Science.gov

Sample records for brain perfusion abnormalities

  1. Affective psychosis, Hashimoto's thyroiditis, and brain perfusion abnormalities: case report

    PubMed Central

    2007-01-01

    Background It has recently become evident that circulating thyroid antibodies are found in excess among patients suffering from mood disorders. Moreover, a manic episode associated with Hashimoto's thyroiditis has recently been reported as the first case of bipolar disorder due to Hashimoto's encephalopathy. We report a case in which Hashimoto's thyroiditis was suspected to be involved in the deteriorating course of mood disorder and discuss potential pathogenic mechanisms linking thyroid autoimmunity with psychopathology. Case presentation A 43-year-old woman, with a history of recurrent depression since the age of 31, developed manic, psychotic, and soft neurological symptoms across the last three years in concomitance with her first diagnosis of Hashimoto's thyroiditis. The patient underwent a thorough medical and neurological workup. Circulating thyroperoxidase antibodies were highly elevated but thyroid function was adequately maintained with L-thyroxine substitution. EEG was normal and no other signs of current CNS inflammation were evidenced. However, brain magnetic resonance imaging evidenced several non-active lesions in the white matter from both hemispheres, suggestive of a non-specific past vasculitis. Brain single-photon emission computed tomography showed cortical perfusion asymmetry particularly between frontal lobes. Conclusion We hypothesize that abnormalities in cortical perfusion might represent a pathogenic link between thyroid autoimmunity and mood disorders, and that the rare cases of severe Hashimoto's encephalopathy presenting with mood disorder might be only the tip of an iceberg. PMID:18096026

  2. 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.

  3. 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.

  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.

  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. Fragile X syndrome and cerebral perfusion abnormalities: single-photon emission computed tomographic study.

    PubMed

    Kabakus, Nimet; Aydin, Mustafa; Akin, Haluk; Balci, Tansel Ansal; Kurt, Abdullah; Kekilli, Ersoy

    2006-12-01

    Fragile X syndrome is an inherited disorder caused by a defective gene on the X chromosome. It is associated with developmental or behavioral symptoms and various degrees of mental retardation. Morphologic abnormalities and altered perfusion of various brain areas can underlie these functional disturbances. The aim of this study was to investigate the cerebral perfusion state in patients with fragile X syndrome using single-photon emission computed tomography (SPECT). Structural and functional assessment was also performed by magnetic resonance imaging (MRI) and electroencephalography (EEG). Eight boys with cytogenetically confirmed fragile X syndrome (mean age 8.8 +/- 4.4 years, range 5-18 years), were included. All patients had mental retardation, with a mean IQ of 58.9 +/- 8.8 (range 40-68), and additional neurobehavioral symptoms. SPECT revealed cerebral perfusion abnormalities in six patients (75%), most commonly in the frontoparietotemporal area and prominent in the right hemisphere. The SPECT and EEG findings were concordant: hypoperfused areas in SPECT corresponded to regions of persistent slow-wave paroxysms on EEG. On the other hand, cranial MRI was abnormal qualitatively only in two patients (25%) showing cerebellar and vermal hypoplasia and cerebral hemispheric asymmetry. Our results indicate that cerebral perfusion abnormalities, which are correlated with electrophysiologic findings but not necessarily with anatomic abnormalities, can underlie the pathogenesis of the clinical findings observed in fragile X syndrome.

  7. 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.

  8. Cerebral perfusion pressure and abnormal intracranial pressure wave forms: their relation to outcome in birth asphyxia.

    PubMed

    Raju, T N; Vidyasagar, D; Papazafiratou, C

    1981-06-01

    Intracranial pressure (ICP) studies were carried out in 14 infants with severe birth asphyxia and brain damage. A markedly low cerebral perfusion pressure (CPP) was noted in infants who died and in 1 infant who survived with cerebral palsy. The long-term ICP tracing revealed negative waves and plateau waves in 2 infants. Cushing response was noted in 2 infants who had elevated ICP. The value and significance of evaluated CPP and of abnormal waveforms are discussed.

  9. 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

  10. 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

  11. 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.

  12. 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

  13. 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.

  14. Abnormal myocardial perfusion and risk of heart failure in patients with type 2 diabetes mellitus

    PubMed Central

    Utrera-Lagunas, Marcelo; Orea-Tejeda, Arturo; Castillo-Martínez, Lilia; Balderas-Muñoz, Karla; Keirns-Davis, Candace; Espinoza-Rosas, Sarahi; Sánchez-Ortíz, Néstor Alonso; Olvera-Mayorga, Gabriela

    2013-01-01

    BACKGROUND: Diabetes is a major risk factor for heart failure (HF), although the pathophysiological processes have not been clarified. OBJECTIVE: To determine the prevalence of HF and of abnormal myocardial perfusion in diabetic patients evaluated using technetium (99m) sestamibi single-photon emission computed tomography. METHODS: An observational cross-sectional study was conducted that included patients with type 2 diabetes mellitus who underwent echocardiography to diagnose HF and a pharmacological stress test with intravenous dipyridamole to examine cardiac scintigraphic perfusion abnormalities. Clinical and biochemical data were also collected. RESULTS: Of the 160 diabetic patients included, 92 (57.6%) were in HF and 68 (42.5%) were not. When patients were stratified according to the presence of abnormal myocardial perfusion, those with abnormal perfusion had a higher prevalence of HF (93%) than those with normal perfusion (44.4%) (P<0.0001). Patients with HF weighed more (P=0.03), used insulin less frequently (P=0.01), had lower total cholesterol (P=0.05) and high-density lipoprotein cholesterol concentrations (P=0.002), and a greater number of their myocardial segments showed abnormal perfusion (P≤0.001). More HF patients had a history of myocardial infarction (P<0.001) compared with those without HF. In a logistic regression analysis, the number of segments exhibiting abnormal myocardial perfusion was an independent risk factor for HF. CONCLUSIONS: The prevalence of HF in diabetic patients was high and HF predominantly occured in association with myocardial ischemia. PMID:24294048

  15. Brain/language relationships identified with diffusion and perfusion MRI: Clinical applications in neurology and neurosurgery.

    PubMed

    Hillis, Argye E

    2005-12-01

    Diffusion and perfusion MRI have contributed to stroke management by identifying patients with tissue "at risk" for further damage in acute stroke. However, the potential usefulness of these imaging modalities, along with diffusion tensor imaging, can be expanded by using these imaging techniques with concurrent assessment of language and other cognitive skills to identify the specific cognitive deficits that are associated with diffusion and perfusion abnormalities in particular brain regions. This paper illustrates how this combined behavioral and imaging methodology can yield information that is useful for predicting specific positive effects of intervention to restore blood flow in hypoperfused regions of brain identified with perfusion MRI, and for predicting negative effects of resection of particular brain regions or fiber bundles. Such data allow decisions about neurological and neurosurgical interventions to be based on specific risks and benefits in terms of functional consequences.

  16. MRI Helps Assess Fetal Brain Abnormalities

    MedlinePlus

    ... decisions about their pregnancy," said lead author Paul Griffiths. He's a professor of radiology at the University ... the fetus may have a suspected brain abnormality," Griffiths said in a journal news release. In this ...

  17. Normal language in abnormal brains.

    PubMed

    Piattelli-Palmarini, Massimo

    2017-02-27

    There is little doubt that, in the adult, specific brain lesions cause specific language deficits. Yet, brain localizations of linguistic functions are made problematic by several reported cases of normal language in spite of major brain anomalies, mostly, but not exclusively, occurring early in life. The signal cases are hydrocephaly, spina bifida and hemispherectomy. These cases are discussed and possible solutions are suggested: namely a vast redundancy of neurons and/or the role of microtubules as neuron-internal processors and key factors in signaling and guiding the growth and reconfiguration of the brain.

  18. Reversible cold-induced abnormalities in myocardial perfusion and function in systemic sclerosis

    SciTech Connect

    Alexander, E.L.; Firestein, G.S.; Weiss, J.L.; Heuser, R.R.; Leitl, G.; Wagner, H.N. Jr.; Brinker, J.A.; Ciuffo, A.A.; Becker, L.C.

    1986-11-01

    The effects of peripheral cold exposure on myocardial perfusion and function were studied in 13 patients with scleroderma without clinically evident myocardial disease. Ten patients had at least one transient, cold-induced, myocardial perfusion defect visualized by thallium-201 scintigraphy, and 12 had reversible, cold-induced, segmental left ventricular hypokinesis by two-dimensional echocardiography. The 10 patients with transient perfusion defects all had anatomically corresponding ventricular wall motion abnormalities. No one in either of two control groups (9 normal volunteers and 7 patients with chest pain and normal coronary arteriograms) had cold-induced abnormalities. This study is the first to show the simultaneous occurrence of cold-induced abnormalities in myocardial perfusion and function in patients with scleroderma. The results suggest that cold exposure in such patients may elicit transient reflex coronary vasoconstriction resulting in reversible myocardial ischemia and dysfunction. Chronic recurrent episodes of coronary spasm may lead to focal myocardial fibrosis.

  19. 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.

  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. Brain perfusion asymmetry in patients with oral somatic delusions.

    PubMed

    Umezaki, Yojiro; Katagiri, Ayano; Watanabe, Motoko; Takenoshita, Miho; Sakuma, Tomomi; Sako, Emi; Sato, Yusuke; Toriihara, Akira; Uezato, Akihito; Shibuya, Hitoshi; Nishikawa, Toru; Motomura, Haruhiko; Toyofuku, Akira

    2013-06-01

    Oral cenesthopathy is a somatic delusion or hallucination involving the oral area and is categorized as a delusional disorder, somatic type. The pathophysiology of this intractable condition remains obscure. In this study, we clarified the pathophysiology of oral cenesthopathy by evaluating regional brain perfusion. We performed single photon emission computed tomography (SPECT) using (99m)Tc-ethylcysteinate dimer in 16 subjects (cenesthopathy:control = 8:8). The SPECT images were visually assessed qualitatively, and quantitative analyses were also performed using a three-dimensional stereotactic region-of-interest template. The visual assessment revealed a right > left perfusion asymmetry in broad areas of the brain among the patients. The quantitative analysis confirmed that the regional cerebral blood flow values on the right side were significantly larger than those on the left side for most areas of the brain in the patients. A comparison of the R/(R + L) ratios in both groups confirmed the significant brain perfusion asymmetry between the two sides in the callosomarginal, precentral, and temporal regions in the patients. Qualitative evaluation of the SPECT images revealed right > left brain perfusion asymmetry in broad regions of the brain. Moreover, the quantitative analyses confirmed the perfusion asymmetry between the two sides in the frontal and temporal areas. Those may provide the key for elucidation of the pathophysiology of oral cenesthopathy.

  2. 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

  3. Blood-brain barrier permeability imaging using perfusion computed tomography

    PubMed Central

    Avsenik, Jernej; Bisdas, Sotirios; Popovic, Katarina Surlan

    2015-01-01

    Background. The blood-brain barrier represents the selective diffusion barrier at the level of the cerebral microvascular endothelium. Other functions of blood-brain barrier include transport, signaling and osmoregulation. Endothelial cells interact with surrounding astrocytes, pericytes and neurons. These interactions are crucial to the development, structural integrity and function of the cerebral microvascular endothelium. Dysfunctional blood-brain barrier has been associated with pathologies such as acute stroke, tumors, inflammatory and neurodegenerative diseases. Conclusions. Blood-brain barrier permeability can be evaluated in vivo by perfusion computed tomography - an efficient diagnostic method that involves the sequential acquisition of tomographic images during the intravenous administration of iodinated contrast material. The major clinical applications of perfusion computed tomography are in acute stroke and in brain tumor imaging. PMID:26029020

  4. 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)

  5. Myocardial perfusion abnormalities in patients with hypertrophic cardiomyopathy: assessment with thallium-201 emission computed tomography

    SciTech Connect

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

    1987-12-01

    Myocardial ischemia may play a critical role in the symptomatic presentation and natural history of hypertrophic cardiomyopathy (HCM). To assess the relative prevalence and functional significance of myocardial perfusion abnormalities in patients comprising the broad clinical spectrum of HCM, we studied 72 patients (ages 12 to 69 years, mean 40) using thallium-201 emission computed tomography. Imaging was performed immediately after maximal exercise and again after a 3 hr delay. Regional perfusion defects were identified in 41 of the 72 patients (57%). Fixed or only partially reversible defects were evident in 17 patients, 14 of whom (82%) had left ventricular ejection fractions of less than 50% at rest. Twenty-four patients demonstrated perfusion defects during exercise that completely reversed at rest; all had normal or hyperdynamic left ventricular systolic function (ejection fraction greater than or equal to 50%). Perfusion abnormalities were present in all regions of the left ventricle. However, the fixed defects were observed predominantly in segments of the left ventricular wall that were of normal or only mildly increased (15 to 20 mm) thickness; in contrast, a substantial proportion (41%) of the completely reversible defects occurred in areas of moderate-to-marked wall thickness (greater than or equal to 20 mm, p less than .001). Neither a history of chest pain nor its provocation with treadmill exercise was predictive of an abnormal thallium study, since regional perfusion defects were present in 10 of 18 (56%) completely asymptomatic patients, compared with 31 of 54 (58%) symptomatic patients. These data indicate that myocardial perfusion abnormalities occur commonly among patients with HCM. Fixed or only partially reversible defects suggestive of myocardial scar and/or severe ischemia occur primarily in patients with impaired systolic performance.

  6. 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.

  7. Automated three-dimensional quantification of myocardial perfusion and brain SPECT.

    PubMed

    Slomka, P J; Radau, P; Hurwitz, G A; Dey, D

    2001-01-01

    To allow automated and objective reading of nuclear medicine tomography, we have developed a set of tools for clinical analysis of myocardial perfusion tomography (PERFIT) and Brain SPECT/PET (BRASS). We exploit algorithms for image registration and use three-dimensional (3D) "normal models" for individual patient comparisons to composite datasets on a "voxel-by-voxel basis" in order to automatically determine the statistically significant abnormalities. A multistage, 3D iterative inter-subject registration of patient images to normal templates is applied, including automated masking of the external activity before final fit. In separate projects, the software has been applied to the analysis of myocardial perfusion SPECT, as well as brain SPECT and PET data. Automatic reading was consistent with visual analysis; it can be applied to the whole spectrum of clinical images, and aid physicians in the daily interpretation of tomographic nuclear medicine images.

  8. Abnormal asymmetry of brain connectivity in schizophrenia.

    PubMed

    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.

  9. Brain perfusion and markers of neurodegeneration in rapid eye movement sleep behavior disorder.

    PubMed

    Vendette, Mélanie; Gagnon, Jean-François; Soucy, Jean-Paul; Gosselin, Nadia; Postuma, Ronald B; Tuineag, Maria; Godin, Isabelle; Montplaisir, Jacques

    2011-08-01

    Potential early markers of neurodegeneration such as subtle motor signs, reduced color discrimination, olfactory impairment, and brain perfusion abnormalities have been reported in idiopathic rapid eye movement sleep behavior disorder, a risk factor for Parkinson's disease and Lewy body dementia. The aim of this study was to reproduce observations of regional cerebral blood flow abnormalities in a larger independent sample of patients and to explore correlations between regional cerebral blood flow and markers of neurodegeneration. Twenty patients with idiopathic rapid eye movement sleep behavior disorder and 20 healthy controls were studied by single-photon emission computerized tomography. Motor examination, color discrimination, and olfactory identification were examined. Patients with rapid eye movement sleep behavior disorder showed decreased regional cerebral blood flow in the frontal cortex and in medial parietal areas and increased regional cerebral blood flow in subcortical regions including the bilateral pons, putamen, and hippocampus. In rapid eye movement sleep behavior disorder, brain perfusion in the frontal cortex and occipital areas was associated with poorer performance in the color discrimination test. Moreover, a relationship between loss of olfactory discrimination and regional cerebral blood flow reduction in the bilateral anterior parahippocampal gyrus, a region known to be involved in olfactory functions, was found. This study provides further evidence of regional cerebral blood flow abnormalities in rapid eye movement sleep behavior disorder that are similar to those seen in Parkinson's disease and Lewy body dementia. Moreover, regional cerebral blood flow anomalies were associated with markers of neurodegeneration.

  10. Novel brain MRI abnormalities in Gitelman syndrome

    PubMed Central

    Norbash, Alexander; Vattoth, Surjith

    2015-01-01

    Gitelman syndrome is an autosomal recessive renal tubular disorder characterized by hypokalemic metabolic alkalosis, hypomagnesemia and hypocalciuria. The syndrome is caused by a defective thiazide-sensitive sodium chloride co-transporter in the distal convoluted tubules of the kidneys. Gitelman syndrome could be confused with Bartter syndrome; the main differentiating feature is the presence of low urinary calcium excretion in the former. Descriptions of neuroradiological imaging findings associated with Gitelman syndrome are very scarce in the literature and include basal ganglia calcification, idiopathic intracranial hypertension and sclerochoroidal calcification. Cauda equina syndrome-like presentation has been reported, but without any corresponding imaging findings on lumbar spine MRI. We report a 13-year-old male with Gitelman syndrome who presented with altered mental status following a fall and scalp laceration and unremarkable brain CT, followed during hospitalization by somnolence and seizures. Metabolically the patient demonstrated hypokalemia and hypomagnesemia. MRI demonstrated features of encephalopathy including predominantly right-sided cerebral hemispheric signal abnormality and cytotoxic edema, with bilateral symmetric involvement of the thalami, midbrain tegmentum and tectum and cerebellar dentate nuclei. MRI after five months obtained during a later episode of encephalopathy showed resolution of the signal abnormalities with setting in of brain atrophy and also areas of newly developed cytotoxic edema in the left thalamus, bilateral dorsal midbrain and right greater than left dentate nuclei. The described abnormalities, either recurrent or in isolation, have not previously been published in patients with Gitelman syndrome. We believe that the findings are due to alteration of respiratory chain function secondary to the metabolic derangement and hence have a similar imaging appearance as encephalopathy related to mitochondrial cytopathy or

  11. Focally perfused succinate potentiates brain metabolism in head injury patients.

    PubMed

    Jalloh, Ibrahim; Helmy, Adel; Howe, Duncan J; Shannon, Richard J; Grice, Peter; Mason, Andrew; Gallagher, Clare N; Stovell, Matthew G; van der Heide, Susan; Murphy, Michael P; Pickard, John D; Menon, David K; Carpenter, T Adrian; Hutchinson, Peter J; Carpenter, Keri Lh

    2016-01-01

    Following traumatic brain injury, complex cerebral energy perturbations occur. Correlating with unfavourable outcome, high brain extracellular lactate/pyruvate ratio suggests hypoxic metabolism and/or mitochondrial dysfunction. We investigated whether focal administration of succinate, a tricarboxylic acid cycle intermediate interacting directly with the mitochondrial electron transport chain, could improve cerebral metabolism. Microdialysis perfused disodium 2,3-(13)C2 succinate (12 mmol/L) for 24 h into nine sedated traumatic brain injury patients' brains, with simultaneous microdialysate collection for ISCUS analysis of energy metabolism biomarkers (nine patients) and nuclear magnetic resonance of (13)C-labelled metabolites (six patients). Metabolites 2,3-(13)C2 malate and 2,3-(13)C2 glutamine indicated tricarboxylic acid cycle metabolism, and 2,3-(13)C2 lactate suggested tricarboxylic acid cycle spinout of pyruvate (by malic enzyme or phosphoenolpyruvate carboxykinase and pyruvate kinase), then lactate dehydrogenase-mediated conversion to lactate. Versus baseline, succinate perfusion significantly decreased lactate/pyruvate ratio (p = 0.015), mean difference -12%, due to increased pyruvate concentration (+17%); lactate changed little (-3%); concentrations decreased for glutamate (-43%) (p = 0.018) and glucose (-15%) (p = 0.038). Lower lactate/pyruvate ratio suggests better redox status: cytosolic NADH recycled to NAD(+) by mitochondrial shuttles (malate-aspartate and/or glycerol 3-phosphate), diminishing lactate dehydrogenase-mediated pyruvate-to-lactate conversion, and lowering glutamate. Glucose decrease suggests improved utilisation. Direct tricarboxylic acid cycle supplementation with 2,3-(13)C2 succinate improved human traumatic brain injury brain chemistry, indicated by biomarkers and (13)C-labelling patterns in metabolites.

  12. Pulmonary ventilation and perfusion abnormalities and ventilation perfusion imbalance in children with pulmonary atresia or extreme tetralogy of Fallot

    SciTech Connect

    Dowdle, S.C.; Human, D.G.; Mann, M.D. )

    1990-08-01

    Xenon-133 lung ventilation and perfusion scans were done preoperatively after cardiac catheterization and cineangiocardiography in 19 children; 6 had pulmonary atresia with an intact ventricular septum and hypoplastic right ventricle, 4 pulmonary atresia with associated complex univentricular heart, and 9 extreme Tetralogy of Fallot. The four patients with discrepancies in the sizes of the left and right pulmonary arteries on angiography had marked asymmetry of pulmonary perfusion and ventilation-perfusion imbalance on scintigraphy. Similar degrees of asymmetry and imbalance were present in 6 of the 15 children with equal-size pulmonary vessels. Asymmetry of pulmonary perfusion and ventilation-perfusion imbalance were associated with a poor prognosis.

  13. Brain Tissue Volumes and Perfusion Change with the Number of Optic Neuritis Attacks in Relapsing Neuromyelitis Optica: A Voxel-Based Correlation Study.

    PubMed

    Sánchez-Catasús, Carlos A; Cabrera-Gomez, José; Almaguer Melián, William; Giroud Benítez, José Luis; Rodríguez Rojas, Rafael; Bayard, Jorge Bosch; Galán, Lídice; Sánchez, Reinaldo Galvizu; Fuentes, Nancy Pavón; Valdes-Sosa, Pedro

    2013-01-01

    Recent neuroimaging studies show that brain abnormalities in neuromyelitis optica (NMO) are more frequent than earlier described. Yet, more research considering multiple aspects of NMO is necessary to better understand these abnormalities. A clinical feature of relapsing NMO (RNMO) is that the incremental disability is attack-related. Therefore, association between the attack-related process and neuroimaging might be expected. On the other hand, the immunopathological analysis of NMO lesions has suggested that CNS microvasculature could be an early disease target, which could alter brain perfusion. Brain tissue volume changes accompanying perfusion alteration could also be expected throughout the attack-related process. The aim of this study was to investigate in RNMO patients, by voxel-based correlation analysis, the assumed associations between regional brain white (WMV) and grey matter volumes (GMV) and/or perfusion on one side, and the number of optic neuritis (ON) attacks, myelitis attacks and/or total attacks on the other side. For this purpose, high resolution T1-weighted MRI and perfusion SPECT imaging were obtained in 15 RNMO patients. The results showed negative regional correlations of WMV, GMV and perfusion with the number of ON attacks, involving important components of the visual system, which could be relevant for the comprehension of incremental visual disability in RNMO. We also found positive regional correlation of perfusion with the number of ON attacks, mostly overlapping the brain area where the WMV showed negative correlation. This provides evidence that brain microvasculature is an early disease target and suggests that perfusion alteration could be important in the development of brain structural abnormalities in RNMO.

  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. Hepatic perfusion abnormalities during treatment with hepatic arterial infusion chemotherapy: Value of CT arteriography using an implantable port system

    SciTech Connect

    Seki, Hiroshi; Kimura, Motomasa; Kamura, Takeshi; Miura, Tsutomu

    1996-05-01

    The purpose of this study was to evaluate CT arteriography (CTA) using an implantable port system in the detection of perfusion abnormalities occurring during hepatic arterial infusion chemotherapy (HAIC). In 51 patients with unresectable primary and metastatic liver tumors, who had implanted port systems for HAIC, CTA examinations through the infusion pump were performed. When perfusion abnormalities were found, selective angiography and/or digital subtraction angiography using the implantable port system were performed to determine the etiology. Forty-nine perfusion abnormalities were detected in 32 patients. Intrahepatic hypoperfusion was found in 24 cases. Of 11 patients in whom correction of the hypoperfusion was attempted, it was successful in 10. Of 13 patients in whom correction was not attempted, 6 patients showed progressive disease in nonperfused areas. Intrahepatic hyperperfusion was found in 14 cases, which showed no subsequent complication. Extrahepatic perfusion was found in 11 cases. We consider CTA to be useful in detecting perfusion abnormalities that may compromise HAIC. 22 refs., 3 figs., 3 tabs.

  17. 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.

  18. 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

  19. Comparison of heterogeneity quantification algorithms for brain SPECT perfusion images

    PubMed Central

    2012-01-01

    Background Several algorithms from the literature were compared with the original random walk (RW) algorithm for brain perfusion heterogeneity quantification purposes. Algorithms are compared on a set of 210 brain single photon emission computed tomography (SPECT) simulations and 40 patient exams. Methods Five algorithms were tested on numerical phantoms. The numerical anthropomorphic Zubal head phantom was used to generate 42 (6 × 7) different brain SPECT simulations. Seven diffuse cortical heterogeneity levels were simulated with an adjustable Gaussian noise function and six focal perfusion defect levels with temporoparietal (TP) defects. The phantoms were successively projected and smoothed with Gaussian kernel with full width at half maximum (FWHM = 5 mm), and Poisson noise was added to the 64 projections. For each simulation, 5 Poisson noise realizations were performed yielding a total of 210 datasets. The SPECT images were reconstructed using filtered black projection (Hamming filter: α = 0.5). The five algorithms or measures tested were the following: the coefficient of variation, the entropy and local entropy, fractal dimension (FD) (box counting and Fourier power spectrum methods), the gray-level co-occurrence matrix (GLCM), and the new RW. The heterogeneity discrimination power was obtained with a linear regression for each algorithm. This regression line is a mean function of the measure of heterogeneity compared to the different diffuse heterogeneity and focal defect levels generated in the phantoms. A greater slope denotes a larger separation between the levels of diffuse heterogeneity. The five algorithms were computed using 40 99mTc-ethyl-cysteinate-dimer (ECD) SPECT images of patients referred for memory impairment. Scans were blindly ranked by two physicians according to the level of heterogeneity, and a consensus was obtained. The rankings obtained by the algorithms were compared with the physicians' consensus ranking. Results The GLCM method

  20. 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.

  1. Selective Heart, Brain and Body Perfusion in Open Aortic Arch Replacement

    PubMed Central

    Maier, Sven; Kari, Fabian; Rylski, Bartosz; Siepe, Matthias; Benk, Christoph; Beyersdorf, Friedhelm

    2016-01-01

    Abstract: Open aortic arch replacement is a complex and challenging procedure, especially in post dissection aneurysms and in redo procedures after previous surgery of the ascending aorta or aortic root. We report our experience with the simultaneous selective perfusion of heart, brain, and remaining body to ensure optimal perfusion and to minimize perfusion-related risks during these procedures. We used a specially configured heart–lung machine with a centrifugal pump as arterial pump and an additional roller pump for the selective cerebral perfusion. Initial arterial cannulation is achieved via femoral artery or right axillary artery. After lower body circulatory arrest and selective antegrade cerebral perfusion for the distal arch anastomosis, we started selective lower body perfusion simultaneously to the selective antegrade cerebral perfusion and heart perfusion. Eighteen patients were successfully treated with this perfusion strategy from October 2012 to November 2015. No complications related to the heart–lung machine and the cannulation occurred during the procedures. Mean cardiopulmonary bypass time was 239 ± 33 minutes, the simultaneous selective perfusion of brain, heart, and remaining body lasted 55 ± 23 minutes. One patient suffered temporary neurological deficit that resolved completely during intensive care unit stay. No patient experienced a permanent neurological deficit or end-organ dysfunction. These high-risk procedures require a concept with a special setup of the heart–lung machine. Our perfusion strategy for aortic arch replacement ensures a selective perfusion of heart, brain, and lower body during this complex procedure and we observed excellent outcomes in this small series. This perfusion strategy is also applicable for redo procedures. PMID:27729705

  2. Abnormal brain synchrony in Down Syndrome☆

    PubMed Central

    Anderson, Jeffrey S.; Nielsen, Jared A.; Ferguson, Michael A.; Burback, Melissa C.; Cox, Elizabeth T.; Dai, Li; Gerig, Guido; Edgin, Jamie O.; Korenberg, Julie R.

    2013-01-01

    Down Syndrome is the most common genetic cause for intellectual disability, yet the pathophysiology of cognitive impairment in Down Syndrome is unknown. We compared fMRI scans of 15 individuals with Down Syndrome to 14 typically developing control subjects while they viewed 50 min of cartoon video clips. There was widespread increased synchrony between brain regions, with only a small subset of strong, distant connections showing underconnectivity in Down Syndrome. Brain regions showing negative correlations were less anticorrelated and were among the most strongly affected connections in the brain. Increased correlation was observed between all of the distributed brain networks studied, with the strongest internetwork correlation in subjects with the lowest performance IQ. A functional parcellation of the brain showed simplified network structure in Down Syndrome organized by local connectivity. Despite increased interregional synchrony, intersubject correlation to the cartoon stimuli was lower in Down Syndrome, indicating that increased synchrony had a temporal pattern that was not in response to environmental stimuli, but idiosyncratic to each Down Syndrome subject. Short-range, increased synchrony was not observed in a comparison sample of 447 autism vs. 517 control subjects from the Autism Brain Imaging Exchange (ABIDE) collection of resting state fMRI data, and increased internetwork synchrony was only observed between the default mode and attentional networks in autism. These findings suggest immature development of connectivity in Down Syndrome with impaired ability to integrate information from distant brain regions into coherent distributed networks. PMID:24179822

  3. Stroke prognosis by applying double thresholds on CT-perfusion-brain images

    NASA Astrophysics Data System (ADS)

    Chokchaitam, Somchart; Santipromwong, Nittaya; Muengtaweepongsa, Sombat

    2013-03-01

    The CT-perfusion image shows information of brain abnormalities such as its size and location. Generally, neurologist diagnoses stroke disease using CT-perfusion images such as Cerebral blood flow (CBF), cerebral blood volume (CBV). In our previous report, we applied threshold technique to divide amount of CBV and CBF into low and high level. Then, their levels are applied to identify normal tissue areas, dead tissue areas (infract core) and blood-cot tissue areas (infract penumbra). However, it's not totally correct, if the same threshold is applied to the whole area (it must depend on size of blood vessel in that area. In this report, we propose double thresholds to divided CBV and CBF into 3 levels: very low, medium and very high levels. Very low and very high levels are definitely implied to bad areas and good areas, respectively. The proposed double thresholds makes stroke prognosis more accurate. The simulation results confirm that our proposed results closed to results defined from neurologist comparing to the conventional results.

  4. A perfusion protocol for lizards, including a method for brain removal

    PubMed Central

    Hoops, Daniel

    2015-01-01

    The goal of fixation is to rapidly and uniformly preserve tissue in a life-like state. Perfusion achieves optimal fixation by pumping fixative directly through an animal’s circulatory system. Standard perfusion techniques were developed primarily for application in mammals, which are traditional neuroscience research models. Increasingly, other vertebrate groups are also being used in neuroscience. Following mammalian perfusion protocols for non-mammalian vertebrates often results in failed perfusions. Here, I present a modified perfusion protocol suitable for lizards. Though geared towards standard brain perfusion, this protocol is easily modified for the perfusion of other tissues and for various specialized histological techniques. • The two aortas of the lizard heart, emerging from a single ventricle, mean that care must be taken to place the perfusion needle in the correct aorta, unlike in mammals. • Only the head and neck perfuse – the visceral organs will not decolour, and the body may not twitch. • I also include a method for removing a lizard brain, which differs from mammals due to the incomplete and thicker skull of the lizard. PMID:26150986

  5. Genes and brain malformations associated with abnormal neuron positioning.

    PubMed

    Moffat, Jeffrey J; Ka, Minhan; Jung, Eui-Man; Kim, Woo-Yang

    2015-11-05

    Neuronal positioning is a fundamental process during brain development. Abnormalities in this process cause several types of brain malformations and are linked to neurodevelopmental disorders such as autism, intellectual disability, epilepsy, and schizophrenia. Little is known about the pathogenesis of developmental brain malformations associated with abnormal neuron positioning, which has hindered research into potential treatments. However, recent advances in neurogenetics provide clues to the pathogenesis of aberrant neuronal positioning by identifying causative genes. This may help us form a foundation upon which therapeutic tools can be developed. In this review, we first provide a brief overview of neural development and migration, as they relate to defects in neuronal positioning. We then discuss recent progress in identifying genes and brain malformations associated with aberrant neuronal positioning during human brain development.

  6. 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

  7. Myocardial perfusion abnormality in the area of ventricular septum-free wall junction and cardiovascular events in nonobstructive hypertrophic cardiomyopathy.

    PubMed

    Kaimoto, Satoshi; Kawasaki, Tatsuya; Kuribayashi, Toshiro; Yamano, Michiyo; Miki, Shigeyuki; Kamitani, Tadaaki; Matsubara, Hiroaki

    2012-10-01

    Myocardial perfusion abnormality in the left ventricle is known to be prognostic in patients with hypertrophic cardiomyopathy (HCM). Magnetic resonance imaging and necropsy studies on HCM hearts revealed myocardial lesions predominating in the area of ventricular septum-free wall junction. We assessed perfusion abnormality in this area and correlated it with the prognosis of HCM patients. We performed exercise Tc-99m tetrofosmin myocardial scintigraphy in 55 patients with nonobstructive HCM. Perfusion abnormalities were semiquantified using a 5-point scoring system in small areas of anterior junctions of basal, mid, and apical short axis views in addition to a conventional 17-segment model. All patients were prospectively followed for sudden death, cardiovascular death and hospitalization for heart failure or stroke associated with atrial fibrillation. Cardiovascular events occurred in 10 patients during an average follow-up period of 5.7 years. Stress and rest scores from anterior junction, and conventional summed stress score were significantly higher in patients with cardiovascular events than without (all P < 0.05). Anterior junction stress score of >2 produced a sensitivity of 50% and a specificity of 98% for cardiovascular events and was an independent predictor (hazard ratio 8.33; 95% confidence interval, 1.61-43.5; P = 0.01), with rest scores producing similar values, which were higher than summed stress score of >8 (5.68; 1.23-26.3; P = 0.03). The absence of myocardial perfusion abnormality in the narrow area of anterior junction differentiated HCM patients with low-risk.

  8. Large brains in autism: the challenge of pervasive abnormality.

    PubMed

    Herbert, Martha R

    2005-10-01

    The most replicated finding in autism neuroanatomy-a tendency to unusually large brains-has seemed paradoxical in relation to the specificity of the abnormalities in three behavioral domains that define autism. We now know a range of things about this phenomenon, including that brains in autism have a growth spurt shortly after birth and then slow in growth a few short years afterward, that only younger but not older brains are larger in autism than in controls, that white matter contributes disproportionately to this volume increase and in a nonuniform pattern suggesting postnatal pathology, that functional connectivity among regions of autistic brains is diminished, and that neuroinflammation (including microgliosis and astrogliosis) appears to be present in autistic brain tissue from childhood through adulthood. Alongside these pervasive brain tissue and functional abnormalities, there have arisen theories of pervasive or widespread neural information processing or signal coordination abnormalities (such as weak central coherence, impaired complex processing, and underconnectivity), which are argued to underlie the specific observable behavioral features of autism. This convergence of findings and models suggests that a systems- and chronic disease-based reformulation of function and pathophysiology in autism needs to be considered, and it opens the possibility for new treatment targets.

  9. Brain growth rate abnormalities visualized in adolescents with autism.

    PubMed

    Hua, Xue; Thompson, Paul M; Leow, Alex D; Madsen, Sarah K; Caplan, Rochelle; Alger, Jeffry R; O'Neill, Joseph; Joshi, Kishori; Smalley, Susan L; Toga, Arthur W; Levitt, Jennifer G

    2013-02-01

    Autism spectrum disorder is a heterogeneous disorder of brain development with wide ranging cognitive deficits. Typically diagnosed before age 3, autism spectrum disorder is behaviorally defined but patients are thought to have protracted alterations in brain maturation. With longitudinal magnetic resonance imaging (MRI), we mapped an anomalous developmental trajectory of the brains of autistic compared with those of typically developing children and adolescents. Using tensor-based morphometry, we created 3D maps visualizing regional tissue growth rates based on longitudinal brain MRI scans of 13 autistic and seven typically developing boys (mean age/interscan interval: autism 12.0 ± 2.3 years/2.9 ± 0.9 years; control 12.3 ± 2.4/2.8 ± 0.8). The typically developing boys demonstrated strong whole brain white matter growth during this period, but the autistic boys showed abnormally slowed white matter development (P = 0.03, corrected), especially in the parietal (P = 0.008), temporal (P = 0.03), and occipital lobes (P = 0.02). We also visualized abnormal overgrowth in autism in gray matter structures such as the putamen and anterior cingulate cortex. Our findings reveal aberrant growth rates in brain regions implicated in social impairment, communication deficits and repetitive behaviors in autism, suggesting that growth rate abnormalities persist into adolescence. Tensor-based morphometry revealed persisting growth rate anomalies long after diagnosis, which has implications for evaluation of therapeutic effects.

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. 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…

  15. 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.

  16. 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.

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

    PubMed

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

    2015-06-01

    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 multimodal integration of brain structure and function analyses links sexual and nonsexual psychopathology in pedophilia.

  18. DRAG REDUCING POLYMER ENCHANCES MICROVASCULAR PERFUSION IN THE TRAUMATIZED BRAIN WITH INTRACRANIAL HYPERTENSION

    PubMed Central

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

    2016-01-01

    SUMMARY Current treatments for traumatic brain injury (TBI) have not focused on improving microvascular perfusion. Drag-reducing polymers (DRP), linear, long-chain, blood soluble non-toxic 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 limb, but have not yet been studied in the brain. Recently, we demonstrated that 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 the in-vivo 2-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 un-traumatized and traumatized rat brains at high ICP. Our study suggests that DRP could be an effective treatment for improving microvascular flow in brain ischemia caused by high ICP after TBI. PMID:27165871

  19. The adverse effects of reduced cerebral perfusion on cognition and brain structure in older adults with cardiovascular disease

    PubMed Central

    Alosco, Michael L; Gunstad, John; Jerskey, Beth A; Xu, Xiaomeng; Clark, Uraina S; Hassenstab, Jason; Cote, Denise M; Walsh, Edward G; Labbe, Donald R; Hoge, Richard; Cohen, Ronald A; Sweet, Lawrence H

    2013-01-01

    Background It is well established that aging and vascular processes interact to disrupt cerebral hemodynamics in older adults. However, the independent effects of cerebral perfusion on neurocognitive function among older adults remain poorly understood. We examined the associations among cerebral perfusion, cognitive function, and brain structure in older adults with varying degrees of vascular disease using perfusion magnetic resonance imaging (MRI) arterial spin labeling (ASL). Materials and methods 52 older adults underwent neuroimaging and were administered the Mini Mental State Examination (MMSE), the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and measures of attention/executive function. ASL and T1-weighted MRI were used to quantify total brain perfusion, total brain volume (TBV), and cortical thickness. Results Regression analyses showed reduced total brain perfusion was associated with poorer performance on the MMSE, RBANS total index, immediate and delayed memory composites, and Trail Making Test B. Reduced frontal lobe perfusion was associated with worse executive and memory function. A similar pattern emerged between temporal lobe perfusion and immediate memory. Regression analyses revealed that decreased total brain perfusion was associated with smaller TBV and mean cortical thickness. Regional effects of reduced total cerebral perfusion were found on temporal and parietal lobe volumes and frontal and temporal cortical thickness. Discussion Reduced cerebral perfusion is independently associated with poorer cognition, smaller TBV, and reduced cortical thickness in older adults. Conclusion Prospective studies are needed to clarify patterns of cognitive decline and brain atrophy associated with cerebral hypoperfusion. PMID:24363966

  20. 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.

  1. Extensive abnormality of brain white matter integrity in pathological gambling.

    PubMed

    Joutsa, Juho; Saunavaara, Jani; Parkkola, Riitta; Niemelä, Solja; Kaasinen, Valtteri

    2011-12-30

    Several magnetic resonance imaging (MRI) studies in substance use disorders have shown brain white matter integrity abnormalities, but there are no studies in pathological gambling, a form of behavioral addiction. Our objective was to investigate possible changes in regional brain gray and white matter volumes, and axonal white matter integrity in pathological gamblers compared to healthy controls. Twenty-four subjects (12 clinically diagnosed male pathological gamblers and 12 age-matched healthy male volunteers) underwent structural and diffusion weighted brain MRI scans, which were analyzed with voxel-based morphometry and tract based spatial statistics. In pathological gamblers, widespread lower white matter integrity (lower fractional anisotropy, higher mean diffusivity) was seen in multiple brain regions including the corpus callosum, the cingulum, the superior longitudinal fascicle, the inferior fronto-occipital fascicle, the anterior limb of internal capsule, the anterior thalamic radiation, the inferior longitudinal fascicle and the uncinate/inferior fronto-occipital fascicle. There were no volumetric differences in gray or white matter between pathological gamblers and controls. The results suggest that pathological gambling is associated with extensive lower integrity of several brain white matter tracts. The diffusion abnormality closely resembles previous findings in individuals with substance addictions.

  2. 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

  3. [CT perfusion for assessment of brain stem ischemic lesions].

    PubMed

    Saifullina, E I; Iksanova, G R

    2007-01-01

    Modern neurovisualization modalities - CT and MRI with cerebral circulation assessment was used for diagnosis of cerebrovascular disturbances in patients admitted to the Emergency Care Hospital of Ufa. CT and MRI perfusion methods appeared to be highly effective both in diagnosis and treatment efficacy monitoring of acute stroke.

  4. Volume estimation of brain abnormalities in MRI data

    NASA Astrophysics Data System (ADS)

    Suprijadi, Pratama, S. H.; Haryanto, F.

    2014-02-01

    The abnormality of brain tissue always becomes a crucial issue in medical field. This medical condition can be recognized through segmentation of certain region from medical images obtained from MRI dataset. Image processing is one of computational methods which very helpful to analyze the MRI data. In this study, combination of segmentation and rendering image were used to isolate tumor and stroke. Two methods of thresholding were employed to segment the abnormality occurrence, followed by filtering to reduce non-abnormality area. Each MRI image is labeled and then used for volume estimations of tumor and stroke-attacked area. The algorithms are shown to be successful in isolating tumor and stroke in MRI images, based on thresholding parameter and stated detection accuracy.

  5. 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

  6. Abnormal brain structure implicated in stimulant drug addiction.

    PubMed

    Ersche, Karen D; Jones, P Simon; Williams, Guy B; Turton, Abigail J; Robbins, Trevor W; Bullmore, Edward T

    2012-02-03

    Addiction to drugs is a major contemporary public health issue, characterized by maladaptive behavior to obtain and consume an increasing amount of drugs at the expense of the individual's health and social and personal life. We discovered abnormalities in fronto-striatal brain systems implicated in self-control in both stimulant-dependent individuals and their biological siblings who have no history of chronic drug abuse; these findings support the idea of an underlying neurocognitive endophenotype for stimulant drug addiction.

  7. 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.

  8. Midline Brain Abnormalities Across Psychotic and Mood Disorders

    PubMed Central

    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. PMID:26187283

  9. 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.

  10. A 4D CT digital phantom of an individual human brain for perfusion analysis

    PubMed Central

    Brune, Christoph; van Ginneken, Bram; Prokop, Mathias

    2016-01-01

    Brain perfusion is of key importance to assess brain function. Modern CT scanners can acquire perfusion maps of the cerebral parenchyma in vivo at submillimeter resolution. These perfusion maps give insights into the hemodynamics of the cerebral parenchyma and are critical for example for treatment decisions in acute stroke. However, the relations between acquisition parameters, tissue attenuation curves, and perfusion values are still poorly understood and cannot be unraveled by studies involving humans because of ethical concerns. We present a 4D CT digital phantom specific for an individual human brain to analyze these relations in a bottom-up fashion. Validation of the signal and noise components was based on 1,000 phantom simulations of 20 patient imaging data. This framework was applied to quantitatively assess the relation between radiation dose and perfusion values, and to quantify the signal-to-noise ratios of penumbra regions with decreasing sizes in white and gray matter. This is the first 4D CT digital phantom that enables to address clinical questions without having to expose the patient to additional radiation dose. PMID:27917312

  11. Early blood gas abnormalities and the preterm brain.

    PubMed

    Leviton, Alan; Allred, Elizabeth; Kuban, Karl C K; Dammann, Olaf; O'Shea, T Michael; Hirtz, Deborah; Schreiber, Michael D; Paneth, Nigel

    2010-10-15

    The authors explored associations between blood gas abnormalities in more than 1,000 preterm infants during the first postnatal days and indicators of neonatal brain damage. During 2002-2004, women delivering infants before 28 weeks' gestation at one of 14 participating institutions in 5 US states were asked to enroll in the study. The authors compared infants with blood gas values in the highest or lowest quintile for gestational age and postnatal day (extreme value) on at least 1 of the first 3 postnatal days with the remainder of the subjects, with separate analyses for blood gas abnormalities on multiple days and for partial pressure of oxygen in the alveolar gas of <35. Outcomes analyzed were ventriculomegaly and an echolucent lesion on an ultrasound scan in the neonatal intensive care unit, and cerebral palsy, microcephaly, and a low score on a Bayley Scale of Infant Development at 24 months. Every blood gas derangement (hypoxemia, hyperoxemia, hypocapnia, hypercapnia, and acidosis) was associated with multiple indicators of brain damage. However, for some, the associations were seen with only 1 day of exposure; others were evident with 2 or more days' exposure. Findings suggest that individual blood gas derangements do not increase brain damage risk. Rather, the multiple derangements associated with indicators of brain damage might be indicators of immaturity/vulnerability and illness severity.

