approach thus avoids prior assumptions about the spatial distribution of brain compartments, while also avoiding coregistration between different image volumes. Simulations based on a digital phantom as well as in vivo measurements in 10 volunteers were used to assess the performance of the proposed segmentation approach. The simulation results indicated that QUASAR data can be used for robust partial volume estimation, and this was confirmed by the in vivo experiments. The proposed PVC method yielded probable perfusion maps, comparable to a reference method based on segmentation of a high-resolution morphological scan. Corrected gray matter (GM) perfusion was 47% higher than uncorrected values, suggesting a significant amount of PVEs in the data. Whereas the reference method failed to completely eliminate the dependence of perfusion estimates on the volume fraction, the novel approach produced GM perfusion values independent of GM volume fraction. The intra-subject coefficient of variation of corrected perfusion values was lowest for the proposed PVC method. As shown in this work, low-resolution partial volume estimation in connection with ASL perfusion

  8. Maternal immune activation and abnormal brain development across CNS disorders.

    PubMed

    Knuesel, Irene; Chicha, Laurie; Britschgi, Markus; Schobel, Scott A; Bodmer, Michael; Hellings, Jessica A; Toovey, Stephen; Prinssen, Eric P

    2014-11-01

    Epidemiological studies have shown a clear association between maternal infection and schizophrenia or autism in the progeny. Animal models have revealed maternal immune activation (mIA) to be a profound risk factor for neurochemical and behavioural abnormalities in the offspring. Microglial priming has been proposed as a major consequence of mIA, and represents a critical link in a causal chain that leads to the wide spectrum of neuronal dysfunctions and behavioural phenotypes observed in the juvenile, adult or aged offspring. Such diversity of phenotypic outcomes in the mIA model are mirrored by recent clinical evidence suggesting that infectious exposure during pregnancy is also associated with epilepsy and, to a lesser extent, cerebral palsy in children. Preclinical research also suggests that mIA might precipitate the development of Alzheimer and Parkinson diseases. Here, we summarize and critically review the emerging evidence that mIA is a shared environmental risk factor across CNS disorders that varies as a function of interactions between genetic and additional environmental factors. We also review ongoing clinical trials targeting immune pathways affected by mIA that may play a part in disease manifestation. In addition, future directions and outstanding questions are discussed, including potential symptomatic, disease-modifying and preventive treatment strategies.

  9. Detection of the brain response during a cognitive task using perfusion-based event-related functional MRI.

    PubMed

    Yee, S H; Liu, H L; Hou, J; Pu, Y; Fox, P T; Gao, J H

    2000-08-01

    Event-related (ER) fMRI has evoked great interest due to the ability to depict the dynamic features of human brain function during various cognitive tasks. Thus far, all cognitive ER-fMRI studies have been based on blood oxygenation level-dependent (BOLD) contrast techniques. Compared with BOLD-based fMRI techniques, perfusion-based fMRI is able to localize the region of neuronal activity more accurately. This report demonstrates, for the first time, the detection of the brain response to a cognitive task using high temporal resolution perfusion-based ER-fMRI. An English verb generation task was used in this study. Results show that perfusion-based ER-fMRI accurately depicts the activation in Broca's area. Average changes in regional relative cerebral blood flow reached a maximum value of 30.7% at approximately 6.5 s after the start of stimulation and returned to 10% of the maximum value at approximately 12.8 s. Our results show that perfusion-based ER-fMRI is a useful tool for cognitive neuroscience studies, providing comparable temporal resolution and better localization of brain function than BOLD ER-fMRI. PMID:10943717

  10. Auditory brain stem response abnormalities in the very low birthweight infant: incidence and risk factors.

    PubMed

    Cox, L C; Hack, M; Metz, D A

    1984-01-01

    Auditory brain stem evoked response (ABR) testing was performed on 50 very low birthweight infants in an effort to assess the effects of multiple neonatal risk factors on auditory function. The results suggested that no single risk factor was predictive of ABR abnormality while combined risk factors were shown to be very predictive.

  11. Preliminary research on abnormal brain detection by wavelet-energy and quantum- behaved PSO.

    PubMed

    Zhang, Yudong; Ji, Genlin; Yang, Jiquan; Wang, Shuihua; Dong, Zhengchao; Phillips, Preetha; Sun, Ping

    2016-04-29

    It is important to detect abnormal brains accurately and early. The wavelet-energy (WE) was a successful feature descriptor that achieved excellent performance in various applications; hence, we proposed a WE based new approach for automated abnormal detection, and reported its preliminary results in this study. The kernel support vector machine (KSVM) was used as the classifier, and quantum-behaved particle swarm optimization (QPSO) was introduced to optimize the weights of the SVM. The results based on a 5 × 5-fold cross validation showed the performance of the proposed WE + QPSO-KSVM was superior to ``DWT + PCA + BP-NN'', ``DWT + PCA + RBF-NN'', ``DWT + PCA + PSO-KSVM'', ``WE + BPNN'', ``WE +$ KSVM'', and ``DWT $+$ PCA $+$ GA-KSVM'' w.r.t. sensitivity, specificity, and accuracy. The work provides a novel means to detect abnormal brains with excellent performance. PMID:27163327

  12. Preliminary research on abnormal brain detection by wavelet-energy and quantum- behaved PSO.

    PubMed

    Zhang, Yudong; Ji, Genlin; Yang, Jiquan; Wang, Shuihua; Dong, Zhengchao; Phillips, Preetha; Sun, Ping

    2016-04-29

    It is important to detect abnormal brains accurately and early. The wavelet-energy (WE) was a successful feature descriptor that achieved excellent performance in various applications; hence, we proposed a WE based new approach for automated abnormal detection, and reported its preliminary results in this study. The kernel support vector machine (KSVM) was used as the classifier, and quantum-behaved particle swarm optimization (QPSO) was introduced to optimize the weights of the SVM. The results based on a 5 × 5-fold cross validation showed the performance of the proposed WE + QPSO-KSVM was superior to ``DWT + PCA + BP-NN'', ``DWT + PCA + RBF-NN'', ``DWT + PCA + PSO-KSVM'', ``WE + BPNN'', ``WE +$ KSVM'', and ``DWT $+$ PCA $+$ GA-KSVM'' w.r.t. sensitivity, specificity, and accuracy. The work provides a novel means to detect abnormal brains with excellent performance.

  13. Increased Brain Perfusion Persists over the First Month of Life in Term Asphyxiated Newborns Treated with Hypothermia: Does it Reflect Activated Angiogenesis?

    PubMed

    Shaikh, Henna; Lechpammer, Mirna; Jensen, Frances E; Warfield, Simon K; Hansen, Anne H; Kosaras, Bela; Shevell, Michael; Wintermark, Pia

    2015-06-01

    Many asphyxiated newborns still develop brain injury despite hypothermia therapy. The development of brain injury in these newborns has been related partly to brain perfusion abnormalities. The purposes of this study were to assess brain hyperperfusion over the first month of life in term asphyxiated newborns and to search for some histopathological clues indicating whether this hyperperfusion may be related to activated angiogenesis following asphyxia. In this prospective cohort study, regional cerebral blood flow was measured in term asphyxiated newborns treated with hypothermia around day 10 of life and around 1 month of life using magnetic resonance imaging (MRI) and arterial spin labeling. A total of 32 MRI scans were obtained from 24 term newborns. Asphyxiated newborns treated with hypothermia displayed an increased cerebral blood flow in the injured brain areas around day 10 of life and up to 1 month of life. In addition, we looked at the histopathological clues in a human asphyxiated newborn and in a rat model of neonatal encephalopathy. Vascular endothelial growth factor (VEGF) was expressed in the injured brain of an asphyxiated newborn treated with hypothermia in the first days of life and of rat pups 24-48 h after the hypoxic-ischemic event, and the endothelial cell count increased in the injured cortex of the pups 7 and 11 days after hypoxia-ischemia. Our data showed that the hyperperfusion measured by imaging persisted in the injured areas up to 1 month of life and that angiogenesis was activated in the injured brain of asphyxiated newborns. PMID:25620793

  14. A brain stress test: Cerebral perfusion during memory encoding in mild cognitive impairment.

    PubMed

    Xie, Long; Dolui, Sudipto; Das, Sandhitsu R; Stockbower, Grace E; Daffner, Molly; Rao, Hengyi; Yushkevich, Paul A; Detre, John A; Wolk, David A

    2016-01-01

    Arterial spin labeled perfusion magnetic resonance imaging (ASL MRI) provides non-invasive quantification of cerebral blood flow, which can be used as a biomarker of brain function due to the tight coupling between cerebral blood flow (CBF) and brain metabolism. A growing body of literature suggests that regional CBF is altered in neurodegenerative diseases. Here we examined ASL MRI CBF in subjects with amnestic mild cognitive impairment (n = 65) and cognitively normal healthy controls (n = 62), both at rest and during performance of a memory-encoding task. As compared to rest, task-enhanced ASL MRI improved group discrimination, which supports the notion that physiologic measures during a cognitive challenge, or "stress test", may increase the ability to detect subtle functional changes in early disease stages. Further, logistic regression analysis demonstrated that ASL MRI and concomitantly acquired structural MRI provide complementary information of disease status. The current findings support the potential utility of task-enhanced ASL MRI as a biomarker in early Alzheimer's disease. PMID:27222794

  15. A brain stress test: Cerebral perfusion during memory encoding in mild cognitive impairment.

    PubMed

    Xie, Long; Dolui, Sudipto; Das, Sandhitsu R; Stockbower, Grace E; Daffner, Molly; Rao, Hengyi; Yushkevich, Paul A; Detre, John A; Wolk, David A

    2016-01-01

    Arterial spin labeled perfusion magnetic resonance imaging (ASL MRI) provides non-invasive quantification of cerebral blood flow, which can be used as a biomarker of brain function due to the tight coupling between cerebral blood flow (CBF) and brain metabolism. A growing body of literature suggests that regional CBF is altered in neurodegenerative diseases. Here we examined ASL MRI CBF in subjects with amnestic mild cognitive impairment (n = 65) and cognitively normal healthy controls (n = 62), both at rest and during performance of a memory-encoding task. As compared to rest, task-enhanced ASL MRI improved group discrimination, which supports the notion that physiologic measures during a cognitive challenge, or "stress test", may increase the ability to detect subtle functional changes in early disease stages. Further, logistic regression analysis demonstrated that ASL MRI and concomitantly acquired structural MRI provide complementary information of disease status. The current findings support the potential utility of task-enhanced ASL MRI as a biomarker in early Alzheimer's disease.

  16. Chapter 5 cerebral perfusion pressure and intracranial pressure in traumatic brain injury.

    PubMed

    Mitchell, Pamela H; Kirkness, Catherine; Blissitt, Patricia A

    2015-01-01

    Nearly 300,000 children and adults are hospitalized annually with traumatic brain injury (TBI) and monitored for many vital signs, including intracranial pressure (ICP) and cerebral perfusion pressure (CPP). Nurses use these monitored values to infer the risk of secondary brain injury. The purpose of this chapter is to review nursing research on the monitoring of ICP and CPP in TBI. In this context, nursing research is defined as the research conducted by nurse investigators or research about the variables ICP and CPP that pertains to the nursing care of the TBI patient, adult or child. A modified systematic review of the literature indicated that, except for sharp head rotation and prone positioning, there are no body positions or nursing activities that uniformly or nearly uniformly result in clinically relevant ICP increase or decrease. In the smaller number of studies in which CPP is also measured, there are few changes in CPP since arterial blood pressure generally increases along with ICP. Considerable individual variation occurs in controlled studies, suggesting that clinicians need to pay close attention to the cerebrodynamic responses of each patient to any care maneuver. We recommend that future research regarding nursing care and ICP/CPP in TBI patients needs to have a more integrated approach, examining comprehensive care in relation to short- and long-term outcomes and incorporating multimodality monitoring. Intervention trials of care aspects within nursing control, such as the reduction of environmental noise, early mobilization, and reduction of complications of immobility, are all sorely needed.

  17. A brain stress test: Cerebral perfusion during memory encoding in mild cognitive impairment

    PubMed Central

    Xie, Long; Dolui, Sudipto; Das, Sandhitsu R.; Stockbower, Grace E.; Daffner, Molly; Rao, Hengyi; Yushkevich, Paul A.; Detre, John A.; Wolk, David A.

    2016-01-01

    Arterial spin labeled perfusion magnetic resonance imaging (ASL MRI) provides non-invasive quantification of cerebral blood flow, which can be used as a biomarker of brain function due to the tight coupling between cerebral blood flow (CBF) and brain metabolism. A growing body of literature suggests that regional CBF is altered in neurodegenerative diseases. Here we examined ASL MRI CBF in subjects with amnestic mild cognitive impairment (n = 65) and cognitively normal healthy controls (n = 62), both at rest and during performance of a memory-encoding task. As compared to rest, task-enhanced ASL MRI improved group discrimination, which supports the notion that physiologic measures during a cognitive challenge, or “stress test”, may increase the ability to detect subtle functional changes in early disease stages. Further, logistic regression analysis demonstrated that ASL MRI and concomitantly acquired structural MRI provide complementary information of disease status. The current findings support the potential utility of task-enhanced ASL MRI as a biomarker in early Alzheimer's disease. PMID:27222794

  18. Development of a realistic, dynamic digital brain phantom for CT perfusion validation

    NASA Astrophysics Data System (ADS)

    Divel, Sarah E.; Segars, W. Paul; Christensen, Soren; Wintermark, Max; Lansberg, Maarten G.; Pelc, Norbert J.

    2016-03-01

    Physicians rely on CT Perfusion (CTP) images and quantitative image data, including cerebral blood flow, cerebral blood volume, and bolus arrival delay, to diagnose and treat stroke patients. However, the quantification of these metrics may vary depending on the computational method used. Therefore, we have developed a dynamic and realistic digital brain phantom upon which CTP scans can be simulated based on a set of ground truth scenarios. Building upon the previously developed 4D extended cardiac-torso (XCAT) phantom containing a highly detailed brain model, this work consisted of expanding the intricate vasculature by semi-automatically segmenting existing MRA data and fitting nonuniform rational B-spline surfaces to the new vessels. Using time attenuation curves input by the user as reference, the contrast enhancement in the vessels changes dynamically. At each time point, the iodine concentration in the arteries and veins is calculated from the curves and the material composition of the blood changes to reflect the expected values. CatSim, a CT system simulator, generates simulated data sets of this dynamic digital phantom which can be further analyzed to validate CTP studies and post-processing methods. The development of this dynamic and realistic digital phantom provides a valuable resource with which current uncertainties and controversies surrounding the quantitative computations generated from CTP data can be examined and resolved.

  19. Early whole-brain CT perfusion for detection of patients at risk for delayed cerebral ischemia after subarachnoid hemorrhage.

    PubMed

    Malinova, Vesna; Dolatowski, Karoline; Schramm, Peter; Moerer, Onnen; Rohde, Veit; Mielke, Dorothee

    2016-07-01

    OBJECT This prospective study investigated the role of whole-brain CT perfusion (CTP) studies in the identification of patients at risk for delayed ischemic neurological deficits (DIND) and of tissue at risk for delayed cerebral infarction (DCI). METHODS Forty-three patients with aneurysmal subarachnoid hemorrhage (aSAH) were included in this study. A CTP study was routinely performed in the early phase (Day 3). The CTP study was repeated in cases of transcranial Doppler sonography (TCD)-measured blood flow velocity (BFV) increase of > 50 cm/sec within 24 hours and/or on Day 7 in patients who were intubated/sedated. RESULTS Early CTP studies revealed perfusion deficits in 14 patients, of whom 10 patients (72%) developed DIND, and 6 of these 10 patients (60%) had DCI. Three of the 14 patients (21%) with early perfusion deficits developed DCI without having had DIND, and the remaining patient (7%) had neither DIND nor DCI. There was a statistically significant correlation between early perfusion deficits and occurrence of DIND and DCI (p < 0.0001). A repeated CTP was performed in 8 patients with a TCD-measured BFV increase > 50 cm/sec within 24 hours, revealing a perfusion deficit in 3 of them (38%). Two of the 3 patients (67%) developed DCI without preceding DIND and 1 patient (33%) had DIND without DCI. In 4 of the 7 patients (57%) who were sedated and/or comatose, additional CTP studies on Day 7 showed perfusion deficits. All 4 patients developed DCI. CONCLUSIONS Whole-brain CTP on Day 3 after aSAH allows early and reliable identification of patients at risk for DIND and tissue at risk for DCI. Additional CTP investigations, guided by TCD-measured BFV increase or persisting coma, do not contribute to information gain.

  20. Abnormal brain magnetic resonance imaging in two patients with Smith-Magenis syndrome.

    PubMed

    Maya, Idit; Vinkler, Chana; Konen, Osnat; Kornreich, Liora; Steinberg, Tamar; Yeshaya, Josepha; Latarowski, Victoria; Shohat, Mordechai; Lev, Dorit; Baris, Hagit N

    2014-08-01

    Smith-Magenis syndrome (SMS) is a clinically recognizable contiguous gene syndrome ascribed to an interstitial deletion in chromosome 17p11.2. Seventy percent of SMS patients have a common deletion interval spanning 3.5 megabases (Mb). Clinical features of SMS include characteristic mild dysmorphic features, ocular anomalies, short stature, brachydactyly, and hypotonia. SMS patients have a unique neurobehavioral phenotype that includes intellectual disability, self-injurious behavior and severe sleep disturbance. Little has been reported in the medical literature about anatomical brain anomalies in patients with SMS. Here we describe two patients with SMS caused by the common deletion in 17p11.2 diagnosed using chromosomal microarray (CMA). Both patients had a typical clinical presentation and abnormal brain magnetic resonance imaging (MRI) findings. One patient had subependymal periventricular gray matter heterotopia, and the second had a thin corpus callosum, a thin brain stem and hypoplasia of the cerebellar vermis. This report discusses the possible abnormal MRI images in SMS and reviews the literature on brain malformations in SMS. Finally, although structural brain malformations in SMS patients are not a common feature, we suggest baseline routine brain imaging in patients with SMS in particular, and in patients with chromosomal microdeletion/microduplication syndromes in general. Structural brain malformations in these patients may affect the decision-making process regarding their management.

  1. Structural Brain Abnormalities in Patients with Schizophrenia and 22q11 Deletion Syndrome

    PubMed Central

    Chow, Eva W.C.; Zipursky, Robert B.; Mikulis, David J.; Bassett, Anne S.

    2012-01-01

    Background 22q11 Deletion Syndrome is a genetic syndrome associated with an increased risk for developing schizophrenia. Brain abnormalities have been reported in 22q11 Deletion Syndrome, but little is known about whether differences in brain structure underlie the psychotic disorders associated with this syndrome. In the current study, we used magnetic resonance imaging to characterize the structural brain abnormalities found in adults who have both 22q11 Deletion Syndrome and schizophrenia. Methods Magnetic resonance imaging brain scans of 14 adults (7 male, 7 female) with 22q11 Deletion Syndrome and schizophrenia and 14 age- and gender-matched healthy volunteers were analyzed to derive measures of gray matter, white matter, and cerebrospinal fluid. Differences between the two groups were tested using student t tests. Results 22q11 Deletion Syndrome and schizophrenia subjects had significantly smaller total gray matter volume (t = 2.88, p < .01) and larger lateral ventricles (t = 4.08, p < .001) than healthy controls. Gray matter deficits were most prominent in the frontal and temporal lobes. Total white matter volumes did not differ between the two groups. Conclusions Findings from this 22q11 Deletion Syndrome and schizophrenia study are similar to those reported in other patients with schizophrenia, but only partially consistent with those reported in nonpsychotic children with 22q11 Deletion Syndrome. 22q11 Deletion Syndrome may provide a valuable genetic neurodevelop-mental model for investigating the relationship between abnormalities in brain development and the expression of schizophrenia. PMID:11839363

  2. Absolute perfusion measurements and associated iodinated contrast agent time course in brain metastasis: a study for contrast-enhanced radiotherapy.

    PubMed

    Obeid, Layal; Deman, Pierre; Tessier, Alexandre; Balosso, Jacques; Estève, François; Adam, Jean-François

    2014-04-01

    Contrast-enhanced radiotherapy is an innovative treatment that combines the selective accumulation of heavy elements in tumors with stereotactic irradiations using medium energy X-rays. The radiation dose enhancement depends on the absolute amount of iodine reached in the tumor and its time course. Quantitative, postinfusion iodine biodistribution and associated brain perfusion parameters were studied in human brain metastasis as key parameters for treatment feasibility and quality. Twelve patients received an intravenous bolus of iodinated contrast agent (CA) (40 mL, 4 mL/s), followed by a steady-state infusion (160 mL, 0.5 mL/s) to ensure stable intratumoral amounts of iodine during the treatment. Absolute iodine concentrations and quantitative perfusion maps were derived from 40 multislice dynamic computed tomography (CT) images of the brain. The postinfusion mean intratumoral iodine concentration (over 30 minutes) reached 1.94 ± 0.12 mg/mL. Reasonable correlations were obtained between these concentrations and the permeability surface area product and the cerebral blood volume. To our knowledge, this is the first quantitative study of CA biodistribution versus time in brain metastasis. The study shows that suitable and stable amounts of iodine can be reached for contrast-enhanced radiotherapy. Moreover, the associated perfusion measurements provide useful information for the patient recruitment and management processes.

  3. Cerebral perfusion pressure and risk of brain hypoxia in severe head injury: a prospective observational study

    PubMed Central

    Marín-Caballos, Antonio J; Murillo-Cabezas, Francisco; Cayuela-Domínguez, Aurelio; Domínguez-Roldán, Jose M; Rincón-Ferrari, M Dolores; Valencia-Anguita, Julio; Flores-Cordero, Juan M; Muñoz-Sánchez, M Angeles

    2005-01-01

    Introduction Higher and lower cerebral perfusion pressure (CPP) thresholds have been proposed to improve brain tissue oxygen pressure (PtiO2) and outcome. We study the distribution of hypoxic PtiO2 samples at different CPP thresholds, using prospective multimodality monitoring in patients with severe traumatic brain injury. Methods This is a prospective observational study of 22 severely head injured patients admitted to a neurosurgical critical care unit from whom multimodality data was collected during standard management directed at improving intracranial pressure, CPP and PtiO2. Local PtiO2 was continuously measured in uninjured areas and snapshot samples were collected hourly and analyzed in relation to simultaneous CPP. Other variables that influence tissue oxygen availability, mainly arterial oxygen saturation, end tidal carbon dioxide, body temperature and effective hemoglobin, were also monitored to keep them stable in order to avoid non-ischemic hypoxia. Results Our main results indicate that half of PtiO2 samples were at risk of hypoxia (defined by a PtiO2 equal to or less than 15 mmHg) when CPP was below 60 mmHg, and that this percentage decreased to 25% and 10% when CPP was between 60 and 70 mmHg and above 70 mmHg, respectively (p < 0.01). Conclusion Our study indicates that the risk of brain tissue hypoxia in severely head injured patients could be really high when CPP is below the normally recommended threshold of 60 mmHg, is still elevated when CPP is slightly over it, but decreases at CPP values above it. PMID:16356218

  4. Cerebral perfusion pressure, microdialysis biochemistry and clinical outcome in patients with traumatic brain injury

    PubMed Central

    2011-01-01

    Background Traumatic Brain Injury (TBI) is a major cause of death and disability. It has been postulated that brain metabolic status, intracranial pressure (ICP) and cerebral perfusion pressure (CPP) are related to patients' outcome. The aim of this study was to investigate the relationship between CPP, ICP and microdialysis parameters and clinical outcome in TBIs. Results Thirty four individuals with severe brain injury hospitalized in an intensive care unit participated in this study. Microdialysis data were collected, along with ICP and CPP values. Glasgow Outcome Scale (GOS) was used to evaluate patient outcome at 6 months after injury. Fifteen patients with a CPP greater than 75 mmHg, L/P ratio lower than 37 and Glycerol concentration lower than 72 mmol/l had an excellent outcome (GOS 4 or 5), as opposed to the remaining 19 patients. No patient with a favorable outcome had a CPP lower than 75 mmHg or Glycerol concentration and L/P ratio greater than 72 mmol/l and 37 respectively. Data regarding L/P ratio and Glycerol concentration were statistically significant at p = 0.05 when patients with favorable and unfavorable outcome were compared. In a logistic regression model adjusted for age, sex and Glasgow Coma Scale on admission, a CPP greater than 75 mmHg was marginally statistically significantly related to outcome at 6 months after injury. Conclusions Patients with favorable outcome had certain common features in terms of microdialysis parameters and CPP values. An individualized approach regarding CPP levels and cut -off points for Glycerol concentration and L/P ratio are proposed. PMID:22168902

  5. Abnormal brain aging as a radical-related disease: A new target for nuclear medicine

    SciTech Connect

    Fujibayashi, Y.; Yamamoto, S.; Waki, A. |

    1996-05-01

    DNA damages caused by endogenously produced radicals are closely correlated with aging. Among them, mitochondrial DNA (mtDNA) deletions have been reported as a memory of DNA damage by oxygen radicals. In fact, clinical as well as experimental studies indicated the accumulation of deleted mtDNA in the brain, myocardium and son on, in aged subjects. In our previous work, radioiodinated radical trapping agent, p-iodophenyl-N-t-butylnitrone, and hypoxia imaging agent, Cu-62 diacetyl-bis-N-4-methyl-thiosemicarbazone have been developed for the diagnosis of radical-related diseases, such as ischemic, inflammation, cancer or aging. The aim of the present work was to evaluate these agents for brain aging studies. In our university, an unique animal model, a senescence accelerated model mouse (SAM), has been established. Among the various substrains, SAMP8 showing memory deterioration in its young age ({approximately}3 month) was basically evaluated as an abnormal brain aging model with mtDNA deletion. As controls, SAMR1 showing normal aging and ddY mice were used. MtDNA deletion n the brain was analyzed with polymerase-chain reaction (PCR) method, and relationship between mtDNA deletion and brain uptake of IPBN or Cu-62-ATSM was studied. In 1-3 month old SAMP8 brain, multiple mtDNa deletions were already found and their content was significantly higher than that of SAMR1 or age-matched ddY control. Thus, it was cleared that SAMP8 brain has high tendency to be attacked by endogenously produced oxygen radicals, possibly from its birth. Both IPBN and Cu-ATSM showed significantly higher accumulation in the SAMP8 brain than in the SAMR1 brain, indicating that these agents have high possibility for the early detection of abnormal brain aging as a radical-related disease.

  6. Nanoparticle-mediated delivery of oligonucleotides to the blood-brain barrier: in vitro and in situ brain perfusion studies on the uptake mechanisms.

    PubMed

    Ko, Young Tag

    2013-11-01

    Except for the few exceptions where topical administration is feasible, progress towards broad clinical application of nucleic acid therapeutics requires development of effective systemic delivery strategies. The central nervous system represents a particularly difficult organ for systemic delivery due to the blood-brain barrier. We previously reported a nanoparticulate delivery system for targeted brain delivery of oligonucleotides upon systemic administration, i.e. liposome-encapsulated polyethylenimine/oligonucleotides polyplexes. In this study, cellular uptake and intracellular trafficking of the nanoparticles were further investigated using in situ brain perfusion technique followed by colocalization and fluorescence resonance energy transfer techniques. The brain endothelial uptake and possibly parenchymal accumulation were readily visualized upon administration via internal carotid artery perfusion. The nanoparticles were colocalized with early-endosome antigen, which confirms the brain endothelial uptake through transferrin receptor-mediated endocytosis. Fluorescence resonance energy transfer analysis also suggested the nanoparticles entered the brain endothelial cells while maintaining their integrity. Together, the enhanced brain uptake, as claimed previously, of the antibody-targeted nanoparticles was clearly confirmed with more convincing evidences. In addition, the experimental techniques described here should be applicable to the studies involving nanoparticle-mediated brain delivery of nucleic acid therapeutics.

  7. Correlation of oxygenation and perfusion sensitive MRI with invasive micro probe measurements in healthy mice brain.

    PubMed

    Sedlacik, Jan; Reitz, Matthias; Bolar, Divya S; Adalsteinsson, Elfar; Schmidt, Nils O; Fiehler, Jens

    2015-03-01

    The non-invasive assessment of (patho-)physiological parameters such as, perfusion and oxygenation, is of great importance for the characterization of pathologies e.g., tumors, which may be helpful to better predict treatment response and potential outcome. To better understand the influence of physiological parameters on the investigated oxygenation and perfusion sensitive MRI methods, MRI measurements were correlated with subsequent invasive micro probe measurements during free breathing conditions of air, air+10% CO2 and 100% O2 in healthy mice brain. MRI parameters were the irreversible (R2), reversible (R2') and effective (R2*) transverse relaxation rates, venous blood oxygenation level assessed by quantitative blood oxygenation level dependent (qBOLD) method and cerebral blood flow (CBF) assessed by arterial spin labeling (ASL) using a 7 T small animal MRI scanner. One to two days after MRI, tissue perfusion and pO2 were measured by Laser-Doppler flowmetry and fluorescence quenching micro probes, respectively. The tissue pO2 values were converted to blood oxygen saturation by using the Hill equation. The animals were anesthetized by intra peritoneal injection of ketamine-xylazine-acepromazine (10-2-0.3 mg/ml · kg). Results for normal/hypercapnia/hyperoxia conditions were: R2[s(∧)-1] = 20.7/20.4/20.1, R2*[s(∧)-1] = 31.6/29.6/25.9, R2'[s-(∧)1] = 10.9/9.2/5.7, qBOLD venous blood oxygenation level = 0.43/0.51/0.56, CBF[ml · min(∧)-1 · 100 g(∧)-1] = 70.6/105.5/81.8, Laser-Doppler flowmetry[a.u.] = 89.2/120.2/90.6 and pO2[mmHg] = 6.3/32.3/46.7. All parameters were statistically significantly different with P < 0.001 between all breathing conditions. All MRI and the corresponding micro probe measurements were also statistically significantly (P ≤ 0.03) correlated with each other. However, converting the tissue pO2 to blood oxygen saturation = 0.02/0.34/0.63, showed only very limited agreement with the qBOLD venous blood oxygenation level. We found

  8. Cranial index of children with normal and abnormal brain development in Sokoto, Nigeria: A comparative study

    PubMed Central

    Musa, Muhammad Awwal; Zagga, Abdullahi Daudu; Danfulani, Mohammed; Tadros, Aziz Abdo; Ahmed, Hamid

    2014-01-01

    Background: Abnormal brain development due to neurodevelopmental disorders in children has always been an important concern, but yet has to be considered as a significant public health problem, especially in the low- and middle-income countries including Nigeria. Aims: The aim of this study is to determine whether abnormal brain development in the form of neurodevelopmental disorders causes any deviation in the cranial index of affected children. Materials and Methods: This is a comparative study on the head length, head width, and cranial index of 112 children (72 males and 40 females) diagnosed with at least one abnormal problem in brain development, in the form of a neurodevelopmental disorder (NDD), in comparison with that of 218 normal growing children without any form of NDD (121 males and 97 females), aged 0-18 years old seen at the Usmanu Danfodiyo University Teaching Hospital, Sokoto, over a period of six months, June to December, 2012. The head length and head width of the children was measured using standard anatomical landmarks and cranial index calculated. The data obtained was entered into the Microsoft excel worksheet and analyzed using SPSS version 17. Results: The mean Cephalic Index for normal growing children with normal brain development was 79.82 ± 3.35 and that of the children with abnormal brain development was 77.78 ± 2.95 and the difference between the two groups was not statistically significant (P > 0.05). Conclusion: It can be deduced from this present study that the cranial index does not change in children with neurodevelopmental disorders. PMID:24966551

  9. Sample collection and amino acids analysis of extracellular fluid of mouse brain slices with low flow push-pull perfusion.

    PubMed

    Ojeda-Torres, G; Williams, L; Featherstone, D E; Shippy, S A

    2015-10-01

    Brain tissue slices are a common neuroscience model that allows relatively sophisticated analysis of neuronal networks in a simplified preparation. Most experimental methodology utilizes electrophysiological tools to probe these model systems. The work here demonstrates the adaptation of low-flow push-pull perfusion sampling (LFPS) to a brain slice system. LFPS is used to sample from the hippocampus of mouse brain slices. Perfusate amino acid levels are quantified following sampling with capillary electrophoresis. Glutamate was measured from the CA1 region of the hippocampus in slices taken from a cystine-glutamate transporter deletion mutant, xCT(-/-), and the background strain C57BL/6J. Sampling is performed over up to 6.5 h with standard tissue slice preparation and experimentation methods. Four amino acids were quantified to demonstrate the ability to perform LFPS and show good agreement with published literature. Perfusate glutamate levels are found to be significantly lower with xCT(-/-) slices (1.9(±0.5) μM) relative to controls (4.90(±1.1) μM). But, experiments with control slices show a significant decrease in glutamate over the 6 h sampling period that are not seen with xCT(-/-) slices. Increasing the LFPS sample collection rate during the first 90 min of sampling did not show a sampling artifact in perfusate glutamate content. Sampling immediately following slicing did not show an early increasing glutamate level that would be indicative of a significant contribution from blood or tissue damage. The data presented here show a complementarity to electrophysiological studies of tissue slices. The ability to characterize extracellular fluid chemical content with LFPS in these slices provides an alternative data stream for probing neurochemical signaling networks in brain tissue slices. PMID:26299259

  10. Brain PET metabolic abnormalities in a case of varicella-zoster virus encephalitis.

    PubMed

    Coiffard, Benjamin; Guedj, Eric; Daumas, Aurélie; Leveque, Pierre; Villani, Patrick

    2014-09-01

    The role of brain 18F-FDG PET in the diagnostic evaluation of encephalitis has been recently suggested, especially in limbic encephalitis, but descriptions are mainly limited to small case reports. However, the evaluation of cerebral metabolism by 18F-FDG PET has never been described for varicella-zoster virus encephalitis. We report the first case of varicella-zoster virus encephalitis in which 18F-FDG PET revealed brain metabolic abnormalities. Brain metabolic PET imaging was analyzed by comparing the patient's brain 18F-FDG PET scans to that of 12 healthy subjects. Compared with healthy subjects, significant hypometabolism and hypermetabolism were found and evolved over time with treatment.

  11. SPECT Perfusion Imaging Demonstrates Improvement of Traumatic Brain Injury With Transcranial Near-infrared Laser Phototherapy.

    PubMed

    Henderson, Theodore A; Morries, Larry D

    2015-01-01

    Traumatic brain injury (TBI) is a growing health concern affecting civilians and military personnel. Near-infrared (NIR) light has shown benefits in animal models and human trials for stroke and in animal models for TBI. Diodes emitting low-level NIR often have lacked therapeutic efficacy, perhaps failing to deliver sufficient radiant energy to the necessary depth. In this case report, a patient with moderate TBI documented in anatomical magnetic resonance imaging (MRI) and perfusion single-photon emission computed tomography (SPECT) received 20 NIR treatments in the course of 2 mo using a high-power NIR laser. Symptoms were monitored by clinical examination and a novel patient diary system specifically designed for this patient population. Clinical application of these levels of infrared energy for this patient with TBI yielded highly favorable outcomes with decreased depression, anxiety, headache, and insomnia, whereas cognition and quality of life improved. Neurological function appeared to improve based on changes in the SPECT by quantitative analysis. NIR in the power range of 10-15 W at 810 and 980 nm can safely and effectively treat chronic symptoms of TBI. PMID:26535475

  12. Reduction in radiation dose with reconstruction technique in the brain perfusion CT

    NASA Astrophysics Data System (ADS)

    Kim, H. J.; Lee, H. K.; Song, H.; Ju, M. S.; Dong, K. R.; Chung, W. K.; Cho, M. S.; Cho, J. H.

    2011-12-01

    The principal objective of this study was to verify the utility of the reconstruction imaging technique in the brain perfusion computed tomography (PCT) scan by assessing reductions in the radiation dose and analyzing the generated images. The setting used for image acquisition had a detector coverage of 40 mm, a helical thickness of 0.625 mm, a helical shuttle mode scan type and a rotation time of 0.5 s as the image parameters used for the brain PCT scan. Additionally, a phantom experiment and an animal experiment were carried out. In the phantom and animal experiments, noise was measured in the scanning with the tube voltage fixed at 80 kVp (kilovolt peak) and the level of the adaptive statistical iterative reconstruction (ASIR) was changed from 0% to 100% at 10% intervals. The standard deviation of the CT coefficient was measured three times to calculate the mean value. In the phantom and animal experiments, the absorbed dose was measured 10 times under the same conditions as the ones for noise measurement before the mean value was calculated. In the animal experiment, pencil-type and CT-dedicated ionization chambers were inserted into the central portion of pig heads for measurement. In the phantom study, as the level of the ASIR changed from 0% to 100% under identical scanning conditions, the noise value and dose were proportionally reduced. In our animal experiment, the noise value was lowest when the ASIR level was 50%, unlike in the phantom study. The dose was reduced as in the phantom study.

  13. A mechanical model predicts morphological abnormalities in the developing human brain

    NASA Astrophysics Data System (ADS)

    Budday, Silvia; Raybaud, Charles; Kuhl, Ellen

    2014-07-01

    The developing human brain remains one of the few unsolved mysteries of science. Advancements in developmental biology, neuroscience, and medical imaging have brought us closer than ever to understand brain development in health and disease. However, the precise role of mechanics throughout this process remains underestimated and poorly understood. Here we show that mechanical stretch plays a crucial role in brain development. Using the nonlinear field theories of mechanics supplemented by the theory of finite growth, we model the human brain as a living system with a morphogenetically growing outer surface and a stretch-driven growing inner core. This approach seamlessly integrates the two popular but competing hypotheses for cortical folding: axonal tension and differential growth. We calibrate our model using magnetic resonance images from very preterm neonates. Our model predicts that deviations in cortical growth and thickness induce morphological abnormalities. Using the gyrification index, the ratio between the total and exposed surface area, we demonstrate that these abnormalities agree with the classical pathologies of lissencephaly and polymicrogyria. Understanding the mechanisms of cortical folding in the developing human brain has direct implications in the diagnostics and treatment of neurological disorders, including epilepsy, schizophrenia, and autism.

  14. A mechanical model predicts morphological abnormalities in the developing human brain

    PubMed Central

    Budday, Silvia; Raybaud, Charles; Kuhl, Ellen

    2014-01-01

    The developing human brain remains one of the few unsolved mysteries of science. Advancements in developmental biology, neuroscience, and medical imaging have brought us closer than ever to understand brain development in health and disease. However, the precise role of mechanics throughout this process remains underestimated and poorly understood. Here we show that mechanical stretch plays a crucial role in brain development. Using the nonlinear field theories of mechanics supplemented by the theory of finite growth, we model the human brain as a living system with a morphogenetically growing outer surface and a stretch-driven growing inner core. This approach seamlessly integrates the two popular but competing hypotheses for cortical folding: axonal tension and differential growth. We calibrate our model using magnetic resonance images from very preterm neonates. Our model predicts that deviations in cortical growth and thickness induce morphological abnormalities. Using the gyrification index, the ratio between the total and exposed surface area, we demonstrate that these abnormalities agree with the classical pathologies of lissencephaly and polymicrogyria. Understanding the mechanisms of cortical folding in the developing human brain has direct implications in the diagnostics and treatment of neurological disorders, including epilepsy, schizophrenia, and autism. PMID:25008163

  15. Brain perfusion SPECT in the mouse: normal pattern according to gender and age.

    PubMed

    Apostolova, Ivayla; Wunder, Andreas; Dirnagl, Ulrich; Michel, Roger; Stemmer, Nina; Lukas, Mathias; Derlin, Thorsten; Gregor-Mamoudou, Betina; Goldschmidt, Jürgen; Brenner, Winfried; Buchert, Ralph

    2012-12-01

    Regional cerebral blood flow (rCBF) is a useful surrogate marker of neuronal activity and a parameter of primary interest in the diagnosis of many diseases. The increasing use of mouse models spawns the demand for in vivo measurement of rCBF in the mouse. Small animal SPECT provides excellent spatial resolution at adequate sensitivity and is therefore a promising tool for imaging the mouse brain. This study evaluates the feasibility of mouse brain perfusion SPECT and assesses the regional pattern of normal Tc-99m-HMPAO uptake and the impact of age and gender. Whole-brain kinetics was compared between Tc-99m-HMPAO and Tc-99m-ECD using rapid dynamic planar scans in 10 mice. Assessment of the regional uptake pattern was restricted to the more suitable tracer, HMPAO. Two HMPAO SPECTs were performed in 18 juvenile mice aged 7.5 ± 1.5weeks, and in the same animals at young adulthood, 19.1 ± 4.0 weeks (nanoSPECT/CTplus, general purpose mouse apertures: 1.2kcps/MBq, 0.7mm FWHM). The 3-D MRI Digital Atlas Database of an adult C57BL/6J mouse brain was used for region-of-interest (ROI) analysis. SPECT images were stereotactically normalized using SPM8 and a custom made, left-right symmetric HMPAO template in atlas space. For testing lateral asymmetry, each SPECT was left-right flipped prior to stereotactical normalization. Flipped and unflipped SPECTs were compared by paired testing. Peak brain uptake was similar for ECD and HMPAO: 1.8 ± 0.2 and 2.1 ± 0.6 %ID (p=0.357). Washout after the peak was much faster for ECD than for HMPAO: 24 ± 7min vs. 4.6 ± 1.7h (p=0.001). The general linear model for repeated measures with gender as an intersubject factor revealed an increase in relative HMPAO uptake with age in the neocortex (p=0.018) and the hippocampus (p=0.012). A decrease was detected in the midbrain (p=0.025). Lateral asymmetry, with HMPAO uptake larger in the left hemisphere, was detected primarily in the neocortex, both at juvenile age (asymmetry index AI=2.7 ± 1

  16. Polysubstance and Alcohol Dependence: Unique Abnormalities of Magnetic Resonance-Derived Brain Metabolite Levels

    PubMed Central

    Abé, Christoph; Mon, Anderson; Durazzo, Timothy C.; Pennington, David L.; Schmidt, Thomas P.; Meyerhoff, Dieter J.

    2012-01-01

    BACKGROUND Although comorbid substance misuse is common in alcohol dependence, and polysubstance abusers (PSU) represent the largest group of individuals seeking treatment for drug abuse today, we know little about potential brain abnormalities in this population. Brain magnetic resonance spectroscopy studies of mono-substance use disorders (e.g., alcohol or cocaine) reveal abnormal levels of cortical metabolites (reflecting neuronal integrity, cell membrane turnover/synthesis, cellular bioenergetics, gliosis) and altered concentrations of glutamate and γ-aminobutyric acid (GABA). The concurrent misuse of several substances may have unique and different effects on brain biology and function compared to any mono-substance misuse. METHODS High field brain magnetic resonance spectroscopy at 4 Tesla and neurocognitive testing were performed at one month of abstinence in 40 alcohol dependent individuals (ALC), 28 alcohol dependent PSU and 16 drug-free controls. Absolute metabolite concentrations were calculated in anterior cingulate (ACC), parieto-occipital (POC) and dorsolateral prefrontal cortices (DLPFC). RESULTS Compared to ALC, PSU demonstrated significant metabolic abnormalities in the DLPFC and strong trends to lower GABA in the ACC. Metabolite levels in ALC and light drinking controls were statistically equivalent. Within PSU, lower DLPFC GABA levels related to greater cocaine consumption. Several cortical metabolite concentrations were associated with cognitive performance. CONCLUSIONS While metabolite concentrations in ALC at one month of abstinence were largely normal, PSU showed persistent and functionally significant metabolic abnormalities, primarily in the DLPFC. Our results point to specific metabolic deficits as biomarkers in polysubstance misuse and as targets for pharmacological and behavioral PSU-specific treatment. PMID:23122599

  17. Effects of subthalamic deep brain stimulation on blink abnormalities of 6-OHDA lesioned rats

    PubMed Central

    Kaminer, Jaime; Thakur, Pratibha

    2015-01-01

    Parkinson's disease (PD) patients and the 6-hydroxydopamine (6-OHDA) lesioned rat model share blink abnormalities. In view of the evolutionarily conserved organization of blinking, characterization of blink reflex circuits in rodents may elucidate the neural mechanisms of PD reflex abnormalities. We examine the extent of this shared pattern of blink abnormalities by measuring blink reflex excitability, blink reflex plasticity, and spontaneous blinking in 6-OHDA lesioned rats. We also investigate whether 130-Hz subthalamic nucleus deep brain stimulation (STN DBS) affects blink abnormalities, as it does in PD patients. Like PD patients, 6-OHDA-lesioned rats exhibit reflex blink hyperexcitability, impaired blink plasticity, and a reduced spontaneous blink rate. At 130 Hz, but not 16 Hz, STN DBS eliminates reflex blink hyperexcitability and restores both short- and long-term blink plasticity. Replicating its lack of effect in PD patients, 130-Hz STN DBS does not reinstate a normal temporal pattern or rate to spontaneous blinking in 6-OHDA lesioned rats. These data show that the 6-OHDA lesioned rat is an ideal model system for investigating the neural bases of reflex abnormalities in PD and highlight the complexity of PD's effects on motor control, by showing that dopamine depletion does not affect all blink systems via the same neural mechanisms. PMID:25673748

  18. Positron Emission Tomography Reveals Abnormal Topological Organization in Functional Brain Network in Diabetic Patients

    PubMed Central

    Qiu, Xiangzhe; Zhang, Yanjun; Feng, Hongbo; Jiang, Donglang

    2016-01-01

    Recent studies have demonstrated alterations in the topological organization of structural brain networks in diabetes mellitus (DM). However, the DM-related changes in the topological properties in functional brain networks are unexplored so far. We therefore used fluoro-D-glucose positron emission tomography (FDG-PET) data to construct functional brain networks of 73 DM patients and 91 sex- and age-matched normal controls (NCs), followed by a graph theoretical analysis. We found that both DM patients and NCs had a small-world topology in functional brain network. In comparison to the NC group, the DM group was found to have significantly lower small-world index, lower normalized clustering coefficients and higher normalized characteristic path length. Moreover, for diabetic patients, the nodal centrality was significantly reduced in the right rectus, the right cuneus, the left middle occipital gyrus, and the left postcentral gyrus, and it was significantly increased in the orbitofrontal region of the left middle frontal gyrus, the left olfactory region, and the right paracentral lobule. Our results demonstrated that the diabetic brain was associated with disrupted topological organization in the functional PET network, thus providing functional evidence for the abnormalities of brain networks in DM. PMID:27303259

  19. Positron Emission Tomography Reveals Abnormal Topological Organization in Functional Brain Network in Diabetic Patients.

    PubMed

    Qiu, Xiangzhe; Zhang, Yanjun; Feng, Hongbo; Jiang, Donglang

    2016-01-01

    Recent studies have demonstrated alterations in the topological organization of structural brain networks in diabetes mellitus (DM). However, the DM-related changes in the topological properties in functional brain networks are unexplored so far. We therefore used fluoro-D-glucose positron emission tomography (FDG-PET) data to construct functional brain networks of 73 DM patients and 91 sex- and age-matched normal controls (NCs), followed by a graph theoretical analysis. We found that both DM patients and NCs had a small-world topology in functional brain network. In comparison to the NC group, the DM group was found to have significantly lower small-world index, lower normalized clustering coefficients and higher normalized characteristic path length. Moreover, for diabetic patients, the nodal centrality was significantly reduced in the right rectus, the right cuneus, the left middle occipital gyrus, and the left postcentral gyrus, and it was significantly increased in the orbitofrontal region of the left middle frontal gyrus, the left olfactory region, and the right paracentral lobule. Our results demonstrated that the diabetic brain was associated with disrupted topological organization in the functional PET network, thus providing functional evidence for the abnormalities of brain networks in DM. PMID:27303259

  20. Evaluating the feasibility of C-arm CT for brain perfusion imaging: an in vitro study

    NASA Astrophysics Data System (ADS)

    Ganguly, A.; Fieselmann, A.; Boese, J.; Rohkohl, C.; Hornegger, J.; Fahrig, R.

    2010-02-01

    C-arm cone-beam CT (CBCT) is increasingly being used to supplement 2D real-time data with 3D information. Temporal resolution is currently limited by the mechanical rotation speed of the C-arm which presents challenges for applications such as imaging of contrast flow in brain perfusion CT (PCT). We present a novel scheme where multiple scans are obtained at different start times with respect to the contrast injection. The data is interleaved temporally and interpolated during 3D reconstruction. For evaluation we developed a phantom to generate the range of temporal frequencies relevant for PCT. The highest requirements are for imaging the arterial input function (AIF) modeled as a gamma-variate function. Fourier transform analysis of the AIF showed that 90% of the spectral energy is contained at frequencies lower than 0.08Hz. We built an acrylic cylinder phantom of diameter 1.9 cm, with 25 sections of 1cm length each. Iodine concentration in each compartment was varied to produce a half-cycle sinusoid variation in HU in version 1, and 2.5 cycles in version 2 of the phantom. The phantom was moved linearly at speeds from 0.5cm/s to 4cm/s (temporal frequencies of 0.02Hz to 0.09Hz) and imaged using a C-arm system. Phantom CT numbers in a slice reconstructed at isocenter were measured and sinusoidal fits to the data were obtained. The fitted sinusoids had frequencies that were within 3+/-2% of the actual temporal frequencies of the sinusoid. This suggests that the imaging and reconstruction scheme is adequate for PCT imaging.

  1. Comparison of Partial Volume Effects in Arterial and Venous Contrast Curves in CT Brain Perfusion Imaging

    PubMed Central

    Riordan, Alan J.; Bennink, Edwin; Dankbaar, Jan Willem; Viergever, Max A.; Velthuis, Birgitta K.; Smit, Ewoud J.; de Jong, Hugo W. A. M.

    2014-01-01

    Purpose In brain CT perfusion (CTP), the arterial contrast bolus is scaled to have the same area under the curve (AUC) as the venous outflow to correct for partial volume effects (PVE). This scaling is based on the assumption that large veins are unaffected by PVE. Measurement of the internal carotid artery (ICA), usually unaffected by PVE due to its large diameter, may avoid the need for partial volume correction. The aims of this work are to examine i) the assumptions behind PVE correction and ii) the potential of selecting the ICA obviating correction for PVE. Methods The AUC of the ICA and sagittal sinus were measured in CTP datasets from 52 patients. The AUCs were determined by i) using commercial CTP software based on a Gaussian curve-fitting to the time attenuation curve, and ii) by simple integration of the time attenuation curve over a time interval. In addition, frames acquired up to 3 minutes after first bolus passage were used to examine the ratio of arterial and venous enhancement. The impact of selecting the ICA without PVE correction was illustrated by reporting cerebral blood volume (CBV) measurements. Results In 49 of 52 patients, the AUC of the ICA was significantly larger than that of the sagittal sinus (p = 0.017). Measured after the first pass bolus, contrast enhancement remained 50% higher in the ICA just after the first pass bolus, and 30% higher 3 minutes later. CBV measurements were significantly lowered when the ICA was used without PVE correction. Conclusions Contradicting the assumptions underlying PVE correction, contrast in the ICA was significantly higher than in the sagittal sinus, even 3 minutes after the first pass of the contrast bolus. PVE correction might lead to overestimation of CBV if the CBV is calculated using the AUC of the time attenuation curves. PMID:24858308

  2. Brain abnormalities, defective meiotic chromosome synapsis and female subfertility in HSF2 null mice

    PubMed Central

    Kallio, Marko; Chang, Yunhua; Manuel, Martine; Alastalo, Tero-Pekka; Rallu, Murielle; Gitton, Yorick; Pirkkala, Lila; Loones, Marie-Thérèse; Paslaru, Liliana; Larney, Severine; Hiard, Sophie; Morange, Michel; Sistonen, Lea; Mezger, Valérie

    2002-01-01

    Heat shock factor 2, one of the four vertebrate HSFs, transcriptional regulators of heat shock gene expression, is active during embryogenesis and spermatogenesis, with unknown functions and targets. By disrupting the Hsf2 gene, we show that, although the lack of HSF2 is not embryonic lethal, Hsf2–/– mice suffer from brain abnormalities, and meiotic and gameto genesis defects in both genders. The disturbances in brain are characterized by the enlargement of lateral and third ventricles and the reduction of hippocampus and striatum, in correlation with HSF2 expression in proliferative cells of the neuroepithelium and in some ependymal cells in adults. Many developing spermatocytes are eliminated via apoptosis in a stage-specific manner in Hsf2–/– males, and pachytene spermatocytes also display structural defects in the synaptonemal complexes between homologous chromosomes. Hsf2–/– females suffer from multiple fertility defects: the production of abnormal eggs, the reduction in ovarian follicle number and the presence of hemorrhagic cystic follicles are consistent with meiotic defects. Hsf2–/– females also display hormone response defects, that can be rescued by superovulation treatment, and exhibit abnormal rates of luteinizing hormone receptor mRNAs. PMID:12032072

  3. Abnormal functional brain asymmetry in depression: evidence of biologic commonality between major depression and dysthymia.

    PubMed

    Bruder, Gerard E; Stewart, Jonathan W; Hellerstein, David; Alvarenga, Jorge E; Alschuler, Daniel; McGrath, Patrick J

    2012-04-30

    Prior studies have found abnormalities of functional brain asymmetry in patients having a major depressive disorder (MDD). This study aimed to replicate findings of reduced right hemisphere advantage for perceiving dichotic complex tones in depressed patients, and to determine whether patients having "pure" dysthymia show the same abnormality of perceptual asymmetry as MDD. It also examined gender differences in lateralization, and the extent to which abnormalities of perceptual asymmetry in depressed patients are dependent on gender. Unmedicated patients having either a MDD (n=96) or "pure" dysthymic disorder (n=42) and healthy controls (n=114) were tested on dichotic fused-words and complex-tone tests. Patient and control groups differed in right hemisphere advantage for complex tones, but not left hemisphere advantage for words. Reduced right hemisphere advantage for tones was equally present in MDD and dysthymia, but was more evident among depressed men than depressed women. Also, healthy men had greater hemispheric asymmetry than healthy women for both words and tones, whereas this gender difference was not seen for depressed patients. Dysthymia and MDD share a common abnormality of hemispheric asymmetry for dichotic listening.

  4. Application of time sampling in brain CT perfusion imaging for dose reduction

    NASA Astrophysics Data System (ADS)

    Lee, S. H.; Kim, J. H.; Kim, K. G.; Park, S. J.; Im, Jung Gi

    2007-03-01

    The purpose of this study is to determine a stable sampling rate not to be affected by sampling shift for reducing radiation exposure with time sampling and interpolation in cerebral perfusion CT examination. Original images were obtained every 1 second for 40 time series from 3 patients, respectively. Time sampling was performed with sampling intervals (SI) from 2 to 10 seconds. Sampling shift was applied from +1 to SI-1 for each sampling rate. For each patient, 30 tissue concentration time-course data were collected, and arterial input curves were fitted by gamma-variate function. The sinc function was introduced for interpolation. Deconvolution analysis based on SVD was performed for quantifying perfusion parameters. The perfusion values through time-varying sampling and interpolation were statistically compared with the original perfusion values. The mean CBF values with increase of sampling interval and shift magnitude from the collected data had a wider fluctuation pattern centering around the original mean CBF. The mean CBV values had a similar tendency to the mean CBF values, but a relatively narrower deviation. The mean MTT values were fluctuated reversely to the trend of the mean CBF values. The stable sampling interval for quantifying perfusion parameters with lower radiation exposure was statistically acceptable up to 4 seconds. These results indicate that sampling shift limits sampling rate for acquiring acceptable perfusion values. This study will help in selecting more reasonable sampling rate for low-radiation-dose CT examination.

  5. Age at First Episode Modulates Diagnosis-Related Structural Brain Abnormalities in Psychosis.

    PubMed

    Pina-Camacho, Laura; Del Rey-Mejías, Ángel; Janssen, Joost; Bioque, Miquel; González-Pinto, Ana; Arango, Celso; Lobo, Antonio; Sarró, Salvador; Desco, Manuel; Sanjuan, Julio; Lacalle-Aurioles, Maria; Cuesta, Manuel J; Saiz-Ruiz, Jerónimo; Bernardo, Miguel; Parellada, Mara

    2016-03-01

    Brain volume and thickness abnormalities have been reported in first-episode psychosis (FEP). However, it is unclear if and how they are modulated by brain developmental stage (and, therefore, by age at FEP as a proxy). This is a multicenter cross-sectional case-control brain magnetic resonance imaging (MRI) study. Patients with FEP (n = 196), 65.3% males, with a wide age at FEP span (12-35 y), and healthy controls (HC) (n = 157), matched for age, sex, and handedness, were scanned at 6 sites. Gray matter volume and thickness measurements were generated for several brain regions using FreeSurfer software. The nonlinear relationship between age at scan (a proxy for age at FEP in patients) and volume and thickness measurements was explored in patients with schizophrenia spectrum disorders (SSD), affective psychoses (AFP), and HC. Earlier SSD cases (ie, FEP before 15-20 y) showed significant volume and thickness deficits in frontal lobe, volume deficits in temporal lobe, and volume enlargements in ventricular system and basal ganglia. First-episode AFP patients had smaller cingulate cortex volume and thicker temporal cortex only at early age at FEP (before 18-20 y). The AFP group also had age-constant (12-35-y age span) volume enlargements in the frontal and parietal lobe. Our study suggests that age at first episode modulates the structural brain abnormalities found in FEP patients in a nonlinear and diagnosis-dependent manner. Future MRI studies should take these results into account when interpreting samples with different ages at onset and diagnosis. PMID:26371339

  6. Age at First Episode Modulates Diagnosis-Related Structural Brain Abnormalities in Psychosis.

    PubMed

    Pina-Camacho, Laura; Del Rey-Mejías, Ángel; Janssen, Joost; Bioque, Miquel; González-Pinto, Ana; Arango, Celso; Lobo, Antonio; Sarró, Salvador; Desco, Manuel; Sanjuan, Julio; Lacalle-Aurioles, Maria; Cuesta, Manuel J; Saiz-Ruiz, Jerónimo; Bernardo, Miguel; Parellada, Mara

    2016-03-01

    Brain volume and thickness abnormalities have been reported in first-episode psychosis (FEP). However, it is unclear if and how they are modulated by brain developmental stage (and, therefore, by age at FEP as a proxy). This is a multicenter cross-sectional case-control brain magnetic resonance imaging (MRI) study. Patients with FEP (n = 196), 65.3% males, with a wide age at FEP span (12-35 y), and healthy controls (HC) (n = 157), matched for age, sex, and handedness, were scanned at 6 sites. Gray matter volume and thickness measurements were generated for several brain regions using FreeSurfer software. The nonlinear relationship between age at scan (a proxy for age at FEP in patients) and volume and thickness measurements was explored in patients with schizophrenia spectrum disorders (SSD), affective psychoses (AFP), and HC. Earlier SSD cases (ie, FEP before 15-20 y) showed significant volume and thickness deficits in frontal lobe, volume deficits in temporal lobe, and volume enlargements in ventricular system and basal ganglia. First-episode AFP patients had smaller cingulate cortex volume and thicker temporal cortex only at early age at FEP (before 18-20 y). The AFP group also had age-constant (12-35-y age span) volume enlargements in the frontal and parietal lobe. Our study suggests that age at first episode modulates the structural brain abnormalities found in FEP patients in a nonlinear and diagnosis-dependent manner. Future MRI studies should take these results into account when interpreting samples with different ages at onset and diagnosis.

  7. Abnormal brain activation during directed forgetting of negative memory in depressed patients.

    PubMed

    Yang, Wenjing; Chen, Qunlin; Liu, Peiduo; Cheng, Hongsheng; Cui, Qian; Wei, Dongtao; Zhang, Qinglin; Qiu, Jiang

    2016-01-15

    The frequent occurrence of uncontrollable negative thoughts and memories is a troubling aspect of depression. Thus, knowledge on the mechanism underlying intentional forgetting of these thoughts and memories is crucial to develop an effective emotion regulation strategy for depressed individuals. Behavioral studies have demonstrated that depressed participants cannot intentionally forget negative memories. However, the neural mechanism underlying this process remains unclear. In this study, participants completed the directed forgetting task in which they were instructed to remember or forget neutral or negative words. Standard univariate analysis based on the General Linear Model showed that the depressed participants have higher activation in the inferior frontal gyrus (IFG), superior frontal gyrus (SFG), superior parietal gyrus (SPG), and inferior temporal gyrus (ITG) than the healthy individuals. The results indicated that depressed participants recruited more frontal and parietal inhibitory control resources to inhibit the TBF items, but the attempt still failed because of negative bias. We also used the Support Vector Machine to perform multivariate pattern classification based on the brain activation during directed forgetting. The pattern of brain activity in directed forgetting of negative words allowed correct group classification with an overall accuracy of 75% (P=0.012). The brain regions which are critical for this discrimination showed abnormal activation when depressed participants were attempting to forget negative words. These results indicated that the abnormal neural circuitry when depressed individuals tried to forget the negative words might provide neurobiological markers for depression.