  12. 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.

  13. 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

  14. Feasibility of Flat Panel Detector CT in Perfusion Assessment of Brain Arteriovenous Malformations: Initial Clinical Experience.

    PubMed

    Garcia, M; Okell, T W; Gloor, M; Chappell, M A; Jezzard, P; Bieri, O; Byrne, J V

    2017-02-16

    The different results from flat panel detector CT in various pathologies have provoked some discussion. Our aim was to assess the role of flat panel detector CT in brain arteriovenous malformations, which has not yet been assessed. Five patients with brain arteriovenous malformations were studied with flat panel detector CT, DSC-MR imaging, and vessel-encoded pseudocontinuous arterial spin-labeling. In glomerular brain arteriovenous malformations, perfusion was highest next to the brain arteriovenous malformation with decreasing values with increasing distance from the lesion. An inverse tendency was observed in the proliferative brain arteriovenous malformation. Flat panel detector CT, originally thought to measure blood volume, correlated more closely with arterial spin-labeling-CBF and DSC-CBF than with DSC-CBV. We conclude that flat panel detector CT perfusion depends on the time point chosen for data collection, which is triggered too early in these patients (ie, when contrast agent appears in the superior sagittal sinus after rapid shunting through the brain arteriovenous malformation). This finding, in combination with high data variability, makes flat panel detector CT inappropriate for perfusion assessment in brain arteriovenous malformations.

  15. Abuse of Amphetamines and Structural Abnormalities in Brain

    PubMed Central

    Berman, Steven; O’Neill, Joseph; Fears, Scott; Bartzokis, George; London, Edythe D.

    2009-01-01

    We review evidence that structural brain abnormalities are associated with abuse of amphetamines. A brief history of amphetamine use/abuse, and evidence for toxicity is followed by a summary of findings from structural magnetic resonance imaging (MRI) studies of human subjects who had abused amphetamines and children who were exposed to amphetamines in utero. Evidence comes from studies that used a variety of techniques that include manual tracing, pattern matching, voxel-based, tensor-based, or cortical thickness mapping, quantification of white matter signal hyperintensities, and diffusion tensor imaging. Ten studies compared controls to individuals who were exposed to methamphetamine. Three studies assessed individuals exposed to 3-4-methylenedioxymethamphetamine (MDMA). Brain structural abnormalities were consistently reported in amphetamine abusers, as compared to control subjects. These included lower cortical gray matter volume and higher striatal volume than control subjects. These differences might reflect brain features that could predispose to substance dependence. High striatal volumes might also reflect compensation for toxicity in the dopamine-rich basal ganglia. Prenatal exposure was associated with striatal volume that was below control values, suggesting that such compensation might not occur in utero. Several forms of white matter abnormality are also common, and may involve gliosis. Many of the limitations and inconsistencies in the literature relate to techniques and cross-sectional designs, which cannot infer causality. Potential confounding influences include effects of pre-existing risk/protective factors, development, gender, severity of amphetamine abuse, abuse of other drugs, abstinence, and differences in lifestyle. Longitudinal designs in which multimodal datasets are acquired and are subjected to multivariate analyses would enhance our ability to provide general conclusions regarding the associations between amphetamine abuse and brain

  16. Abuse of amphetamines and structural abnormalities in the brain.

    PubMed

    Berman, Steven; O'Neill, Joseph; Fears, Scott; Bartzokis, George; London, Edythe D

    2008-10-01

    We review evidence that structural brain abnormalities are associated with abuse of amphetamines. A brief history of amphetamine use/abuse and evidence for toxicity is followed by a summary of findings from structural magnetic resonance imaging (MRI) studies of human subjects who had abused amphetamines and children who were exposed to amphetamines in utero. Evidence comes from studies that used a variety of techniques including manual tracing, pattern matching, voxel-based, tensor-based, or cortical thickness mapping, quantification of white matter signal hyperintensities, and diffusion tensor imaging. Ten studies compared controls to individuals who were exposed to methamphetamine. Three studies assessed individuals exposed to 3-4-methylenedioxymethamphetamine (MDMA). Brain structural abnormalities were consistently reported in amphetamine abusers, as compared to control subjects. These included lower cortical gray matter volume and higher striatal volume than control subjects. These differences might reflect brain features that could predispose to substance dependence. High striatal volumes might also reflect compensation for toxicity in the dopamine-rich basal ganglia. Prenatal exposure was associated with striatal volume that was below control values, suggesting that such compensation might not occur in utero. Several forms of white matter abnormality are also common and may involve gliosis. Many of the limitations and inconsistencies in the literature relate to techniques and cross-sectional designs, which cannot infer causality. Potential confounding influences include effects of pre existing risk/protective factors, development, gender, severity of amphetamine abuse, abuse of other drugs, abstinence, and differences in lifestyle. Longitudinal designs in which multimodal datasets are acquired and are subjected to multivariate analyses would enhance our ability to provide general conclusions regarding the associations between amphetamine abuse and brain

  17. 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.

  18. 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

  19. (13)N-Ammonia PET/CT Detection of Myocardial Perfusion Abnormalities in Beagle Dogs After Local Heart Irradiation.

    PubMed

    Song, Jianbo; Yan, Rui; Wu, Zhifang; Li, Jianguo; Yan, Min; Hao, Xinzhong; Liu, Jianzhong; Li, Sijin

    2017-04-01

    Our objective was to determine the potential value of (13)N-ammonia PET/CT myocardial perfusion imaging (MPI) for early detection of myocardial perfusion changes induced by radiation damage. Methods: Thirty-six Beagle dogs were randomly divided into a control group (n = 18) or an irradiation group (n = 18). The latter underwent local irradiation to the left ventricular anterior cardiac wall with a single dose of 20 Gy, whereas the former received sham irradiation. All dogs underwent (13)N-ammonia PET/CT MPI 1 wk before irradiation and at 3, 6, and 12 mo after sham or local irradiation. One week after undergoing (13)N-ammonia PET/CT MPI, the irradiation group underwent coronary angiography. Six randomly selected dogs from each group were sacrificed and used to detect pathologic cardiac injury at 3, 6, and 12 mo after irradiation. Results: Compared with the control group and baseline, the irradiation group showed significantly increased perfusion in the irradiated area of the heart at 3 mo after irradiation, perfusion reduction at 6 mo after irradiation, and a perfusion defect at 12 mo after irradiation. There was no significant difference in the left ventricular ejection fraction between the control and irradiation groups at baseline or at 3 mo after irradiation. The irradiation group showed a reduction of left ventricular ejection fraction compared with the control group at 6 mo (50.0% ± 8.1% vs. 59.3% ± 4.1%, P = 0.016) and 12 mo (47.2% ± 6.7% vs. 57.4% ± 3.3%, P = 0.002) after irradiation. No coronary stenosis was observed in the irradiation group. Regional wall motion abnormalities appeared in the irradiated area at 6 mo after irradiation, and its extent was enlarged at 12 mo after irradiation. Pathologic changes were observed; radiation-induced myocardial tissue damage and microvascular fibrosis in the irradiated area progressively increased over time. Conclusion:(13)N-ammonia PET/CT MPI can dynamically detect myocardial perfusion changes together with

  20. Resting State Brain Function Analysis Using Concurrent BOLD in ASL Perfusion fMRI

    PubMed Central

    Zhu, Senhua; Fang, Zhuo; Hu, Siyuan; Wang, Ze; Rao, Hengyi

    2013-01-01

    The past decade has seen astounding discoveries about resting-state brain activity patterns in normal brain as well as their alterations in brain diseases. While the vast majority of resting-state studies are based on the blood-oxygen-level-dependent (BOLD) functional MRI (fMRI), arterial spin labeling (ASL) perfusion fMRI can simultaneously capture BOLD and cerebral blood flow (CBF) signals, providing a unique opportunity for assessing resting brain functions with concurrent BOLD (ccBOLD) and CBF signals. Before taking that benefit, it is necessary to validate the utility of ccBOLD signal for resting-state analysis using conventional BOLD (cvBOLD) signal acquired without ASL modulations. To address this technical issue, resting cvBOLD and ASL perfusion MRI were acquired from a large cohort (n = 89) of healthy subjects. Four widely used resting-state brain function analyses were conducted and compared between the two types of BOLD signal, including the posterior cingulate cortex (PCC) seed-based functional connectivity (FC) analysis, independent component analysis (ICA), analysis of amplitude of low frequency fluctuation (ALFF), and analysis of regional homogeneity (ReHo). Consistent default mode network (DMN) as well as other resting-state networks (RSNs) were observed from cvBOLD and ccBOLD using PCC-FC analysis and ICA. ALFF from both modalities were the same for most of brain regions but were different in peripheral regions suffering from the susceptibility gradients induced signal drop. ReHo showed difference in many brain regions, likely reflecting the SNR and resolution differences between the two BOLD modalities. The DMN and auditory networks showed highest CBF values among all RSNs. These results demonstrated the feasibility of ASL perfusion MRI for assessing resting brain functions using its concurrent BOLD in addition to CBF signal, which provides a potentially useful way to maximize the utility of ASL perfusion MRI. PMID:23750275

  1. ASFNR Recommendations for Clinical Performance of MR Dynamic Susceptibility Contrast Perfusion Imaging of the Brain

    PubMed Central

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

    2016-01-01

    SUMMARY 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. PMID:25907520

  2. Clinical Evaluation of Brain Perfusion SPECT with Brodmann Areas Mapping in Early Diagnosis of Alzheimer's Disease.

    PubMed

    Valotassiou, Varvara; Papatriantafyllou, John; Sifakis, Nikolaos; Tzavara, Chara; Tsougos, Ioannis; Psimadas, Dimitrios; Fezoulidis, Ioannis; Kapsalaki, Eftychia; Hadjigeorgiou, George; Georgoulias, Panagiotis

    2015-01-01

    Early diagnosis of Alzheimer's disease (AD) based on clinical criteria alone may be problematic, while current and future treatments should be administered earlier in order to be more effective. Thus, various disease biomarkers could be used for early detection of AD. We evaluated brain perfusion with 99mTc-HMPAO single photon emission computed tomography (SPECT) and Brodmann areas (BAs) mapping in mild AD using an automated software (NeuroGam) for the semi-quantitative evaluation of perfusion in BAs and the comparison with the software's normal database. We studied 34 consecutive patients with mild AD: 9 men, 25 women, mean age 70.9 ± 8.1 years, mean Mini-Mental State Examination 22.6 ± 2.5. BAs 25L, 25R, 38L, 38R, 28L, 28R, 36L, and 36R had the lower mean perfusion values, while BAs 31L, 31R, 19R, 18L, 18R, 17L, and 17R had the higher mean values. Compared with healthy subjects of the same age, perfusion values in BAs 25L, 25R, 28R, 28L, 36L, and 36R had the greatest deviations from the healthy sample, while the lowest deviations were found in BAs 32L, 32R, 19R, 24L, 17L, 17R, 18L, and 18R. A percentage of ≥94% of patients had perfusion values more than -2SDs below the mean of healthy subjects in BAs 38R, 38L, 36L, 36R, 23L, 23R, 22L, 44L, 28L, 28R, 25L, and 25R. The corresponding proportion was less than 38% for BAs 11L, 19R, 32L, 32R, 18L, 18R, 24L, and 17R. In conclusion, brain SPECT studies with automated perfusion mapping could be useful as an ancillary tool in daily practice, revealing perfusion impairments in early AD.

  3. 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

  4. Management of traumatic brain injury: nursing practice guidelines for cerebral perfusion and brain tissue oxygenation (PbtO2) systems.

    PubMed

    Hession, Diane

    2008-01-01

    Traditional modes of preventing brain cell death in traumatic brain injury (TBI) focus on the enhancement of cerebral perfusion pressure and control of intracranial pressure. Brain tissue oxygenation (PbtO2) monitoring systems are currently available to provide early detection of diminished cerebral oxygenation, and ultimately, ischemia. Research has demonstrated that early detection in PbtO2 is a more delicate measurement of cerebral blood flow and oxygenation. Monitoring PbtO2, in conjunction with cerebral perfusion pressure and intracranial pressure, has been shown to be a better guide to the prevention and treatment of secondary cerebral ischemia. This article reviews TBI, a PbtO2 monitor system description and indications for use, and the importance of nursing practice guidelines and education. With proper guidelines and education, this new technology can be used effectively by bedside clinicians and educators in adult and pediatric intensive care units.

  5. 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

  6. Parkinson's disease-related perfusion and glucose metabolic brain patterns identified with PCASL-MRI and FDG-PET imaging

    PubMed Central

    Teune, Laura K.; Renken, Remco J.; de Jong, Bauke M.; Willemsen, Antoon T.; van Osch, Matthias J.; Roerdink, Jos B.T.M.; Dierckx, Rudi A.; Leenders, Klaus L.

    2014-01-01

    Introduction Under normal conditions, the spatial distribution of resting cerebral blood flow and cerebral metabolic rate of glucose are closely related. A relatively new magnetic resonance (MR) technique, pseudo-continuous arterial spin labeling (PCASL), can be used to measure regional brain perfusion. We identified a Parkinson's disease (PD)-related perfusion and metabolic covariance pattern in the same patients using PCASL and FDG-PET imaging and assessed (dis)similarities in the disease-related pattern between perfusion and metabolism in PD patients. Methods Nineteen PD patients and seventeen healthy controls underwent [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging. Of 14 PD patients and all healthy controls PCASL-MRI could be obtained. Data were analyzed using scaled subprofile model/principal component analysis (SSM/PCA). Results Unique Parkinson's disease-related perfusion and metabolic covariance patterns were identified using PCASL and FDG-PET in the same patients. The PD-related metabolic covariance brain pattern is in high accordance with previously reports. Also our disease-related perfusion pattern is comparable to the earlier described perfusion pattern. The most marked difference between our perfusion and metabolic patterns is the larger perfusion decrease in cortical regions including the insula. Conclusion We identified PD-related perfusion and metabolic brain patterns using PCASL and FDG-PET in the same patients which were comparable with results of existing research. In this respect, PCASL appears to be a promising addition in the early diagnosis of individual parkinsonian patients. PMID:25068113

  7. 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.

  8. Enhanced task related brain activation and resting perfusion in healthy older adults after chronic blueberry supplementation.

    PubMed

    Bowtell, Joanna L; Aboo-Bakkar, Zainie; Conway, Myra; Adlam, Anna-Lynne R; Fulford, Jonathan

    2017-03-01

    Blueberries are rich in flavonoids, which possess antioxidant and anti-inflammatory properties. High flavonoid intakes attenuate age-related cognitive decline, but data from human intervention studies are sparse. We investigated whether 12 weeks of blueberry concentrate supplementation improved brain perfusion, task-related activation and cognitive function in healthy older adults. Participants were randomised to consume either 30 ml blueberry concentrate providing 387 mg anthocyanidins (5 female, 7 male; age 67.5±3.0 y; BMI, 25.9±3.3 kg.m-2) or isoenergetic placebo (8 female, 6 male; age 69.0 ±3.3 y; BMI, 27.1±.4.0 kg.m-2). Pre- and post-supplementation, participants undertook a battery of cognitive function tests and a numerical Stroop test within a 1.5T MRI scanner while functional magnetic resonance images (fMRI) were continuously acquired. Quantitative resting brain perfusion was determined using an arterial spin labelling (ASL) technique, and blood biomarkers of inflammation and oxidative stress were measured. Significant increases in brain activity were observed in response to blueberry supplementation relative to the placebo group within Brodmann areas 4/6/10/21/40/44/45, precuneus, anterior cingulate, and insula/thalamus (p<0.001), as well as significant improvements in grey matter perfusion in the parietal (5.0±1.8 vs -2.9±2.4 %, p=0.013) and occipital (8.0±2.6 vs -0.7±3.2 %, p=0.031) lobes. There was also evidence suggesting improvement in working memory (two back test) after blueberry versus placebo supplementation (p=0.05). Supplementation with an anthocyanin rich blueberry concentrate improved brain perfusion and activation in brain areas associated with cognitive function in healthy older adults.

  9. Deconvolution-Based CT and MR Brain Perfusion Measurement: Theoretical Model Revisited and Practical Implementation Details.

    PubMed

    Fieselmann, Andreas; Kowarschik, Markus; Ganguly, Arundhuti; Hornegger, Joachim; Fahrig, Rebecca

    2011-01-01

    Deconvolution-based analysis of CT and MR brain perfusion data is widely used in clinical practice and it is still a topic of ongoing research activities. In this paper, we present a comprehensive derivation and explanation of the underlying physiological model for intravascular tracer systems. We also discuss practical details that are needed to properly implement algorithms for perfusion analysis. Our description of the practical computer implementation is focused on the most frequently employed algebraic deconvolution methods based on the singular value decomposition. In particular, we further discuss the need for regularization in order to obtain physiologically reasonable results. We include an overview of relevant preprocessing steps and provide numerous references to the literature. We cover both CT and MR brain perfusion imaging in this paper because they share many common aspects. The combination of both the theoretical as well as the practical aspects of perfusion analysis explicitly emphasizes the simplifications to the underlying physiological model that are necessary in order to apply it to measured data acquired with current CT and MR scanners.

  10. Neuroanatomical abnormalities in chronic tinnitus in the human brain

    PubMed Central

    Adjamian, Peyman; Hall, Deborah A.; Palmer, Alan R.; Allan, Thomas W.; Langers, Dave R.M.

    2014-01-01

    In this paper, we review studies that have investigated brain morphology in chronic tinnitus in order to better understand the underlying pathophysiology of the disorder. Current consensus is that tinnitus is a disorder involving a distributed network of peripheral and central pathways in the nervous system. However, the precise mechanism remains elusive and it is unclear which structures are involved. Given that brain structure and function are highly related, identification of anatomical differences may shed light upon the mechanism of tinnitus generation and maintenance. We discuss anatomical changes in the auditory cortex, the limbic system, and prefrontal cortex, among others. Specifically, we discuss the gating mechanism of tinnitus and evaluate the evidence in support of the model from studies of brain anatomy. Although individual studies claim significant effects related to tinnitus, outcomes are divergent and even contradictory across studies. Moreover, results are often confounded by the presence of hearing loss. We conclude that, at present, the overall evidence for structural abnormalities specifically related to tinnitus is poor. As this area of research is expanding, we identify some key considerations for research design and propose strategies for future research. PMID:24892904

  11. Contrast MR of the brain after high-perfusion cardiopulmonary bypass

    SciTech Connect

    Simonson, T.M.; Yuh, W.T.C.; Hindman, B.J.; Embrey, R.P.; Halloran, J.I.; Behrendt, D.M. )

    1994-01-01

    To study the efficacy of contrast MR imaging in the evaluation of central nervous system complications in the cardiopulmonary bypass patient and attempt to explain their pathophysiology based on the MR appearance and the cardiopulmonary bypass protocol. Nineteen patients were prospectively studied with contrast MR examinations the day before and 3 to 7 days after cardiopulmonary bypass, to determine the nature, extent, and number of new postoperative MR abnormalities. Cardiopulmonary bypass parameters used in our institution included: membrane oxygenation, arterial filtration with a pore size of 25 [mu]m, and a relatively high perfusion rate to produce a cardiac index of 2.0 to 2.5 L min per m[sup 2]. The preoperative noncontrast MR examination showed age-related changes and/or signs of ischemia in 60% of patients on the day before surgery. However, there was no abnormal enhancement or new T2 abnormalities on any postoperative MR examination to suggest hypoperfusion or emboli. None of the 19 patients developed overt neurologic deficits postoperatively. Review of the cardiopulmonary bypass protocol used indicated significant variations in technique at different institutions. Contrast MR imaging demonstrated no new abnormalities in patients after cardiopulmonary bypass performed with strict in-line arterial filtration and relatively high perfusion. MR imaging is feasible in the early postoperative period after cardiopulmonary bypass and may offer a convenient method for evaluation of the neurologic impact of technical factors associated with cardiopulmonary bypass. 17 refs.

  12. Neuroendocrine abnormalities in patients with traumatic brain injury.

    PubMed

    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

  13. 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

  14. 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

  15. Structural Brain Abnormalities and Suicidal Behavior in Borderline Personality Disorder

    PubMed Central

    Soloff, Paul H.; Pruitt, Patrick; Sharma, Mohit; Radwan, Jacqueline; White, Richard; Diwadkar, Vaibhav A.

    2012-01-01

    Background Structural brain abnormalities have been demonstrated in subjects with BPD in prefrontal and fronto-limbic regions involved in the regulation of emotion and impulsive behavior, executive cognitive function and episodic memory. Impairment in these cognitive functions is associated with increased vulnerability to suicidal behavior. We compared BPD suicide attempters and non-attempters, high and low lethality attempters to healthy controls to identify neural circuits associated with suicidal behavior in BPD. Methods Structural MRI scans were obtained on 68 BPD subjects (16 male, 52 female), defined by IPDE and DIB/R criteria, and 52 healthy controls (HC: 28 male, 24 female). Groups were compared by diagnosis, attempt status, and attempt lethality. ROIs were defined for areas reported to have structural or metabolic abnormalities in BPD, and included: mid-inf. orbitofrontal cortex, mid-sup temporal cortex, anterior cingulate, insula, hippocampus, amygdala, fusiform, lingual and parahippocampal gyri. Data were analyzed using optimized voxel-based morphometry implemented with DARTEL in SPM5, co-varied for age and gender, corrected for cluster extent (p<.001). Results Compared to HC, BPD attempters had significantly diminished gray matter concentrations in 8 of 9 ROIs, non-attempters in 5 of 9 ROIs. Within the BPD sample, attempters had diminished gray matter in Lt. insula compared to non-attempters. High lethality attempters had significant decreases in Rt. mid-sup. temporal gyrus, Rt. mid-inf. orbitofrontal gyrus, Rt. insular cortex, Lt. fusiform gyrus, Lt. lingual gyrus and Rt. parahippocampal gyrus compared to low lethality attempters. Conclusions Specific structural abnormalities discriminate BPD attempters from non-attempters and high from low lethality attempters. PMID:22336640

  16. 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

  17. Multiphysics simulation of a microfluidic perfusion chamber for brain slice physiology.

    PubMed

    Caicedo, Hector H; Hernandez, Maximiliano; Fall, Christopher P; Eddington, David T

    2010-10-01

    Understanding and optimizing fluid flows through in vitro microfluidic perfusion systems is essential in mimicking in vivo conditions for biological research. In a previous study a microfluidic brain slice device (microBSD) was developed for microscale electrophysiology investigations. The device consisted of a standard perfusion chamber bonded to a polydimethylsiloxane (PDMS) microchannel substrate. Our objective in this study is to characterize the flows through the microBSD by using multiphysics simulations of injections into a pourous matrix to identify optimal spacing of ports. Three-dimensional computational fluid dynamic (CFD) simulations are performed with CFD-ACE + software to model, simulate, and assess the transport of soluble factors through the perfusion bath, the microchannels, and a material that mimics the porosity, permeability and tortuosity of brain tissue. Additionally, experimental soluble factor transport through a brain slice is predicted by and compared to simulated fluid flow in a volume that represents a porous matrix material. The computational results are validated with fluorescent dye experiments.

  18. Brain slice stimulation using a microfluidic network and standard perfusion chamber.

    PubMed

    Shaikh Mohammed, Javeed; Caicedo, Hugo; Fall, Christopher P; Eddington, David T

    2007-01-01

    We have demonstrated the fabrication of a two-level microfluidic device that can be easily integrated with existing electrophysiology setups. The two-level microfluidic device is fabricated using a two-step standard negative resist lithography process. The first level contains microchannels with inlet and outlet ports at each end. The second level contains microscale circular holes located midway of the channel length and centered along with channel width. Passive pumping method is used to pump fluids from the inlet port to the outlet port. The microfluidic device is integrated with off-the-shelf perfusion chambers and allows seamless integration with the electrophysiology setup. The fluids introduced at the inlet ports flow through the microchannels towards the outlet ports and also escape through the circular openings located on top of the microchannels into the bath of the perfusion. Thus the bottom surface of the brain slice placed in the perfusion chamber bath and above the microfluidic device can be exposed with different neurotransmitters. The microscale thickness of the microfluidic device and the transparent nature of the materials [glass coverslip and PDMS (polydimethylsiloxane)] used to make the microfluidic device allow microscopy of the brain slice. The microfluidic device allows modulation (both spatial and temporal) of the chemical stimuli introduced to the brain slice microenvironments.

  19. 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.

  20. Abnormal regional brain function in Parkinson's disease: truth or fiction?

    PubMed

    Ma, Yilong; Tang, Chengke; Moeller, James R; Eidelberg, David

    2009-04-01

    Normalization of regional measurements by the global mean is commonly employed to minimize inter-subject variability in functional imaging studies. This practice is based on the assumption that global values do not substantially differ between patient and control groups. In this issue of NeuroImage, Borghammer and colleagues challenge the validity of this assumption. They focus on Parkinson's disease (PD) and use computer simulations to show that lower global values can produce spurious increases in subcortical brain regions. The authors speculate that the increased signal observed in these areas in PD is artefactual and unrelated to localized changes in brain function. In this commentary, we summarize what is currently known of the relationship between regional and global metabolic activity in PD and experimental parkinsonism. We found that early stage PD patients exhibit global values that are virtually identical to those of age-matched healthy subjects. SPM analysis revealed increased normalized metabolic activity in a discrete set of biologically relevant subcortical brain regions. Because of their higher variability, the corresponding absolute regional measures did not differ across the two groups. Longitudinal imaging studies in this population showed that the subcortical elevations in normalized metabolism appeared earlier and progressed faster than did focal cortical or global metabolic reductions. The observed increases in subcortical activity, but not the global changes, correlated with independent clinical measures of disease progression. Multivariate analysis with SSM/PCA further confirmed that the abnormal spatial covariance structure of early PD is dominated by these subcortical increases as opposed to network-related reductions in cortical metabolic activity or global changes. Thus, increased subcortical activity in PD cannot be regarded as a simple artefact of global normalization. Moreover, stability of the normalized measurements, particularly at

  1. Acquisition of brains from the African elephant (Loxodonta africana): perfusion-fixation and dissection.

    PubMed

    Manger, Paul R; Pillay, Praneshri; Maseko, Busisiwe C; Bhagwandin, Adhil; Gravett, Nadine; Moon, Don-Joon; Jillani, Ngalla; Hemingway, Jason

    2009-04-30

    The current correspondence describes the in situ perfusion-fixation of the brain of the African elephant. Due to both the large size of proboscidean brains and the complex behaviour of these species, the acquisition of good quality material for comparative neuroanatomical analysis from these species is important. Three male African elephants (20-30 years) that were to be culled as part of a larger population management strategy were used. The animals were humanely euthanized and the head removed from the body. Large tubes were inserted into to the carotid arteries and the cranial vasculature flushed with a rapid (20 min) rinse of 100 l of cold saline (4 degrees C). Following the rinse the head was perfusion-fixed with a slower rinse (40 min) of 100 l of cold (4 degrees C) 4% paraformaldehyde in 0.1M phosphate buffer. This procedure resulted in well-fixed neural and other tissue. After perfusion the brains were removed from the skull with the aid of power tools, a procedure taking between 2 and 6h. The brains were immediately post-fixed in the same solution for 72 h at 4 degrees C. The brains were subsequently placed in a sucrose solution and finally an antifreeze solution and are stored in a -20 degrees C freezer. The acquisition of high quality neural material from African elephants that can be used for immunohistochemistry and electron microscopy is of importance in understanding the "hardware" underlying the behaviour of this species. This technique can be used on a variety of large mammals to obtain high quality material for comparative neuroanatomical studies.

  2. Evaluating the Role of Reduced Oxygen Saturation and Vascular Damage in Traumatic Brain Injury Using Magnetic Resonance Perfusion-Weighted Imaging and Susceptibility-Weighted Imaging and Mapping.

    PubMed

    Kou, Zhifeng; Ye, Yongquan; Haacke, Ewart Mark

    2015-10-01

    The cerebral vasculature, along with neurons and axons, is vulnerable to biomechanical insult during traumatic brain injury (TBI). Trauma-induced vascular injury is still an underinvestigated area in TBI research. Cerebral blood flow and metabolism could be important future treatment targets in neural critical care. Magnetic resonance imaging offers a number of key methods to probe vascular injury and its relationship with traumatic hemorrhage, perfusion deficits, venous blood oxygen saturation changes, and resultant tissue damage. They make it possible to image the hemodynamics of the brain, monitor regional damage, and potentially show changes induced in the brain's function not only acutely but also longitudinally following treatment. These methods have recently been used to show that even mild TBI (mTBI) subjects can have vascular abnormalities, and thus they provide a major step forward in better diagnosing mTBI patients.

  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. 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.

  5. Indian-ink perfusion based method for reconstructing continuous vascular networks in whole mouse brain.

    PubMed

    Xue, Songchao; Gong, Hui; Jiang, Tao; Luo, Weihua; Meng, Yuanzheng; Liu, Qian; Chen, Shangbin; Li, Anan

    2014-01-01

    The topology of the cerebral vasculature, which is the energy transport corridor of the brain, can be used to study cerebral circulatory pathways. Limited by the restrictions of the vascular markers and imaging methods, studies on cerebral vascular structure now mainly focus on either observation of the macro vessels in a whole brain or imaging of the micro vessels in a small region. Simultaneous vascular studies of arteries, veins and capillaries have not been achieved in the whole brain of mammals. Here, we have combined the improved gelatin-Indian ink vessel perfusion process with Micro-Optical Sectioning Tomography for imaging the vessel network of an entire mouse brain. With 17 days of work, an integral dataset for the entire cerebral vessels was acquired. The voxel resolution is 0.35×0.4×2.0 µm(3) for the whole brain. Besides the observations of fine and complex vascular networks in the reconstructed slices and entire brain views, a representative continuous vascular tracking has been demonstrated in the deep thalamus. This study provided an effective method for studying the entire macro and micro vascular networks of mouse brain simultaneously.

  6. Indian-Ink Perfusion Based Method for Reconstructing Continuous Vascular Networks in Whole Mouse Brain

    PubMed Central

    Xue, Songchao; Gong, Hui; Jiang, Tao; Luo, Weihua; Meng, Yuanzheng; Liu, Qian; Chen, Shangbin; Li, Anan

    2014-01-01

    The topology of the cerebral vasculature, which is the energy transport corridor of the brain, can be used to study cerebral circulatory pathways. Limited by the restrictions of the vascular markers and imaging methods, studies on cerebral vascular structure now mainly focus on either observation of the macro vessels in a whole brain or imaging of the micro vessels in a small region. Simultaneous vascular studies of arteries, veins and capillaries have not been achieved in the whole brain of mammals. Here, we have combined the improved gelatin-Indian ink vessel perfusion process with Micro-Optical Sectioning Tomography for imaging the vessel network of an entire mouse brain. With 17 days of work, an integral dataset for the entire cerebral vessels was acquired. The voxel resolution is 0.35×0.4×2.0 µm3 for the whole brain. Besides the observations of fine and complex vascular networks in the reconstructed slices and entire brain views, a representative continuous vascular tracking has been demonstrated in the deep thalamus. This study provided an effective method for studying the entire macro and micro vascular networks of mouse brain simultaneously. PMID:24498247

  7. Dynamic contrast-enhanced MRI perfusion for differentiating between melanoma and lung cancer brain metastases.

    PubMed

    Hatzoglou, Vaios; Tisnado, Jamie; Mehta, Alpesh; Peck, Kyung K; Daras, Mariza; Omuro, Antonio M; Beal, Kathryn; Holodny, Andrei I

    2017-04-01

    Brain metastases originating from different primary sites overlap in appearance and are difficult to differentiate with conventional MRI. Dynamic contrast-enhanced (DCE)-MRI can assess tumor microvasculature and has demonstrated utility in characterizing primary brain tumors. Our aim was to evaluate the performance of plasma volume (Vp) and volume transfer coefficient (K(trans) ) derived from DCE-MRI in distinguishing between melanoma and nonsmall cell lung cancer (NSCLC) brain metastases. Forty-seven NSCLC and 23 melanoma brain metastases were retrospectively assessed with DCE-MRI. Regions of interest were manually drawn around the metastases to calculate Vpmean and Kmeantrans. The Mann-Whitney U test and receiver operating characteristic analysis (ROC) were performed to compare perfusion parameters between the two groups. The Vpmean of melanoma brain metastases (4.35, standard deviation [SD] = 1.31) was significantly higher (P = 0.03) than Vpmean of NSCLC brain metastases (2.27, SD = 0.96). The Kmeantrans values were higher in melanoma brain metastases, but the difference between the two groups was not significant (P = 0.12). Based on ROC analysis, a cut-off value of 3.02 for Vpmean (area under curve = 0.659 with SD = 0.074) distinguished between melanoma brain metastases and NSCLC brain metastases (P < 0.01) with 72% specificity. Our data show the DCE-MRI parameter Vpmean can differentiate between melanoma and NSCLC brain metastases. The ability to noninvasively predict tumor histology of brain metastases in patients with multiple malignancies can have important clinical implications.

  8. Evolution and resolution of human brain perfusion responses to the stress of induced hypoglycemia.

    PubMed

    Teh, Ming Ming; Dunn, Joel T; Choudhary, Pratik; Samarasinghe, Yohan; Macdonald, Ian; O'Doherty, Michael; Marsden, Paul; Reed, Laurence J; Amiel, Stephanie A

    2010-11-01

    The relationship between the human brain response to acute stress and subjective, behavioural and physiological responses is poorly understood. We have examined the human cerebral response to the intense interoceptive stressor of hypoglycemia, controlling plasma glucose at either normal fasting concentrations (5 mmol/l, n=7) or at hypoglycemia (2.7 mmol/l, n=10) for 1 h in healthy volunteers. Hypoglycemia was associated with symptomatic responses, counterregulatory neuroendocrine responses and a sequential pattern of brain regional engagement, mapped as changes in relative cerebral perfusion using [(15)O]-H(2)O water positron emission tomography. The early cerebral response comprised activation bilaterally in anterior cingulate cortex (ACC) and thalamic pulvinar, with deactivation in posterior parahippocampal gyrus. Later responses (>20 min) engaged bilateral anterior insula, ventral striatum and pituitary. Following resolution of hypoglycemia, the majority of responses returned to baseline, save persistent engagement of the ACC and sustained elevation of growth hormone and cortisol. Catecholamine responses correlated with increased perfusion in pulvinar and medial thalamus, ACC and pituitary, while growth hormone and cortisol responses showed no correlation with thalamic activation but did show additional correlation with the hypothalamus and ventral striatum bilaterally. These data demonstrate complex dynamic responses to the stressor of hypoglycemia that would be expected to drive physiological and behavioural changes to remedy the state. Further, these data show that sustained stress and its aftermath engage distinct sets of brain regions, providing a neural substrate for adaptive or 'allostasic' responses to stressors.

  9. Brain hemorrhage after endovascular reperfusion therapy of ischemic stroke: a threshold-finding whole-brain perfusion CT study.

    PubMed

    Renú, Arturo; Laredo, Carlos; Tudela, Raúl; Urra, Xabier; Lopez-Rueda, Antonio; Llull, Laura; Oleaga, Laura; Amaro, Sergio; Chamorro, Ángel

    2017-01-01

    Endovascular reperfusion therapy is increasingly used for acute ischemic stroke treatment. The occurrence of parenchymal hemorrhage is clinically relevant and increases with reperfusion therapies. Herein we aimed to examine the optimal perfusion CT-derived parameters and the impact of the duration of brain ischemia for the prediction of parenchymal hemorrhage after endovascular therapy. A cohort of 146 consecutive patients with anterior circulation occlusions and treated with endovascular reperfusion therapy was analyzed. Recanalization was assessed at the end of reperfusion treatment, and the rate of parenchymal hemorrhage at follow-up neuroimaging. In regression analyses, cerebral blood volume and cerebral blood flow performed better than Delay Time maps for the prediction of parenchymal hemorrhage. The most informative thresholds (receiver operating curves) for relative cerebral blood volume and relative cerebral blood flow were values lower than 2.5% of normal brain. In binary regression analyses, the volume of regions with reduced relative cerebral blood volume and/or relative cerebral blood flow was significantly associated with an increased risk of parenchymal hemorrhage, as well as delayed vessel recanalization. These results highlight the relevance of the severity and duration of ischemia as drivers of blood-brain barrier disruption in acute ischemic stroke and support the role of perfusion CT for the prediction of parenchymal hemorrhage.

  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. Changes in Regional Brain Perfusion During Functional Brain Activation: Comparison of [64Cu]-PTSM with [14C]-Iodoantipyrine

    PubMed Central

    Holschneider, DP; Yang, J; Sadler, TR; Galifianakis, NB; Bozorgzadeh, MH; Bading, JR; Conti, PS; Maarek, J-M I

    2008-01-01

    A dilemma in behavioral brain mapping is that conventional techniques immobilize the subject, extinguishing all but the simplest behaviors. This is avoided if brain activation is imaged after completion of the behavior and tissue capture of the tracer. A single-pass flow tracer proposed for positron emission tomography (PET) is a radiolabeled copper(II) complex of pyruvaldehyde bis(N4-methylthiosemicarbazone), [Cu64]-PTSM. [Cu64]-PTSM reaches steady-state cerebral distribution more rapidly than the metabolic tracer [18F]-fluorodeoxyglucose, allowing imaging with substantially greater temporal resolution. Using dual-label autoradiography, this study compares the relative regional cerebral blood flow tracer distribution (CBF-TR) of [64Cu]-PTSM to that of the classic perfusion tracer [14C]-iodoantipyrine in a rat model during treadmill walking. Rats were exposed to continuous walking on a treadmill and compared to quiescent controls. [64Cu]-PTSM was bolus injected (iv) after 1 minute, followed by a 5 minute uptake and subsequent bolus injection of [14C]-iodoantipyrine. CBF-TR was quantified by autoradiography and analyzed in the three-dimensionally reconstructed brain by statistical parametric mapping, as well as by region-of-interest analysis. A high homology was found between the [64Cu]-PTSM and [14C]-iodoantipyrine patterns of cerebral activation in cortical and subcortical regions. For white matter, however, [64Cu]-PTSM showed lower perfusion than [14Cu]-iodoantipyrine. [64Cu]-PTSM is a useful tracer for functional brain mapping in freely-moving subjects. Its application in conjunction with PET promises to increase our understanding of the neural circuitry of behaviors dependent on locomotion. PMID:18687316

  12. Total Coronary Atherosclerotic Plaque Burden Assessment by CT Angiography for Detecting Obstructive Coronary Artery Disease Associated with Myocardial Perfusion Abnormalities

    PubMed Central

    Kishi, Satoru; Magalhães, Tiago A.; Cerci, Rodrigo J.; Matheson, Matthew B.; Vavere, Andrea; Tanami, Yutaka; Kitslaar, Pieter H.; George, Richard T.; Brinker, Jeffrey; Miller, Julie M.; Clouse, Melvin E.; Lemos, Pedro A.; Niinuma, Hiroyuki; Reiber, Johan H.C.; Rochitte, Carlos E.; Rybicki, Frank J.; Di Carli, Marcelo F.; Cox, Christopher; Lima, Joao A.C.; Arbab-Zadeh, Armin

    2016-01-01

    Background Total atherosclerotic plaque burden assessment by CT angiography (CTA) is a promising tool for diagnosis and prognosis of coronary artery disease (CAD) but its validation is restricted to small clinical studies. We tested the feasibility of semi-automatically derived coronary atheroma burden assessment for identifying patients with hemodynamically significant CAD in a large cohort of patients with heterogenous characteristics. Methods This study focused on the CTA component of the CORE320 study population. A semi-automated contour detection algorithm quantified total coronary atheroma volume defined as the difference between vessel and lumen volume. Percent atheroma volume (PAV = [total atheroma volume/total vessel volume]×100) was the primary metric for assessment (n=374). The area under the receiver operating characteristic curve (AUC) determined the diagnostic accuracy for identifying patients with hemodynamically significant CAD defined as ≥50% stenosis by quantitative coronary angiography and associated myocardial perfusion abnormality by SPECT. Results Of 374 patients, 139 (37%) had hemodynamically significant CAD. The AUC for PAV was 0.78 (95% confidence interval [CI] 0.73–0.83) compared to 0.84 [0.79–0.88] by standard expert CTA interpretation (p=0.02). Accuracy for both CTA (0.91 [0.87, 0.96]) and PAV (0.86 [0.81–0.91]) increased after excluding patients with history of CAD (p<0.01 for both). Bland-Altman analysis revealed good agreement between two observers ( bias of 280.2 mm3 [161.8, 398.7]). Conclusions A semi-automatically derived index of total coronary atheroma volume yields good accuracy for identifying patients with hemodynamically significant CAD, though marginally inferior to CTA expert reading. These results convey promise for rapid, reliable evaluation of clinically relevant CAD. PMID:26817414

  13. Structural and diffusional brain abnormality related to relatively low level alcohol consumption.

    PubMed

    Sasaki, Hiroki; Abe, Osamu; Yamasue, Hidenori; Fukuda, Rin; Yamada, Haruyasu; Takei, Kunio; Suga, Motomu; Takao, Hidemasa; Kasai, Kiyoto; Aoki, Shigeki; Ohtomo, Kuni

    2009-06-01

    Chronic excessive alcohol intake results in alcohol-related brain damage. Many previous reports have documented alcohol-related global or local brain shrinkage or diffusional abnormalities among alcoholics and heavy to moderate drinkers; however, the influence of relatively low levels of alcohol consumption on brain structural or diffusional abnormality is unclear. We investigated structural or diffusional abnormalities related to lifetime alcohol consumption (LAC) using voxel-based morphometry (VBM) among Japanese non-alcohol-dependent individuals (114 males, 97 females). High-resolution three-dimensional magnetic resonance images and diffusion tensor imaging were acquired in all subjects. The collected images were normalized, segmented, and smoothed using SPM 5. Gray matter volume (GMV) and white matter volume (WMV) were normalized for each total intracranial volume (TIV), and partial correlation coefficients were estimated between normalized GMV or WMV and lifetime alcohol consumption (LAC) adjusted for age. To investigate regional GMV or WMV abnormalities related to LAC, multiple regression analyses were performed among regional GMV or WMV and LAC, age, and TIV. To investigate subtle regional abnormalities, multiple regression analyses were performed among fractional anisotropy (FA) or mean diffusivity (MD), and LAC and age. No LAC-related global or regional GMV or WMV abnormality or LAC-related regional FA abnormality was found among male or female subjects. Significant LAC-related MD increase was found in the right amygdala among female subjects only. The current results suggest female brain vulnerability to alcohol, and a relation between subtle abnormality in the right amygdala and alcohol misuse.

  14. Cerebral perfusion pressure directed therapy following traumatic brain injury and hypotension in swine.

    PubMed

    Malhotra, Ajai K; Schweitzer, John B; Fox, Jerry L; Fabian, Timothy C; Proctor, Kenneth G

    2003-09-01

    There is a paucity of studies, clinical and experimental, attesting to the benefit of cerebral perfusion pressure (CPP) directed pressor therapy following traumatic brain injury (TBI). The current study evaluates this therapy in a swine model of TBI and hypotension. Forty-five anesthetized and ventilated swine received TBI followed by a 45% blood volume bleed. After 1 h, all animals were resuscitated with 0.9% sodium chloride equal to three times the shed blood volume. The experimental group (PHE) received phenylephrine to maintain CPP > 80 mm Hg; the control group (SAL) did not. Outcomes in the first phase (n = 33) of the study were as follows: cerebro-venous oxygen saturation (S(cv)O(2)), cerebro-vascular carbon dioxide reactivity (DeltaS(cv)O(2)), and brain structural damage (beta-amyloid precursor protein [betaAPP] immunoreactivity). In the second phase (n = 12) of the study, extravascular blood free water (EVBFW) was measured in the brain and lung. After resuscitation, intracranial and mean arterial pressures were >15 and >80 mm Hg, respectively, in both groups. CPP declined to 64 +/- 5 mm Hg in the SAL group, despite fluid supplements. CPP was maintained at >80 mm Hg with pressors in the PHE group. PHE animals maintained better S(cv)O(2) (p < 0.05 at 180, 210, 240, 270, and 300 min post-TBI). At baseline, 5% CO(2) evoked a 16 +/- 4% increase in S(cv)O(2), indicating cerebral vasodilatation and luxury perfusion. By 240 min, this response was absent in SAL animals and preserved in PHE animals (p < 0.05). Brain EVBFW was higher in SAL animals; however, lung EVBFW was higher in PHE animals. There was no difference in betaAPP immunoreactivity between the SAL and PHE groups (p > 0.05). In this swine model of TBI and hypotension, CPP directed pressor therapy improved brain oxygenation and maintained cerebro-vascular CO(2) reactivity. Brain edema was lower, but lung edema was greater, suggesting a higher propensity for pulmonary complications.

  15. Multiple resting state network functional connectivity abnormalities in mild traumatic brain injury.

    PubMed

    Stevens, Michael C; Lovejoy, David; Kim, Jinsuh; Oakes, Howard; Kureshi, Inam; Witt, Suzanne T

    2012-06-01

    Several reports show that traumatic brain injury (TBI) results in abnormalities in the coordinated activation among brain regions. Because most previous studies examined moderate/severe TBI, the extensiveness of functional connectivity abnormalities and their relationship to postconcussive complaints or white matter microstructural damage are unclear in mild TBI. This study characterized widespread injury effects on multiple integrated neural networks typically observed during a task-unconstrained "resting state" in mild TBI patients. Whole brain functional connectivity for twelve separate networks was identified using independent component analysis (ICA) of fMRI data collected from thirty mild TBI patients mostly free of macroscopic intracerebral injury and thirty demographically-matched healthy control participants. Voxelwise group comparisons found abnormal mild TBI functional connectivity in every brain network identified by ICA, including visual processing, motor, limbic, and numerous circuits believed to underlie executive cognition. Abnormalities not only included functional connectivity deficits, but also enhancements possibly reflecting compensatory neural processes. Postconcussive symptom severity was linked to abnormal regional connectivity within nearly every brain network identified, particularly anterior cingulate. A recently developed multivariate technique that identifies links between whole brain profiles of functional and anatomical connectivity identified several novel mild TBI abnormalities, and represents a potentially important new tool in the study of the complex neurobiological sequelae of TBI.

  16. Brain white matter abnormality in a newborn infant with congenital adrenal hyperplasia.

    PubMed

    Kaga, Akimune; Saito-Hakoda, Akiko; Uematsu, Mitsugu; Kamimura, Miki; Kanno, Junko; Kure, Shigeo; Fujiwara, Ikuma

    2013-10-01

    Several studies have described brain white matter abnormalities on magnetic resonance imaging (MRI) in children and adults with congenital adrenal hyperplasia (CAH), while the brain MRI findings of newborn infants with CAH have not been clarified. We report a newborn boy with CAH who presented brain white matter abnormality on MRI. He was diagnosed as having salt-wasting CAH with a high 17-OHP level at neonatal screening and was initially treated with hydrocortisone at 8 days of age. On day 11 after birth, he had a generalized tonic seizure. No evidence of serum electrolyte abnormalities was observed. Brain MRI revealed white matter abnormalities that consisted of bilateral small diffuse hyperintensities on T1-weighted images with slightly low intensity on T2-weighted images in the watershed area. Several factors associated with brain white matter abnormalities in adults with CAH, such as increasing age, hypertension, diabetes and corticosteroid replacement, were not applicable. Although the cause of the phenomenon in this case is unclear, brain white matter abnormality could be observed in newborn infants with CAH as well as in adult patients.

  17. Real-time ultrasound brain perfusion imaging with analysis of microbubble replenishment in acute MCA stroke.

    PubMed

    Kern, Rolf; Diels, Anna; Pettenpohl, Johanna; Kablau, Micha; Brade, Joachim; Hennerici, Michael G; Meairs, Stephen

    2011-08-01

    Real-time ultrasound perfusion imaging (rt-UPI) allows visualization of microbubbles flowing through the cerebral microvasculature. We hypothesized that analysis of microbubble tissue replenishment would enable for characterization of perfusion deficits in acute middle cerebral artery (MCA) territory stroke. Twenty-three patients (mean age 70.2 ± 13.2 years, 9 weeks) were included. Sequential images of bubble replenishment were acquired by transcranial rt-UPI at low mechanical index immediately after microbubble destruction. Different parameters were calculated from regions of interest (ROIs): real-time time to peak (rt-TTP), rise rate (β), and plateau (A) of acoustic intensity, and A × β was used as an index of blood flow. Results were compared with diffusion-weighted and perfusion magnetic resonance imaging. Parameters of rt-UPI had lower values in ROIs of ischemic as compared with normal tissue (β=0.58 ± 0.40 versus 1.25 ± 0.83; P=0.001; A=1.44 ± 1.75 versus 2.63 ± 2.31; P=0.05; A × β=1.14 ± 2.25 versus 2.98 ± 2.70; P=0.01). Real-time time to peak was delayed in ischemic tissue (11.43 ± 2.67 versus 8.88 ± 1.66 seconds; P<0.001). From the analysis of receiver operating characteristic curves, β and A × β had the largest areas under the curve with optimal cutoff values of β<0.76 and A × β<1.91. We conclude that rt-UPI with analysis of microbubble replenishment correctly identifies ischemic brain tissue in acute MCA stroke.

  18. 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

  19. Abnormalities of the neonatal brain: MR imaging. Part II. Hypoxic-ischemic brain injury.

    PubMed

    McArdle, C B; Richardson, C J; Hayden, C K; Nicholas, D A; Amparo, E G

    1987-05-01

    Eighty-five infants, 82 of whom were 29-44 weeks postconceptional age, were imaged with a 0.6-T magnet. Eight infants had cerebral infarction. In premature neonates with very water, low-intensity white matter on T1-weighted images, ultrasound was better than both computed tomography and magnetic resonance (MR) imaging in depicting parenchymal changes of infarction or edema. However, after 37 weeks gestation, MR imaging was superior. Cerebral atrophy, present in seven infants, was consistent with subarachnoid space widths of 7 mm or more, or subarachnoid space widths of 5-6 mm with ventricular/brain ratios of 0.36 or greater. Delayed myelination was seen in a total of 18 infants with histories of hypoxic-ischemic insult. MR imaging shows promise in the neonatal period. It facilitates recognition of infarcts in full-term infants and may be used to predict abnormal neurologic outcome in infants who have initial delayed myelination.

  20. 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…

  1. Abnormalities in Human Brain Creatine Metabolism in Gulf War Illness Probed with MRS

    DTIC Science & Technology

    2014-12-01

    TYPE Final 3. DATES COVERED 30 Sep 2012 - 29 Sep 2014 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Abnormalities in Human Brain Creatine Metabolism in...1H transverse relaxation times (T2s) of the methyl peaks of the molecules phosphocreatine (PCr) and free creatine (Cr) in brains of ill and well

  2. Functional brain networks and abnormal connectivity in the movement disorders

    PubMed Central

    Poston, Kathleen L.; Eidelberg, David

    2012-01-01

    Clinical manifestations of movement disorders, such as Parkinson’s disease (PD) and dystonia, arise from neurophysiological changes within the cortico-striato-pallidothalamocortical (CSPTC) and cerebello-thalamo-cortical (CbTC) circuits. Neuroimaging techniques that probe connectivity within these circuits can be used to understand how these disorders develop as well as identify potential targets for medical and surgical therapies. Indeed, network analysis of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) has identified abnormal metabolic networks associated with the cardinal motor symptoms of PD, such as akinesia and tremor, as well as PD-related cognitive dysfunction. More recent task-based and resting state functional magnetic resonance imaging studies have reproduced several of the altered connectivity patterns identified in these abnormal PD-related networks. A similar network analysis approach in dystonia revealed abnormal disease related metabolic patterns in both manifesting and non-manifesting carriers of dystonia mutations. Other multimodal imaging approaches using magnetic resonance diffusion tensor imaging in patients with primary genetic dystonia suggest abnormal connectivity within the CbTC circuits mediate the clinical manifestations of this inherited neurodevelopmental disorder. Ongoing developments in functional imaging and future studies in early patients are likely to enhance our understanding of these movement disorders and guide novel targets for future therapies. PMID:22206967

  3. 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.

  4. Brain abnormalities in antisocial individuals: implications for the law.

    PubMed

    Yang, Yaling; Glenn, Andrea L; Raine, Adrian

    2008-01-01

    With the increasing popularity in the use of brain imaging on antisocial individuals, an increasing number of brain imaging studies have revealed structural and functional impairments in antisocial, psychopathic, and violent individuals. This review summarizes key findings from brain imaging studies on antisocial/aggressive behavior. Key regions commonly found to be impaired in antisocial populations include the prefrontal cortex (particularly orbitofrontal and dorsolateral prefrontal cortex), superior temporal gyrus, amygdala-hippocampal complex, and anterior cingulate cortex. Key functions of these regions are reviewed to provide a better understanding on how deficits in these regions may predispose to antisocial behavior. Objections to the use of imaging findings in a legal context are outlined, and alternative perspectives raised. It is argued that brain dysfunction is a risk factor for antisocial behavior and that it is likely that imaging will play an increasing (albeit limited) role in legal decision-making.

  5. 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

  6. Mutations in LAMB1 cause cobblestone brain malformation without muscular or ocular abnormalities.

    PubMed

    Radmanesh, Farid; Caglayan, Ahmet Okay; Silhavy, Jennifer L; Yilmaz, Cahide; Cantagrel, Vincent; Omar, Tarek; Rosti, Başak; Kaymakcalan, Hande; Gabriel, Stacey; Li, Mingfeng; Sestan, Nenad; Bilguvar, Kaya; Dobyns, William B; Zaki, Maha S; Gunel, Murat; Gleeson, Joseph G

    2013-03-07

    Cobblestone brain malformation (COB) is a neuronal migration disorder characterized by protrusions of neurons beyond the first cortical layer at the pial surface of the brain. It is usually seen in association with dystroglycanopathy types of congenital muscular dystrophies (CMDs) and ocular abnormalities termed muscle-eye-brain disease. Here we report homozygous deleterious mutations in LAMB1, encoding laminin subunit beta-1, in two families with autosomal-recessive COB. Affected individuals displayed a constellation of brain malformations including cortical gyral and white-matter signal abnormalities, severe cerebellar dysplasia, brainstem hypoplasia, and occipital encephalocele, but they had less apparent ocular or muscular abnormalities than are typically observed in COB. LAMB1 is localized to the pial basement membrane, suggesting that defective connection between radial glial cells and the pial surface mediated by LAMB1 leads to this malformation.

  7. Mutations in LAMB1 Cause Cobblestone Brain Malformation without Muscular or Ocular Abnormalities

    PubMed Central

    Radmanesh, Farid; Caglayan, Ahmet Okay; Silhavy, Jennifer L.; Yilmaz, Cahide; Cantagrel, Vincent; Omar, Tarek; Rosti, Başak; Kaymakcalan, Hande; Gabriel, Stacey; Li, Mingfeng; Šestan, Nenad; Bilguvar, Kaya; Dobyns, William B.; Zaki, Maha S.; Gunel, Murat; Gleeson, Joseph G.

    2013-01-01

    Cobblestone brain malformation (COB) is a neuronal migration disorder characterized by protrusions of neurons beyond the first cortical layer at the pial surface of the brain. It is usually seen in association with dystroglycanopathy types of congenital muscular dystrophies (CMDs) and ocular abnormalities termed muscle-eye-brain disease. Here we report homozygous deleterious mutations in LAMB1, encoding laminin subunit beta-1, in two families with autosomal-recessive COB. Affected individuals displayed a constellation of brain malformations including cortical gyral and white-matter signal abnormalities, severe cerebellar dysplasia, brainstem hypoplasia, and occipital encephalocele, but they had less apparent ocular or muscular abnormalities than are typically observed in COB. LAMB1 is localized to the pial basement membrane, suggesting that defective connection between radial glial cells and the pial surface mediated by LAMB1 leads to this malformation. PMID:23472759

  8. EEG abnormalities in clinically diagnosed brain death organ donors in Iranian tissue bank.

    PubMed

    Tavakoli, Seyed Amir Hossein; Khodadadi, Abbas; Azimi Saein, Amir Reza; Bahrami-Nasab, Hasan; Hashemi, Behnam; Tirgar, Niloufar; Nozary Heshmati, Behnaz

    2012-01-01

    Brain death is defined as the permanent, irreversible and concurrent loss of all brain and brain stem functions. Brain death diagnosis is based on clinical criteria and it is not routine to use paraclinical studies. In some countries, electroencephalogram (EEG) is performed in all patients for the determination of brain death while there is some skepticism in relying on EEG as a confirmatory test for brain death diagnosis. In this study, we assessed the validity of EEG and its abnormalities in brain death diagnosis. In this retrospective study, we used 153 EEGs from medical records of 89 brain death patients in organ procurement unit of the Iranian Tissue Bank admitted during 2002-2008. We extracted and analyzed information including EEGs, which were examined by a neurologist for waves, artifacts and EEG abnormalities. The mean age of the patients was 27.2±12.7 years. The most common cause of brain death was multiple traumas due to accident (65%). The most prevalent artifact was electrical transformer. 125 EEGs (82%) were isoelectric (ECS) and seven EEGs (5%) were depictive of some cerebral activity which upon repeat EEGs, they showed ECS patterns too. There was no relationship between cause of brain death and cerebral activity in EEGs of the patients. In this study, we could confirm ECS patterns in all brain death patients whose status had earlier been diagnosed clinically. Considering the results of this study, it seems sensible to perform EEG as a final confirmatory test as an assurance to the patients' families.

  9. d-Amino Acid Levels in Perfused Mouse Brain Tissue and Blood: A Comparative Study.

    PubMed

    Weatherly, Choyce A; Du, Siqi; Parpia, Curran; Santos, Polan T; Hartman, Adam L; Armstrong, Daniel W

    2017-02-16

    The l-enantiomer is the predominant type of amino acid in all living systems. However, d-amino acids, once thought to be "unnatural", have been found to be indigenous even in mammalian systems and increasingly appear to be functioning in essential biological and neurological roles. Both d- and l-amino acid levels in the hippocampus, cortex, and blood samples from NIH Swiss mice are reported. Perfused brain tissues were analyzed for the first time, thereby eliminating artifacts due to endogenous blood, and decreased the mouse-to-mouse variability in amino acid levels. Total amino acid levels (l- plus d-enantiomers) in brain tissue are up to 10 times higher than in blood. However, all measured d-amino acid levels in brain tissue are typically ∼10 to 2000 times higher than blood levels. There was a 13% reduction in almost all measured d-amino acid levels in the cortex compared to those in the hippocampus. There is an approximate inverse relationship between the prevalence of an amino acid and the percentage of its d-enantiomeric form. Interestingly, glutamic acid, unlike all other amino acids, had no quantifiable level of its d-antipode. The bioneurological reason for the unique and conspicuous absence/removal of this d-amino acid is yet unknown. However, results suggest that d-glutamate metabolism is likely a unidirectional process and not a cycle, as per the l-glutamate/glutamine cycle. The results suggest that there might be unreported d-amino acid racemases in mammalian brains. The regulation and function of specific other d-amino acids are discussed.

  10. 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…

  11. 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.…

  12. 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

  13. 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

  14. 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.

  15. 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.

  16. Role of magnetic resonance spectroscopy in evaluation of congenital/developmental brain abnormalities.

    PubMed

    Shekdar, Karuna; Wang, Dah-Jyuu

    2011-12-01

    Magnetic resonance spectroscopy (MRS) is an invaluable tool to study brain development and in vivo metabolism of brain. MRS is a noninvasive method and also does not involve ionizing radiation. The spectral patterns obtained from MRS evaluation provide unique information about the neonatal brain in several disease processes including hypoxic-ischemic injury, white matter and metabolic disorders, seizure disorders, and brain tumors. MRS also provides quantitative information about specific metabolites that is useful in the diagnosis and in evaluating treatment response of the disease. This discussion is limited to the use of MRS in evaluation of congenital or developmental brain abnormalities. The discussion of clinical utility of MRS is preceded by a brief overview of the technical aspects of MRS, followed by description of normal brain spectra in the neonates and the changes with normal brain development.

  17. 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

  18. 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

  19. Assessment of the ability of myocardial contrast echocardiography with harmonic power Doppler imaging to identify perfusion abnormalities in patients with Kawasaki disease at rest and during dipyridamole stress.

    PubMed

    Ishii, M; Himeno, W; Sawa, M; Iemura, M; Furui, J; Muta, H; Sugahara, Y; Egami, K; Akagi, T; Ishibashi, M; Kato, H

    2002-01-01

    The aim of our study was to assess the ability of myocardial contrast echocardiography (MCE) with harmonic power Doppler imaging (HPDI) to identify perfusion abnormalities in patients with Kawasaki disease at rest and during pharmacological stress imaging with dipyridamole. Results were compared with those of 99mTc-tetrofosmin single-photon emission computed tomography (SPECT) imaging as the clinical reference standard. MCE with HPDI was performed on 20 patients with a history of Kawasaki disease. Images were obtained at baseline and during dipyridamole infusion (0.56 mg x kg(-1)) in the apical two- and four-chamber views. Myocardial opacification suitable for the analysis was obtained in all patients. Nine patients with stenotic lesions had a reversible defect after dipyridamole infusion detected by both MCE with HPDI and SPECT, and 3 patients with a history of myocardial infarction had a partially or completely irreversible defect detected by both methods. Three patients with coronary aneurysm without stenotic lesion, 4 patients with regressed coronary aneurysm, and 2 patients with normal coronary artery in acute phase also had normal perfusion at rest and after pharmacological stress by both methods. A 96% concordance (kappa = 0.87) was obtained when comparing the respective segmental perfusion scores using the two methods at baseline, and an 86% concordance (kappa = 0.81) was obtained at postdipyridamole infusion. After combining baseline and postdipyridamole images, each segment was labeled as having normal perfusion, irreversible defects, or reversible defects. Using these classifications, concordance for the two methods was 92% (kappa = 0.87). MCE with HPDI is a safe and feasible method by which to detect asymptomatic ischemia due to severe stenotic lesion, and it may be an important addition to the modalities used to identify patients at risk for myocardial infarction as a complication of Kawasaki disease.

  20. 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

  1. Microstructural Abnormalities Were Found in Brain Gray Matter from Patients with Chronic Myofascial Pain

    PubMed Central

    Xie, Peng; Qin, Bangyong; Song, Ganjun; Zhang, Yi; Cao, Song; Yu, Jin; Wu, Jianjiang; Wang, Jiang; Zhang, Tijiang; Zhang, Xiaoming; Yu, Tian; Zheng, Hong

    2016-01-01

    Myofascial pain, presented as myofascial trigger points (MTrPs)-related pain, is a common, chronic disease involving skeletal muscle, but its underlying mechanisms have been poorly understood. Previous studies have revealed that chronic pain can induce microstructural abnormalities in the cerebral gray matter. However, it remains unclear whether the brain gray matters of patients with chronic MTrPs-related pain undergo alteration. In this study, we employed the Diffusion Kurtosis Imaging (DKI) technique, which is particularly sensitive to brain microstructural perturbation, to monitor the MTrPs-related microstructural alterations in brain gray matter of patients with chronic pain. Our results revealed that, in comparison with the healthy controls, patients with chronic myofascial pain exhibited microstructural abnormalities in the cerebral gray matter and these lesions were mainly distributed in the limbic system and the brain areas involved in the pain matrix. In addition, we showed that microstructural abnormalities in the right anterior cingulate cortex (ACC) and medial prefrontal cortex (mPFC) had a significant negative correlation with the course of disease and pain intensity. The results of this study demonstrated for the first time that there are microstructural abnormalities in the brain gray matter of patients with MTrPs-related chronic pain. Our findings may provide new insights into the future development of appropriate therapeutic strategies to this disease. PMID:28066193

  2. 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

  3. Relationships between perfusion defects and static brain scan positivity in patients with ischaemic completed stroke: considerations about the origin of the increased uptake

    PubMed Central

    Bartolini, Alfredo

    1982-01-01

    The relation between perfusion defects shown by radionuclide angiography and static brain scan positivity was evaluated in patients with ischaemic completed stroke at various intervals from the onset of symptoms. An inverse relation between radionuclide angiography and static scan positivity was found for the period within 15 days of the onset of symptoms. The possible relation between changes in perfusion and static brain scan positivity is discussed. PMID:6279782

  4. Characterization of technetium-99m-L,L-ECD for brain perfusion imaging, Part 2: Biodistribution and brain imaging in humans.

    PubMed

    Léveillé, J; Demonceau, G; De Roo, M; Rigo, P; Taillefer, R; Morgan, R A; Kupranick, D; Walovitch, R C

    1989-11-01

    The safety, biodistribution and kinetics of a new perfusion imaging agent [99mTc-L,L]-ethyl cysteinate dimer (ECD) was evaluated in normal volunteers. Technetium-99m-L,L-ECD is a neutral, lipophilic complex, which is radiochemically pure and stable. Twelve healthy adults were injected with 25-30 mCi of 99mTc-L,L-ECD and imaged periodically for up to 24 hr. Planar imaging showed rapid brain uptake with a peak concentration of 4.9% injected dose and very slow brain washout (approximately 6% per hour during the first 6 hr). Repeat or dynamic tomographic imaging of the brain using either a rotating gamma camera or a multidetector system was performed up to 6 hr postinjection. The distribution of 99mTc-L,L-ECD in the brain did not change and was similar to the pattern seen with other perfusion agents. Background facial areas and lungs cleared rapidly. Peak blood activity was below 10% injected dose at all times and 99mTc-L,L-ECD cleared rapidly through the kidneys. Vital signs, blood and urine chemistries were normal in all volunteers and no adverse reactions were noted. These results suggest that 99mTc-L,L-ECD should be useful for routine assessment of cerebral perfusion in humans.

  5. Gray matter abnormalities in pediatric mild traumatic brain injury.

    PubMed

    Mayer, Andrew R; Hanlon, Faith M; Ling, Josef M

    2015-05-15

    Pediatric mild traumatic brain injury (pmTBI) is the most prevalent neurological insult in children and is associated with both acute and chronic neuropsychiatric sequelae. However, little is known about underlying pathophysiology changes in gray matter diffusion and atrophy from a prospective stand-point. Fifteen semi-acute pmTBI patients and 15 well-matched healthy controls were evaluated with a clinical and neuroimaging battery, with a subset of participants returning for a second visit. Clinical measures included tests of attention, processing speed, executive function, working memory, memory, and self-reported post-concussive symptoms. Measures of diffusion (fractional anisotropy [FA]) and atrophy were also obtained for cortical and subcortical gray matter structures to characterize effects of injury as a function of time. Patients exhibited decreased scores in the domains of attention and processing speed relative to controls during the semi-acute injury stage, in conjunction with increased anisotropic diffusion in the left superior temporal gyrus and right thalamus. Evidence of increased diffusion in these regions was also present at four months post-injury, with performance on cognitive tests partially normalizing. In contrast, signs of cortical atrophy in bilateral frontal areas and other left-hemisphere cortical areas only emerged at four months post-injury for patients. Current results suggest potentially differential time-courses of recovery for neurobehavioral markers, anisotropic diffusion and atrophy following pmTBI. Importantly, these data suggest that relying on patient self-report or standard clinical assessments may underestimate the time for true injury recovery.

  6. 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.

  7. Comparison of BOLD cerebrovascular reactivity mapping and DSC MR perfusion imaging for prediction of neurovascular uncoupling potential in brain tumors.

    PubMed

    Pillai, Jay J; Zacà, Domenico

    2012-08-01

    metrics obtained by T2* gadolinium perfusion MR imaging were compared to BOLD percentage signal change on BH CVR maps in a group of 19 patients with intracranial brain tumors of different nature and grade. Single pixel maximum rCBV and rCBF within holotumoral regions of interest (i.e., "ipsilesional" ROIs) were normalized to contralateral hemispheric homologous (i.e., "contralesional") normal tissue. Furthermore, percentage signal change on BH CVR maps within ipsilesional ROIs were normalized to the percentage signal change within contralesional homologous ROIs. Inverse linear correlation was found between normalized rCBF (r(flow)) or rCBV (r(vol)) and normalized CVR percentage signal change (r(CVR)) in grade IV lesions. In the grade III lesions a less steep inverse linear trend was seen that did not reach statistical significance, whereas no correlation at all was seen in the grade II group. Statistically significant difference was present for r(flow) and r(vol) between the grade II and IV groups and between the grade III and IV groups but not for r(CVR). The r(CVR) was significantly lower than 1 in every group. Our results demonstrate that while T2*MR perfusion maps and CVR maps are both adequate to map tumoral regions at risk of NVU in high grade gliomas, CVR maps can detect areas of decreased CVR also in low and intermediate grade gliomas where NVU may be caused by factors other than tumor neovascularity alone. Comparison of areas of abnormally decreased regional CVR with areas of absent BOLD task-based activation in expected eloquent cortical regions infiltrated by or adjacent to the tumors revealed overall 95% concordance, thus confirming the capability of BH CVR mapping to effectively demonstrate areas of NVU. ed by factors other than tumor neovascularity alone. Comparison of areas of abnormally decreased regional CVR with areas of absent BOLD task-based activation in expected eloquent cortical regions infiltrated by or adjacent to the tumors revealed overall 95

  8. 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

  9. TU-AB-204-01: Advances in C-Arm CBCT for Brain Perfusion Imaging

    SciTech Connect

    Chen, G.

    2015-06-15

    This symposium highlights advanced cone-beam CT (CBCT) technologies in four areas of emerging application in diagnostic imaging and image-guided interventions. Each area includes research that extends the spatial, temporal, and/or contrast resolution characteristics of CBCT beyond conventional limits through advances in scanner technology, acquisition protocols, and 3D image reconstruction techniques. Dr. G. Chen (University of Wisconsin) will present on the topic: Advances in C-arm CBCT for Brain Perfusion Imaging. Stroke is a leading cause of death and disability, and a fraction of people having an acute ischemic stroke are suitable candidates for endovascular therapy. Critical factors that affect both the likelihood of successful revascularization and good clinical outcome are: 1) the time between stroke onset and revascularization; and 2) the ability to distinguish patients who have a small volume of irreversibly injured brain (ischemic core) and a large volume of ischemic but salvageable brain (penumbra) from patients with a large ischemic core and little or no penumbra. Therefore, “time is brain” in the care of the stroke patients. C-arm CBCT systems widely available in angiography suites have the potential to generate non-contrast-enhanced CBCT images to exclude the presence of hemorrhage, time-resolved CBCT angiography to evaluate the site of occlusion and collaterals, and CBCT perfusion parametric images to assess the extent of the ischemic core and penumbra, thereby fulfilling the imaging requirements of a “one-stop-shop” in the angiography suite to reduce the time between onset and revascularization therapy. The challenges and opportunities to advance CBCT technology to fully enable the one-stop-shop C-arm CBCT platform for brain imaging will be discussed. Dr. R. Fahrig (Stanford University) will present on the topic: Advances in C-arm CBCT for Cardiac Interventions. With the goal of providing functional information during cardiac interventions

  10. 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.

  11. Two Cases of Oral Somatic Delusions Ameliorated With Brain Perfusion Asymmetry: A Case Report

    PubMed Central

    Umezaki, Yojiro; Uezato, Akihito; Toriihara, Akira; Nishikawa, Toru; Toyofuku, Akira

    2017-01-01

    Background Oral cenesthopathy is the complaint of abnormal oral sensation where no underlying organic cause can be identified. It is also called oral dysesthesia or oral somatic delusion and classified as delusional disorder, somatic type. The patients with oral cenesthopathy show right > left asymmetric regional cerebral blood flow (rCBF) in the broad brain region. However, the studies scrutinizing the rCBF change before and after the successful treatment are still a few so far. Case We present 2 cases of oral cenesthopathy, who responded well to aripiprazole. The asymmetric rCBF patterns were attenuated after successful treatment in both cases. Conclusions We found a marked improvement of oral cenesthopathy with aripiprazole. It is suggested that right > left rCBF asymmetry in the frontal and temporal lobes and thalamus, and the dopaminergic and serotonergic dysfunctions are involved in the pathology of oral cenesthopathy. PMID:28225385

  12. Diffusion tensor imaging of brain abnormalities induced by prenatal exposure to radiation in rodents.

    PubMed

    Saito, Shigeyoshi; Sawada, Kazuhiko; Hirose, Miwa; Mori, Yuki; Yoshioka, Yoshichika; Murase, Kenya

    2014-01-01

    We assessed brain abnormalities in rats exposed prenatally to radiation (X-rays) using magnetic resonance imaging (MRI) and histological experiments. Pregnant rats were divided into 4 groups: the control group (n = 3) and 3 groups that were exposed to different radiation doses (0.5, 1.0, or 1.5 Gy; n = 3 each). Brain abnormalities were assessed in 32 neonatal male rats (8 per group). Ex vivo T2-weighted imaging and diffusion tensor imaging (DTI) were performed using 11.7-T MRI. The expression of markers of myelin production (Kluver-Barrera staining, KB), nonpyramidal cells (calbindin-D28k staining, CaBP), and pyramidal cells (staining of the nonphosphorylated heavy-chain neurofilament SMI-32) were histologically evaluated. Decreased brain volume, increased ventricle volume, and thinner cortices were observed by MRI in irradiated rats. However, no abnormalities in the cortical 6-layered structure were observed via KB staining in radiation-exposed rats. The DTI color-coded map revealed a dose-dependent reduction in the anisotropic signal (vertical direction), which did not represent reduced numbers of pyramidal cells; rather, it indicated a signal reduction relative to the vertical direction because of low nerve cell density in the entire cortex. We conclude that DTI and histological experiments are useful tools for assessing cortical and hippocampal abnormalities after prenatal exposure to radiation in rats.

  13. Diffusion Tensor Imaging of Brain Abnormalities Induced by Prenatal Exposure to Radiation in Rodents

    PubMed Central

    Saito, Shigeyoshi; Sawada, Kazuhiko; Hirose, Miwa; Mori, Yuki; Yoshioka, Yoshichika; Murase, Kenya

    2014-01-01

    We assessed brain abnormalities in rats exposed prenatally to radiation (X-rays) using magnetic resonance imaging (MRI) and histological experiments. Pregnant rats were divided into 4 groups: the control group (n = 3) and 3 groups that were exposed to different radiation doses (0.5, 1.0, or 1.5 Gy; n = 3 each). Brain abnormalities were assessed in 32 neonatal male rats (8 per group). Ex vivo T2-weighted imaging and diffusion tensor imaging (DTI) were performed using 11.7-T MRI. The expression of markers of myelin production (Kluver–Barrera staining, KB), nonpyramidal cells (calbindin-D28k staining, CaBP), and pyramidal cells (staining of the nonphosphorylated heavy-chain neurofilament SMI-32) were histologically evaluated. Decreased brain volume, increased ventricle volume, and thinner cortices were observed by MRI in irradiated rats. However, no abnormalities in the cortical 6-layered structure were observed via KB staining in radiation-exposed rats. The DTI color-coded map revealed a dose-dependent reduction in the anisotropic signal (vertical direction), which did not represent reduced numbers of pyramidal cells; rather, it indicated a signal reduction relative to the vertical direction because of low nerve cell density in the entire cortex. We conclude that DTI and histological experiments are useful tools for assessing cortical and hippocampal abnormalities after prenatal exposure to radiation in rats. PMID:25202992

  14. 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.

  15. 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

  16. 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.

  17. The electrophysiology of the olfactory-hippocampal circuit in the isolated and perfused adult mammalian brain in vitro.

    PubMed

    de Curtis, M; Paré, D; Llinás, R R

    1991-10-01

    The viability and general electrophysiological properties of the limbic system in the adult mammalian brain isolated and maintained in vitro by arterial perfusion are described. The isolated brain preparation combines the advantages of intact synaptic connectivity and accessibility of different areas of the encephalic mass with those of the in vitro approach, i.e., stability and control of the ionic environment. Extracellular field potential as well as intracellular recordings were performed at different levels in the limbic system of isolated adult guinea pig brains. The results demonstrate that in the piriform, entorhinal, and hippocampal cortices, the intrinsic electrical properties of individual cells as well as the spontaneous and evoked electrical activity in the neuronal ensembles they comprise, were virtually identical to those observed in vivo. The properties of the limbic system loop were determined.

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

    PubMed

    Budday, Silvia; Raybaud, Charles; Kuhl, Ellen

    2014-07-10

    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.

  19. 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

  20. 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.

  1. Abnormal whole-brain functional connectivity in patients with primary insomnia

    PubMed Central

    Li, Chao; Dong, Mengshi; Yin, Yi; Hua, Kelei; Fu, Shishun; Jiang, Guihua

    2017-01-01

    The investigation of the mechanism of insomnia could provide the basis for improved understanding and treatment of insomnia. The aim of this study is to investigate the abnormal functional connectivity throughout the entire brain of insomnia patients, and analyze the global distribution of these abnormalities. Whole brains of 50 patients with insomnia and 40 healthy controls were divided into 116 regions and abnormal connectivities were identified by comparing the Pearson’s correlation coefficients of each pair using general linear model analyses with covariates of age, sex, and duration of education. In patients with insomnia, regions that relate to wakefulness, emotion, worry/rumination, saliency/attention, and sensory-motor showed increased positive connectivity with each other; however, regions that often restrain each other, such as regions in salience network with regions in default mode network, showed decreased positive connectivity. Correlation analysis indicated that some increased positive functional connectivity was associated with the Self-Rating Depression Scale, Insomnia Severity Index, and Pittsburgh Sleep Quality Index scores. According to our findings, increased and decreased positive connectivities suggest function strengthening and function disinhibition, respectively, which offers a parsimonious explanation for the hyperarousal hypothesis in the level of the whole-brain functional connectivity in patients with insomnia. PMID:28243094

  2. Abnormal whole-brain functional connectivity in patients with primary insomnia.

    PubMed

    Li, Chao; Dong, Mengshi; Yin, Yi; Hua, Kelei; Fu, Shishun; Jiang, Guihua

    2017-01-01

    The investigation of the mechanism of insomnia could provide the basis for improved understanding and treatment of insomnia. The aim of this study is to investigate the abnormal functional connectivity throughout the entire brain of insomnia patients, and analyze the global distribution of these abnormalities. Whole brains of 50 patients with insomnia and 40 healthy controls were divided into 116 regions and abnormal connectivities were identified by comparing the Pearson's correlation coefficients of each pair using general linear model analyses with covariates of age, sex, and duration of education. In patients with insomnia, regions that relate to wakefulness, emotion, worry/rumination, saliency/attention, and sensory-motor showed increased positive connectivity with each other; however, regions that often restrain each other, such as regions in salience network with regions in default mode network, showed decreased positive connectivity. Correlation analysis indicated that some increased positive functional connectivity was associated with the Self-Rating Depression Scale, Insomnia Severity Index, and Pittsburgh Sleep Quality Index scores. According to our findings, increased and decreased positive connectivities suggest function strengthening and function disinhibition, respectively, which offers a parsimonious explanation for the hyperarousal hypothesis in the level of the whole-brain functional connectivity in patients with insomnia.

  3. Mapping the dynamics of brain perfusion using functional ultrasound in a rat model of transient middle cerebral artery occlusion.

    PubMed

    Brunner, Clément; Isabel, Clothilde; Martin, Abraham; Dussaux, Clara; Savoye, Anne; Emmrich, Julius; Montaldo, Gabriel; Mas, Jean-Louis; Baron, Jean-Claude; Urban, Alan

    2017-01-01

    Following middle cerebral artery occlusion, tissue outcome ranges from normal to infarcted depending on depth and duration of hypoperfusion as well as occurrence and efficiency of reperfusion. However, the precise time course of these changes in relation to tissue and behavioral outcome remains unsettled. To address these issues, a three-dimensional wide field-of-view and real-time quantitative functional imaging technique able to map perfusion in the rodent brain would be desirable. Here, we applied functional ultrasound imaging, a novel approach to map relative cerebral blood volume without contrast agent, in a rat model of brief proximal transient middle cerebral artery occlusion to assess perfusion in penetrating arterioles and venules acutely and over six days thanks to a thinned-skull preparation. Functional ultrasound imaging efficiently mapped the acute changes in relative cerebral blood volume during occlusion and following reperfusion with high spatial resolution (100 µm), notably documenting marked focal decreases during occlusion, and was able to chart the fine dynamics of tissue reperfusion (rate: one frame/5 s) in the individual rat. No behavioral and only mild post-mortem immunofluorescence changes were observed. Our study suggests functional ultrasound is a particularly well-adapted imaging technique to study cerebral perfusion in acute experimental stroke longitudinally from the hyper-acute up to the chronic stage in the same subject.

  4. Complement inhibition and statins prevent fetal brain cortical abnormalities in a mouse model of preterm birth.

    PubMed

    Pedroni, Silvia M A; Gonzalez, Juan M; Wade, Jean; Jansen, Maurits A; Serio, Andrea; Marshall, Ian; Lennen, Ross J; Girardi, Guillermina

    2014-01-01

    Premature babies are particularly vulnerable to brain injury. In this study we focus on cortical brain damage associated with long-term cognitive, behavioral, attentional or socialization deficits in children born preterm. Using a mouse model of preterm birth (PTB), we demonstrated that complement component C5a contributes to fetal cortical brain injury. Disruption of cortical dendritic and axonal cytoarchitecture was observed in PTB-mice. Fetuses deficient in C5aR (-/-) did not show cortical brain damage. Treatment with antibody anti-C5, that prevents generation of C5a, also prevented cortical fetal brain injury in PTB-mice. C5a also showed a detrimental effect on fetal cortical neuron development and survival in vitro. Increased glutamate release was observed in cortical neurons in culture exposed to C5a. Blockade of C5aR prevented glutamate increase and restored neurons dendritic and axonal growth and survival. Similarly, increased glutamate levels - measured by (1)HMRS - were observed in vivo in PTB-fetuses compared to age-matched controls. The blockade of glutamate receptors prevented C5a-induced abnormal growth and increased cell death in isolated fetal cortical neurons. Simvastatin and pravastatin prevented cortical fetal brain developmental and metabolic abnormalities -in vivo and in vitro. Neuroprotective effects of statins were mediated by Akt/PKB signaling pathways. This study shows that complement activation plays a crucial role in cortical fetal brain injury in PTL and suggests that complement inhibitors and statins might be good therapeutic options to improve neonatal outcomes in preterm birth.

  5. Resting-State Brain Abnormalities in Chronic Subjective Tinnitus: A Meta-Analysis

    PubMed Central

    Chen, Yu-Chen; Wang, Fang; Wang, Jie; Bo, Fan; Xia, Wenqing; Gu, Jian-Ping; Yin, Xindao

    2017-01-01

    Purpose: The neural mechanisms that give rise to the phantom sound of tinnitus have not been fully elucidated. Neuroimaging studies have revealed abnormalities in resting-state activity that could represent the neural signature of tinnitus, but there is considerable heterogeneity in the data. To address this issue, we conducted a meta-analysis of published neuroimaging studies aimed at identifying a common core of resting-state brain abnormalities in tinnitus patients. Methods: A systematic search was conducted for whole-brain resting-state neuroimaging studies with SPECT, PET and functional MRI that compared chronic tinnitus patients with healthy controls. The authors searched PubMed, Science Direct, Web of Knowledge and Embase databases for neuroimaging studies on tinnitus published up to September 2016. From each study, coordinates were extracted from clusters with significant differences between tinnitus subjects and controls. Meta-analysis was performed using the activation likelihood estimation (ALE) method. Results: Data were included from nine resting-state neuroimaging studies that reported a total of 51 distinct foci. The meta-analysis identified consistent regions of increased resting-state brain activity in tinnitus patients relative to controls that included, bilaterally, the insula, middle temporal gyrus (MTG), inferior frontal gyrus (IFG), parahippocampal gyrus, cerebellum posterior lobe and right superior frontal gyrus. Moreover, decreased brain activity was only observed in the left cuneus and right thalamus. Conclusions: The current meta-analysis is, to our knowledge, the first to demonstrate a characteristic pattern of resting-state brain abnormalities that may serve as neuroimaging markers and contribute to the understanding of neuropathophysiological mechanisms for chronic tinnitus. PMID:28174532

  6. Resting-State Brain Abnormalities in Chronic Subjective Tinnitus: A Meta-Analysis.

    PubMed

    Chen, Yu-Chen; Wang, Fang; Wang, Jie; Bo, Fan; Xia, Wenqing; Gu, Jian-Ping; Yin, Xindao

    2017-01-01

    Purpose: The neural mechanisms that give rise to the phantom sound of tinnitus have not been fully elucidated. Neuroimaging studies have revealed abnormalities in resting-state activity that could represent the neural signature of tinnitus, but there is considerable heterogeneity in the data. To address this issue, we conducted a meta-analysis of published neuroimaging studies aimed at identifying a common core of resting-state brain abnormalities in tinnitus patients. Methods: A systematic search was conducted for whole-brain resting-state neuroimaging studies with SPECT, PET and functional MRI that compared chronic tinnitus patients with healthy controls. The authors searched PubMed, Science Direct, Web of Knowledge and Embase databases for neuroimaging studies on tinnitus published up to September 2016. From each study, coordinates were extracted from clusters with significant differences between tinnitus subjects and controls. Meta-analysis was performed using the activation likelihood estimation (ALE) method. Results: Data were included from nine resting-state neuroimaging studies that reported a total of 51 distinct foci. The meta-analysis identified consistent regions of increased resting-state brain activity in tinnitus patients relative to controls that included, bilaterally, the insula, middle temporal gyrus (MTG), inferior frontal gyrus (IFG), parahippocampal gyrus, cerebellum posterior lobe and right superior frontal gyrus. Moreover, decreased brain activity was only observed in the left cuneus and right thalamus. Conclusions: The current meta-analysis is, to our knowledge, the first to demonstrate a characteristic pattern of resting-state brain abnormalities that may serve as neuroimaging markers and contribute to the understanding of neuropathophysiological mechanisms for chronic tinnitus.

  7. Evaluation by quantitative 99m-technetium MIBI SPECT and echocardiography of myocardial perfusion and wall motion abnormalities in patients with dobutamine-induced ST-segment elevation.

    PubMed

    Elhendy, A; Geleijnse, M L; Roelandt, J R; van Domburg, R T; Cornel, J H; TenCate, F J; Postma-Tjoa, J; Reijs, A E; el-Said, G M; Fioretti, P M

    1995-09-01

    ST-segment elevation during exercise testing has been attributed to myocardial ischemia and wall motion abnormalities (WMA). However, the functional significance of ST-segment elevation during dobutamine stress testing (DST) has not been evaluated in patients referred for diagnostic evaluation of myocardial ischemia. DST (up to 40 micrograms/kg/min) with simultaneous echocardiography and technetium-99m sestamibi single-photon emission computed tomography (SPECT) was performed in 229 consecutive patients with suspected myocardial ischemia who were unable to perform an adequate exercise test; 127 (55%) had a previous acute myocardial infarction (AMI). ST elevation was defined as > or = 1 mm new or additional J point elevations with a horizontal or upsloping ST segment lasting 80 ms. Reversible perfusion defects on SPECT and new or worsening WMA during stress on echocardiography were considered diagnostic of ischemia. ST elevation occurred in 40 patients (17%) during the test; 34 of them (85%) had previous AMI. All patients with ST-segment elevation had abnormal scintigrams (fixed or reversible defects, or both) and abnormal wall motion (fixed or transient defect, or both) at peak stress. In patients who had ST elevation and no previous AMI (n = 6), ischemia was detected in all by echocardiography and in 5 (83%) by SPECT. In patients with previous AMI, the prevalence of ischemia was not different with or without ST elevation (53% vs 43% by echocardiography and 53% vs 48% by SPECT, respectively). Baseline regional wall motion score in the infarct zone was higher in patients with ST elevation.(ABSTRACT TRUNCATED AT 250 WORDS)

  8. Abnormal Brain Responses to Action Observation in Complex Regional Pain Syndrome.

    PubMed

    Hotta, Jaakko; Saari, Jukka; Koskinen, Miika; Hlushchuk, Yevhen; Forss, Nina; Hari, Riitta

    2017-03-01

    Patients with complex regional pain syndrome (CRPS) display various abnormalities in central motor function, and their pain is intensified when they perform or just observe motor actions. In this study, we examined the abnormalities of brain responses to action observation in CRPS. We analyzed 3-T functional magnetic resonance images from 13 upper limb CRPS patients (all female, ages 31-58 years) and 13 healthy, age- and sex-matched control subjects. The functional magnetic resonance imaging data were acquired while the subjects viewed brief videos of hand actions shown in the first-person perspective. A pattern-classification analysis was applied to characterize brain areas where the activation pattern differed between CRPS patients and healthy subjects. Brain areas with statistically significant group differences (q < .05, false discovery rate-corrected) included the hand representation area in the sensorimotor cortex, inferior frontal gyrus, secondary somatosensory cortex, inferior parietal lobule, orbitofrontal cortex, and thalamus. Our findings indicate that CRPS impairs action observation by affecting brain areas related to pain processing and motor control.