  8. The MsrA knockout mouse exhibits abnormal behavior and brain dopamine levels

    PubMed Central

    Oien, Derek B.; Osterhaus, Greg L.; Latif, Shaheen A.; Pinkston, Jonathan W.; Fulks, Jenny; Johnson, Michael; Fowler, Stephen C.; Moskovitz, Jackob

    2008-01-01

    Oxidative stress can cause methionine oxidation that has been implicated in various proteins malfunctions, if not adequately reduced by the methionine sulfoxide reductase system. Recent evidence has found oxidized methionine residues in neurodegenerative conditions. Previously, we have described elevated levels of brain pathologies and an abnormal walking pattern in the methionine sulfoxide reductase A knockout (MsrA−/−) mouse. Here we show that MsrA−/− mice have compromised complex task learning capabilities relative to wild-type mice. Likewise, MsrA−/− mice exhibit lower locomotor activity and altered gait that exacerbated with age. Furthermore, MsrA−/− mice were less responsive to amphetamine treatment. Consequently, brain dopamine levels were determined. Surprisingly, relative to wild-type mice, MsrA−/− brains contained significantly higher levels of dopamine up to 12 months of age, while lower level of dopamine was observed at 16 months of age. Moreover, striatal regions of MsrA−/− mice showed an increase of dopamine release parallel to observed dopamine levels. Similarly, the expression pattern of tyrosine hydroxylase activating protein correlated with the age-dependent dopamine levels. Thus, it is suggested that dopamine regulation and signaling pathway are impaired in MsrA−/− mice, which may contribute to their abnormal bio-behavior. These observations may be relevant to age-related neurological diseases associated with oxidative stress. PMID:18466776

  9. MsrA knockout mouse exhibits abnormal behavior and brain dopamine levels.

    PubMed

    Oien, Derek B; Osterhaus, Greg L; Latif, Shaheen A; Pinkston, Jonathan W; Fulks, Jenny; Johnson, Michael; Fowler, Stephen C; Moskovitz, Jackob

    2008-07-15

    Oxidative stress can cause methionine oxidation that has been implicated in various proteins malfunctions, if not adequately reduced by the methionine sulfoxide reductase system. Recent evidence has found oxidized methionine residues in neurodegenerative conditions. Previously, we have described elevated levels of brain pathologies and an abnormal walking pattern in the methionine sulfoxide reductase A knockout (MsrA(-/-)) mouse. Here we show that MsrA(-/-) mice have compromised complex task learning capabilities relative to wild-type mice. Likewise, MsrA(-/-) mice exhibit lower locomotor activity and altered gait that exacerbated with age. Furthermore, MsrA(-/-) mice were less responsive to amphetamine treatment. Consequently, brain dopamine levels were determined. Surprisingly, relative to wild-type mice, MsrA(-/-) brains contained significantly higher levels of dopamine up to 12 months of age, while lower levels of dopamine were observed at 16 months of age. Moreover, striatal regions of MsrA(-/-) mice showed an increase of dopamine release parallel to observed dopamine levels. Similarly, the expression pattern of tyrosine hydroxylase activating protein correlated with the age-dependent dopamine levels. Thus, it is suggested that dopamine regulation and signaling pathways are impaired in MsrA(-/-) mice, which may contribute to their abnormal behavior. These observations may be relevant to age-related neurological diseases associated with oxidative stress.

  10. Sensations of skin infestation linked to abnormal frontolimbic brain reactivity and differences in self-representation.

    PubMed

    Eccles, J A; Garfinkel, S N; Harrison, N A; Ward, J; Taylor, R E; Bewley, A P; Critchley, H D

    2015-10-01

    Some patients experience skin sensations of infestation and contamination that are elusive to proximate dermatological explanation. We undertook a functional magnetic resonance imaging study of the brain to demonstrate, for the first time, that central processing of infestation-relevant stimuli is altered in patients with such abnormal skin sensations. We show differences in neural activity within amygdala, insula, middle temporal lobe and frontal cortices. Patients also demonstrated altered measures of self-representation, with poorer sensitivity to internal bodily (interoceptive) signals and greater susceptibility to take on an illusion of body ownership: the rubber hand illusion. Together, these findings highlight a potential model for the maintenance of abnormal skin sensations, encompassing heightened threat processing within amygdala, increased salience of skin representations within insula and compromised prefrontal capacity for self-regulation and appraisal.

  11. Sensations of skin infestation linked to abnormal frontolimbic brain reactivity and differences in self-representation.

    PubMed

    Eccles, J A; Garfinkel, S N; Harrison, N A; Ward, J; Taylor, R E; Bewley, A P; Critchley, H D

    2015-10-01

    Some patients experience skin sensations of infestation and contamination that are elusive to proximate dermatological explanation. We undertook a functional magnetic resonance imaging study of the brain to demonstrate, for the first time, that central processing of infestation-relevant stimuli is altered in patients with such abnormal skin sensations. We show differences in neural activity within amygdala, insula, middle temporal lobe and frontal cortices. Patients also demonstrated altered measures of self-representation, with poorer sensitivity to internal bodily (interoceptive) signals and greater susceptibility to take on an illusion of body ownership: the rubber hand illusion. Together, these findings highlight a potential model for the maintenance of abnormal skin sensations, encompassing heightened threat processing within amygdala, increased salience of skin representations within insula and compromised prefrontal capacity for self-regulation and appraisal. PMID:26260311

  12. Abnormal Brain Connectivity Patterns in Adults with ADHD: A Coherence Study

    PubMed Central

    Sato, João Ricardo; Hoexter, Marcelo Queiroz; Castellanos, Xavier Francisco; Rohde, Luis A.

    2012-01-01

    Studies based on functional magnetic resonance imaging (fMRI) during the resting state have shown decreased functional connectivity between the dorsal anterior cingulate cortex (dACC) and regions of the Default Mode Network (DMN) in adult patients with Attention-Deficit/Hyperactivity Disorder (ADHD) relative to subjects with typical development (TD). Most studies used Pearson correlation coefficients among the BOLD signals from different brain regions to quantify functional connectivity. Since the Pearson correlation analysis only provides a limited description of functional connectivity, we investigated functional connectivity between the dACC and the posterior cingulate cortex (PCC) in three groups (adult patients with ADHD, n = 21; TD age-matched subjects, n = 21; young TD subjects, n = 21) using a more comprehensive analytical approach – unsupervised machine learning using a one-class support vector machine (OC-SVM) that quantifies an abnormality index for each individual. The median abnormality index for patients with ADHD was greater than for TD age-matched subjects (p = 0.014); the ADHD and young TD indices did not differ significantly (p = 0.480); the median abnormality index of young TD was greater than that of TD age-matched subjects (p = 0.016). Low frequencies below 0.05 Hz and around 0.20 Hz were the most relevant for discriminating between ADHD patients and TD age-matched controls and between the older and younger TD subjects. In addition, we validated our approach using the fMRI data of children publicly released by the ADHD-200 Competition, obtaining similar results. Our findings suggest that the abnormal coherence patterns observed in patients with ADHD in this study resemble the patterns observed in young typically developing subjects, which reinforces the hypothesis that ADHD is associated with brain maturation deficits. PMID:23049834

  13. Abnormal expression of 8-nitroguanine in the brain of mice exposed to arsenic subchronically.

    PubMed

    Piao, Fengyuan; Li, Sheng; Li, Qiujuan; Ye, Jianxin; Liu, Shuang

    2011-01-01

    To provide molecular toxicological evidences for exploring the mechanism of arsenic-induced neurotoxicity the accumulation of arsenic (As), the formation of 8-nitroguanine (8-NO(2)-G) were examined in brain tissue of mice exposed to arsenic. And the gene expressions of inducible NOS (iNOS), superoxide dismutase 1 (SOD1) and peroxiredoxin 2 (Prdx2) were also analyzed by GeneChip. In the result, the concentration of As in the brain tissue of mice was 4.00, 13.70, 21.48 and 29.88 ng/g in the controls and experimental groups exposed to 1, 2 and 4 mg/l As(2)O(3), respectively and increased in dose-response manner. Nervous cells in the brain of mice exposed to As showed disappearances of axons, vacuolar degeneration in cytoplasm and karyolysis, whereas no such pathological changes were observed in the control group. Weak immunoreactivity against 8-NO(2)-G was observed in the brain tissue of mice given 1 or 2 ppm arsenic trioxide. More intensive immunoreactivity was found in cells at 4 ppm and it was mainly distributed in cytoplasm. The expressions of SOD1 and Prdx2 were down-regulated in the brain of mice exposed to As, but iNOS expression was not disturbed by As exposure. No the 8-NO(2)-G immunoreactivity or abnormal expressions of these genes in brain tissue were observed in controls. These results indicate that As induces high expression of 8-NO(2)-G in brain tissues of mice and that RNA in the cells may be modified by overproduced reactive nitrogen species.

  14. Perfusion Imaging of Focal Cortical Dysplasia Using Arterial Spin Labeling: Correlation With Histopathological Vascular Density

    PubMed Central

    Wintermark, Pia; Lechpammer, Mirna; Warfield, Simon K.; Kosaras, Bela; Takeoka, Masanori; Poduri, Annapurna; Madsen, Joseph R.; Bergin, Ann M.; Whalen, Stephen; Jensen, Frances E.

    2016-01-01

    Focal cortical dysplasia is the most common malformation of cortical development, causing intractable epilepsy. This study investigated the relationship between brain perfusion and microvessel density in 7 children with focal cortical dysplasia. The authors analyzed brain perfusion measurements obtained by magnetic resonance imaging of 2 of the children and the microvessel density of brain tissue specimens obtained by epilepsy surgery on all of the children. Brain perfusion was approximately 2 times higher in the area of focal cortical dysplasia compared to the contralateral side. The microvessel density was nearly double in the area of focal cortical dysplasia compared to the surrounding cortex that did not have morphological abnormalities. These findings suggest that hyperperfusion can be related to increased microvessel density in focal cortical dysplasia rather than only to seizures. Further investigations are needed to determine the relationship between brain perfusion, microvessel density, and seizure activity. PMID:23696629

  15. Congenital Brain Abnormalities and Zika Virus: What the Radiologist Can Expect to See Prenatally and Postnatally.

    PubMed

    Soares de Oliveira-Szejnfeld, Patricia; Levine, Deborah; Melo, Adriana Suely de Oliveira; Amorim, Melania Maria Ramos; Batista, Alba Gean M; Chimelli, Leila; Tanuri, Amilcar; Aguiar, Renato Santana; Malinger, Gustavo; Ximenes, Renato; Robertson, Richard; Szejnfeld, Jacob; Tovar-Moll, Fernanda

    2016-10-01

    Purpose To document the imaging findings associated with congenital Zika virus infection as found in the Instituto de Pesquisa in Campina Grande State Paraiba (IPESQ) in northeastern Brazil, where the congenital infection has been particularly severe. Materials and Methods From June 2015 to May 2016, 438 patients were referred to the IPESQ for rash occurring during pregnancy or for suspected fetal central nervous system abnormality. Patients who underwent imaging at IPESQ were included, as well as those with documented Zika virus infection in fluid or tissue (n = 17, confirmed infection cohort) or those with brain findings suspicious for Zika virus infection, with intracranial calcifications (n = 28, presumed infection cohort). Imaging examinations included 12 fetal magnetic resonance (MR) examinations, 42 postnatal brain computed tomographic examinations, and 11 postnatal brain MR examinations. Images were reviewed by four radiologists, with final opinion achieved by means of consensus. Results Brain abnormalities seen in confirmed (n = 17) and presumed (n = 28) congenital Zika virus infections were similar, with ventriculomegaly in 16 of 17 (94%) and 27 of 28 (96%) infections, respectively; abnormalities of the corpus callosum in 16 of 17 (94%) and 22 of 28 (78%) infections, respectively; and cortical migrational abnormalities in 16 of 17 (94%) and 28 of 28 (100%) infections, respectively. Although most fetuses underwent at least one examination that showed head circumference below the 5th percentile, head circumference could be normal in the presence of severe ventriculomegaly (seen in three fetuses). Intracranial calcifications were most commonly seen at the gray matter-white matter junction, in 15 of 17 (88%) and 28 of 28 (100%) confirmed and presumed infections, respectively. The basal ganglia and/or thalamus were also commonly involved with calcifications in 11 of 17 (65%) and 18 of 28 (64%) infections, respectively. The skull frequently had a collapsed

  16. Zika Virus Infection with Prolonged Maternal Viremia and Fetal Brain Abnormalities.

    PubMed

    Driggers, Rita W; Ho, Cheng-Ying; Korhonen, Essi M; Kuivanen, Suvi; Jääskeläinen, Anne J; Smura, Teemu; Rosenberg, Avi; Hill, D Ashley; DeBiasi, Roberta L; Vezina, Gilbert; Timofeev, Julia; Rodriguez, Fausto J; Levanov, Lev; Razak, Jennifer; Iyengar, Preetha; Hennenfent, Andrew; Kennedy, Richard; Lanciotti, Robert; du Plessis, Adre; Vapalahti, Olli

    2016-06-01

    The current outbreak of Zika virus (ZIKV) infection has been associated with an apparent increased risk of congenital microcephaly. We describe a case of a pregnant woman and her fetus infected with ZIKV during the 11th gestational week. The fetal head circumference decreased from the 47th percentile to the 24th percentile between 16 and 20 weeks of gestation. ZIKV RNA was identified in maternal serum at 16 and 21 weeks of gestation. At 19 and 20 weeks of gestation, substantial brain abnormalities were detected on ultrasonography and magnetic resonance imaging (MRI) without the presence of microcephaly or intracranial calcifications. On postmortem analysis of the fetal brain, diffuse cerebral cortical thinning, high ZIKV RNA loads, and viral particles were detected, and ZIKV was subsequently isolated.

  17. Zika Virus Infection with Prolonged Maternal Viremia and Fetal Brain Abnormalities.

    PubMed

    Driggers, Rita W; Ho, Cheng-Ying; Korhonen, Essi M; Kuivanen, Suvi; Jääskeläinen, Anne J; Smura, Teemu; Rosenberg, Avi; Hill, D Ashley; DeBiasi, Roberta L; Vezina, Gilbert; Timofeev, Julia; Rodriguez, Fausto J; Levanov, Lev; Razak, Jennifer; Iyengar, Preetha; Hennenfent, Andrew; Kennedy, Richard; Lanciotti, Robert; du Plessis, Adre; Vapalahti, Olli

    2016-06-01

    The current outbreak of Zika virus (ZIKV) infection has been associated with an apparent increased risk of congenital microcephaly. We describe a case of a pregnant woman and her fetus infected with ZIKV during the 11th gestational week. The fetal head circumference decreased from the 47th percentile to the 24th percentile between 16 and 20 weeks of gestation. ZIKV RNA was identified in maternal serum at 16 and 21 weeks of gestation. At 19 and 20 weeks of gestation, substantial brain abnormalities were detected on ultrasonography and magnetic resonance imaging (MRI) without the presence of microcephaly or intracranial calcifications. On postmortem analysis of the fetal brain, diffuse cerebral cortical thinning, high ZIKV RNA loads, and viral particles were detected, and ZIKV was subsequently isolated. PMID:27028667

  18. Structural brain abnormalities in the frontostriatal system and cerebellum in pedophilia.

    PubMed

    Schiffer, Boris; Peschel, Thomas; Paul, Thomas; Gizewski, Elke; Forsting, Michael; Leygraf, Norbert; Schedlowski, Manfred; Krueger, Tillmann H C

    2007-11-01

    Even though previous neuropsychological studies and clinical case reports have suggested an association between pedophilia and frontocortical dysfunction, our knowledge about the neurobiological mechanisms underlying pedophilia is still fragmentary. Specifically, the brain morphology of such disorders has not yet been investigated using MR imaging techniques. Whole brain structural T1-weighted MR images from 18 pedophile patients (9 attracted to males, 9 attracted to females) and 24 healthy age-matched control subjects (12 hetero- and 12 homosexual) from a comparable socioeconomic stratum were processed by using optimized automated voxel-based morphometry within multiple linear regression analyses. Compared to the homosexual and heterosexual control subjects, pedophiles showed decreased gray matter volume in the ventral striatum (also extending into the nucl. accumbens), the orbitofrontal cortex and the cerebellum. These observations further indicate an association between frontostriatal morphometric abnormalities and pedophilia. In this respect these findings may support the hypothesis that there is a shared etiopathological mechanism in all obsessive-compulsive spectrum disorders.

  19. Brain metabolite abnormalities in the white matter of elderly schizophrenic subjects: implication for glial dysfunction

    PubMed Central

    Chang, Linda; Friedman, Joseph; Ernst, Thomas; Zhong, Kai; Tsopelas, Nicholas D.; Davis, Kenneth

    2008-01-01

    Background Abnormalities in the white matter of the brain may occur in individuals with schizophrenia as well as with normal aging. Therefore, elderly schizophrenic patients may suffer further cognitive decline as they age. This study determined whether elderly schizophrenia participants, especially those with declined cognitive function (CDR>1), show white matter metabolite abnormalities on proton magnetic resonance spectroscopy (1H MRS), and whether there are group differences in age-dependent changes in these brain metabolites. Method 23 elderly schizophrenic and 22 comparison participants fulfilling study criteria were enrolled. Localized, short echo-time 1H MRS at 4 Tesla was used to assess neurometabolite concentrations in several white matter regions. Results Compared to healthy subjects, schizophrenic participants had lower N-acetyl compounds (NA, −12.6%, p=0.0008), lower myoinositol (MI, −16.4%, p=0.026) and higher glutamate+glutamine (GLX, +28.7%, p=0.0016) concentrations across brain regions. Schizophrenic participants with CDR≥1 showed the lowest NA in the frontal and temporal regions compared to controls. Interactions between age and schizophrenia status on total creatine (CR) and choline-containing compounds (CHO) were observed; only schizophrenic participants showed age-related decreases of these two metabolites in the right frontal region. Conclusion Decreased NA in these white matter brain regions likely reflects reduced neuronal content associated with decreased synapses and neuronal cell volumes. The elevated GLX, if reflecting elevated glutamate, could result from excess neuronal glutamate release or glial dysfunction in glutamate re-uptake. The decreased MI in participants with schizophrenia suggests decreased glial content or dysfunctional glia, which might result from glutamate-mediated toxicity. PMID:17693392

  20. Abnormal early brain responses during visual search are evident in schizophrenia but not bipolar affective disorder.

    PubMed

    VanMeerten, Nicolaas J; Dubke, Rachel E; Stanwyck, John J; Kang, Seung Suk; Sponheim, Scott R

    2016-01-01

    People with schizophrenia show deficits in processing visual stimuli but neural abnormalities underlying the deficits are unclear and it is unknown whether such functional brain abnormalities are present in other severe mental disorders or in individuals who carry genetic liability for schizophrenia. To better characterize brain responses underlying visual search deficits and test their specificity to schizophrenia we gathered behavioral and electrophysiological responses during visual search (i.e., Span of Apprehension [SOA] task) from 38 people with schizophrenia, 31 people with bipolar disorder, 58 biological relatives of people with schizophrenia, 37 biological relatives of people with bipolar disorder, and 65 non-psychiatric control participants. Through subtracting neural responses associated with purely sensory aspects of the stimuli we found that people with schizophrenia exhibited reduced early posterior task-related neural responses (i.e., Span Endogenous Negativity [SEN]) while other groups showed normative responses. People with schizophrenia exhibited longer reaction times than controls during visual search but nearly identical accuracy. Those individuals with schizophrenia who had larger SENs performed more efficiently (i.e., shorter reaction times) on the SOA task suggesting that modulation of early visual cortical responses facilitated their visual search. People with schizophrenia also exhibited a diminished P300 response compared to other groups. Unaffected first-degree relatives of people with bipolar disorder and schizophrenia showed an amplified N1 response over posterior brain regions in comparison to other groups. Diminished early posterior brain responses are associated with impaired visual search in schizophrenia and appear to be specifically associated with the neuropathology of schizophrenia.

  1. Abnormal structural connectivity in the brain networks of children with hydrocephalus.

    PubMed

    Yuan, Weihong; Holland, Scott K; Shimony, Joshua S; Altaye, Mekibib; Mangano, Francesco T; Limbrick, David D; Jones, Blaise V; Nash, Tiffany; Rajagopal, Akila; Simpson, Sarah; Ragan, Dustin; McKinstry, Robert C

    2015-01-01

    Increased intracranial pressure and ventriculomegaly in children with hydrocephalus are known to have adverse effects on white matter structure. This study seeks to investigate the impact of hydrocephalus on topological features of brain networks in children. The goal was to investigate structural network connectivity, at both global and regional levels, in the brains in children with hydrocephalus using graph theory analysis and diffusion tensor tractography. Three groups of children were included in the study (29 normally developing controls, 9 preoperative hydrocephalus patients, and 17 postoperative hydrocephalus patients). Graph theory analysis was applied to calculate the global network measures including small-worldness, normalized clustering coefficients, normalized characteristic path length, global efficiency, and modularity. Abnormalities in regional network parameters, including nodal degree, local efficiency, clustering coefficient, and betweenness centrality, were also compared between the two patients groups (separately) and the controls using two tailed t-test at significance level of p < 0.05 (corrected for multiple comparison). Children with hydrocephalus in both the preoperative and postoperative groups were found to have significantly lower small-worldness and lower normalized clustering coefficient than controls. Children with hydrocephalus in the postoperative group were also found to have significantly lower normalized characteristic path length and lower modularity. At regional level, significant group differences (or differences at trend level) in regional network measures were found between hydrocephalus patients and the controls in a series of brain regions including the medial occipital gyrus, medial frontal gyrus, thalamus, cingulate gyrus, lingual gyrus, rectal gyrus, caudate, cuneus, and insular. Our data showed that structural connectivity analysis using graph theory and diffusion tensor tractography is sensitive to detect

  2. Abnormal White Matter Blood-Oxygen-Level–Dependent Signals in Chronic Mild Traumatic Brain Injury

    PubMed Central

    Astafiev, Serguei V.; Shulman, Gordon L.; Metcalf, Nicholas V.; Rengachary, Jennifer; MacDonald, Christine L.; Harrington, Deborah L.; Maruta, Jun; Shimony, Joshua S.; Ghajar, Jamshid; Diwakar, Mithun; Huang, Ming-Xiong; Lee, Roland R.

    2015-01-01

    Abstract Concussion, or mild traumatic brain injury (mTBI), can cause persistent behavioral symptoms and cognitive impairment, but it is unclear if this condition is associated with detectable structural or functional brain changes. At two sites, chronic mTBI human subjects with persistent post-concussive symptoms (three months to five years after injury) and age- and education-matched healthy human control subjects underwent extensive neuropsychological and visual tracking eye movement tests. At one site, patients and controls also performed the visual tracking tasks while blood-oxygen-level–dependent (BOLD) signals were measured with functional magnetic resonance imaging. Although neither neuropsychological nor visual tracking measures distinguished patients from controls at the level of individual subjects, abnormal BOLD signals were reliably detected in patients. The most consistent changes were localized in white matter regions: anterior internal capsule and superior longitudinal fasciculus. In contrast, BOLD signals were normal in cortical regions, such as the frontal eye field and intraparietal sulcus, that mediate oculomotor and attention functions necessary for visual tracking. The abnormal BOLD signals accurately differentiated chronic mTBI patients from healthy controls at the single-subject level, although they did not correlate with symptoms or neuropsychological performance. We conclude that subjects with persistent post-concussive symptoms can be identified years after their TBI using fMRI and an eye movement task despite showing normal structural MRI and DTI. PMID:25758167

  3. Abnormal White Matter Blood-Oxygen-Level-Dependent Signals in Chronic Mild Traumatic Brain Injury.

    PubMed

    Astafiev, Serguei V; Shulman, Gordon L; Metcalf, Nicholas V; Rengachary, Jennifer; MacDonald, Christine L; Harrington, Deborah L; Maruta, Jun; Shimony, Joshua S; Ghajar, Jamshid; Diwakar, Mithun; Huang, Ming-Xiong; Lee, Roland R; Corbetta, Maurizio

    2015-08-15

    Concussion, or mild traumatic brain injury (mTBI), can cause persistent behavioral symptoms and cognitive impairment, but it is unclear if this condition is associated with detectable structural or functional brain changes. At two sites, chronic mTBI human subjects with persistent post-concussive symptoms (three months to five years after injury) and age- and education-matched healthy human control subjects underwent extensive neuropsychological and visual tracking eye movement tests. At one site, patients and controls also performed the visual tracking tasks while blood-oxygen-level-dependent (BOLD) signals were measured with functional magnetic resonance imaging. Although neither neuropsychological nor visual tracking measures distinguished patients from controls at the level of individual subjects, abnormal BOLD signals were reliably detected in patients. The most consistent changes were localized in white matter regions: anterior internal capsule and superior longitudinal fasciculus. In contrast, BOLD signals were normal in cortical regions, such as the frontal eye field and intraparietal sulcus, that mediate oculomotor and attention functions necessary for visual tracking. The abnormal BOLD signals accurately differentiated chronic mTBI patients from healthy controls at the single-subject level, although they did not correlate with symptoms or neuropsychological performance. We conclude that subjects with persistent post-concussive symptoms can be identified years after their TBI using fMRI and an eye movement task despite showing normal structural MRI and DTI.

  4. Use of CT perfusion to discriminate between brain metastases from different primaries.

    PubMed

    Dolgushin, Mikhail B; Pronin, Igor N; Holodny, Elena A; Fadeeva, Liudmila M; Holodny, Andrei I; Kornienko, Valeri N

    2015-01-01

    Thirty-six metastases in 22 patients were studied prospectively using computed tomography perfusion. Regions of interests were drawn around: the enhancing part of the tumor, necrotic central part, periphery, peritumoral edema, and normal white matter. Cerebral blood volume, cerebral blood flow, and mean transit time were calculated for each zone. The enhancing part of the tumor significantly differed from the other zones in 11 of 12. Metastases of different primaries can be differentiated from one another with statistically significance (P<.05) by at least one perfusion parameter in 57% of cases.

  5. mTOR signaling and its roles in normal and abnormal brain development

    PubMed Central

    Takei, Nobuyuki; Nawa, Hiroyuki

    2014-01-01

    Target of rapamycin (TOR) was first identified in yeast as a target molecule of rapamycin, an anti-fugal and immunosuppressant macrolide compound. In mammals, its orthologue is called mammalian TOR (mTOR). mTOR is a serine/threonine kinase that converges different extracellular stimuli, such as nutrients and growth factors, and diverges into several biochemical reactions, including translation, autophagy, transcription, and lipid synthesis among others. These biochemical reactions govern cell growth and cause cells to attain an anabolic state. Thus, the disruption of mTOR signaling is implicated in a wide array of diseases such as cancer, diabetes, and obesity. In the central nervous system, the mTOR signaling cascade is activated by nutrients, neurotrophic factors, and neurotransmitters that enhances protein (and possibly lipid) synthesis and suppresses autophagy. These processes contribute to normal neuronal growth by promoting their differentiation, neurite elongation and branching, and synaptic formation during development. Therefore, disruption of mTOR signaling may cause neuronal degeneration and abnormal neural development. While reduced mTOR signaling is associated with neurodegeneration, excess activation of mTOR signaling causes abnormal development of neurons and glia, leading to brain malformation. In this review, we first introduce the current state of molecular knowledge of mTOR complexes and signaling in general. We then describe mTOR activation in neurons, which leads to translational enhancement, and finally discuss the link between mTOR and normal/abnormal neuronal growth during development. PMID:24795562

  6. Effects of hyperbaric oxygen on eye tracking abnormalities in males after mild traumatic brain injury.

    PubMed

    Cifu, David X; Hoke, Kathy W; Wetzel, Paul A; Wares, Joanna R; Gitchel, George; Carne, William

    2014-01-01

    The effects of hyperbaric oxygen (HBO2) on eye movement abnormalities in 60 military servicemembers with at least one mild traumatic brain injury (TBI) from combat were examined in a single-center, randomized, double-blind, sham-controlled, prospective study at the Naval Medicine Operational Training Center. During the 10 wk of the study, each subject was delivered a series of 40, once a day, hyperbaric chamber compressions at a pressure of 2.0 atmospheres absolute (ATA). At each session, subjects breathed one of three preassigned oxygen fractions (10.5%, 75%, or 100%) for 1 h, resulting in an oxygen exposure equivalent to breathing either surface air, 100% oxygen at 1.5 ATA, or 100% oxygen at 2.0 ATA, respectively. Using a standardized, validated, computerized eye tracking protocol, fixation, saccades, and smooth pursuit eye movements were measured just prior to intervention and immediately postintervention. Between and within groups testing of pre- and postintervention means revealed no significant differences on eye movement abnormalities and no significant main effect for HBO2 at either 1.5 ATA or 2.0 ATA equivalent compared with the sham-control. This study demonstrated that neither 1.5 nor 2.0 ATA equivalent HBO2 had an effect on postconcussive eye movement abnormalities after mild TBI when compared with a sham-control.

  7. Effects of hyperbaric oxygen on eye tracking abnormalities in males after mild traumatic brain injury.

    PubMed

    Cifu, David X; Hoke, Kathy W; Wetzel, Paul A; Wares, Joanna R; Gitchel, George; Carne, William

    2014-01-01

    The effects of hyperbaric oxygen (HBO2) on eye movement abnormalities in 60 military servicemembers with at least one mild traumatic brain injury (TBI) from combat were examined in a single-center, randomized, double-blind, sham-controlled, prospective study at the Naval Medicine Operational Training Center. During the 10 wk of the study, each subject was delivered a series of 40, once a day, hyperbaric chamber compressions at a pressure of 2.0 atmospheres absolute (ATA). At each session, subjects breathed one of three preassigned oxygen fractions (10.5%, 75%, or 100%) for 1 h, resulting in an oxygen exposure equivalent to breathing either surface air, 100% oxygen at 1.5 ATA, or 100% oxygen at 2.0 ATA, respectively. Using a standardized, validated, computerized eye tracking protocol, fixation, saccades, and smooth pursuit eye movements were measured just prior to intervention and immediately postintervention. Between and within groups testing of pre- and postintervention means revealed no significant differences on eye movement abnormalities and no significant main effect for HBO2 at either 1.5 ATA or 2.0 ATA equivalent compared with the sham-control. This study demonstrated that neither 1.5 nor 2.0 ATA equivalent HBO2 had an effect on postconcussive eye movement abnormalities after mild TBI when compared with a sham-control. PMID:25436771

  8. Potential of optical microangiography to monitor cerebral blood perfusion and vascular plasticity following traumatic brain injury in mice in vivo

    NASA Astrophysics Data System (ADS)

    Jia, Yali; Alkayed, Nabil; Wang, Ruikang K.

    2009-07-01

    Optical microanglography (OMAG) is a recently developed imaging modality capable of volumetric imaging of dynamic blood perfusion, down to capillary level resolution, with an imaging depth up to 2.00 mm beneath the tissue surface. We report the use of OMAG to monitor the cerebral blood flow (CBF) over the cortex of mouse brain upon traumatic brain injury (TBI), with the cranium left intact, for a period of two weeks on the same animal. We show the ability of OMAG to repeatedly image 3-D cerebral vasculatures during pre- and post-traumatic phases, and to visualize the changes of regulated CBF and the vascular plasticity after TBI. The results indicate the potential of OMAG to explore the mechanism involved in the rehabilitation of TBI.

  9. Defining Core and Penumbra in Ischemic Stroke: A Voxel- and Volume-Based Analysis of Whole Brain CT Perfusion.

    PubMed

    Yu, Yannan; Han, Quan; Ding, Xinfa; Chen, Qingmeng; Ye, Keqi; Zhang, Sheng; Yan, Shenqiang; Campbell, Bruce C V; Parsons, Mark W; Wang, Shaoshi; Lou, Min

    2016-01-01

    Whole brain computed tomography perfusion (CTP) has the potential to select eligible patients for reperfusion therapy. We aimed to find the optimal thresholds on baseline CTP for ischemic core and penumbra in acute ischemic stroke. We reviewed patients with acute ischemic stroke in the anterior circulation, who underwent baseline whole brain CTP, followed by intravenous thrombolysis and perfusion imaging at 24 hours. Patients were divided into those with major reperfusion (to define the ischemic core) and minimal reperfusion (to define the extent of penumbra). Receiver operating characteristic (ROC) analysis and volumetric consistency analysis were performed separately to determine the optimal threshold by Youden's Index and mean magnitude of volume difference, respectively. From a series of 103 patients, 22 patients with minimal-reperfusion and 47 with major reperfusion were included. Analysis revealed delay time ≥ 3 s most accurately defined penumbra (AUC = 0.813; 95% CI, 0.812-0.814, mean magnitude of volume difference = 29.1 ml). The optimal threshold for ischemic core was rCBF ≤ 30% within delay time ≥ 3 s (AUC = 0.758; 95% CI, 0.757-0.760, mean magnitude of volume difference = 10.8 ml). In conclusion, delay time ≥ 3 s and rCBF ≤ 30% within delay time ≥ 3 s are the optimal thresholds for penumbra and core, respectively. These results may allow the application of the mismatch on CTP to reperfusion therapy.

  10. Delineation of candidate genes responsible for structural brain abnormalities in patients with terminal deletions of chromosome 6q27

    PubMed Central

    Peddibhotla, Sirisha; Nagamani, Sandesh CS; Erez, Ayelet; Hunter, Jill V; Holder Jr, J Lloyd; Carlin, Mary E; Bader, Patricia I; Perras, Helene MF; Allanson, Judith E; Newman, Leslie; Simpson, Gayle; Immken, LaDonna; Powell, Erin; Mohanty, Aaron; Kang, Sung-Hae L; Stankiewicz, Pawel; Bacino, Carlos A; Bi, Weimin; Patel, Ankita; Cheung, Sau W

    2015-01-01

    Patients with terminal deletions of chromosome 6q present with structural brain abnormalities including agenesis of corpus callosum, hydrocephalus, periventricular nodular heterotopia, and cerebellar malformations. The 6q27 region harbors genes that are important for the normal development of brain and delineation of a critical deletion region for structural brain abnormalities may lead to a better genotype–phenotype correlation. We conducted a detailed clinical and molecular characterization of seven unrelated patients with deletions involving chromosome 6q27. All patients had structural brain abnormalities. Using array comparative genomic hybridization, we mapped the size, extent, and genomic content of these deletions. The smallest region of overlap spans 1.7 Mb and contains DLL1, THBS2, PHF10, and C6orf70 (ERMARD) that are plausible candidates for the causation of structural brain abnormalities. Our study reiterates the importance of 6q27 region in normal development of brain and helps identify putative genes in causation of structural brain anomalies. PMID:24736736

  11. Delineation of candidate genes responsible for structural brain abnormalities in patients with terminal deletions of chromosome 6q27.

    PubMed

    Peddibhotla, Sirisha; Nagamani, Sandesh C S; Erez, Ayelet; Hunter, Jill V; Holder, J Lloyd; Carlin, Mary E; Bader, Patricia I; Perras, Helene M F; Allanson, Judith E; Newman, Leslie; Simpson, Gayle; Immken, LaDonna; Powell, Erin; Mohanty, Aaron; Kang, Sung-Hae L; Stankiewicz, Pawel; Bacino, Carlos A; Bi, Weimin; Patel, Ankita; Cheung, Sau W

    2015-01-01

    Patients with terminal deletions of chromosome 6q present with structural brain abnormalities including agenesis of corpus callosum, hydrocephalus, periventricular nodular heterotopia, and cerebellar malformations. The 6q27 region harbors genes that are important for the normal development of brain and delineation of a critical deletion region for structural brain abnormalities may lead to a better genotype-phenotype correlation. We conducted a detailed clinical and molecular characterization of seven unrelated patients with deletions involving chromosome 6q27. All patients had structural brain abnormalities. Using array comparative genomic hybridization, we mapped the size, extent, and genomic content of these deletions. The smallest region of overlap spans 1.7 Mb and contains DLL1, THBS2, PHF10, and C6orf70 (ERMARD) that are plausible candidates for the causation of structural brain abnormalities. Our study reiterates the importance of 6q27 region in normal development of brain and helps identify putative genes in causation of structural brain anomalies.

  12. Changes of Cerebral Perfusion and Functional Brain Network Organization in Patients with Mild Cognitive Impairment.

    PubMed

    Lou, Wutao; Shi, Lin; Wong, Adrian; Chu, Winnie C W; Mok, Vincent C T; Wang, Defeng

    2016-08-10

    Disruptions of the functional brain network and cerebral blood flow (CBF) have been revealed in patients with mild cognitive impairment (MCI). However, the neurophysiological mechanism of hypoperfusion as well as the reorganization of the intrinsic whole brain network due to the neuropathology of MCI are still unclear. In this study, we aimed to investigate the changes of CBF and the whole brain network organization in MCI by using a multimodal MRI approach. Resting state ASL MRI and BOLD MRI were used to evaluate disruptions of CBF and underlying functional connectivity in 27 patients with MCI and 35 cognitive normal controls (NC). The eigenvector centrality mapping (ECM) was used to assess the whole brain network reorganization in MCI, and a seed-based ECM approach was proposed to reveal the contributions of the whole brain network on the ECM alterations. Significantly decreased perfusion in the posterior parietal cortex as well as its connectivity within the default mode network and occipital cortex were found in the MCI group compared to the NC group. The ECM analysis revealed decreased EC in the middle cingulate cortex, parahippocampal gyrus, medial frontal gyrus, and increased EC in the right calcarine sulcus, superior temporal gyrus, and supplementary motor area in the MCI group. The results of this study indicate that there are deficits in cerebral blood flow and functional connectivity in the default mode network, and that sensory-processing networks might play a compensatory role to make up for the decreased connections in MCI.

  13. Changes of Cerebral Perfusion and Functional Brain Network Organization in Patients with Mild Cognitive Impairment.

    PubMed

    Lou, Wutao; Shi, Lin; Wong, Adrian; Chu, Winnie C W; Mok, Vincent C T; Wang, Defeng

    2016-08-10

    Disruptions of the functional brain network and cerebral blood flow (CBF) have been revealed in patients with mild cognitive impairment (MCI). However, the neurophysiological mechanism of hypoperfusion as well as the reorganization of the intrinsic whole brain network due to the neuropathology of MCI are still unclear. In this study, we aimed to investigate the changes of CBF and the whole brain network organization in MCI by using a multimodal MRI approach. Resting state ASL MRI and BOLD MRI were used to evaluate disruptions of CBF and underlying functional connectivity in 27 patients with MCI and 35 cognitive normal controls (NC). The eigenvector centrality mapping (ECM) was used to assess the whole brain network reorganization in MCI, and a seed-based ECM approach was proposed to reveal the contributions of the whole brain network on the ECM alterations. Significantly decreased perfusion in the posterior parietal cortex as well as its connectivity within the default mode network and occipital cortex were found in the MCI group compared to the NC group. The ECM analysis revealed decreased EC in the middle cingulate cortex, parahippocampal gyrus, medial frontal gyrus, and increased EC in the right calcarine sulcus, superior temporal gyrus, and supplementary motor area in the MCI group. The results of this study indicate that there are deficits in cerebral blood flow and functional connectivity in the default mode network, and that sensory-processing networks might play a compensatory role to make up for the decreased connections in MCI. PMID:27567823

  14. Optical monitoring of cardiac and respiratory rhythms in the skin perfusion near the brain under controlled conditions

    NASA Astrophysics Data System (ADS)

    Mukunda Rao, M.; Blazek, Vladimir; Schmitt, Hans J.

    1998-06-01

    In this investigation an attempt is made to find the effects of controlled breathing on brain with the help of optical sensors mounted on the left and right temples of a subject. It has already been established that the brain activity can be monitored in terms of arterial blood volumetric changes to the left and right hemispheres of the brain recorded with the help of optical sensors. To investigate the influence of controlled breathing, an expert in controlled breathing (pranayama) is chosen as the subject. Pranayama is believed to be the controlled intake and outflow of breath in a firmly established posture. Some types of pranayama are believed to relive mental stress. While the subject is practicing one such type of breath control, arterial blood volume changes in the brain are recorded using optical sensors mounted on the left and right temples of the subject. From these measurements at the beginning and end of the pranayama exercise, it could be noticed that the subject could induce changes in the cardiac and respiratory rhythms by controlled breathing. Rhythmic phenomena in the skin perfusion in the vicinity of the brian are also studied when the subject is holding his breath. The arterial blood volume changes to the left and right hemispheres of the brain, as monitored by the optical sensors during this period, exhibit asymmetric reaction when the subject is holding his breath. An attempt is made to understand whether these changes induced by stoppage of breathing are 'chaotic' or 'adaptive' in nature.

  15. The nature of white matter abnormalities in blast-related mild traumatic brain injury

    PubMed Central

    Hayes, Jasmeet P.; Miller, Danielle R.; Lafleche, Ginette; Salat, David H.; Verfaellie, Mieke

    2015-01-01

    Blast-related traumatic brain injury (TBI) has been a common injury among returning troops due to the widespread use of improvised explosive devices in the Iraq and Afghanistan Wars. As most of the TBIs sustained are in the mild range, brain changes may not be detected by standard clinical imaging techniques such as CT. Furthermore, the functional significance of these types of injuries is currently being debated. However, accumulating evidence suggests that diffusion tensor imaging (DTI) is sensitive to subtle white matter abnormalities and may be especially useful in detecting mild TBI (mTBI). The primary aim of this study was to use DTI to characterize the nature of white matter abnormalities following blast-related mTBI, and in particular, examine the extent to which mTBI-related white matter abnormalities are region-specific or spatially heterogeneous. In addition, we examined whether mTBI with loss of consciousness (LOC) was associated with more extensive white matter abnormality than mTBI without LOC, as well as the potential moderating effect of number of blast exposures. A second aim was to examine the relationship between white matter integrity and neurocognitive function. Finally, a third aim was to examine the contribution of PTSD symptom severity to observed white matter alterations. One hundred fourteen OEF/OIF veterans underwent DTI and neuropsychological examination and were divided into three groups including a control group, blast-related mTBI without LOC (mTBI - LOC) group, and blast-related mTBI with LOC (mTBI + LOC) group. Hierarchical regression models were used to examine the extent to which mTBI and PTSD predicted white matter abnormalities using two approaches: 1) a region-specific analysis and 2) a measure of spatial heterogeneity. Neurocognitive composite scores were calculated for executive functions, attention, memory, and psychomotor speed. Results showed that blast-related mTBI + LOC was associated with greater odds of having

  16. The nature of white matter abnormalities in blast-related mild traumatic brain injury.

    PubMed

    Hayes, Jasmeet P; Miller, Danielle R; Lafleche, Ginette; Salat, David H; Verfaellie, Mieke

    2015-01-01

    Blast-related traumatic brain injury (TBI) has been a common injury among returning troops due to the widespread use of improvised explosive devices in the Iraq and Afghanistan Wars. As most of the TBIs sustained are in the mild range, brain changes may not be detected by standard clinical imaging techniques such as CT. Furthermore, the functional significance of these types of injuries is currently being debated. However, accumulating evidence suggests that diffusion tensor imaging (DTI) is sensitive to subtle white matter abnormalities and may be especially useful in detecting mild TBI (mTBI). The primary aim of this study was to use DTI to characterize the nature of white matter abnormalities following blast-related mTBI, and in particular, examine the extent to which mTBI-related white matter abnormalities are region-specific or spatially heterogeneous. In addition, we examined whether mTBI with loss of consciousness (LOC) was associated with more extensive white matter abnormality than mTBI without LOC, as well as the potential moderating effect of number of blast exposures. A second aim was to examine the relationship between white matter integrity and neurocognitive function. Finally, a third aim was to examine the contribution of PTSD symptom severity to observed white matter alterations. One hundred fourteen OEF/OIF veterans underwent DTI and neuropsychological examination and were divided into three groups including a control group, blast-related mTBI without LOC (mTBI - LOC) group, and blast-related mTBI with LOC (mTBI + LOC) group. Hierarchical regression models were used to examine the extent to which mTBI and PTSD predicted white matter abnormalities using two approaches: 1) a region-specific analysis and 2) a measure of spatial heterogeneity. Neurocognitive composite scores were calculated for executive functions, attention, memory, and psychomotor speed. Results showed that blast-related mTBI + LOC was associated with greater odds of having

  17. Abnormalities of functional brain networks in pathological gambling: a graph-theoretical approach

    PubMed Central

    Tschernegg, Melanie; Crone, Julia S.; Eigenberger, Tina; Schwartenbeck, Philipp; Fauth-Bühler, Mira; Lemènager, Tagrid; Mann, Karl; Thon, Natasha; Wurst, Friedrich M.; Kronbichler, Martin

    2013-01-01

    Functional neuroimaging studies of pathological gambling (PG) demonstrate alterations in frontal and subcortical regions of the mesolimbic reward system. However, most investigations were performed using tasks involving reward processing or executive functions. Little is known about brain network abnormalities during task-free resting state in PG. In the present study, graph-theoretical methods were used to investigate network properties of resting state functional magnetic resonance imaging data in PG. We compared 19 patients with PG to 19 healthy controls (HCs) using the Graph Analysis Toolbox (GAT). None of the examined global metrics differed between groups. At the nodal level, pathological gambler showed a reduced clustering coefficient in the left paracingulate cortex and the left juxtapositional lobe (supplementary motor area, SMA), reduced local efficiency in the left SMA, as well as an increased node betweenness for the left and right paracingulate cortex and the left SMA. At an uncorrected threshold level, the node betweenness in the left inferior frontal gyrus was decreased and increased in the caudate. Additionally, increased functional connectivity between fronto-striatal regions and within frontal regions has also been found for the gambling patients. These findings suggest that regions associated with the reward system demonstrate reduced segregation but enhanced integration while regions associated with executive functions demonstrate reduced integration. The present study makes evident that PG is also associated with abnormalities in the topological network structure of the brain during rest. Since alterations in PG cannot be explained by direct effects of abused substances on the brain, these findings will be of relevance for understanding functional connectivity in other addictive disorders. PMID:24098282

  18. Abnormal functional global and local brain connectivity in female patients with anorexia nervosa

    PubMed Central

    Geisler, Daniel; Borchardt, Viola; Lord, Anton R.; Boehm, Ilka; Ritschel, Franziska; Zwipp, Johannes; Clas, Sabine; King, Joseph A.; Wolff-Stephan, Silvia; Roessner, Veit; Walter, Martin; Ehrlich, Stefan

    2016-01-01

    Background Previous resting-state functional connectivity studies in patients with anorexia nervosa used independent component analysis or seed-based connectivity analysis to probe specific brain networks. Instead, modelling the entire brain as a complex network allows determination of graph-theoretical metrics, which describe global and local properties of how brain networks are organized and how they interact. Methods To determine differences in network properties between female patients with acute anorexia nervosa and pairwise matched healthy controls, we used resting-state fMRI and computed well-established global and local graph metrics across a range of network densities. Results Our analyses included 35 patients and 35 controls. We found that the global functional network structure in patients with anorexia nervosa is characterized by increases in both characteristic path length (longer average routes between nodes) and assortativity (more nodes with a similar connectedness link together). Accordingly, we found locally decreased connectivity strength and increased path length in the posterior insula and thalamus. Limitations The present results may be limited to the methods applied during preprocessing and network construction. Conclusion We demonstrated anorexia nervosa–related changes in the network configuration for, to our knowledge, the first time using resting-state fMRI and graph-theoretical measures. Our findings revealed an altered global brain network architecture accompanied by local degradations indicating wide-scale disturbance in information flow across brain networks in patients with acute anorexia nervosa. Reduced local network efficiency in the thalamus and posterior insula may reflect a mechanism that helps explain the impaired integration of visuospatial and homeostatic signals in patients with this disorder, which is thought to be linked to abnormal representations of body size and hunger. PMID:26252451

  19. Multicenter Study of Brain Volume Abnormalities in Children and Adolescent-Onset Psychosis

    PubMed Central

    Reig, Santiago; Parellada, Mara; Castro-Fornieles, Josefina; Janssen, Joost; Moreno, Dolores; Baeza, Inmaculada; Bargalló, Nuria; González-Pinto, Ana; Graell, Montserrat; Ortuño, Felipe; Otero, Soraya; Arango, Celso; Desco, Manuel

    2011-01-01

    The goal of the study is to determine the extent of structural brain abnormalities in a multicenter sample of children and adolescents with a recent-onset first episode of psychosis (FEP), compared with a sample of healthy controls. Total brain and lobar volumes and those of gray matter (GM), white matter, and cerebrospinal fluid (CSF) were measured in 92 patients with a FEP and in 94 controls, matched for age, gender, and years of education. Male patients (n = 64) showed several significant differences when compared with controls (n = 61). GM volume in male patients was reduced in the whole brain and in frontal and parietal lobes compared with controls. Total CSF volume and frontal, temporal, and right parietal CSF volumes were also increased in male patients. Within patients, those with a further diagnosis of “schizophrenia” or “other psychosis” showed a pattern similar to the group of all patients relative to controls. However, bipolar patients showed fewer differences relative to controls. In female patients, only the schizophrenia group showed differences relative to controls, in frontal CSF. GM deficit in male patients with a first episode correlated with negative symptoms. Our study suggests that at least part of the GM deficit in children and adolescent-onset schizophrenia and in other psychosis occurs before onset of the first positive symptoms and that, contrary to what has been shown in children-onset schizophrenia, frontal GM deficits are probably present from the first appearance of positive symptoms in children and adolescents. PMID:20478821

  20. Multidimensional morphometric 3D MRI analyses for detecting brain abnormalities in children: impact of control population.

    PubMed

    Wilke, Marko; Rose, Douglas F; Holland, Scott K; Leach, James L

    2014-07-01

    Automated morphometric approaches are used to detect epileptogenic structural abnormalities in 3D MR images in adults, using the variance of a control population to obtain z-score maps in an individual patient. Due to the substantial changes the developing human brain undergoes, performing such analyses in children is challenging. This study investigated six features derived from high-resolution T1 datasets in four groups: normal children (1.5T or 3T data), normal clinical scans (3T data), and patients with structural brain lesions (3T data), with each n = 10. Normative control data were obtained from the NIH study on normal brain development (n = 401). We show that control group size substantially influences the captured variance, directly impacting the patient's z-scores. Interestingly, matching on gender does not seem to be beneficial, which was unexpected. Using data obtained at higher field scanners produces slightly different base rates of suprathreshold voxels, as does using clinically derived normal studies, suggesting a subtle but systematic effect of both factors. Two approaches for controlling suprathreshold voxels in a multidimensional approach (combining features and requiring a minimum cluster size) were shown to be substantial and effective in reducing this number. Finally, specific strengths and limitations of such an approach could be demonstrated in individual cases. PMID:25050423

  1. Dido mutations trigger perinatal death and generate brain abnormalities and behavioral alterations in surviving adult mice

    PubMed Central

    Villares, Ricardo; Gutiérrez, Julio; Fütterer, Agnes; Trachana, Varvara; Gutiérrez del Burgo, Fernando; Martínez-A, Carlos

    2015-01-01

    Nearly all vertebrate cells have a single cilium protruding from their surface. This threadlike organelle, once considered vestigial, is now seen as a pivotal element for detection of extracellular signals that trigger crucial morphogenetic pathways. We recently proposed a role for Dido3, the main product of the death inducer-obliterator (dido) gene, in histone deacetylase 6 delivery to the primary cilium [Sánchez de Diego A, et al. (2014) Nat Commun 5:3500]. Here we used mice that express truncated forms of Dido proteins to determine the link with cilium-associated disorders. We describe dido mutant mice with high incidence of perinatal lethality and distinct neurodevelopmental, morphogenetic, and metabolic alterations. The anatomical abnormalities were related to brain and orofacial development, consistent with the known roles of primary cilia in brain patterning, hydrocephalus incidence, and cleft palate. Mutant mice that reached adulthood showed reduced life expectancy, brain malformations including hippocampus hypoplasia and agenesis of corpus callosum, as well as neuromuscular and behavioral alterations. These mice can be considered a model for the study of ciliopathies and provide information for assessing diagnosis and therapy of genetic disorders linked to the deregulation of primary cilia. PMID:25825751

  2. Optical monitoring of cardiac and respiratory rhythms in the skin perfusion near the brain under controlled conditions

    NASA Astrophysics Data System (ADS)

    Rao, Mandavilli M.; Blazek, Vladimir; Schmitt, Hans J.

    1998-04-01

    In this investigation an attempt is made to find the effects of controlled breathing on brain with the help of optical sensor mounted on the left and right temples of a subject. It has already been established that the brain activity can be monitored in terms of arterial blood volumetric changes to the left and right hemispheres of the brain recorded with the help of optical sensors. To investigate the influence of controlled breathing, an expert in controlled breathing is chosen as the subject. Pranayama is believed to be the controlled intake and outflow of breath in a firmly established posture. Some types of pranayama are believed to relieve mental stress. While the subject is practicing one such type of breath control, arterial blood volume changes in the brain are recorded using optical sensor mounted on the left and right temples of the subject. From these measurements at the beginning and end of the pranayama exercise, it could be noticed that the subject could induce changes in the cardiac and respiratory rhythms by controlled breathing. Rhythmic phenomena in the skin perfusion in the vicinity of the brian are also studied when the subject is holding his breath. The arterial blood volume changes to the left and right hemispheres of the brian, as monitored by the optical sensors during this period, exhibit asymmetric reaction when the subject is holding his breath. An attempt is made to understand whether these changes induced by stoppage of breathing are 'chaotic' or 'adaptive' in nature.

  3. Framework for cognitive analysis of dynamic perfusion computed tomography with visualization of large volumetric data

    NASA Astrophysics Data System (ADS)

    Hachaj, Tomasz; Ogiela, Marek R.

    2012-10-01

    The proposed framework for cognitive analysis of perfusion computed tomography images is a fusion of image processing, pattern recognition, and image analysis procedures. The output data of the algorithm consists of: regions of perfusion abnormalities, anatomy atlas description of brain tissues, measures of perfusion parameters, and prognosis for infracted tissues. That information is superimposed onto volumetric computed tomography data and displayed to radiologists. Our rendering algorithm enables rendering large volumes on off-the-shelf hardware. This portability of rendering solution is very important because our framework can be run without using expensive dedicated hardware. The other important factors are theoretically unlimited size of rendered volume and possibility of trading of image quality for rendering speed. Such rendered, high quality visualizations may be further used for intelligent brain perfusion abnormality identification, and computer aided-diagnosis of selected types of pathologies.

  4. Brain and Cognition Abnormalities in Long-Term Anabolic-Androgenic Steroid Users

    PubMed Central

    Kaufman, Marc J.; Janes, Amy C.; Hudson, James I.; Brennan, Brian P.; Kanayama, Gen; Kerrigan, Andrew R.; Jensen, J. Eric; Pope, Harrison G.

    2015-01-01

    Background Anabolic-androgenic steroid (AAS) use is associated with psychiatric symptoms including increased aggression as well as with cognitive dysfunction. The brain effects of long-term AAS use have not been assessed in humans. Methods This multimodal magnetic resonance imaging study of the brain compared 10 male weightlifters reporting long-term AAS use with 10 age-matched weightlifters reporting no AAS exposure. Participants were administered visuospatial memory tests and underwent neuroimaging. Brain volumetric analyses were performed; resting-state fMRI functional connectivity (rsFC) was evaluated using a region-of-interest analysis focused on the amygdala; and dorsal anterior cingulate cortex (dACC) metabolites were quantified by proton magnetic resonance spectroscopy (MRS). Results AAS users had larger right amygdala volumes than nonusers (P=0.002) and reduced rsFC between right amygdala and frontal, striatal, limbic, hippocampal, and visual cortical areas. Left amygdala volumes were slightly larger in AAS users (P=0.061) but few group differences were detected in left amygdala rsFC. AAS users also had lower dACC scyllo-inositol levels (P=0.004) and higher glutamine/glutamate ratios (P=0.028), possibly reflecting increased glutamate turnover. On a visuospatial cognitive task, AAS users performed more poorly than nonusers, with the difference approaching significance (P=0.053). Conclusions Long-term AAS use is associated with right amygdala enlargement and reduced right amygdala rsFC with brain areas involved in cognitive control and spatial memory, which could contribute to the psychiatric effects and cognitive dysfunction associated with AAS use. The MRS abnormalities we detected could reflect enhanced glutamate turnover and increased vulnerability to neurotoxic or neurodegenerative processes, which could contribute to AAS-associated cognitive dysfunction. PMID:25986964

  5. Abnormal brain biomechanics in the hydrocephalic child. From: Concepts in Pediatric Neurosurgery, 1982,vol 2.

    PubMed

    Shapiro, K; Marmarou, A; Shulman, K

    1993-01-01

    Sixteen children with active hydrocephalus were studied using the Pressure Volume Index (PVI) technique to characterize neural axis compliance and the resistance to CSF absorption (Ro). Intracranial pressure for the series was 16.2 +/- 6.2/13.3 +/- 6.1 mm Hg. Measured PVI was twice that predicted for each child, indicating abnormally compliant systems. Ro was 7.8 +/- 1.7 mm Hg/ml/min, a three-fold increase above normal. There was no correlation between PVI and ventricular size. These studies indicate that the biomechanical properties of the brain and its coverings are altered by the hydrocephalic process in a way that encourages further accumulation of volume.

  6. Longitudinal assessment of gait abnormalities following penetrating ballistic-like brain injury in rats.

    PubMed

    Mountney, Andrea; Leung, Lai Yee; Pedersen, Rebecca; Shear, Deborah; Tortella, Frank

    2013-01-15

    Traumatic brain injury (TBI) results in enduring motor and cognitive dysfunction. Although gait disturbances have been documented among TBI patients, few studies have profiled gait abnormalities in animal models of TBI. We sought to obtain a comprehensive longitudinal analysis of gait function following severe penetrating ballistic-like brain injury (PBBI) in rats. Rats were subjected to either unilateral frontal PBBI, probe insertion alone, or sham surgery. Sensorimotor performance was assessed using the CatWalk automated gait analysis system. Baseline measurements were taken 3 days prior to injury and detailed analysis of gait was performed at 1, 3, 7, 14, and 28 days post-injury. Both PBBI and probe-inserted rats displayed altered static and dynamic gait parameters that were primarily evident during the early (<7 days) post-injury phase and were resolved by 1 month post-injury. PBBI produced more severe deficits compared to probe-alone which were reflected in the number, magnitude, and resolution time of abnormal gait parameters. While altered parameters were detected in all four paws, they were more apparent on the contralateral side. Gait parameters including paw pressure, print area, swing speed, and stride length were significantly decreased whereas stance, swing, and step cycle duration were increased compared to sham. Overall, altered gait patterns detected using the CatWalk system in the PBBI model were injury-severity dependent, resolved at later time points, and appeared similar to those reported in severe TBI patients. These results indicate that the CatWalk may be most useful for neuroprotection studies that focus on the acute/subacute recovery period after TBI.