  9. Morphometric abnormalities in brains of great blue heron hatchlings exposed in the wild to PCDDs.

    PubMed Central

    Henshel, D S; Martin, J W; Norstrom, R; Whitehead, P; Steeves, J D; Cheng, K M

    1995-01-01

    Great blue heron hatchlings from colonies in the Strait of Georgia, British Columbia, Canada are being monitored for environmental contaminant exposure and effects by the Canadian Wildlife Service. The contaminants of concern are polychlorinated dibenzodioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs), primarily derived from kraft pulp mill effluent. The levels of PCDDs and PCDFs in eggs from the most contaminated colonies peaked in 1988 and 1989 and dropped dramatically through 1990 to 1992. Brains of heron hatchlings (taken as eggs from the wild and hatched in the laboratory) were analyzed for gross morphological abnormalities. Brains from highly contaminated colonies (Crofton, British Columbia and University of British Columbia Endowment Lands) in 1988 exhibited a high frequency of intercerebral asymmetry. The frequency of this abnormality decreased in subsequent years as the levels of TCDD and TCDD-TEQs (toxic equivalence factors) decreased. The asymmetry was significantly correlated with the level of TCDD and TCDD-TEQs in eggs taken from the same nest. Yolk-free body weight negatively correlated and the brain somatic index positively correlated with the TCDD level in such pair-matched eggs. These results indicate that gross brain morphology, and specifically intercerebral asymmetry, may be useful as a biomarker for the developmental neurotoxic effects of PCDDs and related chemicals. Images Figure 1. PMID:7556025

  10. 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

  11. Agrin in Alzheimer's Disease: Altered Solubility and Abnormal Distribution within Microvasculature and Brain Parenchyma

    NASA Astrophysics Data System (ADS)

    Donahue, John E.; Berzin, Tyler M.; Rafii, Michael S.; Glass, David J.; Yancopoulos, George D.; Fallon, Justin R.; Stopa, Edward G.

    1999-05-01

    Agrin is a heparan sulfate proteoglycan that is widely expressed in neurons and microvascular basal lamina in the rodent and avian central nervous system. Agrin induces the differentiation of nerve-muscle synapses, but its function in either normal or diseased brains is not known. Alzheimer's disease (AD) is characterized by loss of synapses, changes in microvascular architecture, and formation of neurofibrillary tangles and senile plaques. Here we have asked whether AD causes changes in the distribution and biochemical properties of agrin. Immunostaining of normal, aged human central nervous system revealed that agrin is expressed in neurons in multiple brain areas. Robust agrin immunoreactivity was observed uniformly in the microvascular basal lamina. In AD brains, agrin is highly concentrated in both diffuse and neuritic plaques as well as neurofibrillary tangles; neuronal expression of agrin also was observed. Furthermore, patients with AD had microvascular alterations characterized by thinning and fragmentation of the basal lamina. Detergent extraction and Western blotting showed that virtually all the agrin in normal brain is soluble in 1% SDS. In contrast, a large fraction of the agrin in AD brains is insoluble under these conditions, suggesting that it is tightly associated with β -amyloid. Together, these data indicate that the agrin abnormalities observed in AD are closely linked to β -amyloid deposition. These observations suggest that altered agrin expression in the microvasculature and the brain parenchyma contribute to the pathogenesis of AD.

  12. Brain FDG-PET metabolic abnormalities in Macrophagic Myofasciitis: Are They Stable?

    PubMed

    Blanc-Durand, Paul; Van Der Gucht, Axel; Aoun Sebaiti, Mehdi; Abulizi, Mukedaisi; Authier, Francois-Jérome; Itti, Emmanuel

    2017-03-16

    We address this letter in addition to our recent published study (1). The aim is to add some insight to the evolution of the brain abnormalities that are observed with macrophagic myofasciitis (MMF). MMF is a chronic disease whom evolution is slow and symptoms first may occurs from months to year after a vaccination containing aluminium hydroxid adjuvants (2). Nevertheless, its evolution is not fully understood or known. MMF associated cognitive dysfunction (MACD) is based on a tripod combining dysexecutive syndrom, visual memory impairment and interhemispheric disconnection. One pilot study suggest that MACD appears clinically stable over time (3). One recent study evaluating a support vector machine classifier also suggest that the abnormalities observed with 18-fluorodeoxyglose positron emission tomography ((18)F-FDG PET) may be sensitive and could be used to monitor patients. The study population comes from cohort followed in our Reference Center for Rare Neuromuscular Diseases and data were collected retrospectively. Among those patients, 15 had two consecutives (18)F-FDG PET brain acquisitions (median age 42.1 [range 20.9 to 63.5]) following the same brain protocol acquisition as previously described (1). Median time duration between the two examinations was 2.3 years (range 0.5 to 4]. Using analysis of covariance and negative or positive contrast in SPM12, a t-test mask was generated from the comparison between the two means of the first cerebral (18)F-FDG PET images and between the mean of the second acquisition. Results of the comparison were collected at a P-value < 0.005 at the voxel level, for clusters k ≥ 200 voxels (corrected for cluster volume) with adjustment for age. Brain abnormalities maps didn't show any statistical difference between the two examinations confirming the idea that MMF is a slowly or not progressive disease and it is in concordance with the fact that neurological symptoms even if fluctuate do not worsen over time (nor ameliorate).

  13. Assessment of intravascular and extravascular mechanisms of myocardial perfusion abnormalities in obstructive hypertrophic cardiomyopathy by myocardial contrast echocardiography

    PubMed Central

    Soliman, Osama I I; Knaapen, Paul; Geleijnse, Marcel L; Dijkmans, Pieter A; Anwar, Ashraf M; Nemes, Attila; Michels, Michelle; Vletter, Wim B; Lammertsma, Adriaan A

    2007-01-01

    Objectives To assess mechanisms of myocardial perfusion impairment in patients with hypertrophic cardiomyopathy (HCM). Methods Fourteen patients with obstructive HCM (mean (SD) age 53 (10) years, 11 men) underwent intravenous adenosine myocardial contrast echocardiography (MCE), positron emission tomography (PET) and cardiac catheterisation. Fourteen healthy volunteers (mean age 31 (4) years, 11 men) served as controls. Relative myocardial blood volume (rBV), exchange flow velocity (β), myocardial blood flow (MBF), MBF reserve (MFR) and endocardial‐to‐subepicardial (endo‐to‐epi) MBF ratio were measured from the steady state and contrast replenishment time–intensity curves. Results Patients with HCM had lower rest MBF (for LVRPP‐corrected)—mean (SD) (0.92 (0.12) vs 1.13 (0.25) ml/min/g, p<0.01)—and hyperaemic MBF—(2.56 (0.49) vs 4.34 (0.78) ml/min/g, p<0.01) than controls. Resting rBV was lower in patients with HCM (0.094 (0.016) vs 0.138 (0.014) ml/ml), and during hyperaemia (0.104 (0.018) ml/ml vs 0.185 (0.024) ml/ml) (all p<0.001) than in controls. β tended to be higher in HCM at rest (9.4 (4.6) vs 7.7 (4.2) ml/min) and during hyperaemia (25.8 (6.4) vs 23.1 (6.2) ml/min) than in controls. Septal endo‐to‐epi MBF decreased during hyperaemia (0.86 (0.15) to 0.64 (0.18), p<0.01). rBV was inversely correlated with left ventricular (LV) mass index (p<0.05). Both hyperaemic and endo‐to‐epi MBF were inversely correlated with LV end‐diastolic pressure, LV mass index, and LV outflow tract pressure gradient (all p<0.05). MCE‐derived MBF correlated well with PET at rest (r = 0.84) and hyperaemia (r = 0.87) (all p<0.001). Conclusions In patients with HCM, LV end‐diastolic pressure, LV outflow tract pressure gradient, and LV mass index are independent predictors of rBV and hyperaemic MBF. PMID:17488767

  14. Resting cerebral blood flow alterations in chronic traumatic brain injury: an arterial spin labeling perfusion FMRI study.

    PubMed

    Kim, Junghoon; Whyte, John; Patel, Sunil; Avants, Brian; Europa, Eduardo; Wang, Jiongjiong; Slattery, John; Gee, James C; Coslett, H Branch; Detre, John A

    2010-08-01

    Non-invasive measurement of resting state cerebral blood flow (CBF) may reflect alterations of brain structure and function after traumatic brain injury (TBI). However, previous imaging studies of resting state brain in chronic TBI have been limited by several factors, including measurement in relative rather than absolute units, use of crude spatial registration methods, exclusion of subjects with substantial focal lesions, and exposure to ionizing radiation, which limits repeated assessments. This study aimed to overcome those obstacles by measuring absolute CBF with an arterial spin labeling perfusion fMRI technique, and using an image preprocessing protocol that is optimized for brains with mixed diffuse and focal injuries characteristic of moderate and severe TBI. Resting state CBF was quantified in 27 individuals with moderate to severe TBI in the chronic stage, and 22 demographically matched healthy controls. In addition to global CBF reductions in the TBI subjects, more prominent regional hypoperfusion was found in the posterior cingulate cortices, the thalami, and multiple locations in the frontal cortices. Diffuse injury, as assessed by tensor-based morphometry, was mainly associated with reduced CBF in the posterior cingulate cortices and the thalami, where the greatest volume losses were detected. Hypoperfusion in superior and middle frontal cortices, in contrast, was associated with focal lesions. These results suggest that structural lesions, both focal and diffuse, are the main contributors to the absolute CBF alterations seen in chronic TBI, and that CBF may serve as a tool to assess functioning neuronal volume. We also speculate that resting reductions in posterior cingulate perfusion may reflect alterations in the default-mode network, and may contribute to the attentional deficits common in TBI.

  15. Longitudinal change of small-vessel disease-related brain abnormalities.

    PubMed

    Schmidt, Reinhold; Seiler, Stephan; Loitfelder, Marisa

    2016-01-01

    Knowledge about the longitudinal change of cerebral small-vessel disease–related magnetic resonance imaging abnormalities increases our pathophysiologic understanding of cerebral microangiopathy. The change of specific lesion types may also serve as secondary surrogate endpoint in clinical trials. A surrogate endpoint needs to progress fast enough to allow monitoring of treatment effects within a reasonable time period, and change of the brain abnormality needs to be correlated with clinical change. Confluent white matter lesions show fast progression and correlations with cognitive decline. Thus, the change of confluent white matter lesions may be used as a surrogate marker in proof-of-concept trials with small patient numbers needed to show treatment effects on lesion progression. Nonetheless if the expected change in cognitive performance resulting from treatment effects on lesion progression is used as outcome, the sample size needed to show small to moderate treatment effects becomes very large. Lacunes may also fulfill the prerequisites of a surrogate marker, but in the general population the incidence of lacunes over short observational periods is small. For other small-vessel disease–related brain abnormalities including microbleeds and microstructural changes in normal-appearing white matter longitudinal change and correlations with clinical decline is not yet fully determined.

  16. Brain abnormalities in bipolar disorder detected by quantitative T1ρ mapping.

    PubMed

    Johnson, C P; Follmer, R L; Oguz, I; Warren, L A; Christensen, G E; Fiedorowicz, J G; Magnotta, V A; Wemmie, J A

    2015-02-01

    Abnormal metabolism has been reported in bipolar disorder, however, these studies have been limited to specific regions of the brain. To investigate whole-brain changes potentially associated with these processes, we applied a magnetic resonance imaging technique novel to psychiatric research, quantitative mapping of T1 relaxation in the rotating frame (T1ρ). This method is sensitive to proton chemical exchange, which is affected by pH, metabolite concentrations and cellular density with high spatial resolution relative to alternative techniques such as magnetic resonance spectroscopy and positron emission tomography. Study participants included 15 patients with bipolar I disorder in the euthymic state and 25 normal controls balanced for age and gender. T1ρ maps were generated and compared between the bipolar and control groups using voxel-wise and regional analyses. T1ρ values were found to be elevated in the cerebral white matter and cerebellum in the bipolar group. However, volumes of these areas were normal as measured by high-resolution T1- and T2-weighted magnetic resonance imaging. Interestingly, the cerebellar T1ρ abnormalities were normalized in participants receiving lithium treatment. These findings are consistent with metabolic or microstructural abnormalities in bipolar disorder and draw attention to roles of the cerebral white matter and cerebellum. This study highlights the potential utility of high-resolution T1ρ mapping in psychiatric research.

  17. 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.

    1998-06-01

    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.

  18. 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.

  19. Abnormal functional MRI BOLD contrast in the vegetative state after severe traumatic brain injury.

    PubMed

    Heelmann, Volker; Lippert-Grüner, Marcela; Rommel, Thomas; Wedekind, Christoph

    2010-06-01

    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 consciousness close to the vegetative state were studied clinically, electrophysiologically, and by means of functional magnetic resonance imaging. Visual, sensory, and acoustic paradigms were used for stimulation. In three patients examined less than 2 months after trauma, a consistent decrease in blood oxygen level dependent (BOLD) signal ('negative activation') was observed for visual stimulation; one case even showed a decrease in BOLD activation for all three activation paradigms. In the remaining three cases examined more than 6 months after trauma, visual stimulation yielded positive BOLD contrast or no activation. In all cases, sensory stimulation was followed by a decrease in BOLD signal or no activation, whereas auditory stimulation failed to elicit any activation with the exception of one case. Functional magnetic resonance imaging in the vegetative state indicates retained yet abnormal brain function; this abnormality can be attributed to the impairment of cerebral vascular autoregulation or an increase in the energy consumption of activated neocortex in severe traumatic brain injury.

  20. 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.

  1. Abnormal Spontaneous Brain Activity in Women with Premenstrual Syndrome Revealed by Regional Homogeneity

    PubMed Central

    Liao, Hai; Pang, Yong; Liu, Peng; Liu, Huimei; Duan, Gaoxiong; Liu, Yanfei; Tang, Lijun; Tao, Jien; Wen, Danhong; Li, Shasha; Liang, Lingyan; Deng, Demao

    2017-01-01

    Background: Previous studies have revealed that the etiologies of premenstrual syndrome (PMS) refer to menstrual cycle related brain changes. However, its intrinsic neural mechanism is still unclear. The aim of the present study was to assess abnormal spontaneous brain activity and to explicate the intricate neural mechanism of PMS using resting state functional magnetic resonance imaging (RS-fMRI). Materials and Methods: The data of 20 PMS patients (PMS group) and 21 healthy controls (HC group) were analyzed by regional homogeneity (ReHo) method during the late luteal phase of menstrual cycle. In addition, all the participants were asked to complete a daily record of severity of problems (DRSP) questionnaire. Results: Compared with HC group, the results showed that PMS group had increased ReHo mainly in the bilateral precuneus, left inferior temporal cortex (ITC), right inferior frontal cortex (IFC) and left middle frontal cortex (MFC) and decreased ReHo in the right anterior cingulate cortex (ACC) at the luteal phase. Moreover, the PMS group had higher DRSP scores, and the DRSP scores positively correlated with ReHo in left MFC and negatively correlated with ReHo in the right ACC. Conclusion: Our results suggest that abnormal spontaneous brain activity is found in PMS patients and the severity of symptom is specifically related to the left MFC and right ACC. The present findings may be beneficial to explicate the intricate neural mechanism of PMS. PMID:28243196

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

    PubMed Central

    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

    2016-01-01

    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

  3. Brain flexibility and balance and gait performances mark morphological and metabolic abnormalities in the elderly.

    PubMed

    Ben Salem, Douraied; Walker, Paul M; Aho, Serge; Tavernier, Béatrice; Giroud, Maurice; Tzourio, Christophe; Ricolfi, Frédéric; Brunotte, François

    2008-12-01

    Although previous studies have found that cerebral white matter hyperintensities are associated with balance-gait disorders, no proton magnetic resonance spectroscopy data at the plane of the basal ganglia have been published. We investigated a possible relationship between balance performance and brain metabolite ratios or structural MRI measurements. We also included neuropsychological tests to determine whether such tests are related to structural or metabolic findings. All 80 participants were taken from the cohort of the Three-City study (Dijon-Bordeaux-Montpellier, France). The ratios of N-acetyl-aspartate to creatine (NAA/Cr) and choline to creatine (Cho/Cr) were calculated in the basal ganglia, thalami and insular cortex. We used univariate regression to identify which variables predicted changes in NAA/Cr and Cho/Cr, and completed the analysis with a multiple linear or logistic regression. After the multivariate analysis including hypertension, age, balance-gait, sex, white matter lesions, brain atrophy and body mass index, only balance-gait performance remained statistically significant for NAA/Cr (p=0.01) and for deep white-matter lesions (p=0.02). The Trail-Making Test is independently associated with brain atrophy and periventricular white-matter hyperintensities. Neuronal and axonal integrity at the plane of the basal ganglia is associated with balance and gait in the elderly, whereas brain flexibility is associated with structural MRI brain abnormalities.

  4. 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.

  5. Cerebrovascular risk factors and brain microstructural abnormalities on diffusion tensor images in HIV-infected individuals.

    PubMed

    Nakamoto, Beau K; Jahanshad, Neda; McMurtray, Aaron; Kallianpur, Kalpana J; Chow, Dominic C; Valcour, Victor G; Paul, Robert H; Marotz, Liron; Thompson, Paul M; Shikuma, Cecilia M

    2012-08-01

    HIV-associated neurocognitive disorder remains prevalent in HIV-infected individuals despite effective antiretroviral therapy. As these individuals age, comorbid cerebrovascular disease will likely impact cognitive function. Effective tools to study this impact are needed. This study used diffusion tensor imaging (DTI) to characterize brain microstructural changes in HIV-infected individuals with and without cerebrovascular risk factors. Diffusion-weighted MRIs were obtained in 22 HIV-infected subjects aged 50 years or older (mean age = 58 years, standard deviation = 6 years; 19 males, three females). Tensors were calculated to obtain fractional anisotropy (FA) and mean diffusivity (MD) maps. Statistical comparisons accounting for multiple comparisons were made between groups with and without cerebrovascular risk factors. Abnormal glucose metabolism (i.e., impaired fasting glucose, impaired glucose tolerance, or diabetes mellitus) was associated with significantly higher MD (false discovery rate (FDR) critical p value = 0.008) and lower FA (FDR critical p value = 0.002) in the caudate and lower FA in the hippocampus (FDR critical p value = 0.004). Pearson correlations were performed between DTI measures in the caudate and hippocampus and age- and education-adjusted composite scores of global cognitive function, memory, and psychomotor speed. There were no detectable correlations between the neuroimaging measures and measures of cognition. In summary, we demonstrate that brain microstructural abnormalities are associated with abnormal glucose metabolism in the caudate and hippocampus of HIV-infected individuals. Deep gray matter structures and the hippocampus may be vulnerable in subjects with comorbid abnormal glucose metabolism, but our results should be confirmed in further studies.

  6. 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

  7. 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

  8. 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.

  9. 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

    2016-06-02

    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.

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

    PubMed Central

    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

  11. 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

  12. 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.

  13. Lesion area detection using source image correlation coefficient for CT perfusion imaging.

    PubMed

    Fan Zhu; Rodriguez Gonzalez, David; Carpenter, Trevor; Atkinson, Malcolm; Wardlaw, Joanna

    2013-09-01

    Computer tomography (CT) perfusion imaging is widely used to calculate brain hemodynamic quantities such as cerebral blood flow, cerebral blood volume, and mean transit time that aid the diagnosis of acute stroke. Since perfusion source images contain more information than hemodynamic maps, good utilization of the source images can lead to better understanding than the hemodynamic maps alone. Correlation-coefficient tests are used in our approach to measure the similarity between healthy tissue time-concentration curves and unknown curves. This information is then used to differentiate penumbra and dead tissues from healthy tissues. The goal of the segmentation is to fully utilize information in the perfusion source images. Our method directly identifies suspected abnormal areas from perfusion source images and then delivers a suggested segmentation of healthy, penumbra, and dead tissue. This approach is designed to handle CT perfusion images, but it can also be used to detect lesion areas in magnetic resonance perfusion images.

  14. Brain Microstructural Abnormalities Are Related to Physiological Alterations in End-Stage Renal Disease

    PubMed Central

    Tian, Junzhang; Dong, Jianwei; He, Jinlong; Zhan, Wenfeng; Xu, Lijuan; Xu, Yikai; Jiang, Guihua

    2016-01-01

    Purpose To study whole-brain microstructural alterations in patients with end-stage renal disease (ESRD) and examine the relationship between brain microstructure and physiological indictors in the disease. Materials and Methods Diffusion tensor imaging data were collected from 35 patients with ESRD (28 men, 18–61 years) and 40 age- and gender-matched healthy controls (HCs, 32 men, 22–58 years). A voxel-wise analysis was then used to identify microstructural alterations over the whole brain in the ESRD patients compared with the HCs. Multiple biochemical measures of renal metabolin, vascular risk factors, general cognitive ability and dialysis duration were correlated with microstructural integrity for the patients. Results Compared to the HCs, the ESRD patients exhibited disrupted microstructural integrity in not only white matter (WM) but also gray matter (GM) regions, as characterized by decreased fractional anisotropy (FA) and increased mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD). Further correlation analyses revealed that the in MD, AD and RD values showed significantly positive correlations with the blood urea nitrogen in the left superior temporal gyrus and significantly negative correlations with the calcium levels in the left superior frontal gyrus (orbital part) in the patients. Conclusion Our findings suggest that ESRD is associated with widespread diffusion abnormalities in both WM and GM regions in the brain, and microstructural integrity of several GM regions are related to biochemical alterations in the disease. PMID:27227649

  15. Sonographic parenchymal and brain perfusion imaging: preliminary results in four patients following decompressive surgery for malignant middle cerebral artery infarct.

    PubMed

    Schlachetzki, F; Hoelscher, T; Dorenbeck, U; Greiffenberg, B; Marienhagen, J; Ullrich, O W; Bogdahn, U

    2001-01-01

    To investigate new methods of diagnostic transcranial sonography for brain parenchymal, vascular and perfusion imaging, we performed 3-D native tissue harmonic transcranial sonography (3D-nthTCS), 3-D transcranial color-coded duplex sonography (3D-TCCS), and "loss-of-correlation" imaging (LOC-TCCS) in four patients following early hemicraniectomy due to space-occupying "malignant" middle cerebral artery infarction (MMCAI). Three-dimensional datasets, utilizing 3D-nthTCS and 3D-TCCS, were created and up to 10 axial 2-D B-mode image planes, similar to CCT, reconstructed in each patient. Three-dimensional reconstructions of the circle of Willis documented one persistent carotid-T occlusion and three recanalizations of the MCA. LOC-TCCS, based on stimulated acoustic emission from an ultrasound (US) contrast agent, demonstrated a perfusion deficit in 2 of 3 patients, with regard to their infarcts. Concluding, 3D-nthTCS, 3D-TCCS and LOC-TCCS are promising tools for bedside monitoring, early prognosis and treatment evaluation for MMCAI in the postoperative period. Further studies should be performed to standardize these new methods and evaluate their applications through the intact calvarina.

  16. A new brain perfusion imaging agent: [I-123]HIPDM:N,N,N'-trimethyl-N'-[2-hydroxy-3-methyl-5-iodobenzyl]-1,3-propanediamine.

    PubMed

    Kung, H F; Tramposch, K M; Blau, M

    1983-01-01

    Based on the pH-shift mechanism, a new brain imaging agent I-124 HIPDM (N,N,N'-trimethyl-N'-[2-hydroxy-3-methyl-5-[123I]iodobenzyl]-1,3-propanediamine ) has been developed. This agent can be prepared by a simple exchange reaction suitable for routine clinical use. The physicochemical parameters, partition coefficient vs. pH profile, and protein binding, as well as biodistribution in rats, were very similar to those of I-123 IMP (N-isopropyl-p-iodoamphetamine). High brain uptake was found in animals after i.v. injection. The brain radioactivity persists for at least 1 hr in rats and monkeys. Regional distribution in sections of rat brain appeared to reflect regional perfusion. In conjunction with single-photon emission tomography (SPECT), this agent may provide useful information on local cerebral perfusion in humans.

  17. Knockout of G protein β5 impairs brain development and causes multiple neurologic abnormalities in mice

    PubMed Central

    Zhang, Jian-Hua; Pandey, Mritunjay; Seigneur, Erica M.; Panicker, Leelamma M.; Koo, Lily; Schwartz, Owen M.; Chen, Weiping; Chen, Ching-Kang; Simonds, William F.

    2011-01-01

    Gβ5 is a divergent member of the signal-transducing G protein β subunit family encoded by GNB5 and expressed principally in brain and neuronal tissue. Among heterotrimeric Gβ isoforms, Gβ5 is unique in its ability to heterodimerize with members of the R7 subfamily of the regulator of G protein signaling (RGS) proteins that contain G protein-γ like domains. Previous studies employing Gnb5 knockout (KO) mice have shown that Gβ5 is an essential stabilizer of such RGS proteins and regulates the deactivation of retinal phototransduction and the proper functioning of retinal bipolar cells. However, little is known of the function of Gβ5 in the brain outside the visual system. We show here that mice lacking Gβ5 have a markedly abnormal neurologic phenotype that includes impaired development, tiptoe-walking, motor learning and coordination deficiencies, and hyperactivity. We further show that Gβ5-deficient mice have abnormalities of neuronal development in cerebellum and hippocampus. We find that the expression of both mRNA and protein from multiple neuronal genes is dysregulated in Gnb5 KO mice. Taken together with previous observations from Gnb5 KO mice, our findings suggest a model in which Gβ5 regulates dendritic arborization and/or synapse formation during development, in part by effects on gene expression. PMID:21883221

  18. 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

  19. 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.

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

    PubMed

    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.

  1. Outcome, Pressure Reactivity and Optimal Cerebral Perfusion Pressure Calculation in Traumatic Brain Injury: A Comparison of Two Variants.

    PubMed

    Lang, Erhard W; Kasprowicz, Magdalena; Smielewski, Peter; Santos, Edgar; Pickard, John; Czosnyka, Marek

    2016-01-01

    This study investigates the outcome prediction and calculation of optimal cerebral perfusion pressure (CPPopt) in 307 patients after severe traumatic brain injury (TBI) based on cerebrovascular reactivity calculation of a moving correlation correlation coefficient, named PRx, between mean arterial pressure (ABP) and intracranial pressure (ICP). The correlation coefficient was calculated from simultaneously recorded data using different frequencies. PRx was calculated from oscillations between 0.008 and 0.05Hz and the longPRx (L-PRx) was calculated from oscillations between 0.0008 and 0.016 Hz. PRx was a significant mortality predictor, whereas L-PRx was not. CPPopt for pooled data was higher for L-PRx than for PRx, with no statistical difference. Mortality was associated with mean CPP below CPPopt. Severe disability was associated with CPP above CPPopt (PRx). These relationships were not statistically significant for CPPopt (L-PRx). We conclude that PRx and L-PRx cannot be used interchangeably.

  2. 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

  3. 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

  4. Perfusion MRI Indexes Variability in the Functional Brain Effects of Theta-Burst Transcranial Magnetic Stimulation

    PubMed Central

    Gratton, Caterina; Lee, Taraz G.; Nomura, Emi M.; D’Esposito, Mark

    2014-01-01

    Transcranial Magnetic Stimulation (TMS) is an important tool for testing causal relationships in cognitive neuroscience research. However, the efficacy of TMS can be variable across individuals and difficult to measure. This variability is especially a challenge when TMS is applied to regions without well-characterized behavioral effects, such as in studies using TMS on multi-modal areas in intrinsic networks. Here, we examined whether perfusion fMRI recordings of Cerebral Blood Flow (CBF), a quantitative measure sensitive to slow functional changes, reliably index variability in the effects of stimulation. Twenty-seven participants each completed four combined TMS-fMRI sessions during which both resting state Blood Oxygen Level Dependent (BOLD) and perfusion Arterial Spin Labeling (ASL) scans were recorded. In each session after the first baseline day, continuous theta-burst TMS (TBS) was applied to one of three locations: left dorsolateral prefrontal cortex (L dlPFC), left anterior insula/frontal operculum (L aI/fO), or left primary somatosensory cortex (L S1). The two frontal targets are components of intrinsic networks and L S1 was used as an experimental control. CBF changes were measured both before and after TMS on each day from a series of interleaved resting state and perfusion scans. Although TBS led to weak selective increases under the coil in CBF measurements across the group, individual subjects showed wide variability in their responses. TBS-induced changes in rCBF were related to TBS-induced changes in functional connectivity of the relevant intrinsic networks measured during separate resting-state BOLD scans. This relationship was selective: CBF and functional connectivity of these networks were not related before TBS or after TBS to the experimental control region (S1). Furthermore, subject groups with different directions of CBF change after TBS showed distinct modulations in the functional interactions of targeted networks. These results suggest

  5. 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.

  6. 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.

  7. 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

  8. 99mTc-HMPAO perfusion SPECT/CT in the diagnosis of brain death.

    PubMed

    Derlin, Thorsten; Weiberg, Desiree

    2016-01-01

    This report describes a case of brain death (BD) evaluated by 99mTc-hexamethylpropylene amine oxime (HMPAO) single photon emission tomography/computed tomography (SPECT/CT). A 16-year-old boy with a history of rapid unexpected brain herniation due to pilocytic astrocytoma underwent 99mTc-HMPAO SPECT/CT for evaluation of brain death in the context of organ donation. Flow images demonstrated lack of blood flow to the brain, and delayed images showed absence of demonstrable radionuclide activity within the brain. SPECT/CT confirmed absence of tracer accumulation, and was deemed helpful for evaluation of the brain stem. 99mTc-HMPAO SPECT/CT is a valuable tool enabling imaging-based confirmation of BD.

  9. 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

  10. Abnormal resting-state brain activities in patients with first-episode obsessive-compulsive disorder

    PubMed Central

    Niu, Qihui; Yang, Lei; Song, Xueqin; Chu, Congying; Liu, Hao; Zhang, Lifang; Li, Yan; Zhang, Xiang; Cheng, Jingliang; Li, Youhui

    2017-01-01

    Objective This paper attempts to explore the brain activity of patients with obsessive-compulsive disorder (OCD) and its correlation with the disease at resting duration in patients with first-episode OCD, providing a forceful imaging basis for clinic diagnosis and pathogenesis of OCD. Methods Twenty-six patients with first-episode OCD and 25 healthy controls (HC group; matched for age, sex, and education level) underwent functional magnetic resonance imaging (fMRI) scanning at resting state. Statistical parametric mapping 8, data processing assistant for resting-state fMRI analysis toolkit, and resting state fMRI data analysis toolkit packages were used to process the fMRI data on Matlab 2012a platform, and the difference of regional homogeneity (ReHo) values between the OCD group and HC group was detected with independent two-sample t-test. With age as a concomitant variable, the Pearson correlation analysis was adopted to study the correlation between the disease duration and ReHo value of whole brain. Results Compared with HC group, the ReHo values in OCD group were decreased in brain regions, including left thalamus, right thalamus, right paracentral lobule, right postcentral gyrus, and the ReHo value was increased in the left angular gyrus region. There was a negative correlation between disease duration and ReHo value in the bilateral orbitofrontal cortex (OFC). Conclusion OCD is a multifactorial disease generally caused by abnormal activities of many brain regions at resting state. Worse brain activity of the OFC is related to the OCD duration, which provides a new insight to the pathogenesis of OCD. PMID:28243104

  11. Neurological Gait Abnormalities Moderate the Functional Brain Signature of the Posture First Hypothesis

    PubMed Central

    Verghese, Joe; Allali, Gilles; Izzetoglu, Meltem; Wang, Cuiling; Mahoney, Jeannette R.

    2015-01-01

    The posture first hypothesis suggests that under dual-task walking conditions older adults prioritize gait over cognitive task performance. Functional neural confirmation of this hypothesis, however, is lacking. Herein, we determined the functional neural correlates of the posture first hypothesis and hypothesized that the presence of neurological gait abnormalities (NGA) would moderate associations between brain activations, gait and cognitive performance. Using functional near-infrared spectroscopy we assessed changes in oxygenated hemoglobin levels in the pre-frontal cortex (PFC) during normal walk and walk while talk (WWT) conditions in a large cohort of non-demented older adults (n = 236; age = 75.5 ± 6.49 years; female = 51.7 %). NGA were defined as central (due to brain diseases) or peripheral (neuropathic gait) following a standardized neurological examination protocol. Double dissociations between brain activations and behavior emerged as a function of NGA. Higher oxygenation levels during WWT were related to better cognitive performance (estimate = 0.145; p < 0.001) but slower gait velocity (estimate = −6.336, p <0.05) among normals. In contrast, higher oxygenation levels during WWT among individuals with peripheral NGA were associated with worse cognitive performance (estimate = −0.355; p <0.001) but faster gait velocity (estimate = 14.855; p <0.05). Increased activation in the PFC during locomotion may have a compensatory function that is designed to support gait among individuals with peripheral NGA. PMID:26613725

  12. Regional brain structural abnormality in ischemic stroke patients: a voxel-based morphometry study

    PubMed Central

    Wu, Ping; Zhou, Yu-mei; Zeng, Fang; Li, Zheng-jie; Luo, Lu; Li, Yong-xin; Fan, Wei; Qiu, Li-hua; Qin, Wei; Chen, Lin; Bai, Lin; Nie, Juan; Zhang, San; Xiong, Yan; Bai, Yu; Yin, Can-xin; Liang, Fan-rong

    2016-01-01

    Our previous study used regional homogeneity analysis and found that activity in some brain areas of patients with ischemic stroke changed significantly. In the current study, we examined structural changes in these brain regions by taking structural magnetic resonance imaging scans of 11 ischemic stroke patients and 15 healthy participants, and analyzing the data using voxel-based morphometry. Compared with healthy participants, patients exhibited higher gray matter density in the left inferior occipital gyrus and right anterior white matter tract. In contrast, gray matter density in the right cerebellum, left precentral gyrus, right middle frontal gyrus, and left middle temporal gyrus was less in ischemic stroke patients. The changes of gray matter density in the middle frontal gyrus were negatively associated with the clinical rating scales of the Fugl-Meyer Motor Assessment (r = –0.609, P = 0.047) and the left middle temporal gyrus was negatively correlated with the clinical rating scales of the nervous functional deficiency scale (r = –0.737, P = 0.010). Our findings can objectively identify the functional abnormality in some brain regions of ischemic stroke patients. PMID:27857744

  13. 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

  14. 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.

  15. Near-Infrared Spectroscopy versus Magnetic Resonance Imaging To Study Brain Perfusion in Newborns with Hypoxic-Ischemic Encephalopathy Treated with Hypothermia

    PubMed Central

    Wintermark, P.; Hansen, A.; Warfield, SK.; Dukhovny, D.; Soul, JS.

    2014-01-01

    Background The measurement of brain perfusion may provide valuable information for assessment and treatment of newborns with hypoxic-ischemic encephalopathy (HIE). While arterial spin labeled perfusion (ASL) magnetic resonance imaging (MRI) provides noninvasive and direct measurements of regional cerebral blood flow (CBF) values, it is logistically challenging to obtain. Near-infrared spectroscopy (NIRS) might be an alternative, as it permits noninvasive and continuous monitoring of cerebral hemodynamics and oxygenation at the bedside. Objective The purpose of this study is to determine the correlation between measurements of brain perfusion by NIRS and by MRI in term newborns with HIE treated with hypothermia. Design/Methods In this prospective cohort study, ASL-MRI and NIRS performed during hypothermia were used to assess brain perfusion in these newborns. Regional cerebral blood flow values (CBF), measured from 1–2 MRI scans for each patient, were compared to mixed venous saturation values (SctO2) recorded by NIRS just before and after each MRI. Analysis included groupings into moderate versus severe HIE based on their initial background pattern of amplitude-integrated electroencephalogram. Results Twelve concomitant recordings were obtained of seven neonates. Strong correlation was found between SctO2 and CBF in asphyxiated newborns with severe HIE (r = 0.88; p value = 0.0085). Moreover, newborns with severe HIE had lower CBF (likely lower oxygen supply) and extracted less oxygen (likely lower oxygen demand or utilization) when comparing SctO2 and CBF to those with moderate HIE. Conclusions NIRS is an effective bedside tool to monitor and understand brain perfusion changes in term asphyxiated newborns, which in conjunction with precise measurements of CBF obtained by MRI at particular times, may help tailor neuroprotective strategies in term newborns with HIE. PMID:23631990

  16. 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

  17. A methodology for generating normal and pathological brain perfusion SPECT images for evaluation of MRI/SPECT fusion methods: application in epilepsy

    NASA Astrophysics Data System (ADS)

    Grova, C.; Jannin, P.; Biraben, A.; Buvat, I.; Benali, H.; Bernard, A. M.; Scarabin, J. M.; Gibaud, B.

    2003-12-01

    Quantitative evaluation of brain MRI/SPECT fusion methods for normal and in particular pathological datasets is difficult, due to the frequent lack of relevant ground truth. We propose a methodology to generate MRI and SPECT datasets dedicated to the evaluation of MRI/SPECT fusion methods and illustrate the method when dealing with ictal SPECT. The method consists in generating normal or pathological SPECT data perfectly aligned with a high-resolution 3D T1-weighted MRI using realistic Monte Carlo simulations that closely reproduce the response of a SPECT imaging system. Anatomical input data for the SPECT simulations are obtained from this 3D T1-weighted MRI, while functional input data result from an inter-individual analysis of anatomically standardized SPECT data. The method makes it possible to control the 'brain perfusion' function by proposing a theoretical model of brain perfusion from measurements performed on real SPECT images. Our method provides an absolute gold standard for assessing MRI/SPECT registration method accuracy since, by construction, the SPECT data are perfectly registered with the MRI data. The proposed methodology has been applied to create a theoretical model of normal brain perfusion and ictal brain perfusion characteristic of mesial temporal lobe epilepsy. To approach realistic and unbiased perfusion models, real SPECT data were corrected for uniform attenuation, scatter and partial volume effect. An anatomic standardization was used to account for anatomic variability between subjects. Realistic simulations of normal and ictal SPECT deduced from these perfusion models are presented. The comparison of real and simulated SPECT images showed relative differences in regional activity concentration of less than 20% in most anatomical structures, for both normal and ictal data, suggesting realistic models of perfusion distributions for evaluation purposes. Inter-hemispheric asymmetry coefficients measured on simulated data were found within

  18. A methodology for generating normal and pathological brain perfusion SPECT images for evaluation of MRI/SPECT fusion methods: application in epilepsy.

    PubMed

    Grova, C; Jannin, P; Biraben, A; Buvat, I; Benali, H; Bernard, A M; Scarabin, J M; Gibaud, B

    2003-12-21

    Quantitative evaluation of brain MRI/SPECT fusion methods for normal and in particular pathological datasets is difficult, due to the frequent lack of relevant ground truth. We propose a methodology to generate MRI and SPECT datasets dedicated to the evaluation of MRI/SPECT fusion methods and illustrate the method when dealing with ictal SPECT. The method consists in generating normal or pathological SPECT data perfectly aligned with a high-resolution 3D T1-weighted MRI using realistic Monte Carlo simulations that closely reproduce the response of a SPECT imaging system. Anatomical input data for the SPECT simulations are obtained from this 3D T1-weighted MRI, while functional input data result from an inter-individual analysis of anatomically standardized SPECT data. The method makes it possible to control the 'brain perfusion' function by proposing a theoretical model of brain perfusion from measurements performed on real SPECT images. Our method provides an absolute gold standard for assessing MRI/SPECT registration method accuracy since, by construction, the SPECT data are perfectly registered with the MRI data. The proposed methodology has been applied to create a theoretical model of normal brain perfusion and ictal brain perfusion characteristic of mesial temporal lobe epilepsy. To approach realistic and unbiased perfusion models, real SPECT data were corrected for uniform attenuation, scatter and partial volume effect. An anatomic standardization was used to account for anatomic variability between subjects. Realistic simulations of normal and ictal SPECT deduced from these perfusion models are presented. The comparison of real and simulated SPECT images showed relative differences in regional activity concentration of less than 20% in most anatomical structures, for both normal and ictal data, suggesting realistic models of perfusion distributions for evaluation purposes. Inter-hemispheric asymmetry coefficients measured on simulated data were found within

  19. Nevirapine uptake into the central nervous system of the Guinea pig: an in situ brain perfusion study.

    PubMed

    Gibbs, J E; Gaffen, Z; Thomas, S A

    2006-05-01

    The presence of human immunodeficiency virus (HIV) in the central nervous system (CNS) is associated with the development of HIV-1-associated dementia (HAD), a major cause of HIV-related mortality. To eradicate HIV in the CNS, anti-HIV drugs need to reach the brain and cerebrospinal fluid (CSF) in therapeutic concentrations. This involves passage through the blood-brain and blood-CSF barriers. Using a well established guinea pig in situ brain perfusion model, this study investigated whether nevirapine [6H-dipyrido(3,2-b:2',3'-e)(1,4)diazepin-6-one,11-cyclopropyl-5,11-dihydro-4-methyl], a non-nucleoside reverse transcriptase inhibitor (NNRTI), could effectively accumulate in the CNS. [(3)H]Nevirapine was coperfused with [(14)C]mannitol (a vascular/paracellular permeability marker) through the carotid arteries for up to 30 min, and accumulation in the brain, CSF, and choroid plexus was measured. [(3)H]Nevirapine uptake into the cerebrum was greater than uptake of [(14)C]mannitol, indicating significant passage across the blood-brain barrier and accumulation into the brain (this was further confirmed with capillary depletion and high-performance liquid chromatography analyses). Likewise, [(3)H]nevirapine showed a great ability to cross the blood-CSF barrier and accumulate in the CSF, compared with [(14)C]mannitol. The CNS accumulation of [(3)H]nevirapine was unaffected by 100 muM nevirapine, suggesting that passage across the blood-brain barrier can occur by diffusion. Furthermore, coperfusion with 100 muM efavirenz [2H-3,1-benzoxazin-2-one, 6-chloro-4-(cyclopropylethynyl)-1,4-dihydro-4-(trifluoromethyl)-, (4S)-; another NNRTI] did not significantly alter CNS accumulation of [(3)H]nevirapine, indicating that the efficacy of nevirapine in the CNS would not be altered by the addition of this drug to a combination therapy. Together, these data indicate that this anti-HIV drug should be beneficial in the eradication of HIV within the CNS and the subsequent treatment of

  20. Abnormal endogenous amino acid release in brain slices from vitamin B-6 restricted neonatal rats.

    PubMed

    Guilarte, T R

    1991-01-02

    The basal and potassium-evoked efflux of glutamate, glycine, taurine, and gamma-aminobutyric acid (GABA) was measured in brain slices from vitamin B-6 restricted and sufficient 14-day-old rats. The results indicate a reduced level of basal glutamate, taurine, and GABA efflux in hippocampal slices and taurine and GABA in cortical slices from vitamin B-6 restricted animals. In the presence of depolarizing potassium concentrations, there was a reduced level of GABA efflux in hippocampal and cortical slices, and a marked reduction in the release of glutamate in cortical slices from B-6 restricted rats. The abnormalities in the secretion process of these neuroactive amino acids may be related to the neurological sequelae associated with neonatal vitamin B-6 restriction.

  1. Correlation between abnormal brain excitability and emotional symptomatology in paediatric migraine.

    PubMed

    Valeriani, M; Galli, F; Tarantino, S; Graceffa, D; Pignata, E; Miliucci, R; Biondi, G; Tozzi, A; Vigevano, F; Guidetti, V

    2009-02-01

    We investigated a possible correlation between brain excitability in children with migraine and tension-type headache (TTH) and their behavioural symptomatology, assessed by using the Child Behaviour Checklist (CBCL). The mismatch negativity (MMN) and P300 response were recorded in three successive blocks to test the amplitude reduction of each response from the first to the third block (habituation). MMN and P300 habituation was significantly lower in migraineurs and TTH children than in control subjects (two-way ANOVA: P < 0.05). In migraineurs, but not in TTH patients, significant positive correlations between the P300 habituation deficit and the CBCL scores were found (P < 0.05), meaning that the migraineurs with the most reduced habituation showed also the worst behavioural symptomatology. To the best of our knowledge, this is the first study showing a correlation between neurophysiological abnormality and emotional symptomatology in migraine, suggesting a role of the latter in producing the migrainous phenotype.

  2. Abnormal connectivity in the sensorimotor network predicts attention deficits in traumatic brain injury.

    PubMed

    Shumskaya, Elena; van Gerven, Marcel A J; Norris, David G; Vos, Pieter E; Kessels, Roy P C

    2017-03-01

    The aim of this study was to explore modifications of functional connectivity in multiple resting-state networks (RSNs) after moderate to severe traumatic brain injury (TBI) and evaluate the relationship between functional connectivity patterns and cognitive abnormalities. Forty-three moderate/severe TBI patients and 34 healthy controls (HC) underwent resting-state fMRI. Group ICA was applied to identify RSNs. Between-subject analysis was performed using dual regression. Multiple linear regressions were used to investigate the relationship between abnormal connectivity strength and neuropsychological outcome. Forty (93%) TBI patients showed moderate disability, while 2 (5%) and 1 (2%) upper severe disability and low good recovery, respectively. TBI patients performed worse than HC on the domains attention and language. We found increased connectivity in sensorimotor, visual, default mode (DMN), executive, and cerebellar RSNs after TBI. We demonstrated an effect of connectivity in the sensorimotor RSN on attention (p < 10(-3)) and a trend towards a significant effect of the DMN connectivity on attention (p = 0.058). A group-by-network interaction on attention was found in the sensorimotor network (p = 0.002). In TBI, attention was positively related to abnormal connectivity within the sensorimotor RSN, while in HC this relation was negative. Our results show altered patterns of functional connectivity after TBI. Attention impairments in TBI were associated with increased connectivity in the sensorimotor network. Further research is needed to test whether attention in TBI patients is directly affected by changes in functional connectivity in the sensorimotor network or whether the effect is actually driven by changes in the DMN.

  3. 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.

  4. 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.

  5. 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

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

    PubMed

    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; Fan, Jin

    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.

  7. Macro- and microelements in the rat liver, kidneys, and brain tissues; sex differences and effect of blood removal by perfusion in vivo.

    PubMed

    Orct, Tatjana; Jurasović, Jasna; Micek, Vedran; Karaica, Dean; Sabolić, Ivan

    2017-03-01

    Concentrations of macro- and microelements in animal organs indicate the animal health status and represent reference data for animal experiments. Their levels in blood and tissues could be different between sexes, and could be different with and without blood in tissues. To test these hypotheses, in adult female and male rats the concentrations of various elements were measured in whole blood, blood plasma, and tissues from blood-containing (nonperfused) and blood-free liver, kidneys, and brain (perfused in vivo with an elements-free buffer). In these samples, 6 macroelements (Na, Mg, P, S, K, Ca) and 14 microelements (Fe, Mn, Co, Cu, Zn, Se, I, As, Cd, Hg, Pb, Li, B, Sr) were determined by inductively coupled plasma mass spectrometry following nitric acid digestion. In blood and plasma, female- or male-dominant sex differences were observed for 6 and 5 elements, respectively. In nonperfused organs, sex differences were observed for 3 (liver, brain) or 9 (kidneys) elements, whereas in perfused organs, similar differences were detected for 9 elements in the liver, 5 in the kidneys, and none in the brain. In females, perfused organs had significantly lower concentrations of 4, 5, and 2, and higher concentrations of 10, 4, and 7 elements, respectively, in the liver, kidneys, and brain. In males, perfusion caused lower concentrations of 4, 7, and 2, and higher concentrations of 1, 1, and 7 elements, respectively, in the liver, kidneys, and brain. Therefore, the residual blood in organs can significantly influence tissue concentrations of various elements and their sex-dependency.

  8. Chemical Gradients within Brain Extracellular Space Measured using Low Flow Push–Pull Perfusion Sampling in Vivo

    PubMed Central

    2012-01-01

    Although populations of neurons are known to vary on the micrometer scale, little is known about whether basal concentrations of neurotransmitters also vary on this scale. We used low-flow push–pull perfusion to test if such chemical gradients exist between several small brain nuclei. A miniaturized polyimide-encased push–pull probe was developed and used to measure basal neurotransmitter spatial gradients within brain of live animals with 0.004 mm3 resolution. We simultaneously measured dopamine (DA), norepinephrine, serotonin (5-HT), glutamate, γ-aminobutyric acid (GABA), aspartate (Asp), glycine (Gly), acetylcholine (ACh), and several neurotransmitter metabolites. Significant differences in basal concentrations between midbrain regions as little as 200 μm apart were observed. For example, dopamine in the ventral tegmental area (VTA) was 4.8 ± 1.5 nM but in the red nucleus was 0.5 ± 0.2 nM. Regions of high glutamate concentration and variability were found within the VTA of some individuals, suggesting hot spots of glutamatergic activity. Measurements were also made within the nucleus accumbens core and shell. Differences were not observed in dopamine and 5-HT in the core and shell; but their metabolites homovanillic acid (460 ± 60 nM and 130 ± 60 nM respectively) and 5-hydroxyindoleacetic acid (720 ± 200 nM and 220 ± 50 nM respectively) did differ significantly, suggesting differences in dopamine and 5-HT activity in these brain regions. Maintenance of these gradients depends upon a variety of mechanisms. Such gradients likely underlie highly localized effects of drugs and control of behavior that have been found using other techniques. PMID:23421683

  9. Peripheral osmotic stimulation inhibits the brain's innate immune response to microdialysis of acidic perfusion fluid adjacent to supraoptic nucleus

    PubMed Central

    Hu, Sanmei

    2009-01-01

    During the brain's innate immune response microglia, astroglia and ependymal cells resolve/repair damaged tissue and control infection. Released interleukin-1β (IL-1β) reaching cerebroventricles stimulates circumventricular organs (CVOs; subfornical organ, SFO; organum vasculosum lamina terminalis, OVLT), the median preoptic nucleus (MePO), and magnocellular and parvocellular neurons in the supraoptic (SON) and paraventricular (PVN) nuclei. Hypertonic saline (HS) also activates these osmosensory CVOs and neuroendocrine systems, but, in contrast to IL-1β, inhibits the peripheral immune response. To examine whether the brain's innate immune response is attenuated by osmotic stimulation, sterile acidic perfusion fluid was microdialyzed (2 μl/min) in the SON area of conscious rats for 6 h with sterile HS (1.5 M NaCl) injected subcutaneously (15 ml/kg) at 5 h. Immunohistochemistry identified cytokine sources (IL-1β+; OX-42+ microglia) and targets (IL-1R+; inducible cyclooxygenase, COX-2+; c-Fos+) near the probe, in CVOs, MePO, ependymal cells, periventricular hypothalamus, SON, and PVN. Inserting the probe stimulated magnocellular neurons (c-Fos+; SON; PVN) via the MePO (c-Fos+), a response enhanced by HS. Microdialysis activated microglia (OX-42+; amoeboid/hypertrophied; IL-1β+) in the adjacent SON and bilaterally in perivascular areas of the PVN, periventricular hypothalamus and ependyma, coincident with c-Fos expression in ependymal cells and COX-2 in the vasculature. These microglial responses were attenuated by HS, coincident with activating parvocellular and magnocellular neuroendocrine systems and elevating circulating IL-1β, oxytocin, and vasopressin. Acidosis-induced cellular injury from microdialysis activated the brain's innate immune response by a mechanism inhibited by peripheral osmotic stimulation. PMID:19759333

  10. 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.

  11. Abnormal Brain Areas Common to the Focal Epilepsies: Multivariate Pattern Analysis of fMRI.

    PubMed

    Pedersen, Mangor; Curwood, Evan K; Vaughan, David N; Omidvarnia, Amir H; Jackson, Graeme D

    2016-04-01

    Individuals with focal epilepsy have heterogeneous sites of seizure origin. However, there may be brain regions that are common to most cases of intractable focal epilepsy. In this study, we aim to identify these using multivariate analysis of task-free functional MRI. Fourteen subjects with extratemporal focal epilepsy and 14 healthy controls were included in the study. Task-free functional MRI data were used to calculate voxel-wise regional connectivity with regional homogeneity (ReHo) and weighted degree centrality (DCw), in addition to regional activity using fraction of amplitude of low-frequency fluctuations (fALFF). Multivariate pattern analysis was applied to each of these metrics to discriminate brain areas that differed between focal epilepsy subjects and healthy controls. ReHo and DCw classified focal epilepsy subjects from healthy controls with high accuracy (89.3% and 75%, respectively). However, fALFF did not significantly classify patients from controls. Increased regional network activity in epilepsy subjects was seen in the ipsilateral piriform cortex, insula, and thalamus, in addition to the dorsal anterior cingulate cortex and lateral frontal cortices. Decreased regional connectivity was observed in the ventromedial prefrontal cortex, as well as lateral temporal cortices. Patients with extratemporal focal epilepsy have common areas of abnormality (ReHo and DCw measures), including the ipsilateral piriform cortex, temporal neocortex, and ventromedial prefrontal cortex. ReHo shows additional increase in the "salience network" that includes anterior insula and anterior cingulate cortex. DCw showed additional effects in the ipsilateral thalamus and striatum. These brain areas may represent key regional network properties underlying focal epilepsy.

  12. Brain (18)F-FDG PET Metabolic Abnormalities in Patients with Long-Lasting Macrophagic Myofascitis.

    PubMed

    Van Der Gucht, Axel; Aoun Sebaiti, Mehdi; Guedj, Eric; Aouizerate, Jessie; Yara, Sabrina; Gherardi, Romain K; Evangelista, Eva; Chalaye, Julia; Cottereau, Anne-Ségolène; Verger, Antoine; Bachoud-Levi, Anne-Catherine; Abulizi, Mukedaisi; Itti, Emmanuel; Authier, François-Jérôme

    2017-03-01

    The aim of this study was to characterize brain metabolic abnormalities in patients with macrophagic myofascitis (MMF) and the relationship with cognitive dysfunction through the use of PET with (18)F-FDG. Methods:(18)F-FDG PET brain imaging and a comprehensive battery of neuropsychological tests were performed in 100 consecutive MMF patients (age [mean ± SD], 45.9 ± 12 y; 74% women). Images were analyzed with statistical parametric mapping (SPM12). Through the use of analysis of covariance, all (18)F-FDG PET brain images of MMF patients were compared with those of a reference population of 44 healthy subjects similar in age (45.4 ± 16 y; P = 0.87) and sex (73% women; P = 0.88). The neuropsychological assessment identified 4 categories of patients: those with no significant cognitive impairment (n = 42), those with frontal subcortical (FSC) dysfunction (n = 29), those with Papez circuit dysfunction (n = 22), and those with callosal disconnection (n = 7). Results: In comparison with healthy subjects, the whole population of patients with MMF exhibited a spatial pattern of cerebral glucose hypometabolism (P < 0.001) involving the occipital lobes, temporal lobes, limbic system, cerebellum, and frontoparietal cortices, as shown by analysis of covariance. The subgroup of patients with FSC dysfunction exhibited a larger extent of involved areas (35,223 voxels vs. 13,680 voxels in the subgroup with Papez circuit dysfunction and 5,453 voxels in patients without cognitive impairment). Nonsignificant results were obtained for the last subgroup because of its small population size. Conclusion: Our study identified a peculiar spatial pattern of cerebral glucose hypometabolism that was most marked in MMF patients with FSC dysfunction. Further studies are needed to determine whether this pattern could represent a diagnostic biomarker of MMF in patients with chronic fatigue syndrome and cognitive dysfunction.

  13. Retrograde cerebral perfusion (RCP) in aortic arch surgery: efficacy and possible mechanisms of brain protection.

    PubMed

    Bavaria, J E; Pochettino, A

    1997-07-01

    Retrograde cerebral perfusion (RCP) was first introduced to treat air embolism during cardiopulmonary bypass (CPB). Its use was reintroduced to extend the safety of hypothermic circulatory arrest (HCA) during operations involving an open aortic arch. RCP seems to prevent cerebral rewarming during HCA. Both clinical and animal data suggest that RCP provides between 10% and 30% of baseline cerebral blood flow when administered through the superior vena cava (SVC) at jugular pressures of 20 to 25 mm Hg. RCP flows producing jugular venous pressures higher than 30 mm Hg may cause cerebral edema. Cerebral blood flow generated by RCP is able to sustain some cerebral metabolic activity, yet is not able to fully meet cerebral energy demands even at temperatures of 12 degrees to 18 degrees C. RCP may further prevent embolic events during aortic arch surgery when administered at moderate jugular vein pressures (< 40 mm Hg). Clinical results suggest that RCP, when applied during aortic arch reconstruction, may extend the safe HCA period and improve morbidity and mortality, especially when HCA times are more than 60 minutes. RCP applied in patients and severe carotid and brachiocephalic occlusive disease may be ineffective, and caution is in order when RCP times are greater than 90 minutes.

  14. Decreased Cerebral Blood Flow in Chronic Pediatric Mild TBI: An MRI Perfusion Study

    PubMed Central

    Wang, Yang; West, John D.; Bailey, Jessica N.; Westfall, Daniel R.; Xiao, Hui; Arnold, Todd W.; Kersey, Patrick A.; Saykin, Andrew J.; McDonald, Brenna C.

    2015-01-01

    We evaluated cerebral blood flow (CBF) in chronic pediatric mild traumatic brain injury (mTBI) using arterial spin labeling (ASL) magnetic resonance imaging perfusion. mTBI patients showed lower CBF than controls in bilateral frontotemporal regions, with no between-group cognitive differences. Findings suggest ASL may be useful to assess functional abnormalities in pediatric mTBI. PMID:25649779

  15. [A 15oxygen positron study of relative local perfusion and oxygen extraction of the brain in lacunar hemiparesis (author's transl)].

    PubMed

    Rougemont, D; Baron, J C; Lebrun-Grandié, P; Bousser, M G; Soisson, T; Comar, D

    1982-05-01

    The oxygen-15 non-invasive continuous inhalation technique coupled with positron emission tomography (PET) allows the local study of cerebral blood flow and oxygen metabolism. Recent PET studied have demonstrated the frequent occurrence of widespread metabolic depression remote from the site of middle cerebral artery territory infarct per se, especially over the cortical mantle and thalamus ipsilaterally, and over the cerebellar hemisphere contralaterally. These phenomena have been taken as indicative of a transneural depression (i.e. diaschisis). We thought interesting to study the possible occurrence of such abnormalities in patients with lacunar syndromes. We have applied the 15O technique to seven patients (2 with pure motor hemiplegia, 5 with ataxic hemiparesis) in whom no large causal ischemic lesion could be demonstrated on CT Scans; in only one patient was a lacunar lesion, presumably responsible for the clinical deficit, evidenced. Compared to a set of 19 patients without brain disease, the semi-quantitative results (analyzed in terms of asymmetry indices between homologous brain regions) in our patients did not disclose any pathophysiologically significant abnormality. More specifically, no evidence of physiological dysfunction similar to that reported in internal carotid artery territory infarcts, was detected over the cerebral or the cerebellar cortices. These original findings are commented upon in view of the presumably small size and the uncertain topography of the causal lesion.

  16. 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.…

  17. Developmental origin of abnormal dendritic growth in the mouse brain induced by in utero disruption of aryl hydrocarbon receptor signaling.

    PubMed

    Kimura, Eiki; Kubo, Ken-Ichiro; Matsuyoshi, Chieri; Benner, Seico; Hosokawa, Mayuko; Endo, Toshihiro; Ling, Wenting; Kohda, Masanobu; Yokoyama, Kazuhito; Nakajima, Kazunori; Kakeyama, Masaki; Tohyama, Chiharu

    2015-01-01

    Increased prevalence of mental disorders cannot be solely attributed to genetic factors and is considered at least partly attributable to chemical exposure. Among various environmental chemicals, in utero and lactational dioxin exposure has been extensively studied and is known to induce higher brain function abnormalities in both humans and laboratory animals. However, how the perinatal dioxin exposure affects neuromorphological alterations has remained largely unknown. Therefore, in this study, we initially studied whether and how the over-expression of aryl hydrocarbon receptor (AhR), a dioxin receptor, would affect the dendritic growth in the hippocampus of the developing brain. Transfecting a constitutively active AhR plasmid into the hippocampus via in utero electroporation on gestational day (GD) 14 induced abnormal dendritic branch growth. Further, we observed that 14-day-old mice born to dams administered with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; dose: 0, 0.6, or 3.0 μg/kg) on GD 12.5 exhibited disrupted dendritic branch growth in both the hippocampus and amygdala. Finally, we observed that 16-month-old mice born to dams exposed to perinatal TCDD as described above exhibited significantly reduced spine densities. These results indicated that abnormal micromorphology observed in the developing brain may persist until adulthood and may induce abnormal higher brain function later in life.

  18. 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

  19. 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.

  20. 3D perfused brain phantom for interstitial ultrasound thermal therapy and imaging: design, construction and characterization.

    PubMed

    Martínez, José M; Jarosz, Boguslaw J

    2015-03-07

    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.

  1. Detection of free radicals by isolated perfusion of the rat brain following hemorrhagic stroke: a novel approach to cerebrovascular biomarker research.

    PubMed

    Grienberger, Hubert J; Pillai, Deepu R; Schlachetzki, Felix; Gruber, Michael; Dittmar, Michael S

    2010-10-01

    Blood-borne biomarkers are a mainstay of diagnosis and follow-up in many diseases. For stroke, however, no reliable biomarkers have thus far been identified. To remedy this situation, we investigated the usefulness of a modified in situ isolated brain perfusion (IBP) technique for screening potential biomarker candidates. As a proof of concept, the production of reactive oxygen species (ROS) was estimated in a rat model of experimental intracerebral hemorrhage (ICH). After stereotactic infusion of whole blood into the rat striatum, we initiated IBP without intracranial manipulation or discontinuation of cerebral blood flow. To detect ROS, we employed the salicylate trapping method, which involves the hydroxylation of salicylic acid during oxidative stress into dihydroxybenzoic acid (DHBA), and quantification of the latter in venous eluate by using high-performance liquid chromatography. Venous eluate was collected separately from both injured and healthy hemispheres (n=10). Control groups consisted of sham-injured (n=4) and healthy animals (n=3). In animals subjected to ICH (n=10), 50% more 2,5-DHBA was detected in venous eluate on the injured side than in eluate on the contralateral side. Hemorrhagic hemispheres produced more 2,5-DHBA than hemispheres in sham-injured and healthy animals (72 and 110% more 2,5-DHBA, respectively). Isolated brain perfusion combined with salicylate trapping produced data indicating an elevation in the formation of ROS subsequent to ICH. Our findings suggest that isolated in situ brain perfusion is a promising approach to detecting biomarkers of cerebrovascular pathologic conditions.

  2. 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.

  3. Sequential thallium-201 myocardial perfusion studies after successful percutaneous transluminal coronary artery angioplasty: delayed resolution of exercise-induced scintigraphic abnormalities

    SciTech Connect

    Manyari, D.E.; Knudtson, M.; Kloiber, R.; Roth, D.

    1988-01-01

    To characterize the sequential changes of myocardial perfusion scintigraphy in patients with coronary artery disease (CAD) after complete revascularization, 43 patients underwent exercise thallium-201 (/sup 201/Tl) myocardial perfusion scintigraphy before and at 9 +/- 5 days, 3.3 +/- 0.6, and 6.8 +/- 1.2 months after percutaneous transluminal coronary angioplasty (PTCA). Only patients with single-vessel CAD, without previous myocardial infarction, and without evidence of restenosis at 6 to 9 months after PTCA were included. Perfusion scans were analyzed blindly with the use of a new quantitative method to define regional myocardial perfusion in the topographic distribution of each coronary artery, which was shown to be reproducible (r = .94 or higher and SEE of 7% or less, between repeated measures by one and two operators). At 4 to 18 days after PTCA, the mean treadmill walking time increased by 123 +/- 42 sec, mean exercise-induced ST segment depression decreased by 0.6 +/- 0.3 mm, group maximal heart rate increased by 20 +/- 9 beats/min, and group systolic blood pressure at peak exercise increased by 24 +/- 10 mm Hg, compared with pre-PTCA values (p less than .001). However, no group differences were noted in these variables between the three post-PTCA stages. Myocardial perfusion in the distribution of the affected (dilated) coronary artery, on the other hand, improved progressively. In the 45 degree left anterior oblique view for instance, myocardial perfusion increased at 9 days after PTCA (from 68 +/- 24% before PTCA to 91 +/- 9%, p less than .001) and at 3.3 months after PTCA (101 +/- 8%, p less than .05 vs 9 days after PTCA), but no further significant changes were seen at 6.8 months after PTCA (102 +/- 8%). Similar changes were noted in the other two views. No relationship between minor complications during PTCA and delayed improvement on the /sup 201/Tl was observed.

  4. 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.

  5. 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

  6. Disrupted Nodal and Hub Organization Account for Brain Network Abnormalities in Parkinson’s Disease

    PubMed Central

    Koshimori, Yuko; Cho, Sang-Soo; Criaud, Marion; Christopher, Leigh; Jacobs, Mark; Ghadery, Christine; Coakeley, Sarah; Harris, Madeleine; Mizrahi, Romina; Hamani, Clement; Lang, Anthony E.; Houle, Sylvain; Strafella, Antonio P.

    2016-01-01

    The recent application of graph theory to brain networks promises to shed light on complex diseases such as Parkinson’s disease (PD). This study aimed to investigate functional changes in sensorimotor and cognitive networks in Parkinsonian patients, with a focus on inter- and intra-connectivity organization in the disease-associated nodal and hub regions using the graph theoretical analyses. Resting-state functional MRI data of a total of 65 participants, including 23 healthy controls (HCs) and 42 patients, were investigated in 120 nodes for local efficiency, betweenness centrality, and degree. Hub regions were identified in the HC and patient groups. We found nodal and hub changes in patients compared with HCs, including the right pre-supplementary motor area (SMA), left anterior insula, bilateral mid-insula, bilateral dorsolateral prefrontal cortex (DLPFC), and right caudate nucleus. In general, nodal regions within the sensorimotor network (i.e., right pre-SMA and right mid-insula) displayed weakened connectivity, with the former node associated with more severe bradykinesia, and impaired integration with default mode network regions. The left mid-insula also lost its hub properties in patients. Within the executive networks, the left anterior insular cortex lost its hub properties in patients, while a new hub region was identified in the right caudate nucleus, paralleled by an increased level of inter- and intra-connectivity in the bilateral DLPFC possibly representing compensatory mechanisms. These findings highlight the diffuse changes in nodal organization and regional hub disruption accounting for the distributed abnormalities across brain networks and the clinical manifestations of PD. PMID:27891090

  7. No evidence of perfusion abnormalities in the basal ganglia of a patient with generalized chorea-ballism and polycythaemia vera: analysis using subtraction SPECT co-registered to MRI.

    PubMed

    Kim, Woojun; Kim, Joong-Seok; Lee, Kwang-Soo; Kim, Yeong-In; Park, Chong-Won; Chung, Yong-An

    2008-10-01

    Polycythaemia vera is a well-known cause of symptomatic chorea, however, the pathophysiology of this correlation remains unclear. We report on a patient with generalized chorea-ballism associated with polycythaemia vera, and we present the findings of 99mTc-hexamethylpropylene amine oxime (HMPAO) SPECT done in both the choreic state and the non-choreic state. The SPECT during both the choreic and the non-choreic states did not reveal any definite perfusion changes in specific regions of the brain, as compared with 6 age-matched controls. In addition, the subtraction SPECT co-registered to MRI (SISCOM) analysis did not show any difference in cerebral blood flow during the choreic and non-choreic states. This result suggests that the basic mechanism of chorea associated with polycythaemia vera does not appear to be associated with a reduction in cerebral perfusion to a specific cerebral area, such as the basal ganglia or its thalamocortical connections.

  8. 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.

  9. 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

  10. Abnormal Error Monitoring in Math-Anxious Individuals: Evidence from Error-Related Brain Potentials

    PubMed Central

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

    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. PMID:24236212

  11. 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.

  12. Arterial Spin Labeling Magnetic Resonance Perfusion for Traumatic Brain Injury: Technical Challenges and Potentials.

    PubMed

    Andre, Jalal B

    2015-10-01

    Traumatic brain injury (TBI), including concussion, is a public health concern, as it affects over 1.7 million persons in the United States per year. Yet, the diagnosis of TBI, particularly mild TBI (mTBI), can be controversial, as neuroimaging findings can be sparse on conventional magnetic resonance and computed tomography examinations, and when present, often poorly correlate with clinical signs and symptoms. Furthermore, the discussion of TBI, concussion, and head impact exposure is immediately complicated by the many differing opinions of what constitutes each, their respective severities, and how the underlying biomechanics of the inciting head impact might alter the distribution, severity, and prognosis of the underlying brain injury. Advanced imaging methodologies hold promise in improving the sensitivity and detectability of associated imaging biomarkers that might better correlate with patient outcome and prognostication, allowing for improved triage and therapeutic guidance in the setting of TBI, particularly in mTBI. This work will examine the defining symptom complex associated with mTBI and explore changes in cerebral blood flow measured by arterial spin labeling, as a potential imaging biomarker for TBI, and briefly correlate these observations with findings identified by single photon emission computed tomography and positron emission tomography imaging.

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

    PubMed Central

    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; 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

    2016-01-01

    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

  14. 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.

  15. Cerebral Perfusion Pressure Targets Individualized to Pressure-Reactivity Index in Moderate to Severe Traumatic Brain Injury: A Systematic Review.

    PubMed

    Needham, Edward; McFadyen, Charles; Newcombe, Virginia; Synnot, Anneliese J; Czosnyka, Marek; Menon, David

    2017-03-01

    Traumatic brain injury (TBI) frequently triggers a disruption of cerebral autoregulation. The cerebral perfusion pressure (CPP) at which autoregulation is optimal ("CPPopt") varies between individuals, and can be calculated based on fluctuations between arterial blood pressure and intracranial pressure. This review assesses the effect of individualizing CPP targets to pressure reactivity index (a measure of autoregulation) in patients with TBI. Cochrane Central Register of Controlled Trials, MEDLINE®, Embase, and Cumulative Index of Nursing and Allied Health Literature were searched in March 2015 for studies assessing the effect of targeting CPPopt in TBI. We included all studies that assessed the impact of targeting CPPopt on outcomes including mortality, neurological outcome, and physiological changes. Risk of bias was assessed using the RTI Item Bank and evidence quality was considered using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. Eight cohort studies (based on six distinct data sets) assessing the association between CPPopt and mortality, Glasgow Outcome Scale and physiological measures in TBI were included. The quality of evidence was deemed very low based on the GRADE criteria. Although the data suggest an association between variation from CPPopt and poor clinical outcome at 6 months, the quality of evidence prevents firm conclusions, particularly regarding causality, from being drawn. Available data suggest that targeting CPPopt might represent a technique to improve outcomes following TBI, but currently there is insufficient high-quality data to support a recommendation for use in clinical practice. Further prospective, randomized controlled studies should be undertaken to clarify its role in the acute management of TBI.

  16. 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

  17. Dynamic abnormalities of spontaneous brain activity in women with primary dysmenorrhea

    PubMed Central

    Jin, Lingmin; Yang, Xuejuan; Liu, Peng; Sun, Jinbo; Chen, Fei; Xu, Ziliang; Qin, Wei; Tian, Jie

    2017-01-01

    Purpose This study aimed to investigate the regional spontaneous brain activity changes in primary dysmenorrhea (PD) patients in different phases of the menstrual cycle by regional homogeneity (ReHo) analysis. Patients and methods Thirty-three PD patients and 32 healthy controls (HCs) separately received resting-state functional magnetic resonance imaging during menstrual phase and follicular phase (non-menstrual phase). Cox retrospective symptom scale (RSS), Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS) were applied to assess related symptoms and emotions. Results There was no significant difference between the two groups in demographic data. The PD patients obtained higher RSS score, SAS score and SDS score than HCs. Compared with HCs, the ReHo values of the PD patients were increased in left midbrain and hippocampus, right posterior cingulate cortex (PCC), insula and middle temporal cortex (MTC) and decreased in left dorsolateral prefrontal cortex and right medial prefrontal cortex (mPFC) in menstrual phase. In non-menstrual phase, enhanced ReHo values were found in bilateral S1 and precuneus, left S2 and MTC, and reduced ReHo values were observed in left mPFC and orbital frontal cortex. RSS score positively correlated with ReHo values of midbrain and negatively correlated with mPFC and PCC. Conclusion Our results suggested that PD is accompanied by dynamic regional spontaneous activity changes across the menstrual cycle, and the altered regions were involved in descending pain modulation, default mode network and sensory modulation. These abnormal activations might contribute to maintain the menstrual pain. PMID:28392711

  18. An electrophysiological study of the in vitro, perfused brain stem-cerebellum of adult guinea-pig.

    PubMed Central

    Llinás, R; Mühlethaler, M

    1988-01-01

    1. We describe here a technique which allows the long-term in vitro survival of the perfused isolated brain stem-cerebellum of adult guinea-pig. The viability of this preparation was assessed by comparing the electrophysiological properties of individual neurones and of neuronal pools to those obtained in vivo or in brain slices. The areas investigated included the cerebellar cortex, the inferior olive and the pontine nuclei. 2. Cerebellar field potential and intra- and extracellular single-cell recordings could be obtained for as long as 15 h after the preparation was initially isolated. The waveforms of field potentials recorded at various depths in the cerebellar cortex following surface folial stimulation were similar to those recorded in vivo. Extracellular recordings from single Purkinje cells following white matter stimulation demonstrated antidromic as well as mossy- and climbing fibre-mediated excitation. Stimulation of the cerebellar surface elicited orthodromic parallel fibre excitation of Purkinje cells and basket-stellate and Golgi cell inhibition. 3. Intrasomatic and intradendritic recordings from Purkinje cells reproduced all the phenomenology described earlier under in vivo conditions and in vitro slice preparations. In addition, spontaneous excitatory synaptic potentials generating simple spikes (mossy fibre-parallel fibre-mediated activity) and complex spikes (climbing fibre-mediated activity) were consistently observed. 4. Extracellular field potentials and extra- and intracellular recordings from inferior olive neurones were similar to those previously shown for the mammalian inferior olive. 5. Intracellular recordings were also obtained from pontine nuclei neurones, a major source of mossy fibre afferents to the cerebellum. Stimulation of the contralateral superior cerebellar peduncle produced antidromic invasion of these neurones whereas stimulation of the ipsilateral inferior cerebral peduncle resulted in their orthodromic activation. 6. The

  19. 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.

  20. 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

  1. 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.

  2. 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

  3. Thyroxine transfer from cerebrospinal fluid into choroid plexus and brain is affected by brefeldin A, low sodium, BCH, and phloretin, in ventriculo-cisternal perfused rabbits

    PubMed Central

    Zibara, Kazem; El-Zein, Ali; Joumaa, Wissam; El-Sayyad, Mohammad; Mondello, Stefania; Kassem, Nouhad

    2015-01-01

    Background: Thyroxine (T4) hormone is synthesized by the thyroid gland and then released into the systemic circulation where it binds to a number of proteins. Dysfunction in T4 transport mechanisms has been demonstrated in multiple central nervous system (CNS) diseases including Alzheimer's disease. In the presence of different compounds that inhibit potential T4 transport mechanisms, this study investigated the transfer of T4 from cerebrospinal fluid (CSF) into Choroid Plexus (CP) and other brain tissues. The compounds used were brefeldin A, low sodium artificial CSF (aCSF), BCH, phloretin, and taurocholate (TA). Methods: Radiolabeled T4 (125I-T4) was perfused continuously into the CSF and was assessed in several brain compartments with reference molecule 14C-mannitol and blue dextran, using the in vivo ventriculo-cisternal perfusion (V-C) technique in the rabbit. The aCSF containing the drug of interest was infused after 1 h of perfusion. Drugs were applied independently to the aCSF after 1 h of control perfusion. Results: Of interest, in presence of low sodium or BCH, the percentage recovery of 125I-T4, was increased compared to controls, with concomitant increase in T4 clearance. Conversely, brefeldin A, phloretin, and TA did not exert any significant effect on the recovery and clearance of 125I-T4 assessed in aCSF. On the other hand, the uptake of 125I-T4 into CP was raised by 18 fold compared to controls in the presence of brefeldin A. In addition, low sodium, BCH, or phloretin alone, enhanced the uptake of 125I-T4 by almost 3-fold, whereas TA did not show any significant effect. Finally, the uptake and distribution of 125I-T4 into other brain regions including ependymal region (ER) and caudate putamen (CAP) were significantly higher than in controls. Conclusion: Our study suggests the involvement of different mechanisms for the transfer of 125I-T4 from CSF into CP and other brain regions. This transfer may implicate sodium-dependent mechanisms, amino acid

  4. 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

  5. Spiral Perfusion Imaging With Consecutive Echoes (SPICE™) for the Simultaneous Mapping of DSC- and DCE-MRI Parameters in Brain Tumor Patients: Theory and Initial Feasibility.

    PubMed

    Paulson, Eric S; Prah, Douglas E; Schmainda, Kathleen M

    2016-12-01

    Dynamic contrast-enhanced (DCE) and dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI) are the perfusion imaging techniques most frequently used to probe the angiogenic character of brain neoplasms. With these methods, T1- and T2/T2*-weighted imaging sequences are used to image the distribution of gadolinium (Gd)-based contrast agents. However, it is well known that Gd exhibits combined T1, T2, and T2* shortening effects in tissue, and therefore, the results of both DCE- and DSC-MRI can be confounded by these opposing effects. In particular, residual susceptibility effects compete with T1 shortening, which can confound DCE-MRI parameters, whereas dipolar T1 and T2 leakage and residual susceptibility effects can confound DSC-MRI parameters. We introduce here a novel perfusion imaging acquisition and postprocessing method termed Spiral Perfusion Imaging with Consecutive Echoes (SPICE) that can be used to simultaneously acquire DCE- and DSC-MRI data, which requires only a single dose of the Gd contrast agent, does not require the collection of a precontrast T1 map for DCE-MRI processing, and eliminates the confounding contrast agent effects due to contrast extravasation. A detailed mathematical description of SPICE is provided here along with a demonstration of its utility in patients with high-grade glioma.

  6. Discrepancies in brain perfusion SPECT findings between Tc-99m HMPAO and Tc-99m ECD: evaluation using dynamic SPECT in patients with hyperemia.

    PubMed

    Miyazawa, N; Koizumi, K; Mitsuka, S; Nukui, H

    1998-10-01

    Discrepancies have been reported between the findings of Tc-99m HMPAO and Tc-99m ECD brain perfusion SPECT imaging. This study investigated the discrepancies in the accumulation of these tracers using dynamic SPECT to detect the super early phase of distribution. Thirteen patients with luxury perfusion or high flow states were studied with both dynamic and standard SPECT using Tc-99m HMPAO and Tc-99m ECD within 1-3 days. Standard SPECT showed discrepancies in 6 of 13 patients. Patients with meningioma and cerebral thrombosis had increased accumulation of Tc-99m HMPAO and decreased uptake of Tc-99m ECD. Patients with arteriovenous malformation, subarachnoid hemorrhage, and cavernous angioma had decreased accumulation of both tracers, but to different degrees. Dynamic SPECT showed increased or normal accumulation (i.e., essentially no discrepancy) in the first few minutes. However, Tc-99m HMPAO had a longer retention time than Tc-99m ECD in the ensuing 5-10 minutes. Dynamic SPECT revealed a similar accumulation pattern but different washout rates for the two tracers. Tc-99m HMPAO might be a more suitable tracer to detect high flow states or luxury perfusion because the findings on standard SPECT were more in agreement with those of dynamic SPECT using this tracer.

  7. Spiral Perfusion Imaging With Consecutive Echoes (SPICE™) for the Simultaneous Mapping of DSC- and DCE-MRI Parameters in Brain Tumor Patients: Theory and Initial Feasibility

    PubMed Central

    Paulson, Eric S.; Prah, Douglas E.; Schmainda, Kathleen M.

    2017-01-01

    Dynamic contrast-enhanced (DCE) and dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI) are the perfusion imaging techniques most frequently used to probe the angiogenic character of brain neoplasms. With these methods, T1- and T2/T2*-weighted imaging sequences are used to image the distribution of gadolinium (Gd)-based contrast agents. However, it is well known that Gd exhibits combined T1, T2, and T2* shortening effects in tissue, and therefore, the results of both DCE- and DSC-MRI can be confounded by these opposing effects. In particular, residual susceptibility effects compete with T1 shortening, which can confound DCE-MRI parameters, whereas dipolar T1 and T2 leakage and residual susceptibility effects can confound DSC-MRI parameters. We introduce here a novel perfusion imaging acquisition and postprocessing method termed Spiral Perfusion Imaging with Consecutive Echoes (SPICE) that can be used to simultaneously acquire DCE- and DSC-MRI data, which requires only a single dose of the Gd contrast agent, does not require the collection of a precontrast T1 map for DCE-MRI processing, and eliminates the confounding contrast agent effects due to contrast extravasation. A detailed mathematical description of SPICE is provided here along with a demonstration of its utility in patients with high-grade glioma. PMID:28090589

  8. Monitoring stroke progression: in vivo imaging of cortical perfusion, blood-brain barrier permeability and cellular damage in the rat photothrombosis model.

    PubMed

    Schoknecht, Karl; Prager, Ofer; Vazana, Udi; Kamintsky, Lyn; Harhausen, Denise; Zille, Marietta; Figge, Lena; Chassidim, Yoash; Schellenberger, Eyk; Kovács, Richard; Heinemann, Uwe; Friedman, Alon

    2014-11-01

    Focal cerebral ischemia is among the main causes of death and disability worldwide. The ischemic core often progresses, invading the peri-ischemic brain; however, assessing the propensity of the peri-ischemic brain to undergo secondary damage, understanding the underlying mechanisms, and adjusting treatment accordingly remain clinically unmet challenges. A significant hallmark of the peri-ischemic brain is dysfunction of the blood-brain barrier (BBB), yet the role of disturbed vascular permeability in stroke progression is unclear. Here we describe a longitudinal in vivo fluorescence imaging approach for the evaluation of cortical perfusion, BBB dysfunction, free radical formation and cellular injury using the photothrombosis vascular occlusion model in male Sprague Dawley rats. Blood-brain barrier dysfunction propagated within the peri-ischemic brain in the first hours after photothrombosis and was associated with free radical formation and cellular injury. Inhibiting free radical signaling significantly reduced progressive cellular damage after photothrombosis, with no significant effect on blood flow and BBB permeability. Our approach allows a dynamic follow-up of cellular events and their response to therapeutics in the acutely injured cerebral cortex.

  9. Role of Brain Perfusion SPECT with 99mTc HMPAO in the Assessment of Response to Drug Therapy in Patients with Autoimmune Vasculitis: A Prospective Study

    PubMed Central

    Mauro, Liberatore; Manuela, Morreale; Valentina, Megna; Sara, Collorone; Chondrogiannis, Sotirios; Maria, Drudi Francesco; Christos, Anagnostou; Liana, Civitelli; Ada, Francia; Maffione, Anna Margherita; Marzola, Maria Cristina; Rubello, Domenico

    2015-01-01

    Background: The diagnosis of vasculitis in the brain remains a quite difficult achievement. To the best of our knowledge, there is no imaging method reported in literature which is capable of reaching to a diagnosis of vasculitis with very high sensitivity. Aim: The aim of this study was to determine whether perfusion brain single photon emission computed tomography (SPECT) can be usefully employed in monitoring the treatment of vasculitis, allowing treating only potentially responder patients and avoiding the side effects on patients who do not respond. Materials and Methods: Twenty patients (two males and 18 females) suffering from systemic lupus erythematosus (SLE; n = 5), Behcet's disease (BD; n = 5), undifferentiated vasculitis (UV; n = 5), and Sjogren's syndrome (SS; n = 5) were included in the study. All patients underwent a wide neurological anamnestic investigation, a complete objective neurological examination and SPECT of the brain with 99mTc-hexamethyl-propylene-aminoxime (HMPAO). The brain SPECT was then repeated after appropriate medical treatment. The neurological and neuropsychiatric follow-up was performed at 6 months after the start of the treatment. Results: Overall, the differences between the scintigraphic results obtained after and before the medical treatment indicated a statistically significant increase of the cerebral perfusion (CP). In 19 out of 200 regions of interest (ROI) studied, the difference between pre- and post treatment percentages had negative sign, indicating a worsening of CP. This latter event has occurred six times (five in the same patients) in the UV, 10 times (eight in the same patients) in the SLE, never in BD, and three times (two in the same patient) in the SS. Conclusion: The reported results seem to indicate the possibility of identifying, by the means of a brain SPECT, responder and nonresponder (unchanged or worsened CP) patients, affected by autoimmune vasculitis, to the therapy. PMID:25973400

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

    PubMed Central

    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

  11. 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.

  12. Structural abnormalities develop in the brain after ablation of the gene encoding nonmuscle myosin II-B heavy chain.

    PubMed

    Tullio, A N; Bridgman, P C; Tresser, N J; Chan, C C; Conti, M A; Adelstein, R S; Hara, Y

    2001-04-23

    Ablation of nonmuscle myosin heavy chain II-B (NMHC-B) in mice results in severe hydrocephalus with enlargement of the lateral and third ventricles. All B(-)/B(-) mice died either during embryonic development or on the day of birth (PO). Neurons cultured from superior cervical ganglia of B(-)/B(-) mice between embryonic day (E) 18 and P0 showed decreased rates of neurite outgrowth, and their growth cones had a distinctive narrow morphology compared with those from normal mice. Serial sections of E12.5, E13.5, and E15 mouse brains identified developmental defects in the ventricular neuroepithelium. On E12.5, disruption of the coherent ventricular surface and disordered cell migration of neuroepithelial and differentiated cells were seen at various points in the ventricular walls. These abnormalities resulted in the formation of rosettes in various regions of the brain and spinal cord. On E13.5 and E15, disruption of the ventricular surface and aberrant protrusions of neural cells into the ventricles became more prominent. By E18.5 and P0, the defects in cells lining the ventricular wall resulted in an obstructive hydrocephalus due to stenosis or occlusion of the third ventricle and cerebral aqueduct. These defects may be caused by abnormalities in the cell adhesive properties of neuroepithelial cells and suggest that NMHC-B is essential for both early and late developmental processes in the mammalian brain.

  13. NCAM-deficient mice show prominent abnormalities in serotonergic and BDNF systems in brain - Restoration by chronic amitriptyline.

    PubMed

    Aonurm-Helm, Anu; Anier, Kaili; Zharkovsky, Tamara; Castrén, Eero; Rantamäki, Tomi; Stepanov, Vladimir; Järv, Jaak; Zharkovsky, Alexander

    2015-12-01

    Mood disorders are associated with alterations in serotonergic system, deficient BDNF (brain-derived neurotrophic factor) signaling and abnormal synaptic plasticity. Increased degradation and reduced functions of NCAM (neural cell adhesion molecule) have recently been associated with depression and NCAM deficient mice show depression-related behavior and impaired learning. The aim of the present study was to investigate potential changes in serotonergic and BDNF systems in NCAM knock-out mice. Serotonergic nerve fiber density and SERT (serotonin transporter) protein levels were robustly reduced in the hippocampus, prefrontal cortex and basolateral amygdala of adult NCAM(-)(/-) mice. This SERT reduction was already evident during early postnatal development. [(3)H]MADAM binding experiments further demonstrated reduced availability of SERT in cell membranes of NCAM(-)(/-) mice. Moreover, the levels of serotonin and its major metabolite 5-HIAA were down regulated in the brains of NCAM(-)(/-) mice. NCAM(-)(/-) mice also showed a dramatic reduction in the BDNF protein levels in the hippocampus and prefrontal cortex. This BDNF deficiency was associated with reduced phosphorylation of its receptor TrkB. Importantly, chronic administration of antidepressant amitriptyline partially or completely restored these changes in serotonergic and BDNF systems, respectively. In conclusion, NCAM deficiency lead to prominent and persistent abnormalities in brain serotonergic and BDNF systems, which likely contributes to the behavioral and neurobiological phenotype of NCAM(-/-) mice.

  14. Characterization of subtle brain abnormalities in a mouse model of Hedgehog pathway antagonist-induced cleft lip and palate.

    PubMed

    Lipinski, Robert J; Holloway, Hunter T; O'Leary-Moore, Shonagh K; Ament, Jacob J; Pecevich, Stephen J; Cofer, Gary P; Budin, Francois; Everson, Joshua L; Johnson, G Allan; Sulik, Kathleen K

    2014-01-01

    Subtle behavioral and cognitive deficits have been documented in patient cohorts with orofacial clefts (OFCs). Recent neuroimaging studies argue that these traits are associated with structural brain abnormalities but have been limited to adolescent and adult populations where brain plasticity during infancy and childhood may be a confounding factor. Here, we employed high resolution magnetic resonance microscopy to examine primary brain morphology in a mouse model of OFCs. Transient in utero exposure to the Hedgehog (Hh) signaling pathway antagonist cyclopamine resulted in a spectrum of facial dysmorphology, including unilateral and bilateral cleft lip and palate, cleft of the secondary palate only, and a non-cleft phenotype marked by midfacial hypoplasia. Relative to controls, cyclopamine-exposed fetuses exhibited volumetric differences in several brain regions, including hypoplasia of the pituitary gland and olfactory bulbs, hyperplasia of the forebrain septal region, and expansion of the third ventricle. However, in affected fetuses the corpus callosum was intact and normal division of the forebrain was observed. This argues that temporally-specific Hh signaling perturbation can result in typical appearing OFCs in the absence of holoprosencephaly--a condition classically associated with Hh pathway inhibition and frequently co-occurring with OFCs. Supporting the premise that some forms of OFCs co-occur with subtle brain malformations, these results provide a possible ontological basis for traits identified in clinical populations. They also argue in favor of future investigations into genetic and/or environmental modulation of the Hh pathway in the etiopathogenesis of orofacial clefting.

  15. Characterization of Subtle Brain Abnormalities in a Mouse Model of Hedgehog Pathway Antagonist-Induced Cleft Lip and Palate

    PubMed Central

    Lipinski, Robert J.; Holloway, Hunter T.; O'Leary-Moore, Shonagh K.; Ament, Jacob J.; Pecevich, Stephen J.; Cofer, Gary P.; Budin, Francois; Everson, Joshua L.; Johnson, G. Allan; Sulik, Kathleen K.