  7. Apert and Crouzon syndromes-Cognitive development, brain abnormalities, and molecular aspects.

    PubMed

    Fernandes, Marilyse B L; Maximino, Luciana P; Perosa, Gimol B; Abramides, Dagma V M; Passos-Bueno, Maria Rita; Yacubian-Fernandes, Adriano

    2016-06-01

    Apert and Crouzon are the most common craniosynostosis syndromes associated with mutations in the fibroblast growth factor receptor 2 (FGFR2) gene. We conducted a study to examine the molecular biology, brain abnormalities, and cognitive development of individuals with these syndromes. A retrospective longitudinal review of 14 patients with Apert and Crouzon syndromes seen at the outpatient Craniofacial Surgery Hospital for Rehabilitation of Craniofacial Anomalies in Brazil from January 1999 through August 2010 was performed. Patients between 11 and 36 years of age (mean 18.29 ± 5.80), received cognitive evaluations, cerebral magnetic resonance imaging, and molecular DNA analyses. Eight patients with Apert syndrome (AS) had full scale intelligence quotients (FSIQs) that ranged from 47 to 108 (mean 76.9 ± 20.2), and structural brain abnormalities were identified in five of eight patients. Six patients presented with a gain-of-function mutation (p.Ser252Trp) in FGFR2 and FSIQs in those patients ranged from 47 to78 (mean 67.2 ± 10.7). One patient with a gain-of-function mutation (p.Pro253Arg) had a FSIQ of 108 and another patient with an atypical splice mutation (940-2A →G) had a FSIQ of 104. Six patients with Crouzon syndrome had with mutations in exons IIIa and IIIc of FGFR2 and their FSIQs ranged from 82 to 102 (mean 93.5 ± 6.7). These reveal that molecular aspects are another factor that can be considered in studies of global and cognitive development of patients with Apert and Crouzon syndrome (CS). © 2016 Wiley Periodicals, Inc. PMID:27028366

  8. Abnormal brain processing of cutaneous pain in patients with chronic migraine.

    PubMed

    de Tommaso, Marina; Valeriani, Massimiliano; Guido, Marco; Libro, Giuseppe; Specchio, Luigi Maria; Tonali, Pietro; Puca, Francomichele

    2003-01-01

    Syndromes with chronic daily headache include chronic migraine (CM). The reason for the transformation of migraine into chronic daily headache is still unknown. In this study, we aimed to evaluate heat pain thresholds and event-related potentials following CO(2)-laser thermal stimulation (LEPS) in hand and facial regions in patients with CM, to show changes in nociceptive brain responses related to dysfunction of pain elaboration at the cortical level. The results were compared with findings from normal control subjects and from subjects who suffer from migraine without aura. The effects of stimulus intensity, subjective pain perception and attention were monitored and compared with features of the LEPS. Twenty-five CM patients, 15 subjects suffering from migraine without aura and 15 normal control subjects were enrolled in the study. LEPS amplitude variation was reduced in CM patients with respect to the perceived stimulus intensity, in comparison with migraine without aura patients and control subjects. In both headache groups, the distraction from the painful laser stimulus induced by an arithmetic task failed to suppress the LEPS amplitude, in comparison with control subjects. These results suggest an abnormal cortical processing of nociceptive input in CM patients, which could lead to the chronic state of pain. In both headache groups, an inability to reduce pain elaboration during an alternative cognitive task emerged as an abnormal behaviour probably predisposing to migraine. PMID:12507697

  9. Abnormal brain processing of cutaneous pain in patients with chronic migraine.

    PubMed

    de Tommaso, Marina; Valeriani, Massimiliano; Guido, Marco; Libro, Giuseppe; Specchio, Luigi Maria; Tonali, Pietro; Puca, Francomichele

    2003-01-01

    Syndromes with chronic daily headache include chronic migraine (CM). The reason for the transformation of migraine into chronic daily headache is still unknown. In this study, we aimed to evaluate heat pain thresholds and event-related potentials following CO(2)-laser thermal stimulation (LEPS) in hand and facial regions in patients with CM, to show changes in nociceptive brain responses related to dysfunction of pain elaboration at the cortical level. The results were compared with findings from normal control subjects and from subjects who suffer from migraine without aura. The effects of stimulus intensity, subjective pain perception and attention were monitored and compared with features of the LEPS. Twenty-five CM patients, 15 subjects suffering from migraine without aura and 15 normal control subjects were enrolled in the study. LEPS amplitude variation was reduced in CM patients with respect to the perceived stimulus intensity, in comparison with migraine without aura patients and control subjects. In both headache groups, the distraction from the painful laser stimulus induced by an arithmetic task failed to suppress the LEPS amplitude, in comparison with control subjects. These results suggest an abnormal cortical processing of nociceptive input in CM patients, which could lead to the chronic state of pain. In both headache groups, an inability to reduce pain elaboration during an alternative cognitive task emerged as an abnormal behaviour probably predisposing to migraine.

  10. Sensory Abnormalities in Focal Hand Dystonia and Non-Invasive Brain Stimulation

    PubMed Central

    Quartarone, Angelo; Rizzo, Vincenzo; Terranova, Carmen; Milardi, Demetrio; Bruschetta, Daniele; Ghilardi, Maria Felice; Girlanda, Paolo

    2014-01-01

    It has been proposed that synchronous and convergent afferent input arising from repetitive motor tasks may play an important role in driving the maladaptive cortical plasticity seen in focal hand dystonia (FHD). This hypothesis receives support from several sources. First, it has been reported that in subjects with FHD, paired associative stimulation produces an abnormal increase in corticospinal excitability, which was not confined to stimulated muscles. These findings provide support for the role of excessive plasticity in FHD. Second, the genetic contribution to the dystonias is increasingly recognized indicating that repetitive, stereotyped afferent inputs may lead to late-onset dystonia, such as FHD, more rapidly in genetically susceptible individuals. It can be postulated, according to the two factor hypothesis that dystonia is triggered and maintained by the concurrence of environmental factors such as repetitive training and subtle abnormal mechanisms of plasticity within somatosensory loop. In the present review, we examine the contribution of sensory-motor integration in the pathophysiology of primary dystonia. In addition, we will discuss the role of non-invasive brain stimulation as therapeutic approach in FHD. PMID:25538594

  11. Abnormal neuronal activity in Tourette syndrome and its modulation using deep brain stimulation

    PubMed Central

    Israelashvili, Michal; Loewenstern, Yocheved

    2015-01-01

    Tourette syndrome (TS) is a common childhood-onset disorder characterized by motor and vocal tics that are typically accompanied by a multitude of comorbid symptoms. Pharmacological treatment options are limited, which has led to the exploration of deep brain stimulation (DBS) as a possible treatment for severe cases. Multiple lines of evidence have linked TS with abnormalities in the motor and limbic cortico-basal ganglia (CBG) pathways. Neurophysiological data have only recently started to slowly accumulate from multiple sources: noninvasive imaging and electrophysiological techniques, invasive electrophysiological recordings in TS patients undergoing DBS implantation surgery, and animal models of the disorder. These converging sources point to system-level physiological changes throughout the CBG pathway, including both general altered baseline neuronal activity patterns and specific tic-related activity. DBS has been applied to different regions along the motor and limbic pathways, primarily to the globus pallidus internus, thalamic nuclei, and nucleus accumbens. In line with the findings that also draw on the more abundant application of DBS to Parkinson's disease, this stimulation is assumed to result in changes in the neuronal firing patterns and the passage of information through the stimulated nuclei. We present an overview of recent experimental findings on abnormal neuronal activity associated with TS and the changes in this activity following DBS. These findings are then discussed in the context of current models of CBG function in the normal state, during TS, and finally in the wider context of DBS in CBG-related disorders. PMID:25925326

  12. Brain perfusion single photon emission computed tomography in major psychiatric disorders: From basics to clinical practice

    PubMed Central

    Santra, Amburanjan; Kumar, Rakesh

    2014-01-01

    Brain single photon emission computed tomography (SPECT) is a well-established and reliable method to assess brain function through measurement of regional cerebral blood flow (rCBF). It can be used to define a patient's pathophysiological status when neurological or psychiatric symptoms cannot be explained by anatomical neuroimaging findings. Though there is ample evidence validating brain SPECT as a technique to track human behavior and correlating psychiatric disorders with dysfunction of specific brain regions, only few psychiatrists have adopted brain SPECT in routine clinical practice. It can be utilized to evaluate the involvement of brain regions in a particular patient, to individualize treatment on basis of SPECT findings, to monitor the treatment response and modify treatment, if necessary. In this article, we have reviewed the available studies in this regard from existing literature and tried to present the evidence for establishing the clinical role of brain SPECT in major psychiatric illnesses. PMID:25400359

  13. Metabolic Abnormalities in Lobar and Subcortical Brain Regions of Abstinent Polysubstance Users: Magnetic Resonance Spectroscopic Imaging

    PubMed Central

    Abé, Christoph; Mon, Anderson; Hoefer, Michael E.; Durazzo, Timothy C.; Pennington, David L.; Schmidt, Thomas P.; Meyerhoff, Dieter J.

    2013-01-01

    Aims: The aim of the study was to explore neurometabolic and associated cognitive characteristics of patients with polysubstance use (PSU) in comparison with patients with predominant alcohol use using proton magnetic resonance spectroscopy. Methods: Brain metabolite concentrations were examined in lobar and subcortical brain regions of three age-matched groups: 1-month-abstinent alcohol-dependent PSU, 1-month-abstinent individuals dependent on alcohol alone (ALC) and light drinking controls (CON). Neuropsychological testing assessed cognitive function. Results: While CON and ALC had similar metabolite levels, persistent metabolic abnormalities (primarily higher myo-inositol) were present in temporal gray matter, cerebellar vermis and lenticular nuclei of PSU. Moreover, lower cortical gray matter concentration of the neuronal marker N-acetylaspartate within PSU correlated with higher cocaine (but not alcohol) use quantities and with a reduced cognitive processing speed. Conclusions: These metabolite group differences reflect cellular/astroglial injury and/or dysfunction in alcohol-dependent PSU. Associations of other metabolite concentrations with neurocognitive performance suggest their functional relevance. The metabolic alterations in PSU may represent polydrug abuse biomarkers and/or potential targets for pharmacological and behavioral PSU-specific treatment. PMID:23797281

  14. Cognitive impairment as marker of diffuse brain abnormalities in early relapsing remitting multiple sclerosis

    PubMed Central

    Deloire, M; Salort, E; Bonnet, M; Arimone, Y; Boudineau, M; Amieva, H; Barroso, B; Ouallet, J; Pachai, C; Galliaud, E; Petry, K; Dousset, V; Fabrigoule, C; Brochet, B

    2005-01-01

    Objectives: To establish the frequency of cognitive impairment in a population based sample of patients with recently diagnosed relapsing-remitting multiple sclerosis (RRMS), and to determine the relation between cognitive abnormalities and the extent of macroscopic and microscopic tissue damage revealed by magnetic resonance imaging (MRI) and magnetisation transfer (MT) imaging. Methods: 58 patients with RRMS consecutively diagnosed in the previous six months in Aquitaine and 70 healthy controls underwent a battery of neuropsychological tests. Lesion load and atrophy indices (brain parenchymal fraction and ventricular fraction) were measured on brain MRI. MT ratio (MTR) histograms were obtained from lesions, normal appearing white matter (NAWM), and normal appearing grey matter (NAGM). Gadolinium enhanced lesions were counted. Results: 44 RRMS patients could be individually matched with healthy controls for age, sex, and education. Patients performed worse in tests of verbal and spatial memory, attention, information processing speed, inhibition, and conceptualisation. Measures of attention and information processing speed were correlated with lesion load, mean NAWM MTR, and the peak location of the NAGM MTR histogram in the patients. Multivariate regression analysis showed that lesion load and mean NAWM MTR were among the MR indices that were most significantly associated with impairment of attention and information processing speed in these early RRMS cases. Conclusions: Cognitive impairment appears to be common in the early stages of RRMS, mainly affecting attention, information processing speed, memory, inhibition, and conceptualisation. The severity of these deficits reflects the extent of the lesions and the severity of tissue disorganisation outside lesions. PMID:15774439

  15. Abnormal autonomic and associated brain activities during rest in autism spectrum disorder

    PubMed Central

    Eilam-Stock, Tehila; Xu, Pengfei; Cao, Miao; Gu, Xiaosi; Van Dam, Nicholas T.; Anagnostou, Evdokia; Kolevzon, Alexander; Soorya, Latha; Park, Yunsoo; Siller, Michael; He, Yong; Hof, Patrick R.

    2014-01-01

    Autism spectrum disorders are associated with social and emotional deficits, the aetiology of which are not well understood. A growing consensus is that the autonomic nervous system serves a key role in emotional processes, by providing physiological signals essential to subjective states. We hypothesized that altered autonomic processing is related to the socio-emotional deficits in autism spectrum disorders. Here, we investigated the relationship between non-specific skin conductance response, an objective index of sympathetic neural activity, and brain fluctuations during rest in high-functioning adults with autism spectrum disorder relative to neurotypical controls. Compared with control participants, individuals with autism spectrum disorder showed less skin conductance responses overall. They also showed weaker correlations between skin conductance responses and frontal brain regions, including the anterior cingulate and anterior insular cortices. Additionally, skin conductance responses were found to have less contribution to default mode network connectivity in individuals with autism spectrum disorders relative to controls. These results suggest that autonomic processing is altered in autism spectrum disorders, which may be related to the abnormal socio-emotional behaviours that characterize this condition. PMID:24424916

  16. Predicting the Probability of Abnormal Stimulated Growth Hormone Response in Children After Radiotherapy for Brain Tumors

    SciTech Connect

    Hua Chiaho; Wu Shengjie; Chemaitilly, Wassim; Lukose, Renin C.; Merchant, Thomas E.

    2012-11-15

    Purpose: To develop a mathematical model utilizing more readily available measures than stimulation tests that identifies brain tumor survivors with high likelihood of abnormal growth hormone secretion after radiotherapy (RT), to avoid late recognition and a consequent delay in growth hormone replacement therapy. Methods and Materials: We analyzed 191 prospectively collected post-RT evaluations of peak growth hormone level (arginine tolerance/levodopa stimulation test), serum insulin-like growth factor 1 (IGF-1), IGF-binding protein 3, height, weight, growth velocity, and body mass index in 106 children and adolescents treated for ependymoma (n = 72), low-grade glioma (n = 28) or craniopharyngioma (n = 6), who had normal growth hormone levels before RT. Normal level in this study was defined as the peak growth hormone response to the stimulation test {>=}7 ng/mL. Results: Independent predictor variables identified by multivariate logistic regression with high statistical significance (p < 0.0001) included IGF-1 z score, weight z score, and hypothalamic dose. The developed predictive model demonstrated a strong discriminatory power with an area under the receiver operating characteristic curve of 0.883. At a potential cutoff point of probability of 0.3 the sensitivity was 80% and specificity 78%. Conclusions: Without unpleasant and expensive frequent stimulation tests, our model provides a quantitative approach to closely follow the growth hormone secretory capacity of brain tumor survivors. It allows identification of high-risk children for subsequent confirmatory tests and in-depth workup for diagnosis of growth hormone deficiency.

  17. Technetium-99m bis (aminoethanethiol) complexes with amine sidechains--potential brain perfusion imaging agents for SPECT

    SciTech Connect

    Efange, S.M.; Kung, H.F.; Billings, J.; Guo, Y.Z.; Blau, M.

    1987-06-01

    In an effort to develop new clinically useful technetium-99m bis(aminoethanethiol) ((/sup 99m/Tc)BAT) complexes for the evaluation of regional cerebral perfusion, two new BAT ligands containing amines in the sidechain were synthesized and subsequently complexed with /sup 99m/Tc to yield the target complexes: (/sup 99m/Tc)DEA and (/sup 99m/Tc)TMPDA. Each complex was obtained as mixtures of two isomers, syn and anti, which were separated chromatographically. In biodistribution studies, both isomers of (/sup 99m/Tc)TMPDA showed little uptake in the brain. In contrast, the brain uptake values at 2 and 15 min for (/sup 99m/Tc)DEA-anti were 0.99 and 0.26, whereas, the corresponding values for DEA-syn were 2.27, 0.64% dose/organ, respectively. Autoradiographic studies (in rats) using both isomers of (/sup 99m/Tc)DEA show a fixed regional distribution and a higher concentration of radioactivity in the gray matter relative to the white matter. Planar imaging using (/sup 99m/Tc)DEA-syn clearly demonstrates localization of the complex in the brain with a T 1/2 of 41 min, suggesting some potential for use with single photon emission computed tomography.

  18. 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.

  19. Defining Core and Penumbra in Ischemic Stroke: A Voxel- and Volume-Based Analysis of Whole Brain CT Perfusion

    PubMed Central

    Yu, Yannan; Han, Quan; Ding, Xinfa; Chen, Qingmeng; Ye, Keqi; Zhang, Sheng; Yan, Shenqiang; Campbell, Bruce C. V.; Parsons, Mark W.; Wang, Shaoshi; Lou, Min

    2016-01-01

    Whole brain computed tomography perfusion (CTP) has the potential to select eligible patients for reperfusion therapy. We aimed to find the optimal thresholds on baseline CTP for ischemic core and penumbra in acute ischemic stroke. We reviewed patients with acute ischemic stroke in the anterior circulation, who underwent baseline whole brain CTP, followed by intravenous thrombolysis and perfusion imaging at 24 hours. Patients were divided into those with major reperfusion (to define the ischemic core) and minimal reperfusion (to define the extent of penumbra). Receiver operating characteristic (ROC) analysis and volumetric consistency analysis were performed separately to determine the optimal threshold by Youden’s Index and mean magnitude of volume difference, respectively. From a series of 103 patients, 22 patients with minimal-reperfusion and 47 with major reperfusion were included. Analysis revealed delay time ≥ 3 s most accurately defined penumbra (AUC = 0.813; 95% CI, 0.812-0.814, mean magnitude of volume difference = 29.1 ml). The optimal threshold for ischemic core was rCBF ≤ 30% within delay time ≥ 3 s (AUC = 0.758; 95% CI, 0.757-0.760, mean magnitude of volume difference = 10.8 ml). In conclusion, delay time ≥ 3 s and rCBF ≤ 30% within delay time ≥ 3 s are the optimal thresholds for penumbra and core, respectively. These results may allow the application of the mismatch on CTP to reperfusion therapy. PMID:26860196

  20. Early Cerebral Circulation Disturbance in Patients Suffering from Severe Traumatic Brain Injury (TBI): A Xenon CT and Perfusion CT Study

    PubMed Central

    HONDA, Mitsuru; ICHIBAYASHI, Ryo; YOKOMURO, Hiroki; YOSHIHARA, Katsunori; MASUDA, Hiroyuki; HAGA, Daisuke; SEIKI, Yoshikatsu; KUDOH, Chiaki; KISHI, Taichi

    2016-01-01

    Traumatic brain injury (TBI) is widely known to cause dynamic changes in cerebral blood flow (CBF). Ischemia is a common and deleterious secondary injury following TBI. Detecting early ischemia in TBI patients is important to prevent further advancement and deterioration of the brain tissue. The purpose of this study was to clarify the cerebral circulatory disturbance during the early phase and whether it can be used to predict patient outcome. A total of 90 patients with TBI underwent a xenon-computed tomography (Xe-CT) and subsequently perfusion CT to evaluate the cerebral circulation on days 1–3. We measured CBF using Xe-CT and mean transit time (MTT: the width between two inflection points [maximum upward slope and maximum downward slope from inflow to outflow of the contrast agent]) using perfusion CT and calculated the cerebral blood volume (CBV) using the AZ-7000W98 computer system. The relationships of the hemodynamic parameters CBF, MTT, and CBV to the Glasgow Coma Scale (GCS) score and the Glasgow Outcome Scale (GOS) score were examined. There were no significant differences in CBF, MTT, and CBV among GCS3–4, GCS5–6, and GCS7–8 groups. The patients with a favorable outcome (GR and MD) had significantly higher CBF and lower MTT than those with an unfavorable one (SD, VS, or D). The discriminant analysis of these parameters could predict patient outcome with a probability of 70.6%. During the early phase, CBF reduction and MTT prolongation might influence the clinical outcome of TBI. These parameters are helpful for evaluating the severity of cerebral circulatory disturbance and predicting the outcome of TBI patients. PMID:27356957

  1. Early Cerebral Circulation Disturbance in Patients Suffering from Severe Traumatic Brain Injury (TBI): A Xenon CT and Perfusion CT Study.

    PubMed

    Honda, Mitsuru; Ichibayashi, Ryo; Yokomuro, Hiroki; Yoshihara, Katsunori; Masuda, Hiroyuki; Haga, Daisuke; Seiki, Yoshikatsu; Kudoh, Chiaki; Kishi, Taichi

    2016-08-15

    Traumatic brain injury (TBI) is widely known to cause dynamic changes in cerebral blood flow (CBF). Ischemia is a common and deleterious secondary injury following TBI. Detecting early ischemia in TBI patients is important to prevent further advancement and deterioration of the brain tissue. The purpose of this study was to clarify the cerebral circulatory disturbance during the early phase and whether it can be used to predict patient outcome. A total of 90 patients with TBI underwent a xenon-computed tomography (Xe-CT) and subsequently perfusion CT to evaluate the cerebral circulation on days 1-3. We measured CBF using Xe-CT and mean transit time (MTT: the width between two inflection points [maximum upward slope and maximum downward slope from inflow to outflow of the contrast agent]) using perfusion CT and calculated the cerebral blood volume (CBV) using the AZ-7000W98 computer system. The relationships of the hemodynamic parameters CBF, MTT, and CBV to the Glasgow Coma Scale (GCS) score and the Glasgow Outcome Scale (GOS) score were examined. There were no significant differences in CBF, MTT, and CBV among GCS3-4, GCS5-6, and GCS7-8 groups. The patients with a favorable outcome (GR and MD) had significantly higher CBF and lower MTT than those with an unfavorable one (SD, VS, or D). The discriminant analysis of these parameters could predict patient outcome with a probability of 70.6%. During the early phase, CBF reduction and MTT prolongation might influence the clinical outcome of TBI. These parameters are helpful for evaluating the severity of cerebral circulatory disturbance and predicting the outcome of TBI patients. PMID:27356957

  2. Intrathoracic Pressure Regulation Improves Cerebral Perfusion and Cerebral Blood Flow in a Porcine Model of Brain Injury.

    PubMed

    Metzger, Anja; Rees, Jennifer; Kwon, Young; Matsuura, Timothy; McKnite, Scott; Lurie, Keith G

    2015-08-01

    Brain injury is a leading cause of death and disability in children and adults in their most productive years. Use of intrathoracic pressure regulation (IPR) to generate negative intrathoracic pressure during the expiratory phase of positive pressure ventilation improves mean arterial pressure and 24-h survival in porcine models of hemorrhagic shock and cardiac arrest and has been demonstrated to decrease intracranial pressure (ICP) and cerebral perfusion pressure (CPP) in these models. Application of IPR for 240 min in a porcine model of intracranial hypertension (ICH) will increase CPP when compared with controls. Twenty-three female pigs were subjected to focal brain injury by insertion of an epidural Foley catheter inflated with 3 mL of saline. Animals were randomized to treatment for 240 min with IPR set to a negative expiratory phase pressure of -12 cmH2O or no IPR therapy. Intracranial pressure, mean arterial pressure, CPP, and cerebral blood flow (CBF) were evaluated. Intrathoracic pressure regulation significantly improved mean CPP and CBF. Specifically, mean CPP after 90, 120, 180, and 240 min of IPR use was 43.7 ± 2.8 mmHg, 44.0 ± 2.7 mmHg, 44.5 ± 2.8 mmHg, and 43.1 ± 1.9 mmHg, respectively; a significant increase from ICH study baseline (39.5 ± 1.7 mmHg) compared with control animals in which mean CPP was 36.7 ± 1.4 mmHg (ICH study baseline) and then 35.9 ± 2.1 mmHg, 33.7 ± 2.8 mmHg, 33.9 ± 3.0 mmHg, and 36.0 ± 2.7 mmHg at 90, 120, 180, and 240 min, respectively (P < 0.05 for all time points). Cerebral blood flow, as measured by an invasive CBF probe, increased in the IPR group (34 ± 4 mL/100 g-min to 49 ± 7 mL/100 g-min at 90 min) but not in controls (27 ± 1 mL/100 g-min to 25 ± 5 mL/100 g-min at 90 min) (P = 0.01). Arterial pH remained unchanged during the entire period of IPR compared with baseline values and control values. In this anesthetized pig model of ICH, treatment with IPR significantly improved CPP and CBF. This therapy may be

  3. Cross-Sectional and Longitudinal Abnormalities in Brain Structure in Children with Severe Mood Dysregulation or Bipolar Disorder

    ERIC Educational Resources Information Center

    Adleman, Nancy E.; Fromm, Stephen J.; Razdan, Varun; Kayser, Reilly; Dickstein, Daniel P.; Brotman, Melissa A.; Pine, Daniel S.; Leibenluft, Ellen

    2012-01-01

    Background: There is debate as to whether chronic irritability (operationalized as severe mood dysregulation, SMD) is a developmental form of bipolar disorder (BD). Although structural brain abnormalities in BD have been demonstrated, no study compares neuroanatomy among SMD, BD, and healthy volunteers (HV) either cross-sectionally or over time.…

  4. Brain Gray Matter Abnormalities in First-Episode, Treatment-Naive Children with Obsessive-Compulsive Disorder.

    PubMed

    Cheng, Bochao; Cai, Wu; Wang, Xiuli; Lei, Du; Guo, Yingkun; Yang, Xun; Wu, Qizhu; Gong, Jianping; Gong, Qiyong; Ning, Gang

    2016-01-01

    Although several magnetic resonance imaging (MRI) studies have been conducted in children with obsessive-compulsive disorder (OCD), the brain structural abnormalities in OCD, especially in children, are not yet well characterized. We aimed to identify gray matter (GM) abnormalities in the early stage of pediatric OCD and examine the relationship between these structural abnormalities with clinical characteristics. Examinations of 30 first-episode, treatment-naive pediatric OCD patients without any comorbidities and 30 matched healthy controls (HCs) were performed with 3.0 T magnetic resonance imaging (MRI). Voxel-based morphometry (VBM) following Diffeomorphic Anatomical Registration using Exponentiated Lie algebra (DARTEL) was used to conduct voxel-wise tests for group differences in regional gray matter volume (GMV). Compared to HCs, the patient group exhibited more GMV in the bilateral putamen and left orbitofrontal cortex (OFC) and less GMV in the left inferior parietal lobule (IPL). The GMV alternation in the right putamen of OCD patients was positively correlated with Hamilton Anxiety Rating Scale (HAM-A) scores, while the GMV alternation in the left IPL exhibited a trend to negatively correlate with HAM-A scores. Our current results suggest that the GM abnormalities were defined in the early stage of pediatric OCD. Moreover, these findings provided further evidence of brain GM abnormalities that are not only present in the classical fronto-striatal-thalamic circuit but also in the default mode network (DMN), which may represent the interaction of abnormally functional organization of both network in pediatric OCD. PMID:27445736

  5. Brain Gray Matter Abnormalities in First-Episode, Treatment-Naive Children with Obsessive-Compulsive Disorder

    PubMed Central

    Cheng, Bochao; Cai, Wu; Wang, Xiuli; Lei, Du; Guo, Yingkun; Yang, Xun; Wu, Qizhu; Gong, Jianping; Gong, Qiyong; Ning, Gang

    2016-01-01

    Although several magnetic resonance imaging (MRI) studies have been conducted in children with obsessive-compulsive disorder (OCD), the brain structural abnormalities in OCD, especially in children, are not yet well characterized. We aimed to identify gray matter (GM) abnormalities in the early stage of pediatric OCD and examine the relationship between these structural abnormalities with clinical characteristics. Examinations of 30 first-episode, treatment-naive pediatric OCD patients without any comorbidities and 30 matched healthy controls (HCs) were performed with 3.0 T magnetic resonance imaging (MRI). Voxel-based morphometry (VBM) following Diffeomorphic Anatomical Registration using Exponentiated Lie algebra (DARTEL) was used to conduct voxel-wise tests for group differences in regional gray matter volume (GMV). Compared to HCs, the patient group exhibited more GMV in the bilateral putamen and left orbitofrontal cortex (OFC) and less GMV in the left inferior parietal lobule (IPL). The GMV alternation in the right putamen of OCD patients was positively correlated with Hamilton Anxiety Rating Scale (HAM-A) scores, while the GMV alternation in the left IPL exhibited a trend to negatively correlate with HAM-A scores. Our current results suggest that the GM abnormalities were defined in the early stage of pediatric OCD. Moreover, these findings provided further evidence of brain GM abnormalities that are not only present in the classical fronto–striatal–thalamic circuit but also in the default mode network (DMN), which may represent the interaction of abnormally functional organization of both network in pediatric OCD. PMID:27445736

  6. Brain state-dependent abnormal LFP activity in the auditory cortex of a schizophrenia mouse model

    PubMed Central

    Nakao, Kazuhito; Nakazawa, Kazu

    2014-01-01

    In schizophrenia, evoked 40-Hz auditory steady-state responses (ASSRs) are impaired, which reflects the sensory deficits in this disorder, and baseline spontaneous oscillatory activity also appears to be abnormal. It has been debated whether the evoked ASSR impairments are due to the possible increase in baseline power. GABAergic interneuron-specific NMDA receptor (NMDAR) hypofunction mutant mice mimic some behavioral and pathophysiological aspects of schizophrenia. To determine the presence and extent of sensory deficits in these mutant mice, we recorded spontaneous local field potential (LFP) activity and its click-train evoked ASSRs from primary auditory cortex of awake, head-restrained mice. Baseline spontaneous LFP power in the pre-stimulus period before application of the first click trains was augmented at a wide range of frequencies. However, when repetitive ASSR stimuli were presented every 20 s, averaged spontaneous LFP power amplitudes during the inter-ASSR stimulus intervals in the mutant mice became indistinguishable from the levels of control mice. Nonetheless, the evoked 40-Hz ASSR power and their phase locking to click trains were robustly impaired in the mutants, although the evoked 20-Hz ASSRs were also somewhat diminished. These results suggested that NMDAR hypofunction in cortical GABAergic neurons confers two brain state-dependent LFP abnormalities in the auditory cortex; (1) a broadband increase in spontaneous LFP power in the absence of external inputs, and (2) a robust deficit in the evoked ASSR power and its phase-locking despite of normal baseline LFP power magnitude during the repetitive auditory stimuli. The “paradoxically” high spontaneous LFP activity of the primary auditory cortex in the absence of external stimuli may possibly contribute to the emergence of schizophrenia-related aberrant auditory perception. PMID:25018691

  7. Effects of minocycline add-on treatment on brain morphometry and cerebral perfusion in recent-onset schizophrenia.

    PubMed

    Chaves, Cristiano; Marque, Cristiane R; Maia-de-Oliveira, João P; Wichert-Ana, Lauro; Ferrari, Thiago B; Santos, Antonio C; Araújo, David; Machado-de-Sousa, João P; Bressan, Rodrigo A; Elkis, Helio; Crippa, José A; Guimarães, Francisco S; Zuardi, Antônio W; Baker, Glen B; Dursun, Serdar M; Hallak, Jaime E C

    2015-02-01

    Increasing evidence suggests that the tetracycline antibiotic minocycline has neuroprotective effects and is a potential treatment for schizophrenia. However, the mechanisms of action of minocycline in the CNS remain elusive. The aim of this study was to investigate the effects of minocycline on brain morphology and cerebral perfusion in patients with recent-onset schizophrenia after 12months of a randomized double-blind, placebo-controlled clinical trial of minocycline add-on treatment. This study included 24 outpatients with recent-onset schizophrenia randomized for 12months of adjuvant treatment with minocycline (200mg/d) or placebo. MRI (1.5T) and [(99m)Tc]-ECD SPECT brain scans were performed at the end of the 12-month of trial. Between-condition comparisons of SPECT and MRI brain images were performed using statistical parametric mapping and analyzed by voxel-based morphometry (VBM). Minocycline adjuvant treatment significantly reduced positive and negative symptoms when compared with placebo. The VBM analysis of MRI scans showed that the patients in the placebo group had significant lower gray matter volumes in the midposterior cingulate cortex and in the precentral gyrus in comparison with the patients in the minocycline group. In addition, a decreased ECD uptake in the minocycline condition was observed in fronto-temporal areas. These results suggest that minocycline may protect against gray matter loss and modulate fronto-temporal areas involved in the pathophysiology of schizophrenia. Furthermore, minocycline add-on treatment may be a potential treatment in the early stages of schizophrenia and may ameliorate clinical deterioration and brain alterations observed in this period.

  8. Are structural brain abnormalities associated with suicidal behavior in patients with psychotic disorders?

    PubMed

    Giakoumatos, Christoforos I; Tandon, Neeraj; Shah, Jai; Mathew, Ian T; Brady, Roscoe O; Clementz, Brett A; Pearlson, Godfrey D; Thaker, Gunvant K; Tamminga, Carol A; Sweeney, John A; Keshavan, Matcheri S

    2013-10-01

    Suicide represents a major health problem world-wide. Nevertheless, the understanding of the neurobiological underpinnings of suicidal behavior remains far from complete. We compared suicide attempters to non-attempters, and high vs. low lethality attempters, to identify brain regions associated with suicidal behavior in patients with psychotic disorders. 489 individuals with schizophrenia, schizoaffective disorder, or psychotic bipolar disorder I and 262 healthy controls enrolled in the B-SNIP study were studied. Groups were compared by attempt history and the highest medical lethality of previous suicide attempts. 97 patients had a history of a high lethality attempt, 51 of a low lethality attempt and 341 had no attempt history. Gray matter volumes were obtained from 3T structural MRI scans using FreeSurfer. ANCOVAs were used to examine differences between groups, followed by Hochberg multiple comparison correction. Compared to non-attempters, attempters had significantly less gray matter volume in bilateral inferior temporal and superior temporal cortices, left superior parietal, thalamus and supramarginal regions, right insula, superior frontal and rostral middle frontal regions. Among attempters, a history of high lethality attempts was associated with significantly smaller volumes in the left lingual gyrus and right cuneus. Compared to non-attempters, low lethality attempters had significant decreases in the left supramarginal gyrus, thalamus and the right insula. Structural brain abnormalities may distinguish suicide attempters from non-attempters and high from low lethality attempters among individuals with psychotic disorders. Regions in which differences were observed are part of neural circuitries that mediate inhibition, impulsivity and emotion, visceral, visual and auditory perception.

  9. Abnormal Subcortical Brain Morphology in Patients with Knee Osteoarthritis: A Cross-sectional Study

    PubMed Central

    Mao, Cui Ping; Bai, Zhi Lan; Zhang, Xiao Na; Zhang, Qiu Juan; Zhang, Lei

    2016-01-01

    Despite the involvement of subcortical brain structures in the pathogenesis of chronic pain and persistent pain as the defining symptom of knee osteoarthritis (KOA), little attention has been paid to the morphometric measurements of these subcortical nuclei in patients with KOA. The purpose of this study is to explore the potential morphological abnormalities of subcortical brain structures in patients with KOA as compared to the healthy control subjects by using high-resolution MRI. Structural MR data were acquired from 26 patients with KOA and 31 demographically similar healthy individuals. The MR data were analyzed by using FMRIB’s integrated registration and segmentation tool. Both volumetric analysis and surface-based shape analysis were performed to characterize the subcortical morphology. The normalized volumes of bilateral caudate nucleus were significantly smaller in the KOA group than in the control group (P = 0.004). There was also a trend toward smaller volume of the hippocampus in KOA as compared to the control group (P = 0.027). Detailed surface analyses further localized these differences with a greater involvement of the left hemisphere (P < 0.05, corrected) for the caudate nucleus. Hemispheric asymmetry (right larger than left) of the caudate nucleus was found in both KOA and control groups. Besides, no significant correlation was found between the structural data and pain intensities. Our results indicated that patients with KOA had statistically significant smaller normalized volumes of bilateral caudate nucleus and a trend toward smaller volume of the hippocampus as compared to the control subjects. Further investigations are necessary to characterize the role of caudate nucleus in the course of chronicity of pain associated with KOA. PMID:26834629

  10. Sources of abnormal EEG activity in the presence of brain lesions.

    PubMed

    Fernández-Bouzas, A; Harmony, T; Bosch, J; Aubert, E; Fernández, T; Valdés, P; Silva, J; Marosi, E; Martínez-López, M; Casián, G

    1999-04-01

    In routine clinical EEG, a common origin is assumed for delta and theta rhythms produced by brain lesions. In previous papers, we have provided some experimental support, based on High Resolution qEEG and dipole fitting in the frequency domain, for the hypothesis that delta and theta spectral power have independent origins related to lesion and edema respectively. This paper describes the results obtained with Frequency Domain VARETA (FD-VARETA) in a group of 13 patients with cortical space-occupying lesions, in order to: 1) Test the accuracy of FD-VARETA for the localization of brain lesions, and 2) To provide further support for the independent origin of delta and theta components. FD VARETA is a distributed inverse solution, constrained by the Montreal Neurological Institute probabilistic atlas that estimates the spectra of EEG sources. In all patients, logarithmic transformed source spectra were compared with age-matched normative values, defining the Z source spectrum. Maximum Z values were found in 10 patients within the delta band (1.56 to 3.12 Hz); the spatial extent of these sources in the atlas corresponded with the location of the tumors in the CT. In 2 patients with small metastases and large volumes of edema and in a patient showing only edema, maximum Z values were found between 4.29 and 5.12 Hz. The spatial extent of the sources at these frequencies was within the volume of the edema in the CT. These results provided strong support to the hypothesis that both delta and theta abnormal EEG activities are the counterparts of two different pathophysiological processes. PMID:10358783

  11. Brain perfusion monitoring with frequency-domain and continuous-wave near-infrared spectroscopy: a cross-correlation study in newborn piglets

    NASA Astrophysics Data System (ADS)

    Zhang, G.; Katz, A.; Alfano, R. R.; Kofinas, A. D.; Kofinas, D. A.; Stubblefield, P. G.; Rosenfeld, W.; Beyer, D.; Maulik, D.; Stankovic, M. R.

    2000-11-01

    The newborn piglet brain model was used to correlate continuous-wave (CW) and frequency-domain (FD) near-infrared spectroscopy. Six ventilated and instrumented newborn piglets were subjected to a series of manipulations in blood oxygenation with the effects on brain perfusion known to be associated with brain hypoxia-ischaemia. An excellent agreement between the CW and FD was demonstrated. This agreement improved when the scattering properties (determined by the FD device) were employed to calculate the differential pathlength factor, an important step in CW data processing.

  12. Maternal autoantibodies are associated with abnormal brain enlargement in a subgroup of children with autism spectrum disorder.

    PubMed

    Nordahl, Christine Wu; Braunschweig, Daniel; Iosif, Ana-Maria; Lee, Aaron; Rogers, Sally; Ashwood, Paul; Amaral, David G; Van de Water, Judy

    2013-05-01

    Autism spectrum disorder (ASD) is very heterogeneous and multiple subtypes and etiologies likely exist. The maternal immune system has been implicated in the pathogenesis of some forms of ASD. Previous studies have identified the presence of specific maternal IgG autoantibodies with reactivity to fetal brain proteins at 37 and 73kDa in up to 12% of mothers of children with ASD. The current study evaluates the presence of these autoantibodies in an independent cohort of mothers of 181 preschool-aged male children (131 ASD, 50 typically developing (TD) controls). We also investigated whether ASD children born to mothers with these autism-specific maternal IgG autoantibodies exhibit a distinct neural phenotype by evaluating total brain volume using structural magnetic resonance imaging (MRI). Of the 131 ASD children, 10 (7.6%) were born to mothers with the 37/73kDa IgG autoantibodies (ASD-IgG). The mothers of the remaining ASD children and all TD controls were negative for these paired autoantibodies. While both ASD groups exhibited abnormal brain enlargement that is commonly observed in this age range, the ASD-IgG group exhibited a more extreme 12.1% abnormal brain enlargement relative to the TD controls. In contrast, the remaining ASD children exhibited a smaller 4.4% abnormal brain enlargement relative to TD controls. Lobar and tissue type analyses revealed that the frontal lobe is selectively enlarged in the ASD-IgG group and that both gray and white matter are similarly affected. These results suggest that maternal autoantibodies associated with autism spectrum disorder may impact brain development leading to abnormal enlargement.

  13. Abnormal high-energy phosphate molecule metabolism during regional brain activation in patients with bipolar disorder.

    PubMed

    Yuksel, C; Du, F; Ravichandran, C; Goldbach, J R; Thida, T; Lin, P; Dora, B; Gelda, J; O'Connor, L; Sehovic, S; Gruber, S; Ongur, D; Cohen, B M

    2015-09-01

    Converging evidence suggests bioenergetic abnormalities in bipolar disorder (BD). In the brain, phosphocreatine (PCr) acts a reservoir of high-energy phosphate (HEP) bonds, and creatine kinases (CK) catalyze the transfer of HEP from adenosine triphosphate (ATP) to PCr and from PCr back to ATP, at times of increased need. This study examined the activity of this mechanism in BD by measuring the levels of HEP molecules during a stimulus paradigm that increased local energy demand. Twenty-three patients diagnosed with BD-I and 22 healthy controls (HC) were included. Levels of phosphorus metabolites were measured at baseline and during visual stimulation in the occipital lobe using (31)P magnetic resonance spectroscopy at 4T. Changes in metabolite levels showed different patterns between the groups. During stimulation, HC had significant reductions in PCr but not in ATP, as expected. In contrast, BD patients had significant reductions in ATP but not in PCr. In addition, PCr/ATP ratio was lower at baseline in patients, and there was a higher change in this measure during stimulation. This pattern suggests a disease-related failure to replenish ATP from PCr through CK enzyme catalysis during tissue activation. Further studies measuring the CK flux in BD are required to confirm and extend this finding.

  14. Functional Connectivity Abnormalities of Brain Regions with Structural Deficits in Young Adult Male Smokers

    PubMed Central

    Bu, Limei; Yu, Dahua; Su, Shaoping; Ma, Yao; von Deneen, Karen M.; Luo, Lin; Zhai, Jinquan; Liu, Bo; Cheng, Jiadong; Guan, Yanyan; Li, Yangding; Bi, Yanzhi; Xue, Ting; Lu, Xiaoqi; Yuan, Kai

    2016-01-01

    Smoking is one of the most prevalent dependence disorders. Previous studies have detected structural and functional deficits in smokers. However, few studies focused on the changes of resting state functional connectivity (RSFC) of the brain regions with structural deficits in young adult smokers. Twenty-six young adult smokers and 26 well-matched healthy non-smokers participated in our study. Voxel-based morphometry (VBM) and RSFC were employed to investigate the structural and functional changes in young adult smokers. Compared with healthy non-smokers, young smokers showed increased gray matter (GM) volume in the left putamen and decreased GM volume in the left anterior cingulate cortex (ACC). Moreover, GM volume in the left ACC has a negative correlation trend with pack-years and GM volume in the left putamen was positively correlated with pack-years. The left ACC and putamen with abnormal volumes were chosen as the regions of interest (ROIs) for the RSFC analysis. We found that smokers showed increased RSFC between the left ACC and right amygdala and between the left putamen and right anterior insula. We revealed structural and functional deficits within the frontostriatal circuits in young smokers, which may shed new insights into the neural mechanisms of smoking. PMID:27757078

  15. Abnormal error monitoring in math-anxious individuals: evidence from error-related brain potentials.

    PubMed

    Suárez-Pellicioni, Macarena; Núñez-Peña, María Isabel; Colomé, Angels

    2013-01-01

    This study used event-related brain potentials to investigate whether math anxiety is related to abnormal error monitoring processing. Seventeen high math-anxious (HMA) and seventeen low math-anxious (LMA) individuals were presented with a numerical and a classical Stroop task. Groups did not differ in terms of trait or state anxiety. We found enhanced error-related negativity (ERN) in the HMA group when subjects committed an error on the numerical Stroop task, but not on the classical Stroop task. Groups did not differ in terms of the correct-related negativity component (CRN), the error positivity component (Pe), classical behavioral measures or post-error measures. The amplitude of the ERN was negatively related to participants' math anxiety scores, showing a more negative amplitude as the score increased. Moreover, using standardized low resolution electromagnetic tomography (sLORETA) we found greater activation of the insula in errors on a numerical task as compared to errors in a non-numerical task only for the HMA group. The results were interpreted according to the motivational significance theory of the ERN.

  16. Neural tube defects and abnormal brain development in F52-deficient mice.

    PubMed Central

    Wu, M; Chen, D F; Sasaoka, T; Tonegawa, S

    1996-01-01

    F52 is a myristoylated, alanine-rich substrate for protein kinase C. We have generated F52-deficient mice by the gene targeting technique. These mutant mice manifest severe neural tube defects that are not associated with other complex malformations, a phenotype reminiscent of common human neural tube defects. The neural tube defects observed include both exencephaly and spina bifida, and the phenotype exhibits partial penetrance with about 60% of homozygous embryos developing neural tube defects. Exencephaly is the prominent type of defect and leads to high prenatal lethality. Neural tube defects are observed in a smaller percentage of heterozygous embryos (about 10%). Abnormal brain development and tail formation occur in homozygous mutants and are likely to be secondary to the neural tube defects. Disruption of F52 in mice therefore identifies a gene whose mutation results in isolated neural tube defects and may provide an animal model for common human neural tube defects. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:8700893

  17. Diffusion abnormalities of the corpus callosum in patients receiving bevacizumab for malignant brain tumors: suspected treatment toxicity.

    PubMed

    Futterer, Stephen F; Nemeth, Alexander J; Grimm, Sean A; Ragin, Ann B; Chandler, James P; Muro, Kenji; Marymont, Maryanne H; Raizer, Jeffrey J

    2014-05-01

    Bevacizumab has been reported to cause diffusion restriction in the tumor bed of patients with malignant gliomas. This study evaluated prolonged diffusion restriction, in the corpus callosum (CC), of patients with malignant brain tumors treated with bevacizumab. We retrospectively reviewed our database of patients treated with bevacizumab for malignant brain tumors looking for those with restricted diffusion in the CC. CC ADC ratio measurements were obtained prior to and following treatment. Correlation was made with biopsy (n = 3) and MR perfusion (n = 7) and PET (n = 4). The temporal evolution of these changes relative to therapy was examined with mixed effects regression analysis. Nine patients (eight malignant gliomas, one malignant meningioma) out of 146 patients were found to have developed areas of diffusion restriction in the CC. These areas tended to enlarge and coalesce over serial MRIs and persisted for up to 22 months. Hypoperfusion was demonstrated in MR perfusion in 7/7. PET was hypometabolic in all 4. Biopsy of the CC showed no tumor in 3/3. ADC ratio measurements indicated a significant overall effect of time (F(16,60) = 11.2; p < 0.0001), consistent with persistent diffusion restriction over the measured time periods. Bevacizumab causes prolonged diffusion restriction in the CC. The negative MR perfusion, FDG PET and histopathology suggest this is a toxicity of bevacizumab and not active tumor. Awareness of these changes can assist in patient care. PMID:24574050

  18. Subcortical brain volume abnormalities in 2028 individuals with schizophrenia and 2540 healthy controls via the ENIGMA consortium.

    PubMed

    van Erp, T G M; Hibar, D P; Rasmussen, J M; Glahn, D C; Pearlson, G D; Andreassen, O A; Agartz, I; Westlye, L T; Haukvik, U K; Dale, A M; Melle, I; Hartberg, C B; Gruber, O; Kraemer, B; Zilles, D; Donohoe, G; Kelly, S; McDonald, C; Morris, D W; Cannon, D M; Corvin, A; Machielsen, M W J; Koenders, L; de Haan, L; Veltman, D J; Satterthwaite, T D; Wolf, D H; Gur, R C; Gur, R E; Potkin, S G; Mathalon, D H; Mueller, B A; Preda, A; Macciardi, F; Ehrlich, S; Walton, E; Hass, J; Calhoun, V D; Bockholt, H J; Sponheim, S R; Shoemaker, J M; van Haren, N E M; Hulshoff Pol, H E; Pol, H E H; Ophoff, R A; Kahn, R S; Roiz-Santiañez, R; Crespo-Facorro, B; Wang, L; Alpert, K I; Jönsson, E G; Dimitrova, R; Bois, C; Whalley, H C; McIntosh, A M; Lawrie, S M; Hashimoto, R; Thompson, P M; Turner, J A

    2016-04-01

    The profile of brain structural abnormalities in schizophrenia is still not fully understood, despite decades of research using brain scans. To validate a prospective meta-analysis approach to analyzing multicenter neuroimaging data, we analyzed brain MRI scans from 2028 schizophrenia patients and 2540 healthy controls, assessed with standardized methods at 15 centers worldwide. We identified subcortical brain volumes that differentiated patients from controls, and ranked them according to their effect sizes. Compared with healthy controls, patients with schizophrenia had smaller hippocampus (Cohen's d=-0.46), amygdala (d=-0.31), thalamus (d=-0.31), accumbens (d=-0.25) and intracranial volumes (d=-0.12), as well as larger pallidum (d=0.21) and lateral ventricle volumes (d=0.37). Putamen and pallidum volume augmentations were positively associated with duration of illness and hippocampal deficits scaled with the proportion of unmedicated patients. Worldwide cooperative analyses of brain imaging data support a profile of subcortical abnormalities in schizophrenia, which is consistent with that based on traditional meta-analytic approaches. This first ENIGMA Schizophrenia Working Group study validates that collaborative data analyses can readily be used across brain phenotypes and disorders and encourages analysis and data sharing efforts to further our understanding of severe mental illness. PMID:26033243

  19. Brain positron emission tomography in splenectomized adults with β-thalassemia intermedia: uncovering yet another covert abnormality.

    PubMed

    Musallam, Khaled M; Nasreddine, Wassim; Beydoun, Ahmad; Hourani, Roula; Hankir, Ahmed; Koussa, Suzanne; Haidar, Mohamad; Taher, Ali T

    2012-02-01

    Covert brain infarction is an emerging concern in patients with β-thalassemia intermedia (TI). We have recently observed a high prevalence (60%) of silent brain infarction on brain magnetic resonance imaging (MRI) in 30 splenectomized adults with TI. In this work, we further evaluate cerebral involvement in the same 30 patients using fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) scanning. The median age was 32 years (range, 18-54 years) with a male to female ratio of 13:17. Nineteen patients (63.3%) had evidence of decreased neuronal function on PET-CT. Involvement was mostly left sided, multiple, and most commonly in the temporal and parietal lobes. Elevated liver iron concentration, beyond 15 mg Fe/g dry weight, characterized patients with decreased neuronal function. The concordance rate between brain MRI and PET-CT for the detection of brain abnormality was only 36.7% (Kappa 0.056, P = 0.757), highlighting that both modalities reveal different types of brain pathology. Decreased neuronal function is a common finding in patients with TI and is associated with iron overload. Moreover, the addition of PET-CT to MRI identifies a greater proportion of TI patients with silent neuroimaging abnormalities.

  20. 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

  1. Altered structure of cortical sulci in gilles de la Tourette syndrome: Further support for abnormal brain development.

    PubMed

    Muellner, Julia; Delmaire, Christine; Valabrégue, Romain; Schüpbach, Michael; Mangin, Jean-François; Vidailhet, Marie; Lehéricy, Stéphane; Hartmann, Andreas; Worbe, Yulia

    2015-04-15

    Gilles de la Tourette syndrome is a neurodevelopmental disorder characterized by the presence of motor and vocal tics. We hypothesized that patients with this syndrome would present an aberrant pattern of cortical formation, which could potentially reflect global alterations of brain development. Using 3 Tesla structural neuroimaging, we compared sulcal depth, opening, and length and thickness of sulcal gray matter in 52 adult patients and 52 matched controls. Cortical sulci were automatically reconstructed and identified over the whole brain, using BrainVisa software. We focused on frontal, parietal, and temporal cortical regions, in which abnormal structure and functional activity were identified in previous neuroimaging studies. Partial correlation analysis with age, sex, and treatment as covariables of noninterest was performed amongst relevant clinical and neuroimaging variables in patients. Patients with Gilles de la Tourette syndrome showed lower depth and reduced thickness of gray matter in the pre- and post-central as well as superior, inferior, and internal frontal sulci. In patients with associated obsessive-compulsive disorder, additional structural changes were found in temporal, insular, and olfactory sulci. Crucially, severity of tics and of obsessive-compulsive disorder measured by Yale Global Tic severity scale and Yale-Brown Obsessive-Compulsive scale, respectively, correlated with structural sulcal changes in sensorimotor, temporal, dorsolateral prefrontal, and middle cingulate cortical areas. Patients with Gilles de la Tourette syndrome displayed an abnormal structural pattern of cortical sulci, which correlated with severity of clinical symptoms. Our results provide further evidence of abnormal brain development in GTS.

  2. Brain tissue- and region-specific abnormalities on volumetric MRI scans in 21 patients with Bardet-Biedl syndrome (BBS)

    PubMed Central

    2011-01-01

    Background Bardet-Biedl syndrome (BBS) is a heterogeneous human disorder inherited in an autosomal recessive pattern, and characterized by the primary findings of obesity, polydactyly, hypogonadism, and learning and behavioural problems. BBS mouse models have a neuroanatomical phenotype consisting of third and lateral ventriculomegaly, thinning of the cerebral cortex, and reduction in the size of the corpus striatum and hippocampus. These abnormalities raise the question of whether humans with BBS have a characteristic morphologic brain phenotype. Further, although behavioral, developmental, neurological and motor defects have been noted in patients with BBS, to date, there are limited reports of brain findings in BBS. The present study represents the largest systematic evaluation for the presence of structural brain malformations and/or progressive changes, which may contribute to these functional problems. Methods A case-control study of 21 patients, most aged 13-35 years, except for 2 patients aged 4 and 8 years, who were diagnosed with BBS by clinical criteria and genetic analysis of known BBS genes, and were evaluated by qualitative and volumetric brain MRI scans. Healthy controls were matched 3:1 by age, sex and race. Statistical analysis was performed using SAS language with SAS STAT procedures. Results All 21 patients with BBS were found to have statistically significant region- and tissue-specific patterns of brain abnormalities. There was 1) normal intracranial volume; 2) reduced white matter in all regions of the brain, but most in the occipital region; 3) preserved gray matter volume, with increased cerebral cortex volume in only the occipital lobe; 4) reduced gray matter in the subcortical regions of the brain, including the caudate, putamen and thalamus, but not in the cerebellum; and 5) increased cerebrospinal fluid volume. Conclusions There are distinct and characteristic abnormalities in tissue- and region- specific volumes of the brain in patients

  3. Bernoulli's Principle Applied to Brain Fluids: Intracranial Pressure Does Not Drive Cerebral Perfusion or CSF Flow.

    PubMed

    Schmidt, Eric; Ros, Maxime; Moyse, Emmanuel; Lorthois, Sylvie; Swider, Pascal

    2016-01-01

    In line with the first law of thermodynamics, Bernoulli's principle states that the total energy in a fluid is the same at all points. We applied Bernoulli's principle to understand the relationship between intracranial pressure (ICP) and intracranial fluids. We analyzed simple fluid physics along a tube to describe the interplay between pressure and velocity. Bernoulli's equation demonstrates that a fluid does not flow along a gradient of pressure or velocity; a fluid flows along a gradient of energy from a high-energy region to a low-energy region. A fluid can even flow against a pressure gradient or a velocity gradient. Pressure and velocity represent part of the total energy. Cerebral blood perfusion is not driven by pressure but by energy: the blood flows from high-energy to lower-energy regions. Hydrocephalus is related to increased cerebrospinal fluid (CSF) resistance (i.e., energy transfer) at various points. Identification of the energy transfer within the CSF circuit is important in understanding and treating CSF-related disorders. Bernoulli's principle is not an abstract concept far from clinical practice. We should be aware that pressure is easy to measure, but it does not induce resumption of fluid flow. Even at the bedside, energy is the key to understanding ICP and fluid dynamics. PMID:27165887

  4. Cerebral perfusion in children with Alice in Wonderland syndrome.

    PubMed

    Kuo, Y T; Chiu, N C; Shen, E Y; Ho, C S; Wu, M C

    1998-08-01

    Alice in Wonderland syndrome (AIWS) is characterized by visual hallucinations and bizarre perceptual distortions. Technetium-99m hexamethylpropyleneamine tomography (SPECT) brain scans were performed in four patients during the acute stage of AIWS. Two patients were demonstrated to have Epstein-Barr virus infections. One had abnormal (EEG) findings. The visual-evoked potential, cranial CT, and MRI findings were negative. The decreased cerebral perfusion areas in all patients were near the visual tract and visual cortex. All involved some regions of the temporal lobe. In most patients with AIWS, the EEG, CT, and MRI are unable to determine the precise pathologic areas. However, a SPECT brain scan may demonstrate abnormal perfusion areas and explain the clinical presentations. PMID:9744628

  5. Quantitative Analysis of Metabolic Abnormality Associated with Brain Developmental Venous Anomalies

    PubMed Central

    Timerman, Dmitriy; Thum, Jasmine A

    2016-01-01

    Background and Purpose: Abnormal hypometabolism is common in the brain parenchyma surrounding developmental venous anomalies (DVAs), although the degree of DVA-associated hypometabolism (DVAAh) has not been quantitatively analyzed. In this study, we demonstrate a simple method for the measurement of DVAAh and test the hypothesis that DVAs are associated with a quantifiable decrement in metabolic activity. Materials and Methods: Measurements of DVAAh using ratios of standardized uptake values (SUVs) and comparison to a normal database were performed on a cohort of 25 patients (12 male, 13 female), 14 to 76 years old, with a total of 28 DVAs (20 with DVAAh, seven with isometabolic activity, and one with hypermetabolic activity). Results: Qualitative classification of none, mild, moderate, and severe DVAAh corresponded to quantitative measurements of DVAAh of 1 ± 3%, 12 ± 7%, 18 ± 6%, and 37 ± 6%, respectively. A statistically significant linear correlation between DVAAh and age was observed (P = 0.003), with a 3% reduction in metabolic activity per decade. A statistically significant linear correlation between DVAAh and DVA size was observed (P = 0.01), with a 4% reduction in metabolic activity per each 1 cm in the longest dimension. The SUVDVA-based measures of DVAAh correlated (P = 0.001) with measures derived from comparison with a standardized database. Conclusion: We present a simple method for the quantitative measurement of DVAAh using ratios of SUVs, and find that this quantitative analysis is consistent with a qualitative classification. We find that 54% (15 of 28) of DVAs are associated with a greater than 10% decrease in metabolic activity. PMID:27774365

  6. Dentate gyrus abnormalities in sudden unexplained death in infants: morphological marker of underlying brain vulnerability.

    PubMed

    Kinney, Hannah C; Cryan, Jane B; Haynes, Robin L; Paterson, David S; Haas, Elisabeth A; Mena, Othon J; Minter, Megan; Journey, Kelley W; Trachtenberg, Felicia L; Goldstein, Richard D; Armstrong, Dawna D

    2015-01-01

    Sudden unexplained death in infants, including the sudden infant death syndrome, is likely due to heterogeneous causes that involve different intrinsic vulnerabilities and/or environmental factors. Neuropathologic research focuses upon the role of brain regions, particularly the brainstem, that regulate or modulate autonomic and respiratory control during sleep or transitions to waking. The hippocampus is a key component of the forebrain-limbic network that modulates autonomic/respiratory control via brainstem connections, but its role in sudden infant death has received little attention. We tested the hypothesis that a well-established marker of hippocampal pathology in temporal lobe epilepsy-focal granule cell bilamination in the dentate, a variant of granule cell dispersion-is associated with sudden unexplained death in infants. In a blinded study of hippocampal morphology in 153 infants with sudden and unexpected death autopsied in the San Diego County medical examiner's office, deaths were classified as unexplained or explained based upon autopsy and scene investigation. Focal granule cell bilamination was present in 41.2% (47/114) of the unexplained group compared to 7.7% (3/39) of the explained (control) group (p < 0.001). It was associated with a cluster of other dentate developmental abnormalities that reflect defective neuronal proliferation, migration, and/or survival. Dentate lesions in a large subset of infants with sudden unexplained death may represent a developmental vulnerability that leads to autonomic/respiratory instability or autonomic seizures, and sleep-related death when the infants are challenged with homeostatic stressors. Importantly, these lesions can be recognized in microscopic sections prepared in current forensic practice. Future research is needed to determine the relationship between hippocampal and previously reported brainstem pathology in sudden infant death. PMID:25421424

  7. 3D perfused brain phantom for interstitial ultrasound thermal therapy and imaging: design, construction and characterization.

    PubMed

    Martínez, José M; Jarosz, Boguslaw J

    2015-03-01

    Thermal therapy has emerged as an independent modality of treating some tumors. In many clinics the hyperthermia, one of the thermal therapy modalities, has been used adjuvant to radio- or chemotherapy to substantially improve the clinical treatment outcomes. In this work, a methodology for building a realistic brain phantom for interstitial ultrasound low dose-rate thermal therapy of the brain is proposed. A 3D brain phantom made of the tissue mimicking material (TMM) had the acoustic and thermal properties in the 20-32 °C range, which is similar to that of a brain at 37 °C. The phantom had 10-11% by mass of bovine gelatin powder dissolved in ethylene glycol. The TMM sonicated at 1 MHz, 1.6 MHz and 2.5 MHz yielded the amplitude attenuation coefficients of 62  ±  1 dB m(-1), 115  ±  4 dB m(-1) and 175  ±  9 dB m(-1), respectively. The density and acoustic speed determination at room temperature (~24 °C) gave 1040  ±  40 kg m(-3) and 1545  ±  44 m s(-1), respectively. The average thermal conductivity was 0.532 W m(-1) K(-1). The T1 and T2 values of the TMM were 207  ±  4 and 36.2  ±  0.4 ms, respectively. We envisage the use of our phantom for treatment planning and for quality assurance in MRI based temperature determination. Our phantom preparation methodology may be readily extended to other thermal therapy technologies.

  8. 3D perfused brain phantom for interstitial ultrasound thermal therapy and imaging: design, construction and characterization

    NASA Astrophysics Data System (ADS)

    Martínez, José M.; Jarosz, Boguslaw J.