    2014-01-01

    Subtle behavioral and cognitive deficits have been documented in patient cohorts with orofacial clefts (OFCs). Recent neuroimaging studies argue that these traits are associated with structural brain abnormalities but have been limited to adolescent and adult populations where brain plasticity during infancy and childhood may be a confounding factor. Here, we employed high resolution magnetic resonance microscopy to examine primary brain morphology in a mouse model of OFCs. Transient in utero exposure to the Hedgehog (Hh) signaling pathway antagonist cyclopamine resulted in a spectrum of facial dysmorphology, including unilateral and bilateral cleft lip and palate, cleft of the secondary palate only, and a non-cleft phenotype marked by midfacial hypoplasia. Relative to controls, cyclopamine-exposed fetuses exhibited volumetric differences in several brain regions, including hypoplasia of the pituitary gland and olfactory bulbs, hyperplasia of the forebrain septal region, and expansion of the third ventricle. However, in affected fetuses the corpus callosum was intact and normal division of the forebrain was observed. This argues that temporally-specific Hh signaling perturbation can result in typical appearing OFCs in the absence of holoprosencephaly—a condition classically associated with Hh pathway inhibition and frequently co-occurring with OFCs. Supporting the premise that some forms of OFCs co-occur with subtle brain malformations, these results provide a possible ontological basis for traits identified in clinical populations. They also argue in favor of future investigations into genetic and/or environmental modulation of the Hh pathway in the etiopathogenesis of orofacial clefting. PMID:25047453

  16. Dyslexic brain activation abnormalities in deep and shallow orthographies: A meta‐analysis of 28 functional neuroimaging studies

    PubMed Central

    Martin, Anna; Kronbichler, Martin

    2016-01-01

    Abstract We used coordinate‐based meta‐analysis to objectively quantify commonalities and differences of dyslexic functional brain abnormalities between alphabetic languages differing in orthographic depth. Specifically, we compared foci of under‐ and overactivation in dyslexic readers relative to nonimpaired readers reported in 14 studies in deep orthographies (DO: English) and in 14 studies in shallow orthographies (SO: Dutch, German, Italian, Swedish). The separate meta‐analyses of the two sets of studies showed universal reading‐related dyslexic underactivation in the left occipitotemporal cortex (including the visual word form area (VWFA)). The direct statistical comparison revealed higher convergence of underactivation for DO compared with SO in bilateral inferior parietal regions, but this abnormality disappeared when foci resulting from stronger dyslexic task‐negative activation (i.e., deactivation relative to baseline) were excluded. Higher convergence of underactivation for DO compared with SO was further identified in the left inferior frontal gyrus (IFG) pars triangularis, left precuneus, and right superior temporal gyrus, together with higher convergence of overactivation in the left anterior insula. Higher convergence of underactivation for SO compared with DO was found in the left fusiform gyrus, left temporoparietal cortex, left IFG pars orbitalis, and left frontal operculum, together with higher convergence of overactivation in the left precentral gyrus. Taken together, the findings support the notion of a biological unity of dyslexia, with additional orthography‐specific abnormalities and presumably different compensatory mechanisms. The results are discussed in relation to current functional neuroanatomical models of developmental dyslexia. Hum Brain Mapp 37:2676–2699, 2016. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. PMID:27061464

  17. 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

  18. 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 Central

    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 vCJD-infected human

  19. 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

  20. Thallium-201 myocardial perfusion imaging in myocarditis

    SciTech Connect

    Tamaki, N.; Yonekura, Y.; Kadota, K.; Kambara, H.; Torizuka, K.

    1985-08-01

    TI-201 myocardial perfusion imaging was performed in six patients with clinically documented myocarditis. Each case manifested electrocardiographic abnormalities with elevation of serum cardiac enzymes and no significant stenosis of the coronary arteries observed on angiogram. Resting TI-201 images were visually assessed by three observers. Focal perfusion defects were observed in three cases (50%), among which two showed multiple perfusion defects. Emission computed tomography using TI-201 clearly delineated multifocal lesions in the first case. On the other hand, no significant perfusion defects were noted in the remaining three cases. Thus, myocarditis should be considered as one of the disease entities that may produce perfusion defects on TI-201 myocardial imaging.

  1. 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.

  2. Zika Virus Infection as a Cause of Congenital Brain Abnormalities and Guillain–Barré Syndrome: Systematic Review

    PubMed Central

    Reveiz, Ludovic; Oladapo, Olufemi T.; Martínez-Vega, Ruth; Haefliger, Anina

    2017-01-01

    Background The World Health Organization (WHO) stated in March 2016 that there was scientific consensus that the mosquito-borne Zika virus was a cause of the neurological disorder Guillain–Barré syndrome (GBS) and of microcephaly and other congenital brain abnormalities based on rapid evidence assessments. Decisions about causality require systematic assessment to guide public health actions. The objectives of this study were to update and reassess the evidence for causality through a rapid and systematic review about links between Zika virus infection and (a) congenital brain abnormalities, including microcephaly, in the foetuses and offspring of pregnant women and (b) GBS in any population, and to describe the process and outcomes of an expert assessment of the evidence about causality. Methods and Findings The study had three linked components. First, in February 2016, we developed a causality framework that defined questions about the relationship between Zika virus infection and each of the two clinical outcomes in ten dimensions: temporality, biological plausibility, strength of association, alternative explanations, cessation, dose–response relationship, animal experiments, analogy, specificity, and consistency. Second, we did a systematic review (protocol number CRD42016036693). We searched multiple online sources up to May 30, 2016 to find studies that directly addressed either outcome and any causality dimension, used methods to expedite study selection, data extraction, and quality assessment, and summarised evidence descriptively. Third, WHO convened a multidisciplinary panel of experts who assessed the review findings and reached consensus statements to update the WHO position on causality. We found 1,091 unique items up to May 30, 2016. For congenital brain abnormalities, including microcephaly, we included 72 items; for eight of ten causality dimensions (all except dose–response relationship and specificity), we found that more than half the

  3. Countercurrent transfer of dopamine from venous blood in the cavernous sinus to the arterial blood supplying the brain - the perfused rabbit head as an experimental model.

    PubMed

    Muszak, J; Krzymowski, T; Gilun, P; Stefanczyk-Krzymowska, S

    2014-10-01

    The objective of the current study was to check whether countercurrent transfer of dopamine occurs in the cavernous sinus of the rabbit and whether the rabbit can be used as an animal model to study cavernous sinus function. After exsanguination of the animal, oxygenated and warmed (37°C) Hanseneleit-Krebs buffer with autologous or homologous blood (in a 3:1 or 1:1 ratio) was pumped through both common carotid arteries into the head (60 ml/min; 80-100 mm Hg) and radiolabeled dopamine (3(H)-DA, 10 μCi) was infused into the cavernous sinus through the angular oculi vein. Cerebral blood from the basilar artery was collected from the cannulated vertebral artery during 3(H)-DA infusion and for 10 minutes after completion of infusion. Selected brain tissue samples were collected after completion of the head perfusion. It was demonstrated that dopamine can penetrate from the rabbit's cavernous sinus to the internal carotid artery supplying the brain. Dopamine permeation was greater when the rabbit head was perfused with buffer and blood in a 3:1 ratio than with 1:1 (P<0.01). When the head was perfused with buffer and blood in a 3:1 ratio, significant radioactivity was found in samples collected from the brain basilar artery during and after 3(H)-DA infusion (P<0.001). The radioactivity was identified as 34.13 ± 2.7% unmetabolized 3(H)-DA and 65.9 ± 2.7% its metabolites. Significant radioactivity was also found in some brain tissue samples in both groups (P<0.05). The concentration of free radiolabeled dopamine particles in the dialysate of blood plasma and plasma diluted with buffer did not differ significantly. Because the structures of the cavernous sinus and cavernous fragment of the internal carotid artery of the rabbit are similar to those in humans, it suggests that rabbits can serve as a model for experimental physiological studies of cavernous sinus function and retrograde dopamine transfer in the cavernous sinus should be considered as an important link in

  4. Brain MRI abnormalities in the adult form of myotonic dystrophy type 1: A longitudinal case series study.

    PubMed

    Conforti, Renata; de Cristofaro, Mario; Cristofano, Adriana; Brogna, Barbara; Sardaro, Angela; Tedeschi, Gioacchino; Cirillo, Sossio; Di Costanzo, Alfonso

    2016-02-01

    This study aimed to verify whether brain abnormalities, previously described in patients with myotonic dystrophy type 1 (DM1) by magnetic resonance imaging (MRI), progressed over time and, if so, to characterize their progression. Thirteen DM1 patients, who had at least two MRI examinations, were retrospectively evaluated and included in the study. The mean duration (± standard deviation) of follow-up was 13.4 (±3.8) years, over a range of 7-20 years. White matter lesions (WMLs) were rated by semi-quantitative method, the signal intensity of white matter poster-superior to trigones (WMPST) by reference to standard images and brain atrophy by ventricular/brain ratio (VBR). At the end of MRI follow-up, the scores relative to lobar, temporal and periventricular WMLs, to WMPST signal intensity and to VBR were significantly increased compared to baseline, and MRI changes were more evident in some families than in others. No correlation was found between the MRI changes and age, onset, disease duration, muscular involvement, CTG repetition and follow-up duration. These results demonstrated that white matter involvement and brain atrophy were progressive in DM1 and suggested that progression rate varied from patient to patient, regardless of age, disease duration and genetic defect.

  5. Glucose Metabolism during Resting State Reveals Abnormal Brain Networks Organization in the Alzheimer’s Disease and Mild Cognitive Impairment

    PubMed Central

    Martínez-Montes, Eduardo

    2013-01-01

    This paper aims to study the abnormal patterns of brain glucose metabolism co-variations in Alzheimer disease (AD) and Mild Cognitive Impairment (MCI) patients compared to Normal healthy controls (NC) using the Alzheimer Disease Neuroimaging Initiative (ADNI) database. The local cerebral metabolic rate for glucose (CMRgl) in a set of 90 structures belonging to the AAL atlas was obtained from Fluro-Deoxyglucose Positron Emission Tomography data in resting state. It is assumed that brain regions whose CMRgl values are significantly correlated are functionally associated; therefore, when metabolism is altered in a single region, the alteration will affect the metabolism of other brain areas with which it interrelates. The glucose metabolism network (represented by the matrix of the CMRgl co-variations among all pairs of structures) was studied using the graph theory framework. The highest concurrent fluctuations in CMRgl were basically identified between homologous cortical regions in all groups. Significant differences in CMRgl co-variations in AD and MCI groups as compared to NC were found. The AD and MCI patients showed aberrant patterns in comparison to NC subjects, as detected by global and local network properties (global and local efficiency, clustering index, and others). MCI network’s attributes showed an intermediate position between NC and AD, corroborating it as a transitional stage from normal aging to Alzheimer disease. Our study is an attempt at exploring the complex association between glucose metabolism, CMRgl covariations and the attributes of the brain network organization in AD and MCI. PMID:23894356

  6. Guidelines for brain radionuclide imaging. Perfusion single photon computed tomography (SPECT) using Tc-99m radiopharmaceuticals and brain metabolism positron emission tomography (PET) using F-18 fluorodeoxyglucose. The Belgian Society for Nuclear Medicine.

    PubMed

    Vander Borght, T; Laloux, P; Maes, A; Salmon, E; Goethals, I; Goldman, S

    2001-12-01

    The purpose of these guidelines is to assist nuclear medicine practitioners in recommending, performing, interpreting, and reporting the results of brain perfusion SPECT studies using Tc-99m radiopharmaceuticals and brain metabolism PET studies using F-18 fluorodeoxyglucose (FDG). These guidelines have been adapted and extended from those produced by the Society of Nuclear Medicine (Juni et al., 1998) and the European Association of Nuclear Medicine by a Belgian group of experts in the field trained in neurology and/or nuclear medicine. Some indications are not universally approved (e.g. brain death), but largely supported by the literature. They have been included in these guidelines in order to provide recommendations and a standardised protocol.

  7. Microstructural callosal abnormalities in normal-appearing brain of children with developmental delay detected with diffusion tensor imaging.

    PubMed

    Ding, Xiao-Qi; Sun, Yimeng; Kruse, Bernd; Illies, Till; Zeumer, Hermann; Fiehler, Jens; Lanfermann, Heinrich

    2009-06-01

    Callosal fibres play an important role in psychomotor and cognitive functions. The purpose of this study was to investigate possible microstructural abnormalities of the corpus callosum in children with developmental delay, who have normal conventional brain MR imaging results. Seventeen pediatric patients (aged 1-9 years) with developmental delay were studied. Quantitative T2 and fractional anisotropy (FA) values were measured at the genu and splenium of the corpus callosum (CC). Fibre tracking, volumetric determination, as well as fibre density calculations of the CC were also carried out. The results were compared with those of the age-matched healthy subjects. A general elevation of T2 relaxation times (105 ms in patients vs. 95 ms in controls) and reduction of the FA values (0.66 in patients vs. 0.74 in controls) at the genu of the CC were found in patients. Reductions of the fibre numbers (5,464 in patients vs. 8,886 in controls) and volumes (3,415 ml in patients vs. 5,235 ml in controls) of the CC were found only in patients older than 5 years. The study indicates that despite their inconspicuous findings in conventional MRI microstructural brain abnormalities are evident in these pediatric patients suffering from developmental delay.

  8. Abnormal brain functional connectivity leads to impaired mood and cognition in hyperthyroidism: a resting-state functional MRI study

    PubMed Central

    Li, Ling; Zhi, Mengmeng; Hou, Zhenghua; Zhang, Yuqun; Yue, Yingying; Yuan, Yonggui

    2017-01-01

    Patients with hyperthyroidism frequently have neuropsychiatric complaints such as lack of concentration, poor memory, depression, anxiety, nervousness, and irritability, suggesting brain dysfunction. However, the underlying process of these symptoms remains unclear. Using resting-state functional magnetic resonance imaging (rs-fMRI), we depicted the altered graph theoretical metric degree centrality (DC) and seed-based resting-state functional connectivity (FC) in 33 hyperthyroid patients relative to 33 healthy controls. The peak points of significantly altered DC between the two groups were defined as the seed regions to calculate FC to the whole brain. Then, partial correlation analyses were performed between abnormal DC, FC and neuropsychological performances, as well as some clinical indexes. The decreased intrinsic functional connectivity in the posterior lobe of cerebellum (PLC) and medial frontal gyrus (MeFG), as well as the abnormal seed-based FC anchored in default mode network (DMN), attention network, visual network and cognitive network in this study, possibly constitutes the latent mechanism for emotional and cognitive changes in hyperthyroidism, including anxiety and impaired processing speed. PMID:28009983

  9. 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.

  10. Sodium sulfide prevents water diffusion abnormality in the brain and improves long term outcome after cardiac arrest in mice

    PubMed Central

    Kida, Kotaro; Minamishima, Shizuka; Wang, Huifang; Ren, JiaQian; Yigitkanli, Kazim; Nozari, Ala; Mandeville, Joseph B.; Liu, Philip K.; Liu, Christina H.; Ichinose, Fumito

    2012-01-01

    Aim of the study Sudden cardiac arrest (CA) is one of the leading causes of death worldwide. Previously we demonstrated that administration of sodium sulfide (Na2S), a hydrogen sulfide (H2S) donor, markedly improved the neurological outcome and survival rate at 24h after CA and cardiopulmonary resuscitation (CPR) in mice. In this study, we sought to elucidate the mechanism responsible for the neuroprotective effects of Na2S and its impact on the long-term survival after CA/CPR in mice. Methods Adult male mice were subjected to potassium-induced CA for 7.5 min at 37°C whereupon CPR was performed with chest compression and mechanical ventilation. Mice received Na2S (0.55 mg/kg i.v.) or vehicle 1 min before CPR. Results Mice that were subjected to CA/CPR and received vehicle exhibited a poor 10-day survival rate (4/12) and depressed neurological function. Cardiac arrest and CPR induced abnormal water diffusion in the vulnerable regions of the brain, as demonstrated by hyperintense diffusion-weighted imaging (DWI) 24h after CA/CPR. Extent of hyperintense DWI was associated with matrix metalloproteinase 9 (MMP-9) activation, worse neurological outcomes, and poor survival rate at 10 days after CA/CPR. Administration of Na2S prevented the development of abnormal water diffusion and MMP-9 activation and markedly improved neurological function and long-term survival (9/12, P<0.05 vs. vehicle) after CA/CPR. Conclusion These results suggest that administration of Na2S 1 min before CPR improves neurological function and survival rate at 10 days after CA/CPR by preventing water diffusion abnormality in the brain potentially via inhibiting MMP-9 activation early after resuscitation. PMID:22370005

  11. Comparison of nine tractography algorithms for detecting abnormal structural brain networks in Alzheimer’s disease

    PubMed Central

    Zhan, Liang; Zhou, Jiayu; Wang, Yalin; Jin, Yan; Jahanshad, Neda; Prasad, Gautam; Nir, Talia M.; Leonardo, Cassandra D.; Ye, Jieping; Thompson, Paul M.; for the Alzheimer’s Disease Neuroimaging Initiative

    2015-01-01

    Alzheimer’s disease (AD) involves a gradual breakdown of brain connectivity, and network analyses offer a promising new approach to track and understand disease progression. Even so, our ability to detect degenerative changes in brain networks depends on the methods used. Here we compared several tractography and feature extraction methods to see which ones gave best diagnostic classification for 202 people with AD, mild cognitive impairment or normal cognition, scanned with 41-gradient diffusion-weighted magnetic resonance imaging as part of the Alzheimer’s Disease Neuroimaging Initiative (ADNI) project. We computed brain networks based on whole brain tractography with nine different methods – four of them tensor-based deterministic (FACT, RK2, SL, and TL), two orientation distribution function (ODF)-based deterministic (FACT, RK2), two ODF-based probabilistic approaches (Hough and PICo), and one “ball-and-stick” approach (Probtrackx). Brain networks derived from different tractography algorithms did not differ in terms of classification performance on ADNI, but performing principal components analysis on networks helped classification in some cases. Small differences may still be detectable in a truly vast cohort, but these experiments help assess the relative advantages of different tractography algorithms, and different post-processing choices, when used for classification. PMID:25926791

  12. 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.

  13. 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.

  14. Imaging brain fatigue from sustained mental workload: an ASL perfusion study of the time-on-task effect.

    PubMed

    Lim, Julian; Wu, Wen-Chau; Wang, Jiongjiong; Detre, John A; Dinges, David F; Rao, Hengyi

    2010-02-15

    During sustained periods of a taxing cognitive workload, humans typically display time-on-task (TOT) effects, in which performance gets steadily worse over the period of task engagement. Arterial spin labeling (ASL) perfusion functional magnetic resonance imaging (fMRI) was used in this study to investigate the neural correlates of TOT effects in a group of 15 subjects as they performed a 20-min continuous psychomotor vigilance test (PVT). Subjects displayed significant TOT effects, as seen in progressively slower reaction times and significantly increased mental fatigue ratings after the task. Perfusion data showed that the PVT activates a right lateralized fronto-parietal attentional network in addition to the basal ganglia and sensorimotor cortices. The fronto-parietal network was less active during post-task rest compared to pre-task rest, and regional CBF decrease in this network correlated with performance decline. These results demonstrate the persistent effects of cognitive fatigue in the fronto-parietal network after a period of heavy mental work and indicate the critical role of this attentional network in mediating TOT effects. Furthermore, resting regional CBF in the thalamus and right middle frontal gyrus prior to task onset was predictive of subjects' subsequent performance decline, suggesting that resting CBF quantified by ASL perfusion fMRI may be a useful indicator of performance potential and a marker of the level of fatigue in the neural attentional system.

  15. Abnormal brain white matter network in young smokers: a graph theory analysis study.

    PubMed

    Zhang, Yajuan; Li, Min; Wang, Ruonan; Bi, Yanzhi; Li, Yangding; Yi, Zhang; Liu, Jixin; Yu, Dahua; Yuan, Kai

    2017-03-13

    Previous diffusion tensor imaging (DTI) studies had investigated the white matter (WM) integrity abnormalities in some specific fiber bundles in smokers. However, little is known about the changes in topological organization of WM structural network in young smokers. In current study, we acquired DTI datasets from 58 male young smokers and 51 matched nonsmokers and constructed the WM networks by the deterministic fiber tracking approach. Graph theoretical analysis was used to compare the topological parameters of WM network (global and nodal) and the inter-regional fractional anisotropy (FA) weighted WM connections between groups. The results demonstrated that both young smokers and nonsmokers had small-world topology in WM network. Further analysis revealed that the young smokers exhibited the abnormal topological organization, i.e., increased network strength, global efficiency, and decreased shortest path length. In addition, the increased nodal efficiency predominately was located in frontal cortex, striatum and anterior cingulate gyrus (ACG) in smokers. Moreover, based on network-based statistic (NBS) approach, the significant increased FA-weighted WM connections were mainly found in the PFC, ACG and supplementary motor area (SMA) regions. Meanwhile, the network parameters were correlated with the nicotine dependence severity (FTND) scores, and the nodal efficiency of orbitofrontal cortex was positive correlation with the cigarette per day (CPD) in young smokers. We revealed the abnormal topological organization of WM network in young smokers, which may improve our understanding of the neural mechanism of young smokers form WM topological organization level.

  16. Abnormal brain activation during movement observation in patients with conversion paralysis.

    PubMed

    Burgmer, Markus; Konrad, Carsten; Jansen, Andreas; Kugel, Harald; Sommer, Jens; Heindel, Walter; Ringelstein, Erich B; Heuft, Gereon; Knecht, Stefan

    2006-02-15

    Dissociative paralysis in conversion disorders has variably been attributed to a lack of movement initiation or an inhibition of movement. While psychodynamic theory suggests altered movement conceptualization, brain activation associated with observation and replication of movements has so far not been assessed neurobiologically. Here, we measured brain activation by functional magnetic resonance imaging during observation and subsequent imitative execution of movements in four patients with dissociative hand paralysis. Compared to healthy controls conversion disorder patients showed decreased activation of cortical hand areas during movement observation. This effect was specific to the side of their dissociative paralysis. No brain activation compatible with movement inhibition was observed. These findings indicate that in dissociative paralysis, there is not only derangement of movement initiation but already of movement conceptualization. This raises the possibility that strategies targeted at reestablishing appropriate movement conceptualization may contribute to the therapy of dissociative paralysis.

  17. White Matter Abnormalities are Associated with Chronic Postconcussion Symptoms in Blast-Related Mild Traumatic Brain Injury

    PubMed Central

    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 non-specific 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 co-morbid 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. PMID:26497829

  18. 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…

  19. 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…

  20. 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…

  1. 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…

  2. 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.

  3. Time-resolved multi-channel optical system for assessment of brain oxygenation and perfusion by monitoring of diffuse reflectance and fluorescence

    NASA Astrophysics Data System (ADS)

    Milej, D.; Gerega, A.; Kacprzak, M.; Sawosz, P.; Weigl, W.; Maniewski, R.; Liebert, A.

    2014-03-01

    Time-resolved near-infrared spectroscopy is an optical technique which can be applied in tissue oxygenation assessment. In the last decade this method is extensively tested as a potential clinical tool for noninvasive human brain function monitoring and imaging. In the present paper we show construction of an instrument which allows for: (i) estimation of changes in brain tissue oxygenation using two-wavelength spectroscopy approach and (ii) brain perfusion assessment with the use of single-wavelength reflectometry or fluorescence measurements combined with ICG-bolus tracking. A signal processing algorithm based on statistical moments of measured distributions of times of flight of photons is implemented. This data analysis method allows for separation of signals originating from extra- and intracerebral tissue compartments. In this paper we present compact and easily reconfigurable system which can be applied in different types of time-resolved experiments: two-wavelength measurements at 687 and 832 nm, single wavelength reflectance measurements at 760 nm (which is at maximum of ICG absorption spectrum) or fluorescence measurements with excitation at 760 nm. Details of the instrument construction and results of its technical tests are shown. Furthermore, results of in-vivo measurements obtained for various modes of operation of the system are presented.

  4. Dyrk1A Haploinsufficiency Affects Viability and Causes Developmental Delay and Abnormal Brain Morphology in Mice

    PubMed Central

    Fotaki, Vassiliki; Dierssen, Mara; Alcántara, Soledad; Martínez, Salvador; Martí, Eulàlia; Casas, Caty; Visa, Joana; Soriano, Eduardo; Estivill, Xavier; Arbonés, Maria L.

    2002-01-01

    DYRK1A is the human orthologue of the Drosophila minibrain (mnb) gene, which is involved in postembryonic neurogenesis in flies. Because of its mapping position on chromosome 21 and the neurobehavioral alterations shown by mice overexpressing this gene, involvement of DYRK1A in some of the neurological defects of Down syndrome patients has been suggested. To gain insight into its physiological role, we have generated mice deficient in Dyrk1A function by gene targeting. Dyrk1A−/− null mutants presented a general growth delay and died during midgestation. Mice heterozygous for the mutation (Dyrk1A+/−) showed decreased neonatal viability and a significant body size reduction from birth to adulthood. General neurobehavioral analysis revealed preweaning developmental delay of Dyrk1A+/− mice and specific alterations in adults. Brains of Dyrk1A+/− mice were decreased in size in a region-specific manner, although the cytoarchitecture and neuronal components in most areas were not altered. Cell counts showed increased neuronal densities in some brain regions and a specific decrease in the number of neurons in the superior colliculus, which exhibited a significant size reduction. These data provide evidence about the nonredundant, vital role of Dyrk1A and suggest a conserved mode of action that determines normal growth and brain size in both mice and flies. PMID:12192061

  5. Abnormal Brain Dynamics Underlie Speech Production in Children with Autism Spectrum Disorder.

    PubMed

    Pang, Elizabeth W; Valica, Tatiana; MacDonald, Matt J; Taylor, Margot J; Brian, Jessica; Lerch, Jason P; Anagnostou, Evdokia

    2016-02-01

    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.

  6. 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

  7. 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

  8. 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

  9. 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

  10. Reversal of focal "misery-perfusion syndrome" by extra-intracranial arterial bypass in hemodynamic cerebral ischemia. A case study with 15O positron emission tomography.

    PubMed

    Baron, J C; Bousser, M G; Rey, A; Guillard, A; Comar, D; Castaigne, P

    1981-01-01

    Tomographic images of cerebral blood flow (CBF) and oxygen extraction fraction (OEF) using the 15O continuous inhalation technique, and positron emission tomography, were obtained from a patient with cerebral ischemia distal to an occluded left internal carotid artery. There was a focal mismatch between CBF and oxygen metabolism in the brain supplied by the middle cerebral artery where CBF was decreased and OEF increased ("misery-perfusion syndrome" as opposed to "luxury-perfusion syndrome"). These abnormalities were most marked in the parieto-occipital watershed area. After left superficial temporal to middle cerebral artery anastomosis, the clinical attacks ceased and a repeat study did not demonstrate the previous CBF and OEF abnormalities. This suggests that this pattern of abnormalities indicates potential viable tissue. The concept of "misery-perfusion" may be of some importance in the pathophysiological mechanisms of hemodynamic cerebral ischemia and serve as a rational basis for revascularization procedures.

  11. Higher frequency of brain abnormalities in neuromyelitis optica spectrum disorder patients without primary Sjögren's syndrome.

    PubMed

    Gu, Li-Na; Zhang, Min; Zhu, Hui; Liu, Jing-Yao

    2016-10-01

    Neuromyelitis optica spectrum disorder often co-exists with primary Sjögren's syndrome. We compared the clinical features of 16 neuromyelitis optica spectrum disorder patients with (n = 6) or without primary Sjögren's syndrome (n = 10). All patients underwent extensive clinical, laboratory, and MRI evaluations. There were no statistical differences in demographics or first neurological involvement at onset between neuromyelitis optica spectrum disorder patients with and without primary Sjögren's syndrome. The laboratory findings of cerebrospinal fluid oligoclonal banding, serum C-reactive protein, antinuclear autoantibody, anti-Sjögren's-syndrome-related antigen A antibodies, anti-Sjögren's-syndrome-related antigen B antibodies, and anti-Sm antibodies were significantly higher in patients with primary Sjögren's syndrome than those without. Anti-aquaporin 4 antibodies were detectable in 67% (4/6) of patients with primary Sjögren's syndrome and in 60% (6/10) of patients without primary Sjögren's syndrome. More brain abnormalities were observed in patients without primary Sjögren's syndrome than in those with primary Sjögren's syndrome. Segments lesions (> 3 centrum) were noted in 50% (5/10) of patients without primary Sjögren's syndrome and in 67% (4/6) of patients with primary Sjögren's syndrome. These findings indicate that the clinical characteristics of neuromyelitis optica spectrum disorder patients with and without primary Sjögren's syndrome are similar. However, neuromyelitis optica spectrum disorder patients without primary Sjögren's syndrome have a high frequency of brain abnormalities.

  12. Higher frequency of brain abnormalities in neuromyelitis optica spectrum disorder patients without primary Sjögren's syndrome

    PubMed Central

    Gu, Li-na; Zhang, Min; Zhu, Hui; Liu, Jing-yao

    2016-01-01

    Neuromyelitis optica spectrum disorder often co-exists with primary Sjögren's syndrome. We compared the clinical features of 16 neuromyelitis optica spectrum disorder patients with (n = 6) or without primary Sjögren's syndrome (n = 10). All patients underwent extensive clinical, laboratory, and MRI evaluations. There were no statistical differences in demographics or first neurological involvement at onset between neuromyelitis optica spectrum disorder patients with and without primary Sjögren's syndrome. The laboratory findings of cerebrospinal fluid oligoclonal banding, serum C-reactive protein, antinuclear autoantibody, anti-Sjögren's-syndrome-related antigen A antibodies, anti-Sjögren's-syndrome-related antigen B antibodies, and anti-Sm antibodies were significantly higher in patients with primary Sjögren's syndrome than those without. Anti-aquaporin 4 antibodies were detectable in 67% (4/6) of patients with primary Sjögren's syndrome and in 60% (6/10) of patients without primary Sjögren's syndrome. More brain abnormalities were observed in patients without primary Sjögren's syndrome than in those with primary Sjögren's syndrome. Segments lesions (> 3 centrum) were noted in 50% (5/10) of patients without primary Sjögren's syndrome and in 67% (4/6) of patients with primary Sjögren's syndrome. These findings indicate that the clinical characteristics of neuromyelitis optica spectrum disorder patients with and without primary Sjögren's syndrome are similar. However, neuromyelitis optica spectrum disorder patients without primary Sjögren's syndrome have a high frequency of brain abnormalities. PMID:27904495

  13. 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

  14. Functional Changes after Recombinant Human Growth Hormone Replacement in Patients with Chronic Traumatic Brain Injury and Abnormal Growth Hormone Secretion.

    PubMed

    Mossberg, Kurt A; Durham, William J; Zgaljardic, Dennis J; Gilkison, Charles R; Danesi, Christopher P; Sheffield-Moore, Melinda; Masel, Brent E; Urban, Randall J

    2017-02-15

    We explored the effects of recombinant human growth hormone (rhGH) replacement on physical and cognitive functioning in subjects with a moderate-to-severe traumatic brain injury (TBI) with abnormal growth hormone (GH) secretion. Fifteen individuals who sustained a TBI at least 12 months prior to study enrollment were identified as having abnormal GH secretion by glucagon stimulation testing (maximum GH response less than 8 ng/mL). Peak cardiorespiratory capacity, body composition, and muscle force testing were assessed at baseline and one year after rhGH replacement. Additionally, standardized neuropsychological tests that assess memory, processing speed, and cognitive flexibility, as well as self-report inventories related to depression and fatigue, were administered at baseline and 1 year after rhGH replacement. Comparison tests were performed with proper post hoc analyses. All analyses were carried out at α < 0.05. Peak O2 consumption, peak oxygen pulse (estimate of cardiac stroke volume), and peak ventilation all significantly increased (p < 0.05). Maximal isometric and isokinetic force production were not altered. Skeletal muscle fatigue did not change but the perceptual rating of fatigue was reduced by ∼25% (p = 0.06). Cognitive performance did not change significantly over time, whereas self-reported symptoms related to depression and fatigue significantly improved. The observed changes suggest that rhGH replacement has a positive impact on cardiorespiratory fitness and a positive impact on perceptual fatigue in survivors of TBI with altered GH secretion.

  15. Apathy is associated with white matter abnormalities in anterior, medial brain regions in persons with HIV infection.

    PubMed

    Kamat, Rujvi; Brown, Gregory G; Bolden, Khalima; Fennema-Notestein, Christine; Archibald, Sarah; Marcotte, Thomas D; Letendre, Scott L; Ellis, Ronald J; Woods, Steven Paul; Grant, Igor; Heaton, Robert K

    2014-01-01

    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, which 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 cluster of differentiation 4 (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.

  16. 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

  17. Steroid abnormalities and the developing brain: declarative memory for emotionally arousing and neutral material in children with congenital adrenal hyperplasia.

    PubMed

    Maheu, Françoise S; Merke, Deborah P; Schroth, Elizabeth A; Keil, Margaret F; Hardin, Julie; Poeth, Kaitlin; Pine, Daniel S; Ernst, Monique

    2008-02-01

    Steroid hormones modulate memory in animals and human adults. Little is known on the developmental effects 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 12-14 years) completed the study. Subjects were presented positive, negative and neutral pictures. Memory recall occurred about 30min 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>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.

  18. Intracranial Intra-arachnoid Diverticula and Cyst-like Abnormalities of the Brain.

    PubMed

    Platt, Simon; Hicks, Jill; Matiasek, Lara

    2016-03-01

    Primary intracranial cystic or cyst-like lesions include intra-arachnoid, epidermoid, dermoid, and choroid plexus cysts. Differentiation of these cystic lesions can usually be accomplished by imaging studies alone; however, some cysts are similar in appearance and require histopathology for definitive diagnosis. Clinical signs often reflect the location of the cysts within the intracranial cavity rather than the type of cyst. If clinical signs are significant and progressive, surgical removal is warranted and may be successful, although cystic contents could be harmful if allowed to contact surrounding brain parenchyma or meninges.

  19. Neurovascular abnormalities in brain disorders: highlights with angiogenesis and magnetic resonance imaging studies

    PubMed Central

    2013-01-01

    The coupling between neuronal activity and vascular responses is controlled by the neurovascular unit (NVU), which comprises multiple cell types. Many different types of dysfunction in these cells may impair the proper control of vascular responses by the NVU. Magnetic resonance imaging, which is the most powerful tool available to investigate neurovascular structures or functions, will be discussed in the present article in relation to its applications and discoveries. Because aberrant angiogenesis and vascular remodeling have been increasingly reported as being implicated in brain pathogenesis, this review article will refer to this hallmark event when suitable. PMID:23829868

  20. Early neuromodulation prevents the development of brain and behavioral abnormalities in a rodent model of schizophrenia.

    PubMed

    Hadar, R; Bikovski, L; Soto-Montenegro, M L; Schimke, J; Maier, P; Ewing, S; Voget, M; Wieske, F; Götz, T; Desco, M; Hamani, C; Pascau, J; Weiner, I; Winter, C

    2017-04-04

    The notion that schizophrenia is a neurodevelopmental disorder in which neuropathologies evolve gradually over the developmental course indicates a potential therapeutic window during which pathophysiological processes may be modified to halt disease progression or reduce its severity. Here we used a neurodevelopmental maternal immune stimulation (MIS) rat model of schizophrenia to test whether early targeted modulatory intervention would affect schizophrenia's neurodevelopmental course. We applied deep brain stimulation (DBS) or sham stimulation to the medial prefrontal cortex (mPFC) of adolescent MIS rats and respective controls, and investigated its behavioral, biochemical, brain-structural and -metabolic effects in adulthood. We found that mPFC-DBS successfully prevented the emergence of deficits in sensorimotor gating, attentional selectivity and executive function in adulthood, as well as the enlargement of lateral ventricle volumes and mal-development of dopaminergic and serotonergic transmission. These data suggest that the mPFC may be a valuable target for effective preventive treatments. This may have significant translational value, suggesting that targeting the mPFC before the onset of psychosis via less invasive neuromodulation approaches may be a viable preventive strategy.Molecular Psychiatry advance online publication, 4 April 2017; doi:10.1038/mp.2017.52.

  1. High fat diet produces brain insulin resistance, synaptodendritic abnormalities and altered behavior in mice.

    PubMed

    Arnold, Steven E; Lucki, Irwin; Brookshire, Bethany R; Carlson, Gregory C; Browne, Caroline A; Kazi, Hala; Bang, Sookhee; Choi, Bo-Ran; Chen, Yong; McMullen, Mary F; Kim, Sangwon F

    2014-07-01

    Insulin resistance and other features of the metabolic syndrome are increasingly recognized for their effects on cognitive health. To ascertain mechanisms by which this occurs, we fed mice a very high fat diet (60% kcal by fat) for 17days or a moderate high fat diet (HFD, 45% kcal by fat) for 8weeks and examined changes in brain insulin signaling responses, hippocampal synaptodendritic protein expression, and spatial working memory. Compared to normal control diet mice, cerebral cortex tissues of HFD mice were insulin-resistant as evidenced by failed activation of Akt, S6 and GSK3β with ex-vivo insulin stimulation. Importantly, we found that expression of brain IPMK, which is necessary for mTOR/Akt signaling, remained decreased in HFD mice upon activation of AMPK. HFD mouse hippocampus exhibited increased expression of serine-phosphorylated insulin receptor substrate 1 (IRS1-pS(616)), a marker of insulin resistance, as well as decreased expression of PSD-95, a scaffolding protein enriched in post-synaptic densities, and synaptopodin, an actin-associated protein enriched in spine apparatuses. Spatial working memory was impaired as assessed by decreased spontaneous alternation in a T-maze. These findings indicate that HFD is associated with telencephalic insulin resistance and deleterious effects on synaptic integrity and cognitive behaviors.

  2. High Fat Diet Produces Brain Insulin Resistance, Synaptodendritic Abnormalities and Altered Behavior in Mice

    PubMed Central

    Arnold, Steven E.; Lucki, Irwin; Brookshire, Bethany R.; Carlson, Gregory C.; Browne, Carolyn A.; Kazi, Hala; Bang, Sookhee; Choi, Bo-Ran; Chen, Yong; McMullen, Mary F.; Kim, Sangwon F.

    2014-01-01

    Insulin resistance and other features of the metabolic syndrome are increasingly recognized for their effects on cognitive health. To ascertain mechanisms by which this occurs, we fed mice a very high fat diet (60% kcal by fat) for 17 days or a moderate high fat diet (HFD, 45% kcal by fat) for 8 weeks and examined changes in brain insulin signaling responses, hippocampal synaptodendritic protein expression, and spatial working memory. Compared to normal control diet mice, cerebral cortex tissues of HFD mice were insulin-resistant as evidenced by failed activation of Akt, S6 and GSK3β with ex-vivo insulin stimulation. Importantly, we found that expression of brain IPMK, which is necessary for mTOR/Akt signaling, remained decreased in HFD mice upon activation of AMPK. HFD mouse hippocampus exhibited increased expression of serine-phosphorylated insulin receptor substrate 1 (IRS1-pS616), a marker of insulin resistance, as well as decreased expression of PSD-95, a scaffolding protein enriched in post-synaptic densities, and synaptopodin, an actin-associated protein enriched in spine apparatuses. Spatial working memory was impaired as assessed by decreased spontaneous alternation in a T-maze. These findings indicate that HFD is associated with telencephalic insulin resistance and deleterious effects on synaptic integrity and cognitive behaviors. PMID:24686304

  3. 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

  4. Deficiency of the Chromatin Regulator Brpf1 Causes Abnormal Brain Development*

    PubMed Central

    You, Linya; Zou, Jinfeng; Zhao, Hong; Bertos, Nicholas R.; Park, Morag; Wang, Edwin; Yang, Xiang-Jiao

    2015-01-01

    Epigenetic mechanisms are important in different neurological disorders, and one such mechanism is histone acetylation. The multivalent chromatin regulator BRPF1 (bromodomain- and plant homeodomain-linked (PHD) zinc finger-containing protein 1) recognizes different epigenetic marks and activates three histone acetyltransferases, so it is both a reader and a co-writer of the epigenetic language. The three histone acetyltransferases are MOZ, MORF, and HBO1, which are also known as lysine acetyltransferase 6A (KAT6A), KAT6B, and KAT7, respectively. The MORF gene is mutated in four neurodevelopmental disorders sharing the characteristic of intellectual disability and frequently displaying callosal agenesis. Here, we report that forebrain-specific inactivation of the mouse Brpf1 gene caused early postnatal lethality, neocortical abnormalities, and partial callosal agenesis. With respect to the control, the mutant forebrain contained fewer Tbr2-positive intermediate neuronal progenitors and displayed aberrant neurogenesis. Molecularly, Brpf1 loss led to decreased transcription of multiple genes, such as Robo3 and Otx1, important for neocortical development. Surprisingly, elevated expression of different Hox genes and various other transcription factors, such as Lhx4, Foxa1, Tbx5, and Twist1, was also observed. These results thus identify an important role of Brpf1 in regulating forebrain development and suggest that it acts as both an activator and a silencer of gene expression in vivo. PMID:25568313

  5. Deficiency of the chromatin regulator BRPF1 causes abnormal brain development.

    PubMed

    You, Linya; Zou, Jinfeng; Zhao, Hong; Bertos, Nicholas R; Park, Morag; Wang, Edwin; Yang, Xiang-Jiao

    2015-03-13

    Epigenetic mechanisms are important in different neurological disorders, and one such mechanism is histone acetylation. The multivalent chromatin regulator BRPF1 (bromodomain- and plant homeodomain-linked (PHD) zinc finger-containing protein 1) recognizes different epigenetic marks and activates three histone acetyltransferases, so it is both a reader and a co-writer of the epigenetic language. The three histone acetyltransferases are MOZ, MORF, and HBO1, which are also known as lysine acetyltransferase 6A (KAT6A), KAT6B, and KAT7, respectively. The MORF gene is mutated in four neurodevelopmental disorders sharing the characteristic of intellectual disability and frequently displaying callosal agenesis. Here, we report that forebrain-specific inactivation of the mouse Brpf1 gene caused early postnatal lethality, neocortical abnormalities, and partial callosal agenesis. With respect to the control, the mutant forebrain contained fewer Tbr2-positive intermediate neuronal progenitors and displayed aberrant neurogenesis. Molecularly, Brpf1 loss led to decreased transcription of multiple genes, such as Robo3 and Otx1, important for neocortical development. Surprisingly, elevated expression of different Hox genes and various other transcription factors, such as Lhx4, Foxa1, Tbx5, and Twist1, was also observed. These results thus identify an important role of Brpf1 in regulating forebrain development and suggest that it acts as both an activator and a silencer of gene expression in vivo.

  6. 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.

  7. 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.

  8. Susceptibility Weighted Imaging and White Matter Abnormality Findings in Service Members With Persistent Cognitive Symptoms Following Mild Traumatic Brain Injury.

    PubMed

    Tate, David F; Gusman, Maria; Kini, Jonathan; Reid, Matthew; Velez, Carmen S; Drennon, Ann Marie; Cooper, Douglas B; Kennedy, Jan E; Bowles, Amy O; Bigler, Erin D; Lewis, Jeffrey D; Ritter, John; York, Gerald E

    2017-03-01

    Mild traumatic brain injury (mTBI) is a major health concern among active duty service members and Veterans returning from combat operations, and it can result in variable clinical and cognitive outcomes. Identifying biomarkers that can improve diagnosis and prognostication has been at the forefront of recent research efforts. The purpose of this study was to compare the sensitivity and specificity of abnormalities identified using more traditional magnetic resonance imaging (MRI) sequences such as fluid attenuation inversion recovery (FLAIR) to more advanced MRI sequences such as susceptibility weighted imaging (SWI) among a cohort of active duty service members experiencing persistent cognitive symptoms after mTBI. One-hundred and fifty-two active duty service members (77 mTBI, 58 orthopedically injured [OI] only, 17 post-traumatic stress disorder [PTSD] only) underwent MRI and neuropsychological evaluation at a large military treatment facility. Results demonstrated that FLAIR white matter hyperintensities (WMHs) were present in all three groups at statistically similar rates (41% mTBI, 49% OI, and 29% PTSD). With the exception of a single OI participant showing a small discrete SWI lesion, SWI abnormalities were overwhelmingly present in mTBI patients (22% mTBI, 1% OI, and 0% PTSD). Functionally, mTBI participants with and without SWI abnormalities did not differ in demographics, symptom reporting, or cognitive performance. However, mTBI participants with and without WMH did differ for on measures of working memory with the mTBI participants with WMH having worse cognitive performance. No other significant differences were noted for those participants with and without imaging abnormalities for either the OI or PTSD only cohorts. These results appear to illustrate the sensitivity and specificity of SWI findings though these results did not have any significant functional impact in this cohort. In contrast, WMHs noted on FLAIR imaging were not sensitive or

  9. Do Subjects at Clinical High Risk for Psychosis Differ from those with a Genetic High Risk? – A Systematic Review of Structural and Functional Brain Abnormalities

    PubMed Central

    Smieskova, R; Marmy, J; Schmidt, A; Bendfeldt, K; Riecher-Rössler, A; Walter, M; Lang, UE; Borgwardt, S

    2013-01-01

    Introduction: Pre-psychotic and early psychotic characteristics are investigated in the high-risk (HR) populations for psychosis. There are two different approaches based either on hereditary factors (genetic high risk, G-HR) or on the clinically manifested symptoms (clinical high risk, C-HR). Common features are an increased risk for development of psychosis and similar cognitive as well as structural and functional brain abnormalities. Methods: We reviewed the existing literature on longitudinal structural, and on functional imaging studies, which included G-HR and/or C-HR individuals for psychosis, healthy controls (HC) and/or first episode of psychosis (FEP) or schizophrenia patients (SCZ). Results: With respect to structural brain abnormalities, vulnerability to psychosis was associated with deficits in frontal, temporal, and cingulate regions in HR, with additional insular and caudate deficits in C-HR population. Furthermore, C-HR had progressive prefrontal deficits related to the transition to psychosis. With respect to functional brain abnormalities, vulnerability to psychosis was associated with prefrontal, cingulate and middle temporal abnormalities in HR, with additional parietal, superior temporal, and insular abnormalities in C-HR population. Transition-to-psychosis related differences emphasized prefrontal, hippocampal and striatal components, more often detectable in C-HR population. Multimodal studies directly associated psychotic symptoms displayed in altered prefrontal and hippocampal activations with striatal dopamine and thalamic glutamate functions. Conclusion: There is an evidence for similar structural and functional brain abnormalities within the whole HR population, with more pronounced deficits in the C-HR population. The most consistent evidence for abnormality in the prefrontal cortex reported in structural, functional and multimodal studies of HR population may underlie the complexity of higher cognitive functions that are impaired

  10. 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 ...

  11. Detection, visualization and animation of abnormal anatomic structure with a deformable probabilistic brain atlas based on random vector field transformations.

    PubMed

    Thompson, P M; Toga, A W

    1997-09-01

    This paper describes the design, implementation and preliminary results of a technique for creating a comprehensive probabilistic atlas of the human brain based on high-dimensional vector field transformations. The goal of the atlas is to detect and quantify distributed patterns of deviation from normal anatomy, in a 3-D brain image from any given subject. The algorithm analyzes a reference population of normal scans and automatically generates color-coded probability maps of the anatomy of new subjects. Given a 3-D brain image of a new subject, the algorithm calculates a set of high-dimensional volumetric maps (with typically 384(2) x 256 x 3 approximately 10(8) degrees of freedom) elastically deforming this scan into structural correspondence with other scans, selected one by one from an anatomic image database. The family of volumetric warps thus constructed encodes statistical properties and directional biases of local anatomical variation throughout the architecture of the brain. A probability space of random transformations, based on the theory of anisotropic Gaussian random fields, is then developed to reflect the observed variability in stereotaxic space of the points whose correspondences are found by the warping algorithm. A complete system of 384(2) x 256 probability density functions is computed, yielding confidence limits in stereotaxic space for the location of every point represented in the 3-D image lattice of the new subject's brain. Color-coded probability maps are generated, densely defined throughout the anatomy of the new subject. These indicate locally the probability of each anatomic point being unusually situated, given the distributions of corresponding points in the scans of normal subjects. 3-D MRI and high-resolution cryosection volumes are analyzed from subjects with metastatic tumors and Alzheimer's disease. Gradual variations and continuous deformations of the underlying anatomy are simulated and their dynamic effects on regional

  12. Potential Adverse Effects of Prolonged Sevoflurane Exposure on Developing Monkey Brain: From Abnormal Lipid Metabolism to Neuronal Damage

    PubMed Central

    Liu, Fang; Rainosek, Shuo W.; Frisch-Daiello, Jessica L.; Patterson, Tucker A.; Paule, Merle G.; Slikker, William; Wang, Cheng; Han, Xianlin

    2015-01-01

    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. PMID:26206149

  13. 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.

  14. Alterations of the Blood-Brain Barrier and Regional Perfusion in Tumor Development: MRI Insights from a Rat C6 Glioma Model

    PubMed Central

    Huhndorf, Monika; Moussavi, Amir; Kramann, Nadine; Will, Olga; Hattermann, Kirsten; Stadelmann, Christine; Jansen, Olav

    2016-01-01

    Objectives Angiogenesis and anti-angiogenetic medications play an important role in progression and therapy of glioblastoma. In this context, in vivo characterization of the blood-brain-barrier and tumor vascularization may be important for individual prognosis and therapy optimization. Methods We analyzed perfusion and capillary permeability of C6-gliomas in rats at different stages of tumor-growth by contrast enhanced MRI and dynamic susceptibility contrast (DSC) MRI at 7 Tesla. The analyses included maps of relative cerebral blood volume (CBV) and signal recovery derived from DSC data over a time period of up to 35 days after tumor cell injections. Results In all rats tumor progression was accompanied by temporal and spatial changes in CBV and capillary permeability. A leakage of the blood-brain barrier (slow contrast enhancement) was observed as soon as the tumor became detectable on T2-weighted images. Interestingly, areas of strong capillary permeability (fast signal enhancement) were predominantly localized in the center of the tumor. In contrast, the tumor rim was dominated by an increased CBV and showed the highest vessel density compared to the tumor center and the contralateral hemisphere as confirmed by histology. Conclusion Substantial regional differences in the tumor highlight the importance of parameter maps in contrast or in addition to region-of-interest analyses. The data vividly illustrate how MRI including contrast-enhanced and DSC-MRI may contribute to a better understanding of tumor development. PMID:28005983

  15. [Compromized myocardial perfusion in arrhythmias (author's transl)].

    PubMed

    Simon, H; Neumann, G; Felix, R; Hedde, H; Schaede, A; Thurn, P; Winkler, C

    1977-09-15

    In 7 patients with arrhythmias of various origin the myocardial scintigram displayed either a diffuse or circumscript defect of the perfusion. The coronary arteriogram was normal in all patients. The localized defect of the perfusion in 2 patients was in the region of the upper part of the interventricular septum. Both had a left bundle brunch block. A correlation between the perfusion defect and the electrophysiological abnormality seems probable. The perfusion defect in one of the patients is most probably caused by a previous myocarditis followed by fibrous changes. In the other 6 patients the cause for the perfusion defect is not obvious. A history of myocarditis is missing. The presence of "small vessel disease" in those patients has however to be considered. Our results point to the relation between an abnormality of the microcirculation and arrhythmias in younger patients.

  16. Structural brain abnormalities in postural tachycardia syndrome: A VBM-DARTEL study.

    PubMed

    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.

  17. 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

  18. Abnormal functional lateralization and activity of language brain areas in typical specific language impairment (developmental dysphasia).

    PubMed

    de Guibert, Clément; Maumet, Camille; Jannin, Pierre; Ferré, Jean-Christophe; Tréguier, Catherine; Barillot, Christian; Le Rumeur, Elisabeth; Allaire, Catherine; Biraben, Arnaud

    2011-10-01

    Atypical functional lateralization and specialization for language have been proposed to account for developmental language disorders, yet results from functional neuroimaging studies are sparse and inconsistent. This functional magnetic resonance imaging study compared children with a specific subtype of specific language impairment affecting structural language (n = 21), to a matched group of typically developing children using a panel of four language tasks neither requiring reading nor metalinguistic skills, including two auditory lexico-semantic tasks (category fluency and responsive naming) and two visual phonological tasks based on picture naming. Data processing involved normalizing the data with respect to a matched pairs paediatric template, groups and between-groups analysis, and laterality indices assessment within regions of interest using single and combined task analysis. Children with specific language impairment exhibited a significant lack of left lateralization in all core language regions (inferior frontal gyrus-opercularis, inferior frontal gyrus-triangularis, supramarginal gyrus and superior temporal gyrus), across single or combined task analysis, but no difference of lateralization for the rest of the brain. Between-group comparisons revealed a left hypoactivation of Wernicke's area at the posterior superior temporal/supramarginal junction during the responsive naming task, and a right hyperactivation encompassing the anterior insula with adjacent inferior frontal gyrus and the head of the caudate nucleus during the first phonological task. This study thus provides evidence that this subtype of specific language impairment is associated with atypical lateralization and functioning of core language areas.

  19. Abnormal functional lateralization and activity of language brain areas in typical specific language impairment (developmental dysphasia)

    PubMed Central

    De Guibert, Clément; Maumet, Camille; Jannin, Pierre; Ferré, Jean-Christophe; Tréguier, Catherine; Barillot, Christian; Le Rumeur, Elisabeth; Allaire, Catherine; Biraben, Arnaud

    2011-01-01

    Atypical functional lateralization and specialization for language have been proposed to account for developmental language disorders, yet results from functional neuroimaging studies are sparse and inconsistent. This functional magnetic resonance imaging study compared children with a specific subtype of specific language impairment affecting structural language (n=21), to a matched group of typically-developing children using a panel of four language tasks neither requiring reading nor metalinguistic skills, including two auditory lexico-semantic tasks (category fluency and responsive naming) and two visual phonological tasks based on picture naming. Data processing involved normalizing the data with respect to a matched pairs pediatric template, groups and between-groups analysis, and laterality indexes assessment within regions of interest using single and combined task analysis. Children with specific language impairment exhibited a significant lack of left lateralization in all core language regions (inferior frontal gyrus-opercularis, inferior frontal gyrus-triangularis, supramarginal gyrus, superior temporal gyrus), across single or combined task analysis, but no difference of lateralization for the rest of the brain. Between-group comparisons revealed a left hypoactivation of Wernicke’s area at the posterior superior temporal/supramarginal junction during the responsive naming task, and a right hyperactivation encompassing the anterior insula with adjacent inferior frontal gyrus and the head of the caudate nucleus during the first phonological task. This study thus provides evidence that this specific subtype of specific language impairment is associated with atypical lateralization and functioning of core language areas. PMID:21719430

  20. 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…

  1. BRAIN ABNORMALITIES IN YOUNG ADULTS AT GENETIC RISK FOR AUTOSOMAL DOMINANT ALZHEIMER’S DISEASE: A CROSS-SECTIONAL STUDY

    PubMed Central

    Reiman, Eric M.; Quiroz, Yakeel T.; Fleisher, Adam S.; Chen, Kewei; Velez-Pardo, Carlos; Jimenez-Del-Rio, Marlene; Fagan, Anne M.; Shah, Aarti R.; Alvarez, Sergio; Arbelaez, Andrés; Giraldo, Margarita; Acosta-Baena, Natalia; Sperling, Reisa A.; Dickerson, Brad; Stern, Chantal E.; Tirado, Victoria; Munoz, Claudia; Reiman, Rebecca A.; Huentelman, Matthew J.; Alexander, Gene E.; Langbaum, Jessica B.S.; Kosik, Kenneth S.; Tariot, Pierre N.; Lopera, Francisco

    2013-01-01

    Summary Background We previously detected functional brain imaging abnormalities in young adults at genetic risk for late-onset Alzheimer’s disease (AD). Here, we sought to characterize structural and functional magnetic resonance imaging (MRI), cerebrospinal fluid (CSF), and plasma biomarker abnormalities in young adults at risk for autosomal dominant early-onset AD. Biomarker measurements were characterized and compared in presenilin 1 (PSEN1) E280A mutation carriers and non-carriers from the world’s largest known autosomal dominant early-onset AD kindred, more than two decades before the carriers’ estimated median age of 44 at the onset of mild cognitive impairment (MCI) and before their estimated age of 28 at the onset of amyloid-β (Aβ) plaque deposition. Methods Biomarker data for this cross-sectional study were acquired in Antioquia, Colombia between July and August, 2010. Forty-four participants from the Colombian Alzheimer’s Prevention Initiative (API) Registry had structural MRIs, functional MRIs during associative memory encoding/novel viewing and control tasks, and cognitive assessments. They included 20 mutation carriers and 24 non-carriers, who were cognitively normal, 18-26 years old and matched for their gender, age, and educational level. Twenty of the participants, including 10 mutation carriers and 10 non-carriers, had lumbar punctures and venipunctures. Primary outcome measures included task-dependent hippocampal/parahippocampal activations and precuneus/posterior cingulate deactivations, regional gray matter reductions, CSF Aβ1-42, total tau and phospho-tau181 levels, and plasma Aβ1-42 levels and Aβ1-42/Aβ1-40 ratios. Structural and functional MRI data were compared using automated brain mapping algorithms and AD-related search regions. Cognitive and fluid biomarkers were compared using Mann-Whitney tests. Findings The mutation carrier and non-carrier groups did not differ significantly in their dementia ratings, neuropsychological

  2. [Intracranial, cerebral perfusion pressure and systemic hemodynamic parameters during anesthesia induction in patients with traumatic brain compression].

    PubMed

    2012-01-01

    The study reports the dynamic of ICP, CPP and systemic hemodynamic rates during midazolam induction of anesthesia in patients with traumatic brain compression. Patients who need urgent surgery to eliminate brain compression of various degrees generally have intracranial hypertension. Midazolam administration decreases ICP by 22% from baseline under condition of stable hemodynamic and CPP. Depolarizing neuromuscular blocking agents' administration, mechanical ventilation and tracheal intubation lead to ICP elevation and CPP decreasing. The combination of midazolam and fentanil provides more reliable protection from hypertensive reactions.

  3. [Evaluation by statistical brain perfusion SPECT analysis on MRI findings, kana pick-out test and Mini-Mental State Examination results in patients with forgetfulness].

    PubMed

    Nakatsuka, Hiroki; Matsubara, Ichirou; Ohtani, Haruhiko

    2003-04-01

    The aim of this single photon emission computed tomography(SPECT) study was to determine the abnormality of the regional cerebral blood flow(rCBF) using a three-dimensional stereotactic surface projection (3 D-SSP) in 18 patients who were referred to the hospital because of forgetfulness. Two intergroup comparison by 3 D-SSP analysis was conducted based on MRI, kana pick-out test and Mini-Mental State Examination (MMSE) results. Of the MRI findings, in the brain atrophy group, rCBF was decreased in the posterior cingulate gyrus, medial temporal structure and parieto-temporal association cortex; these rCBF-decreased areas are similar to the Alzheimer disease pattern. In the group where the MMSE was normal but the kana pick-out test was abnormal, rCBF was decreased in the posterior cingulate gyrus and cinguloparietal transitional area. In the group where both the MMSE and kana pick-out test were abnormal, rCBF was decreased in the parieto-temporal association cortex, temporal cortex and medial temporal structure. These results suggest that 3 D-SSP analysis of the SPECT with MMSE and the kana pick-out test provides the possibility of early diagnosis of initial stage of Alzheimer's disease.

  4. Abnormal expression of stathmin 1 in brain tissue of patients with intractable temporal lobe epilepsy and a rat model.

    PubMed

    Zhao, Fenghua; Hu, Yida; Zhang, Ying; Zhu, Qiong; Zhang, Xiaogang; Luo, Jing; Xu, Yali; Wang, Xuefeng

    2012-09-01

    Microtubule dynamics have been shown to contribute to neurite outgrowth, branching, and guidance. Stathmin 1 is a potent microtubule-destabilizing factor that is involved in the regulation of microtubule dynamics and plays an essential role in neurite elongation and synaptic plasticity. Here, we investigate the expression of stathmin 1 in the brain tissues of patients with intractable temporal lobe epilepsy (TLE) and experimental animals using immunohistochemistry, immunofluorescence and western blotting. We obtained 32 temporal neocortex tissue samples from patients with intractable TLE and 12 histologically normal temporal lobe tissues as controls. In addition, 48 Sprague Dawley rats were randomly divided into six groups, including one control group and five groups with epilepsy induced by lithium chloride-pilocarpine. Hippocampal and temporal lobe tissues were obtained from control and epileptic rats on Days 1, 7, 14, 30, and 60 after kindling. Stathmin 1 was mainly expressed in the neuronal membrane and cytoplasm in the human controls, and its expression levels were significantly higher in patients with intractable TLE. Moreover, stathmin 1 was also expressed in the neurons of both the control and the experimental rats. Stathmin 1 expression was decreased in the experimental animals from 1 to 14 days postseizure and then significantly increased at Days 30 and 60 compared with the control group. Many protruding neuronal processes were observed in the TLE patients and in the chronic stage epileptic rats. These data suggest that stathmin 1 may participate in the abnormal network reorganization of synapses and contribute to the pathogenesis of TLE.

  5. The INTERPRET Decision-Support System version 3.0 for evaluation of Magnetic Resonance Spectroscopy data from human brain tumours and other abnormal brain masses

    PubMed Central

    2010-01-01

    Background Proton Magnetic Resonance (MR) Spectroscopy (MRS) is a widely available technique for those clinical centres equipped with MR scanners. Unlike the rest of MR-based techniques, MRS yields not images but spectra of metabolites in the tissues. In pathological situations, the MRS profile changes and this has been particularly described for brain tumours. However, radiologists are frequently not familiar to the interpretation of MRS data and for this reason, the usefulness of decision-support systems (DSS) in MRS data analysis has been explored. Results This work presents the INTERPRET DSS version 3.0, analysing the improvements made from its first release in 2002. Version 3.0 is aimed to be a program that 1st, can be easily used with any new case from any MR scanner manufacturer and 2nd, improves the initial analysis capabilities of the first version. The main improvements are an embedded database, user accounts, more diagnostic discrimination capabilities and the possibility to analyse data acquired under additional data acquisition conditions. Other improvements include a customisable graphical user interface (GUI). Most diagnostic problems included have been addressed through a pattern-recognition based approach, in which classifiers based on linear discriminant analysis (LDA) were trained and tested. Conclusions The INTERPRET DSS 3.0 allows radiologists, medical physicists, biochemists or, generally speaking, any person with a minimum knowledge of what an MR spectrum is, to enter their own SV raw data, acquired at 1.5 T, and to analyse them. The system is expected to help in the categorisation of MR Spectra from abnormal brain masses. PMID:21114820

  6. Perfusion MRI: The Five Most Frequently Asked Clinical Questions

    PubMed Central

    Essig, Marco; Nguyen, Thanh Binh; Shiroishi, Mark S.; Saake, Marc; Provenzale, James M.; Enterline, David S.; Anzalone, Nicoletta; Dörfler, Arnd; Rovira, Àlex; Wintermark, Max; Law, Meng

    2013-01-01

    OBJECTIVE This article addresses questions that radiologists frequently ask when planning, performing, processing, and interpreting MRI perfusion studies in CNS imaging. CONCLUSION Perfusion MRI is a promising tool in assessing stroke, brain tumors, and neurodegenerative diseases. Most of the impediments that have limited the use of perfusion MRI can be overcome to allow integration of these methods into modern neuroimaging protocols. PMID:23971482

  7. Whole-brain CT perfusion combined with CT angiography for ischemic complications following microsurgical clipping and endovascular coiling of ruptured intracranial aneurysms.

    PubMed

    Cheng, Xiao Qing; Chen, Qian; Zhou, Chang Sheng; Li, Jian Rui; Zhang, Zong Jun; Zhang, Long Jiang; Huang, Wei; Lu, Guang Ming

    2016-04-01

    Ischemic complications associated with microsurgical clipping and endovascular coiling affects the outcome of patients with intracranial aneurysms. We prospectively evaluated 58 intracranial aneurysm patients who had neurological deterioration or presented with poor grade (Hunt-Hess grades III and IV), aneurysm size >13 mm and multiple aneurysms after clipping or coiling. Thirty patients had ischemic complications (52%) as demonstrated by whole-brain CT perfusion (WB-CTP) combined with CT angiography (CTA). Half of these 30 patients had treatment-associated reduction in the diameter of the parent vessels (n=6), ligation of the parent vessels or perforating arteries (n=2), and unexplained or indistinguishable vascular injury (n=7); seven of these 15 (73%) patients suffered infarction. The remaining 15 patients had disease-associated cerebral ischemia caused by generalized vasospasm (n=6) and focal vessel vasospasm (n=9); six of these 15 (40%) patients developed infarction. Three hemodynamic patterns of ischemic complications were found on WB-CTP, of which increased time to peak, time to delay and mean transit time associated with decreased cerebral blood flow and cerebral blood volume were the main predictors of irreversible ischemic lesions. In conclusion, WB-CTP combined with CTA can accurately determine the cause of neurological deterioration and classify ischemic complications. This combined approach may be helpful in assessing hemodynamic patterns and monitoring operative outcomes.

  8. 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

  9. Reflection imaging of China ink-perfused brain vasculature using confocal laser-scanning microscopy after clarification of brain tissue by the Spalteholz method.

    PubMed

    Gutierre, R C; Vannucci Campos, D; Mortara, R A; Coppi, A A; Arida, R M

    2017-01-05

    Confocal laser-scanning microscopy is a useful tool for visualizing neurons and glia in transparent preparations of brain tissue from laboratory animals. Currently, imaging capillaries and venules in transparent brain tissues requires the use of fluorescent proteins. Here, we show that vessels can be imaged by confocal laser-scanning microscopy in transparent cortical, hippocampal and cerebellar preparations after clarification of China ink-injected specimens by the Spalteholz method. This method may be suitable for global, three-dimensional, quantitative analyses of vessels, including stereological estimations of total volume and length and of surface area of vessels, which constitute indirect approaches to investigate angiogenesis.

  10. Early Support of Intracranial Perfusion

    DTIC Science & Technology

    2013-10-01

    automated real-time vital signs monitoring data” was funded by USAF (MSA); UM PI: Deborah Stein  The project, titled “Noninvasive intracranial pressure ...scoring of cerebral perfusion pressure and intracranial pressure provides a Brain Trauma Index that predicts outcome in patients with severe TBI... intracranial pressure dose index: Dynamic 3-D scoring in the assessment of Traumatic Brain Injury Proceedings of American Association for the Surgery of

  11. Residual Effects of THC via Novel Measures of Brain Perfusion and Metabolism in a Large Group of Chronic Cannabis Users.

    PubMed

    Filbey, Francesca M; Aslan, Sina; Lu, Hanzhang; Peng, Shin-Lei

    2017-03-22

    Given the known vascular effects of cannabis, this study examined the neurophysiological factors that may affect studies of brain activity in cannabis users. We conducted a systematic evaluation in 72 h abstinent, chronic cannabis users (N=74) and nonusing controls (N=101) to determine the association between prolonged cannabis use and the following neurophysiological indicators: (1) global and regional resting cerebral blood flow (CBF), (2) oxygen extraction fraction (OEF), and (3) cerebral metabolic rate of oxygen (CMRO2). We found that cannabis users had greater global OEF and CMRO2 compared with nonusers. Regionally, we found higher CBF in the right pallidum/putamen of the cannabis users compared with nonusers. Global resting CBF and regional CBF of right superior frontal cortex correlated positively with creatinine-normalized Δ9-tetrahydrocannabinol (THC) levels. These findings demonstrate residual effects of cannabis use whereby global and regional brain metabolism are altered in those with prolonged cannabis exposure. These neurophysiological alterations should be considered in both research and clinical applications.Neuropsychopharmacology advance online publication, 22 March 2017; doi:10.1038/npp.2017.44.

  12. 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.

  13. High-Resolution Magnetic Resonance Microscopy and Diffusion Tensor Imaging to Assess Brain Structural Abnormalities in the Murine Mucopolysaccharidosis VII Model

    PubMed Central

    Poptani, Harish; Kumar, Manoj; Nasrallah, Ilya M; Kim, Sungheon; Ittyerah, Ranjit; Pickup, Stephen; Li, Joel; Parente, Michael K; Wolfe, John H.

    2014-01-01

    High-resolution microscopic magnetic resonance imaging (μMRI) and diffusion tensor imaging (DTI) were performed to characterize brain structural abnormalities in a mouse model of mucopolysaccharidosis type VII (MPS VII). μMRI demonstrated a decrease in the volume of anterior commissure and corpus callosum and a slight increase in the volume of the hippocampus in MPS VII vs. wild-type mice. DTI indices were analyzed in gray and white matter. In vivo and ex vivo DTI demonstrated significantly reduced fractional anisotropy in the anterior commissure, corpus callosum, external capsule and hippocampus in MPS VII vs. control brains. Significantly increased mean diffusivity was also found in the anterior commissure and corpus callosum from ex-vivo DTI. Significantly reduced linear anisotropy was observed from the hippocampus from in-vivo DTI, whereas significantly decreased planar anisotropy and spherical anisotropy were observed in the external capsule from only ex-vivo DTI. There were corresponding morphological differences in the brains of MPS VII mice by hematoxylin and eosin staining. Luxol fast blue staining demonstrated less intense staining of the corpus callosum and external capsule; myelin abnormalities in the corpus callosum were also demonstrated quantitatively in toluidine blue-stained sections and confirmed by electron microscopy. These results demonstrate the potential for μMRI and DTI for quantitative assessment of brain pathology in murine models of brain diseases. PMID:24335527

  14. 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

  15. 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

  16. 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.

  17. 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.

  18. Intracranial pressure monitoring, cerebral perfusion pressure estimation, and ICP/CPP-guided therapy: a standard of care or optional extra after brain injury?

    PubMed

    Kirkman, M A; Smith, M

    2014-01-01

    Measurement of intracranial pressure (ICP) and mean arterial pressure (MAP) is used to derive cerebral perfusion pressure (CPP) and to guide targeted therapy of acute brain injury (ABI) during neurointensive care. Here we provide a narrative review of the evidence for ICP monitoring, CPP estimation, and ICP/CPP-guided therapy after ABI. Despite its widespread use, there is currently no class I evidence that ICP/CPP-guided therapy for any cerebral pathology improves outcomes; indeed some evidence suggests that it makes no difference, and some that it may worsen outcomes. Similarly, no class I evidence can currently advise the ideal CPP for any form of ABI. 'Optimal' CPP is likely patient-, time-, and pathology-specific. Further, CPP estimation requires correct referencing (at the level of the foramen of Monro as opposed to the level of the heart) for MAP measurement to avoid CPP over-estimation and adverse patient outcomes. Evidence is emerging for the role of other monitors of cerebral well-being that enable the clinician to employ an individualized multimodality monitoring approach in patients with ABI, and these are briefly reviewed. While acknowledging difficulties in conducting robust prospective randomized studies in this area, such high-quality evidence for the utility of ICP/CPP-directed therapy in ABI is urgently required. So, too, is the wider adoption of multimodality neuromonitoring to guide optimal management of ICP and CPP, and a greater understanding of the underlying pathophysiology of the different forms of ABI and what exactly the different monitoring tools used actually represent.

  19. Sequential hypothesis testing for automatic detection of task-related changes in cerebral perfusion in a brain-computer interface.

    PubMed

    Faulkner, Hayley G; Myrden, Andrew; Li, Michael; Mamun, Khondaker; Chau, Tom

    2015-11-01

    Evidence suggests that the cerebral blood flow patterns accompanying cognitive activity are retained in many locked-in patients. These patterns can be monitored using transcranial Doppler ultrasound (TCD), a medical imaging technique that measures bilateral cerebral blood flow velocities. Recently, TCD has been proposed as an alternative imaging modality for brain-computer interfaces (BCIs). However, most previous TCD-BCI studies have performed offline analyses with impractically lengthy tasks. In this study, we designed a BCI that automatically differentiates between counting and verbal fluency tasks using sequential hypothesis testing to make decisions as quickly as possible. Ten able-bodied participants silently alternated between counting and verbal fluency tasks within the paradigm of a simulated on-screen keyboard. During this experiment, blood flow velocities were recorded within the left and right middle cerebral arteries using bilateral TCD. Twelve features were used to characterize TCD signals. In a simulated online analysis, sequential hypothesis testing was used to update estimates of class probability every 250 ms as TCD data were processed. Classification was terminated once a threshold level of certainty was reached. Mean classification accuracy across all participants was 72% after an average of 23s, compared to an offline analysis which obtained a classification accuracy of 80% after 45 s. This represents a substantial gain in data transmission rate, while maintaining classification accuracies exceeding 70%. Furthermore, a range of decision times between 19 and 28s was observed, suggesting that the ability of sequential hypothesis testing to adapt the task duration for each individual participant is critical to achieving consistent performance across participants. These results indicate that sequential hypothesis testing is a promising alternative for online TCD-BCIs.

  20. 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

  1. An improved FSL-FIRST pipeline for subcortical gray matter segmentation to study abnormal brain anatomy using quantitative susceptibility mapping (QSM).

    PubMed

    Feng, Xiang; Deistung, Andreas; Dwyer, Michael G; Hagemeier, Jesper; Polak, Paul; Lebenberg, Jessica; Frouin, Frédérique; Zivadinov, Robert; Reichenbach, Jürgen R; Schweser, Ferdinand

    2017-02-07

    Accurate and robust segmentation of subcortical gray matter (SGM) nuclei is required in many neuroimaging applications. FMRIB's Integrated Registration and Segmentation Tool (FIRST) is one of the most popular software tools for automated subcortical segmentation based on T1-weighted (T1w) images. In this work, we demonstrate that FIRST tends to produce inaccurate SGM segmentation results in the case of abnormal brain anatomy, such as present in atrophied brains, due to a poor spatial match of the subcortical structures with the training data in the MNI space as well as due to insufficient contrast of SGM structures on T1w images. Consequently, such deviations from the average brain anatomy may introduce analysis bias in clinical studies, which may not always be obvious and potentially remain unidentified. To improve the segmentation of subcortical nuclei, we propose to use FIRST in combination with a special Hybrid image Contrast (HC) and Non-Linear (nl) registration module (HC-nlFIRST), where the hybrid image contrast is derived from T1w images and magnetic susceptibility maps to create subcortical contrast that is similar to that in the Montreal Neurological Institute (MNI) template. In our approach, a nonlinear registration replaces FIRST's default linear registration, yielding a more accurate alignment of the input data to the MNI template. We evaluated our method on 82 subjects with particularly abnormal brain anatomy, selected from a database of >2000 clinical cases. Qualitative and quantitative analyses revealed that HC-nlFIRST provides improved segmentation compared to the default FIRST method.

  2. 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

  3. 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

  4. 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…

  5. The oral administration of D-galactose induces abnormalities within the mitochondrial respiratory chain in the brain of rats.

    PubMed

    Budni, Josiane; Garcez, Michelle Lima; Mina, Francielle; Bellettini-Santos, Tatiani; da Silva, Sabrina; Luz, Aline Pereira da; Schiavo, Gustavo Luiz; Batista-Silva, Hemily; Scaini, Giselli; Streck, Emílio Luiz; Quevedo, João

    2017-02-24

    D-Galactose (D-gal) chronic administration via intraperitoneal and subcutaneous routes has been used as a model of aging and Alzheimer disease in rodents. Intraperitoneal and subcutaneous administration of D-gal causes memory impairments, a reduction in the neurogenesis of adult mice, an increase in the levels of the amyloid precursor protein and oxidative damage; However, the effects of oral D-gal remain unclear. The aim of this study was to evaluate whether the oral administration of D-gal induces abnormalities within the mitochondrial respiratory chain of rats. Male Wistar rats (4 months old) received D-gal (100 mg/kg v.o.), during the 1st, 2nd, 4th, 6th or 8th weeks by oral gavage. The activity of the mitochondrial respiratory chain complexes was measured in the 1st, 2nd, 4th, 6th and 8th weeks after the administration of D-gal. The activity of the respiratory chain complex I was found to have increased in the prefrontal cortex and hippocampus in the 1st, 6th and 8th weeks, while the activity of the respiratory chain complex II increased in the 1st, 2nd, 4th, 6th and 8th weeks within the hippocampus and in the 2nd, 4th, 6th and 8th weeks within the prefrontal cortex. The activity of complex II-III increased within the prefrontal cortex and hippocampus in each week of oral D-gal treatment. The activity of complex IV increased within the prefrontal cortex and hippocampus in the 1st, 2nd, 6th and 8th weeks of treatment. After 4 weeks of treatment the activity increased only in hippocampus. In conclusion, the present study showed that the oral administration of D-gal increased the activity of the mitochondrial respiratory chain complexes I, II, II-III and IV in the prefrontal cortex and hippocampus. Furthermore, the administration of D-gal via the oral route seems to cause the alterations in the mitochondrial respiratory complexes observed in brain neurodegeneration.

  6. Congenital Abnormalities

    MedlinePlus

    ... Listen Español Text Size Email Print Share Congenital Abnormalities Page Content Article Body About 3% to 4% ... of congenital abnormalities earlier. 5 Categories of Congenital Abnormalities Chromosome Abnormalities Chromosomes are structures that carry genetic ...

  7. 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.

  8. 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

  9. 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.

  10. Brain luxury perfusion during cardiopulmonary bypass in humans. A study of the cerebral blood flow response to changes in CO2, O2, and blood pressure.

    PubMed

    Henriksen, L

    1986-06-01

    CBF and related parameters were studied in 68 patients before, during, and following cardiopulmonary bypass. CBF was measured using the intraarterial 133Xe injection method. The extracorporeal circuit was nonpulsatile with a bubble oxygenator administering 3-5% CO2 in the main group of hypercapnic patients (n = 59) and no CO2 in a second group of hypocapnic patients. In the hypercapnic patients, marked changes in CBF occurred during bypass. Evidence was found of a brain luxury perfusion that could not be related to the effect of CO2 per se. Mean CBF was 29 ml/100 g/min just before bypass, 49 ml/100 g/min at steady-state hypothermia (27 degrees C), reached a maximum of 73 ml/100 g/min during the rewarming phase (32 degrees C), fell to 56 ml/100 g/min at steady-state normothermic bypass (37 degrees C), and was 48 ml/100 g/min shortly after bypass was stopped. Addition of CO2 evoked systemic vasodilation with low blood pressure and a rebound hyperemia. The hypocapnic group responded more physiologically to the induced changes in hematocrit (Htc) and temperature, CBF being 25, 23, 25, 34, and 35 ml/100 g/min, respectively, during the five corresponding periods. Carbon dioxide was an important regulator of CBF during all phases of cardiac surgery, the responsiveness of CBF being approximately 4% for each 1-mm Hg change of PaCO2. The level of MABP was important for the CO2 response. At low blood pressure states, the CBF responsiveness to changes in PaCO2 was almost abolished. An optimal level of PaCO2 during hypothermic bypass of approximately 25 mm Hg (at actual temperature) is recommended. A normal autoregulatory response of CBF to changes in blood pressure was found during and following bypass. The lower limit of autoregulation was at pressure levels of approximately 50-60 mm Hg. CBF autoregulation was almost abolished at PaCO2 levels of greater than 50 mm Hg. The degree of hemodilution neither affected the CO2 response nor impaired CBF autoregulation, although, as

  11. Investigating Microstructural Abnormalities and Neurocognition in Sub-Acute and Chronic Traumatic Brain Injury Patients with Normal-Appearing White Matter: A Preliminary Diffusion Tensor Imaging Study

    PubMed Central

    Hashim, Eyesha; Caverzasi, Eduardo; Papinutto, Nico; Lewis, Caroline E.; Jing, Ruiwei; Charles, Onella; Zhang, Shudong; Lin, Amy; Graham, Simon J.; Schweizer, Tom A.; Bharatha, Aditya; Cusimano, Michael D.

    2017-01-01

    For a significant percentage of subjects, with chronic traumatic brain injury (TBI), who report persisting cognitive impairment and functional loss, the diagnosis is often impeded by the fact that routine neuroimaging often does not reveal any abnormalities. In this paper, we used diffusion tensor imaging (DTI) to investigate the apparently normal white matter (as assessed by routine magnetic resonance imaging) in the brains of 19 subjects with sub-acute (9) and chronic (10) TBI. We also assessed memory, executive function, and visual-motor coordination in these subjects. Using a voxel-wise approach, we investigated if parameters of diffusion were significantly different between TBI subjects and 17 healthy controls (HC), who were demographically matched to the TBI group. We also investigated if changes in DTI parameters were associated with neuropsychological performance in either group. Our results indicate significantly increased mean and axial diffusivity (MD and AD, respectively) values in widespread brain locations in TBI subjects, while controlling for age, sex, and time since injury. HC performed significantly better than the TBI subjects on tests of memory and executive function, indicating the persisting functional loss in chronic TBI. We found no correlation between diffusion parameters and performance on test of executive function in either group. We found negative correlation between FA and composite memory scores, and positive correlation between RD and visuomotor coordination test scores, in various tracts in both groups. Our study suggests that changes in MD and AD can indicate persisting micro-structure abnormalities in normal-appearing white matter in the brains of subjects with chronic TBI. Our results also suggest that FA in major white matter tracts is correlated with memory in health and in disease, alike; larger and longitudinal studies are needed to discern potential differences in these correlations in the two groups. PMID:28373856

  12. Investigating Microstructural Abnormalities and Neurocognition in Sub-Acute and Chronic Traumatic Brain Injury Patients with Normal-Appearing White Matter: A Preliminary Diffusion Tensor Imaging Study.

    PubMed

    Hashim, Eyesha; Caverzasi, Eduardo; Papinutto, Nico; Lewis, Caroline E; Jing, Ruiwei; Charles, Onella; Zhang, Shudong; Lin, Amy; Graham, Simon J; Schweizer, Tom A; Bharatha, Aditya; Cusimano, Michael D

    2017-01-01

    For a significant percentage of subjects, with chronic traumatic brain injury (TBI), who report persisting cognitive impairment and functional loss, the diagnosis is often impeded by the fact that routine neuroimaging often does not reveal any abnormalities. In this paper, we used diffusion tensor imaging (DTI) to investigate the apparently normal white matter (as assessed by routine magnetic resonance imaging) in the brains of 19 subjects with sub-acute (9) and chronic (10) TBI. We also assessed memory, executive function, and visual-motor coordination in these subjects. Using a voxel-wise approach, we investigated if parameters of diffusion were significantly different between TBI subjects and 17 healthy controls (HC), who were demographically matched to the TBI group. We also investigated if changes in DTI parameters were associated with neuropsychological performance in either group. Our results indicate significantly increased mean and axial diffusivity (MD and AD, respectively) values in widespread brain locations in TBI subjects, while controlling for age, sex, and time since injury. HC performed significantly better than the TBI subjects on tests of memory and executive function, indicating the persisting functional loss in chronic TBI. We found no correlation between diffusion parameters and performance on test of executive function in either group. We found negative correlation between FA and composite memory scores, and positive correlation between RD and visuomotor coordination test scores, in various tracts in both groups. Our study suggests that changes in MD and AD can indicate persisting micro-structure abnormalities in normal-appearing white matter in the brains of subjects with chronic TBI. Our results also suggest that FA in major white matter tracts is correlated with memory in health and in disease, alike; larger and longitudinal studies are needed to discern potential differences in these correlations in the two groups.

  13. Association of a Guardian’s Report of a Child Acting Abnormally With Traumatic Brain Injury After Minor Blunt Head Trauma

    PubMed Central

    Nishijima, Daniel K.; Holmes, James F.; Dayan, Peter S.; Kuppermann, Nathan

    2016-01-01

    IMPORTANCE Increased use of computed tomography (CT) in children is concerning owing to the cancer risk from ionizing radiation, particularly in children younger than 2 years. A guardian report that a child is acting abnormally is a risk factor for clinically important traumatic brain injury (ciTBI) and may be a driving factor for CT use in the emergency department. OBJECTIVE To determine the prevalence of ciTBIs and TBIs in children younger than 2 years with minor blunt head trauma and a guardian report of acting abnormally with (1) no other findings or (2) other concerning findings for TBI. DESIGN, SETTING, AND PARTICIPANTS Secondary analysis of a large, prospective, multicenter cohort study that included 43 399 children younger than 18 years with minor blunt head trauma evaluated in 25 emergency departments. The study was conducted on data obtained between June 2004 and September 2006. Data analysis was performed between August 21, 2014, and March 9, 2015. EXPOSURES A guardian report that the child was acting abnormally after minor blunt head trauma. MAIN OUTCOMES AND MEASURES The prevalence of ciTBI (defined as death, neurosurgery, intubation for >24 hours, or hospitalization for ≥2 nights in association with TBI on CT imaging) and TBI on CT imaging in children with a guardian report of acting abnormally with (1) no other findings and (2) other concerning findings for TBI. RESULTS Of 43 399 children in the cohort study, a total of 1297 children had reports of acting abnormally, of whom 411 (31.7%) had this report as their only finding. Reported as percentage (95% CI), 1 of 411 (0.2% [0–1.3%]) had a ciTBI, and 4 TBIs were noted on the CT scans in 185 children who underwent imaging (2.2% [0.6%–5.4%]). In children with reports of acting abnormally and other concerning findings for TBI, 29 of 886 (3.3% [2.2%–4.7%]) had ciTBIs and 66 of 674 (9.8% [7.7%–12.3%]) had TBIs on CT. CONCLUSIONS AND RELEVANCE Clinically important TBIs are very uncommon, and TBIs

  14. Lung Perfusion Scanning in Hepatic Cirrhosis

    PubMed Central

    Stanley, N. N.; Ackrill, P.; Wood, J.

    1972-01-01

    Abnormal lung perfusion scans using radioactive particles were found in five out of six cases of hepatic cirrhosis with arterial hypoxaemia. None had clinical evidence of cardiopulmonary disease or signs of pulmonary embolism on arteriography. The scan defects are probably caused by a disorder of the pulmonary microvasculature, which may show regional variation in severity. ImagesFIG. 1FIG. 2 PMID:4645896

  15. Abnormal regional activity and functional connectivity in resting-state brain networks associated with etiology confirmed unilateral pulsatile tinnitus in the early stage of disease.

    PubMed

    Lv, Han; Zhao, Pengfei; Liu, Zhaohui; Li, Rui; Zhang, Ling; Wang, Peng; Yan, Fei; Liu, Liheng; Wang, Guopeng; Zeng, Rong; Li, Ting; Dong, Cheng; Gong, Shusheng; Wang, Zhenchang

    2017-03-01

    Abnormal neural activities can be revealed by resting-state functional magnetic resonance imaging (rs-fMRI) using analyses of the regional activity and functional connectivity (FC) of the networks in the brain. This study was designed to demonstrate the functional network alterations in the patients with pulsatile tinnitus (PT). In this study, we recruited 45 patients with unilateral PT in the early stage of disease (less than 48 months of disease duration) and 45 normal controls. We used regional homogeneity (ReHo) and seed-based FC computational methods to reveal resting-state brain activity features associated with pulsatile tinnitus. Compared with healthy controls, PT patients showed regional abnormalities mainly in the left middle occipital gyrus (MOG), posterior cingulate gyrus (PCC), precuneus and right anterior insula (AI). When these regions were defined as seeds, we demonstrated widespread modification of interaction between the auditory and non-auditory networks. The auditory network was positively connected with the cognitive control network (CCN), which may associate with tinnitus related distress. Both altered regional activity and changed FC were found in the visual network. The modification of interactions of higher order networks were mainly found in the DMN, CCN and limbic networks. Functional connectivity between the left MOG and left parahippocampal gyrus could also be an index to reflect the disease duration. This study helped us gain a better understanding of the characteristics of neural network modifications in patients with pulsatile tinnitus.

  16. 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

  17. 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.

  18. Magnetization transfer and T2 quantitation in normal appearing cortical gray matter and white matter adjacent to focal abnormality in patients with traumatic brain injury.

    PubMed

    Kumar, Rajesh; Gupta, Rakesh K; Rao, Sajja B; Chawla, Sanjeev; Husain, Mazhar; Rathore, Ram K S

    2003-10-01

    Traumatic brain injury (TBI) is one of the commonest causes of morbidity and mortality in the developed countries with posttraumatic epilepsy and functional disability being its major sequelae. The purpose of this study was to test the hypothesis whether the normal appearing adjacent gray and white matter regions on T2 and T1 weighted magnetization transfer (MT) weighted images show any abnormality on quantitative imaging in patients with TBI. A total of 51 patients with TBI and 10 normal subjects were included in this study. There were significant differences in T2 and MT ratio values of T2 weighted and T1 weighted MT normal appearing gray matter regions adjacent to focal image abnormality compared to normal gray matter regions in the normal individuals as corresponding contralateral regions of the TBI patient's group (p < 0.05). However the adjoining normal appearing white matter quantitative values did not show any significant change compared to the corresponding contralateral normal white matter values. We conclude that quantitative T2 and MT ratio values provide additional abnormality in patients with TBI that is not discernable on conventional T2 weighted and T1 weighted MT imaging especially in gray matter. This additional information may be of value in overall management of these patients with TBI.