    2015-03-01

    Thermal therapy has emerged as an independent modality of treating some tumors. In many clinics the hyperthermia, one of the thermal therapy modalities, has been used adjuvant to radio- or chemotherapy to substantially improve the clinical treatment outcomes. In this work, a methodology for building a realistic brain phantom for interstitial ultrasound low dose-rate thermal therapy of the brain is proposed. A 3D brain phantom made of the tissue mimicking material (TMM) had the acoustic and thermal properties in the 20-32 °C range, which is similar to that of a brain at 37 °C. The phantom had 10-11% by mass of bovine gelatin powder dissolved in ethylene glycol. The TMM sonicated at 1 MHz, 1.6 MHz and 2.5 MHz yielded the amplitude attenuation coefficients of 62  ±  1 dB m-1, 115  ±  4 dB m-1 and 175  ±  9 dB m-1, respectively. The density and acoustic speed determination at room temperature (~24 °C) gave 1040  ±  40 kg m-3 and 1545  ±  44 m s-1, respectively. The average thermal conductivity was 0.532 W m-1 K-1. The T1 and T2 values of the TMM were 207  ±  4 and 36.2  ±  0.4 ms, respectively. We envisage the use of our phantom for treatment planning and for quality assurance in MRI based temperature determination. Our phantom preparation methodology may be readily extended to other thermal therapy technologies.

  9. Regional brain perfusion in 12 cats measured with technetium-99m-ethyl cysteinate dimer pinhole single photon emission computed tomography (SPECT).

    PubMed

    Waelbers, Tim; Peremans, Kathelijne; Vermeire, Simon; Dobbeleir, André; Boer, Vo; de Leeuw, Hendrik; Vente, Maarten A D; Piron, Koen; Hesta, Myriam; Polis, Ingeborgh

    2013-02-01

    With the use of perfusion tracers, in vivo examination of the regional cerebral blood flow in cats can be performed with single photon emission computed tomography (SPECT). Reliable perfusion data of normal, healthy cats are necessary for future clinical studies or other research use. Therefore, this dataset of the regional perfusion pattern of the normal feline brain was created. Twelve cats were used in this study. Technetium-99m-ethyl cysteinate dimer ((99m)Tc-ECD) was injected intravenously and the acquisition, using a triple head gamma camera equipped with three multi-pinhole collimators (pinhole SPECT), was started 40 mins after tracer administration under general anaesthesia. Nineteen regions of interest were defined using 7T magnetic resonance images of the feline brain and a topographical atlas. Regional counts were normalised to the counts of two reference regions: the total brain and the cerebellum. The highest tracer uptake was noticed in the subcortical structures, and the lowest in the frontal cortex and the cerebellum. Also left-right asymmetry in the temporal cortex and a rostrocaudal gradient of 5% were observed.

  10. Assessment of brain perfusion using parametric and factor images extracted from dynamic contrast-enhanced MRI images

    NASA Astrophysics Data System (ADS)

    Martel, Anne L.; Moody, Alan R.

    1998-07-01

    Contrast-enhanced magnetic resonance (MR) imaging offers a minimally invasive method of investigating brain blood flow. This paper describes two different methods of extracting quantitative and qualitative information from this data. The first approach is to generate parametric images showing blood flow, blood volume and time-to-peak activity on a pixel by pixel basis. The second approach uses factor analysis. Principal components are extracted from the data and these orthogonal factors are then rotated to give a set of oblique factors, which satisfy certain simple constraints. In most cases three factors can be identified: a background or non- enhancing factor, an early vascular factor which is strongly correlated to arterial flow, and a late vascular factor which is strongly correlated to venous flow. The parametric and factor images are complimentary in nature: the former provides quantitative information that is readily understood by the clinician, while the latter makes no a priori assumptions about the underlying physiology and also allows more subtle changes in cerebral blood flow to be assessed. The factor images may also be of great value in defining regions of interest over which to carry out a more detailed quantitative analysis. This dual approach can be readily adapted to assess perfusion in other organs such as the heart or kidneys.

  11. CT-based attenuation and scatter correction compared with uniform attenuation correction in brain perfusion SPECT imaging for dementia

    NASA Astrophysics Data System (ADS)

    Gillen, Rebecca; Firbank, Michael J.; Lloyd, Jim; O'Brien, John T.

    2015-09-01

    This study investigated if the appearance and diagnostic accuracy of HMPAO brain perfusion SPECT images could be improved by using CT-based attenuation and scatter correction compared with the uniform attenuation correction method. A cohort of subjects who were clinically categorized as Alzheimer’s Disease (n=38 ), Dementia with Lewy Bodies (n=29 ) or healthy normal controls (n=30 ), underwent SPECT imaging with Tc-99m HMPAO and a separate CT scan. The SPECT images were processed using: (a) correction map derived from the subject’s CT scan or (b) the Chang uniform approximation for correction or (c) no attenuation correction. Images were visually inspected. The ratios between key regions of interest known to be affected or spared in each condition were calculated for each correction method, and the differences between these ratios were evaluated. The images produced using the different corrections were noted to be visually different. However, ROI analysis found similar statistically significant differences between control and dementia groups and between AD and DLB groups regardless of the correction map used. We did not identify an improvement in diagnostic accuracy in images which were corrected using CT-based attenuation and scatter correction, compared with those corrected using a uniform correction map.

  12. CT-based attenuation and scatter correction compared with uniform attenuation correction in brain perfusion SPECT imaging for dementia.

    PubMed

    Gillen, Rebecca; Firbank, Michael J; Lloyd, Jim; O'Brien, John T

    2015-09-01

    This study investigated if the appearance and diagnostic accuracy of HMPAO brain perfusion SPECT images could be improved by using CT-based attenuation and scatter correction compared with the uniform attenuation correction method. A cohort of subjects who were clinically categorized as Alzheimer's Disease (n = 38), Dementia with Lewy Bodies (n = 29) or healthy normal controls (n = 30), underwent SPECT imaging with Tc-99m HMPAO and a separate CT scan. The SPECT images were processed using: (a) correction map derived from the subject's CT scan or (b) the Chang uniform approximation for correction or (c) no attenuation correction. Images were visually inspected. The ratios between key regions of interest known to be affected or spared in each condition were calculated for each correction method, and the differences between these ratios were evaluated. The images produced using the different corrections were noted to be visually different. However, ROI analysis found similar statistically significant differences between control and dementia groups and between AD and DLB groups regardless of the correction map used.We did not identify an improvement in diagnostic accuracy in images which were corrected using CT-based attenuation and scatter correction, compared with those corrected using a uniform correction map.

  13. Method for measurement of the blood-brain barrier permeability in the perfused mouse brain: application to amyloid-beta peptide in wild type and Alzheimer's Tg2576 mice.

    PubMed

    LaRue, Barbra; Hogg, Elizabeth; Sagare, Abhay; Jovanovic, Suzana; Maness, Lawrence; Maurer, Calvin; Deane, Rashid; Zlokovic, Berislav V

    2004-09-30

    The role of transport exchanges of neuroactive solutes across the blood-brain barrier (BBB) is increasingly recognized. To take full advantage of genetically altered mouse models of neurodegenerative disorders for BBB transport studies, we adapted a brain perfusion technique to the mouse. During a carotid brain perfusion with a medium containing sheep red blood cells and mock plasma, the physiological parameters in the arterial inflow, regional cerebral blood flow (14C-iodoantipyrine autoradiography), ultrastructural integrity of the tissue, barrier to lanthanum, brain water content, energy metabolites and lactate levels remain unchanged. Amyloid-beta peptides (Abeta) were iodinated by lactoperoxidase method. Non-oxidized mono-iodinated Abeta monomers were separated by HPLC (as confirmed by MALDI-TOF spectrometry) and used in transport measurements. Transport of intact 125I-Abeta40 across the BBB was time- and concentration-dependent in contrast to negligible 14C-inulin uptake. In 5-6 months old Alzheimer's Tg2576 mice, Abeta40 BBB transport was increased by >eight-fold compared to age-matched littermate controls, and was mediated via the receptor for advanced glycation endproducts. We conclude the present arterial brain perfusion method provides strictly controlled environment in cerebral microcirculation suitable for examining transport of rapidly and slowly penetrating molecules across the BBB in normal and transgenic mice.

  14. Optical fiber spectroscopy measures perfusion of the brain in a murine Alzheimer's disease model

    NASA Astrophysics Data System (ADS)

    Ahn, Hyung Jin; Strickland, Sidney; Krueger, James; Gareau, Daniel

    2014-02-01

    Optical fiber spectroscopy is a versatile tool for measuring diffuse reflectance and extracting absorption information that can noninvasively quantify the presence of chromophores such as oxyhemoglobin and deoxy-hemoglobin in tissues. Cerebrovascular abnormalities were widely recognized in Alzheimer's disease (AD) patients. We analyzed blood volume fraction and level of oxygenated hemoglobin in Tg6799 mice, which are transgenic mice expressing five different familial Alzheimer disease-associated mutations in the human amyloid precursor protein and presenilin-1 genes. Diffuse reflectance spectra were iteratively fit as weighted sums of oxy- and deoxy-hemoglobin. Our observations showed slightly hypoxic conditions and significantly increased blood volume in the Alzheimer's mice versus wild type. These results suggest that hyperperfusion of our AD mice may be a compensating mechanism for impaired cerebral vascular function and somehow relevant with early stage of AD patients. Ongoing work focuses on developing a cannula fixture that allows measurement in awake, behaving animals.

  15. Assessment of SPM in perfusion brain SPECT studies. A numerical simulation study using bootstrap resampling methods.

    PubMed

    Pareto, Deborah; Aguiar, Pablo; Pavía, Javier; Gispert, Juan Domingo; Cot, Albert; Falcón, Carles; Benabarre, Antoni; Lomeña, Francisco; Vieta, Eduard; Ros, Domènec

    2008-07-01

    Statistical parametric mapping (SPM) has become the technique of choice to statistically evaluate positron emission tomography (PET), functional magnetic resonance imaging (fMRI), and single photon emission computed tomography (SPECT) functional brain studies. Nevertheless, only a few methodological studies have been carried out to assess the performance of SPM in SPECT. The aim of this paper was to study the performance of SPM in detecting changes in regional cerebral blood flow (rCBF) in hypo- and hyperperfused areas in brain SPECT studies. The paper seeks to determine the relationship between the group size and the rCBF changes, and the influence of the correction for degradations. The assessment was carried out using simulated brain SPECT studies. Projections were obtained with Monte Carlo techniques, and a fan-beam collimator was considered in the simulation process. Reconstruction was performed by using the ordered subsets expectation maximization (OSEM) algorithm with and without compensation for attenuation, scattering, and spatial variant collimator response. Significance probability maps were obtained with SPM2 by using a one-tailed two-sample t-test. A bootstrap resampling approach was used to determine the sample size for SPM to detect the between-group differences. Our findings show that the correction for degradations results in a diminution of the sample size, which is more significant for small regions and low-activation factors. Differences in sample size were found between hypo- and hyperperfusion. These differences were larger for small regions and low-activation factors, and when no corrections were included in the reconstruction algorithm.

  16. Annual Research Review: Growth connectomics – the organization and reorganization of brain networks during normal and abnormal development

    PubMed Central

    Vértes, Petra E; Bullmore, Edward T

    2015-01-01

    Background We first give a brief introduction to graph theoretical analysis and its application to the study of brain network topology or connectomics. Within this framework, we review the existing empirical data on developmental changes in brain network organization across a range of experimental modalities (including structural and functional MRI, diffusion tensor imaging, magnetoencephalography and electroencephalography in humans). Synthesis We discuss preliminary evidence and current hypotheses for how the emergence of network properties correlates with concomitant cognitive and behavioural changes associated with development. We highlight some of the technical and conceptual challenges to be addressed by future developments in this rapidly moving field. Given the parallels previously discovered between neural systems across species and over a range of spatial scales, we also review some recent advances in developmental network studies at the cellular scale. We highlight the opportunities presented by such studies and how they may complement neuroimaging in advancing our understanding of brain development. Finally, we note that many brain and mind disorders are thought to be neurodevelopmental in origin and that charting the trajectory of brain network changes associated with healthy development also sets the stage for understanding abnormal network development. Conclusions We therefore briefly review the clinical relevance of network metrics as potential diagnostic markers and some recent efforts in computational modelling of brain networks which might contribute to a more mechanistic understanding of neurodevelopmental disorders in future. PMID:25441756

  17. Brain microstructure reveals early abnormalities more than two years prior to clinical progression from mild cognitive impairment to Alzheimer's disease.

    PubMed

    Douaud, Gwenaëlle; Menke, Ricarda A L; Gass, Achim; Monsch, Andreas U; Rao, Anil; Whitcher, Brandon; Zamboni, Giovanna; Matthews, Paul M; Sollberger, Marc; Smith, Stephen

    2013-01-30

    Diffusion imaging is a promising marker of microstructural damage in neurodegenerative disorders, but interpretation of its relationship with underlying neuropathology can be complex. Here, we examined both volumetric and brain microstructure abnormalities in 13 amnestic patients with mild cognitive impairment (MCI), who progressed to probable Alzheimer's disease (AD) no earlier than 2 years after baseline scanning, in order to focus on early, and hence more sensitive, imaging markers. We compared them to 22 stable amnestic MCI patients with similar cognitive performance and episodic memory impairment but who did not show progression of symptoms for at least 3 years. Significant group differences were mainly found in the volume and microstructure of the left hippocampus, while white matter group differences were also found in the body of the fornix, left fimbria, and superior longitudinal fasciculus (SLF). Diffusion index abnormalities in the SLF were the sign of a subtle microstructural injury not detected by standard atrophy measures in the corresponding gray matter regions. The microstructural measure obtained in the left hippocampus using diffusion imaging showed the most substantial differences between the two groups and was the best single predictor of future progression to AD. An optimal prediction model (91% accuracy, 85% sensitivity, 96% specificity) was obtained by combining MRI measures and CSF protein biomarkers. These results highlight the benefit of using the information of brain microstructural damage, in addition to traditional gray matter volume, to detect early, subtle abnormalities in MCI prior to clinical progression to probable AD and, in combination with CSF markers, to accurately predict such progression.

  18. Analysis of dynamic cerebral contrast-enhanced perfusion MRI time-series based on unsupervised clustering methods

    NASA Astrophysics Data System (ADS)

    Lange, Oliver; Meyer-Baese, Anke; Wismuller, Axel; Hurdal, Monica

    2005-03-01

    We employ unsupervised clustering techniques for the analysis of dynamic contrast-enhanced perfusion MRI time-series in patients with and without stroke. "Neural gas" network, fuzzy clustering based on deterministic annealing, self-organizing maps, and fuzzy c-means clustering enable self-organized data-driven segmentation w.r.t.fine-grained differences of signal amplitude and dynamics, thus identifying asymmetries and local abnormalities of brain perfusion. We conclude that clustering is a useful extension to conventional perfusion parameter maps.

  19. Single-subject-based whole-brain MEG slow-wave imaging approach for detecting abnormality in patients with mild traumatic brain injury.

    PubMed

    Huang, Ming-Xiong; Nichols, Sharon; Baker, Dewleen G; Robb, Ashley; Angeles, Annemarie; Yurgil, Kate A; Drake, Angela; Levy, Michael; Song, Tao; McLay, Robert; Theilmann, Rebecca J; Diwakar, Mithun; Risbrough, Victoria B; Ji, Zhengwei; Huang, Charles W; Chang, Douglas G; Harrington, Deborah L; Muzzatti, Laura; Canive, Jose M; Christopher Edgar, J; Chen, Yu-Han; Lee, Roland R

    2014-01-01

    Traumatic brain injury (TBI) is a leading cause of sustained impairment in military and civilian populations. However, mild TBI (mTBI) can be difficult to detect using conventional MRI or CT. Injured brain tissues in mTBI patients generate abnormal slow-waves (1-4 Hz) that can be measured and localized by resting-state magnetoencephalography (MEG). In this study, we develop a voxel-based whole-brain MEG slow-wave imaging approach for detecting abnormality in patients with mTBI on a single-subject basis. A normative database of resting-state MEG source magnitude images (1-4 Hz) from 79 healthy control subjects was established for all brain voxels. The high-resolution MEG source magnitude images were obtained by our recent Fast-VESTAL method. In 84 mTBI patients with persistent post-concussive symptoms (36 from blasts, and 48 from non-blast causes), our method detected abnormalities at the positive detection rates of 84.5%, 86.1%, and 83.3% for the combined (blast-induced plus with non-blast causes), blast, and non-blast mTBI groups, respectively. We found that prefrontal, posterior parietal, inferior temporal, hippocampus, and cerebella areas were particularly vulnerable to head trauma. The result also showed that MEG slow-wave generation in prefrontal areas positively correlated with personality change, trouble concentrating, affective lability, and depression symptoms. Discussion is provided regarding the neuronal mechanisms of MEG slow-wave generation due to deafferentation caused by axonal injury and/or blockages/limitations of cholinergic transmission in TBI. This study provides an effective way for using MEG slow-wave source imaging to localize affected areas and supports MEG as a tool for assisting the diagnosis of mTBI. PMID:25009772

  20. A mouse model for eukaryotic translation initiation factor 2B-leucodystrophy reveals abnormal development of brain white matter.

    PubMed

    Geva, Michal; Cabilly, Yuval; Assaf, Yaniv; Mindroul, Nina; Marom, Liraz; Raini, Gali; Pinchasi, Dalia; Elroy-Stein, Orna

    2010-08-01

    Eukaryotic translation initiation factor 2B is a major housekeeping complex that governs the rate of global protein synthesis under normal and stress conditions. Mutations in any of its five subunits lead to leucoencephalopathy with vanishing white matter, an inherited chronic-progressive fatal brain disease with unknown aetiology, which is among the most prevalent childhood white matter disorders. We generated the first animal model for the disease by introducing a point mutation into the mouse Eif2b5 gene locus, leading to R132H replacement corresponding to the clinically significant human R136H mutation in the catalytic subunit. In contrast to human patients, mice homozygous for the mutant Eif2b5 allele (Eif2b5(R132H/R132H) mice) enable multiple analyses under a defined genetic background during the pre-symptomatic stages and during recovery from a defined brain insult. Time-course magnetic resonance imaging revealed for the first time the delayed development of the brain white matter due to the mutation. Electron microscopy demonstrated a higher proportion of small-calibre nerve fibres. Immunohistochemistry detected an abnormal abundance of oligodendrocytes and astrocytes in the brain of younger animals, as well as an abnormal level of major myelin proteins. Most importantly, mutant mice failed to recover from cuprizone-induced demyelination, reflecting an increased sensitivity to brain insults. The anomalous development of white matter in Eif2b5(R132H/R132H) mice underscores the importance of tight translational control to normal myelin formation and maintenance.

  1. Diffusion Tensor Imaging for Assessing Brain Gray and White Matter Abnormalities in a Feline Model of α-Mannosidosis.

    PubMed

    Kumar, Manoj; Duda, Jeff T; Yoon, Sea Young; Bagel, Jessica; O'Donnell, Patricia; Vite, Charles; Pickup, Stephen; Gee, James C; Wolfe, John H; Poptani, Harish

    2016-01-01

    α-Mannosidosis (AMD) is an autosomal recessively inherited lysosomal storage disorder affecting brain function and structure. We performed ex vivo and in vivo diffusion tensor imaging (DTI) on the brains of AMD-affected cats to assess gray and white matter abnormalities. A multi-atlas approach was used to generate a brain template to process the ex vivo DTI data. The probabilistic label method was used to measure fractional anisotropy (FA), mean diffusivity, axial diffusivity, and radial diffusivity values from gray and white matter regions from ex vivo DTI. Regional analysis from various regions of the gray matter (frontal cortex, cingulate gyrus, caudate nucleus, hippocampus, thalamus, and occipital cortex), and white matter (corpus callosum, corticospinal tract, cerebral peduncle, external and internal capsule) was also performed on both ex vivo and in vivo DTI. Ex vivo DTI revealed significantly reduced FA from both gray and white matter regions in AMD-affected cats compared to controls. Significantly reduced FA was also observed from in vivo DTI of AMD-affected cats compared to controls, with lower FA values observed in all white matter regions. We also observed significantly increased axial and radial diffusivity values in various gray and white matter regions in AMD cats from both ex vivo and in vivo DTI data. Imaging findings were correlated with histopathologic analyses suggesting that DTI studies can further aid in the characterization of AMD by assessing the microstructural abnormalities in both white and gray matter.

  2. Regional brain abnormalities in 22q11.2 deletion syndrome: association with cognitive abilities and behavioral symptoms.

    PubMed

    Bearden, Carrie E; van Erp, Theo G M; Monterosso, John R; Simon, Tony J; Glahn, David C; Saleh, Peter A; Hill, Nicole M; McDonald-McGinn, Donna M; Zackai, Elaine; Emanuel, Beverly S; Cannon, Tyrone D

    2004-06-01

    Children with 22q11.2 microdeletions (Velocardiofacial Syndrome; VCFS) have previously been shown to exhibit learning deficits and elevated rates of psychopathology. The aim of this study was to assess regional brain abnormalities in children with 22q11DS, and to determine the relationship of these measures to neurocognitive and behavioral function. Thirteen children with confirmed deletions and 9 demographically matched comparison subjects were assessed with a neurocognitive battery, behavioral measures, and high-resolution MRI. Twenty-two qllDS children showed a nonsignificant 4.3% global decrease in total brain volume as compared to healthy controls,with differential reduction in white matter, and significantly increased sulcal cerebrospinal fluid (CSF) in temporal and posterior brain regions. In 22q11 DS subjects, but not controls, bilateral temporal gray and white matter volumes were significant predictors of overall cognitive performance. Further, reduced temporal gray matter was associated with elevated Thought Problems score on the CBCL. Results indicate that global alterations in brain volume are common in children with 22q deletions, particularly those with low IQ and/or behavioral disturbance. Although preliminary,these findings suggest a possible underlying pathophysiology of the cognitive deficits seen in this syndrome,and provide insight into complex gene-brain-behavior relationships. PMID:15788257

  3. Evaluation of brain perfusion in specific Brodmann areas in Frontotemporal dementia and Alzheimer disease using automated 3-D voxel based analysis

    NASA Astrophysics Data System (ADS)

    Valotassiou, V.; Papatriantafyllou, J.; Sifakis, N.; Karageorgiou, C.; Tsougos, I.; Tzavara, C.; Zerva, C.; Georgoulias, P.

    2009-05-01

    Introduction. Brain perfusion studies with single-photon emission computed tomography (SPECT) have been applied in demented patients to provide better discrimination between frontotemporal dementia (FTD) and Alzheimer's disease (AD). Aim. To assess the perfusion of specific Brodmann (Br) areas of the brain cortex in FTD and AD patients, using NeuroGam processing program to provide 3D voxel-by-voxel cerebral SPECT analysis. Material and methods. We studied 34 consecutive patients. We used the established criteria for the diagnosis of dementia and the specific established criteria for the diagnosis of FTD and AD. All the patients had a neuropsychological evaluation with a battery of tests including the mini-mental state examination (MMSE).Twenty-six patients (16 males, 10 females, mean age 68.76±6.51 years, education 11.81±4.25 years, MMSE 16.69±9.89) received the diagnosis of FTD and 8 patients (all females, mean age 71.25±10.48 years, education 10±4.6 years, MMSE 12.5±3.89) the diagnosis of AD. All the patients underwent a brain SPECT. We applied the NeuroGam Software for the evaluation of brain perfusion in specific Br areas in the left (L) and right (R) hemispheres. Results. Statistically significant hypoperfusion in FTD compared to AD patients, was found in the following Br areas: 11L (p<0.0001), 11R, 20L, 20R, 32L, 38L, 38R, 44L (p<0.001), 32R, 36L, 36R, 45L, 45R, 47R (p<0.01), 9L, 21L, 39R, 44R, 46R, 47L (p<0.05). On the contrary, AD patients presented significant (p<0.05) hypoperfusion in 7R and 39R Br areas. Conclusion. NeuroGam processing program of brain perfusion SPECT could result in enhanced accuracy for the differential diagnosis between AD and FTD patients.

  4. Red-backed vole brain promotes highly efficient in vitro amplification of abnormal prion protein from macaque and human brains infected with variant Creutzfeldt-Jakob disease agent.

    USGS Publications Warehouse

    Nemecek, Julie; Nag, Nabanita; Carlson, Christina M.; Schneider, Jay R.; Heisey, Dennis M.; Johnson, Christopher J.; Asher, David M.; Gregori, Luisa

    2013-01-01

    Rapid antemortem tests to detect individuals with transmissible spongiform encephalopathies (TSE) would contribute to public health. We investigated a technique known as protein misfolding cyclic amplification (PMCA) to amplify abnormal prion protein (PrPTSE) from highly diluted variant Creutzfeldt-Jakob disease (vCJD)-infected human and macaque brain homogenates, seeking to improve the rapid detection of PrPTSE in tissues and blood. Macaque vCJD PrPTSE did not amplify using normal macaque brain homogenate as substrate (intraspecies PMCA). Next, we tested interspecies PMCA with normal brain homogenate of the southern red-backed vole (RBV), a close relative of the bank vole, seeded with macaque vCJD PrPTSE. The RBV has a natural polymorphism at residue 170 of the PrP-encoding gene (N/N, S/S, and S/N). We investigated the effect of this polymorphism on amplification of human and macaque vCJD PrPTSE. Meadow vole brain (170N/N PrP genotype) was also included in the panel of substrates tested. Both humans and macaques have the same 170S/S PrP genotype. Macaque PrPTSE was best amplified with RBV 170S/S brain, although 170N/N and 170S/N were also competent substrates, while meadow vole brain was a poor substrate. In contrast, human PrPTSE demonstrated a striking narrow selectivity for PMCA substrate and was successfully amplified only with RBV 170S/S brain. These observations suggest that macaque PrPTSE was more permissive than human PrPTSE in selecting the competent RBV substrate. RBV 170S/S brain was used to assess the sensitivity of PMCA with PrPTSE from brains of humans and macaques with vCJD. PrPTSE signals were reproducibly detected by Western blot in dilutions through 10-12 of vCJD-infected 10% brain homogenates. This is the first report showing PrPTSE from vCJD-infected human and macaque brains efficiently amplified with RBV brain as the substrate. Based on our estimates, PMCA showed a sensitivity that might be sufficient to detect PrPTSE in v

  5. Red-backed vole brain promotes highly efficient in vitro amplification of abnormal prion protein from macaque and human brains infected with variant Creutzfeldt-Jakob disease agent.

    PubMed

    Nemecek, Julie; Nag, Nabanita; Carlson, Christina M; Schneider, Jay R; Heisey, Dennis M; Johnson, Christopher J; Asher, David M; Gregori, Luisa

    2013-01-01

    Rapid antemortem tests to detect individuals with transmissible spongiform encephalopathies (TSE) would contribute to public health. We investigated a technique known as protein misfolding cyclic amplification (PMCA) to amplify abnormal prion protein (PrP(TSE)) from highly diluted variant Creutzfeldt-Jakob disease (vCJD)-infected human and macaque brain homogenates, seeking to improve the rapid detection of PrP(TSE) in tissues and blood. Macaque vCJD PrP(TSE) did not amplify using normal macaque brain homogenate as substrate (intraspecies PMCA). Next, we tested interspecies PMCA with normal brain homogenate of the southern red-backed vole (RBV), a close relative of the bank vole, seeded with macaque vCJD PrP(TSE). The RBV has a natural polymorphism at residue 170 of the PrP-encoding gene (N/N, S/S, and S/N). We investigated the effect of this polymorphism on amplification of human and macaque vCJD PrP(TSE). Meadow vole brain (170N/N PrP genotype) was also included in the panel of substrates tested. Both humans and macaques have the same 170S/S PrP genotype. Macaque PrP(TSE) was best amplified with RBV 170S/S brain, although 170N/N and 170S/N were also competent substrates, while meadow vole brain was a poor substrate. In contrast, human PrP(TSE) demonstrated a striking narrow selectivity for PMCA substrate and was successfully amplified only with RBV 170S/S brain. These observations suggest that macaque PrP(TSE) was more permissive than human PrP(TSE) in selecting the competent RBV substrate. RBV 170S/S brain was used to assess the sensitivity of PMCA with PrP(TSE) from brains of humans and macaques with vCJD. PrP(TSE) signals were reproducibly detected by Western blot in dilutions through 10⁻¹² of vCJD-infected 10% brain homogenates. This is the first report showing PrP(TSE) from vCJD-infected human and macaque brains efficiently amplified with RBV brain as the substrate. Based on our estimates, PMCA showed a sensitivity that might be sufficient to detect Pr

  6. Better Glasgow outcome score, cerebral perfusion pressure and focal brain oxygenation in severely traumatized brain following direct regional brain hypothermia therapy: A prospective randomized study

    PubMed Central

    Idris, Zamzuri; Zenian, Mohd Sofan; Muzaimi, Mustapha; Hamid, Wan Zuraida Wan Abdul

    2014-01-01

    Background: Induced hypothermia for treatment of traumatic brain injury is controversial. Since many pathways involved in the pathophysiology of secondary brain injury are temperature dependent, regional brain hypothermia is thought capable to mitigate those processes. The objectives of this study are to assess the therapeutic effects and complications of regional brain cooling in severe head injury with Glasgow coma scale (GCS) 6-7. Materials and Methods: A prospective randomized controlled pilot study involving patients with severe traumatic brain injury with GCS 6 and 7 who required decompressive craniectomy. Patients were randomized into two groups: Cooling and no cooling. For the cooling group, analysis was made by dividing the group into mild and deep cooling. Brain was cooled by irrigating the brain continuously with cold Hartmann solution for 24-48 h. Main outcome assessments were a dichotomized Glasgow outcome score (GOS) at 6 months posttrauma. Results: A total of 32 patients were recruited. The cooling-treated patients did better than no cooling. There were 63.2% of patients in cooling group attained good GOS at 6 months compared to only 15.4% in noncooling group (P = 0.007). Interestingly, the analysis at 6 months post-trauma disclosed mild-cooling-treated patients did better than no cooling (70% vs. 15.4% attained good GOS, P = 0.013) and apparently, the deep-cooling-treated patients failed to be better than either no cooling (P = 0.074) or mild cooling group (P = 0.650). Conclusion: Data from this pilot study imply direct regional brain hypothermia appears safe, feasible and maybe beneficial in treating severely head-injured patients. PMID:25685201

  7. The abnormal isoform of the prion protein accumulates in late-endosome-like organelles in scrapie-infected mouse brain.

    PubMed

    Arnold, J E; Tipler, C; Laszlo, L; Hope, J; Landon, M; Mayer, R J

    1995-08-01

    The prion encephalopathies are characterized by accumulation in the brain of the abnormal form PrPsc of a normal host gene product PrPc. The mechanism and site of formation of PrPsc from PrPc are currently unknown. In this study, ME7 scrapie-infected mouse brain was used to show, both biochemically and by double-labelled immunogold electron microscopy, that proteinase K-resistant PrPsc is enriched in subcellular structures which contain the cation-independent mannose 6-phosphate receptor, ubiquitin-protein conjugates, beta-glucuronidase, and cathepsin B, termed late endosome-like organelles. The glycosylinositol phospholipid membrane-anchored PrPc will enter such compartment for normal degradation and the organelles may therefore act as chambers for the conversion of PrPc into infectious PrPsc in this murine model of scrapie.

  8. Optimising Golgi–Cox staining for use with perfusion-fixed brain tissue validated in the zQ175 mouse model of Huntington's disease

    PubMed Central

    Bayram-Weston, Zubeyde; Olsen, Elliott; Harrison, David J.; Dunnett, Stephen B.; Brooks, Simon P.

    2016-01-01

    Background The Golgi–Cox stain is an established method for characterising neuron cell morphology. The method highlights neurite processes of stained cells allowing the complexity of dendritic branching to be measured. New methods Conventional rapid Golgi and Golgi–Cox methods all require fresh impregnation in unfixed brain blocks. Here, we describe a modified method that gives high quality staining on brain tissue blocks perfusion-fixed with 4% paraformaldehyde (PFA) and post-fixed by immersion for 24 h. Results Tissue perfused with 4% PFA and post fixed for 24 h remained viable for the modified Golgi–Cox silver impregnation staining of mouse striatum from perfused wild type and zQ175. It was not found necessary to impregnate tissue blocks with Golgi solutions prior to sectioning, as post-sectioned tissues yielded equally good impregnation. Impregnation for 14 days resulted in optimal visualisation of striatal neuron and dendritic morphology. Although no modifications applied to the rapid Golgi method were reliable, the modified Golgi–Cox method yielded consistently reliable high-quality staining. Comparison with existing methods The current method used fixed tissues to reduce damage and preserve cell morphology. The revised method was found to be fast, reliable and cost effective without the need for expensive staining kits and could be performed in any neuroscience lab with limited specialist equipment. Conclusions The present study introduces a robust reproducible and inexpensive staining method for identifying neuronal morphological changes in the post fixed mouse brain, and is suitable for assessing changes in cell morphology in models of neurodegeneration and in response to experimental treatment. PMID:26459195

  9. Temporary extra-anatomic brain perfusion followed by total rerouting of the supra-aortic vessels for hybrid repair of a ruptured aortic arch aneurysm.

    PubMed

    Joyeux, Frederic; Canaud, Ludovic; Hireche, Kheira; Berthet, Jean-Philippe; Marty-Ane, Charles; Alric, Pierre

    2011-10-01

    Hybrid repair of ruptured aortic arch repair has been proposed as a valuable approach. However, the presence of an anterior mediastinal hematoma must be carefully detected because of the inherent risk of rupture at sternotomy. We report the case of a patient presenting a ruptured aortic arch aneurysm with anterior rupture who underwent hybrid repair using a temporary extra-anatomic brain perfusion followed by total rerouting of the supra-aortic trunks. We propose this adjunctive technique as a means of allowing a safe endovascular exclusion of aortic arch lesions and avoiding the risk of acute and total aortic rupture in case of anterior rupture of aortic arch aneurysms.

  10. Biphasic thallium 201 SPECT-imaging for the noninvasive diagnosis of myocardial perfusion abnormalities in a child with Kawasaki disease--a case report

    SciTech Connect

    Hausdorf, G.; Nienaber, C.A.; Spielman, R.P.

    1988-02-01

    The mucocutaneous lymph node syndrome (Kawasaki disease) is of increasing importance for the pediatric cardiologist, for coronary aneurysms with the potential of thrombosis and subsequent stenosis can develop in the course of the disease. The authors report a 2 1/2-year-old female child in whom, fourteen months after the acute phase of Kawasaki disease, myocardial infarction occurred. Biphasic thallium 201 SPECT-imaging using dipyridamole depicted anterior wall ischemia and inferolateral infarction. This case demonstrates that noninvasive vasodilation-redistribution thallium 201 SPECT-imaging has the potential to predict reversible myocardial perfusion defects and myocardial necrosis, even in small infants with Kawasaki disease.

  11. Structural, Metabolic, and Functional Brain Abnormalities as a Result of Prenatal Exposure to Drugs of Abuse: Evidence from Neuroimaging

    PubMed Central

    Roussotte, Florence; Soderberg, Lindsay

    2010-01-01

    Prenatal exposure to alcohol and stimulants negatively affects the developing trajectory of the central nervous system in many ways. Recent advances in neuroimaging methods have allowed researchers to study the structural, metabolic, and functional abnormalities resulting from prenatal exposure to drugs of abuse in living human subjects. Here we review the neuroimaging literature of prenatal exposure to alcohol, cocaine, and methamphetamine. Neuroimaging studies of prenatal alcohol exposure have reported differences in the structure and metabolism of many brain systems, including in frontal, parietal, and temporal regions, in the cerebellum and basal ganglia, as well as in the white matter tracts that connect these brain regions. Functional imaging studies have identified significant differences in brain activation related to various cognitive domains as a result of prenatal alcohol exposure. The published literature of prenatal exposure to cocaine and methamphetamine is much smaller, but evidence is beginning to emerge suggesting that exposure to stimulant drugs in utero may be particularly toxic to dopamine-rich basal ganglia regions. Although the interpretation of such findings is somewhat limited by the problem of polysubstance abuse and by the difficulty of obtaining precise exposure histories in retrospective studies, such investigations provide important insights into the effects of drugs of abuse on the structure, function, and metabolism of the developing human brain. These insights may ultimately help clinicians develop better diagnostic tools and devise appropriate therapeutic interventions to improve the condition of children with prenatal exposure to drugs of abuse. PMID:20978945

  12. Abnormal Baseline Brain Activity in Patients with Pulsatile Tinnitus: A Resting-State fMRI Study

    PubMed Central

    Han, Lv; Zhaohui, Liu; Fei, Yan; Ting, Li; Pengfei, Zhao; Wang, Du; Cheng, Dong; Pengde, Guo; Xiaoyi, Han; Xiao, Wang; Rui, Li; Zhenchang, Wang

    2014-01-01

    Numerous investigations studying the brain functional activity of the tinnitus patients have indicated that neurological changes are important findings of this kind of disease. However, the pulsatile tinnitus (PT) patients were excluded in previous studies because of the totally different mechanisms of the two subtype tinnitus. The aim of this study is to investigate whether altered baseline brain activity presents in patients with PT using resting-state functional magnetic resonance imaging (rs-fMRI) technique. The present study used unilateral PT patients (n = 42) and age-, sex-, and education-matched normal control subjects (n = 42) to investigate the changes in structural and amplitude of low-frequency (ALFF) of the brain. Also, we analyzed the relationships between these changes with clinical data of the PT patients. Compared with normal controls, PT patients did not show any structural changes. PT patients showed significant increased ALFF in the bilateral precuneus, and bilateral inferior frontal gyrus (IFG) and decreased ALFF in multiple occipital areas. Moreover, the increased THI score and PT duration was correlated with increased ALFF in precuneus and bilateral IFG. The abnormalities of spontaneous brain activity reflected by ALFF measurements in the absence of structural changes may provide insights into the neural reorganization in PT patients. PMID:24872895

  13. Abnormal structure of frontostriatal brain systems is associated with aspects of impulsivity and compulsivity in cocaine dependence

    PubMed Central

    Barnes, Anna; Simon Jones, P.; Morein-Zamir, Sharon; Robbins, Trevor W.; Bullmore, Edward T.

    2011-01-01

    A growing body of preclinical evidence indicates that addiction to cocaine is associated with neuroadaptive changes in frontostriatal brain systems. Human studies in cocaine-dependent individuals have shown alterations in brain structure, but it is less clear how these changes may be related to the clinical phenotype of cocaine dependence characterized by impulsive behaviours and compulsive drug-taking. Here we compared self-report, behavioural and structural magnetic resonance imaging data on a relatively large sample of cocaine-dependent individuals (n = 60) with data on healthy volunteers (n = 60); and we investigated the relationships between grey matter volume variation, duration of cocaine use, and measures of impulsivity and compulsivity in the cocaine-dependent group. Cocaine dependence was associated with an extensive system of abnormally decreased grey matter volume in orbitofrontal, cingulate, insular, temporoparietal and cerebellar cortex, and with a more localized increase in grey matter volume in the basal ganglia. Greater duration of cocaine dependence was correlated with greater grey matter volume reduction in orbitofrontal, cingulate and insular cortex. Greater impairment of attentional control was associated with reduced volume in insular cortex and increased volume of caudate nucleus. Greater compulsivity of drug use was associated with reduced volume in orbitofrontal cortex. Cocaine-dependent individuals had abnormal structure of corticostriatal systems, and variability in the extent of anatomical changes in orbitofrontal, insular and striatal structures was related to individual differences in duration of dependence, inattention and compulsivity of cocaine consumption. PMID:21690575

  14. Air pollution, cognitive deficits and brain abnormalities: a pilot study with children and dogs.

    PubMed

    Calderón-Garcidueñas, Lilian; Mora-Tiscareño, Antonieta; Ontiveros, Esperanza; Gómez-Garza, Gilberto; Barragán-Mejía, Gerardo; Broadway, James; Chapman, Susan; Valencia-Salazar, Gildardo; Jewells, Valerie; Maronpot, Robert R; Henríquez-Roldán, Carlos; Pérez-Guillé, Beatriz; Torres-Jardón, Ricardo; Herrit, Lou; Brooks, Diane; Osnaya-Brizuela, Norma; Monroy, Maria E; González-Maciel, Angelica; Reynoso-Robles, Rafael; Villarreal-Calderon, Rafael; Solt, Anna C; Engle, Randall W

    2008-11-01

    Exposure to air pollution is associated with neuroinflammation in healthy children and dogs in Mexico City. Comparative studies were carried out in healthy children and young dogs similarly exposed to ambient pollution in Mexico City. Children from Mexico City (n: 55) and a low polluted city (n:18) underwent psychometric testing and brain magnetic resonance imaging MRI. Seven healthy young dogs with similar exposure to Mexico City air pollution had brain MRI, measurement of mRNA abundance of two inflammatory genes cyclooxygenase-2, and interleukin 1 beta in target brain areas, and histopathological evaluation of brain tissue. Children with no known risk factors for neurological or cognitive disorders residing in a polluted urban environment exhibited significant deficits in a combination of fluid and crystallized cognition tasks. Fifty-six percent of Mexico City children tested showed prefrontal white matter hyperintense lesions and similar lesions were observed in dogs (57%). Exposed dogs had frontal lesions with vascular subcortical pathology associated with neuroinflammation, enlarged Virchow-Robin spaces, gliosis, and ultrafine particulate matter deposition. Based on the MRI findings, the prefrontal cortex was a target anatomical region in Mexico City children and its damage could have contributed to their cognitive dysfunction. The present work presents a groundbreaking, interdisciplinary methodology for addressing relationships between environmental pollution, structural brain alterations by MRI, and cognitive deficits/delays in healthy children.

  15. 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.

  16. Abnormal EEG Complexity and Functional Connectivity of Brain in Patients with Acute Thalamic Ischemic Stroke

    PubMed Central

    Liu, Shuang; Guo, Jie; Meng, Jiayuan; Wang, Zhijun; Yao, Yang; Yang, Jiajia; Qi, Hongzhi; Ming, Dong

    2016-01-01

    Ischemic thalamus stroke has become a serious cardiovascular and cerebral disease in recent years. To date the existing researches mostly concentrated on the power spectral density (PSD) in several frequency bands. In this paper, we investigated the nonlinear features of EEG and brain functional connectivity in patients with acute thalamic ischemic stroke and healthy subjects. Electroencephalography (EEG) in resting condition with eyes closed was recorded for 12 stroke patients and 11 healthy subjects as control group. Lempel-Ziv complexity (LZC), Sample Entropy (SampEn), and brain network using partial directed coherence (PDC) were calculated for feature extraction. Results showed that patients had increased mean LZC and SampEn than the controls, which implied the stroke group has higher EEG complexity. For the brain network, the stroke group displayed a trend of weaker cortical connectivity, which suggests a functional impairment of information transmission in cortical connections in stroke patients. These findings suggest that nonlinear analysis and brain network could provide essential information for better understanding the brain dysfunction in the stroke and assisting monitoring or prognostication of stroke evolution. PMID:27403202

  17. Microstructural abnormalities of the brain white matter in attention-deficit/hyperactivity disorder

    PubMed Central

    Chen, Lizhou; Huang, Xiaoqi; Lei, Du; He, Ning; Hu, Xinyu; Chen, Ying; Li, Yuanyuan; Zhou, Jinbo; Guo, Lanting; Kemp, Graham J.; Gong, Qiyong

    2015-01-01

    Background Attention-deficit/hyperactivity disorder (ADHD) is an early-onset neurodevelopmental disorder with multiple behavioural problems and executive dysfunctions for which neuroimaging studies have reported a variety of abnormalities, with inconsistencies partly owing to confounding by medication and concurrent psychiatric disease. We aimed to investigate the microstructural abnormalities of white matter in unmedicated children and adolescents with pure ADHD and to explore the association between these abnormalities and behavioural symptoms and executive functions. Methods We assessed children and adolescents with ADHD and healthy controls using psychiatric interviews. Behavioural problems were rated using the revised Conners’ Parent Rating Scale, and executive functions were measured using the Stroop Colour-Word Test and the Wisconsin Card Sorting test. We acquired diffusion tensor imaging data using a 3 T MRI system, and we compared diffusion parameters, including fractional anisotropy (FA) and mean, axial and radial diffusivities, between the 2 groups. Results Thirty-three children and adolescents with ADHD and 35 healthy controls were included in our study. In patients compared with controls, FA was increased in the left posterior cingulum bundle as a result of both increased axial diffusivity and decreased radial diffusivity. In addition, the averaged FA of the cluster in this region correlated with behavioural measures as well as executive function in patients with ADHD. Limitations This study was limited by its cross-sectional design and small sample size. The cluster size of the significant result was small. Conclusion Our findings suggest that white matter abnormalities within the limbic network could be part of the neural underpinning of behavioural problems and executive dysfunction in patients with ADHD. PMID:25853285

  18. White matter abnormalities are associated with chronic postconcussion symptoms in blast-related mild traumatic brain injury.

    PubMed

    Miller, Danielle R; Hayes, Jasmeet P; Lafleche, Ginette; Salat, David H; Verfaellie, Mieke

    2016-01-01

    Blast-related mild traumatic brain injury (mTBI) is a common injury among Iraq and Afghanistan military veterans due to the frequent use of improvised explosive devices. A significant minority of individuals with mTBI report chronic postconcussion symptoms (PCS), which include physical, emotional, and cognitive complaints. However, chronic PCS are nonspecific and are also associated with mental health disorders such as posttraumatic stress disorder (PTSD). Identifying the mechanisms that contribute to chronic PCS is particularly challenging in blast-related mTBI, where the incidence of comorbid PTSD is high. In this study, we examined whether blast-related mTBI is associated with diffuse white matter changes, and whether these neural changes are associated with chronic PCS. Ninety Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) veterans were assigned to one of three groups including a blast-exposed no--TBI group, a blast-related mTBI without loss of consciousness (LOC) group (mTBI--LOC), and a blast-related mTBI with LOC group (mTBI + LOC). PCS were measured with the Rivermead Postconcussion Questionnaire. Results showed that participants in the mTBI + LOC group had more spatially heterogeneous white matter abnormalities than those in the no--TBI group. These white matter abnormalities were significantly associated with physical PCS severity even after accounting for PTSD symptoms, but not with cognitive or emotional PCS severity. A mediation analysis revealed that mTBI + LOC significantly influenced physical PCS severity through its effect on white matter integrity. These results suggest that white matter abnormalities are associated with chronic PCS independent of PTSD symptom severity and that these abnormalities are an important mechanism explaining the relationship between mTBI and chronic physical PCS.

  19. R6/2 Huntington’s disease Mice Develop Early and Progressive Abnormal Brain Metabolism and Seizures

    PubMed Central

    Cepeda-Prado, E; Popp, S; Khan, U; Stefanov, D; Rodriguez, J; Menalled, L; Dow-Edwards, D; Small, SA; Moreno, H

    2012-01-01

    A hallmark feature of Huntington's disease pathology is the atrophy of brain regions including, but not limited to, the striatum. Though MRI studies have identified structural CNS changes in several HD mouse models, the functional consequences of HD pathology during the progression of the disease have yet to be investigated using in vivo functional magnetic resonance imaging (fMRI). To address this issue, we first established the structural and functional MRI phenotype of juvenile HD mouse model R6/2 at early and advanced stages of disease. Significantly higher fMRI-signals (relative cerebral blood volumes-rCBV) and atrophy were observed in both age groups in specific brain regions. Next, fMRI results were correlated with electrophysiological analysis, which showed abnormal increases in neuronal activity in affected brain regions- thus identifying a mechanism accounting for the abnormal fMRI findings. [14C] deoxyglucose (2DG) maps to investigate patterns of glucose utilization were also generated. An interesting mismatch between increases in rCBV and decreases in glucose uptake was observed. Finally, we evaluated the sensitivity of this mouse line to audiogenic seizures early in the disease course. We found that R6/2 mice had an increased susceptibility to develop seizures. Together, these findings identified seizure activity in R6/2 mice, and show that neuroimaging measures sensitive to oxygen metabolism can be used as in vivo biomarkers, preceding the onset of an overt behavioral phenotype. Since fMRI-rCBV can also be obtained in patients, we propose that it may serve as a translational tool to evaluate therapeutic responses in humans and HD mouse models. PMID:22573668

  20. Abnormal Functional MRI BOLD Contrast in the Vegetative State after Severe Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Heelmann, Volker

    2010-01-01

    For the rehabilitation process, the treatment of patients surviving brain injury in a vegetative state is still a serious challenge. The aim of this study was to investigate patients exhibiting severely disturbed consciousness using functional magnetic resonance imaging. Five cases of posttraumatic vegetative state and one with minimal…

  1. Air Pollution, Cognitive Deficits and Brain Abnormalities: A Pilot Study with Children and Dogs

    ERIC Educational Resources Information Center

    Calderon-Garciduenas, Lilian; Mora-Tiscareno, Antonieta; Ontiveros, Esperanza; Gomez-Garza, Gilberto; Barragan-Mejia, Gerardo; Broadway, James; Chapman, Susan; Valencia-Salazar, Gildardo; Jewells, Valerie; Maronpot, Robert R.; Henriquez-Roldan, Carlos; Perez-Guille, Beatriz; Torres-Jardon, Ricardo; Herrit, Lou; Brooks, Diane; Osnaya-Brizuela, Norma; Monroy, Maria E.; Gonzalez-Maciel, Angelica; Reynoso-Robles, Rafael; Villarreal-Calderon, Rafael; Solt, Anna C.; Engle, Randall W.

    2008-01-01

    Exposure to air pollution is associated with neuroinflammation in healthy children and dogs in Mexico City. Comparative studies were carried out in healthy children and young dogs similarly exposed to ambient pollution in Mexico City. Children from Mexico City (n:55) and a low polluted city (n:18) underwent psychometric testing and brain magnetic…

  2. Brief Report: Abnormal Association between the Thalamus and Brain Size in Asperger's Disorder

    ERIC Educational Resources Information Center

    Hardan, Antonio Y.; Girgis, Ragy R.; Adams, Jason; Gilbert, Andrew R.; Melhem, Nadine M.; Keshavan, Matcheri S.; Minshew, Nancy J.

    2008-01-01

    The objective of this study was to examine the relationship between thalamic volume and brain size in individuals with Asperger's disorder (ASP). Volumetric measurements of the thalamus were performed on MRI scans obtained from 12 individuals with ASP (age range: 10-35 years) and 12 healthy controls (age range: 9-33 years). A positive correlation…

  3. Tobacco Smoking and MRI/MRS Brain Abnormalities Compared to Nonsmokers

    PubMed Central

    Domino, E.F.

    2008-01-01

    This mini review emphasizes the fact that tobacco smoking causes small but real biologic brain changes that need to be studied in depth. A crucial question is whether these anatomical/chemical changes reverse toward normal when smokers quit. This review is presented to stimulate further research to answer this question. PMID:18817837

  4. Co-Localisation of Abnormal Brain Structure and Function in Specific Language Impairment

    ERIC Educational Resources Information Center

    Badcock, Nicholas A.; Bishop, Dorothy V. M.; Hardiman, Mervyn J.; Barry, Johanna G.; Watkins, Kate E.

    2012-01-01

    We assessed the relationship between brain structure and function in 10 individuals with specific language impairment (SLI), compared to six unaffected siblings, and 16 unrelated control participants with typical language. Voxel-based morphometry indicated that grey matter in the SLI group, relative to controls, was increased in the left inferior…

  5. Modified total variation norm for the maximum a posteriori ordered subsets expectation maximization reconstruction in fan-beam SPECT brain perfusion imaging

    NASA Astrophysics Data System (ADS)

    Krol, Andrzej; Yang, Zhaoxia; Xu, Yuesheng; Wismüller, Axel; Feiglin, David H.

    2011-03-01

    The anisotropic geometry of Fan-Beam Collimator (FBC) Single Photon Emission Tomography (SPECT) is used in brain perfusion imaging with clinical goals to quantify regional cerebral blood flow and to accurately determine the location and extent of the brain perfusion defects. One of the difficult issues that need to be addressed is partial volume effect. The purpose of this study was to minimize the partial volume effect while preserving the optimal tradeoff between noise and bias, and maintaining spatial resolution in the reconstructed images acquired in FBC geometry. We modified conventional isotropic TV (L1) norm, which has only one hyperparameter, and replaced it with two independent TV (L1u) norms (TVxy and TVz) along two orthogonal basis vectors (XY, Z) in 3D reconstruction space. We investigated if the anisotropic norm with two hyperparameters (βxy and βz, where z is parallel to the axis-of-rotation) performed better in FBC-SPECT reconstruction, as compared to the conventional isotropic norm with one hyperparameter (β) only. We found that MAP-OSEM reconstruction with modified TV norm produced images with smaller partial volume effect, as compared to the conventional TV norm at a cost of slight increase in the bias and noise.

  6. Abnormal hemodynamic response to forepaw stimulation in rat brain after cocaine injection

    NASA Astrophysics Data System (ADS)

    Chen, Wei; Park, Kicheon; Choi, Jeonghun; Pan, Yingtian; Du, Congwu

    2015-03-01

    Simultaneous measurement of hemodynamics is of great importance to evaluate the brain functional changes induced by brain diseases such as drug addiction. Previously, we developed a multimodal-imaging platform (OFI) which combined laser speckle contrast imaging with multi-wavelength imaging to simultaneously characterize the changes in cerebral blood flow (CBF), oxygenated- and deoxygenated- hemoglobin (HbO and HbR) from animal brain. Recently, we upgraded our OFI system that enables detection of hemodynamic changes in response to forepaw electrical stimulation to study potential brain activity changes elicited by cocaine. The improvement includes 1) high sensitivity to detect the cortical response to single forepaw electrical stimulation; 2) high temporal resolution (i.e., 16Hz/channel) to resolve dynamic variations in drug-delivery study; 3) high spatial resolution to separate the stimulation-evoked hemodynamic changes in vascular compartments from those in tissue. The system was validated by imaging the hemodynamic responses to the forepaw-stimulations in the somatosensory cortex of cocaine-treated rats. The stimulations and acquisitions were conducted every 2min over 40min, i.e., from 10min before (baseline) to 30min after cocaine challenge. Our results show that the HbO response decreased first (at ~4min) followed by the decrease of HbR response (at ~6min) after cocaine, and both did not fully recovered for over 30min. Interestingly, while CBF decreased at 4min, it partially recovered at 18min after cocaine administration. The results indicate the heterogeneity of cocaine's effects on vasculature and tissue metabolism, demonstrating the unique capability of optical imaging for brain functional studies.

  7. Abnormal Activation of the Social Brain Network in Children with Autism Spectrum Disorder: An fMRI Study

    PubMed Central

    Kim, Sun-Young; Choi, Uk-Su; Park, Sung-Yeon; Oh, Se-Hong; Yoon, Hyo-Woon; Koh, Yun-Joo; Im, Woo-Young; Park, Jee-In; Song, Dong-Ho

    2015-01-01

    Objective The aim of this study is to investigate abnormal findings of social brain network in Korean children with autism spectrum disorder (ASD) compared with typically developing children (TDC). Methods Functional magnetic resonance imaging (fMRI) was performed to examine brain activations during the processing of emotional faces (happy, fearful, and neutral) in 17 children with ASD, 24 TDC. Results When emotional face stimuli were given to children with ASD, various areas of the social brain relevant to social cognition showed reduced activation. Specifically, ASD children exhibited less activation in the right amygdala (AMY), right superior temporal sulcus (STS) and right inferior frontal gyrus (IFG) than TDC group when fearful faces were shown. Activation of left insular cortex and right IFG in response to happy faces was less in the ASD group. Similar findings were also found in left superior insular gyrus and right insula in case of neutral stimulation. Conclusion These findings suggest that children with ASD have different processing of social and emotional experience at the neural level. In other words, the deficit of social cognition in ASD could be explained by the deterioration of the capacity for visual analysis of emotional faces, the subsequent inner imitation through mirror neuron system (MNS), and the ability to transmit it to the limbic system and to process the transmitted emotion. PMID:25670944

  8. A database for estimating organ dose for coronary angiography and brain perfusion CT scans for arbitrary spectra and angular tube current modulation

    SciTech Connect

    Rupcich, Franco; Badal, Andreu; Kyprianou, Iacovos; Schmidt, Taly Gilat

    2012-09-15

    Purpose: The purpose of this study was to develop a database for estimating organ dose in a voxelized patient model for coronary angiography and brain perfusion CT acquisitions with any spectra and angular tube current modulation setting. The database enables organ dose estimation for existing and novel acquisition techniques without requiring Monte Carlo simulations. Methods: The study simulated transport of monoenergetic photons between 5 and 150 keV for 1000 projections over 360 Degree-Sign through anthropomorphic voxelized female chest and head (0 Degree-Sign and 30 Degree-Sign tilt) phantoms and standard head and body CTDI dosimetry cylinders. The simulations resulted in tables of normalized dose deposition for several radiosensitive organs quantifying the organ dose per emitted photon for each incident photon energy and projection angle for coronary angiography and brain perfusion acquisitions. The values in a table can be multiplied by an incident spectrum and number of photons at each projection angle and then summed across all energies and angles to estimate total organ dose. Scanner-specific organ dose may be approximated by normalizing the database-estimated organ dose by the database-estimated CTDI{sub vol} and multiplying by a physical CTDI{sub vol} measurement. Two examples are provided demonstrating how to use the tables to estimate relative organ dose. In the first, the change in breast and lung dose during coronary angiography CT scans is calculated for reduced kVp, angular tube current modulation, and partial angle scanning protocols relative to a reference protocol. In the second example, the change in dose to the eye lens is calculated for a brain perfusion CT acquisition in which the gantry is tilted 30 Degree-Sign relative to a nontilted scan. Results: Our database provides tables of normalized dose deposition for several radiosensitive organs irradiated during coronary angiography and brain perfusion CT scans. Validation results indicate

  9. Abnormalities of brain function during a nonverbal theory of mind task in schizophrenia.

    PubMed

    Brunet, Eric; Sarfati, Yves; Hardy-Baylé, Marie-Christine; Decety, Jean

    2003-01-01

    Theory of mind (ToM), the specific ability to attribute thoughts and feelings to oneself and others is generally impaired in schizophrenia. Previous studies demonstrated a deficit of the attribution of intentions to others among patients having formal thought disorder. During nonverbal tasks, such a function requires both the visual perception of human figures and the understanding of their intentions. These processes are considered to involve the superior temporal sulcus and the medial prefrontal cortex, respectively. Are the functional patterns of activation associated with those processes abnormal in schizophrenia? Seven schizophrenic patients on medication performed a nonverbal attribution of intentions task as well as two matched physical logic tasks, with and without human figures, while H2O15 PET-scanning was performed. Data from the patients were compared to those of eight healthy controls matched for verbal IQ and sex. The experimental design allowed dissociating the effect of the perception of human figures from that of the attribution of intentions. During attribution of intentions, significant activations in the right prefrontal cortex were detected in the control subjects. Those activations were not found in the schizophrenic group. However, in both groups, the perception of human figure elicited bilateral activation of the occipitotemporal regions and of the posterior part of the superior temporal sulcus. Schizophrenic patients performing a nonverbal attribution of intentions task have an abnormal cerebral activity. PMID:12887982

  10. Brain gene expression differences are associated with abnormal tail biting behavior in pigs.

    PubMed

    Brunberg, E; Jensen, P; Isaksson, A; Keeling, L J

    2013-03-01

    Knowledge about gene expression in animals involved in abnormal behaviors can contribute to the understanding of underlying biological mechanisms. This study aimed to explore the motivational background to tail biting, an abnormal injurious behavior and severe welfare problem in pig production. Affymetrix microarrays were used to investigate gene expression differences in the hypothalamus and prefrontal cortex of pigs performing tail biting, pigs receiving bites to the tail and neutral pigs who were not involved in the behavior. In the hypothalamus, 32 transcripts were differentially expressed (P < 0.05) when tail biters were compared with neutral pigs, 130 when comparing receiver pigs with neutrals, and two when tail biters were compared with receivers. In the prefrontal cortex, seven transcripts were differently expressed in tail biters when compared with neutrals, seven in receivers vs. neutrals and none in the tail biters vs. receivers. In total, 19 genes showed a different expression pattern in neutral pigs when compared with both performers and receivers. This implies that the functions of these may provide knowledge about why the neutral pigs are not involved in tail biting behavior as performers or receivers. Among these 19 transcripts were genes associated with production traits in pigs (PDK4), sociality in humans and mice (GTF2I) and novelty seeking in humans (EGF). These are in line with hypotheses linking tail biting with reduced back fat thickness and explorative behavior. PMID:23146156

  11. Midline abnormalities and psychopathology: how reliable is the midsagittal magnetic resonance "window" into the brain?

    PubMed

    Coppola, R; Myslobodsky, M; Weinberger, D R

    1995-05-31

    The argument is made that mensuration of midsagittal magnetic resonance (MR) images is plagued with methodological errors due to confusion of the midsagittal MR image and the mesial brain surface. Several examples are given to demonstrate the effects of slice thickness and orientation on the size and shape of mesial structures. The benefits of examining contiguous slices and the necessity of consulting coronal and transaxial cuts in mensuration efforts of midsagittal cuts are emphasized.

  12. Dynamic susceptibility contrast-enhanced perfusion MR imaging in late radiation-induced injury of the brain.

    PubMed

    Chan, Y L; Yeung, D K W; Leung, S F; Lee, S F; Ching, A S C

    2005-01-01

    The objective of the study was to evaluate radiation-induced cerebral injury on dynamic susceptibility contrast-enhanced (DSCE) perfusion MR imaging and study its relationship with morphological severity and disease progression. Thirty-one patients with known radiation injury to the temporal lobes where studied. Gradient and spin-echo T2-weighted, gadolinium-enhanced T1-weighted and DSCE perfusion MR imaging were obtained in the coronal plane through the anterior temporal lobe. Regions of interest where selected in the anterior temporal lobes and the superior frontal lobe as control for analysis of perfusion parameters. The mean transit time (MTT) was prolonged in both the High Dose Zone (HDZ) receiving from two-thirds to the total dose of 66-71.2 Gy, and the Intermediary Dose Zone (IDZ) receiving up to 87% of the total dose. The HDZ but not the IDZ showed a low relative cerebral blood volume (rCBV) and relative cerebral blood flow index (rCBFi). The rCBV and rCBFi were significantly lower in both HDZ and LBZ in temporal lobes with severe lesions compared to the temporal lobes with mild lesions but there was no significant difference in bolus transit parameters. The rCBV and rCBFi were significantly lower in both HDZ and IDZ of the swollen temporal lobes compared to those without swelling. It was concluded that DSCE perfusion MR imaging demonstrated a derangement in perfusion in radiation-induced cerebral injury in rCBV, rCBFi and MTT, which were related to the severity of the radiation-induced injury and the dose of irradiation delivered.

  13. Abnormal Brain Dynamics Underlie Speech Production in Children with Autism Spectrum Disorder

    PubMed Central

    Valica, Tatiana; MacDonald, Matt J.; Taylor, Margot J.; Brian, Jessica; Lerch, Jason P.; Anagnostou, Evdokia

    2015-01-01

    A large proportion of children with autism spectrum disorder (ASD) have speech and/or language difficulties. While a number of structural and functional neuroimaging methods have been used to explore the brain differences in ASD with regards to speech and language comprehension and production, the neurobiology of basic speech function in ASD has not been examined. Magnetoencephalography (MEG) is a neuroimaging modality with high spatial and temporal resolution that can be applied to the examination of brain dynamics underlying speech as it can capture the fast responses fundamental to this function. We acquired MEG from 21 children with high‐functioning autism (mean age: 11.43 years) and 21 age‐ and sex‐matched controls as they performed a simple oromotor task, a phoneme production task and a phonemic sequencing task. Results showed significant differences in activation magnitude and peak latencies in primary motor cortex (Brodmann Area 4), motor planning areas (BA 6), temporal sequencing and sensorimotor integration areas (BA 22/13) and executive control areas (BA 9). Our findings of significant functional brain differences between these two groups on these simple oromotor and phonemic tasks suggest that these deficits may be foundational and could underlie the language deficits seen in ASD. Autism Res 2016, 9: 249–261. © 2015 International Society for Autism Research, Wiley Periodicals, Inc. PMID:26363154

  14. Functional brain abnormalities localized in 55 chronic tinnitus patients: fusion of SPECT coincidence imaging and MRI

    PubMed Central

    Farhadi, Mohammad; Mahmoudian, Saeid; Saddadi, Fariba; Karimian, Ali Reza; Mirzaee, Mohammad; Ahmadizadeh, Majid; Ghasemikian, Khosro; Gholami, Saeid; Ghoreyshi, Esmaeel; Beyty, Saeid; Shamshiri, Ahmadreza; Madani, Sedighe; Bakaev, Valery; Moradkhani, Seddighe; Raeisali, Gholamreza

    2010-01-01

    Tinnitus is often defined as the perception of sounds or noise in the absence of any external auditory stimuli. The pathophysiology of subjective idiopathic tinnitus remains unclear. The aim of this study was to investigate the functional brain activities and possible involved cerebral areas in subjective idiopathic tinnitus patients by means of single photon emission computerized tomography (SPECT) coincidence imaging, which was fused with magnetic resonance imaging (MRI). In this cross-sectional study, 56 patients (1 subject excluded) with subjective tinnitus and 8 healthy controls were enrolled. After intravenous injection of 5 mCi F18-FDG (fluorodeoxyglucose), all subjects underwent a brain SPECT coincidence scan, which was then superimposed on their MRIs. In the eight regions of interest (middle temporal, inferotemporal, medial temporal, lateral temporal, temporoparietal, frontal, frontoparietal, and parietal areas), the more pronounced values were represented in medial temporal, inferotemporal, and temporoparietal areas, which showed more important proportion of associative auditory cortices in functional attributions of tinnitus than primary auditory cortex. Brain coincidence SPECT scan, when fused on MRI is a valuable technique in the assessment of patients with tinnitus and could show the significant role of different regions of central nervous system in functional attributions of tinnitus. PMID:20068582

  15. Functional brain abnormalities localized in 55 chronic tinnitus patients: fusion of SPECT coincidence imaging and MRI.

    PubMed

    Farhadi, Mohammad; Mahmoudian, Saeid; Saddadi, Fariba; Karimian, Ali Reza; Mirzaee, Mohammad; Ahmadizadeh, Majid; Ghasemikian, Khosro; Gholami, Saeid; Ghoreyshi, Esmaeel; Beyty, Saeid; Shamshiri, Ahmadreza; Madani, Sedighe; Bakaev, Valery; Moradkhani, Seddighe; Raeisali, Gholamreza

    2010-04-01

    Tinnitus is often defined as the perception of sounds or noise in the absence of any external auditory stimuli. The pathophysiology of subjective idiopathic tinnitus remains unclear. The aim of this study was to investigate the functional brain activities and possible involved cerebral areas in subjective idiopathic tinnitus patients by means of single photon emission computerized tomography (SPECT) coincidence imaging, which was fused with magnetic resonance imaging (MRI). In this cross-sectional study, 56 patients (1 subject excluded) with subjective tinnitus and 8 healthy controls were enrolled. After intravenous injection of 5 mCi F18-FDG (fluorodeoxyglucose), all subjects underwent a brain SPECT coincidence scan, which was then superimposed on their MRIs. In the eight regions of interest (middle temporal, inferotemporal, medial temporal, lateral temporal, temporoparietal, frontal, frontoparietal, and parietal areas), the more pronounced values were represented in medial temporal, inferotemporal, and temporoparietal areas, which showed more important proportion of associative auditory cortices in functional attributions of tinnitus than primary auditory cortex. Brain coincidence SPECT scan, when fused on MRI is a valuable technique in the assessment of patients with tinnitus and could show the significant role of different regions of central nervous system in functional attributions of tinnitus.

  16. Reversible Brain Abnormalities in People Without Signs of Mountain Sickness During High-Altitude Exposure

    PubMed Central

    Fan, Cunxiu; Zhao, Yuhua; Yu, Qian; Yin, Wu; Liu, Haipeng; Lin, Jianzhong; Yang, Tianhe; Fan, Ming; Gesang, Luobu; Zhang, Jiaxing

    2016-01-01

    A large proportion of lowlanders ascending to high-altitude (HA) show no signs of mountain sickness. Whether their brains have indeed suffered from HA environment and the persistent sequelae after return to lowland remain unknown. Thirty-one sea-level college students, who had a 30-day teaching on Qinghai-Tibet plateau underwent MRI scans before, during, and two months after HA exposure. Brain volume, cortical structures, and white matter microstructure were measured. Besides, serum neuron-specific enolase (NSE), C-reactive protein, and interleukin-6 and neuropsychiatric behaviors were tested. After 30-day HA exposure, the gray and white matter volumes and cortical surface areas significantly increased, with cortical thicknesses and curvatures changed in a wide spread regions; Anisotropy decreased with diffusivities increased in multiple sites of white matter tracts. Two months after HA exposure, cortical measurements returned to basal level. However, increased anisotropy with decreased diffusivities was observed. Behaviors and serum inflammatory factor did not significant changed during three time-point tests. NSE significantly decreased during HA but increased after HA exposure. Results suggest brain swelling occurred in people without neurological signs at HA, but no negative sequelae in cortical structures and neuropsychiatric functions were left after the return to lowlands. Reoxygenation changed white matter microstructure. PMID:27633944

  17. Reversible Brain Abnormalities in People Without Signs of Mountain Sickness During High-Altitude Exposure.

    PubMed

    Fan, Cunxiu; Zhao, Yuhua; Yu, Qian; Yin, Wu; Liu, Haipeng; Lin, Jianzhong; Yang, Tianhe; Fan, Ming; Gesang, Luobu; Zhang, Jiaxing

    2016-01-01

    A large proportion of lowlanders ascending to high-altitude (HA) show no signs of mountain sickness. Whether their brains have indeed suffered from HA environment and the persistent sequelae after return to lowland remain unknown. Thirty-one sea-level college students, who had a 30-day teaching on Qinghai-Tibet plateau underwent MRI scans before, during, and two months after HA exposure. Brain volume, cortical structures, and white matter microstructure were measured. Besides, serum neuron-specific enolase (NSE), C-reactive protein, and interleukin-6 and neuropsychiatric behaviors were tested. After 30-day HA exposure, the gray and white matter volumes and cortical surface areas significantly increased, with cortical thicknesses and curvatures changed in a wide spread regions; Anisotropy decreased with diffusivities increased in multiple sites of white matter tracts. Two months after HA exposure, cortical measurements returned to basal level. However, increased anisotropy with decreased diffusivities was observed. Behaviors and serum inflammatory factor did not significant changed during three time-point tests. NSE significantly decreased during HA but increased after HA exposure. Results suggest brain swelling occurred in people without neurological signs at HA, but no negative sequelae in cortical structures and neuropsychiatric functions were left after the return to lowlands. Reoxygenation changed white matter microstructure. PMID:27633944

  18. Differential Impact of Hyponatremia and Hepatic Encephalopathy on Health-Related Quality of Life and Brain Metabolite Abnormalities in Cirrhosis

    PubMed Central

    Ahluwalia, Vishwadeep; Wade, James B; Thacker, Leroy; Kraft, Kenneth A; Sterling, Richard K; Stravitz, R Todd; Fuchs, Michael; Bouneva, Iliana; Puri, Puneet; Luketic, Velimir; Sanyal, Arun J; Gilles, HoChong; Heuman, Douglas M; Bajaj, Jasmohan S

    2013-01-01

    Background Hyponatremia (HN) and hepatic encephalopathy (HE) together can impair health-related quality-of-life (HRQOL) and cognition in cirrhosis. Aim To study effect of hyponatremia on cognition, HRQOL and brain MR spectroscopy (MRS) independent of HE. Methods Four cirrhotic groups(no HE/HN, HE alone, HN alone (sodium<130mEq/L),HE+HN) underwent cognitive testing, HRQOL using Sickness Impact Profile (SIP: higher score is worse; has psycho-social and physical sub-scores) and brain MRS (myoinositol(mI) and glutamate+glutamine(Glx)), which were compared across groups. A subset underwent HRQOL testing before/after diuretic withdrawal. Results 82 cirrhotics (30 no HE/HN, 25 HE, 17 HE+HN and 10 HN, MELD 12, 63% Hepatitis C) were included. Cirrhotics with HN alone and without HE/HN had better cognition compared to HE groups (median abnormal tests no-HE/HN:3, HN:3.5, HE:6.5,HE+HN:7, p=0.008). Despite better cognition, HN only patients had worse HRQOL in total and psychosocial SIP while both HN groups (with/without HE) had a significantly worse physical SIP(p<0.0001, all comparisons). Brain MRS showed lowest Glx in HN and highest in HE groups (p<0.02). mI levels were comparably decreased in the three affected (HE,HE+HN and HN) groups compared to no HE/HN and were associated with poor HRQOL. Six HE+HN cirrhotics underwent diuretic withdrawal which improved serum sodium and total/psycho-social SIP scores. Conclusions Hyponatremic cirrhotics without HE have poor HRQOL despite better cognition than those with concomitant HE. Glx levels were lowest in HN without HE but mI was similar across affected groups. HRQOL improved after diuretic withdrawal. Hyponatremia has a complex, non-linear relationship with brain Glx and mI, cognition and HRQOL. PMID:23665182

  19. Abnormal thalamocortical dynamics may be altered by deep brain stimulation: using magnetoencephalography to study phantom limb pain.

    PubMed

    Ray, N J; Jenkinson, N; Kringelbach, M L; Hansen, P C; Pereira, E A; Brittain, J S; Holland, P; Holliday, I E; Owen, S; Stein, J; Aziz, T

    2009-01-01

    Deep brain stimulation (DBS) is used to alleviate chronic pain. Using magnetoencephalography (MEG) to study the mechanisms of DBS for pain is difficult because of the artefact caused by the stimulator. We were able to record activity over the occipital lobe of a patient using DBS for phantom limb pain during presentation of a visual stimulus. This demonstrates that MEG can be used to study patients undergoing DBS provided control stimuli are used to check the reliability of the data. We then asked the patient to rate his pain during and off DBS. Correlations were found between these ratings and power in theta (6-9) and beta bands (12-30). Further, there was a tendency for frequencies under 25 Hz to correlate with each other after a period off stimulation compared with immediately after DBS. The results are interpreted as reflecting abnormal thalamocortical dynamics, previously implicated in painful syndromes.

  20. Functional brain abnormalities in psychiatric disorders: neural mechanisms to detect and resolve cognitive conflict and interference.

    PubMed

    Melcher, Tobias; Falkai, Peter; Gruber, Oliver

    2008-11-01

    In the present article, we review functional neuroimaging studies on interference processing and performance monitoring in three groups of psychiatric disorders, (1) mood disorders, (2) schizophrenia, and (3) obsessive-compulsive disorder (OCD). Ad (1) Behavioral performance measures suggest an impaired interference resolution capability in symptomatic bipolar disorder patients. A series of neuroimaging analyses found alterations in the ACC-DLPFC system in mood disorder (unipolar depressed and bipolar) patients, putatively reflective of an abnormal interplay of monitoring and executive neurocognitive functions. Other studies of euthymic bipolar patients showed relatively decreased interference-related activation in rostroventral PFC which conceivably underlies defective inhibitory control. Ad (2) Behavioral Stroop studies revealed a specific performance pattern of schizophrenia patients (normal RT interference but increased error interference and RT facilitation) suggestive of a deficit in ignoring irrelevant (word) information. Moreover, reduced/absent behavioral post-error and post-conflict adaptation effects suggest alterations in performance monitoring and/or adjustment capability in these patients. Neuroimaging findings converge to suggest a disorder-related abnormal neurophysiology in ACC which consistently showed conflict- and error-related hypoactivation that, however, appeared to be modulated by different factors. Moreover, studies suggest a specific deficit in context processing in schizophrenia, evidently related to activation reduction in DLPFC. Ad (3) Behavioral findings provide evidence for impaired interference resolution in OCD. Neuroimaging results consistently showed conflict- and error-related ACC hyperactivation which--conforming OCD pathogenesis models--can be conclusively interpreted as reflecting overactive performance monitoring. Taken together, interference resolution and performance monitoring appeared to be fruitful concepts in the

  1. Asymmetric Di-methyl Arginine is Strongly Associated with Cognitive Dysfunction and Brain MR Spectroscopic Abnormalities in Cirrhosis

    PubMed Central

    Bajaj, Jasmohan S; Ahluwalia, Vishwadeep; Wade, James B; Sanyal, Arun J; White, Melanie B; Noble, Nicole A; Monteith, Pamela; Fuchs, Michael; Sterling, Richard K; Luketic, Velimir; Bouneva, Iliana; Stravitz, Richard T; Puri, Puneet; Kraft, Kenneth A; Gilles, HoChong; Heuman, Douglas M

    2012-01-01

    Background Asymmetric di-methyl arginine (ADMA) is an inhibitor of nitric oxide synthase that accumulates in liver disease and may contribute to hepatic encephalopathy(HE). Aim To evaluate the association of ADMA with cognition and brain MR spectroscopy(MRS) in cirrhosis. Methods Cirrhotic patients with/without prior HE and non-cirrhotic controls underwent cognitive testing and ADMA determination. A subgroup underwent brain MRS [Glutamine/glutamate(Glx), myoinositol(mI), N-acetyl-aspartate(NAA) in parietal white, occipital gray and anterior cingulate(ACC)]. We also tested cognition and ADMA in a cirrhotic subgroup before and 1 month after transjugular intrahepatic portosystemic shunting (TIPS). Cognition and MRS values were correlated with ADMA and compared between groups using multi-variable regression. ADMA levels were compared between those who did/did not develop post-TIPS HE. Results 90 cirrhotics (MELD13, 54 prior HE) and 16 controls were included. Controls had better cognition and lower ADMA, Glx and higher mI compared to cirrhotics. Prior HE patients had worse cognition, higher ADMA and Glx and lower mI compared to non-HE cirrhotics. ADMA was positively correlated with MELD (r=0.58,p<0.0001), abnormal cognitive test number(r=0.66,p<0.0001) and Glx and NAAA (white matter,ACC) and negatively with mI. On regression, ADMA predicted number of abnormal tests and mean Z-score independent of prior HE and MELD. 12 patients underwent TIPS;7 developed HE post-TIPS. ADMA increased post-TIPS in patients who developed HE(p=0.019) but not in others(p=0.89). Conclusions A strong association of ADMA with cognition and prior HE was found independent of MELD score in cirrhosis. PMID:22889958

  2. Large-scale brain network abnormalities in Huntington's disease revealed by structural covariance.

    PubMed

    Minkova, Lora; Eickhoff, Simon B; Abdulkadir, Ahmed; Kaller, Christoph P; Peter, Jessica; Scheller, Elisa; Lahr, Jacob; Roos, Raymund A; Durr, Alexandra; Leavitt, Blair R; Tabrizi, Sarah J; Klöppel, Stefan

    2016-01-01

    Huntington's disease (HD) is a progressive neurodegenerative disorder that can be diagnosed with certainty decades before symptom onset. Studies using structural MRI have identified grey matter (GM) loss predominantly in the striatum, but also involving various cortical areas. So far, voxel-based morphometric studies have examined each brain region in isolation and are thus unable to assess the changes in the interrelation of brain regions. Here, we examined the structural covariance in GM volumes in pre-specified motor, working memory, cognitive flexibility, and social-affective networks in 99 patients with manifest HD (mHD), 106 presymptomatic gene mutation carriers (pre-HD), and 108 healthy controls (HC). After correction for global differences in brain volume, we found that increased GM volume in one region was associated with increased GM volume in another. When statistically comparing the groups, no differences between HC and pre-HD were observed, but increased positive correlations were evident for mHD, relative to pre-HD and HC. These findings could be explained by a HD-related neuronal loss heterogeneously affecting the examined network at the pre-HD stage, which starts to dominate structural covariance globally at the manifest stage. Follow-up analyses identified structural connections between frontoparietal motor regions to be linearly modified by disease burden score (DBS). Moderator effects of disease load burden became significant at a DBS level typically associated with the onset of unequivocal HD motor signs. Together with existing findings from functional connectivity analyses, our data indicates a critical role of these frontoparietal regions for the onset of HD motor signs.

  3. Steroid abnormalities and the developing brain: Declarative memory for emotionally arousing and neutral material in children with congenital adrenal hyperplasia

    PubMed Central

    Maheu, Françoise S.; Merke, Deborah P.; Schroth, Elizabeth A.; Keil, Margaret F.; Hardin, Julie; Poeth, Kaitlin; Pine, Daniel S.; Ernst, Monique

    2008-01-01

    Summary Steroid hormones modulate memory in animals and human adults. Little is known on the developmental effect of these hormones on the neural networks underlying memory. Using Congenital Adrenal Hyperplasia (CAH) as a naturalistic model of early steroid abnormalities, this study examines the consequences of CAH on memory and its neural correlates for emotionally arousing and neutral material in children. Seventeen patients with CAH and 17 age- and sex-matched healthy children (ages 12 to 14 years) completed the study. Subjects were presented positive, negative and neutral pictures. Memory recall occurred about 30 minutes after viewing the pictures. Children with CAH showed memory deficits for negative pictures compared to healthy children (p < 0.01). There were no group differences on memory performance for either positive or neutral pictures (p’s >0.1). In patients, 24h urinary-free cortisol levels (reflecting glucocorticoid replacement therapy) and testosterone levels were not associated with memory performance. These findings suggest that early steroid imbalances affect memory for negative material in children with CAH. Such memory impairments may result from abnormal brain organization and function following hormonal dysfunction during critical periods of development. PMID:18162329

  4. Apathy is associated with white matter abnormalities in anterior, medial brain regions in persons with HIV infection

    PubMed Central

    Kamat, Rujvi; Brown, Gregory G.; Bolden, Khalima; Fennema-Notestine, Christine; Archibald, Sarah; Marcotte, Thomas D.; Letendre, Scott L.; Ellis, Ronald J.; Woods, Steven Paul; Grant, Igor; Heaton, Robert K.

    2015-01-01

    Apathy is a relatively common psychiatric syndrome in HIV infection, but little is known about its neural correlates. In the present study, we examined the associations between apathy and diffusion tensor imaging (DTI) indices in key frontal white matter regions in the thalamocorticostriatal circuit that has been implicated in the expression of apathy. Nineteen participants with HIV infection and 19 demographically comparable seronegative comparison subjects completed the Apathy subscale of the Frontal Systems Behavioral Scale as a part of a comprehensive neuropsychiatric research evaluation. When compared to the seronegative participants, the HIV+ group had significantly more frontal white matter abnormalities. Within HIV+ persons, and as predicted, higher ratings of apathy were associated with greater white matter alterations in the anterior corona radiata, genu, and orbital medial prefrontal cortex. The associations between white matter alterations and apathy were independent of depression and were stronger among participants with lower current CD4 counts. All told, these findings indicate that apathy is independently associated with white matter abnormalities in anterior, medial brain regions in persons infected with HIV, particularly in the setting of lower current immune functioning, which may have implications for antiretroviral therapy. PMID:25275424

  5. Characterization of technetium-99m-L,L-ECD for brain perfusion imaging, Part 1: Pharmacology of technetium-99m ECD in nonhuman primates

    SciTech Connect

    Walovitch, R.C.; Hill, T.C.; Garrity, S.T.; Cheesman, E.H.; Burgess, B.A.; O'Leary, D.H.; Watson, A.D.; Ganey, M.V.; Morgan, R.A.; Williams, S.J. )

    1989-11-01

    Technetium-99m ethyl cysteinate dimer (({sup 99m}Tc)ECD) is a neutral, lipophilic complex which rapidly crosses the blood-brain barrier. Brain retention and tissue metabolism of ({sup 99m}Tc)ECD is dependent upon the stereochemical configuration of the complex. While both L,L and D,D enantiomers are extracted by the brain, only the L,L but not the D,D form, is metabolized and retained in the monkey brain (4.7% injected dose initially, T 1/2 greater than 24 hr). Dynamic single photon emission computed tomography imaging studies in one monkey indicates {sup 99m}Tc-L,L-ECD to be distributed in a pattern consistent with regional cerebral blood flow for up to 16 hr postinjection. Dual-labeled {sup 99m}Tc-L,L-ECD and ({sup 14}C)iodoantipyrine autoradiography studies performed 1 hr after administration show cortical gray to white matter ratios of both isotopes to be equivalent (approximately 4-5:1). These data suggest that {sup 99m}Tc-L,L-ECD will be useful for the scintigraphic assessment of cerebral perfusion in humans.

  6. Thallium-201 is comparable to technetium-99m-sestamibi for estimating cardiac function in patients with abnormal myocardial perfusion imaging.

    PubMed

    Wu, Ming-Che; Tsai, Cheng-Ting; Lin, Hui-Chun; Sun, Fang-Ju; Lin, Ku-Hung

    2015-11-01

    We analyzed the left-ventricular functional data obtained by cardiac-gated single-photon emission computed tomography myocardial perfusion imaging (MPI) with thallium-201 (Tl-201) and technetium-99m-sestamibi (MIBI) protocols in different groups of patients, and compared the data between Tl-201 and MIBI. Two hundred and seventy-two patients undergoing dipyridamole stress/redistribution Tl-201 MPI and 563 patients undergoing 1-day rest/dipyridamole stress MIBI MPI were included. Higher mean stress ejection fraction (EF), rest EF, and change in EF (ΔEF) were noticed in the normal MPI groups by both Tl-201 and MIBI protocols. Higher mean EF was observed in the females with normal MPI results despite their higher mean age. Comparisons between the Tl-201 and MIBI groups suggested a significant difference in all functional parameters, except for the rest end diastolic volume/end systolic volume and ΔEF between groups with negative MPI results. For the positive MPI groups, there was no significant difference in all parameters, except for the change in end diastolic volume and change in end systolic volume after stress between both protocols. The Tl-201 provides comparable left-ventricular functional data to MIBI cardiac-gated single-photon emission computed tomography in patients with positive MPI results, and may therefore be undertaken routinely for incremental functional information that is especially valuable to this patient group.

  7. Thallium-201 is comparable to technetium-99m-sestamibi for estimating cardiac function in patients with abnormal myocardial perfusion imaging.

    PubMed

    Wu, Ming-Che; Tsai, Cheng-Ting; Lin, Hui-Chun; Sun, Fang-Ju; Lin, Ku-Hung

    2015-11-01

    We analyzed the left-ventricular functional data obtained by cardiac-gated single-photon emission computed tomography myocardial perfusion imaging (MPI) with thallium-201 (Tl-201) and technetium-99m-sestamibi (MIBI) protocols in different groups of patients, and compared the data between Tl-201 and MIBI. Two hundred and seventy-two patients undergoing dipyridamole stress/redistribution Tl-201 MPI and 563 patients undergoing 1-day rest/dipyridamole stress MIBI MPI were included. Higher mean stress ejection fraction (EF), rest EF, and change in EF (ΔEF) were noticed in the normal MPI groups by both Tl-201 and MIBI protocols. Higher mean EF was observed in the females with normal MPI results despite their higher mean age. Comparisons between the Tl-201 and MIBI groups suggested a significant difference in all functional parameters, except for the rest end diastolic volume/end systolic volume and ΔEF between groups with negative MPI results. For the positive MPI groups, there was no significant difference in all parameters, except for the change in end diastolic volume and change in end systolic volume after stress between both protocols. The Tl-201 provides comparable left-ventricular functional data to MIBI cardiac-gated single-photon emission computed tomography in patients with positive MPI results, and may therefore be undertaken routinely for incremental functional information that is especially valuable to this patient group. PMID:26678935

  8. Acute caffeine administration impact on working memory-related brain activation and functional connectivity in the elderly: a BOLD and perfusion MRI study.

    PubMed

    Haller, S; Rodriguez, C; Moser, D; Toma, S; Hofmeister, J; Sinanaj, I; Van De Ville, D; Giannakopoulos, P; Lovblad, K-O

    2013-10-10

    In young individuals, caffeine-mediated blockade of adenosine receptors and vasoconstriction has direct repercussions on task-related activations, changes in functional connectivity, as well as global vascular effects. To date, no study has explored the effect of caffeine on brain activation patterns during highly demanding cognitive tasks in the elderly. This prospective, placebo-controlled crossover design comprises 24 healthy elderly individuals (mean age 68.8 ± 4.0 years, 17 females) performing a 2-back working memory (WM) task in functional magnetic resonance imaging (fMRI). Analyses include complimentary assessment of task-related activations (general linear model, GLM), functional connectivity (tensorial independent component analysis, TICA), and baseline perfusion (arterial spin labeling). Despite a reduction in whole-brain global perfusion (-22.7%), caffeine-enhanced task-related GLM activation in a local and distributed network is most pronounced in the bilateral striatum and to a lesser degree in the right middle and inferior frontal gyrus, bilateral insula, left superior and inferior parietal lobule as well as in the cerebellum bilaterally. TICA was significantly enhanced (+8.2%) in caffeine versus placebo in a distributed and task-relevant network including the pre-frontal cortex, the supplementary motor area, the ventral premotor cortex and the parietal cortex as well as the occipital cortex (visual stimuli) and basal ganglia. The inverse comparison of placebo versus caffeine had no significant difference. Activation strength of the task-relevant-network component correlated with response accuracy for caffeine yet not for placebo, indicating a selective cognitive effect of caffeine. The present findings suggest that acute caffeine intake enhances WM-related brain activation as well as functional connectivity of blood oxygen level-dependent fMRI in elderly individuals.

  9. Post mTBI fatigue is associated with abnormal brain functional connectivity.

    PubMed

    Nordin, Love Engström; Möller, Marika Christina; Julin, Per; Bartfai, Aniko; Hashim, Farouk; Li, Tie-Qiang

    2016-02-16

    This study set out to investigate the behavioral correlates of changes in resting-state functional connectivity before and after performing a 20 minute continuous psychomotor vigilance task (PVT) for patients with chronic post-concussion syndrome. Ten patients in chronic phase after mild traumatic brain injury (mTBI) with persisting symptoms of fatigue and ten matched healthy controls participated in the study. We assessed the participants' fatigue levels and conducted resting-state fMRI before and after a sustained PVT. We evaluated the changes in brain functional connectivity indices in relation to the subject's fatigue behavior using a quantitative data-driven analysis approach. We found that the PVT invoked significant mental fatigue and specific functional connectivity changes in mTBI patients. Furthermore, we found a significant linear correlation between self-reported fatigue and functional connectivity in the thalamus and middle frontal cortex. Our findings indicate that resting-state fMRI measurements may be a useful indicator of performance potential and a marker of fatigue level in the neural attentional system.

  10. Post mTBI fatigue is associated with abnormal brain functional connectivity

    PubMed Central

    Nordin, Love Engström; Möller, Marika Christina; Julin, Per; Bartfai, Aniko; Hashim, Farouk; Li, Tie-Qiang

    2016-01-01

    This study set out to investigate the behavioral correlates of changes in resting-state functional connectivity before and after performing a 20 minute continuous psychomotor vigilance task (PVT) for patients with chronic post-concussion syndrome. Ten patients in chronic phase after mild traumatic brain injury (mTBI) with persisting symptoms of fatigue and ten matched healthy controls participated in the study. We assessed the participants’ fatigue levels and conducted resting-state fMRI before and after a sustained PVT. We evaluated the changes in brain functional connectivity indices in relation to the subject’s fatigue behavior using a quantitative data-driven analysis approach. We found that the PVT invoked significant mental fatigue and specific functional connectivity changes in mTBI patients. Furthermore, we found a significant linear correlation between self-reported fatigue and functional connectivity in the thalamus and middle frontal cortex. Our findings indicate that resting-state fMRI measurements may be a useful indicator of performance potential and a marker of fatigue level in the neural attentional system. PMID:26878885

  11. Investigating brain community structure abnormalities in bipolar disorder using path length associated community estimation.

    PubMed

    Gadelkarim, Johnson J; Ajilore, Olusola; Schonfeld, Dan; Zhan, Liang; Thompson, Paul M; Feusner, Jamie D; Kumar, Anand; Altshuler, Lori L; Leow, Alex D

    2014-05-01

    In this article, we present path length associated community estimation (PLACE), a comprehensive framework for studying node-level community structure. Instead of the well-known Q modularity metric, PLACE utilizes a novel metric, Ψ(PL), which measures the difference between intercommunity versus intracommunity path lengths. We compared community structures in human healthy brain networks generated using these two metrics and argued that Ψ(PL) may have theoretical advantages. PLACE consists of the following: (1) extracting community structure using top-down hierarchical binary trees, where a branch at each bifurcation denotes a collection of nodes that form a community at that level, (2) constructing and assessing mean group community structure, and (3) detecting node-level changes in community between groups. We applied PLACE and investigated the structural brain networks obtained from a sample of 25 euthymic bipolar I subjects versus 25 gender- and age-matched healthy controls. Results showed community structural differences in posterior default mode network regions, with the bipolar group exhibiting left-right decoupling.

  12. Post mTBI fatigue is associated with abnormal brain functional connectivity.

    PubMed

    Nordin, Love Engström; Möller, Marika Christina; Julin, Per; Bartfai, Aniko; Hashim, Farouk; Li, Tie-Qiang

    2016-01-01

    This study set out to investigate the behavioral correlates of changes in resting-state functional connectivity before and after performing a 20 minute continuous psychomotor vigilance task (PVT) for patients with chronic post-concussion syndrome. Ten patients in chronic phase after mild traumatic brain injury (mTBI) with persisting symptoms of fatigue and ten matched healthy controls participated in the study. We assessed the participants' fatigue levels and conducted resting-state fMRI before and after a sustained PVT. We evaluated the changes in brain functional connectivity indices in relation to the subject's fatigue behavior using a quantitative data-driven analysis approach. We found that the PVT invoked significant mental fatigue and specific functional connectivity changes in mTBI patients. Furthermore, we found a significant linear correlation between self-reported fatigue and functional connectivity in the thalamus and middle frontal cortex. Our findings indicate that resting-state fMRI measurements may be a useful indicator of performance potential and a marker of fatigue level in the neural attentional system. PMID:26878885

  13. Central motor conduction in multiple sclerosis: evaluation of abnormalities revealed by transcutaneous magnetic stimulation of the brain.

    PubMed Central

    Ingram, D A; Thompson, A J; Swash, M

    1988-01-01

    Magnetic stimulation of the brain and spinal column was used to assess conduction in the descending central motor pathways controlling arm and leg muscles of 20 patients with multiple sclerosis, and 10 normal subjects. The multiple sclerosis patients had relapsing and remitting disease but all were ambulant and in stable clinical remission. Increased central motor conduction times (CMCTs), up to three times normal, were frequently encountered in multiple sclerosis patients and in leg muscles these correlated closely with clinical signs of upper motor neuron disturbance; in the upper limb muscles a higher proportion of subclinical lesions was present. Weak muscles were almost invariably associated with abnormal central conduction but increased CMCTs were also found for 52 of the 104 muscles with normal strength. CMCTs for lower limb muscles were directly related (p less than 0.005) to functional motor disability (Kurtzke and Ambulatory Index Scales). No patient developed clinical evidence of relapse during follow-up of at least 8 months. Magnetic brain stimulation is easy to perform, painless, and safe, and provides clinically relevant information in the diagnosis and monitoring of multiple sclerosis patients. PMID:2837538

  14. Theory of mind mediates the prospective relationship between abnormal social brain network morphology and chronic behavior problems after pediatric traumatic brain injury.

    PubMed

    Ryan, Nicholas P; Catroppa, Cathy; Beare, Richard; Silk, Timothy J; Crossley, Louise; Beauchamp, Miriam H; Yeates, Keith Owen; Anderson, Vicki A

    2016-04-01

    Childhood and adolescence coincide with rapid maturation and synaptic reorganization of distributed neural networks that underlie complex cognitive-affective behaviors. These regions, referred to collectively as the 'social brain network' (SBN) are commonly vulnerable to disruption from pediatric traumatic brain injury (TBI); however, the mechanisms that link morphological changes in the SBN to behavior problems in this population remain unclear. In 98 children and adolescents with mild to severe TBI, we acquired 3D T1-weighted MRIs at 2-8 weeks post-injury. For comparison, 33 typically developing controls of similar age, sex and education were scanned. All participants were assessed on measures of Theory of Mind (ToM) at 6 months post-injury and parents provided ratings of behavior problems at 24-months post-injury. Severe TBI was associated with volumetric reductions in the overall SBN package, as well as regional gray matter structural change in multiple component regions of the SBN. When compared with TD controls and children with milder injuries, the severe TBI group had significantly poorer ToM, which was associated with more frequent behavior problems and abnormal SBN morphology. Mediation analysis indicated that impaired theory of mind mediated the prospective relationship between abnormal SBN morphology and more frequent chronic behavior problems. Our findings suggest that sub-acute alterations in SBN morphology indirectly contribute to long-term behavior problems via their influence on ToM. Volumetric change in the SBN and its putative hub regions may represent useful imaging biomarkers for prediction of post-acute social cognitive impairment, which may in turn elevate risk for chronic behavior problems.

  15. Theory of mind mediates the prospective relationship between abnormal social brain network morphology and chronic behavior problems after pediatric traumatic brain injury.

    PubMed

    Ryan, Nicholas P; Catroppa, Cathy; Beare, Richard; Silk, Timothy J; Crossley, Louise; Beauchamp, Miriam H; Yeates, Keith Owen; Anderson, Vicki A

    2016-04-01

    Childhood and adolescence coincide with rapid maturation and synaptic reorganization of distributed neural networks that underlie complex cognitive-affective behaviors. These regions, referred to collectively as the 'social brain network' (SBN) are commonly vulnerable to disruption from pediatric traumatic brain injury (TBI); however, the mechanisms that link morphological changes in the SBN to behavior problems in this population remain unclear. In 98 children and adolescents with mild to severe TBI, we acquired 3D T1-weighted MRIs at 2-8 weeks post-injury. For comparison, 33 typically developing controls of similar age, sex and education were scanned. All participants were assessed on measures of Theory of Mind (ToM) at 6 months post-injury and parents provided ratings of behavior problems at 24-months post-injury. Severe TBI was associated with volumetric reductions in the overall SBN package, as well as regional gray matter structural change in multiple component regions of the SBN. When compared with TD controls and children with milder injuries, the severe TBI group had significantly poorer ToM, which was associated with more frequent behavior problems and abnormal SBN morphology. Mediation analysis indicated that impaired theory of mind mediated the prospective relationship between abnormal SBN morphology and more frequent chronic behavior problems. Our findings suggest that sub-acute alterations in SBN morphology indirectly contribute to long-term behavior problems via their influence on ToM. Volumetric change in the SBN and its putative hub regions may represent useful imaging biomarkers for prediction of post-acute social cognitive impairment, which may in turn elevate risk for chronic behavior problems. PMID:26796967

  16. A small number of abnormal brain connections predicts adult autism spectrum disorder.

    PubMed

    Yahata, Noriaki; Morimoto, Jun; Hashimoto, Ryuichiro; Lisi, Giuseppe; Shibata, Kazuhisa; Kawakubo, Yuki; Kuwabara, Hitoshi; Kuroda, Miho; Yamada, Takashi; Megumi, Fukuda; Imamizu, Hiroshi; Náñez, José E; Takahashi, Hidehiko; Okamoto, Yasumasa; Kasai, Kiyoto; Kato, Nobumasa; Sasaki, Yuka; Watanabe, Takeo; Kawato, Mitsuo

    2016-01-01

    Although autism spectrum disorder (ASD) is a serious lifelong condition, its underlying neural mechanism remains unclear. Recently, neuroimaging-based classifiers for ASD and typically developed (TD) individuals were developed to identify the abnormality of functional connections (FCs). Due to over-fitting and interferential effects of varying measurement conditions and demographic distributions, no classifiers have been strictly validated for independent cohorts. Here we overcome these difficulties by developing a novel machine-learning algorithm that identifies a small number of FCs that separates ASD versus TD. The classifier achieves high accuracy for a Japanese discovery cohort and demonstrates a remarkable degree of generalization for two independent validation cohorts in the USA and Japan. The developed ASD classifier does not distinguish individuals with major depressive disorder and attention-deficit hyperactivity disorder from their controls but moderately distinguishes patients with schizophrenia from their controls. The results leave open the viable possibility of exploring neuroimaging-based dimensions quantifying the multiple-disorder spectrum. PMID:27075704

  17. A small number of abnormal brain connections predicts adult autism spectrum disorder

    PubMed Central

    Yahata, Noriaki; Morimoto, Jun; Hashimoto, Ryuichiro; Lisi, Giuseppe; Shibata, Kazuhisa; Kawakubo, Yuki; Kuwabara, Hitoshi; Kuroda, Miho; Yamada, Takashi; Megumi, Fukuda; Imamizu, Hiroshi; Náñez Sr, José E.; Takahashi, Hidehiko; Okamoto, Yasumasa; Kasai, Kiyoto; Kato, Nobumasa; Sasaki, Yuka; Watanabe, Takeo; Kawato, Mitsuo

    2016-01-01

    Although autism spectrum disorder (ASD) is a serious lifelong condition, its underlying neural mechanism remains unclear. Recently, neuroimaging-based classifiers for ASD and typically developed (TD) individuals were developed to identify the abnormality of functional connections (FCs). Due to over-fitting and interferential effects of varying measurement conditions and demographic distributions, no classifiers have been strictly validated for independent cohorts. Here we overcome these difficulties by developing a novel machine-learning algorithm that identifies a small number of FCs that separates ASD versus TD. The classifier achieves high accuracy for a Japanese discovery cohort and demonstrates a remarkable degree of generalization for two independent validation cohorts in the USA and Japan. The developed ASD classifier does not distinguish individuals with major depressive disorder and attention-deficit hyperactivity disorder from their controls but moderately distinguishes patients with schizophrenia from their controls. The results leave open the viable possibility of exploring neuroimaging-based dimensions quantifying the multiple-disorder spectrum. PMID:27075704

  18. Endocrine abnormalities in severe traumatic brain injury--a cue to prognosis in severe craniocerebral trauma?

    PubMed

    Hackl, J M; Gottardis, M; Wieser, C; Rumpl, E; Stadler, C; Schwarz, S; Monkayo, R

    1991-01-01

    Patients with severe craniocerebral trauma (sCCT) display metabolic and endocrine changes. The question is raised whether hormonal patterns give cues to the prognosis of outcome or not. In 21 patients the function of the adrenocortical, gonadal, thyroid and human growth hormone (hGH)-insulin system was assessed. LH, FSH, TSH, prolactin and hGH were stimulated. 3 groups of patients were formed. Group I: patients in acute phase with a Glasgow Coma Score (GCS) more than 6 (group Ia) and less than 6 (group Ib). Group II: patients in transition to traumatic apallic syndrome (TAS). Group III: patients with full-blown or resolving TAS. The values of group Ia comprised low T3, T4 and testosterone, elevated insulin, normal hGH. Group Ib had hypothyroid T3 and T4 and an attenuated response of LH, TSH, prolactin and hGH to stimulation. Group III: there was seen an endocrine normalisation with elevated T4 and TBG and an altered response of hGH and prolactin to stimulation. Endocrine abnormalities were not helpful in predicting which course, either to better or to worse, a given patient would follow.

  19. Facial emotion recognition impairments are associated with brain volume abnormalities in individuals with HIV.

    PubMed

    Clark, Uraina S; Walker, Keenan A; Cohen, Ronald A; Devlin, Kathryn N; Folkers, Anna M; Pina, Matthew J; Tashima, Karen T

    2015-04-01

    Impaired facial emotion recognition abilities in HIV+ patients are well documented, but little is known about the neural etiology of these difficulties. We examined the relation of facial emotion recognition abilities to regional brain volumes in 44 HIV-positive (HIV+) and 44 HIV-negative control (HC) adults. Volumes of structures implicated in HIV-associated neuropathology and emotion recognition were measured on MRI using an automated segmentation tool. Relative to HC, HIV+ patients demonstrated emotion recognition impairments for fearful expressions, reduced anterior cingulate cortex (ACC) volumes, and increased amygdala volumes. In the HIV+ group, fear recognition impairments correlated significantly with ACC, but not amygdala volumes. ACC reductions were also associated with lower nadir CD4 levels (i.e., greater HIV-disease severity). These findings extend our understanding of the neurobiological substrates underlying an essential social function, facial emotion recognition, in HIV+ individuals and implicate HIV-related ACC atrophy in the impairment of these abilities.

  20. Facial Emotion Recognition Impairments are Associated with Brain Volume Abnormalities in Individuals with HIV

    PubMed Central

    Clark, Uraina S.; Walker, Keenan A.; Cohen, Ronald A.; Devlin, Kathryn N.; Folkers, Anna M.; Pina, Mathew M.; Tashima, Karen T.

    2015-01-01

    Impaired facial emotion recognition abilities in HIV+ patients are well documented, but little is known about the neural etiology of these difficulties. We examined the relation of facial emotion recognition abilities to regional brain volumes in 44 HIV-positive (HIV+) and 44 HIV-negative control (HC) adults. Volumes of structures implicated in HIV− associated neuropathology and emotion recognition were measured on MRI using an automated segmentation tool. Relative to HC, HIV+ patients demonstrated emotion recognition impairments for fearful expressions, reduced anterior cingulate cortex (ACC) volumes, and increased amygdala volumes. In the HIV+ group, fear recognition impairments correlated significantly with ACC, but not amygdala volumes. ACC reductions were also associated with lower nadir CD4 levels (i.e., greater HIV-disease severity). These findings extend our understanding of the neurobiological substrates underlying an essential social function, facial emotion recognition, in HIV+ individuals and implicate HIV-related ACC atrophy in the impairment of these abilities. PMID:25744868

  1. Facial emotion recognition impairments are associated with brain volume abnormalities in individuals with HIV.

    PubMed

    Clark, Uraina S; Walker, Keenan A; Cohen, Ronald A; Devlin, Kathryn N; Folkers, Anna M; Pina, Matthew J; Tashima, Karen T

    2015-04-01

    Impaired facial emotion recognition abilities in HIV+ patients are well documented, but little is known about the neural etiology of these difficulties. We examined the relation of facial emotion recognition abilities to regional brain volumes in 44 HIV-positive (HIV+) and 44 HIV-negative control (HC) adults. Volumes of structures implicated in HIV-associated neuropathology and emotion recognition were measured on MRI using an automated segmentation tool. Relative to HC, HIV+ patients demonstrated emotion recognition impairments for fearful expressions, reduced anterior cingulate cortex (ACC) volumes, and increased amygdala volumes. In the HIV+ group, fear recognition impairments correlated significantly with ACC, but not amygdala volumes. ACC reductions were also associated with lower nadir CD4 levels (i.e., greater HIV-disease severity). These findings extend our understanding of the neurobiological substrates underlying an essential social function, facial emotion recognition, in HIV+ individuals and implicate HIV-related ACC atrophy in the impairment of these abilities. PMID:25744868

  2. Abnormal intrinsic brain activity patterns in leukoaraiosis with and without cognitive impairment.

    PubMed

    Li, Chuanming; Yang, Jun; Yin, Xuntao; Liu, Chen; Zhang, Lin; Zhang, Xiaochun; Gui, Li; Wang, Jian

    2015-10-01

    The amplitude of low frequency fluctuations (ALFF) from resting-state functional MRI (rs-fMRI) signals can be used to detect intrinsic spontaneous brain activity and provide valuable insights into the pathomechanism of neural disease. In this study, we recruited 56 patients who had been diagnosed as having mild to severe leukoaraiosis. According to the neuropsychological tests, they were subdivided into a leukoaraiosis with cognitive impairment group (n = 28) and a leukoaraiosis without cognitive impairment group (n = 28). 28 volunteers were included as normal controls. We found that the three groups showed significant differences in ALFF in the brain regions of the right inferior occipital gyrus (IOG_R), left middle temporal gyrus (MTG_L), left precuneus (Pcu_L), right superior frontal gyrus (SFG_R) and right superior occipital gyrus (SOG_R). Compared with normal controls, the leukoaraiosis without cognitive impairment group exhibited significantly increased ALFF in the IOG_R, Pcu_L, SFG_R and SOG_R. While compared with leukoaraiosis without cognitive impairment group, the leukoaraiosis with cognitive impairment group showed significantly decreased ALFF in IOG_R, MTG_L, Pcu_L and SOG_R. A close negative correlation was found between the ALFF values of the MTG_L and the Montreal Cognitive Assessment (MoCA) scores. Our data demonstrate that white matter integrity and cognitive impairment are associated with different amplitude fluctuations of rs-fMRI signals. Leukoaraiosis is related to ALFF increases in IOG_R, Pcu_L, SFG_Orb_R and SOG_R. Decreased ALFF in MTG_L is characteristic of cognitive impairment and may aid in its early detection.

  3. Potential Adverse Effects of Prolonged Sevoflurane Exposure on Developing Monkey Brain: From Abnormal Lipid Metabolism to Neuronal Damage.

    PubMed

    Liu, Fang; Rainosek, Shuo W; Frisch-Daiello, Jessica L; Patterson, Tucker A; Paule, Merle G; Slikker, William; Wang, Cheng; Han, Xianlin

    2015-10-01

    Sevoflurane is a volatile anesthetic that has been widely used in general anesthesia, yet its safety in pediatric use is a public concern. This study sought to evaluate whether prolonged exposure of infant monkeys to a clinically relevant concentration of sevoflurane is associated with any adverse effects on the developing brain. Infant monkeys were exposed to 2.5% sevoflurane for 9 h, and frontal cortical tissues were harvested for DNA microarray, lipidomics, Luminex protein, and histological assays. DNA microarray analysis showed that sevoflurane exposure resulted in a broad identification of differentially expressed genes (DEGs) in the monkey brain. In general, these genes were associated with nervous system development, function, and neural cell viability. Notably, a number of DEGs were closely related to lipid metabolism. Lipidomic analysis demonstrated that critical lipid components, (eg, phosphatidylethanolamine, phosphatidylserine, and phosphatidylglycerol) were significantly downregulated by prolonged exposure of sevoflurane. Luminex protein analysis indicated abnormal levels of cytokines in sevoflurane-exposed brains. Consistently, Fluoro-Jade C staining revealed more degenerating neurons after sevoflurane exposure. These data demonstrate that a clinically relevant concentration of sevoflurane (2.5%) is capable of inducing and maintaining an effective surgical plane of anesthesia in the developing nonhuman primate and that a prolonged exposure of 9 h resulted in profound changes in gene expression, cytokine levels, lipid metabolism, and subsequently, neuronal damage. Generally, sevoflurane-induced neuronal damage was also associated with changes in lipid content, composition, or both; and specific lipid changes could provide insights into the molecular mechanism(s) underlying anesthetic-induced neurotoxicity and may be sensitive biomarkers for the early detection of anesthetic-induced neuronal damage.

  4. Epilepsy in the setting of full trisomy 18: A multicenter study on 18 affected children with and without structural brain abnormalities.

    PubMed

    Matricardi, Sara; Spalice, Alberto; Salpietro, Vincenzo; Di Rosa, Gabriella; Balistreri, Maria Cristina; Grosso, Salvatore; Parisi, Pasquale; Elia, Maurizio; Striano, Pasquale; Accorsi, Patrizia; Cusmai, Raffaella; Specchio, Nicola; Coppola, Giangennaro; Savasta, Salvatore; Carotenuto, Marco; Tozzi, Elisabetta; Ferrara, Pietro; Ruggieri, Martino; Verrotti, Alberto

    2016-09-01

    This paper reports on the clinical aspects, electroencephalographic (EEG) features, and neuroimaging findings in children with full trisomy 18 and associated epilepsy, and compares the evolution and outcome of their neurological phenotype. We retrospectively studied 18 patients (10 males and 8 females; aged 14 months to 9 years) with full trisomy 18 and epilepsy. All patients underwent comprehensive assessment including neuroimaging studies of the brain. We divided patients into two groups according to neuroimaging findings: (Group 1) 10 patients harboring structural brain malformations, and (Group 2) 8 patients with normal brain images. Group 1 had a significantly earlier age at seizure onset (2 months) compared to Group 2 (21 months). The seizure semiology was more severe in Group 1, who presented multiple seizure types, need for polytherapy (80% of patients), multifocal EEG abnormalities and poorer outcome (drug resistant epilepsy in 90% of patients) than Group 2 who presented a single seizure type, generalized or focal, and non-specific EEG pattern; these patients were successfully treated with monotherapy with good outcome. Imaging revealed a wide and complex spectrum of structural brain abnormalities including anomalies of the commissures, cerebellar malformations, cortical abnormalities, and various degrees of cortical atrophy. Epilepsy in full trisomy 18 may develop during the first months of life and can be associated with structural brain malformations. Patients with brain malformations can show multiple seizure types and can frequently be resistant to therapy with antiepileptic drugs. © 2016 Wiley Periodicals, Inc. PMID:27519909

  5. Abnormalities in brain structure and behavior in GSK-3alpha mutant mice

    PubMed Central

    2009-01-01

    Background Glycogen synthase kinase-3 (GSK-3) is a widely expressed and highly conserved serine/threonine protein kinase encoded by two genes that generate two related proteins: GSK-3α and GSK-3β. Mice lacking a functional GSK-3α gene were engineered in our laboratory; they are viable and display insulin sensitivity. In this study, we have characterized brain functions of GSK-3α KO mice by using a well-established battery of behavioral tests together with neurochemical and neuroanatomical analysis. Results Similar to the previously described behaviours of GSK-3β+/-mice, GSK-3α mutants display decreased exploratory activity, decreased immobility time and reduced aggressive behavior. However, genetic inactivation of the GSK-3α gene was associated with: decreased locomotion and impaired motor coordination, increased grooming activity, loss of social motivation and novelty; enhanced sensorimotor gating and impaired associated memory and coordination. GSK-3α KO mice exhibited a deficit in fear conditioning, however memory formation as assessed by a passive avoidance test was normal, suggesting that the animals are sensitized for active avoidance of a highly aversive stimulus in the fear-conditioning paradigm. Changes in cerebellar structure and function were observed in mutant mice along with a significant decrease of the number and size of Purkinje cells. Conclusion Taken together, these data support a role for the GSK-3α gene in CNS functioning and possible involvement in the development of psychiatric disorders. PMID:19925672

  6. Structural brain abnormalities in postural tachycardia syndrome: A VBM-DARTEL study

    PubMed Central

    Umeda, Satoshi; Harrison, Neil A.; Gray, Marcus A.; Mathias, Christopher J.; Critchley, Hugo D.

    2015-01-01

    Postural tachycardia syndrome (PoTS), a form of dysautonomia, is characterized by orthostatic intolerance, and is frequently accompanied by a range of symptoms including palpitations, lightheadedness, clouding of thought, blurred vision, fatigue, anxiety, and depression. Although the estimated prevalence of PoTS is approximately 5–10 times as common as the better-known condition orthostatic hypotension, the neural substrates of the syndrome are poorly characterized. In the present study, we used magnetic resonance imaging (MRI) with voxel-based morphometry (VBM) applying the diffeomorphic anatomical registration through exponentiated lie algebra (DARTEL) procedure to examine variation in regional brain structure associated with PoTS. We recruited 11 patients with established PoTS and 23 age-matched normal controls. Group comparison of gray matter volume revealed diminished gray matter volume within the left anterior insula, right middle frontal gyrus and right cingulate gyrus in the PoTS group. We also observed lower white matter volume beneath the precentral gyrus and paracentral lobule, right pre- and post-central gyrus, paracentral lobule and superior frontal gyrus in PoTS patients. Subsequent ROI analyses revealed significant negative correlations between left insula volume and trait anxiety and depression scores. Together, these findings of structural differences, particularly within insular and cingulate components of the salience network, suggest a link between dysregulated physiological reactions arising from compromised central autonomic control (and interoceptive representation) and increased vulnerability to psychiatric symptoms in PoTS patients. PMID:25852449

  7. Automated Detection of Brain Abnormalities in Neonatal Hypoxia Ischemic Injury from MR Images

    PubMed Central

    Ghosh, Nirmalya; Sun, Yu; Bhanu, Bir; Ashwal, Stephen; Obenaus, Andre

    2014-01-01

    We compared the efficacy of three automated brain injury detection methods, namely symmetry-integrated region growing (SIRG), hierarchical region splitting (HRS) and modified watershed segmentation (MWS) in human and animal magnetic resonance imaging (MRI) datasets for the detection of hypoxic ischemic injuries (HII). Diffusion weighted imaging (DWI, 1.5T) data from neonatal arterial ischemic stroke (AIS) patients, as well as T2-weighted imaging (T2WI, 11.7T, 4.7T) at seven different time-points (1, 4, 7, 10, 17, 24 and 31 days post HII) in rat-pup model of hypoxic ischemic injury were used to check the temporal efficacy of our computational approaches. Sensitivity, specificity, similarity were used as performance metrics based on manual (‘gold standard’) injury detection to quantify comparisons. When compared to the manual gold standard, automated injury location results from SIRG performed the best in 62% of the data, while 29% for HRS and 9% for MWS. Injury severity detection revealed that SIRG performed the best in 67% cases while HRS for 33% data. Prior information is required by HRS and MWS, but not by SIRG. However, SIRG is sensitive to parameter-tuning, while HRS and MWS are not. Among these methods, SIRG performs the best in detecting lesion volumes; HRS is the most robust, while MWS lags behind in both respects. PMID:25000294

  8. Optimization of the method for assessment of brain perfusion in humans using contrast-enhanced reflectometry: multidistance time-resolved measurements

    NASA Astrophysics Data System (ADS)

    Milej, Daniel; Janusek, Dariusz; Gerega, Anna; Wojtkiewicz, Stanislaw; Sawosz, Piotr; Treszczanowicz, Joanna; Weigl, Wojciech; Liebert, Adam

    2015-10-01

    The aim of the study was to determine optimal measurement conditions for assessment of brain perfusion with the use of optical contrast agent and time-resolved diffuse reflectometry in the near-infrared wavelength range. The source-detector separation at which the distribution of time of flights (DTOF) of photons provided useful information on the inflow of the contrast agent to the intracerebral brain tissue compartments was determined. Series of Monte Carlo simulations was performed in which the inflow and washout of the dye in extra- and intracerebral tissue compartments was modeled and the DTOFs were obtained at different source-detector separations. Furthermore, tests on diffuse phantoms were carried out using a time-resolved setup allowing the measurement of DTOFs at 16 source-detector separations. Finally, the setup was applied in experiments carried out on the heads of adult volunteers during intravenous injection of indocyanine green. Analysis of statistical moments of the measured DTOFs showed that the source-detector separation of 6 cm is recommended for monitoring of inflow of optical contrast to the intracerebral brain tissue compartments with the use of continuous wave reflectometry, whereas the separation of 4 cm is enough when the higher-order moments of DTOFs are available.

  9. Autism Spectrum Disorder as Early Neurodevelopmental Disorder: Evidence from the Brain Imaging Abnormalities in 2-3 Years Old Toddlers

    ERIC Educational Resources Information Center

    Xiao, Zhou; Qiu, Ting; Ke, Xiaoyan; Xiao, Xiang; Xiao, Ting; Liang, Fengjing; Zou, Bing; Huang, Haiqing; Fang, Hui; Chu, Kangkang; Zhang, Jiuping; Liu, Yijun

    2014-01-01

    Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that occurs within the first 3 years of life, which is marked by social skills and communication deficits along with stereotyped repetitive behavior. Although great efforts have been made to clarify the underlying neuroanatomical abnormalities and brain-behavior relationships…

  10. Brain metabolite abnormalities in ventromedial prefrontal cortex are related to duration of hypercortisolism and anxiety in patients with Cushing's syndrome.

    PubMed

    Crespo, Iris; Santos, Alicia; Gómez-Ansón, Beatriz; López-Mourelo, Olga; Pires, Patricia; Vives-Gilabert, Yolanda; Webb, Susan M; Resmini, Eugenia

    2016-09-01

    Chronic exposure to excessive glucocorticoid (GC) concentration in Cushing's syndrome (CS) can affect the brain structurally and functionally; ventromedial prefrontal cortex (vmPFC) is rich in GC receptors and therefore particularly vulnerable to excessive GC concentration. Proton magnetic resonance spectroscopy ((1)H-MRS) is a sensitive, non-invasive imaging technique that provides information on brain metabolites in vivo. Our aim was to investigate metabolite concentrations in vmPFC of CS patients and their relationship with clinical outcome. Twenty-two right-handed CS patients (7 active/15 in remission, 19 females, 41.6 ± 12.3 years) and 22 right-handed healthy controls (14 females, 41.7 ± 11 years) underwent brain MRI and (1)H-MRS exams at 3 Tesla. Concentrations of glutamate (Glu), glutamate + glutamine (Glx), creatine (Cr), N-Acetyl-aspartate (NAA), N-Acetyl-aspartate + N-acetylaspartylglutamate (total NAA), choline-containing compounds (Cho) and myoinositol (MI) were determined. Moreover, anxiety and depressive symptoms were evaluated with the State-Trait Anxiety Inventory (STAI) and the Beck Depression Inventory-II (BDI-II) test, respectively. CS patients had lower concentrations of glutamate and total NAA in the vmPFC than healthy controls (8.6 ± 1.2 vs. 9.3 ± 0.7 mmol/L, and 6.4 ± 0.8 vs. 6.8 ± 0.4 mmol/L, respectively; p < 0.05). Duration of hypercortisolism was negatively correlated with total NAA (r = -0.488, p < 0.05). Moreover, the concentration of total NAA was negatively correlated with anxiety state (r = -0.359, p < 0.05). Brain metabolites are abnormal in the vmPFC of patients with CS. Decreased total NAA and glutamate concentrations indicate neuronal dysfunction that appear to be related with duration of hypercortisolism and anxiety. PMID:27103571

  11. Brain metabolite abnormalities in ventromedial prefrontal cortex are related to duration of hypercortisolism and anxiety in patients with Cushing's syndrome.

    PubMed

    Crespo, Iris; Santos, Alicia; Gómez-Ansón, Beatriz; López-Mourelo, Olga; Pires, Patricia; Vives-Gilabert, Yolanda; Webb, Susan M; Resmini, Eugenia

    2016-09-01

    Chronic exposure to excessive glucocorticoid (GC) concentration in Cushing's syndrome (CS) can affect the brain structurally and functionally; ventromedial prefrontal cortex (vmPFC) is rich in GC receptors and therefore particularly vulnerable to excessive GC concentration. Proton magnetic resonance spectroscopy ((1)H-MRS) is a sensitive, non-invasive imaging technique that provides information on brain metabolites in vivo. Our aim was to investigate metabolite concentrations in vmPFC of CS patients and their relationship with clinical outcome. Twenty-two right-handed CS patients (7 active/15 in remission, 19 females, 41.6 ± 12.3 years) and 22 right-handed healthy controls (14 females, 41.7 ± 11 years) underwent brain MRI and (1)H-MRS exams at 3 Tesla. Concentrations of glutamate (Glu), glutamate + glutamine (Glx), creatine (Cr), N-Acetyl-aspartate (NAA), N-Acetyl-aspartate + N-acetylaspartylglutamate (total NAA), choline-containing compounds (Cho) and myoinositol (MI) were determined. Moreover, anxiety and depressive symptoms were evaluated with the State-Trait Anxiety Inventory (STAI) and the Beck Depression Inventory-II (BDI-II) test, respectively. CS patients had lower concentrations of glutamate and total NAA in the vmPFC than healthy controls (8.6 ± 1.2 vs. 9.3 ± 0.7 mmol/L, and 6.4 ± 0.8 vs. 6.8 ± 0.4 mmol/L, respectively; p < 0.05). Duration of hypercortisolism was negatively correlated with total NAA (r = -0.488, p < 0.05). Moreover, the concentration of total NAA was negatively correlated with anxiety state (r = -0.359, p < 0.05). Brain metabolites are abnormal in the vmPFC of patients with CS. Decreased total NAA and glutamate concentrations indicate neuronal dysfunction that appear to be related with duration of hypercortisolism and anxiety.

  12. Knockdown of zebrafish Lgi1a results in abnormal development, brain defects and a seizure-like behavioral phenotype

    PubMed Central

    Teng, Yong; Xie, Xiayang; Walker, Steven; Rempala, Grzegorz; Kozlowski, David J.; Mumm, Jeff S.; Cowell, John K.

    2010-01-01

    Epilepsy is a common disorder, typified by recurrent seizures with underlying neurological disorders or disease. Approximately one-third of patients are unresponsive to currently available therapies. Thus, a deeper understanding of the genetics and etiology of epilepsy is needed to advance the development of new therapies. Previously, treatment of zebrafish with epilepsy-inducing pharmacological agents was shown to result in a seizure-like phenotype, suggesting that fish provide a tractable model to understand the function of epilepsy-predisposing genes. Here, we report the first model of genetically linked epilepsy in zebrafish and provide an initial characterization of the behavioral and neurological phenotypes associated with morpholino (MO) knockdown of leucine-rich, glioma-inactivated 1a (lgi1a) expression. Mutations in the LGI1 gene in humans have been shown to predispose to a subtype of autosomal dominant epilepsy. Low-dose Lgi1a MO knockdown fish (morphants) appear morphologically normal but are sensitized to epilepsy-inducing drugs. High-dose Lgi1a morphants have morphological defects which persist into adult stages that are typified by smaller brains and eyes and abnormalities in tail shape, and display hyperactive swimming behaviors. Increased apoptosis was observed throughout the central nervous system of high-dose morphant fish, accounting for the size reduction of neural tissues. These observations demonstrate that zebrafish can be exploited to dissect the embryonic function(s) of genes known to predispose to seizure-like behavior in humans, and offer potential insight into the relationship between developmental neurobiological abnormalities and seizure. PMID:20819949

  13. In vivo evaluation of brain damage in the course of systemic lupus erythematosus using magnetic resonance spectroscopy, perfusion-weighted and diffusion-tensor imaging.

    PubMed

    Zimny, A; Szmyrka-Kaczmarek, M; Szewczyk, P; Bladowska, J; Pokryszko-Dragan, A; Gruszka, E; Wiland, P; Sasiadek, M

    2014-01-01

    Twenty-two neuropsychiatric (NPSLE) and 13 systemic lupus erythematosus (SLE) patients with a normal appearing brain on plain magnetic resonance (MR) as well as 20 age-matched healthy controls underwent MR spectroscopy (MRS), perfusion-weighted (PWI) and diffusion-tensor imaging (DTI). In MRS NAA/Cr, Cho/Cr and mI/Cr ratios were calculated from the posterior cingulate cortex and left parietal white matter. In PWI, values of cerebral blood volume (CBV) were assessed from 14 regions, including gray and white matter. In DTI fractional anisotropy (FA) values were obtained from 14 white matter tracts including projection, commissural and association fibers. All MR measurements were correlated with clinical data. SLE and NPSLE patients showed significantly (p < 0.05) lower NAA/Cr ratios within both evaluated regions and FA values within the cingulum, as well as a tendency to cortical hypoperfusion. Compared to SLE, NPSLE subjects revealed lower FA values within a wide range of association fibers and corpus callosum. Advanced MR techniques are capable of in vivo detection of complex microstructural brain damage in SLE and NPSLE subjects regarding neuronal loss, mild hypoperfusion and white matter disintegrity. MRS and DTI seem to show the highest usefulness in depicting early changes in normal appearing gray and white matter in SLE patients. PMID:24192079

  14. A New In Situ Brain Perfusion Flow Correction Method for Lipophilic Drugs Based on the pH-Dependent Crone-Renkin Equation

    PubMed Central

    Sun, Na

    2011-01-01

    Purpose To determine the flow-corrected luminal permeability, Pc, of lipophilic drugs measured by the in situ brain perfusion method under circumstances where the traditional Crone-Renkin equation (CRE) method, using diazepam as a flow marker, often fails. Methods The pH-dependent rate of brain penetration of five lipophilic drugs (amitriptyline, atomoxetine, imipramine, indomethacin, maprotiline, sertraline), as well as of atenolol and antipyrine, were measured in Sprague-Dawley rats. A new pH-dependent CRE was derived and applied to remove the hydrodynamic component of effective permeability, Pe, to produce Pc values. Results It was shown by the analysis of the in situ data in the pH 6.5–8.5 interval for the lipophilic bases that the average vascular flow Fpf = 0.036 mL·g−1·s−1, centered in a “flow-limit window” (FLW) bounded by Pemin = 170 and Pemax = 776 (10−6 cm·s−1 units). It was shown that the traditional CRE is expected not to work for half of the molecules in the FLW and is expected to underestimate (up to 64-fold) the other half of the molecules. Conclusion The new pH-CRE flow correction method applied to lipophilic ionizable drugs, based on the pH partition hypothesis, can overcome the limitations of the traditional CRE. PMID:21042838

  15. Landau-Kleffner syndrome: relation of clinical, EEG and Tc-99m-HMPAO brain SPECT findings and improvement in EEG after treatment.

    PubMed

    Sayit, E; Dirik, E; Durak, H; Uzuner, N; Anal, O; Cevik, N T

    1999-12-01

    Landau-Kleffner syndrome (LKS) is a rare childhood disorder characterized by acquired aphasia with seizures and electroencephalogram (EEG) abnormalities. Tc-99m-HMPAO SPECT was performed in three right handed children with LKS. A relative decrease in perfusion was found in the left temporal cortex of all three patients and also in the left frontoparietal cortex of one patient with hyperkinetic behavior. Degree of regional cerebral perfusion impairment did not correlate with the severity of clinical and EEG abnormalities. Asymmetrical temporoparietal perfusion appears characteristic of LKS. SPECT findings in LKS were evaluated as useful in elucidating the pathogenic features of the disorder in the brain.

  16. Physiological abnormalities in experimental allergic encephalomyelitis (EAE): II. Correlation between clinical signs and vestibular hyperreactivity and other signs of brain-stem dysfunction in rats with EAE.

    PubMed

    Brinkman, C J; Huygen, P L

    1984-09-01

    12 Lewis rats were inoculated with a guinea pig spinal cord tissue preparation. They developed experimental allergic encephalomyelitis (EAE) after 12-14 days manifested by weight loss, tail flaccidity, ataxia, hind limb paresis or paralysis and urinary incontinence. Concomitantly with EAE, all animals developed vestibular hyperreactivity (VH) of canal and otolith reflexes. Other signs of brain-stem dysfunction were also observed: abducens paralysis, facial weakness, tachypnoe and mydriasis with defective pupillary light reflex. The vestibular and other abnormalities subsided with some delay after recovery from clinical EAE, whilst histological abnormalities were still present in the CNS.

  17. Spectrum of brain abnormalities detected on whole body F-18 FDG PET/CT in patients undergoing evaluation for non-CNS malignancies

    PubMed Central

    Tripathi, Madhavi; Jaimini, Abhinav; D’Souza, Maria M; Sharma, Rajnish; Jain, Jyotika; Garg, Gunjan; Singh, Dinesh; Kumar, Nitin; Mishra, Anil K; Grover, Rajesh K; Mondal, Anupam

    2011-01-01

    We present the pattern of metabolic brain abnormalities detected in patients undergoing whole body (WB) F-18 flurodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) examination for non-central nervous system (CNS) malignancies. Knowledge of the PET/CT appearance of various intracranial metabolic abnormalities enables correct interpretation of PET scans in oncological patients where differentiation of metastasis from benign intracranial pathologies is important and improves specificity of the PET study. A complete clinical history and correlation with CT and MRI greatly helps in arriving at a correct imaging diagnosis. PMID:22174526

  18. Technetium-99m HM-PAO-SPECT study of regional cerebral perfusion in early Alzheimer's disease

    SciTech Connect

    Perani, D.; Di Piero, V.; Vallar, G.; Cappa, S.; Messa, C.; Bottini, G.; Berti, A.; Passafiume, D.; Scarlato, G.; Gerundini, P.

    1988-09-01

    Regional cerebral perfusion was evaluated by single photon emission computed tomography (SPECT) using technetium-99m hexamethylpropyleneamine oxime ((/sup 99m/Tc)HM-PAO) in sixteen patients with Alzheimer's disease (AD) in early clinical phase and in 16 healthy elderly controls. In all patients transmission computed tomography (TCT) and/or magnetic resonance imaging (MRI) did not show focal brain abnormalities. Relative to normal subjects, AD patients showed significant reductions in cortical/cerebellar activity ratio: cortical perfusion was globally depressed with the largest reductions in frontal and posterior temporo-parietal cortices. Asymmetries of relative perfusion between cerebral hemispheres were also demonstrated when language was affected or visuospatial functions were unevenly impaired. In patients with early AD, SPECT provides functional information to be compared with clinical and psychometric data.

  19. Central Nervous System Lymphoma in a 3-Year-Old Male Suffering from a Severe Juvenile Xanthogranuloma – the Usefulness of Perfusion Weighted Imaging and Diffusion Weighted Imaging in the Diagnostics of Pediatric Brain Tumors

    PubMed Central

    Neska-Matuszewska, Małgorzata; Zimny, Anna; Kałwak, Krzysztof; Sąsiadek, Marek J.

    2015-01-01

    Summary Background Primary Central Nervous System Lymphomas (PCNSLs) are rare, malignant brain tumors derived from lymphocytes B. Juvenile xanthogranuloma (JXG) is a non-Langerhans histiocytic cell disorder in children which mostly affects the skin. Rare fatalities have been reported in extracutaneous manifestation. Brain magnetic resonance imaging (MRI) is a method of choice in the diagnostics of all neoplastic CNS lesions. Perfusion weighted imaging (PWI) and diffusion weighted imaging (DWI) allow for more detailed analysis of brain tumors including the rate of neoangiogenesis and cellularity. We presented a pediatric patient suffering from JXG with CNS involvement and the role of brain MRI including DWI and PWI in the evaluation of brain focal lesions. Case Report A 3-year-old male with severe JXG underwent two stem cell transplantations with a development of neurological complications. The patient underwent emergency CT and MRI which revealed a non-specific enhancing focal brain lesion. In DWI it showed restricted diffusion while PWI revealed low values of rCBV and the signal intensity curve returning above the baseline level. Advanced MRI techniques such as DWI and PWI suggested PCNSL. Stereotactic biopsy confirmed PCNSL due to Ebstein-Barr virus reactivation. Conclusions The use of advanced MRI sequences is important to differentiate brain lesions in pediatric patients. The use of PWI and DWI facilitated the diagnosis of PCNSL. It is important to remember that PCNSLs show a very typical pattern of changes visualized with MRI such as: usually strong homogenous enhancement, restricted diffusion and low perfusion. PMID:25624957

  20. Abnormal N-glycosylation pattern for brain nucleotide pyrophosphatase-5 (NPP-5) in Mecp2-mutant murine models of Rett syndrome.

    PubMed

    Cortelazzo, Alessio; De Felice, Claudio; Guerranti, Roberto; Signorini, Cinzia; Leoncini, Silvia; Pecorelli, Alessandra; Scalabrì, Francesco; Madonna, Michele; Filosa, Stefania; Della Giovampaola, Cinzia; Capone, Antonietta; Durand, Thierry; Mirasole, Cristiana; Zolla, Lello; Valacchi, Giuseppe; Ciccoli, Lucia; Guy, Jacky; D'Esposito, Maurizio; Hayek, Joussef

    2016-04-01

    Neurological disorders can be associated with protein glycosylation abnormalities. Rett syndrome is a devastating genetic brain disorder, mainly caused by de novo loss-of-function mutations in the methyl-CpG binding protein 2 (MECP2) gene. Although its pathogenesis appears to be closely associated with a redox imbalance, no information on glycosylation is available. Glycoprotein detection strategies (i.e., lectin-blotting) were applied to identify target glycosylation changes in the whole brain of Mecp2 mutant murine models of the disease. Remarkable glycosylation pattern changes for a peculiar 50kDa protein, i.e., the N-linked brain nucleotide pyrophosphatase-5 were evidenced, with decreased N-glycosylation in the presymptomatic and symptomatic mutant mice. Glycosylation changes were rescued by selected brain Mecp2 reactivation. Our findings indicate that there is a causal link between the amount of Mecp2 and the N-glycosylation of NPP-5.

  1. Brain imaging and blood biomarker abnormalities in children with autosomal-dominant Alzheimer's disease: A cross-sectional Study

    PubMed Central

    Quiroz, Y.T.; Schultz, A.; Chen, K.; Protas, H.; Brickhouse, M.; Fleisher, A.S.; Langbaum, J.B.; Thiyyagura, P.; Fagan, A.M.; Shah, A.R.; Muniz, M.; Arboleda-Velasquez, JF; Munoz, C.; Garcia, G.; Acosta-Baena, N.; Giraldo, M.; Tirado, V.; Ramirez, D.; Tariot, PN; Dickerson, B.C.; Sperling, R.A.; Lopera, F.; Reiman, E.M.

    2015-01-01

    -carrying children demonstrated increased functional connectivity of the posterior cingulate cortex with medial temporal lobe regions (mean [SD] parameter estimates were 0.038 [0.070] for noncarriers and 0.190 [0.057] for carriers), as well as greater gray matter volumes in temporal regions (eg, left parahippocampus; P < . 049, corrected for multiple comparisons). CONCLUSIONS AND RELEVANCE Children at genetic risk for ADAD have functional and structural brain changes and abnormal levels of plasma Aβ1-42. The extent to which the underlying brain changes are either neurodegenerative or developmental remains to be determined. This study provides additional information about the earliest known biomarker changes associated with ADAD. PMID:26121081

  2. Early social enrichment rescues adult behavioral and brain abnormalities in a mouse model of fragile X syndrome.

    PubMed

    Oddi, Diego; Subashi, Enejda; Middei, Silvia; Bellocchio, Luigi; Lemaire-Mayo, Valerie; Guzmán, Manuel; Crusio, Wim E; D'Amato, Francesca R; Pietropaolo, Susanna

    2015-03-13

    Converging lines of evidence support the use of environmental stimulation to ameliorate the symptoms of a variety of neurodevelopmental disorders. Applying these interventions at very early ages is critical to achieve a marked reduction of the pathological phenotypes. Here we evaluated the impact of early social enrichment in Fmr1-KO mice, a genetic mouse model of fragile X syndrome (FXS), a major developmental disorder and the most frequent monogenic cause of autism. Enrichment was achieved by providing male KO pups and their WT littermates with enhanced social stimulation, housing them from birth until weaning with the mother and an additional nonlactating female. At adulthood they were tested for locomotor, social, and cognitive abilities; furthermore, dendritic alterations were assessed in the hippocampus and amygdala, two brain regions known to be involved in the control of the examined behaviors and affected by spine pathology in Fmr1-KOs. Enrichment rescued the behavioral FXS-like deficits displayed in adulthood by Fmr1-KO mice, that is, hyperactivity, reduced social interactions, and cognitive deficits. Early social enrichment also eliminated the abnormalities shown by adult KO mice in the morphology of hippocampal and amygdala dendritic spines, namely an enhanced density of immature vs mature types. Importantly, enrichment did not induce neurobehavioral changes in WT mice, thus supporting specific effects on FXS-like pathology. These findings show that early environmental stimulation has profound and long-term beneficial effects on the pathological FXS phenotype, thereby encouraging the use of nonpharmacological interventions for the treatment of this and perhaps other neurodevelopmental diseases.

  3. Early Social Enrichment Rescues Adult Behavioral and Brain Abnormalities in a Mouse Model of Fragile X Syndrome

    PubMed Central

    Oddi, Diego; Subashi, Enejda; Middei, Silvia; Bellocchio, Luigi; Lemaire-Mayo, Valerie; Guzmán, Manuel; Crusio, Wim E; D'Amato, Francesca R; Pietropaolo, Susanna

    2015-01-01

    Converging lines of evidence support the use of environmental stimulation to ameliorate the symptoms of a variety of neurodevelopmental disorders. Applying these interventions at very early ages is critical to achieve a marked reduction of the pathological phenotypes. Here we evaluated the impact of early social enrichment in Fmr1-KO mice, a genetic mouse model of fragile X syndrome (FXS), a major developmental disorder and the most frequent monogenic cause of autism. Enrichment was achieved by providing male KO pups and their WT littermates with enhanced social stimulation, housing them from birth until weaning with the mother and an additional nonlactating female. At adulthood they were tested for locomotor, social, and cognitive abilities; furthermore, dendritic alterations were assessed in the hippocampus and amygdala, two brain regions known to be involved in the control of the examined behaviors and affected by spine pathology in Fmr1-KOs. Enrichment rescued the behavioral FXS-like deficits displayed in adulthood by Fmr1-KO mice, that is, hyperactivity, reduced social interactions, and cognitive deficits. Early social enrichment also eliminated the abnormalities shown by adult KO mice in the morphology of hippocampal and amygdala dendritic spines, namely an enhanced density of immature vs mature types. Importantly, enrichment did not induce neurobehavioral changes in WT mice, thus supporting specific effects on FXS-like pathology. These findings show that early environmental stimulation has profound and long-term beneficial effects on the pathological FXS phenotype, thereby encouraging the use of nonpharmacological interventions for the treatment of this and perhaps other neurodevelopmental diseases. PMID:25348604

  4. BIANCA (Brain Intensity AbNormality Classification Algorithm): A new tool for automated segmentation of white matter hyperintensities.

    PubMed

    Griffanti, Ludovica; Zamboni, Giovanna; Khan, Aamira; Li, Linxin; Bonifacio, Guendalina; Sundaresan, Vaanathi; Schulz, Ursula G; Kuker, Wilhelm; Battaglini, Marco; Rothwell, Peter M; Jenkinson, Mark

    2016-11-01

    Reliable quantification of white matter hyperintensities of presumed vascular origin (WMHs) is increasingly needed, given the presence of these MRI findings in patients with several neurological and vascular disorders, as well as in elderly healthy subjects. We present BIANCA (Brain Intensity AbNormality Classification Algorithm), a fully automated, supervised method for WMH detection, based on the k-nearest neighbour (k-NN) algorithm. Relative to previous k-NN based segmentation methods, BIANCA offers different options for weighting the spatial information, local spatial intensity averaging, and different options for the choice of the number and location of the training points. BIANCA is multimodal and highly flexible so that the user can adapt the tool to their protocol and specific needs. We optimised and validated BIANCA on two datasets with different MRI protocols and patient populations (a "predominantly neurodegenerative" and a "predominantly vascular" cohort). BIANCA was first optimised on a subset of images for each dataset in terms of overlap and volumetric agreement with a manually segmented WMH mask. The correlation between the volumes extracted with BIANCA (using the optimised set of options), the volumes extracted from the manual masks and visual ratings showed that BIANCA is a valid alternative to manual segmentation. The optimised set of options was then applied to the whole cohorts and the resulting WMH volume estimates showed good correlations with visual ratings and with age. Finally, we performed a reproducibility test, to evaluate the robustness of BIANCA, and compared BIANCA performance against existing methods. Our findings suggest that BIANCA, which will be freely available as part of the FSL package, is a reliable method for automated WMH segmentation in large cross-sectional cohort studies. PMID:27402600

  5. High Prevalence of Chronic Pituitary and Target-Organ Hormone Abnormalities after Blast-Related Mild Traumatic Brain Injury

    PubMed Central

    Wilkinson, Charles W.; Pagulayan, Kathleen F.; Petrie, Eric C.; Mayer, Cynthia L.; Colasurdo, Elizabeth A.; Shofer, Jane B.; Hart, Kim L.; Hoff, David; Tarabochia, Matthew A.; Peskind, Elaine R.

    2011-01-01

    Studies of traumatic brain injury from all causes have found evidence of chronic hypopituitarism, defined by deficient production of one or more pituitary hormones at least 1 year after injury, in 25–50% of cases. Most studies found the occurrence of posttraumatic hypopituitarism (PTHP) to be unrelated to injury severity. Growth hormone deficiency (GHD) and hypogonadism were reported most frequently. Hypopituitarism, and in particular adult GHD, is associated with symptoms that resemble those of PTSD, including fatigue, anxiety, depression, irritability, insomnia, sexual dysfunction, cognitive deficiencies, and decreased quality of life. However, the prevalence of PTHP after blast-related mild TBI (mTBI), an extremely common injury in modern military operations, has not been characterized. We measured concentrations of 12 pituitary and target-organ hormones in two groups of male US Veterans of combat in Iraq or Afghanistan. One group consisted of participants with blast-related mTBI whose last blast exposure was at least 1 year prior to the study. The other consisted of Veterans with similar military deployment histories but without blast exposure. Eleven of 26, or 42% of participants with blast concussions were found to have abnormal hormone levels in one or more pituitary axes, a prevalence similar to that found in other forms of TBI. Five members of the mTBI group were found with markedly low age-adjusted insulin-like growth factor-I (IGF-I) levels indicative of probable GHD, and three had testosterone and gonadotropin concentrations consistent with hypogonadism. If symptoms characteristic of both PTHP and PTSD can be linked to pituitary dysfunction, they may be amenable to treatment with hormone replacement. Routine screening for chronic hypopituitarism after blast concussion shows promise for appropriately directing diagnostic and therapeutic decisions that otherwise may remain unconsidered and for markedly facilitating recovery and rehabilitation. PMID

  6. Renal perfusion scintiscan

    MedlinePlus

    Renal perfusion scintigraphy; Radionuclide renal perfusion scan; Perfusion scintiscan - renal; Scintiscan - renal perfusion ... supply the kidneys. This is a condition called renal artery stenosis. Significant renal artery stenosis may be ...

  7. Large national series of patients with Xq28 duplication involving MECP2: Delineation of brain MRI abnormalities in 30 affected patients.

    PubMed

    El Chehadeh, Salima; Faivre, Laurence; Mosca-Boidron, Anne-Laure; Malan, Valérie; Amiel, Jeanne; Nizon, Mathilde; Touraine, Renaud; Prieur, Fabienne; Pasquier, Laurent; Callier, Patrick; Lefebvre, Mathilde; Marle, Nathalie; Dubourg, Christèle; Julia, Sophie; Sarret, Catherine; Francannet, Christine; Laffargue, Fanny; Boespflug-Tanguy, Odile; David, Albert; Isidor, Bertrand; Le Caignec, Cédric; Vigneron, Jacqueline; Leheup, Bruno; Lambert, Laetitia; Philippe, Christophe; Cuisset, Jean-Marie; Andrieux, Joris; Plessis, Ghislaine; Toutain, Annick; Goldenberg, Alice; Cormier-Daire, Valérie; Rio, Marlène; Bonnefont, Jean-Paul; Thevenon, Julien; Echenne, Bernard; Journel, Hubert; Afenjar, Alexandra; Burglen, Lydie; Bienvenu, Thierry; Addor, Marie-Claude; Lebon, Sébastien; Martinet, Danièle; Baumann, Clarisse; Perrin, Laurence; Drunat, Séverine; Jouk, Pierre-Simon; Devillard, Françoise; Coutton, Charles; Lacombe, Didier; Delrue, Marie-Ange; Philip, Nicole; Moncla, Anne; Badens, Catherine; Perreton, Nathalie; Masurel, Alice; Thauvin-Robinet, Christel; Des Portes, Vincent; Guibaud, Laurent

    2016-01-01

    Xq28 duplications encompassing MECP2 have been described in male patients with a severe neurodevelopmental disorder associated with hypotonia and spasticity, severe learning disability, stereotyped movements, and recurrent pulmonary infections. We report on standardized brain magnetic resonance imaging (MRI) data of 30 affected patients carrying an Xq28 duplication involving MECP2 of various sizes (228 kb to 11.7 Mb). The aim of this study was to seek recurrent malformations and attempt to determine whether variations in imaging features could be explained by differences in the size of the duplications. We showed that 93% of patients had brain MRI abnormalities such as corpus callosum abnormalities (n = 20), reduced volume of the white matter (WM) (n = 12), ventricular dilatation (n = 9), abnormal increased hyperintensities on T2-weighted images involving posterior periventricular WM (n = 6), and vermis hypoplasia (n = 5). The occipitofrontal circumference varied considerably between >+2SD in five patients and <-2SD in four patients. Among the nine patients with dilatation of the lateral ventricles, six had a duplication involving L1CAM. The only patient harboring bilateral posterior subependymal nodular heterotopia also carried an FLNA gene duplication. We could not demonstrate a correlation between periventricular WM hyperintensities/delayed myelination and duplication of the IKBKG gene. We thus conclude that patients with an Xq28 duplication involving MECP2 share some similar but non-specific brain abnormalities. These imaging features, therefore, could not constitute a diagnostic clue. The genotype-phenotype correlation failed to demonstrate a relationship between the presence of nodular heterotopia, ventricular dilatation, WM abnormalities, and the presence of FLNA, L1CAM, or IKBKG, respectively, in the duplicated segment.

  8. Large national series of patients with Xq28 duplication involving MECP2: Delineation of brain MRI abnormalities in 30 affected patients.

    PubMed

    El Chehadeh, Salima; Faivre, Laurence; Mosca-Boidron, Anne-Laure; Malan, Valérie; Amiel, Jeanne; Nizon, Mathilde; Touraine, Renaud; Prieur, Fabienne; Pasquier, Laurent; Callier, Patrick; Lefebvre, Mathilde; Marle, Nathalie; Dubourg, Christèle; Julia, Sophie; Sarret, Catherine; Francannet, Christine; Laffargue, Fanny; Boespflug-Tanguy, Odile; David, Albert; Isidor, Bertrand; Le Caignec, Cédric; Vigneron, Jacqueline; Leheup, Bruno; Lambert, Laetitia; Philippe, Christophe; Cuisset, Jean-Marie; Andrieux, Joris; Plessis, Ghislaine; Toutain, Annick; Goldenberg, Alice; Cormier-Daire, Valérie; Rio, Marlène; Bonnefont, Jean-Paul; Thevenon, Julien; Echenne, Bernard; Journel, Hubert; Afenjar, Alexandra; Burglen, Lydie; Bienvenu, Thierry; Addor, Marie-Claude; Lebon, Sébastien; Martinet, Danièle; Baumann, Clarisse; Perrin, Laurence; Drunat, Séverine; Jouk, Pierre-Simon; Devillard, Françoise; Coutton, Charles; Lacombe, Didier; Delrue, Marie-Ange; Philip, Nicole; Moncla, Anne; Badens, Catherine; Perreton, Nathalie; Masurel, Alice; Thauvin-Robinet, Christel; Des Portes, Vincent; Guibaud, Laurent

    2016-01-01

    Xq28 duplications encompassing MECP2 have been described in male patients with a severe neurodevelopmental disorder associated with hypotonia and spasticity, severe learning disability, stereotyped movements, and recurrent pulmonary infections. We report on standardized brain magnetic resonance imaging (MRI) data of 30 affected patients carrying an Xq28 duplication involving MECP2 of various sizes (228 kb to 11.7 Mb). The aim of this study was to seek recurrent malformations and attempt to determine whether variations in imaging features could be explained by differences in the size of the duplications. We showed that 93% of patients had brain MRI abnormalities such as corpus callosum abnormalities (n = 20), reduced volume of the white matter (WM) (n = 12), ventricular dilatation (n = 9), abnormal increased hyperintensities on T2-weighted images involving posterior periventricular WM (n = 6), and vermis hypoplasia (n = 5). The occipitofrontal circumference varied considerably between >+2SD in five patients and <-2SD in four patients. Among the nine patients with dilatation of the lateral ventricles, six had a duplication involving L1CAM. The only patient harboring bilateral posterior subependymal nodular heterotopia also carried an FLNA gene duplication. We could not demonstrate a correlation between periventricular WM hyperintensities/delayed myelination and duplication of the IKBKG gene. We thus conclude that patients with an Xq28 duplication involving MECP2 share some similar but non-specific brain abnormalities. These imaging features, therefore, could not constitute a diagnostic clue. The genotype-phenotype correlation failed to demonstrate a relationship between the presence of nodular heterotopia, ventricular dilatation, WM abnormalities, and the presence of FLNA, L1CAM, or IKBKG, respectively, in the duplicated segment. PMID:26420639

  9. Sensory neuron-specific sodium channel SNS is abnormally expressed in the brains of mice with experimental allergic encephalomyelitis and humans with multiple sclerosis

    NASA Astrophysics Data System (ADS)

    Black, Joel A.; Dib-Hajj, Sulayman; Baker, David; Newcombe, Jia; Cuzner, M. Louise; Waxman, Stephen G.

    2000-10-01

    Clinical abnormalities in multiple sclerosis (MS) have classically been considered to be caused by demyelination and/or axonal degeneration; the possibility of molecular changes in neurons, such as the deployment of abnormal repertoires of ion channels that would alter neuronal electrogenic properties, has not been considered. Sensory Neuron-Specific sodium channel SNS displays a depolarized voltage dependence, slower activation and inactivation kinetics, and more rapid recovery from inactivation than classical "fast" sodium channels. SNS is selectively expressed in spinal sensory and trigeminal ganglion neurons within the peripheral nervous system and is not expressed within the normal brain. Here we show that sodium channel SNS mRNA and protein, which are not present within the cerebellum of control mice, are expressed within cerebellar Purkinje cells in a mouse model of MS, chronic relapsing experimental allergic encephalomyelitis. We also demonstrate SNS mRNA and protein expression within Purkinje cells from tissue obtained postmortem from patients with MS, but not in control subjects with no neurological disease. These results demonstrate a change in sodium channel expression in neurons within the brain in an animal model of MS and in humans with MS and suggest that abnormal patterns of neuronal ion channel expression may contribute to clinical abnormalities such as ataxia in these disorders.

  10. Neurological and behavioral abnormalities, ventricular dilatation, altered cellular functions, inflammation, and neuronal injury in brains of mice due to common, persistent, parasitic infection

    PubMed Central

    Hermes, Gretchen; Ajioka, James W; Kelly, Krystyna A; Mui, Ernest; Roberts, Fiona; Kasza, Kristen; Mayr, Thomas; Kirisits, Michael J; Wollmann, Robert; Ferguson, David JP; Roberts, Craig W; Hwang, Jong-Hee; Trendler, Toria; Kennan, Richard P; Suzuki, Yasuhiro; Reardon, Catherine; Hickey, William F; Chen, Lieping; McLeod, Rima

    2008-01-01

    Background Worldwide, approximately two billion people are chronically infected with Toxoplasma gondii with largely unknown consequences. Methods To better understand long-term effects and pathogenesis of this common, persistent brain infection, mice were infected at a time in human years equivalent to early to mid adulthood and studied 5–12 months later. Appearance, behavior, neurologic function and brain MRIs were studied. Additional analyses of pathogenesis included: correlation of brain weight and neurologic findings; histopathology focusing on brain regions; full genome microarrays; immunohistochemistry characterizing inflammatory cells; determination of presence of tachyzoites and bradyzoites; electron microscopy; and study of markers of inflammation in serum. Histopathology in genetically resistant mice and cytokine and NRAMP knockout mice, effects of inoculation of isolated parasites, and treatment with sulfadiazine or αPD1 ligand were studied. Results Twelve months after infection, a time equivalent to middle to early elderly ages, mice had behavioral and neurological deficits, and brain MRIs showed mild to moderate ventricular dilatation. Lower brain weight correlated with greater magnitude of neurologic abnormalities and inflammation. Full genome microarrays of brains reflected inflammation causing neuronal damage (Gfap), effects on host cell protein processing (ubiquitin ligase), synapse remodeling (Complement 1q), and also increased expression of PD-1L (a ligand that allows persistent LCMV brain infection) and CD 36 (a fatty acid translocase and oxidized LDL receptor that mediates innate immune response to beta amyloid which is associated with pro-inflammation in Alzheimer's disease). Immunostaining detected no inflammation around intra-neuronal cysts, practically no free tachyzoites, and only rare bradyzoites. Nonetheless, there were perivascular, leptomeningeal inflammatory cells, particularly contiguous to the aqueduct of Sylvius and hippocampus

  11. Wavelet-based cluster analysis: data-driven grouping of voxel time courses with application to perfusion-weighted and pharmacological MRI of the rat brain.

    PubMed

    Whitcher, Brandon; Schwarz, Adam J; Barjat, Hervé; Smart, Sean C; Grundy, Robert I; James, Michael F

    2005-01-15

    MRI time series experiments produce a wealth of information contained in two or three spatial dimensions that evolve over time. Such experiments can, for example, localize brain response to pharmacological stimuli, but frequently the spatiotemporal characteristics of the cerebral response are unknown a priori and variable, and thus difficult to evaluate using hypothesis-based methods alone. Here we used features in the temporal dimension to group voxels with similar time courses based on a nonparametric discrete wavelet transform (DWT) representation of each time course. Applying the DWT to each voxel decomposes its temporal information into coefficients associated with both time and scale. Discarding scales in the DWT that are associated with high-frequency oscillations (noise) provided a straight-forward data reduction step and decreased the computational burden. Optimization-based clustering was then applied to the remaining wavelet coefficients in order to produce a finite number of voxel clusters. This wavelet-based cluster analysis (WCA) was evaluated using two representative classes of MRI neuroimaging experiments. In perfusion-weighted MRI, following occlusion of the middle cerebral artery (MCAO), WCA differentiated healthy tissue and different regions within the ischemic hemisphere. Following an acute cocaine challenge, WCA localized subtle differences in the pharmacokinetic profile of the cerebral response. We conclude that WCA provides a robust method for blind analysis of time series image data.

  12. Contrast adaptive total p-norm variation minimization approach to CT reconstruction for artifact reduction in reduced-view brain perfusion CT

    NASA Astrophysics Data System (ADS)

    Kim, Chang-Won; Kim, Jong-Hyo

    2011-03-01

    Perfusion CT (PCT) examinations are getting more frequently used for diagnosis of acute brain diseases such as hemorrhage and infarction, because the functional map images it produces such as regional cerebral blood flow (rCBF), regional cerebral blood volume (rCBV), and mean transit time (MTT) may provide critical information in the emergency work-up of patient care. However, a typical PCT scans the same slices several tens of times after injection of contrast agent, which leads to much increased radiation dose and is inevitability of growing concern for radiation-induced cancer risk. Reducing the number of views in projection in combination of TV minimization reconstruction technique is being regarded as an option for radiation reduction. However, reconstruction artifacts due to insufficient number of X-ray projections become problematic especially when high contrast enhancement signals are present or patient's motion occurred. In this study, we present a novel reconstruction technique using contrast-adaptive TpV minimization that can reduce reconstruction artifacts effectively by using different p-norms in high contrast and low contrast objects. In the proposed method, high contrast components are first reconstructed using thresholded projection data and low p-norm total variation to reflect sparseness in both projection and reconstruction spaces. Next, projection data are modified to contain only low contrast objects by creating projection data of reconstructed high contrast components and subtracting them from original projection data. Then, the low contrast projection data are reconstructed by using relatively high p-norm TV minimization technique, and are combined with the reconstructed high contrast component images to produce final reconstructed images. The proposed algorithm was applied to numerical phantom and a clinical data set of brain PCT exam, and the resultant images were compared with those using filtered back projection (FBP) and conventional TV

  13. An in vivo and in vitro H-magnetic resonance spectroscopy study of mdx mouse brain: abnormal development or neural necrosis?

    PubMed

    Tracey, I; Dunn, J F; Parkes, H G; Radda, G K

    1996-09-15

    Duchenne muscular dystrophy (DMD) is an X-linked genetic disorder primarily affecting young boys, often causing mental retardation in addition to the well-known progressive muscular weakness. Normal dystrophin expression is lacking in skeletal muscle and the central nervous system (CNS) of both DMD children and the mdx mouse model. The underlying biochemical lesion causing mental impairment in DMD is unknown. 1H-magnetic resonance spectroscopy (1H-MRS) detects choline-containing compounds, creatine and N-acetyl aspartate (NAA) in vivo. NAA is commonly used as a chemical marker for neurons, and a decline in NAA is thought to correlate with neuronal loss. Control mice were compared to mdx using a combination of in vivo and in vitro 1H-MRS methods to determine whether neural necrosis or developmental abnormalities occur in dystrophic brain. NAA levels were normal in mdx brain compared to controls suggesting minor, if any, neuronal necrosis in dystrophic brain. In contrast, choline compounds and myo-inositol levels were increased, indicative of gliosis or developmental abnormalities in dystrophic brain. PMID:8880686

  14. Effects of Steroid Hormones on Sex Differences in Cerebral Perfusion.

    PubMed

    Ghisleni, Carmen; Bollmann, Steffen; Biason-Lauber, Anna; Poil, Simon-Shlomo; Brandeis, Daniel; Martin, Ernst; Michels, Lars; Hersberger, Martin; Suckling, John; Klaver, Peter; O'Gorman, Ruth L

    2015-01-01

    Sex differences in the brain appear to play an important role in the prevalence and progression of various neuropsychiatric disorders, but to date little is known about the cerebral mechanisms underlying these differences. One widely reported finding is that women demonstrate higher cerebral perfusion than men, but the underlying cause of this difference in perfusion is not known. This study investigated the putative role of steroid hormones such as oestradiol, testosterone, and dehydroepiandrosterone sulphate (DHEAS) as underlying factors influencing cerebral perfusion. We acquired arterial spin labelling perfusion images of 36 healthy adult subjects (16 men, 20 women). Analyses on average whole brain perfusion levels included a multiple regression analysis to test for the relative impact of each hormone on the global perfusion. Additionally, voxel-based analyses were performed to investigate the sex difference in regional perfusion as well as the correlations between local perfusion and serum oestradiol, testosterone, and DHEAS concentrations. Our results replicated the known sex difference in perfusion, with women showing significantly higher global and regional perfusion. For the global perfusion, DHEAS was the only significant predictor amongst the steroid hormones, showing a strong negative correlation with cerebral perfusion. The voxel-based analyses revealed modest sex-dependent correlations between local perfusion and testosterone, in addition to a strong modulatory effect of DHEAS in cortical, subcortical, and cerebellar regions. We conclude that DHEAS in particular may play an important role as an underlying factor driving the difference in cerebral perfusion between men and women.

  15. Retina restored and brain abnormalities ameliorated by single-copy knock-in of human NR2E1 in null mice.

    PubMed

    Schmouth, J-F; Banks, K G; Mathelier, A; Gregory-Evans, C Y; Castellarin, M; Holt, R A; Gregory-Evans, K; Wasserman, W W; Simpson, E M

    2012-04-01

    Nr2e1 encodes a stem cell fate determinant of the mouse forebrain and retina. Abnormal regulation of this gene results in retinal, brain, and behavioral abnormalities in mice. However, little is known about the functionality of human NR2E1. We investigated this functionality using a novel knock-in humanized-mouse strain carrying a single-copy bacterial artificial chromosome (BAC). We also documented, for the first time, the expression pattern of the human BAC, using an NR2E1-lacZ reporter strain. Unexpectedly, cerebrum and olfactory bulb hypoplasia, hallmarks of the Nr2e1-null phenotype, were not fully corrected in animals harboring one functional copy of human NR2E1. These results correlated with an absence of NR2E1-lacZ reporter expression in the dorsal pallium of embryos and proliferative cells of adult brains. Surprisingly, retinal histology and electroretinograms demonstrated complete correction of the retina-null phenotype. These results correlated with appropriate expression of the NR2E1-lacZ reporter in developing and adult retina. We conclude that the human BAC contained all the elements allowing correction of the mouse-null phenotype in the retina, while missing key regulatory regions important for proper spatiotemporal brain expression. This is the first time a separation of regulatory mechanisms governing NR2E1 has been demonstrated. Furthermore, candidate genomic regions controlling expression in proliferating cells during neurogenesis were identified.

  16. Lack of Evidence for Regional Brain Volume or Cortical Thickness Abnormalities in Youths at Clinical High Risk for Psychosis: Findings From the Longitudinal Youth at Risk Study.

    PubMed

    Klauser, Paul; Zhou, Juan; Lim, Joseph K W; Poh, Joann S; Zheng, Hui; Tng, Han Ying; Krishnan, Ranga; Lee, Jimmy; Keefe, Richard S E; Adcock, R Alison; Wood, Stephen J; Fornito, Alex; Chee, Michael W L

    2015-11-01

    There is cumulative evidence that young people in an "at-risk mental state" (ARMS) for psychosis show structural brain abnormalities in frontolimbic areas, comparable to, but less extensive than those reported in established schizophrenia. However, most available data come from ARMS samples from Australia, Europe, and North America while large studies from other populations are missing. We conducted a structural brain magnetic resonance imaging study from a relatively large sample of 69 ARMS individuals and 32 matched healthy controls (HC) recruited from Singapore as part of the Longitudinal Youth At-Risk Study (LYRIKS). We used 2 complementary approaches: a voxel-based morphometry and a surface-based morphometry analysis to extract regional gray and white matter volumes (GMV and WMV) and cortical thickness (CT). At the whole-brain level, we did not find any statistically significant difference between ARMS and HC groups concerning total GMV and WMV or regional GMV, WMV, and CT. The additional comparison of 2 regions of interest, hippocampal, and ventricular volumes, did not return any significant difference either. Several characteristics of the LYRIKS sample like Asian origins or the absence of current illicit drug use could explain, alone or in conjunction, the negative findings and suggest that there may be no dramatic volumetric or CT abnormalities in ARMS. PMID:25745033

  17. Downstream targets of methyl CpG binding protein 2 and their abnormal expression in the frontal cortex of the human Rett syndrome brain

    PubMed Central

    2010-01-01

    Background The Rett Syndrome (RTT) brain displays regional histopathology and volumetric reduction, with frontal cortex showing such abnormalities, whereas the occipital cortex is relatively less affected. Results Using microarrays and quantitative PCR, the mRNA expression profiles of these two neuroanatomical regions were compared in postmortem brain tissue from RTT patients and normal controls. A subset of genes was differentially expressed in the frontal cortex of RTT brains, some of which are known to be associated with neurological disorders (clusterin and cytochrome c oxidase subunit 1) or are involved in synaptic vesicle cycling (dynamin 1). RNAi-mediated knockdown of MeCP2 in vitro, followed by further expression analysis demonstrated that the same direction of abnormal expression was recapitulated with MeCP2 knockdown, which for cytochrome c oxidase subunit 1 was associated with a functional respiratory chain defect. Chromatin immunoprecipitation (ChIP) analysis showed that MeCP2 associated with the promoter regions of some of these genes suggesting that loss of MeCP2 function may be responsible for their overexpression. Conclusions This study has shed more light on the subset of aberrantly expressed genes that result from MECP2 mutations. The mitochondrion has long been implicated in the pathogenesis of RTT, however it has not been at the forefront of RTT research interest since the discovery of MECP2 mutations. The functional consequence of the underexpression of cytochrome c oxidase subunit 1 indicates that this is an area that should be revisited. PMID:20420693

  18. Reversal of brain metabolic abnormalities following treatment of AIDS dementia complex with 3'-azido-2',3'-dideoxythymidine (AZT, zidovudine): a PET-FDG study

    SciTech Connect

    Brunetti, A.; Berg, G.; Di Chiro, G.; Cohen, R.M.; Yarchoan, R.; Pizzo, P.A.; Broder, S.; Eddy, J.; Fulham, M.J.; Finn, R.D.

    1989-05-01

    Brain glucose metabolism was evaluated in four patients with acquired immunodeficiency syndrome (AIDS) dementia complex using (/sup 18/F)fluorodeoxyglucose (FDG) and positron emission tomography (PET) scans at the beginning of therapy with 3'-azido-2',3'-dideoxythymidine (AZT, zidovudine), and later in the course of therapy. In two patients, baseline, large focal cortical abnormalities of glucose utilization were reversed during the course of therapy. In the other two patients, the initial PET study did not reveal pronounced focal alterations, while the post-treatment scans showed markedly increased cortical glucose metabolism. The improved cortical glucose utilization was accompanied in all patients by immunologic and neurologic improvement. PET-FDG studies can detect cortical metabolic abnormalities associated with AIDS dementia complex, and may be used to monitor the metabolic improvement in response to AZT treatment.

  19. Brain MRI abnormalities and spectrum of neurological and clinical findings in three patients with proximal 16p11.2 microduplication.

    PubMed

    Filges, Isabel; Sparagana, Steven; Sargent, Michael; Selby, Kathryn; Schlade-Bartusiak, Kamilla; Lueder, Gregg T; Robichaux-Viehoever, Amy; Schlaggar, Bradley L; Shimony, Joshua S; Shinawi, Marwan

    2014-08-01

    The phenotype of recurrent ∼600 kb microdeletion and microduplication on proximal 16p11.2 is characterized by a spectrum of neurodevelopmental impairments including developmental delay and intellectual disability, epilepsy, autism and psychiatric disorders which are all subject to incomplete penetrance and variable expressivity. A variety of brain MRI abnormalities were reported in patients with 16p11.2 rearrangements, but no systematic correlation has been studied among patients with similar brain anomalies, their neurodevelopmental and clinical phenotypes. We present three patients with the proximal 16p11.2 microduplication exhibiting significant developmental delay, anxiety disorder and other variable clinical features. Our patients have abnormal brain MRI findings of cerebral T2 hyperintense foci (3/3) and ventriculomegaly (2/3). The neuroradiological or neurological findings in two cases prompted an extensive diagnostic work-up. One patient has exhibited neurological regression and progressive vision impairment and was diagnosed with juvenile neuronal ceroid-lipofuscinosis. We compare the clinical course and phenotype of these patients in regard to the clinical significance of the cerebral lesions and the need for MRI surveillance. We conclude that in all three patients the lesions were not progressive, did not show any sign of malignant transformation and could not be correlated to specific clinical features. We discuss potential etiologic mechanisms that may include overexpression of genes within the duplicated region involved in control of cell proliferation and complex molecular mechanisms such as the MAPK/ERK pathway. Systematic studies in larger cohorts are needed to confirm our observation and to establish the prevalence and clinical significance of these neuroanatomical abnormalities in patients with 16p11.2 duplications. PMID:24891046

  20. Evaluation of a multiple spin- and gradient-echo (SAGE) EPI acquisition with SENSE acceleration: applications for perfusion imaging in and outside the brain.

    PubMed

    Skinner, Jack T; Robison, Ryan K; Elder, Christopher P; Newton, Allen T; Damon, Bruce M; Quarles, C Chad

    2014-12-01

    Perfusion-based changes in MR signal intensity can occur in response to the introduction of exogenous contrast agents and endogenous tissue properties (e.g. blood oxygenation). MR measurements aimed at capturing these changes often implement single-shot echo planar imaging (ssEPI). In recent years ssEPI readouts have been combined with parallel imaging (PI) to allow fast dynamic multi-slice imaging as well as the incorporation of multiple echoes. A multiple spin- and gradient-echo (SAGE) EPI acquisition has recently been developed to allow measurement of transverse relaxation rate (R2 and R2(*)) changes in dynamic susceptibility contrast (DSC)-MRI experiments in the brain. With SAGE EPI, the use of PI can influence image quality, temporal resolution, and achievable echo times. The effect of PI on dynamic SAGE measurements, however, has not been evaluated. In this work, a SAGE EPI acquisition utilizing SENSE PI and partial Fourier (PF) acceleration was developed and evaluated. Voxel-wise measures of R2 and R2(*) in healthy brain were compared using SAGE EPI and conventional non-EPI multiple echo acquisitions with varying SENSE and PF acceleration. A conservative SENSE factor of 2 with PF factor of 0.73 was found to provide accurate measures of R2 and R2(*) in white (WM) (rR2=[0.55-0.79], rR2*=[0.47-0.71]) and gray (GM) matter (rR2=[0.26-0.59], rR2*=[0.39-0.74]) across subjects. The combined use of SENSE and PF allowed the first dynamic SAGE EPI measurements in muscle, with a SENSE factor of 3 and PF factor of 0.6 providing reliable relaxation rate estimates when compared to multi-echo methods. Application of the optimized SAGE protocol in DSC-MRI of high-grade glioma patients provided T1 leakage-corrected estimates of CBV and CBF as well as mean vessel diameter (mVD) and simultaneous measures of DCE-MRI parameters K(trans) and ve. Likewise, application of SAGE in a muscle reperfusion model allowed dynamic measures of R2', a parameter that has been shown to correlate

  1. Evaluation of a multiple spin- and gradient-echo (SAGE) EPI acquisition with SENSE acceleration: applications for perfusion imaging in and outside the brain.

    PubMed

    Skinner, Jack T; Robison, Ryan K; Elder, Christopher P; Newton, Allen T; Damon, Bruce M; Quarles, C Chad

    2014-12-01

    Perfusion-based changes in MR signal intensity can occur in response to the introduction of exogenous contrast agents and endogenous tissue properties (e.g. blood oxygenation). MR measurements aimed at capturing these changes often implement single-shot echo planar imaging (ssEPI). In recent years ssEPI readouts have been combined with parallel imaging (PI) to allow fast dynamic multi-slice imaging as well as the incorporation of multiple echoes. A multiple spin- and gradient-echo (SAGE) EPI acquisition has recently been developed to allow measurement of transverse relaxation rate (R2 and R2(*)) changes in dynamic susceptibility contrast (DSC)-MRI experiments in the brain. With SAGE EPI, the use of PI can influence image quality, temporal resolution, and achievable echo times. The effect of PI on dynamic SAGE measurements, however, has not been evaluated. In this work, a SAGE EPI acquisition utilizing SENSE PI and partial Fourier (PF) acceleration was developed and evaluated. Voxel-wise measures of R2 and R2(*) in healthy brain were compared using SAGE EPI and conventional non-EPI multiple echo acquisitions with varying SENSE and PF acceleration. A conservative SENSE factor of 2 with PF factor of 0.73 was found to provide accurate measures of R2 and R2(*) in white (WM) (rR2=[0.55-0.79], rR2*=[0.47-0.71]) and gray (GM) matter (rR2=[0.26-0.59], rR2*=[0.39-0.74]) across subjects. The combined use of SENSE and PF allowed the first dynamic SAGE EPI measurements in muscle, with a SENSE factor of 3 and PF factor of 0.6 providing reliable relaxation rate estimates when compared to multi-echo methods. Application of the optimized SAGE protocol in DSC-MRI of high-grade glioma patients provided T1 leakage-corrected estimates of CBV and CBF as well as mean vessel diameter (mVD) and simultaneous measures of DCE-MRI parameters K(trans) and ve. Likewise, application of SAGE in a muscle reperfusion model allowed dynamic measures of R2', a parameter that has been shown to correlate

  2. Value of Dynamic Susceptibility Contrast Perfusion MRI in the Acute Phase of Transient Global Amnesia

    PubMed Central

    Förster, Alex; Al-Zghloul, Mansour; Kerl, Hans U.; Böhme, Johannes; Mürle, Bettina; Groden, Christoph

    2015-01-01

    Purpose Transient global amnesia (TGA) is a transitory, short-lasting neurological disorder characterized by a sudden onset of antero- and retrograde amnesia. Perfusion abnormalities in TGA have been evaluated mainly by use of positron emission tomography (PET) or single-photon emission computed tomography (SPECT). In the present study we explore the value of dynamic susceptibility contrast perfusion-weighted MRI (PWI) in TGA in the acute phase. Methods From a MRI report database we identified TGA patients who underwent MRI including PWI in the acute phase and compared these to control subjects. Quantitative perfusion maps (cerebral blood flow (CBF) and volume (CBV)) were generated and analyzed by use of Signal Processing In NMR-Software (SPIN). CBF and CBV values in subcortical brain regions were assessed by use of VOI created in FIRST, a model-based segmentation tool in the Oxford Centre for Functional Magnetic Resonance Imaging of the Brain (FMRIB) Software Library (FSL). Results Five TGA patients were included (2 men, 3 women). On PWI, no relevant perfusion alterations were found by visual inspection in TGA patients. Group comparisons for possible differences between TGA patients and control subjects showed significant lower rCBF values bilaterally in the hippocampus, in the left thalamus and globus pallidus as well as bilaterally in the putamen and the left caudate nucleus. Correspondingly, significant lower rCBV values were observed bilaterally in the hippocampus and the putamen as well as in the left caudate nucleus. Group comparisons for possible side differences in rCBF and rCBV values in TGA patients revealed a significant lower rCBV value in the left caudate nucleus. Conclusions Mere visual inspection of PWI is not sufficient for the assessment of perfusion changes in TGA in the acute phase. Group comparisons with healthy control subjects might be useful to detect subtle perfusion changes on PWI in TGA patients. However, this should be confirmed in

  3. Association of brain amyloid-β with cerebral perfusion and structure in Alzheimer's disease and mild cognitive impairment.

    PubMed

    Mattsson, Niklas; Tosun, Duygu; Insel, Philip S; Simonson, Alix; Jack, Clifford R; Beckett, Laurel A; Donohue, Michael; Jagust, William; Schuff, Norbert; Weiner, Michael W

    2014-05-01

    Patients with Alzheimer's disease have reduced cerebral blood flow measured by arterial spin labelling magnetic resonance imaging, but it is unclear how this is related to amyloid-β pathology. Using 182 subjects from the Alzheimer's Disease Neuroimaging Initiative we tested associations of amyloid-β with regional cerebral blood flow in healthy controls (n = 51), early (n = 66) and late (n = 41) mild cognitive impairment, and Alzheimer's disease with dementia (n = 24). Based on the theory that Alzheimer's disease starts with amyloid-β accumulation and progresses with symptoms and secondary pathologies in different trajectories, we tested if cerebral blood flow differed between amyloid-β-negative controls and -positive subjects in different diagnostic groups, and if amyloid-β had different associations with cerebral blood flow and grey matter volume. Global amyloid-β load was measured by florbetapir positron emission tomography, and regional blood flow and volume were measured in eight a priori defined regions of interest. Cerebral blood flow was reduced in patients with dementia in most brain regions. Higher amyloid-β load was related to lower cerebral blood flow in several regions, independent of diagnostic group. When comparing amyloid-β-positive subjects with -negative controls, we found reductions of cerebral blood flow in several diagnostic groups, including in precuneus, entorhinal cortex and hippocampus (dementia), inferior parietal cortex (late mild cognitive impairment and dementia), and inferior temporal cortex (early and late mild cognitive impairment and dementia). The associations of amyloid-β with cerebral blood flow and volume differed across the disease spectrum, with high amyloid-β being associated with greater cerebral blood flow reduction in controls and greater volume reduction in late mild cognitive impairment and dementia. In addition to disease stage, amyloid-β pathology affects cerebral blood flow across the span from controls to

  4. Association of brain amyloid-β with cerebral perfusion and structure in Alzheimer's disease and mild cognitive impairment.

    PubMed

    Mattsson, Niklas; Tosun, Duygu; Insel, Philip S; Simonson, Alix; Jack, Clifford R; Beckett, Laurel A; Donohue, Michael; Jagust, William; Schuff, Norbert; Weiner, Michael W

    2014-05-01

    Patients with Alzheimer's disease have reduced cerebral blood flow measured by arterial spin labelling magnetic resonance imaging, but it is unclear how this is related to amyloid-β pathology. Using 182 subjects from the Alzheimer's Disease Neuroimaging Initiative we tested associations of amyloid-β with regional cerebral blood flow in healthy controls (n = 51), early (n = 66) and late (n = 41) mild cognitive impairment, and Alzheimer's disease with dementia (n = 24). Based on the theory that Alzheimer's disease starts with amyloid-β accumulation and progresses with symptoms and secondary pathologies in different trajectories, we tested if cerebral blood flow differed between amyloid-β-negative controls and -positive subjects in different diagnostic groups, and if amyloid-β had different associations with cerebral blood flow and grey matter volume. Global amyloid-β load was measured by florbetapir positron emission tomography, and regional blood flow and volume were measured in eight a priori defined regions of interest. Cerebral blood flow was reduced in patients with dementia in most brain regions. Higher amyloid-β load was related to lower cerebral blood flow in several regions, independent of diagnostic group. When comparing amyloid-β-positive subjects with -negative controls, we found reductions of cerebral blood flow in several diagnostic groups, including in precuneus, entorhinal cortex and hippocampus (dementia), inferior parietal cortex (late mild cognitive impairment and dementia), and inferior temporal cortex (early and late mild cognitive impairment and dementia). The associations of amyloid-β with cerebral blood flow and volume differed across the disease spectrum, with high amyloid-β being associated with greater cerebral blood flow reduction in controls and greater volume reduction in late mild cognitive impairment and dementia. In addition to disease stage, amyloid-β pathology affects cerebral blood flow across the span from controls to

  5. Magnetic Resonance Perfusion Imaging in the Study of Language

    ERIC Educational Resources Information Center

    Hillis, Argye E.

    2007-01-01

    This paper provides a brief review of various uses of magnetic resonance perfusion imaging in the investigation of brain/language relationships. The reviewed studies illustrate how perfusion imaging can reveal areas of brain where dysfunction due to low blood flow is associated with specific language deficits, and where restoration of blood flow…

  6. Cocaine addiction related reproducible brain regions of abnormal default-mode network functional connectivity: a group ICA study with different model orders.

    PubMed

    Ding, Xiaoyu; Lee, Seong-Whan

    2013-08-26

    Model order selection in group independent component analysis (ICA) has a significant effect on the obtained components. This study investigated the reproducible brain regions of abnormal default-mode network (DMN) functional connectivity related with cocaine addiction through different model order settings in group ICA. Resting-state fMRI data from 24 cocaine addicts and 24 healthy controls were temporally concatenated and processed by group ICA using model orders of 10, 20, 30, 40, and 50, respectively. For each model order, the group ICA approach was repeated 100 times using the ICASSO toolbox and after clustering the obtained components, centrotype-based anterior and posterior DMN components were selected for further analysis. Individual DMN components were obtained through back-reconstruction and converted to z-score maps. A whole brain mixed effects factorial ANOVA was performed to explore the differences in resting-state DMN functional connectivity between cocaine addicts and healthy controls. The hippocampus, which showed decreased functional connectivity in cocaine addicts for all the tested model orders, might be considered as a reproducible abnormal region in DMN associated with cocaine addiction. This finding suggests that using group ICA to examine the functional connectivity of the hippocampus in the resting-state DMN may provide an additional insight potentially relevant for cocaine-related diagnoses and treatments. PMID:23707901

  7. An Abnormal Nitric Oxide Metabolism Contributes to Brain Oxidative Stress in the Mouse Model for the Fragile X Syndrome, a Possible Role in Intellectual Disability

    PubMed Central

    Lima-Cabello, Elena; Garcia-Guirado, Francisco; Calvo-Medina, Rocio; el Bekay, Rajaa; Perez-Costillas, Lucia; Quintero-Navarro, Carolina; Sanchez-Salido, Lourdes

    2016-01-01

    Background. Fragile X syndrome is the most common genetic cause of mental disability. Although many research has been performed, the mechanism underlying the pathogenesis is unclear and needs further investigation. Oxidative stress played major roles in the syndrome. The aim was to investigate the nitric oxide metabolism, protein nitration level, the expression of NOS isoforms, and furthermore the activation of the nuclear factor NF-κB-p65 subunit in different brain areas on the fragile X mouse model. Methods. This study involved adult male Fmr1-knockout and wild-type mice as controls. We detected nitric oxide metabolism and the activation of the nuclear factor NF-κBp65 subunit, comparing the mRNA expression and protein content of the three NOS isoforms in different brain areas. Results. Fmr1-KO mice showed an abnormal nitric oxide metabolism and increased levels of protein tyrosine nitrosylation. Besides that, nuclear factor NF-κB-p65 and inducible nitric oxide synthase appeared significantly increased in the Fmr1-knockout mice. mRNA and protein levels of the neuronal nitric oxide synthase appeared significantly decreased in the knockout mice. However, the epithelial nitric oxide synthase isoform displayed no significant changes. Conclusions. These data suggest the potential involvement of an abnormal nitric oxide metabolism in the pathogenesis of the fragile X syndrome. PMID:26788253

  8. Abnormal Brain Iron Metabolism in Irp2 Deficient Mice Is Associated with Mild Neurological and Behavioral Impairments

    PubMed Central

    Zumbrennen-Bullough, Kimberly B.; Becker, Lore; Garrett, Lillian; Hölter, Sabine M.; Calzada-Wack, Julia; Mossbrugger, Ilona; Quintanilla-Fend, Leticia; Racz, Ildiko; Rathkolb, Birgit; Klopstock, Thomas; Wurst, Wolfgang; Zimmer, Andreas; Wolf, Eckhard; Fuchs, Helmut; Gailus-Durner, Valerie; de Angelis, Martin Hrabě; Romney, Steven J.; Leibold, Elizabeth A.

    2014-01-01

    Iron Regulatory Protein 2 (Irp2, Ireb2) is a central regulator of cellular iron homeostasis in vertebrates. Two global knockout mouse models have been generated to explore the role of Irp2 in regulating iron metabolism. While both mouse models show that loss of Irp2 results in microcytic anemia and altered body iron distribution, discrepant results have drawn into question the role of Irp2 in regulating brain iron metabolism. One model shows that aged Irp2 deficient mice develop adult-onset progressive neurodegeneration that is associated with axonal degeneration and loss of Purkinje cells in the central nervous system. These mice show iron deposition in white matter tracts and oligodendrocyte soma throughout the brain. A contrasting model of global Irp2 deficiency shows no overt or pathological signs of neurodegeneration or brain iron accumulation, and display only mild motor coordination and balance deficits when challenged by specific tests. Explanations for conflicting findings in the severity of the clinical phenotype, brain iron accumulation and neuronal degeneration remain unclear. Here, we describe an additional mouse model of global Irp2 deficiency. Our aged Irp2−/− mice show marked iron deposition in white matter and in oligodendrocytes while iron content is significantly reduced in neurons. Ferritin and transferrin receptor 1 (TfR1, Tfrc), expression are increased and decreased, respectively, in the brain from Irp2−/− mice. These mice show impairments in locomotion, exploration, motor coordination/balance and nociception when assessed by neurological and behavioral tests, but lack overt signs of neurodegenerative disease. Ultrastructural studies of specific brain regions show no evidence of neurodegeneration. Our data suggest that Irp2 deficiency dysregulates brain iron metabolism causing cellular dysfunction that ultimately leads to mild neurological, behavioral and nociceptive impairments. PMID:24896637

  9. Abnormal brain iron metabolism in Irp2 deficient mice is associated with mild neurological and behavioral impairments.

    PubMed

    Zumbrennen-Bullough, Kimberly B; Becker, Lore; Garrett, Lillian; Hölter, Sabine M; Calzada-Wack, Julia; Mossbrugger, Ilona; Quintanilla-Fend, Leticia; Racz, Ildiko; Rathkolb, Birgit; Klopstock, Thomas; Wurst, Wolfgang; Zimmer, Andreas; Wolf, Eckhard; Fuchs, Helmut; Gailus-Durner, Valerie; de Angelis, Martin Hrabě; Romney, Steven J; Leibold, Elizabeth A

    2014-01-01

    Iron Regulatory Protein 2 (Irp2, Ireb2) is a central regulator of cellular iron homeostasis in vertebrates. Two global knockout mouse models have been generated to explore the role of Irp2 in regulating iron metabolism. While both mouse models show that loss of Irp2 results in microcytic anemia and altered body iron distribution, discrepant results have drawn into question the role of Irp2 in regulating brain iron metabolism. One model shows that aged Irp2 deficient mice develop adult-onset progressive neurodegeneration that is associated with axonal degeneration and loss of Purkinje cells in the central nervous system. These mice show iron deposition in white matter tracts and oligodendrocyte soma throughout the brain. A contrasting model of global Irp2 deficiency shows no overt or pathological signs of neurodegeneration or brain iron accumulation, and display only mild motor coordination and balance deficits when challenged by specific tests. Explanations for conflicting findings in the severity of the clinical phenotype, brain iron accumulation and neuronal degeneration remain unclear. Here, we describe an additional mouse model of global Irp2 deficiency. Our aged Irp2-/- mice show marked iron deposition in white matter and in oligodendrocytes while iron content is significantly reduced in neurons. Ferritin and transferrin receptor 1 (TfR1, Tfrc), expression are increased and decreased, respectively, in the brain from Irp2-/- mice. These mice show impairments in locomotion, exploration, motor coordination/balance and nociception when assessed by neurological and behavioral tests, but lack overt signs of neurodegenerative disease. Ultrastructural studies of specific brain regions show no evidence of neurodegeneration. Our data suggest that Irp2 deficiency dysregulates brain iron metabolism causing cellular dysfunction that ultimately leads to mild neurological, behavioral and nociceptive impairments.

  10. Is the Cerebellum the Optimal Reference Region for Intensity Normalization of Perfusion MR Studies in Early Alzheimer’s Disease?

    PubMed Central

    Lacalle-Aurioles, María; Alemán-Gómez, Yasser; Guzmán-De-Villoria, Juan Adán; Cruz-Orduña, Isabel; Olazarán, Javier; Mateos-Pérez, José María; Martino, María Elena; Desco, Manuel

    2013-01-01

    The cerebellum is the region most commonly used as a reference when normalizing the intensity of perfusion images acquired using magnetic resonance imaging (MRI) in Alzheimer’s disease (AD) studies. In addition, the cerebellum provides unbiased estimations with nuclear medicine techniques. However, no reports confirm the cerebellum as an optimal reference region in MRI studies or evaluate the consequences of using different normalization regions. In this study, we address the effect of using the cerebellum, whole-brain white matter, and whole-brain cortical gray matter in the normalization of cerebral blood flow (CBF) parametric maps by comparing patients with stable mild cognitive impairment (MCI), patients with AD and healthy controls. According to our results, normalization by whole-brain cortical gray matter enables more sensitive detection of perfusion abnormalities in AD patients and reveals a larger number of affected regions than data normalized by the cerebellum or whole-brain white matter. Therefore, the cerebellum is not the most valid reference region in MRI studies for early stages of AD. After normalization by whole-brain cortical gray matter, we found a significant decrease in CBF in both parietal lobes and an increase in CBF in the right medial temporal lobe. We found no differences in perfusion between patients with stable MCI and healthy controls either before or after normalization. PMID:24386081

  11. Is the cerebellum the optimal reference region for intensity normalization of perfusion MR studies in early Alzheimer's disease?

    PubMed

    Lacalle-Aurioles, María; Alemán-Gómez, Yasser; Guzmán-De-Villoria, Juan Adán; Cruz-Orduña, Isabel; Olazarán, Javier; Mateos-Pérez, José María; Martino, María Elena; Desco, Manuel

    2013-01-01

    The cerebellum is the region most commonly used as a reference when normalizing the intensity of perfusion images acquired using magnetic resonance imaging (MRI) in Alzheimer's disease (AD) studies. In addition, the cerebellum provides unbiased estimations with nuclear medicine techniques. However, no reports confirm the cerebellum as an optimal reference region in MRI studies or evaluate the consequences of using different normalization regions. In this study, we address the effect of using the cerebellum, whole-brain white matter, and whole-brain cortical gray matter in the normalization of cerebral blood flow (CBF) parametric maps by comparing patients with stable mild cognitive impairment (MCI), patients with AD and healthy controls. According to our results, normalization by whole-brain cortical gray matter enables more sensitive detection of perfusion abnormalities in AD patients and reveals a larger number of affected regions than data normalized by the cerebellum or whole-brain white matter. Therefore, the cerebellum is not the most valid reference region in MRI studies for early stages of AD. After normalization by whole-brain cortical gray matter, we found a significant decrease in CBF in both parietal lobes and an increase in CBF in the right medial temporal lobe. We found no differences in perfusion between patients with stable MCI and healthy controls either before or after normalization.

  12. PEX13 deficiency in mouse brain as a model of Zellweger syndrome: abnormal cerebellum formation, reactive gliosis and oxidative stress

    PubMed Central

    Müller, C. Catharina; Nguyen, Tam H.; Ahlemeyer, Barbara; Meshram, Mallika; Santrampurwala, Nishreen; Cao, Siyu; Sharp, Peter; Fietz, Pamela B.; Baumgart-Vogt, Eveline; Crane, Denis I.

    2011-01-01

    SUMMARY Delayed cerebellar development is a hallmark of Zellweger syndrome (ZS), a severe neonatal neurodegenerative disorder. ZS is caused by mutations in PEX genes, such as PEX13, which encodes a protein required for import of proteins into the peroxisome. The molecular basis of ZS pathogenesis is not known. We have created a conditional mouse mutant with brain-restricted deficiency of PEX13 that exhibits cerebellar morphological defects. PEX13 brain mutants survive into the postnatal period, with the majority dying by 35 days, and with survival inversely related to litter size and weaning body weight. The impact on peroxisomal metabolism in the mutant brain is mixed: plasmalogen content is reduced, but very-long-chain fatty acids are normal. PEX13 brain mutants exhibit defects in reflex and motor development that correlate with impaired cerebellar fissure and cortical layer formation, granule cell migration and Purkinje cell layer development. Astrogliosis and microgliosis are prominent features of the mutant cerebellum. At the molecular level, cultured cerebellar neurons from E19 PEX13-null mice exhibit elevated levels of reactive oxygen species and mitochondrial superoxide dismutase-2 (MnSOD), and show enhanced apoptosis together with mitochondrial dysfunction. PEX13 brain mutants show increased levels of MnSOD in cerebellum. Our findings suggest that PEX13 deficiency leads to mitochondria-mediated oxidative stress, neuronal cell death and impairment of cerebellar development. Thus, PEX13-deficient mice provide a valuable animal model for investigating the molecular basis and treatment of ZS cerebellar pathology. PMID:20959636

  13. Abnormal activity of the MAPK- and cAMP-associated signaling pathways in frontal cortical areas in postmortem brain in schizophrenia.

    PubMed

    Funk, Adam J; McCullumsmith, Robert E; Haroutunian, Vahram; Meador-Woodruff, James H

    2012-03-01

    Recent evidence suggests that schizophrenia may result from alterations of integration of signaling mediated by multiple neurotransmitter systems. Abnormalities of associated intracellular signaling pathways may contribute to the pathophysiology of schizophrenia. Proteins and phospho-proteins comprising mitogen activated protein kinase (MAPK) and 3'-5'-cyclic adenosine monophosphate (cAMP)-associated signaling pathways may be abnormally expressed in the anterior cingulate (ACC) and dorsolateral prefrontal cortex (DLPFC) in schizophrenia. Using western blot analysis we examined proteins of the MAPK- and cAMP-associated pathways in these two brain regions. Postmortem samples were used from a well-characterized collection of elderly patients with schizophrenia (ACC=36, DLPFC=35) and a comparison (ACC=33, DLPFC=31) group. Near-infrared intensity of IR-dye labeled secondary antisera bound to targeted proteins of the MAPK- and cAMP-associated signaling pathways was measured using LiCor Odyssey imaging system. We found decreased expression of Rap2, JNK1, JNK2, PSD-95, and decreased phosphorylation of JNK1/2 at T183/Y185 and PSD-95 at S295 in the ACC in schizophrenia. In the DLPFC, we found increased expression of Rack1, Fyn, Cdk5, and increased phosphorylation of PSD-95 at S295 and NR2B at Y1336. MAPK- and cAMP-associated molecules constitute ubiquitous intracellular signaling pathways that integrate extracellular stimuli, modify receptor expression and function, and regulate cell survival and neuroplasticity. These data suggest abnormal activity of the MAPK- and cAMP-associated pathways in frontal cortical areas in schizophrenia. These alterations may underlie the hypothesized hypoglutamatergic function in this illness. Together with previous findings, these data suggest that abnormalities of intracellular signaling pathways may contribute to the pathophysiology of schizophrenia. PMID:22048463

  14. Cortico-striato-thalamo-cortical circuit abnormalities in obsessive-compulsive disorder: A voxel-based morphometric and fMRI study of the whole brain.

    PubMed

    Tang, Wenxin; Zhu, Qifeng; Gong, Xiangyang; Zhu, Cheng; Wang, Yiquan; Chen, Shulin

    2016-10-15

    The primary aim of this study was to identify structural and functional abnormalities in the brains of obsessive-compulsive disorder (OCD) patients. Another aim was to assess the effect of serotonin selective reuptake inhibitors (SSRIs) on brain structure of OCD patients. All subjects underwent brain magnetic resonance imaging (MRI) and resting functional MRI (fMRI). High-resolution three-dimensional images were processed using the voxel-based morphometry (VBM) method. The final analysis included 18 OCD patients and 16 healthy controls. In the OCD patients there was a decrease in gray matter volume in the bilateral cingulate cortex and bilateral striatum. In some cortical structures including the cerebellar anterior lobe, left orbital frontal gyrus, right middle frontal gyrus, left middle temporal gyrus, precentral gyrus, and postcentral gyrus, there was an increase in gray matter volume. On fMRI the OCD patients had overactivation of the right cerebellum and right parietal lobe and reduced activation of the left cingulate gyrus, putamen, and caudate nucleus. Eleven OCD patients who improved during 12 weeks of drug treatment with sertraline hydrochloride had a significant increase in gray matter volume in several brain structures but no significant differences were found on resting fMRI. The results indicated a consistent trend between structural and functional images. Higher cortical structures showed increased gray matter volume and increased activation as did the cerebellum whereas subcortical structures showed decreased gray matter volume and decreased activation. And brain structure improvement consisted with symptom improvement after SSRIs treatment in OCD patients. PMID:27388149

  15. Transient global amnesia: implicit/explicit memory dissociation and PET assessment of brain perfusion and oxygen metabolism in the acute stage

    PubMed Central

    Eustache, F.; Desgranges, B.; Petit-Taboue, M.; de la Sayette, V.; Piot, V.; Sable, C.; Marchal, G.; Baron, J.

    1997-01-01

    OBJECTIVES—To assess explicit memory and two components of implicit memory—that is, perceptual-verbal skill learning and lexical-semantic priming effects—as well as resting cerebral blood flow (CBF) and oxygen metabolism (CMRO2) during the acute phase of transient global amnesia.
METHODS—In a 59 year old woman, whose amnestic episode fulfilled all current criteria for transient global amnesia, a neuropsychological protocol was administered, including word learning, story recall, categorical fluency, mirror reading, and word stem completion tasks. PET was performed using the 15O steady state inhalation method, while the patient still exhibited severe anterograde amnesia and was interleaved with the cognitive tests.
RESULTS—There was a clear cut dissociation between impaired long term episodic memory and preserved implicit memory for its two components. Categorical fluency was significantly altered, suggesting word retrieval strategy—rather than semantic memory—impairment. The PET study disclosed a reduced CMRO2 with relatively or fully preserved CBF in the left prefrontotemporal cortex and lentiform nucleus, and the reverse pattern over the left occipital cortex.
CONCLUSIONS—The PET alterations with patchy CBF-CMRO2 uncoupling would be compatible with a migraine-like phenomenon and indicate that the isolated assessment of perfusion in transient global amnesia may be misleading. The pattern of metabolic depression, with sparing of the hippocampal area, is one among the distinct patterns of brain dysfunction that underlie the (apparently) uniform clinical presentation of transient global amnesia. The finding of a left prefrontal hypometabolism in the face of impaired episodic memory and altered verbal fluency would fit present day concepts from PET activation studies about the role of this area in episodic and semantic memory encoding/retrieval. Likewise, the changes affecting the lenticular nucleus but sparing the caudate would be consistent

  16. Impaired Associative Taste Learning and Abnormal Brain Activation in Kinase-Defective eEF2K Mice

    ERIC Educational Resources Information Center

    Gildish, Iness; Manor, David; David, Orit; Sharma, Vijendra; Williams, David; Agarwala, Usha; Wang, Xuemin; Kenney, Justin W.; Proud, Chris G.; Rosenblum, Kobi

    2012-01-01

    Memory consolidation is defined temporally based on pharmacological interventions such as inhibitors of mRNA translation (molecular consolidation) or post-acquisition deactivation of specific brain regions (systems level consolidation). However, the relationship between molecular and systems consolidation are poorly understood. Molecular…

  17. Functional magnetic resonance imaging reveals abnormal brain connectivity in EGR3 gene transfected rat model of schizophrenia.

    PubMed

    Song, Tianbin; Nie, Binbin; Ma, Ensen; Che, Jing; Sun, Shilong; Wang, Yuli; Shan, Baoci; Liu, Yawu; Luo, Senlin; Ma, Guolin; Li, Kefeng

    2015-05-01

    Schizophrenia is characterized by the disorder of "social brain". However, the alternation of connectivity density in brain areas of schizophrenia patients remains largely unknown. In this study, we successfully created a rat model of schizophrenia by the transfection of EGR3 gene into rat brain. We then investigated the connectivity density of schizophrenia susceptible regions in rat brain using functional magnetic resonance imaging (fMRI) in combination with multivariate Granger causality (GC) model. We found that the average signal strength in prefrontal lobe and hippocampus of schizophrenia model group was significantly higher than the control group. Bidirectional Granger causality connection was observed between hippocampus and thalamic in schizophrenia model group. Both connectivity density and Granger causality connection were changed in prefrontal lobe, hippocampus and thalamus after risperidone treatment. Our results indicated that fMRI in combination with GC connection analysis may be used as an important method in diagnosis of schizophrenia and evaluation the effect of antipsychotic treatment. These findings support the connectivity disorder hypothesis of schizophrenia and increase our understanding of the neural mechanisms of schizophrenia.

  18. The Philadelphia Neurodevelopmental Cohort: A publicly available resource for the study of normal and abnormal brain development in youth.

    PubMed

    Satterthwaite, Theodore D; Connolly, John J; Ruparel, Kosha; Calkins, Monica E; Jackson, Chad; Elliott, Mark A; Roalf, David R; Ryan Hopsona, Karthik Prabhakaran; Behr, Meckenzie; Qiu, Haijun; Mentch, Frank D; Chiavacci, Rosetta; Sleiman, Patrick M A; Gur, Ruben C; Hakonarson, Hakon; Gur, Raquel E

    2016-01-01

    The Philadelphia Neurodevelopmental Cohort (PNC) is a large-scale study of child development that combines neuroimaging, diverse clinical and cognitive phenotypes, and genomics. Data from this rich resource is now publicly available through the Database of Genotypes and Phenotypes (dbGaP). Here we focus on the data from the PNC that is available through dbGaP and describe how users can access this data, which is evolving to be a significant resource for the broader neuroscience community for studies of normal and abnormal neurodevelopment.

  19. Microfluidic perfusion culture.

    PubMed

    Hattori, Koji; Sugiura, Shinji; Kanamori, Toshiyuki

    2014-01-01

    Microfluidic perfusion culture is a novel technique to culture animal cells in a small-scale microchamber with medium perfusion. Polydimethylsiloxane (PDMS) is the most popular material to fabricate a microfluidic perfusion culture chip. Photolithography and replica molding techniques are generally used for fabrication of a microfluidic perfusion culture chip. Pressure-driven perfusion culture system is convenient technique to carry out the perfusion culture of animal cells in a microfluidic device. Here, we describe a general theory on microfluid network design, microfabrication technique, and experimental technique for pressure-driven perfusion culture in an 8 × 8 microchamber array on a glass slide-sized microchip made out of PDMS. PMID:24297421

  20. [A case report of mirror writing with low perfusion of bilateral anterior cerebral arteries].

    PubMed

    Shimamura, N; Sekiya, T; Ohkuma, H; Tabata, H; Yagihashi, A; Suzuki, S

    2001-06-01

    A 20-year-old female experienced temporary unintentional mirror writing associated with low perfusion of the bilateral anterior cerebral arteries. When she was 17 years old, she had developed multiple idiopathic intracerebral hemorrhages and right hemiparesis. At the age of 20, she had a generalized convulsion for which she was transferred to our department. Computed tomography (CT) and magnetic resonance images of the brain were obtained, but no fresh abnormal lesion could be detected. The following day, after she had recovered from postictal symptoms, she wrote mirror image words, and her mirror writing then gradually improved within one week. Single photon emission CT showed low perfusion of both anterior cerebral arteries. We concluded that bilateral vascular insufficiency to the supplementary motor areas and corpus callosum caused mirror writing in this case.

  1. Demonstration of Normal and Abnormal Fetal Brains Using 3D Printing from In Utero MR Imaging Data.

    PubMed

    Jarvis, D; Griffiths, P D; Majewski, C

    2016-09-01

    3D printing is a new manufacturing technology that produces high-fidelity models of complex structures from 3D computer-aided design data. Radiology has been particularly quick to embrace the new technology because of the wide access to 3D datasets. Models have been used extensively to assist orthopedic, neurosurgical, and maxillofacial surgical planning. In this report, we describe methods used for 3D printing of the fetal brain by using data from in utero MR imaging.

  2. Demonstration of Normal and Abnormal Fetal Brains Using 3D Printing from In Utero MR Imaging Data.

    PubMed

    Jarvis, D; Griffiths, P D; Majewski, C

    2016-09-01

    3D printing is a new manufacturing technology that produces high-fidelity models of complex structures from 3D computer-aided design data. Radiology has been particularly quick to embrace the new technology because of the wide access to 3D datasets. Models have been used extensively to assist orthopedic, neurosurgical, and maxillofacial surgical planning. In this report, we describe methods used for 3D printing of the fetal brain by using data from in utero MR imaging. PMID:27079366

  3. Involvement of oxidative stress-induced abnormalities in ceramide and cholesterol metabolism in brain aging and Alzheimer's disease

    NASA Astrophysics Data System (ADS)

    Cutler, Roy G.; Kelly, Jeremiah; Storie, Kristin; Pedersen, Ward A.; Tammara, Anita; Hatanpaa, Kimmo; Troncoso, Juan C.; Mattson, Mark P.

    2004-02-01

    Alzheimer's disease (AD) is an age-related disorder characterized by deposition of amyloid -peptide (A) and degeneration of neurons in brain regions such as the hippocampus, resulting in progressive cognitive dysfunction. The pathogenesis of AD is tightly linked to A deposition and oxidative stress, but it remains unclear as to how these factors result in neuronal dysfunction and death. We report alterations in sphingolipid and cholesterol metabolism during normal brain aging and in the brains of AD patients that result in accumulation of long-chain ceramides and cholesterol. Membrane-associated oxidative stress occurs in association with the lipid alterations, and exposure of hippocampal neurons to A induces membrane oxidative stress and the accumulation of ceramide species and cholesterol. Treatment of neurons with -tocopherol or an inhibitor of sphingomyelin synthesis prevents accumulation of ceramides and cholesterol and protects them against death induced by A. Our findings suggest a sequence of events in the pathogenesis of AD in which A induces membrane-associated oxidative stress, resulting in perturbed ceramide and cholesterol metabolism which, in turn, triggers a neurodegenerative cascade that leads to clinical disease. amyloid | apoptosis | hippocampus | lipid peroxidation | sphingomyelin

  4. Detection of whole-brain abnormalities in temporal lobe epilepsy using tensor-based morphometry with DARTEL

    NASA Astrophysics Data System (ADS)

    Li, Wenjing; He, Huiguang; Lu, Jingjing; Lv, Bin; Li, Meng; Jin, Zhengyu

    2009-10-01

    Tensor-based morphometry (TBM) is an automated technique for detecting the anatomical differences between populations by examining the gradients of the deformation fields used to nonlinearly warp MR images. The purpose of this study was to investigate the whole-brain volume changes between the patients with unilateral temporal lobe epilepsy (TLE) and the controls using TBM with DARTEL, which could achieve more accurate inter-subject registration of brain images. T1-weighted images were acquired from 21 left-TLE patients, 21 right-TLE patients and 21 healthy controls, which were matched in age and gender. The determinants of the gradient of deformation fields at voxel level were obtained to quantify the expansion or contraction for individual images relative to the template, and then logarithmical transformation was applied on it. A whole brain analysis was performed using general lineal model (GLM), and the multiple comparison was corrected by false discovery rate (FDR) with p<0.05. For left-TLE patients, significant volume reductions were found in hippocampus, cingulate gyrus, precentral gyrus, right temporal lobe and cerebellum. These results potentially support the utility of TBM with DARTEL to study the structural changes between groups.

  5. Metabolic and vascular determinants of impaired cognitive performance and abnormalities on brain magnetic resonance imaging in patients with type 2 diabetes

    PubMed Central

    Biessels, G. J.; de Valk, H.; Algra, A.; Rutten, G. E. H. M.; van der Grond, J.; Kappelle, L. J.

    2007-01-01

    Aims/hypothesis The determinants of cerebral complications of type 2 diabetes are unclear. The present study aimed to identify metabolic and vascular factors that are associated with impaired cognitive performance and abnormalities on brain MRI in patients with type 2 diabetes. Methods The study included 122 patients and 56 controls. Neuropsychological test scores were divided into five cognitive domains and expressed as standardised z values. Brain MRI scans were rated for white matter lesions (WML), cortical and subcortical atrophy, and infarcts. Data on glucose metabolism, vascular risk factors and micro- and macrovascular disease were collected. Results Patients with type 2 diabetes had more cortical (p < 0.001) and subcortical (p < 0.01) atrophy and deep WML (p = 0.02) than the control group and their cognitive performance was worse. In multivariate regression analyses within the type 2 diabetes group, hypertension (p < 0.05) and a history of vascular events (p < 0.01) were associated with worse cognitive performance, while statin use was associated (p < 0.05) with better performance. Retinopathy and brain infarcts on MRI were associated with more severe cortical atrophy (both p < 0.01) and statin use with less atrophy (p < 0.05). Insulin level and brain infarcts were associated with more severe WML and statin use with less severe WML (all p < 0.05). Conclusions/interpretation Type 2 diabetes is associated with modest impairments in cognition, as well as atrophy and vascular lesions on MRI. This ‘diabetic encephalopathy’ is a multifactorial condition, for which atherosclerotic (macroangiopathic) vascular disease is an important determinant. Chronic hyperglycaemia, hyperinsulinaemia and hypertension may play additional roles. Electronic supplementary material The online version of this article (doi:10.1007/s00125-007-0792-z) contains details of the Utrecht Diabetic Encephalopathy Study Group, which are available to

  6. Understanding brain dysfunction in sepsis

    PubMed Central

    2013-01-01

    Sepsis often is characterized by an acute brain dysfunction, which is associated with increased morbidity and mortality. Its pathophysiology is highly complex, resulting from both inflammatory and noninflammatory processes, which may induce significant alterations in vulnerable areas of the brain. Important mechanisms include excessive microglial activation, impaired cerebral perfusion, blood–brain-barrier dysfunction, and altered neurotransmission. Systemic insults, such as prolonged inflammation, severe hypoxemia, and persistent hyperglycemia also may contribute to aggravate sepsis-induced brain dysfunction or injury. The diagnosis of brain dysfunction in sepsis relies essentially on neurological examination and neurological tests, such as EEG and neuroimaging. A brain MRI should be considered in case of persistent brain dysfunction after control of sepsis and exclusion of major confounding factors. Recent MRI studies suggest that septic shock can be associated with acute cerebrovascular lesions and white matter abnormalities. Currently, the management of brain dysfunction mainly consists of control of sepsis and prevention of all aggravating factors, including metabolic disturbances, drug overdoses, anticholinergic medications, withdrawal syndromes, and Wernicke’s encephalopathy. Modulation of microglial activation, prevention of blood–brain-barrier alterations, and use of antioxidants represent relevant therapeutic targets that may impact significantly on neurologic outcomes. In the future, investigations in patients with sepsis should be undertaken to reduce the duration of brain dysfunction and to study the impact of this reduction on important health outcomes, including functional and cognitive status in survivors. PMID:23718252

  7. Whole-brain functional connectivity during emotional word classification in medication-free Major Depressive Disorder: Abnormal salience circuitry and relations to positive emotionality☆

    PubMed Central

    van Tol, Marie-José; Veer, Ilya M.; van der Wee, Nic J.A.; Aleman, André; van Buchem, Mark A.; Rombouts, Serge A.R.B.; Zitman, Frans G.; Veltman, Dick J.; Johnstone, Tom

    2013-01-01

    Major Depressive Disorder (MDD) has been associated with biased processing and abnormal regulation of negative and positive information, which may result from compromised coordinated activity of prefrontal and subcortical brain regions involved in evaluating emotional information. We tested whether patients with MDD show distributed changes in functional connectivity with a set of independently derived brain networks that have shown high correspondence with different task demands, including stimulus salience and emotional processing. We further explored if connectivity during emotional word processing related to the tendency to engage in positive or negative emotional states. In this study, 25 medication-free MDD patients without current or past comorbidity and matched controls (n = 25) performed an emotional word-evaluation task during functional MRI. Using a dual regression approach, individual spatial connectivity maps representing each subject's connectivity with each standard network were used to evaluate between-group differences and effects of positive and negative emotionality (extraversion and neuroticism, respectively, as measured with the NEO-FFI). Results showed decreased functional connectivity of the medial prefrontal cortex, ventrolateral prefrontal cortex, and ventral striatum with the fronto-opercular salience network in MDD patients compared to controls. In patients, abnormal connectivity was related to extraversion, but not neuroticism. These results confirm the hypothesis of a relative (para)limbic–cortical decoupling that may explain dysregulated affect in MDD. As connectivity of these regions with the salience network was related to extraversion, but not to general depression severity or negative emotionality, dysfunction of this network may be responsible for the failure to sustain engagement in rewarding behavior. PMID:24179829

  8. Abnormal brain activation during working memory in children with prenatal exposure to drugs of abuse: the effects of methamphetamine, alcohol, and polydrug exposure.

    PubMed

    Roussotte, Florence F; Bramen, Jennifer E; Nunez, S Christopher; Quandt, Lorna C; Smith, Lynne; O'Connor, Mary J; Bookheimer, Susan Y; Sowell, Elizabeth R

    2011-02-14

    Structural and metabolic abnormalities in fronto-striatal structures have been reported in children with prenatal methamphetamine (MA) exposure. The current study was designed to quantify functional alterations to the fronto-striatal circuit in children with prenatal MA exposure using functional magnetic resonance imaging (fMRI). Because many women who use MA during pregnancy also use alcohol, a known teratogen, we examined 50 children (age range 7-15), 19 with prenatal MA exposure, 15 of whom had concomitant prenatal alcohol exposure (the MAA group), 13 with heavy prenatal alcohol but no MA exposure (ALC group), and 18 unexposed controls (CON group). We hypothesized that MA exposed children would demonstrate abnormal brain activation during a visuospatial working memory (WM) "N-Back" task. As predicted, the MAA group showed less activation than the CON group in many brain areas, including the striatum and frontal lobe in the left hemisphere. The ALC group showed less activation than the MAA group in several regions, including the right striatum. We found an inverse correlation between performance and activity in the striatum in both the CON and MAA groups. However, this relationship was significant in the caudate of the CON group but not the MAA group, and in the putamen of the MAA group but not the CON group. These findings suggest that structural damage in the fronto-striatal circuit after prenatal MA exposure leads to decreased recruitment of this circuit during a WM challenge, and raise the possibility that a rewiring of cortico-striatal networks may occur in children with prenatal MA exposure.

  9. [Assessing myocardial perfusion with positron emission tomography].

    PubMed

    vom Dahl, J

    2001-11-01

    Positron emission tomography (PET) of the heart has gained widespread scientific and clinical acceptance with regard to two indications: 1) The detection of perfusion abnormalities by qualitative and semiquantitative analyses of perfusion images at rest and during physical or pharmacological stress using well-validated perfusion tracers, such as N-13 ammonia, Rb-82 rubidium chloride, or O-15 labeled water. 2) Viability imaging of myocardial regions with reduced contractility by combining perfusion measurements with substrate metabolism as assessed from F-18 deoxyglucose utilization. This overview summarizes the use of PET as a perfusion imaging method. With a sensitivity > 90% in combination with high specificity, PET is today the best-validated available nuclear imaging technique for the diagnosis of coronary artery disease (CAD). The short half-life of the perfusion tracers in combination with highly sophisticated hard- and software enables rapid PET studies with high patient throughput. The high diagnostic accuracy and the methological advantages as compared to conventional scintigraphy allows one to use PET perfusion imaging to detect subtle changes in the perfusion reserve for the detection of CAD in high risk but asymptomatic patients as well as in patients with proven CAD undergoing various treatment forms such as risk factor reduction or coronary revascularization. In patients following orthotopic heart transplantation, evolving transplant vasculopathy can be detected at an early stage. Quantitative PET imaging at rest allows for detection of myocardial viability since cellular survival is based on maintenance of a minimal perfusion and structural changes correlate to the degree of perfusion reduction. Furthermore, quantitative assessment of the myocardial perfusion reserve detects the magnitude and competence of collaterals in regions with occluded epicardial collaterals and, thus, imaging of several coronary distribution territories in one noninvasive

  10. A two-year follow-up of cognitive deficits and brain perfusion in mild cognitive impairment and mild Alzheimer's disease.

    PubMed

    Alegret, Montserrat; Cuberas-Borrós, Gemma; Vinyes-Junqué, Georgina; Espinosa, Ana; Valero, Sergi; Hernández, Isabel; Roca, Isabel; Ruíz, Agustín; Rosende-Roca, Maitée; Mauleón, Ana; Becker, James T; Castell-Conesa, Joan; Tárraga, Lluís; Boada, Mercè

    2012-01-01

    The 15-Objects Test (15-OT) provides useful gradation of visuoperceptual impairment from normal aging through Alzheimer's disease (AD) and correlates with temporo-parietal perfusion. The objectives of this study were to analyze progression of 15-OT performance in mild cognitive impairment (MCI) and AD, and its correlates with cognition and single photon emission computerized tomography (SPECT), as well as to examine neuropsychological and SPECT differences between the MCI patients who developed AD and those who did not. From the initial 126 participants (42/group), 38 AD, 39 MCI, and 38 elderly controls (EC) were reassessed (SPECT: 35 AD, 33 MCI, 35 EC) after two years. The progression of cognitive and SPECT scores during this period was compared between groups, and baseline data between converters and non-converters. The 15-OT was the only measure of progression that differed between the three groups; worsening scores on 15-OT were associated with worsening in verbal and visual retention, and decreased perfusion on left postsubicular area. In the MCI patients, cerebral perfusion fell over the two years in medial-posterior cingulate and fronto-temporo-parietal regions; AD showed extensive changes involving almost all cerebral regions. No SPECT changes were detected in controls. At baseline, the MCI patients who developed AD differed from non-converters in verbal recognition memory, but not in SPECT perfusion. In conclusion, SPECT and 15-OT appear to provide a potential measure to differentiate between normal aging, MCI, and AD. Worsening on 15-OT was related to decreased perfusion in postsubicular area; but further longitudinal studies are needed to determine the contribution of 15-OT as a predictor of AD from MCI.

  11. Abnormal spontaneous regional brain activity in primary insomnia: a resting-state functional magnetic resonance imaging study

    PubMed Central

    Li, Chao; Ma, Xiaofen; Dong, Mengshi; Yin, Yi; Hua, Kelei; Li, Meng; Li, Changhong; Zhan, Wenfeng; Li, Cheng; Jiang, Guihua

    2016-01-01

    Objective Investigating functional specialization is crucial for a complete understanding of the neural mechanisms of primary insomnia (PI). Resting-state functional magnetic resonance imaging (fMRI) is a useful tool to explore the functional specialization of PI. However, only a few studies have focused on the functional specialization of PI using resting-state fMRI and results of these studies were far from consistent. Thus, the current study aimed to investigate functional specialization of PI using resting-state fMRI with amplitude of low frequency fluctuations (ALFFs) algorithm. Methods In this study, 55 PI patients and 44 healthy controls were included. ALFF values were compared between the two groups using two-sample t-test. The relationship of abnormal ALFF values with clinical characteristics and duration of insomnia was investigated using Pearson’s correlation analysis. Results PI patients showed lower ALFF values in the left orbitofrontal cortex/inferior frontal gyrus, right middle frontal gyrus, left inferior parietal lobule, and bilateral cerebellum posterior lobes, while higher ALFF values in the right middle/inferior temporal that extended to the right occipital lobe. In addition, we found that the duration of PI negatively correlated with ALFF values in the left orbitofrontal cortex/inferior frontal gyrus, and the Pittsburgh Sleep Quality Index score negatively correlated with ALFF values in the left inferior parietal lobule. Conclusion The present study added information to limited studies on functional specialization and provided evidence for hyperarousal hypothesis in PI. PMID:27366068

  12. Structural brain abnormalities in patients with Parkinson's disease with visual hallucinations: a comparative voxel-based analysis.

    PubMed

    Gama, Romulo Lopes; Bruin, Veralice Meireles Sales; Távora, Daniel Gurgel Fernandes; Duran, Fábio L S; Bittencourt, Lia; Tufik, Sergio

    2014-06-01

    The objective is to evaluate clinical characteristics and cerebral alterations in Parkinson's disease (PD) patients with diurnal visual hallucinations (VHs). Assessment was performed using magnetic resonance image (MRI) and voxel-based morphometry (VBM). Thirty-nine patients with PD (53.8%) and ten controls were studied. Voxel based morphology analysis was performed. Eleven patients presented diurnal VHs and among these, six had cognitive dysfunction. Patients with VHs performed worse in the mentation-related UPDRS I (p=0.005) and motor-related UPDRS III (p=0.02). Patients with VHs showed significant clusters of reduced grey matter volume compared to controls in the left opercula frontal gyrus and left superior frontal gyrus. PD without hallucinations demonstrated reduced grey matter volume in the left superior frontal gyrus compared to controls. Comparisons between patients with VHs regarding the presence of cognitive dysfunction showed that cases with cognitive dysfunction as compared to those without cognitive dysfunction showed significant clusters of reduced grey matter volume in the left opercular frontal gyrus. Cases without cognitive dysfunction had reduced grey matter substance in the left insula and left trigonal frontal gyrus. Judging from our findings, an abnormal frontal cortex, particularly left sided insula, frontal opercular, trigonal frontal gyrus and orbital frontal would make PD patients vulnerable to hallucinations. Compromise of the left operculum distinguished cases with VHs and cognitive dysfunction. Our findings reinforce the theoretical concept of a top-down visual processing in the genesis of VHs in PD.

  13. Methylphenidate treatment leads to abnormalities on krebs cycle enzymes in the brain of young and adult rats.

    PubMed

    Réus, Gislaine Z; Scaini, Giselli; Furlanetto, Camila B; Morais, Meline O S; Jeremias, Isabela C; Mello-Santos, Lis Mairá; Freitas, Karolina V; Quevedo, João; Streck, Emilio L

    2013-08-01

    Studies have shown a relationship between energy metabolism and methylphenidate (MPH); however, there are no studies evaluating the effects of MPH in Krebs cycle. So, we investigated if MPH treatment could alter the activity of citrate synthase (CS), malate dehydrogenase (MD), and isocitrate dehydrogenase (ID) in the brain of young and adult Wistar rats. Our results showed that MPH (2 and 10 mg/kg) reduced CS in the striatum and prefrontal cortex (PF), with MPH at all doses in the cerebellum and hippocampus after chronic treatment in young rats. In adult rats the CS was reduced in the cerebellum after acute treatment with MPH at all doses, and after chronic treatment in the PF and cerebellum with MPH (10 mg/kg), and in the hippocampus with MPH (2 and 10 mg/kg). The ID decreased in the hippocampus and striatum with MPH (2 and 10 mg/kg), and in the cortex (10 mg/kg) after acute treatment in young rats. In adult rats acute treatment with MPH (2 and 10 mg/kg) reduced ID in the cerebellum, and with MPH (10 mg/kg) in the cortex; chronic treatment with MPH (10 mg/kg) decreased ID in the PF; with MPH (2 and 10 mg/kg) in the cerebellum, and with MPH at all doses in the hippocampus. The MD did not alter. In conclusion, our results suggest that MPH can alter enzymes of Krebs cycle in brain areas involved with circuits related with attention deficit hyperactivity disorder; however, such effects depend on age of animal and treatment regime.

  14. Pulmonary ventilation/perfusion scan

    MedlinePlus

    V/Q scan; Ventilation/perfusion scan; Lung ventilation/perfusion scan ... A pulmonary ventilation/perfusion scan is actually two tests. They may be done separately or together. During the perfusion scan, a health care ...

  15. The “Skull Flap” a new conceived device for decompressive craniectomy experimental study on dogs to evaluate the safety and efficacy in reducing intracranial pressure and subsequent impact on brain perfusion

    PubMed Central

    Salvatore, Chibbaro; Fabrice, Vallee; Marco, Marsella; Leonardo, Tigan; Thomas, Lilin; Benoit, Lecuelle; Bernard, George; Pierre, Kehrli; Eric, Vicaut; Paolo, Diemidio

    2013-01-01

    Background: Decompressive craniectomy (DC) is a procedure performed increasingly often in current neurosurgical practice. Significant perioperative morbidity may be associated to this procedure because of the large skull defect; also, later closure of the skull defect (cranioplasty) may be associated to post-operative morbidity as much as any other reconstructive operation. The authors present a newly conceived/developed device: The “Skull Flap” (SF). This system, placed at the time of the craniectomy, offers the possibility to provide cranial reconstruction sparing patients a second operation. In other words, DC and cranioplasty essentially take place at the same time and in addition, patients retain their own bone flap. The current study conducted on animal models, represents the logical continuation of a prior recent study, realized on cadaver specimens, to assess the efficacy and safety of this recently developed device. Materials and Methods: This is an experimental pilot study on dogs to assess both safety and efficacy of the SF device. Two groups of experimental raised intracranial pressure animal models underwent DC; in the first group of dogs, the bone flap was left in raised position above the skull defect using the SF device; on the second group the flap was discarded. All dogs underwent transcranial Doppler (TCD) to assess brain perfusion. Head computed tomography (CT) scan to determine flap position was also obtained in the group in which the SF device was placed. Results: SF has proved to be a strong fixation device that allows satisfactory brain decompression by keeping the bone flap elevated from the swollen brain; later on, the SF allows cranial reconstruction in a simple way without requiring a second staged operation. In addition, it is relevant to note that brain perfusion was measured and found to be better in the group receiving the SF (while the flap being in a raised as well as in its natural position) comparing to the other group

  16. Brain

    MedlinePlus

    ... will return after updating. Resources Archived Modules Updates Brain Cerebrum The cerebrum is the part of the ... the outside of the brain and spinal cord. Brain Stem The brain stem is the part of ...

  17. Frequency Matters: Beta Band Subthalamic Nucleus Deep Brain Stimulation Induces Parkinsonian-like Blink Abnormalities in Normal Rats

    PubMed Central

    Kaminer, Jaime; Thakur, Pratibha; Evinger, Craig

    2014-01-01

    The synchronized beta band oscillations in the basal ganglia-cortical networks in Parkinson's disease (PD) may be responsible for PD motor symptoms or an epiphenomenon of dopamine loss. We investigated the causal role of beta band activity in PD motor symptoms by testing the effects of beta frequency subthalamic nucleus deep brain stimulation (STN DBS) on blink reflex excitability, amplitude, and plasticity in normal rats. Delivering 16 Hz STN DBS produced the same increase in blink reflex excitability and impairment in blink reflex plasticity in normal rats as occurs in rats with 6-OHDA lesions and PD patients. These deficits were not an artifact of STN DBS because when these normal rats received 130 Hz STN DBS, their blink characteristics were the same as without STN DBS. To demonstrate the blink reflex disturbances with 16 Hz STN DBS were frequency specific, we tested the same rats with 7 Hz STN DBS, a theta band frequency typical of dystonia. In contrast to beta stimulation, 7 Hz DBS exaggerated blink reflex plasticity as occurs in focal dystonia. Thus, without destroying dopamine neurons or blocking dopamine receptors, frequency specific STN DBS can be used to create PD- or dystonic-like symptoms in a normal rat. PMID:25146113

  18. Sequential relationships between grey matter and white matter atrophy and brain metabolic abnormalities in early Alzheimer's disease.

    PubMed

    Villain, Nicolas; Fouquet, Marine; Baron, Jean-Claude; Mézenge, Florence; Landeau, Brigitte; de La Sayette, Vincent; Viader, Fausto; Eustache, Francis; Desgranges, Béatrice; Chételat, Gaël

    2010-11-01

    Hippocampal atrophy, posterior cingulate and frontal glucose hypometabolism, and white-matter tract disruption are well described early macroscopic events in Alzheimer's disease. The relationships between these three types of alterations have been documented in previous studies, but their chronology still remains to be established. The present study used multi-modal fluorodeoxyglucose-positron emission tomography and magnetic resonance imaging longitudinal data to address this question in patients with amnestic mild cognitive impairment. We found unidirectional, specific sequential relationships between: (i) baseline hippocampal atrophy and both cingulum bundle (r = 0.70; P = 3 × 10⁻³) and uncinate fasciculus (r = 0.75; P = 7 × 10⁻⁴) rate of atrophy; (ii) baseline cingulum bundle atrophy and rate of decline of posterior (r = 0.72; P = 2 × 10⁻³); and anterior (r = 0.74; P = 1 × 10⁻³) cingulate metabolism; and (iii) baseline uncinate white matter atrophy and subgenual metabolism rate of change (r = 0.65; P = 6 × 10⁻³). Baseline local grey matter atrophy was not found to contribute to hypometabolism progression within the posterior and anterior cingulate as well as subgenual cortices. These findings suggest that hippocampal atrophy progressively leads to disruption of the cingulum bundle and uncinate fasciculus, which in turn leads to glucose hypometabolism of the cingulate and subgenual cortices, respectively. This study reinforces the relevance of remote mechanisms above local interactions to account for the pattern of metabolic brain alteration observed in amnestic mild cognitive impairment, and provides new avenues to assess the sequence of events in complex diseases characterized by multiple manifestations.

  19. Brain Tumors

    MedlinePlus

    A brain tumor is a growth of abnormal cells in the tissues of the brain. Brain tumors can be benign, with no cancer cells, ... cancer cells that grow quickly. Some are primary brain tumors, which start in the brain. Others are ...

  20. The effect of head size/shape, miscentering, and bowtie filter on peak patient tissue doses from modern brain perfusion 256-slice CT: How can we minimize the risk for deterministic effects?

    SciTech Connect

    Perisinakis, Kostas; Seimenis, Ioannis; Tzedakis, Antonis; Papadakis, Antonios E.; Damilakis, John

    2013-01-15

    Purpose: To determine patient-specific absorbed peak doses to skin, eye lens, brain parenchyma, and cranial red bone marrow (RBM) of adult individuals subjected to low-dose brain perfusion CT studies on a 256-slice CT scanner, and investigate the effect of patient head size/shape, head position during the examination and bowtie filter used on peak tissue doses. Methods: The peak doses to eye lens, skin, brain, and RBM were measured in 106 individual-specific adult head phantoms subjected to the standard low-dose brain perfusion CT on a 256-slice CT scanner using a novel Monte Carlo simulation software dedicated for patient CT dosimetry. Peak tissue doses were compared to corresponding thresholds for induction of cataract, erythema, cerebrovascular disease, and depression of hematopoiesis, respectively. The effects of patient head size/shape, head position during acquisition and bowtie filter used on resulting peak patient tissue doses were investigated. The effect of eye-lens position in the scanned head region was also investigated. The effect of miscentering and use of narrow bowtie filter on image quality was assessed. Results: The mean peak doses to eye lens, skin, brain, and RBM were found to be 124, 120, 95, and 163 mGy, respectively. The effect of patient head size and shape on peak tissue doses was found to be minimal since maximum differences were less than 7%. Patient head miscentering and bowtie filter selection were found to have a considerable effect on peak tissue doses. The peak eye-lens dose saving achieved by elevating head by 4 cm with respect to isocenter and using a narrow wedge filter was found to approach 50%. When the eye lies outside of the primarily irradiated head region, the dose to eye lens was found to drop to less than 20% of the corresponding dose measured when the eye lens was located in the middle of the x-ray beam. Positioning head phantom off-isocenter by 4 cm and employing a narrow wedge filter results in a moderate reduction of

  1. Alzheimer Disease in a Mouse Model: MR Imaging–guided Focused Ultrasound Targeted to the Hippocampus Opens the Blood-Brain Barrier and Improves Pathologic Abnormalities and Behavior

    PubMed Central

    Dubey, Sonam; Yeung, Sharon; Hough, Olivia; Eterman, Naomi; Aubert, Isabelle; Hynynen, Kullervo

    2014-01-01

    Purpose To validate whether repeated magnetic resonance (MR) imaging–guided focused ultrasound treatments targeted to the hippocampus, a brain structure relevant for Alzheimer disease (ADAlzheimer disease), could modulate pathologic abnormalities, plasticity, and behavior in a mouse model. Materials and Methods All animal procedures were approved by the Animal Care Committee and are in accordance with the Canadian Council on Animal Care. Seven-month-old transgenic (TgCRND8) (Tg) mice and their nontransgenic (non-Tg) littermates were entered in the study. Mice were treated weekly with MR imaging–guided focused ultrasound in the bilateral hippocampus (1.68 MHz, 10-msec bursts, 1-Hz burst repetition frequency, 120-second total duration). After 1 month, spatial memory was tested in the Y maze with the novel arm prior to sacrifice and immunohistochemical analysis. The data were compared by using unpaired t tests and analysis of variance with Tukey post hoc analysis. Results Untreated Tg mice spent 61% less time than untreated non-Tg mice exploring the novel arm of the Y maze because of spatial memory impairments (P < .05). Following MR imaging–guided focused ultrasound, Tg mice spent 99% more time exploring the novel arm, performing as well as their non-Tg littermates. Changes in behavior were correlated with a reduction of the number and size of amyloid plaques in the MR imaging–guided focused ultrasound–treated animals (P < .01). Further, after MR imaging–guided focused ultrasound treatment, there was a 250% increase in the number of newborn neurons in the hippocampus (P < .01). The newborn neurons had longer dendrites and more arborization after MR imaging–guided focused ultrasound, as well (P < .01). Conclusion Repeated MR imaging–guided focused ultrasound treatments led to spatial memory improvement in a Tg mouse model of ADAlzheimer disease. The behavior changes may be mediated by decreased amyloid pathologic abnormalities and increased neuronal

  2. Comparison between antegrade and retrograde cerebral perfusion or profound hypothermia as brain protection strategies during repair of type A aortic dissection

    PubMed Central

    Rausch, Laura A.; Kouchoukos, Nicholas T.; Lobdell, Kevin W.; Khabbaz, Kamal; Murphy, Edward; Hagberg, Robert C.

    2016-01-01

    Background The goal of this study was to compare early postoperative outcomes and actuarial-free survival between patients who underwent repair of acute type A aortic dissection by the method of cerebral perfusion used. Methods A total of 324 patients from five academic medical centers underwent repair of acute type A aortic dissection between January 2000 and December 2010. Of those, antegrade cerebral perfusion (ACP) was used for 84 patients, retrograde cerebral perfusion (RCP) was used for 55 patients, and deep hypothermic circulatory arrest (DHCA) was used for 184 patients during repair. Major morbidity, operative mortality, and 5-year actuarial survival were compared between groups. Multivariate logistic regression was used to determine predictors of operative mortality and Cox Regression hazard ratios were calculated to determine the predictors of long term mortality. Results Operative mortality was not influenced by the type of cerebral protection (19% for ACP, 14.5% for RCP and 19.1% for DHCA, P=0.729). In multivariable logistic regression analysis, hemodynamic instability [odds ratio (OR) =19.6, 95% confidence intervals (CI), 0.102–0.414, P<0.001] and CPB time >200 min(OR =4.7, 95% CI, 1.962–1.072, P=0.029) emerged as independent predictors of operative mortality. Actuarial 5-year survival was unchanged by cerebral protection modality (48.8% for ACP, 61.8% for RCP and 66.8% for no cerebral protection, log-rank P=0.844). Conclusions During surgical repair of type A aortic dissection, ACP, RCP or DHCA are safe strategies for cerebral protection in selected patients with type A aortic dissection. PMID:27563545

  3. Nifedipine and thallium-201 myocardial perfusion in progressive systemic sclerosis

    SciTech Connect

    Kahan, A.; Devaux, J.Y.; Amor, B.; Menkes, C.J.; Weber, S.; Nitenberg, A.; Venot, A.; Guerin, F.; Degeorges, M.; Roucayrol, J.C.

    1986-05-29

    Heart disease in patients with progressive systemic sclerosis may be due in part to myocardial ischemia caused by a disturbance of the coronary microcirculation. To determine whether abnormalities of myocardial perfusion in this disorder are potentially reversible, we evaluated the effect of the coronary vasodilator nifedipine on myocardial perfusion assessed by thallium-201 scanning in 20 patients. Thallium-201 single-photon-emission computerized tomography was performed under control conditions and 90 minutes after 20 mg of oral nifedipine. The mean (+/- SD) number of left ventricular segments with perfusion defects decreased from 5.3 +/- 2.0 to 3.3 +/- 2.2 after nifedipine (P = 0.0003). Perfusion abnormalities were quantified by a perfusion score (0 to 2.0) assigned to each left ventricular segment and by a global perfusion score (0 to 18) for the entire left ventricle. The mean perfusion score in segments with resting defects increased from 0.97 +/- 0.24 to 1.26 +/- 0.44 after nifedipine (P less than 0.00001). The mean global perfusion score increased from 11.2 +/- 1.7 to 12.8 +/- 2.4 after nifedipine (P = 0.003). The global perfusion score increased by at least 2.0 in 10 patients and decreased by at least 2.0 in only 1. These observations reveal short-term improvement in thallium-201 myocardial perfusion with nifedipine in patients with progressive systemic sclerosis. The results are consistent with a potentially reversible abnormality of coronary vasomotion in this disorder, but the long-term therapeutic effects of nifedipine remain to be determined.

  4. Meiotic abnormalities

    SciTech Connect

    1993-12-31

    Chapter 19, describes meiotic abnormalities. These include nondisjunction of autosomes and sex chromosomes, genetic and environmental causes of nondisjunction, misdivision of the centromere, chromosomally abnormal human sperm, male infertility, parental age, and origin of diploid gametes. 57 refs., 2 figs., 1 tab.

  5. Understanding Brain Tumors

    MedlinePlus

    ... to Know About Brain Tumors . What is a Brain Tumor? A brain tumor is an abnormal growth
 ... Tumors” from Frankly Speaking Frankly Speaking About Cancer: Brain Tumors Download the full book Questions to ask ...

  6. Brain perfusion and permeability in patients with advanced, refractory glioblastoma treated with lomustine and the transforming growth factor-β receptor I kinase inhibitor LY2157299 monohydrate

    PubMed Central

    SEPULVEDA-SANCHEZ, JUAN; RAMOS, ANA; HILARIO, AMAYA; DE VELASCO, GUILLERMO; CASTELLANO, DANIEL; GARCIA DE LA TORRE, MARTA; RODON, JORDI; LAHN, MICHAEL F.

    2015-01-01

    Transforming growth factor-β (TGF-β) signaling is associated with tumor progression and vascularization in malignant glioma. In the present study, magnetic resonance imaging was used to evaluate changes in the size and vascularity of glioblastomas in 12 patients who were treated with lomustine and the novel inhibitor of TGF-β signaling, LY2157299 monohydrate. A response in tumor size was observed in 2 of the 12 patients; in 1 of these 2 patients, a reduction in vascular permeability and perfusion was also detected. The effect was observed following 4 cycles of treatment (~3 months). Changes in vascularity have not previously been attributed to treatment with lomustine; therefore, the effect may be associated with LY2157299 treatment. LY2157299 does not appear to have an anti-angiogenic effect when combined with lomustine, and hence may have a different mechanism of action profile compared with anti-angiogenic drugs. PMID:26137087

  7. Factors restricting maximal preservation of neuronal glycogen after perfusion fixation with dimethyl sulfoxide and iodoacetic acid in Bouin's solution. Histochemical observations in the brain of the Netherlands dwarf rabbit.

    PubMed

    Cammermeyer, J; Fenton, I M

    1982-01-01

    Thirty seconds after an initial intracardial epinephrine injection, deeply anesthetized animals are perfused consecutively with saline, Bouin's and 100% ethanol solutions, each containing 1% or 5% DMSO (Me2SO) and 0.01 M iodoacetic acid. In the Netherlands dwarf rabbit and the guinea pig, a maximal preservation of dimedone PAS-stainable, saliva-digestible glycogen is achieved, without signs of polarization of glycogen, in many neuronal and neuroglial cells occupying either brain stem nuclei or occasionally narrow perivascular zones. Tentatively, these results are ascribed to a combined effect of (a) the alleged capacity of DMSO to accelerate fixation and to suppress activation of adenylate cyclase and (b) the rapid action of Bouin's solution so that the glycogen particles become instantaneously enclosed in situ in a skeleton of coagulated proteinaceous elements. The paradoxical over-all reduction in preservation of neuronal and astrocytic glycogen may be associated either with a demonstrable loss of the fixative into the peripheral vasculature, because of contrary actions of DMSO and epinephrine, or with a transvascular passage of epinephrine resulting in neuronal glycogenolysis where the blood-brain barrier is absent or affected by DMSO. Other defects are the occurrence of myriad pericapillary foci of inadequate tissue preservation, rare petechial hemorrhages, post mortem fat emboli, and ubiquitous Buscaino plaques. Despite these adverse results preventing utilization of this technique in systematic histochemical investigations on neuronal glycogen, remarkable qualitative characteristics such as the neurons' capacity to store glycogen throughout their perikarya have been revealed. PMID:6187714

  8. Craniofacial Abnormalities

    MedlinePlus

    ... of the skull and face. Craniofacial abnormalities are birth defects of the face or head. Some, like cleft ... palate, are among the most common of all birth defects. Others are very rare. Most of them affect ...

  9. Chromosome Abnormalities

    MedlinePlus

    ... decade, newer techniques have been developed that allow scientists and doctors to screen for chromosomal abnormalities without using a microscope. These newer methods compare the patient's DNA to a normal DNA ...

  10. Walking abnormalities

    MedlinePlus

    ... include: Arthritis of the leg or foot joints Conversion disorder (a psychological disorder) Foot problems (such as a ... injuries. For an abnormal gait that occurs with conversion disorder, counseling and support from family members are strongly ...

  11. Nail abnormalities

    MedlinePlus

    Beau's lines; Fingernail abnormalities; Spoon nails; Onycholysis; Leukonychia; Koilonychia; Brittle nails ... Just like the skin, the fingernails tell a lot about your health: ... the fingernail. These lines can occur after illness, injury to ...

  12. Hepatic Perfusion Therapy.

    PubMed

    Rajeev, Rahul; Gamblin, T Clark; Turaga, Kiran K

    2016-04-01

    Isolated hepatic perfusion uses the unique vascular supply of hepatic malignancies to deliver cytotoxic chemotherapy. The procedure involves vascular isolation of the liver and delivery of chemotherapy via the hepatic artery and extraction from retrohepatic vena cava. Benefits of hepatic perfusion have been observed in hepatic metastases of ocular melanoma and colorectal cancer and primary hepatocellular carcinoma. Percutaneous and prophylactic perfusions are avenues of ongoing research.

  13. Deep Vein Thrombosis Presenting on Pulmonary Ventilation and Perfusion Scintigraphy.

    PubMed

    Itani, Malak; Fair, Joanna; Hillman, Zachary; Behnia, Fatemeh; Elojeimy, Saeed

    2016-10-01

    A 52-year-old woman presenting with dyspnea was referred for a ventilation and perfusion scan (VQ). VQ images (with Tc-DTPA [diethylene triamine pentaacetic acid aerosol] and Tc-MAA [macroaggregated albumin]) initially appeared normal; however, count rates on perfusion images were similar to ventilation images, implying little Tc-MAA had reached the lungs. Spot images of the injected extremity demonstrated focal Tc-MAA accumulation worrisome for a venous thrombus, subsequently confirmed by Doppler ultrasound. Careful attention to relative radiotracer count rates on VQ scans is crucial to ensure diagnostic utility. In addition, abnormal low perfusion radiotracer counts may unveil other pathology with important clinical implications. PMID:27556796

  14. Brain edema and breakdown of the blood-brain barrier during methamphetamine intoxication: critical role of brain hyperthermia.

    PubMed

    Kiyatkin, Eugene A; Brown, P Leon; Sharma, Hari S

    2007-09-01

    To clarify the role of brain temperature in permeability of the blood-brain barrier (BBB), rats were injected with methamphetamine (METH 9 mg/kg) at normal (23 degrees C) and warm (29 degrees C) environmental conditions and internal temperatures were monitored both centrally (nucleus accumbens, NAcc) and peripherally (skin and nonlocomotor muscle). Once NAcc temperatures peaked or reached 41.5 degrees C (a level suggesting possible lethality), animals were administered Evans blue dye (protein tracer that does not normally cross the BBB), rapidly anaesthetized, perfused and had their brains removed. All METH-treated animals showed brain and body hyperthermia associated with relative skin hypothermia, suggesting metabolic activation coupled with peripheral vasoconstriction. While METH-induced NAcc temperature elevation varied from 37.60 to 42.46 degrees C (or 1.2-5.1 degrees C above baseline), it was stronger at 29 degrees C (+4.13 degrees C) than 23 degrees C (+2.31 degrees C). Relative to control, METH-treated animals had significantly higher brain levels of water, Na(+), K(+) and Cl(-), suggesting brain edema, and intense immunostaining for albumin, indicating breakdown of the BBB. METH-treated animals also showed strong immunoreactivity for glial fibrillary acidic protein (GFAP), possibly suggesting acute abnormality or damage of astrocytes. METH-induced changes in brain water, albumin and GFAP correlated linearly with NAcc temperature (r = 0.93, 0.98 and 0.98, respectively), suggesting a key role of brain hyperthermia in BBB permeability, development of brain edema and subsequent functional and structural neural abnormalities. Therefore, along with a direct destructive action on neural cells and functions, brain hyperthermia, via breakdown of the BBB, may be crucial for both decompensation of brain functions and cell injury following acute METH intoxication, possibly contributing to neurodegeneration resulting from chronic drug use.

  15. Radionuclide cerebral perfusion imaging: Normal pattern

    SciTech Connect

    Goldsmith, S.J.; Stritzke, P.; Losonczy, M.; Vallabhajosula, S.; Holan, V.; DaCosta, M.; Muzinic, M.

    1991-12-31

    Regional cerebral perfusion imaging using a new class of {sup 99m}Tc and {sup 123}I labeled compounds which traverse the blood brain barrier and SPECT imaging technology provides an opportunity to assess this physiologic phenomenon during normal cerebral function and as a manifestation of disease in the central nervous system disease. These applications pose a challenge to the nuclear medicine physician for several reasons: (a) the complex and somewhat unfamiliar functional anatomy, (b) the marked regional differences in regional cerebral perfusion at rest, (c) the lack of understanding of the effect of variations in ambient conditions on regional cerebral perfusion. The difficulties in interpretation are augmented by the display itself. There is frequently no difficulty in differentiating between gray and white matter. However, the frequently used {open_quotes}hot body{close_quotes} color maps, introduce a good deal of contrast, producing displays with apparent interruption in regional cortical perfusion whereas black and white displays provide minimal contrast in the regional cortical activity. The authors sought to define how much variation in regional cerebral perfusion is {open_quotes}allowed{close_quotes} under controlled conditions, to establish a basis to interpret if changes in the environment, psychological interventions, or disease states are accompanied by a measurable change. 2 figs., 1 tab.

  16. N-isopropy(/sup 123/I)p-iodoamphetamine brain scans with single-photon emission tomagraphy: discordacne with transmission computed tomography

    SciTech Connect

    Lee, R.G.; Hill, T.C.; Holman, B.L.; Clouse, M.E.

    1982-12-01

    Transmission computed tomography (CT) brain scans were compared with N-isopropyl (/sup 123/I)-p-iodoamphetamine (IMP) single-photon emission computed tomography (SPECT) brain scans to determine if there was a correlation between morphology, as seen on CT, and cerebral perfusion changes detected by IMP SPECT. In 12 patients with acute stroke, four showed no discordance between the edema seen on CT and perfusion deficits seen on IMP SPECT; five had positive IMP scans while initial CT scans were negative and follow-up CT scans demonstrated edema in the region of perfusion deficit seen on the IMP scans; and in four patients, the average perfusion deficit was 2.3 times greater than the edema shown on CT at 2 cm above the canthal-meatal line. In nine control patients, there was a 2.3% difference in IMP activity between the right and left hemispheres. The 12 stroke patients showed 30.3% less IMP activity in the abnormal hemisphere compared with the normal side. Three patients, one with temporal lobe seizure, one with hemiballismus, and the third with idiopathic intention tumor, had 54% greater IMP activity on the side of movement or seizure than on the normal side. The discordance between IMP and CT scans was clearly demonstrated in cases in which CT showed no abnormality but IMP provided information on function, reflected in increased or decreased cerebral perfusion.

  17. N-isopropyl(I-123)p-lodoamphetamine brain scans with single-photon emission tomography discordance with transmission computed tomography

    SciTech Connect

    Lee, R.G.; Hill, T.C.; Holman, B.L.; Clouse, M.E.

    1982-12-01

    Transmission computed tomography (CT) brain scans were compared with N-isopropyl (I-123)p-iodoamphetamine (IMP) single-photon emission computed tomography (SPECT) brain scans to determine if there was a correlation between morphology, as seen on CT, and cerebral perfusion changes detected by IMP SPECT. In 12 patients with acute stroke, four showed no discordance between the edema seen on CT and perfusion deficits seen on IMP SPECT; five had positive IMP scans while initial CT scans were negative and follow-up CT scans demonstrated edema in the region of perfusion deficit seen on the IMP scans; and in four patients, the average perfusion deficit was 2.3 times greater than the edema shown on CT at 2 cm above the canthalmeatal line. In nine control patients, there was a 2.3% difference in IMP activity between the right and left hemispheres. The 12 stroke patients showed 30.3% less IMP activity in the abnormal hemisphere compared with the normal side. Three patients, one with temporal lobe seizure, one with hemiballismus, and the third with idiopathic intention tumor, had 54% greater IMP activity on the side of movement or seizure than on the normal side. The discordance between IMP and CT scans was clearly demonstrated in cases in which CT showed no abnormality but IMP provided information on function, reflected in increased or decreased cerebral perfusion.

  18. Pleiotrophin promotes vascular abnormalization in gliomas and correlates with poor survival in patients with astrocytomas.

    PubMed

    Zhang, Lei; Kundu, Soumi; Feenstra, Tjerk; Li, Xiujuan; Jin, Chuan; Laaniste, Liisi; El Hassan, Tamador Elsir Abu; Ohlin, K Elisabet; Yu, Di; Olofsson, Tommie; Olsson, Anna-Karin; Pontén, Fredrik; Magnusson, Peetra U; Nilsson, Karin Forsberg; Essand, Magnus; Smits, Anja; Dieterich, Lothar C; Dimberg, Anna

    2015-12-01

    Glioblastomas are aggressive astrocytomas characterized by endothelial cell proliferation and abnormal vasculature, which can cause brain edema and increase patient morbidity. We identified the heparin-binding cytokine pleiotrophin as a driver of vascular abnormalization in glioma. Pleiotrophin abundance was greater in high-grade human astrocytomas and correlated with poor survival. Anaplastic lymphoma kinase (ALK), which is a receptor that is activated by pleiotrophin, was present in mural cells associated with abnormal vessels. Orthotopically implanted gliomas formed from GL261 cells that were engineered to produce pleiotrophin showed increased microvessel density and enhanced tumor growth compared with gliomas formed from control GL261 cells. The survival of mice with pleiotrophin-producing gliomas was shorter than that of mice with gliomas that did not produce pleiotrophin. Vessels in pleiotrophin-producing gliomas were poorly perfused and abnormal, a phenotype that was associated with increased deposition of vascular endothelial growth factor (VEGF) in direct proximity to the vasculature. The growth of pleiotrophin-producing GL261 gliomas was inhibited by treatment with the ALK inhibitor crizotinib, the ALK inhibitor ceritinib, or the VEGF receptor inhibitor cediranib, whereas control GL261 tumors did not respond to either inhibitor. Our findings link pleiotrophin abundance in gliomas with survival in humans and mice, and show that pleiotrophin promotes glioma progression through increased VEGF deposition and vascular abnormalization. PMID:26645582

  19. Genetics Home Reference: X-linked lissencephaly with abnormal genitalia

    MedlinePlus

    ... often in males. XLAG is characterized by abnormal brain development that results in the brain having a smooth ... for interneuron migration. In addition to impairing normal brain development, a lack of functional ARX protein disrupts cell ...

  20. Cerebral blood flow in patients with peritoneal dialysis by an easy Z-score imaging system for brain perfusion single-photon emission tomography.

    PubMed

    Isshiki, Rei; Kobayashi, Shuzo; Iwagami, Masao; Tsutumi, Daimu; Mochida, Yasuhiro; Ishioka, Kunihiro; Oka, Machiko; Maesato, Kyoko; Moriya, Hidekazu; Ohtake, Takayasu; Hidaka, Sumi

    2014-06-01

    Cognitive impairment has long been recognized as a complication of chronic kidney disease. However, there is little information available regarding regional cerebral blood flow (rCBF) in patients with peritoneal dialysis (PD). Therefore, we evaluated rCBF using brain single photon emission computed tomography (SPECT). We conducted a cross-sectional study in our hospital. Eighteen consecutive PD patients who could visit the hospital by themselves without any history of stroke were examined by Technetium-99 m-labeled ethylcrysteinate dimer brain SPECT. An easy Z-score imaging system (eZIS) was used to compare rCBF in PD patients with those in age-matched healthy controls. We also evaluated cognitive dysfunction with the mini-mental state examination (MMSE) questionnaire. Only one patient showed an MMSE score of 18 points, and the remaining 14 patients were considered as normal (MMSE ≥ 27), and three patients were considered to have mild cognitive impairment (24 ≤ MMSE ≤ 26). In all patients, rCBF in the posterior cingulated gyri, precunei, and parietal cortices was significantly decreased. The ratio of the reduction of rCBF in each region relative to that of rCBF across the whole brain correlated positively with the PD duration (r = 0.559; P < 0.05). The serum β2-microglobulin level was significantly higher in patients who had a higher ratio of rCBF reduction compared with those with lower ratios. In conclusion, all PD patients in the present study had decreased rCBF irrespective of MMSE scores.

  1. Low dose CT perfusion using k-means clustering

    NASA Astrophysics Data System (ADS)

    Pisana, Francesco; Henzler, Thomas; Schönberg, Stefan; Klotz, Ernst; Schmidt, Bernhard; Kachelrieß, Marc

    2016-03-01

    We aim at improving low dose CT perfusion functional parameters maps and CT images quality, preserving quantitative information. In a dynamic CT perfusion dataset, each voxel is measured T times, where T is the number of acquired time points. In this sense, we can think about a voxel as a point in a T-dimensional space, where the coordinates of the voxels would be the values of its time attenuation curve (TAC). Starting from this idea, a k-means algorithm was designed to group voxels in K classes. A modified guided time-intensity profile similarity (gTIPS) filter was implemented and applied only for those voxels belonging to the same class. The approach was tested on a digital brain perfusion phantom as well as on clinical brain and body perfusion datasets, and compared to the original TIPS implementation. The TIPS filter showed the highest CNR improvement, but lowest spatial resolution. gTIPS proved to have the best combination of spatial resolution and CNR improvement for CT images, while k-gTIPS was superior to both gTIPS and TIPS in terms of perfusion maps image quality. We demonstrate k-means clustering analysis can be applied to denoise dynamic CT perfusion data and to improve functional maps. Beside the promising results, this approach has the major benefit of being independent from the perfusion model employed for functional parameters calculation. No similar approaches were found in literature.

  2. Higher Brain Perfusion May Not Support Memory Functions in Cognitively Normal Carriers of the ApoE ε4 Allele Compared to Non-Carriers

    PubMed Central

    Zlatar, Zvinka Z.; Bischoff-Grethe, Amanda; Hays, Chelsea C.; Liu, Thomas T.; Meloy, M. J.; Rissman, Robert A.; Bondi, Mark W.; Wierenga, Christina E.

    2016-01-01

    Age-related changes in cerebral blood flow (CBF), which carries necessary nutrients to the brain, are associated with increased risk for mild cognitive impairment (MCI) and Alzheimer’s disease (AD). Whether the association between CBF and cognition is moderated by apolipoprotein E (ApoE) ε4 genotype, a known risk factor for AD, remains understudied, with most research focusing on exploring brain regions in which there are diagnostic group differences in CBF (i.e., cognitively normal vs. MCI vs. AD). This study measured resting CBF via arterial spin labeling (ASL) magnetic resonance imaging (MRI) and verbal memory functions using a composite score in 59 older adults with normal cognition (38 ε3; 21 ε4). Linear mixed effect models were employed to investigate if the voxel-wise relationship between verbal memory performance and resting CBF was modified by ApoE genotype. Results indicated that carriers of the ApoE ε4 allele display negative associations between verbal memory functions and CBF in medial frontal cortex, medial and lateral temporal cortex, parietal regions, insula, and the basal ganglia. Contrarily, ε3 carriers exhibited positive associations between verbal memory functions and CBF in medial frontal cortex, thalamus, insula, and basal ganglia. Findings suggest that higher CBF was associated with worse verbal memory functions in cognitively normal ε4 carriers, perhaps reflecting dysregulation within the neurovascular unit, which is no longer supportive of cognition. Results are discussed within the context of the vascular theory of AD risk. PMID:27445794

  3. Higher Brain Perfusion May Not Support Memory Functions in Cognitively Normal Carriers of the ApoE ε4 Allele Compared to Non-Carriers.

    PubMed

    Zlatar, Zvinka Z; Bischoff-Grethe, Amanda; Hays, Chelsea C; Liu, Thomas T; Meloy, M J; Rissman, Robert A; Bondi, Mark W; Wierenga, Christina E

    2016-01-01

    Age-related changes in cerebral blood flow (CBF), which carries necessary nutrients to the brain, are associated with increased risk for mild cognitive impairment (MCI) and Alzheimer's disease (AD). Whether the association between CBF and cognition is moderated by apolipoprotein E (ApoE) ε4 genotype, a known risk factor for AD, remains understudied, with most research focusing on exploring brain regions in which there are diagnostic group differences in CBF (i.e., cognitively normal vs. MCI vs. AD). This study measured resting CBF via arterial spin labeling (ASL) magnetic resonance imaging (MRI) and verbal memory functions using a composite score in 59 older adults with normal cognition (38 ε3; 21 ε4). Linear mixed effect models were employed to investigate if the voxel-wise relationship between verbal memory performance and resting CBF was modified by ApoE genotype. Results indicated that carriers of the ApoE ε4 allele display negative associations between verbal memory functions and CBF in medial frontal cortex, medial and lateral temporal cortex, parietal regions, insula, and the basal ganglia. Contrarily, ε3 carriers exhibited positive associations between verbal memory functions and CBF in medial frontal cortex, thalamus, insula, and basal ganglia. Findings suggest that higher CBF was associated with worse verbal memory functions in cognitively normal ε4 carriers, perhaps reflecting dysregulation within the neurovascular unit, which is no longer supportive of cognition. Results are discussed within the context of the vascular theory of AD risk.

  4. Unusual ventilation perfusion scintigram in a case of immunologic pulmonary edema clinically simulating pulmonary embolism

    SciTech Connect

    Campeau, R.J.; Faust, J.M.; Ahmad, S.

    1987-11-01

    A case of immunologic pulmonary edema secondary to hydrochlorothiazide allergy developed in a 55-year-old woman that clinically simulated pulmonary embolism. The patient had abnormal washin images with normal washout images on an Xe-133 ventilation study. On the perfusion study, large bilateral central and posterior perfusion defects were present that showed an unusual mirror image pattern on the lateral and posterior oblique views. Resolution of radiographic and scintigraphic abnormalities occurred over a 3-day period in conjunction with corticosteroid therapy.

  5. See the brain at work: intraoperative laser Doppler functional brain imaging

    NASA Astrophysics Data System (ADS)

    Martin-Williams, E. J.; Raabe, A.; Van De Ville, D.; Leutenegger, M.; Szelényi, A.; Hattingen, E.; Gerlach, R.; Seifert, V.; Hauger, C.; Lopez, A.; Leitgeb, R.; Unser, M.; Lasser, T.

    2009-07-01

    During open brain surgery we acquire perfusion images non-invasively using laser Doppler imaging. The regions of brain activity show a distinct signal in response to stimulation providing intraoperative functional brain maps of remarkably strong contrast.

  6. Brain Aneurysm

    MedlinePlus

    A brain aneurysm is an abnormal bulge or "ballooning" in the wall of an artery in the brain. They are sometimes called berry aneurysms because they ... often the size of a small berry. Most brain aneurysms produce no symptoms until they become large, ...

  7. Mathematical Modelling of a Brain Tumour Initiation and Early Development: A Coupled Model of Glioblastoma Growth, Pre-Existing Vessel Co-Option, Angiogenesis and Blood Perfusion.

    PubMed

    Cai, Yan; Wu, Jie; Li, Zhiyong; Long, Quan

    2016-01-01

    We propose a coupled mathematical modelling system to investigate glioblastoma growth in response to dynamic changes in chemical and haemodynamic microenvironments caused by pre-existing vessel co-option, remodelling, collapse and angiogenesis. A typical tree-like architecture network with different orders for vessel diameter is designed to model pre-existing vasculature in host tissue. The chemical substances including oxygen, vascular endothelial growth factor, extra-cellular matrix and matrix degradation enzymes are calculated based on the haemodynamic environment which is obtained by coupled modelling of intravascular blood flow with interstitial fluid flow. The haemodynamic changes, including vessel diameter and permeability, are introduced to reflect a series of pathological characteristics of abnormal tumour vessels including vessel dilation, leakage, angiogenesis, regression and collapse. Migrating cells are included as a new phenotype to describe the migration behaviour of malignant tumour cells. The simulation focuses on the avascular phase of tumour development and stops at an early phase of angiogenesis. The model is able to demonstrate the main features of glioblastoma growth in this phase such as the formation of pseudopalisades, cell migration along the host vessels, the pre-existing vasculature co-option, angiogenesis and remodelling. The model also enables us to examine the influence of initial conditions and local environment on the early phase of glioblastoma growth.

  8. Mathematical Modelling of a Brain Tumour Initiation and Early Development: A Coupled Model of Glioblastoma Growth, Pre-Existing Vessel Co-Option, Angiogenesis and Blood Perfusion

    PubMed Central

    Cai, Yan; Wu, Jie; Li, Zhiyong; Long, Quan

    2016-01-01

    We propose a coupled mathematical modelling system to investigate glioblastoma growth in response to dynamic changes in chemical and haemodynamic microenvironments caused by pre-existing vessel co-option, remodelling, collapse and angiogenesis. A typical tree-like architecture network with different orders for vessel diameter is designed to model pre-existing vasculature in host tissue. The chemical substances including oxygen, vascular endothelial growth factor, extra-cellular matrix and matrix degradation enzymes are calculated based on the haemodynamic environment which is obtained by coupled modelling of intravascular blood flow with interstitial fluid flow. The haemodynamic changes, including vessel diameter and permeability, are introduced to reflect a series of pathological characteristics of abnormal tumour vessels including vessel dilation, leakage, angiogenesis, regression and collapse. Migrating cells are included as a new phenotype to describe the migration behaviour of malignant tumour cells. The simulation focuses on the avascular phase of tumour development and stops at an early phase of angiogenesis. The model is able to demonstrate the main features of glioblastoma growth in this phase such as the formation of pseudopalisades, cell migration along the host vessels, the pre-existing vasculature co-option, angiogenesis and remodelling. The model also enables us to examine the influence of initial conditions and local environment on the early phase of glioblastoma growth. PMID:26934465

  9. Mathematical Modelling of a Brain Tumour Initiation and Early Development: A Coupled Model of Glioblastoma Growth, Pre-Existing Vessel Co-Option, Angiogenesis and Blood Perfusion.

    PubMed

    Cai, Yan; Wu, Jie; Li, Zhiyong; Long, Quan

    2016-01-01

    We propose a coupled mathematical modelling system to investigate glioblastoma growth in response to dynamic changes in chemical and haemodynamic microenvironments caused by pre-existing vessel co-option, remodelling, collapse and angiogenesis. A typical tree-like architecture network with different orders for vessel diameter is designed to model pre-existing vasculature in host tissue. The chemical substances including oxygen, vascular endothelial growth factor, extra-cellular matrix and matrix degradation enzymes are calculated based on the haemodynamic environment which is obtained by coupled modelling of intravascular blood flow with interstitial fluid flow. The haemodynamic changes, including vessel diameter and permeability, are introduced to reflect a series of pathological characteristics of abnormal tumour vessels including vessel dilation, leakage, angiogenesis, regression and collapse. Migrating cells are included as a new phenotype to describe the migration behaviour of malignant tumour cells. The simulation focuses on the avascular phase of tumour development and stops at an early phase of angiogenesis. The model is able to demonstrate the main features of glioblastoma growth in this phase such as the formation of pseudopalisades, cell migration along the host vessels, the pre-existing vasculature co-option, angiogenesis and remodelling. The model also enables us to examine the influence of initial conditions and local environment on the early phase of glioblastoma growth. PMID:26934465

  10. Incidentally detected diaphragmatic hernia mimicking angina pectoris with Tc-99m MIBI myocardial perfusion imaging

    PubMed Central

    Cınar, Alev; Sadıc, Murat; Demırel, Koray; Korkmaz, Meliha

    2013-01-01

    In recent years 99mTechnetium methoxy-isobutyl-isonitrile (99mTc MIBI) is widely used in the evaluation of myocardial perfusion imaging (MPI). In this imaging protocol besides the cardiac evaluation, numerous other organs are included in the field of view. 99mTechnetium MIBI is taken up in all metabolically active tissue in the body except for the brain. Extracardiac uptake patterns as benign or serious conditions can be revealed during the MPI. In the imaging protocol, we should be aware of distribution of this radiotracer in order to recognize the abnormal uptake. Here in, we present a large diaphragmatic hernia, seemed as a mirror vision of myocardium that was determined incidentally during the MPI with 99mTc MIBI. PMID:24379540

  11. Towards robust deconvolution of low-dose perfusion CT: Sparse perfusion deconvolution using online dictionary learning

    PubMed Central

    Fang, Ruogu; Chen, Tsuhan; Sanelli, Pina C.

    2014-01-01

    Computed tomography perfusion (CTP) is an important functional imaging modality in the evaluation of cerebrovascular diseases, particularly in acute stroke and vasospasm. However, the post-processed parametric maps of blood flow tend to be noisy, especially in low-dose CTP, due to the noisy contrast enhancement profile and the oscillatory nature of the results generated by the current computational methods. In this paper, we propose a robust sparse perfusion deconvolution method (SPD) to estimate cerebral blood flow in CTP performed at low radiation dose. We first build a dictionary from high-dose perfusion maps using online dictionary learning and then perform deconvolution-based hemodynamic parameters estimation on the low-dose CTP data. Our method is validated on clinical data of patients with normal and pathological CBF maps. The results show that we achieve superior performance than existing methods, and potentially improve the differentiation between normal and ischemic tissue in the brain. PMID:23542422

  12. Idiopathic pulmonary fibrosis. A rare cause of scintigraphic ventilation-perfusion mismatch

    SciTech Connect

    Pochis, W.T.; Krasnow, A.Z.; Collier, B.D.; Mewissen, M.W.; Almagro, U.A.; Hellman, R.S.; Isitman, A.T. )

    1990-05-01

    A case of idiopathic pulmonary fibrosis with multiple areas of mismatch on ventilation-perfusion lung imaging in the absence of pulmonary embolism is presented. Idiopathic pulmonary fibrosis is one of the few nonembolic diseases producing a pulmonary ventilation-perfusion mismatch. In this condition, chest radiographs may not detect the full extent of disease, and xenon-133 ventilation imaging may be relatively insensitive to morbid changes in small airways. Thus, when examining patients with idiopathic pulmonary fibrosis, one should be aware that abnormal perfusion imaging patterns without matching ventilation abnormalities are not always due to embolism. In this setting, contrast pulmonary angiography is often needed for accurate differential diagnosis.

  13. Imaging of activated complement using ultrasmall superparamagnetic iron oxide particles (USPIO) - conjugated vectors: an in vivo in utero non-invasive method to predict placental insufficiency and abnormal fetal brain development

    PubMed Central

    Girardi, G; Fraser, J; Lennen, R; Vontell, R; Jansen, M; Hutchison, G

    2015-01-01

    In the current study, we have developed a magnetic resonance imaging-based method for non-invasive detection of complement activation in placenta and foetal brain in vivo in utero. Using this method, we found that anti-complement C3-targeted ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles bind within the inflamed placenta and foetal brain cortical tissue, causing a shortening of the T2* relaxation time. We used two mouse models of pregnancy complications: a mouse model of obstetrics antiphospholipid syndrome (APS) and a mouse model of preterm birth (PTB). We found that detection of C3 deposition in the placenta in the APS model was associated with placental insufficiency characterised by increased oxidative stress, decreased vascular endothelial growth factor and placental growth factor levels and intrauterine growth restriction. We also found that foetal brain C3 deposition was associated with cortical axonal cytoarchitecture disruption and increased neurodegeneration in the mouse model of APS and in the PTB model. In the APS model, foetuses that showed increased C3 in their brains additionally expressed anxiety-related behaviour after birth. Importantly, USPIO did not affect pregnancy outcomes and liver function in the mother and the offspring, suggesting that this method may be useful for detecting complement activation in vivo in utero and predicting placental insufficiency and abnormal foetal neurodevelopment that leads to neuropsychiatric disorders. PMID:25245499

  14. Ex vivo lung perfusion.

    PubMed

    Reeb, Jeremie; Cypel, Marcelo

    2016-03-01

    Lung transplantation is an established life-saving therapy for patients with end-stage lung disease. Unfortunately, greater success in lung transplantation is hindered by a shortage of lung donors and the relatively poor early-, mid-, and long-term outcomes associated with severe primary graft dysfunction. Ex vivo lung perfusion has emerged as a modern preservation technique that allows for a more accurate lung assessment and improvement in lung quality. This review outlines the: (i) rationale behind the method; (ii) techniques and protocols; (iii) Toronto ex vivo lung perfusion method; (iv) devices available; and (v) clinical experience worldwide. We also highlight the potential of ex vivo lung perfusion in leading a new era of lung preservation. PMID:26700566

  15. Isolated lung perfusion.

    PubMed

    Cypel, Marcelo; Keshavjee, Shaf

    2012-01-01

    Isolated lung perfusion (ILP) has been historically used as a method to study basic lung physiologic concepts using animal models. More recently, ILP has been applied in lung transplantation and thoracic oncology. In lung transplantation, ILP has been used to assess physiological integrity of donor lungs after the organ is removed from the donor. This procedure is called Ex vivo Lung Perfusion (EVLP), and it has also been proposed as a method for active treatment and repair of injured unsuitable donor organs ex vivo. In oncology, ILP is an attractive method to deliver high dose chemotherapy to treat pulmonary metastatic disease. Since the lung vasculature is isolated in vivo, this technique is called in vivo lung perfusion (IVLP). This review will focus on the rationale, technical aspects, experimental and clinical experience of EVLP and IVLP. A perspective on the future use of these techniques is described. PMID:22202033

  16. Effect of vasodilators on pulmonary perfusion defects in asthma using sequential Kr-81m perfusion imaging

    SciTech Connect

    Ertle, A.R.; Tashkin, D.P.; Webber, M.M.; Soffer, M.J.; Frank, G.W.

    1984-01-01

    The investigation was undertaken to determine if vasodilator agents may enhance the diagnostic utility of perfusion lung imaging (Q) by normalizing regional perfusion abnormalities in bronchospastic patients. The effect of oxygen (02), nitroglycerine (NTG), hydralazine (H), and nifedipine (N) on regional lung perfusion defects was studied in 6 mild to severe asthmatics (ages defects was studied in 6 mild to severe asthmatics (ages 31-72yrs) using sequential Kr-81m imaging which permits repetitive imaging due to very low radiation dose and 13 sec T-1/2. Each patient was studied once weekly for 3 wks. Baseline Q scans were obtained using 10mCi of I.V. Kr-81m. the best view showing perfusion defects was used for subsequent images. At each visits, 30% 02 by ventimask was given for 20 min followed by a repeat Q scan. Subsequently, on separate visits, subjects were given either 1 dose of sublingual (sl)N 20 mg or 2 doses (1 hr between) of s1 NTG 1/150gr or po H 25mg according to a random-order crossover design. Q scans were obtained 2 min after NTG, 60 min after H, and 30 and 60 min after N. 30% 02 was given again for 20 min, and a final scan was obtained. Scan were reviewed by 2 observers and showed relatively fixed defects in 4 pts improvement in defects in 3 pts with NTG, 1 with N, 1 with H, and 2 with 02 alone. Additive effects of 02 and N or NTG were seen in 2 pts. These preliminary results suggest that vasodilators and 02 may improve regional perfusion in patients with bronchospastic disease and that this effect may be additive. These medications may thus improve the specificity of perfusion lung scanning in the diagnostic evaluation of pulmonary embolism.

  17. Dynamic chest image analysis: model-based pulmonary perfusion analysis with pyramid images

    NASA Astrophysics Data System (ADS)

    Liang, Jianming; Haapanen, Arto; Jaervi, Timo; Kiuru, Aaro J.; Kormano, Martti; Svedstrom, Erkki; Virkki, Raimo

    1998-07-01

    The aim of the study 'Dynamic Chest Image Analysis' is to develop computer analysis and visualization methods for showing focal and general abnormalities of lung ventilation and perfusion based on a sequence of digital chest fluoroscopy frames collected at different phases of the respiratory/cardiac cycles in a short period of time. We have proposed a framework for ventilation study with an explicit ventilation model based on pyramid images. In this paper, we extend the framework to pulmonary perfusion study. A perfusion model and the truncated pyramid are introduced. The perfusion model aims at extracting accurate, geographic perfusion parameters, and the truncated pyramid helps in understanding perfusion at multiple resolutions and speeding up the convergence process in optimization. Three cases are included to illustrate the experimental results.

  18. 5D CNS+ Software for Automatically Imaging Axial, Sagittal, and Coronal Planes of Normal and Abnormal Second-Trimester Fetal Brains.

    PubMed

    Rizzo, Giuseppe; Capponi, Alessandra; Persico, Nicola; Ghi, Tullio; Nazzaro, Giovanni; Boito, Simona; Pietrolucci, Maria Elena; Arduini, Domenico

    2016-10-01

    The purpose of this study was to test new 5D CNS+ software (Samsung Medison Co, Ltd, Seoul, Korea), which is designed to image axial, sagittal, and coronal planes of the fetal brain from volumes obtained by 3-dimensional sonography. The study consisted of 2 different steps. First in a prospective study, 3-dimensional fetal brain volumes were acquired in 183 normal consecutive singleton pregnancies undergoing routine sonographic examinations at 18 to 24 weeks' gestation. The 5D CNS+ software was applied, and the percentage of adequate visualization of brain diagnostic planes was evaluated by 2 independent observers. In the second step, the software was also tested in 22 fetuses with cerebral anomalies. In 180 of 183 fetuses (98.4%), 5D CNS+ successfully reconstructed all of the diagnostic planes. Using the software on healthy fetuses, the observers acknowledged the presence of diagnostic images with visualization rates ranging from 97.7% to 99.4% for axial planes, 94.4% to 97.7% for sagittal planes, and 92.2% to 97.2% for coronal planes. The Cohen κ coefficient was analyzed to evaluate the agreement rates between the observers and resulted in values of 0.96 or greater for axial planes, 0.90 or greater for sagittal planes, and 0.89 or greater for coronal planes. All 22 fetuses with brain anomalies were identified among a series that also included healthy fetuses, and in 21 of the 22 cases, a correct diagnosis was made. 5D CNS+ was efficient in successfully imaging standard axial, sagittal, and coronal planes of the fetal brain. This approach may simplify the examination of the fetal central nervous system and reduce operator dependency.

  19. Schizophrenia patients differentiation based on MR vascular perfusion and volumetric imaging

    NASA Astrophysics Data System (ADS)

    Spanier, A. B.; Joskowicz, L.; Moshel, S.; Israeli, D.

    2015-03-01

    Candecomp/Parafac Decomposition (CPD) has emerged as a framework for modeling N-way arrays (higher-order matrices). CPD is naturally well suited for the analysis of data sets comprised of observations of a function of multiple discrete indices. In this study we evaluate the prospects of using CPD for modeling MRI brain properties (i.e. brain volume and gray-level) for schizophrenia diagnosis. Taking into account that 3D imaging data consists of millions of pixels per patient, the diagnosis of a schizophrenia patient based on pixel analysis constitutes a methodological challenge (e.g. multiple comparison problem). We show that the CPD could potentially be used as a dimensionality redaction method and as a discriminator between schizophrenia patients and match control, using the gradient of pre- and post Gd-T1-weighted MRI data, which is strongly correlated with cerebral blood perfusion. Our approach was tested on 68 MRI scans: 40 first-episode schizophrenia patients and 28 matched controls. The CPD subject's scores exhibit statistically significant result (P < 0.001). In the context of diagnosing schizophrenia with MRI, the results suggest that the CPD could potentially be used to discriminate between schizophrenia patients and matched control. In addition, the CPD model suggests for brain regions that might exhibit abnormalities in schizophrenia patients for future research.

  20. Neurocognitive and electrophysiological evidence of altered face processing in parents of children with autism: implications for a model of abnormal development of social brain circuitry in autism.

    PubMed

    Dawson, Geraldine; Webb, Sara Jane; Wijsman, Ellen; Schellenberg, Gerard; Estes, Annette; Munson, Jeffrey; Faja, Susan

    2005-01-01

    Neuroimaging and behavioral studies have shown that children and adults with autism have impaired face recognition. Individuals with autism also exhibit atypical event-related brain potentials to faces, characterized by a failure to show a negative component (N170) latency advantage to face compared to nonface stimuli and a bilateral, rather than right lateralized, pattern of N170 distribution. In this report, performance by 143 parents of children with autism on standardized verbal, visual-spatial, and face recognition tasks was examined. It was found that parents of children with autism exhibited a significant decrement in face recognition ability relative to their verbal and visual spatial abilities. Event-related brain potentials to face and nonface stimuli were examined in 21 parents of children with autism and 21 control adults. Parents of children with autism showed an atypical event-related potential response to faces, which mirrored the pattern shown by children and adults with autism. These results raise the possibility that face processing might be a functional trait marker of genetic susceptibility to autism. Discussion focuses on hypotheses regarding the neurodevelopmental and genetic basis of altered face processing in autism. A general model of the normal emergence of social brain circuitry in the first year of life is proposed, followed by a discussion of how the trajectory of normal development of social brain circuitry, including cortical specialization for face processing, is altered in individuals with autism. The hypothesis that genetic-mediated dysfunction of the dopamine reward system, especially its functioning in social contexts, might account for altered face processing in individuals with autism and their relatives is discussed.

  1. Abnormalities of Inter- and Intra-Hemispheric Functional Connectivity in Autism Spectrum Disorders: A Study Using the Autism Brain Imaging Data Exchange Database

    PubMed Central

    Lee, Jung Min; Kyeong, Sunghyun; Kim, Eunjoo; Cheon, Keun-Ah

    2016-01-01

    Recently, the Autism Brain Imaging Data Exchange (ABIDE) project revealed decreased functional connectivity in individuals with Autism Spectrum Disorders (ASD) relative to the typically developing controls (TDCs). However, it is still questionable whether the source of functional under-connectivity in subjects with ASD is equally contributed by the ipsilateral and contralateral parts of the brain. In this study, we decomposed the inter- and intra-hemispheric regions and compared the functional connectivity density (FCD) between 458 subjects with ASD and 517 TDCs from the ABIDE database. We quantified the inter- and intra-hemispheric FCDs in the brain by counting the number of functional connectivity with all voxels in the opposite and same hemispheric brain regions, respectively. Relative to TDCs, both inter- and intra-hemispheric FCDs in the posterior cingulate cortex, lingual/parahippocampal gyrus, and postcentral gyrus were significantly decreased in subjects with ASD. Moreover, in the ASD group, the restricted and repetitive behavior subscore of the Autism Diagnostic Observation Schedule (ADOS-RRB) score showed significant negative correlations with the average inter-hemispheric FCD and contralateral FCD in the lingual/parahippocampal gyrus cluster. Also, the ADOS-RRB score showed significant negative correlations with the average contralateral FCD in the default mode network regions such as the posterior cingulate cortex and precuneus. Taken together, our findings imply that a deficit of non-social functioning processing in ASD such as restricted and repetitive behaviors and sensory hypersensitivity could be determined via both inter- and intra-hemispheric functional disconnections. PMID:27199653

  2. Dietary omega-3 fatty acid deficiency and high fructose intake in the development of metabolic syndrome, brain metabolic abnormalities, and non-alcoholic fatty liver disease.

    PubMed

    Simopoulos, Artemis P

    2013-08-01

    Western diets are characterized by both dietary omega-3 fatty acid deficiency and increased fructose intake. The latter found in high amounts in added sugars such as sucrose and high fructose corn syrup (HFCS). Both a low intake of omega-3 fatty acids or a high fructose intake contribute to metabolic syndrome, liver steatosis or non-alcoholic fatty liver disease (NAFLD), promote brain insulin resistance, and increase the vulnerability to cognitive dysfunction. Insulin resistance is the core perturbation of metabolic syndrome. Multiple cognitive domains are affected by metabolic syndrome in adults and in obese adolescents, with volume losses in the hippocampus and frontal lobe, affecting executive function. Fish oil supplementation maintains proper insulin signaling in the brain, ameliorates NAFLD and decreases the risk to metabolic syndrome suggesting that adequate levels of omega-3 fatty acids in the diet can cope with the metabolic challenges imposed by high fructose intake in Western diets which is of major public health importance. This review presents the current status of the mechanisms involved in the development of the metabolic syndrome, brain insulin resistance, and NAFLD a most promising area of research in Nutrition for the prevention of these conditions, chronic diseases, and improvement of Public Health. PMID:23896654

  3. [Emotion Disorders and Abnormal Perspiration].

    PubMed

    Umeda, Satoshi

    2016-08-01

    This article reviewed the relationship between emotional disorders and abnormal perspiration. First, I focused on local brain areas related to emotional processing, and summarized the functions of the emotional network involving those local areas. Functional disorders followed by the damage in the amygdala, orbitofrontal cortex, and insular cortex were reviewed, including related abnormal perspiration. I then addressed the mechanisms of how autonomic disorders influence emotional processing. Finally, possible future directions for integrated understanding of the connection between neural activities and bodily reactions were discussed. PMID:27503817

  4. [Emotion Disorders and Abnormal Perspiration].

    PubMed

    Umeda, Satoshi

    2016-08-01

    This article reviewed the relationship between emotional disorders and abnormal perspiration. First, I focused on local brain areas related to emotional processing, and summarized the functions of the emotional network involving those local areas. Functional disorders followed by the damage in the amygdala, orbitofrontal cortex, and insular cortex were reviewed, including related abnormal perspiration. I then addressed the mechanisms of how autonomic disorders influence emotional processing. Finally, possible future directions for integrated understanding of the connection between neural activities and bodily reactions were discussed.

  5. Myocardial perfusion scintigraphy and coronary disease risk factors in systemic lupus erythematosus

    PubMed Central

    Sella, E; Sato, E; Leite, W; Filho, J; Barbieri, A

    2003-01-01

    Objective: To evaluate the prevalence of myocardial perfusion abnormalities and the possible association between myocardial perfusion defects and traditional coronary artery disease (CAD) risk factors as well as systemic lupus erythematosus (SLE) related risk factors. Patients and methods: Female patients with SLE, disease duration >5 years, age 18–55 years, who had used steroids for at least one year were enrolled. Traditional CAD risk factors evaluated were arterial hypertension, diabetes mellitus, dyslipidaemia, postmenopausal status, smoking, obesity, and premature family CAD profile. Myocardial perfusion scintigraphy was evaluated by single photon emission computed tomography with technetium 99m-sestamibi at rest and after dipyridamole induced stress. Results: Eight two female patients with SLE without angina pectoris with mean (SD) age 37 (10) years, disease duration 127 (57) months, SLE Disease Activity Index (SLEDAI) score 6 (5), and SLICC/ACR-DI score 2 (2) were evaluated. Myocardial perfusion abnormalities were found in 23 patients (28%). The mean (SD) number of CAD risk factors was 2.2 (1.6). There was a significant positive correlation between age and number of CAD risk factors. Lower high density lipoprotein (HDL) cholesterol level showed a significant association with abnormal scintigraphy. Logistic regression analysis showed that lower HDL cholesterol level and diabetes mellitus were associated with myocardial perfusion abnormalities. Current vasculitis was also associated with abnormal scintigraphy. Conclusions: Lower HDL cholesterol level and diabetes mellitus have a significant influence on abnormal myocardial perfusion results found in asymptomatic patients with SLE. Current vasculitis was associated with abnormal myocardial scintigraphy. These data suggest that abnormal myocardial scintigraphy may be related to subclinical atherosclerosis. PMID:14583569

  6. Effect of Myocardial Perfusion Pattern on Frequency and Severity of Mitral Regurgitation in Patients With Known or Suspected Coronary Artery Disease

    PubMed Central

    Volo, Samuel C.; Kim, Jiwon; Gurevich, Sergey; Petashnick, Maya; Kampaktsis, Polydoros; Feher, Attila; Szulc, Massimiliano; Wong, Franklin J.; Devereux, Richard B.; Okin, Peter M.; Girardi, Leonard N.; Min, James K.; Levine, Robert A.; Weinsaft, Jonathan W.

    2014-01-01

    Mitral regurgitation (MR) is common with coronary artery disease (CAD), as altered myocardial substrate can impact valve performance. SPECT myocardial perfusion imaging (MPI) enables assessment of myocardial perfusion alterations. This study examined perfusion pattern in relation to MR. 2377 consecutive patients with known or suspected CAD underwent stress MPI and echocardiography (echo) within 1.6±2.3 days. MR was present on echo in 34% of patients, among whom 13% had advanced (≥moderate) MR. MR prevalence was higher among patients with abnormal MPI (44% vs. 29%, p<0.001), corresponding to increased global ischemia (p<0.001). Regional perfusion varied in left ventricular (LV) segments adjacent to each papillary muscle: Adjacent to the anterolateral papillary muscle, magnitude of baseline and stress-induced anterior/anterolateral perfusion abnormalities was greater among patients with MR (both p<0.001). Adjacent to the posteromedial papillary muscle, baseline inferior/inferolateral perfusion abnormalities were greater with MR (p<0.001), whereas stress inducibility was similar (p=0.39). In multivariate analysis, stress-induced anterior/anterolateral and rest inferior/inferolateral perfusion abnormalities were independently associated with MR (both p<0.05) even after controlling for perfusion in reference segments not adjacent to the papillary muscles. MR severity increased in relation to magnitude of perfusion abnormalities in each territory adjacent to the papillary muscles, as evidenced by greater prevalence of advanced MR among patients with ≥moderate anterior/anterolateral stress perfusion abnormalities (10.7% vs. 3.6%), with similar results when MR was stratified based on rest inferior/inferolateral perfusion (10.4% vs. 3.0%, both p<0.001). In conclusion, findings demonstrate that myocardial perfusion pattern in LV segments adjacent to the papillary muscles influences presence and severity of MR. PMID:24948494

  7. Neurological Abnormalities in Full-Term Asphyxiated Newborns and Salivary S100B Testing: The “Cooperative Multitask against Brain Injury of Neonates” (CoMBINe) International Study

    PubMed Central

    Gazzolo, Diego; Pluchinotta, Francesca; Bashir, Moataza; Aboulgar, Hanna; Said, Hala Mufeed; Iman, Iskander; Ivani, Giorgio; Conio, Alessandra; Tina, Lucia Gabriella; Nigro, Francesco; Li Volti, Giovanni; Galvano, Fabio; Michetti, Fabrizio; Di Iorio, Romolo; Marinoni, Emanuela; Zimmermann, Luc J.; Gavilanes, Antonio D. W.; Vles, Hans J. S.; Kornacka, Maria; Gruszfeld, Darek; Frulio, Rosanna; Sacchi, Renata; Ciotti, Sabina; Risso, Francesco M.; Sannia, Andrea; Florio, Pasquale

    2015-01-01

    Background Perinatal asphyxia (PA) is a leading cause of mortality and morbidity in newborns: its prognosis depends both on the severity of the asphyxia and on the immediate resuscitation to restore oxygen supply and blood circulation. Therefore, we investigated whether measurement of S100B, a consolidated marker of brain injury, in salivary fluid of PA newborns may constitute a useful tool for the early detection of asphyxia-related brain injury. Methods We conducted a cross-sectional study in 292 full-term newborns admitted to our NICUs, of whom 48 suffered PA and 244 healthy controls admitted at our NICUs. Saliva S100B levels measurement longitudinally after birth; routine laboratory variables, neurological patterns, cerebral ultrasound and, magnetic resonance imaging were performed. The primary end-point was the presence of neurological abnormalities at 12-months after birth. Results S100B salivary levels were significantly (P<0.001) higher in newborns with PA than in normal infants. When asphyxiated infants were subdivided according to a good (Group A; n = 15) or poor (Group B; n = 33) neurological outcome at 12-months, S100B was significantly higher at all monitoring time-points in Group B than in Group A or controls (P<0.001, for all). A cut-off >3.25 MoM S100B achieved a sensitivity of 100% (CI5-95%: 89.3%-100%) and a specificity of 100% (CI5-95%: 98.6%-100%) as a single marker for predicting the occurrence of abnormal neurological outcome (area under the ROC curve: 1.000; CI5-95%: 0.987-1.0). Conclusions S100B protein measurement in saliva, soon after birth, is a useful tool to identify which asphyxiated infants are at risk of neurological sequelae. PMID:25569796

  8. Abnormal brain activation of adolescent internet addict in a ball-throwing animation task: possible neural correlates of disembodiment revealed by fMRI.

    PubMed

    Kim, Yeoung-Rang; Son, Jung-Woo; Lee, Sang-Ick; Shin, Chul-Jin; Kim, Sie-Kyeong; Ju, Gawon; Choi, Won-Hee; Oh, Jong-Hyun; Lee, Seungbok; Jo, Seongwoo; Ha, Tae Hyon

    2012-10-01

    While adolescent internet addicts are immersed in cyberspace, they are easily able to experience 'disembodied state'. The purposes of this study were to investigate the difference of brain activity between adolescent internet addicts and normal adolescents in a state of disembodiment, and to find the correlation between the activities of disembodiment-related areas and the behavioral characteristics related to internet addiction. The fMRI images were taken while the addiction group (N=17) and the control group (N=17) were asked to perform the task composed with ball-throwing animations. The task reflected on either self-agency about ball-throwing or location of a ball. And each block was shown with either different (Changing View) or same animations (Fixed View). The disembodiment-related condition was the interaction between Agency Task and Changing View. Within-group analyses revealed that the addiction group exhibited higher activation in the thalamus, bilateral precentral area, bilateral middle frontal area, and the area around the right temporo-parietal junction. And between-group analyses showed that the addiction group exhibited higher activation in the area near the left temporo-parieto-occipital junction, right parahippocampal area, and other areas than the control group. Finally, the duration of internet use was significantly correlated with the activity of posterior area of left middle temporal gyrus in the addiction group. These results show that the disembodiment-related activation of the brain is easily manifested in adolescent internet addicts. Internet addiction of adolescents could be significantly unfavorable for their brain development related with identity formation. PMID:22687465

  9. Abnormal Changes of Brain Cortical Anatomy and the Association with Plasma MicroRNA107 Level in Amnestic Mild Cognitive Impairment

    PubMed Central

    Wang, Tao; Shi, Feng; Jin, Yan; Jiang, Weixiong; Shen, Dinggang; Xiao, Shifu

    2016-01-01

    MicroRNA107 (Mir107) has been thought to relate to the brain structure phenotype of Alzheimer’s disease. In this study, we evaluated the cortical anatomy in amnestic mild cognitive impairment (aMCI) and the relation between cortical anatomy and plasma levels of Mir107 and beta-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1). Twenty aMCI (20 aMCI) and 24 cognitively normal control (NC) subjects were recruited, and T1-weighted MR images were acquired. Cortical anatomical measurements, including cortical thickness (CT), surface area (SA), and local gyrification index (LGI), were assessed. Quantitative RT-PCR was used to examine plasma expression of Mir107, BACE1 mRNA. Thinner cortex was found in aMCI in areas associated with episodic memory and language, but with thicker cortex in other areas. SA decreased in aMCI in the areas associated with working memory and emotion. LGI showed a significant reduction in aMCI in the areas involved in language function. Changes in Mir107 and BACE1 messenger RNA plasma expression were correlated with changes in CT and SA. We found alterations in key left brain regions associated with memory, language, and emotion in aMCI that were significantly correlated with plasma expression of Mir107 and BACE1 mRNA. This combination study of brain anatomical alterations and gene information may shed lights on our understanding of the pathology of AD. Clinical Trial Registration: http://www.ClinicalTrials.gov, identifier NCT01819545. PMID:27242521

  10. Voxel-wise meta-analyses of brain blood flow and local synchrony abnormalities in medication-free patients with major depressive disorder

    PubMed Central

    Chen, Zi-Qi; Du, Ming-Ying; Zhao, You-Jin; Huang, Xiao-Qi; Li, Jing; Lui, Su; Hu, Jun-Mei; Sun, Huai-Qiang; Liu, Jia; Kemp, Graham J.; Gong, Qi-Yong

    2015-01-01

    Background Published meta-analyses of resting-state regional cerebral blood flow (rCBF) studies of major depressive disorder (MDD) have included patients receiving antidepressants, which might affect brain activity and thus bias the results. To our knowledge, no meta-analysis has investigated regional homogeneity changes in medication-free patients with MDD. Moreover, an association between regional homogeneity and rCBF has been demonstrated in some brain regions in healthy controls. We sought to explore to what extent resting-state rCBF and regional homogeneity changes co-occur in the depressed brain without the potential confound of medication. Methods Using the effect-size signed differential mapping method, we conducted 2 meta-analyses of rCBF and regional homogeneity studies of medication-free patients with MDD. Results Our systematic search identified 14 rCBF studies and 9 regional homogeneity studies. We identified conjoint decreases in resting-state rCBF and regional homogeneity in the insula and superior temporal gyrus in medication-free patients with MDD compared with controls. Other changes included altered resting-state rCBF in the precuneus and in the frontal–limbic–thalamic–striatal neural circuit as well as altered regional homogeneity in the uncus and parahippocampal gyrus. Meta-regression revealed that the percentage of female patients with MDD was negatively associated with resting-state rCBF in the right anterior cingulate cortex and that the age of patients with MDD was negatively associated with rCBF in the left insula and with regional homogeneity in the left uncus. Limitations The analysis techniques, patient characteristics and clinical variables of the included studies were heterogeneous. Conclusion The conjoint alterations of rCBF and regional homogeneity in the insula and superior temporal gyrus may be core neuropathological changes in medication-free patients with MDD and serve as a specific region of interest for further studies

  11. Regional pulmonary perfusion following human heart-lung transplantation

    SciTech Connect

    Lisbona, R.; Hakim, T.S.; Dean, G.W.; Langleben, D.; Guerraty, A.; Levy, R.D. )

    1989-08-01

    Ventilation and perfusion scans were obtained in six subjects who had undergone heart-lung transplantation with consequent denervation of the cardiopulmonary axis. Two of the subjects had developed obliterative bronchiolitis, which is believed to be a form of chronic rejection. Their pulmonary function tests demonstrated airflow obstruction and their scintigraphic studies were abnormal. In the remaining four subjects without obstructive airways disease, ventilation and planar perfusion scans were normal. Single photon emission computed tomography imaging of pulmonary perfusion in these patients revealed a layered distribution of blood flow indistinguishable from that of normal individuals. It is concluded that neurogenic mechanisms have little influence on the pattern of local pulmonary blood flow at rest.

  12. Goal-directed-perfusion in neonatal aortic arch surgery

    PubMed Central

    Purbojo, Ariawan; Muench, Frank; Juengert, Joerg; Rueffer, André

    2016-01-01

    Reduction of mortality and morbidity in congenital cardiac surgery has always been and remains a major target for the complete team involved. As operative techniques are more and more standardized and refined, surgical risk and associated complication rates have constantly been reduced to an acceptable level but are both still present. Aortic arch surgery in neonates seems to be of particular interest, because perfusion techniques differ widely among institutions and an ideal form of a so called “total body perfusion (TBP)” is somewhat difficult to achieve. Thus concepts of deep hypothermic circulatory arrest (DHCA), regional cerebral perfusion (RCP/with cardioplegic cardiac arrest or on the perfused beating heart) and TBP exist in parallel and all carry an individual risk for organ damage related to perfusion management, chosen core temperature and time on bypass. Patient safety relies more and more on adequate end organ perfusion on cardiopulmonary bypass, especially sensitive organs like the brain, heart, kidney, liver and the gut, whereby on adequate tissue protection, temperature management and oxygen delivery should be visualized and monitored. PMID:27709094

  13. CT Perfusion Characteristics Identify Metastatic Sites in Liver.

    PubMed

    Wang, Yuan; Hobbs, Brian P; Ng, Chaan S

    2015-01-01

    Tissue perfusion plays a critical role in oncology because growth and migration of cancerous cells require proliferation of new blood vessels through the process of tumor angiogenesis. Computed tomography (CT) perfusion is an emerging functional imaging modality that measures tissue perfusion through dynamic CT scanning following intravenous administration of contrast medium. This noninvasive technique provides a quantitative basis for assessing tumor angiogenesis. CT perfusion has been utilized on a variety of organs including lung, prostate, liver, and brain, with promising results in cancer diagnosis, disease prognostication, prediction, and treatment monitoring. In this paper, we focus on assessing the extent to which CT perfusion characteristics can be used to discriminate liver metastases from neuroendocrine tumors from normal liver tissues. The neuroendocrine liver metastases were analyzed by distributed parameter modeling to yield tissue blood flow (BF), blood volume (BV), mean transit time (MTT), permeability (PS), and hepatic arterial fraction (HAF), for tumor and normal liver. The result reveals the potential of CT perfusion as a tool for constructing biomarkers from features of the hepatic vasculature for guiding cancer detection, prognostication, and treatment selection.

  14. Mathematical modeling of human brain physiological data

    NASA Astrophysics Data System (ADS)

    Böhm, Matthias; Faltermeier, Rupert; Brawanski, Alexander; Lang, Elmar W.

    2013-12-01

    Recently, a mathematical model of the basic physiological processes regulating the cerebral perfusion and oxygen supply was introduced [Jung , J. Math. Biol.JMBLAJ0303-681210.1007/s00285-005-0343-5 51, 491 (2005)]. Although this model correctly describes the interdependence of arterial blood pressure (ABP) and intracranial pressure (ICP), it fails badly when it comes to explaining certain abnormal correlations seen in about 80% of the recordings of ABP together with ICP and the partial oxygen pressure (TiPO2) of the neuronal tissue, taken at an intensive care unit during neuromonitoring of patients with a severe brain trauma. Such recordings occasionally show segments, where the mean arterial blood pressure is correlated with the partial oxygen pressure in tissue but anticorrelated with the intracranial pressure. The origin of such abnormal correlations has not been fully understood yet. Here, two extensions to the previous approach are proposed which can reproduce such abnormal correlations in simulations quantitatively. Furthermore, as the simulations are based on a mathematical model, additional insight into the physiological mechanisms from which such abnormal correlations originate can be gained.

  15. Visuospatial deficits and hemispheric perfusion asymmetries in posterior cortical atrophy.

    PubMed

    Andrade, Katia; Kas, Aurélie; Samri, Dalila; Sarazin, Marie; Dubois, Bruno; Habert, Marie-Odile; Bartolomeo, Paolo

    2013-04-01

    We studied visuospatial performance and obtained brain perfusion scintigraphy in 27 patients with posterior cortical atrophy (PCA) and 24 healthy controls, with two aims: (1) to determine inter-hemispheric perfusion imbalances underlying signs of spatial neglect and (2) to establish the functional substrates of patients' performance on distinct visuospatial tasks (line bisection and target cancellation). Between-groups and correlation analyses were performed on a voxel-wise basis with Statistical Parametric Mapping, and right-to-left hemispheric perfusion ratios were calculated in anatomical regions of interest. Nineteen patients had pathological spatial biases. Compared with controls, patients with signs of left-sided and right-sided neglect presented prominent hypoperfusion in the right and left parietal cortex, respectively. Importantly, hypoperfusion extended to the ipsilateral prefrontal regions. Correlation analyses between task scores and brain perfusion showed that shifts in line bisection correlated with hypoperfusion in parieto-frontal regions, whereas omissions on target cancellation mainly correlated with hypoperfusion in prefrontal structures. Overall, the results indicate that spatial neglect in PCA is related to inter-hemispheric perfusion asymmetries in fronto-parietal networks, with partially different neural correlates for line bisection and target cancellation.

  16. CT perfusion: principles, applications, and problems

    NASA Astrophysics Data System (ADS)

    Lee, Ting-Yim

    2004-10-01

    The fast scanning speed of current slip-ring CT scanners has enabled the development of perfusion imaging techniques with intravenous injection of contrast medium. In a typical CT perfusion study, contrast medium is injected and rapid scanning at a frequency of 1-2 Hz is used to monitor the first circulation of the injected contrast medium through a 1-2 cm thick slab of tissue. From the acquired time-series of CT images, arteries can be identified within the tissue slab to derive the arterial contrast concentration curve, Ca(t) while each individual voxel produces a tissue residue curve, Q(t) for the corresponding tissue region. Deconvolution between the measured Ca(t) and Q(t) leads to the determination of cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) in brain studies. In this presentation, an important application of CT perfusion in acute stroke studies - the identification of the ischemic penumbra via the CBF/CBV mismatch and factors affecting the quantitative accuracy of deconvolution, including partial volume averaging, arterial delay and dispersion are discussed.

  17. Childhood Brain Tumors

    MedlinePlus

    Brain tumors are abnormal growths inside the skull. They are among the most common types of childhood ... still be serious. Malignant tumors are cancerous. Childhood brain and spinal cord tumors can cause headaches and ...

  18. Classification Accuracy of Serum Apo A-I and S100B for the Diagnosis of Mild Traumatic Brain Injury and Prediction of Abnormal Initial Head Computed Tomography Scan

    PubMed Central

    Blyth, Brian J.; He, Hua; Mookerjee, Sohug; Jones, Courtney; Kiechle, Karin; Moynihan, Ryan; Wojcik, Susan M.; Grant, William D.; Secreti, LaLainia M.; Triner, Wayne; Moscati, Ronald; Leinhart, August; Ellis, George L.; Khan, Jawwad

    2013-01-01

    Abstract The objective of the current study was to determine the classification accuracy of serum S100B and apolipoprotein (apoA-I) for mild traumatic brain injury (mTBI) and abnormal initial head computed tomography (CT) scan, and to identify ethnic, racial, age, and sex variation in classification accuracy. We performed a prospective, multi-centered study of 787 patients with mTBI who presented to the emergency department within 6 h of injury and 467 controls who presented to the outpatient laboratory for routine blood work. Serum was analyzed for S100B and apoA-I. The outcomes were disease status (mTBI or control) and initial head CT scan. At cutoff values defined by 90% of controls, the specificity for mTBI using S100B (0.899 [95% confidence interval (CI): 0.78–0.92]) was similar to that using apoA-I (0.902 [0.87–0.93]), and the sensitivity using S100B (0.252 [0.22–0.28]) was similar to that using apoA-I (0.249 [0.22–0.28]). The area under the receiver operating characteristic curve (AUC) for the combination of S100B and apoA-I (0.738, 95% CI: 0.71, 0.77), however, was significantly higher than the AUC for S100B alone (0.709, 95% CI: 0.68, 0.74, p=0.001) and higher than the AUC for apoA-I alone (0.645, 95% CI: 0.61, 0.68, p<0.0001). The AUC for prediction of abnormal initial head CT scan using S100B was 0.694 (95%CI: 0.62, 0.77) and not significant for apoA-I. At a S100B cutoff of <0.060 μg/L, the sensitivity for abnormal head CT was 98%, and 22.9% of CT scans could have been avoided. There was significant age and race-related variation in the accuracy of S100B for the diagnosis of mTBI. The combined use of serum S100B and apoA-I maximizes classification accuracy for mTBI, but only S100B is needed to classify abnormal head CT scan. Because of significant subgroup variation in classification accuracy, age and race need to be considered when using S100B to classify subjects for mTBI. PMID:23758329