  19. 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

  20. Subanesthetic Ketamine Treatment Promotes Abnormal Interactions between Neural Subsystems and Alters the Properties of Functional Brain Networks

    PubMed Central

    Dawson, Neil; McDonald, Martin; Higham, Desmond J; Morris, Brian J; Pratt, Judith A

    2014-01-01

    Acute treatment with subanesthetic ketamine, a non-competitive N-methyl-D-aspartic acid (NMDA) receptor antagonist, is widely utilized as a translational model for schizophrenia. However, how acute NMDA receptor blockade impacts on brain functioning at a systems level, to elicit translationally relevant symptomatology and behavioral deficits, has not yet been determined. Here, for the first time, we apply established and recently validated topological measures from network science to brain imaging data gained from ketamine-treated mice to elucidate how acute NMDA receptor blockade impacts on the properties of functional brain networks. We show that the effects of acute ketamine treatment on the global properties of these networks are divergent from those widely reported in schizophrenia. Where acute NMDA receptor blockade promotes hyperconnectivity in functional brain networks, pronounced dysconnectivity is found in schizophrenia. We also show that acute ketamine treatment increases the connectivity and importance of prefrontal and thalamic brain regions in brain networks, a finding also divergent to alterations seen in schizophrenia. In addition, we characterize how ketamine impacts on bipartite functional interactions between neural subsystems. A key feature includes the enhancement of prefrontal cortex (PFC)-neuromodulatory subsystem connectivity in ketamine-treated animals, a finding consistent with the known effects of ketamine on PFC neurotransmitter levels. Overall, our data suggest that, at a systems level, acute ketamine-induced alterations in brain network connectivity do not parallel those seen in chronic schizophrenia. Hence, the mechanisms through which acute ketamine treatment induces translationally relevant symptomatology may differ from those in chronic schizophrenia. Future effort should therefore be dedicated to resolve the conflicting observations between this putative translational model and schizophrenia. PMID:24492765

  1. Perfusion MRI: The Five Most Frequently Asked Technical Questions

    PubMed Central

    Essig, Marco; Shiroishi, Mark S.; Nguyen, Thanh Binh; Saake, Marc; Provenzale, James M.; Enterline, David; Anzalone, Nicoletta; Dörfler, Arnd; Rovira, Àlex; Wintermark, Max; Law, Meng

    2013-01-01

    OBJECTIVE This and its companion article address the 10 most frequently asked questions that radiologists face when planning, performing, processing, and interpreting different MR perfusion studies in CNS imaging. CONCLUSION Perfusion MRI is a promising tool in assessing stroke, brain tumors, and patients with neurodegenerative diseases. Most of the impediments that have limited the use of perfusion MRI can be overcome to allow integration of these methods into modern neuroimaging protocols. PMID:23255738

  2. Brain Anatomical Abnormalities in High-Risk Individuals, First-Episode, and Chronic Schizophrenia: An Activation Likelihood Estimation Meta-analysis of Illness Progression

    PubMed Central

    Chan, Raymond C. K.; Di, Xin; McAlonan, Grainne M.; Gong, Qi-yong

    2011-01-01

    Objective: The present study reviewed voxel-based morphometry (VBM) studies on high-risk individuals with schizophrenia, patients experiencing their first-episode schizophrenia (FES), and those with chronic schizophrenia. We predicted that gray matter abnormalities would show progressive changes, with most extensive abnormalities in the chronic group relative to FES and least in the high-risk group. Method: Forty-one VBM studies were reviewed. Eight high-risk studies, 14 FES studies, and 19 chronic studies were analyzed using anatomical likelihood estimation meta-analysis. Results: Less gray matter in the high-risk group relative to controls was observed in anterior cingulate regions, left amygdala, and right insula. Lower gray matter volumes in FES compared with controls were also found in the anterior cingulate and right insula but not the amygdala. Lower gray matter volumes in the chronic group were most extensive, incorporating similar regions to those found in FES and high-risk groups but extending to superior temporal gyri, thalamus, posterior cingulate, and parahippocampal gryus. Subtraction analysis revealed less frontotemporal, striatal, and cerebellar gray matter in FES than the high-risk group; the high-risk group had less gray matter in left subcallosal gyrus, left amygdala, and left inferior frontal gyrus compared with FES. Subtraction analysis confirmed lower gray matter volumes through ventral-dorsal anterior cingulate, right insula, left amygdala and thalamus in chronic schizophrenia relative to FES. Conclusions: Frontotemporal brain structural abnormalities are evident in nonpsychotic individuals at high risk of developing schizophrenia. The present meta-analysis indicates that these gray matter abnormalities become more extensive through first-episode and chronic illness. Thus, schizophrenia appears to be a progressive cortico-striato-thalamic loop disorder. PMID:19633214

  3. Swimming attenuates D-galactose-induced brain aging via suppressing miR-34a-mediated autophagy impairment and abnormal mitochondrial dynamics.

    PubMed

    Kou, Xianjuan; Li, Jie; Liu, Xingran; Chang, Jingru; Zhao, Qingxia; Jia, Shaohui; Fan, Jingjing; Chen, Ning

    2017-03-16

    MicroRNAs (miRNAs) have been reported to be involved in many neurodegenerative diseases. In order to explore the regulatory role of miR-34a in aging-related diseases such as Alzheimer's disease (AD) during exercise intervention, we constructed a rat model with (D-galactose) D-gal-induced oxidative stress and cognitive impairment coupled with dysfunctional autophagy and abnormal mitochondrial dynamics, determined the mitigation of cognitive impairment of D-gal-induced aging rats during swimming intervention, and evaluated miR-34a-mediated functional status of autophagy and abnormal mitochondrial dynamics. Meanwhile, whether the up-regulation of miR-34a can lead to dysfunctional autophagy and abnormal mitochondrial dynamics was confirmed in human SH-SY5Y cells with silenced miR-34a by the transfection of miR-34a inhibitor. Results indicated that swimming intervention could significantly attenuate cognitive impairment, rescue the up-regulation of miR-34a, mitigate the dysfunctional autophagy, and inhibit the increase of Drp1 in D-gal-induced aging model rats. In contrast, miR-34a inhibitor in cell model not only attenuated D-gal-induced autophagy impairment, but also decreased the expression of Drp1 and Mfn2. Therefore, swimming training can attenuate the impairment of miR-34a-mediated autophagy and abnormal mitochondrial dynamics during D-gal-induced aging process in rat hippocampal tissue, which may be one of the mechanisms for delaying brain aging through swimming training, and miR-34a could be the novel therapeutic target for aging-related diseases such as AD.

  4. Abnormal Coupling Between Default Mode Network and Delta and Beta Band Brain Electric Activity in Psychotic Patients.

    PubMed

    Baenninger, Anja; Palzes, Vanessa A; Roach, Brian J; Mathalon, Daniel H; Ford, Judith M; Koenig, Thomas

    2017-02-01

    Common-phase synchronization of neuronal oscillations is a mechanism by which distributed brain regions can be integrated into transiently stable networks. Based on the hypothesis that schizophrenia is characterized by deficits in functional integration within neuronal networks, this study aimed to explore whether psychotic patients exhibit differences in brain regions involved in integrative mechanisms. We report an electroencephalography (EEG)-informed functional magnetic resonance imaging analysis of eyes-open resting-state data collected from patients and healthy controls at two study sites. Global field synchronization (GFS) was chosen as an EEG measure indicating common-phase synchronization across electrodes. Several brain clusters appeared to be coupled to GFS differently in patients and controls. Activation in brain areas belonging to the default mode network was negatively associated to GFS delta (1-3.5 Hz) and positively to GFS beta (13-30 Hz) bands in patients, whereas controls showed an opposite pattern for both GFS frequency bands in those regions; activation in the extrastriate visual cortex was inversely related to GFS alpha1 (8.5-10.5 Hz) band in healthy controls, while patients had a tendency toward a positive relationship. Taken together, the GFS measure might be useful for detecting additional aspects of deficient functional network integration in psychosis.

  5. 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…

  6. Triple-transgenic Alzheimer's disease mice exhibit region-specific abnormalities in brain myelination patterns prior to appearance of amyloid and tau pathology

    PubMed Central

    Desai, Maya K.; Sudol, Kelly L.; Janelsins, Michelle C.; Mastrangelo, Michael A.; Frazer, Maria E.; Bowers, William J.

    2008-01-01

    Alzheimer's disease (AD) is a progressively debilitating brain disorder pathologically defined by extracellular amyloid plaques, intraneuronal neurofibrillary tangles, and synaptic disintegrity. AD has not been widely considered a disease of white matter, but more recent evidence suggests the existence of abnormalities in myelination patterns and myelin attrition in AD-afflicted human brains. Herein, we demonstrate that triple-transgenic AD (3xTg-AD) mice, which harbor the human amyloid precursor protein Swedish mutant transgene, presenilin knock-in mutation, and tau P301L mutant transgene, exhibit significant region-specific alterations in myelination patterns and in oligodendrocyte marker expression profiles at time points preceding the appearance of amyloid and tau pathology. These immunohistochemical signatures are coincident with age-related alterations in axonal and myelin sheath ultrastructure as visualized by comparative electron microscopic examination of 3xTg-AD and non-transgenic mouse brain tissue. Overall, these findings indicate 3xTg-AD mice represent a viable model in which to examine mechanisms underlying AD-related myelination and neural transmission defects that occur early during pre-symptomatic stages of the disease process. PMID:18661556

  7. Abnormalities of regional brain function in Parkinson’s disease: a meta-analysis of resting state functional magnetic resonance imaging studies

    PubMed Central

    Pan, PingLei; Zhang, Yang; Liu, Yi; Zhang, He; Guan, DeNing; Xu, Yun

    2017-01-01

    There is convincing evidence that abnormalities of regional brain function exist in Parkinson’s disease (PD). However, many resting-state functional magnetic resonance imaging (rs-fMRI) studies using amplitude of low-frequency fluctuations (ALFF) have reported inconsistent results about regional spontaneous neuronal activity in PD. Therefore, we conducted a comprehensive meta-analysis using the Seed-based d Mapping and several complementary analyses. We searched PubMed, Embase, and Web of Science databases for eligible whole-brain rs-fMRI studies that measured ALFF differences between patients with PD and healthy controls published from January 1st, 2000 until June 24, 2016. Eleven studies reporting 14 comparisons, comparing 421 patients and 381 healthy controls, were included. The most consistent and replicable findings in patients with PD compared with healthy controls were identified, including the decreased ALFFs in the bilateral supplementary motor areas, left putamen, left premotor cortex, and left inferior parietal gyrus, and increased ALFFs in the right inferior parietal gyrus. The altered ALFFs in these brain regions are related to motor deficits and compensation in PD, which contribute to understanding its neurobiological underpinnings and could serve as specific regions of interest for further studies. PMID:28079169

  8. 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.

  9. A reappraisal of retrograde cerebral perfusion

    PubMed Central

    2013-01-01

    Brain protection during aortic arch surgery by perfusing cold oxygenated blood into the superior vena cava was first reported by Lemole et al. In 1990 Ueda and associates first described the routine use of continuous retrograde cerebral perfusion (RCP) in thoracic aortic surgery for the purpose of cerebral protection during the interval of obligatory interruption of anterograde cerebral flow. The beneficial effects of RCP may be its ability to sustain brain hypothermia during hypothermic circulatory arrest (HCA) and removal of embolic material from the arterial circulation of the brain. RCP can offer effective brain protection during HCA for about 40 to 60 minutes. Animal experiments revealed that RCP provided inadequate cerebral perfusion and that neurological recovery was improved with selective antegrade cerebral perfusion (ACP), however, both RCP and ACP provide comparable clinical outcomes regarding both the mortality and stroke rates by risk-adjusted and case-matched comparative study. RCP still remains a valuable adjunct for brain protection during aortic arch repair in particular pathologies and patients. PMID:23977600

  10. CAD of myocardial perfusion

    NASA Astrophysics Data System (ADS)

    Storm, Corstiaan J.; Slump, Cornelis H.

    2007-03-01

    Our purpose is in the automated evaluation of the physiological relevance of lesions in coronary angiograms. We aim to extract as much as possible quantitative information about the physiological condition of the heart from standard angiographic image sequences. Coronary angiography is still the gold standard for evaluating and diagnosing coronary abnormalities as it is able to locate precisely the coronary artery lesions. The dimensions of the stenosis can be assessed nowadays successfully with image processing based Quantitative Coronary Angiography (QCA) techniques. Our purpose is to assess the clinical relevance of the pertinent stenosis. We therefore analyze the myocardial perfusion as revealed in standard angiographic image sequences. In a Region-of-Interest (ROI) on the angiogram (without an overlaying major blood vessel) the contrast is measured as a function of time (the so-called time-density curve). The required hyperemic state of exercise is induced artificially by the injection of a vasodilator drug e.g. papaverine. In order to minimize motion artifacts we select based on the recorded ECG signal end-diastolic images in both a basal and a hyperemic run in the same projection to position the ROI. We present the development of the algorithms together with results of a small study of 20 patients which have been catheterized following the standard protocol.

  11. 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

  12. A familial case of Coffin-Lowry syndrome caused by RPS6KA3 C.898C>T mutation associated with multiple abnormal brain imaging findings.

    PubMed

    Tos, T; Alp, M Y; Aksoy, A; Ceylaner, S; Hanauer, A

    2015-01-01

    Coffin-Lowry syndrome (CLS) is a rare X linked mental retardation syndrome characterised by severe psychomotor and growth retardation, distinct facial phenotype, and progressive skeletal malformations. It is caused by mutations in the RPS6KA3 gene located at Xp22.2. In this report we describe a family with CLS consists of three affected males, and two affected females, arising from c.898C>T mutation in RPS6KA3 gene. A 6 year-old, and a 3 year-old boy both had distinct clinical features of Coffin-Lowry syndrome; severe mental and motor retardation, microcephaly, prominent forehead, hypertelorism, large mouth, large ears, large soft hands, puffy tapered fingers, and pectus carinatum. In addition, they had multiple abnormal brain MRI findings. Other siblings presented with a mild and variable phenotype.

  13. 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

  14. 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.

  15. 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

  16. Tight junctional abnormality in multiple sclerosis white matter affects all calibres of vessel and is associated with blood-brain barrier leakage and active demyelination.

    PubMed

    Kirk, John; Plumb, Jonnie; Mirakhur, Meenakshi; McQuaid, Stephen

    2003-10-01

    Blood-brain barrier (BBB) hyperpermeability in multiple sclerosis (MS) is associated with lesion pathogenesis and has been linked to pathology in microvascular tight junctions (TJs). This study quantifies the uneven distribution of TJ pathology and its association with BBB leakage. Frozen sections from plaque and normal-appearing white matter (NAWM) in 14 cases were studied together with white matter from six neurological and five normal controls. Using single and double immunofluorescence and confocal microscopy, the TJ-associated protein zonula occludens-1 (ZO-1) was examined across lesion types and tissue categories, and in relation to fibrinogen leakage. Confocal image data sets were analysed for 2198 MS and 1062 control vessels. Significant differences in the incidence of TJ abnormalities were detected between the different lesion types in MS and between MS and control white matter. These were frequent in oil-red O (ORO)(+) active plaques, affecting 42% of vessel segments, but less frequent in ORO(-) inactive plaques (23%), NAWM (13%), and normal (3.7%) and neurological controls (8%). A similar pattern was found irrespective of the vessel size, supporting a causal role for diffusible inflammatory mediators. In both NAWM and inactive lesions, dual labelling showed that vessels with the most TJ abnormality also showed most fibrinogen leakage. This was even more pronounced in active lesions, where 41% of vessels in the highest grade for TJ alteration showed severe leakage. It is concluded that disruption of TJs in MS, affecting both paracellular and transcellular paths, contributes to BBB leakage. TJ abnormality and BBB leakage in inactive lesions suggests either failure of TJ repair or a continuing pathological process. In NAWM, it suggests either pre-lesional change or secondary damage. Clinically inapparent TJ pathology has prognostic implications and should be considered when planning disease-modifying therapy.

  17. Whole-brain gray matter volume abnormalities in patients with generalized anxiety disorder: voxel-based morphometry.

    PubMed

    Moon, Chung-Man; Kim, Gwang-Won; Jeong, Gwang-Woo

    2014-02-12

    Patients with generalized anxiety disorder (GAD) experience psychological distress because of excessive and uncontrollable anxiety in everyday life. Only a few morphological studies have so far focused on specific brain regions of interest as well as the gray matter volume changes in GAD patients. This study evaluated gray matter volume alterations in whole-brain areas between GAD patients and healthy controls, and sex differences between the specific brain areas with significant volume changes in GAD patients using voxel-based morphometry. Twenty-two patients with GAD (13 men and nine women), who were diagnosed using the DSM-IV-TR, and 22 age-matched healthy controls (13 men and nine women) participated in this study. The high-resolution MRI data were processed using voxel-based morphometry analysis on the basis of diffeomorphic anatomical registration through an exponentiated Lie algebra algorithm in Statistical Parametric Mapping 8. There was no significant difference in the total intracranial volume between GAD patients and controls, but a significant difference was observed between sexes (P<0.05). Patients with GAD showed significant volume reductions in the hippocampus, midbrain, thalamus, insula, and superior temporal gyrus compared with the controls. As for the sex comparison, female patients showed a significant increase in the volume of the dorsolateral prefrontal cortex relative to male patients. Also, the volume of the dorsolateral prefrontal cortex in female patients was correlated positively with the Hamilton Anxiety Rating Scale score (γ=0.68, P=0.04). The specific morphological variations in patient with GAD will be helpful to understand the neural mechanism associated with a symptom of GAD. Furthermore, the findings would be valuable for the diagnostic accuracy of GAD using morphometric MRI analysis.

  18. Alveolar abnormalities

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/001093.htm Alveolar abnormalities To use the sharing features on this page, please enable JavaScript. Alveolar abnormalities are changes in the tiny air sacs in ...

  19. Nail abnormalities

    MedlinePlus

    Beau's lines; Fingernail abnormalities; Spoon nails; Onycholysis; Leukonychia; Koilonychia; Brittle nails ... 2012:chap 71. Zaiac MN, Walker A. Nail abnormalities associated with systemic pathologies. Clin Dermatol . 2013;31: ...

  20. 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.

  1. HMG-CoA reductase inhibitor rosuvastatin improves abnormal brain electrical activity via mechanisms involving eNOS.

    PubMed

    Seker, F B; Kilic, U; Caglayan, B; Ethemoglu, M S; Caglayan, A B; Ekimci, N; Demirci, S; Dogan, A; Oztezcan, S; Sahin, F; Yilmaz, B; Kilic, E

    2015-01-22

    Apart from its repressing effect on plasma lipid levels, 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase inhibitors exert neuroprotective functions in animal models of neurodegenerative disorders. In view of these promising observations, we were interested in whether HMG-CoA reductase inhibition would affect epileptiform activity in the brain. To elucidate this issue, atorvastatin, simvastatin and rosuvastatin were administered orally at a dose of 20 mg/kg each for 3 days and their anti-epileptic activities were tested and compared in rats. Epileptiform activity in the brain was induced by an intracortical penicillin G injection. Among HMG-CoA reductase inhibitors, simvastatin-treatment was less effective in terms of spike frequency as compared with atorvastatin- and rosuvastatin-treated animals. Atorvastatin treatment reduced spike frequencies and amplitudes significantly throughout the experiment. However, the most pronounced anti-epileptic effect was observed in rosuvastatin-treated animals, which was associated with improved blood-brain barrier (BBB) integrity, increased expression of endothelial nitric oxide synthase (eNOS) mRNA and decreased expressions of pro-apoptotic p53, Bax and caspase-3 mRNAs. Inhibition of eNOS activity with L-NG-Nitroarginine Methyl Ester (L-NAME) reversed the anti-epileptic effect of rosuvastatin significantly. However, L-NAME did not alter the effect of rosuvastatin on the levels of p53, Bax and caspase-3 mRNA expression. Here, we provide evidence that among HMG-CoA reductase inhibitors, rosuvastatin was the most effective statin on the reduction of epileptiform activity, which was associated with improved BBB permeability, increased expression of eNOS and decreased expressions of pro-apoptotic p53, Bax and caspase-3. Our observation also revealed that the anti-epileptic effect of rosuvastatin was dependent on the increased expression level of eNOS. The robust anti-epileptic effect encourages proof-of-concept studies with

  2. 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

  3. 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.

  4. Impaired associative taste learning and abnormal brain activation in kinase-defective eEF2K mice.

    PubMed

    Gildish, Iness; Manor, David; David, Orit; Sharma, Vijendra; Williams, David; Agarwala, Usha; Wang, Xuemin; Kenney, Justin W; Proud, Chris G; Rosenblum, Kobi

    2012-02-24

    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 consolidation mechanisms involved in translation initiation and elongation have previously been studied in the cortex using taste-learning paradigms. For example, the levels of phosphorylation of eukaryotic elongation factor 2 (eEF2) were found to be correlated with taste learning in the gustatory cortex (GC), minutes following learning. In order to isolate the role of the eEF2 phosphorylation state at Thr-56 in both molecular and system consolidation, we analyzed cortical-dependent taste learning in eEF2K (the only known kinase for eEF2) ki mice, which exhibit reduced levels of eEF2 phosphorylation but normal levels of eEF2 and eEF2K. These mice exhibit clear attenuation of cortical-dependent associative, but not of incidental, taste learning. In order to gain a better understanding of the underlying mechanisms, we compared brain activity as measured by MEMRI (manganese-enhanced magnetic resonance imaging) between eEF2K ki mice and WT mice during conditioned taste aversion (CTA) learning and observed clear differences between the two but saw no differences under basal conditions. Our results demonstrate that adequate levels of phosphorylation of eEF2 are essential for cortical-dependent associative learning and suggest that malfunction of memory processing at the systems level underlies this associative memory impairment.

  5. Impaired associative taste learning and abnormal brain activation in kinase-defective eEF2K mice

    PubMed Central

    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 consolidation mechanisms involved in translation initiation and elongation have previously been studied in the cortex using taste-learning paradigms. For example, the levels of phosphorylation of eukaryotic elongation factor 2 (eEF2) were found to be correlated with taste learning in the gustatory cortex (GC), minutes following learning. In order to isolate the role of the eEF2 phosphorylation state at Thr-56 in both molecular and system consolidation, we analyzed cortical-dependent taste learning in eEF2K (the only known kinase for eEF2) ki mice, which exhibit reduced levels of eEF2 phosphorylation but normal levels of eEF2 and eEF2K. These mice exhibit clear attenuation of cortical-dependent associative, but not of incidental, taste learning. In order to gain a better understanding of the underlying mechanisms, we compared brain activity as measured by MEMRI (manganese-enhanced magnetic resonance imaging) between eEF2K ki mice and WT mice during conditioned taste aversion (CTA) learning and observed clear differences between the two but saw no differences under basal conditions. Our results demonstrate that adequate levels of phosphorylation of eEF2 are essential for cortical-dependent associative learning and suggest that malfunction of memory processing at the systems level underlies this associative memory impairment. PMID:22366775

  6. Cortical abnormalities in adults and adolescents with major depression based on brain scans from 20 cohorts worldwide in the ENIGMA Major Depressive Disorder Working Group.

    PubMed

    Schmaal, L; Hibar, D P; Sämann, P G; Hall, G B; Baune, B T; Jahanshad, N; Cheung, J W; van Erp, T G M; Bos, D; Ikram, M A; Vernooij, M W; Niessen, W J; Tiemeier, H; Hofman, A; Wittfeld, K; Grabe, H J; Janowitz, D; Bülow, R; Selonke, M; Völzke, H; Grotegerd, D; Dannlowski, U; Arolt, V; Opel, N; Heindel, W; Kugel, H; Hoehn, D; Czisch, M; Couvy-Duchesne, B; Rentería, M E; Strike, L T; Wright, M J; Mills, N T; de Zubicaray, G I; McMahon, K L; Medland, S E; Martin, N G; Gillespie, N A; Goya-Maldonado, R; Gruber, O; Krämer, B; Hatton, S N; Lagopoulos, J; Hickie, I B; Frodl, T; Carballedo, A; Frey, E M; van Velzen, L S; Penninx, B W J H; van Tol, M-J; van der Wee, N J; Davey, C G; Harrison, B J; Mwangi, B; Cao, B; Soares, J C; Veer, I M; Walter, H; Schoepf, D; Zurowski, B; Konrad, C; Schramm, E; Normann, C; Schnell, K; Sacchet, M D; Gotlib, I H; MacQueen, G M; Godlewska, B R; Nickson, T; McIntosh, A M; Papmeyer, M; Whalley, H C; Hall, J; Sussmann, J E; Li, M; Walter, M; Aftanas, L; Brack, I; Bokhan, N A; Thompson, P M; Veltman, D J

    2016-05-03

    The neuro-anatomical substrates of major depressive disorder (MDD) are still not well understood, despite many neuroimaging studies over the past few decades. Here we present the largest ever worldwide study by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Major Depressive Disorder Working Group on cortical structural alterations in MDD. Structural T1-weighted brain magnetic resonance imaging (MRI) scans from 2148 MDD patients and 7957 healthy controls were analysed with harmonized protocols at 20 sites around the world. To detect consistent effects of MDD and its modulators on cortical thickness and surface area estimates derived from MRI, statistical effects from sites were meta-analysed separately for adults and adolescents. Adults with MDD had thinner cortical gray matter than controls in the orbitofrontal cortex (OFC), anterior and posterior cingulate, insula and temporal lobes (Cohen's d effect sizes: -0.10 to -0.14). These effects were most pronounced in first episode and adult-onset patients (>21 years). Compared to matched controls, adolescents with MDD had lower total surface area (but no differences in cortical thickness) and regional reductions in frontal regions (medial OFC and superior frontal gyrus) and primary and higher-order visual, somatosensory and motor areas (d: -0.26 to -0.57). The strongest effects were found in recurrent adolescent patients. This highly powered global effort to identify consistent brain abnormalities showed widespread cortical alterations in MDD patients as compared to controls and suggests that MDD may impact brain structure in a highly dynamic way, with different patterns of alterations at different stages of life.Molecular Psychiatry advance online publication, 3 May 2016; doi:10.1038/mp.2016.60.

  7. Modeling propagation delays in the development of SOMs--a parallel with abnormal brain growth in autism.

    PubMed

    Noriega, Gerardo

    2008-01-01

    Brain overgrowth in early developmental stages of children with autism is well documented. This paper explores the possibility that increases in propagation delays of stimuli and the signals triggered by them, resulting from this overgrowth, may be conducive to the development of poorly structured cortical maps, which may in turn be associated with autistic characteristics. We use a framework based on Self-Organizing Maps (SOMs). Unlike the conventional SOM model that assumes that all neurons in the neighborhood of the neuron closest to a stimulus instantaneously react to it and adjust their weights, we propose a more biologically realistic model that acknowledges delays inherent in the propagation of signals. We show that propagation delays can significantly affect the performance of SOMs. Coverage of stimuli is negatively affected by either an increase in the dilution factor (a parameter in the proposed model that controls the adjustment of responses to overlapping stimuli), or a decrease in propagation speed. For large dilution factors the topological structure of the maps is also compromised. We also demonstrate the model's robustness to different input stimuli layouts and distributions.

  8. Clinical Use of CT Perfusion For Diagnosis and Prediction of Lesion Growth in Acute Ischemic Stroke

    PubMed Central

    Huisa, Branko N; Neil, William P; Schrader, Ronald; Maya, Marcel; Pereira, Benedict; Bruce, Nhu T; Lyden, Patrick D

    2012-01-01

    Background and Purpose CT perfusion (CTP) mapping in research centers correlates well with diffusion weighted imaging (DWI) lesions and may accurately differentiate the infarct core from ischemic penumbra. The value of CTP in real-world clinical practice has not been fully established. We investigated the yield of CTP– derived cerebral blood volume (CBV) and mean transient time (MTT) for the detection of cerebral ischemia and ischemic penumbra in a sample of acute ischemic stroke (AIS) patients. Methods We studied 165 patients with initial clinical symptoms suggestive of AIS. All patients had an initial non-contrast head CT, CT Perfusion (CTP), CT angiogram (CTA) and follow up brain MRI. The obtained perfusion images were used for image processing. CBV, MTT and DWI lesion volumes were visually estimated and manually traced. Statistical analysis was done using R-2.14.and SAS 9.1. Results All normal DWI sequences had normal CBV and MTT studies (N=89). Seventy-three patients had acute DWI lesions. CBV was abnormal in 23.3% and MTT was abnormal in 42.5% of these patients. There was a high specificity (91.8%)but poor sensitivity (40.0%) for MTT maps predicting positive DWI. Spearman correlation was significant between MTT and DWI lesions (ρ=0.66, p>0.0001) only for abnormal MTT and DWI lesions>0cc. CBV lesions did not correlate with final DWI. Conclusions In real-world use, acute imaging with CTP did not predict stroke or DWI lesions with sufficient accuracy. Our findings argue against the use of CTP for screening AIS patients until real-world implementations match the accuracy reported from specialized research centers. PMID:23253533

  9. Myocardial perfusion as an indicator of graft patency after coronary artery bypass surgery. [Thallium 201

    SciTech Connect

    Kolibash, A.J.; Call, T.D.; Bush, C.A.; Tetalman, M.R.; Lewis, R.P.

    1980-05-01

    Stress and resting myocardial perfusion were assessed in 38 patients who received 96 grafts. Stress perfusion was evaluated with thallium-201 and resting myocardial blood flow distribution with radiolabeled particles. When both stress and rest perfusion were normal, graft patency was 82% (51 of 62 grafts). Graft patency was also high (81%, 13 of 16) in areas where stress perfusion abnormalities resolved or become less apparent at rest. However, when stress perfusion defects remained unchanged at rest, the graf was likely to be occuluded (73%, 11 of 15). Maintenance of normal rest perfusion or improvement of rest perfusion postoperatively was also associated with a high graft patency rate (80%, 35 of 44), whereas the development of new rest perfusion defects postoperatively implied graft occlusion (86%, six of seven).

  10. Insulin-like growth factor binding protein-6 transgenic mice: postnatal growth, brain development, and reproduction abnormalities.

    PubMed

    Bienvenu, Géraldine; Seurin, Danielle; Grellier, Pascale; Froment, Pascal; Baudrimont, Marielle; Monget, Philippe; Le Bouc, Yves; Babajko, Sylvie

    2004-05-01

    In biological fluids, IGFs bind to six distinct binding proteins (IGFBP-1 to -6). IGFBP-6 is of particular interest because it has been shown to inhibit proliferation in many cell types and to be synthesized in the central nervous system (CNS). It also has the strongest affinity for IGF-II among the IGFBPs. To study IGFBP-6 function in vivo, we established IGFBP-6 transgenic mice in which human IGFBP-6 (hIGFBP-6) cDNA is expressed under the control of the glial fibrillary acidic protein (GFAP) promoter. Northern and Western blot analysis revealed strong transgene expression in the CNS. With histological examination of the CNS, cerebellum size and weight proved to be reduced by about 25% and 35%, respectively, and there were smaller numbers of differentiated, GFAP-expressing astrocytes than in wild-type mice. Between birth and 1 month of age, transgenic mice had high levels of circulating hIGFBP-6 and reduced plasma IGF-I, and, as a result, body weight was significantly reduced. Reproductive physiology was also affected. Litter size was reduced by 27% when wild-type males were mated with 3-month-old transgenic females and by 66% when mated with 6-month-old transgenic females. Histological examination of ovaries of transgenic mice revealed a marked decrease in weight and in the number of corpora lutea, suggesting altered ovulation, and circulating LH levels were reduced by 50%. Our results indicate that this new model of transgenic mouse may prove to be a useful tool in elucidating the in vivo role of IGFBP-6 in the brain, especially in regard to hypothalamic control, and in reproductive physiology.

  11. Coupling between resting cerebral perfusion and EEG.

    PubMed

    O'Gorman, R L; Poil, S-S; Brandeis, D; Klaver, P; Bollmann, S; Ghisleni, C; Lüchinger, R; Martin, E; Shankaranarayanan, A; Alsop, D C; Michels, L

    2013-07-01

    While several studies have investigated interactions between the electroencephalography (EEG) and functional magnetic resonance imaging BOLD signal fluctuations, less is known about the associations between EEG oscillations and baseline brain haemodynamics, and few studies have examined the link between EEG power outside the alpha band and baseline perfusion. Here we compare whole-brain arterial spin labelling perfusion MRI and EEG in a group of healthy adults (n = 16, ten females, median age: 27 years, range 21-48) during an eyes closed rest condition. Correlations emerged between perfusion and global average EEG power in low (delta: 2-4 Hz and theta: 4-7 Hz), middle (alpha: 8-13 Hz), and high (beta: 13-30 Hz and gamma: 30-45 Hz) frequency bands in both cortical and sub-cortical regions. The correlations were predominately positive in middle and high-frequency bands, and negative in delta. In addition, central alpha frequency positively correlated with perfusion in a network of brain regions associated with the modulation of attention and preparedness for external input, and central theta frequency correlated negatively with a widespread network of cortical regions. These results indicate that the coupling between average EEG power/frequency and local cerebral blood flow varies in a frequency specific manner. Our results are consistent with longstanding concepts that decreasing EEG frequencies which in general map onto decreasing levels of activation.

  12. 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 ...

  13. Siblings with the adult-onset slowly progressive type of pantothenate kinase-associated neurodegeneration and a novel mutation, Ile346Ser, in PANK2: clinical features and (99m)Tc-ECD brain perfusion SPECT findings.

    PubMed

    Doi, Hiroshi; Koyano, Shigeru; Miyatake, Satoko; Matsumoto, Naomichi; Kameda, Tomoaki; Tomita, Atsuko; Miyaji, Yosuke; Suzuki, Yume; Sawaishi, Yukio; Kuroiwa, Yoshiyuki

    2010-03-15

    Pantothenate kinase-associated neurodegeneration (PKAN), formerly known as Hallervorden-Spatz syndrome (HSS), is an autosomal recessive neurodegenerative disorder characterized by iron accumulation in the brain. Mutations in the pantothenate kinase 2 (PANK2) gene are known to be responsible for PKAN. Several studies have revealed correlations between clinical phenotypes and particular PANK2 mutations. The adult-onset slowly progressive type of PKAN with PANK2 mutations is very rare. In this report, we describe siblings with the adult-onset slowly progressive type of PKAN with a novel mutation, Ile346Ser, in PANK2. The siblings had the same mutation in PANK2 and had common clinical signs such as misalignment of teeth, a high arched palate, hollow feet, a slight cognitive decline, and an apparent executive dysfunction, although they showed different patterns of movement disorders. Thus, even if PKAN patients have identical mutations, it is likely that they will present with different types of movement disorders. Brain perfusion single photon emission computed tomography in both patients showed decreased regional cerebral blood flow in the bilateral frontoparietal lobes, the globus pallidus, the striatum, and around the ventriculus quartus. Cardiac uptake of [(123)I] meta-iodobenzylguanidine was normal in both patients. Analysis of genotype-phenotype correlations and the elucidation of mutational effects on pantothenate kinase 2 function, expression, and structure are important for understanding the mechanisms of PKAN.

  14. 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.

  15. Pathophysiology of white matter perfusion in Alzheimer's disease and vascular dementia.

    PubMed

    Barker, Rachel; Ashby, Emma L; Wellington, Dannielle; Barrow, Vivienne M; Palmer, Jennifer C; Kehoe, Patrick G; Esiri, Margaret M; Love, Seth

    2014-05-01

    Little is known about the contributors and physiological responses to white matter hypoperfusion in the human brain. We previously showed the ratio of myelin-associated glycoprotein to proteolipid protein 1 in post-mortem human brain tissue correlates with the degree of ante-mortem ischaemia. In age-matched post-mortem cohorts of Alzheimer's disease (n = 49), vascular dementia (n = 17) and control brains (n = 33) from the South West Dementia Brain Bank (Bristol), we have now examined the relationship between the ratio of myelin-associated glycoprotein to proteolipid protein 1 and several other proteins involved in regulating white matter vascularity and blood flow. Across the three cohorts, white matter perfusion, indicated by the ratio of myelin-associated glycoprotein to proteolipid protein 1, correlated positively with the concentration of the vasoconstrictor, endothelin 1 (P = 0.0005), and negatively with the concentration of the pro-angiogenic protein, vascular endothelial growth factor (P = 0.0015). The activity of angiotensin-converting enzyme, which catalyses production of the vasoconstrictor angiotensin II was not altered. In samples of frontal white matter from an independent (Oxford, UK) cohort of post-mortem brains (n = 74), we confirmed the significant correlations between the ratio of myelin-associated glycoprotein to proteolipid protein 1 and both endothelin 1 and vascular endothelial growth factor. We also assessed microvessel density in the Bristol (UK) samples, by measurement of factor VIII-related antigen, which we showed to correlate with immunohistochemical measurements of vessel density, and found factor VIII-related antigen levels to correlate with the level of vascular endothelial growth factor (P = 0.0487), suggesting that upregulation of vascular endothelial growth factor tends to increase vessel density in the white matter. We propose that downregulation of endothelin 1 and upregulation of vascular endothelial growth factor in the context

  16. Abdominal perfusion computed tomography.

    PubMed

    Ogul, Hayri; Bayraktutan, Ummugulsum; Kizrak, Yesim; Pirimoglu, Berhan; Yuceler, Zeynep; Sagsoz, M Erdem; Yilmaz, Omer; Aydinli, Bulent; Ozturk, Gurkan; Kantarci, Mecit

    2013-02-01

    The purpose of this article is to provide an up to date review on the spectrum of applications of perfusion computed tomography (CT) in the abdomen. New imaging techniques have been developed with the objective of obtaining a structural and functional analysis of different organs. Recently, perfusion CT has aroused the interest of many researchers who are studying the applicability of imaging modalities in the evaluation of abdominal organs and diseases. Per-fusion CT enables fast, non-invasive imaging of the tumor vascular physiology. Moreover, it can act as an in vivo biomarker of tumor-related angiogenesis.

  17. Abdominal Perfusion Computed Tomography

    PubMed Central

    Ogul, Hayri; Bayraktutan, Ummugulsum; Kizrak, Yesim; Pirimoglu, Berhan; Yuceler, Zeynep; Sagsoz, M. Erdem; Yilmaz, Omer; Aydinli, Bulent; Ozturk, Gurkan; Kantarci, Mecit

    2013-01-01

    The purpose of this article is to provide an up to date review on the spectrum of applications of perfusion computed tomography (CT) in the abdomen. New imaging techniques have been developed with the objective of obtaining a structural and functional analysis of different organs. Recently, perfusion CT has aroused the interest of many researchers who are studying the applicability of imaging modalities in the evaluation of abdominal organs and diseases. Per-fusion CT enables fast, non-invasive imaging of the tumor vascular physiology. Moreover, it can act as an in vivo biomarker of tumor-related angiogenesis. PMID:25610249

  18. Reversible changes in diffusion- and perfusion-based imaging in cerebral venous sinus thrombosis.

    PubMed

    Lin, Ning; Wong, Andrew K; Lipinski, Lindsay J; Mokin, Maxim; Siddiqui, Adnan H

    2016-02-01

    Diffusion- and perfusion-based imaging studies are regularly used in patients with ischemic stroke. Cerebral venous sinus thrombosis (CVST) is a rare cause of stroke and is primarily treated by systemic anticoagulation. Endovascular intervention can be considered in cases of failed medical therapy, yet the prognostic value of diffusion- and perfusion-based imaging for CVST has not been clearly established. We present a patient with CVST whose abnormal findings on MRI and CT perfusion images were largely reversed after endovascular treatment.

  19. 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 ...

  20. Repetitive Model of Mild Traumatic Brain Injury Produces Cortical Abnormalities Detectable by Magnetic Resonance Diffusion Imaging (DTI/DKI), Histopathology, and Behavior.

    PubMed

    Yu, Fengshan; Shukla, Dinesh K; Armstrong, Regina C; Marion, Christina M; Radomski, Kryslaine L; Selwyn, Reed G; Dardzinski, Bernard J

    2016-12-20

    Noninvasive detection of mild traumatic brain injury (mTBI) is important for evaluating acute through chronic effects of head injuries, particularly after repetitive impacts. To better detect abnormalities from mTBI, we performed longitudinal studies (baseline, 3, 6, and 42 days) using magnetic resonance diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI) in adult mice after repetitive mTBI (r-mTBI; daily × 5) or sham procedure. This r-mTBI produced righting reflex delay and was first characterized in the corpus callosum to demonstrate low levels of axon damage, astrogliosis, and microglial activation, without microhemorrhages. High-resolution DTI-DKI was then combined with post-imaging pathological validation along with behavioral assessments targeted for the impact regions. In the corpus callosum, only DTI fractional anisotropy at 42 days showed significant change post-injury. Conversely, cortical regions under the impact site (M1-M2, anterior cingulate) had reduced axial diffusivity (AD) at all time points with a corresponding increase in axial kurtosis (Ka) at 6 days. Post-imaging neuropathology showed microglial activation in both the corpus callosum and cortex at 42 days after r-mTBI. Increased cortical microglial activation correlated with decreased cortical AD after r-mTBI (r = -0.853; n = 5). Using Thy1-YFP-16 mice to fluorescently label neuronal cell bodies and processes revealed low levels of axon damage in the cortex after r-mTBI. Finally, r-mTBI produced social deficits consistent with the function of this anterior cingulate region of cortex. Overall, vulnerability of cortical regions is demonstrated after mild repetitive injury, with underlying differences of DTI and DKI, microglial activation, and behavioral deficits.

  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. A review of fronto-striatal and fronto-cortical brain abnormalities in children and adults with Attention Deficit Hyperactivity Disorder (ADHD) and new evidence for dysfunction in adults with ADHD during motivation and attention.

    PubMed

    Cubillo, Ana; Halari, Rozmin; Smith, Anna; Taylor, Eric; Rubia, Katya

    2012-02-01

    Attention Deficit Hyperactivity Disorder (ADHD) has long been associated with abnormalities in frontal brain regions. In this paper we review the current structural and functional imaging evidence for abnormalities in children and adults with ADHD in fronto-striatal, fronto-parieto-temporal, fronto-cerebellar and fronto-limbic regions and networks. While the imaging studies in children with ADHD are more numerous and consistent, an increasing number of studies suggests that these structural and functional abnormalities in fronto-cortical and fronto-subcortical networks persist into adulthood, despite a relative symptomatic improvement in the adult form of the disorder. We furthermore present new data that support the notion of a persistence of neurofunctional deficits in adults with ADHD during attention and motivation functions. We show that a group of medication-naïve young adults with ADHD behaviours who were followed up 20 years from a childhood ADHD diagnosis show dysfunctions in lateral fronto-striato-parietal regions relative to controls during sustained attention, as well as in ventromedial orbitofrontal regions during reward, suggesting dysfunctions in cognitive-attentional as well as motivational neural networks. The lateral fronto-striatal deficit findings, furthermore, were strikingly similar to those we have previously observed in children with ADHD during the same task, reinforcing the notion of persistence of fronto-striatal dysfunctions in adult ADHD. The ventromedial orbitofrontal deficits, however, were associated with comorbid conduct disorder (CD), highlighting the potential confound of comorbid antisocial conditions on paralimbic brain deficits in ADHD. Our review supported by the new data therefore suggest that both adult and childhood ADHD are associated with brain abnormalities in fronto-cortical and fronto-subcortical systems that mediate the control of cognition and motivation. The brain deficits in ADHD therefore appear to be multi

  3. 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

  4. Quantitative myocardial perfusion SPECT.

    PubMed

    Tsui, B M; Frey, E C; LaCroix, K J; Lalush, D S; McCartney, W H; King, M A; Gullberg, G T

    1998-01-01

    In recent years, there has been much interest in the clinical application of attenuation compensation to myocardial perfusion single photon emission computed tomography (SPECT) with the promise that accurate quantitative images can be obtained to improve clinical diagnoses. The different attenuation compensation methods that are available create confusion and some misconceptions. Also, attenuation-compensated images reveal other image-degrading effects including collimator-detector blurring and scatter that are not apparent in uncompensated images. This article presents basic concepts of the major factors that degrade the quality and quantitative accuracy of myocardial perfusion SPECT images, and includes a discussion of the various image reconstruction and compensation methods and misconceptions and pitfalls in implementation. The differences between the various compensation methods and their performance are demonstrated. Particular emphasis is directed to an approach that promises to provide quantitative myocardial perfusion SPECT images by accurately compensating for the 3-dimensional (3-D) attenuation, collimator-detector response, and scatter effects. With advances in the computer hardware and optimized implementation techniques, quantitatively accurate and high-quality myocardial perfusion SPECT images can be obtained in clinically acceptable processing time. Examples from simulation, phantom, and patient studies are used to demonstrate the various aspects of the investigation. We conclude that quantitative myocardial perfusion SPECT, which holds great promise to improve clinical diagnosis, is an achievable goal in the near future.

  5. Effect of cardiac dysrhythmia on cerebral perfusion.

    PubMed

    Sand, B J; Rose, H B; Barker, W F

    1976-07-01

    Extracranial carotid arterial obstructive disease has been the entity most commonly associated with transient cerebrovascular insufficiency. A nonobstructive, frequently overlooked cause of cerebral ischemia is cardiac dysrhythmia. We have explored this by observations of experimental animals and of man. Blood flow and pressure in the carotid arteries of dogs were shown to be decreased by mechnically induced premature ventricular contractions. The significance of the cardiogenic contribution to altered cerebrovascular perfusion was studied by ocular and brachial plethysmography in 210 patients suspected by history of having carotid arterial insufficiency. Of the 210 patients, 62 demonstrated abnormal ocular plethysmographic recordings, and of those, nine had dysrhythmias associated with significant deficits of ocular perfusion. Five patients whose recordings were technically suitable for publication are presented to demonstrate the bizarre ocular plethysmographic recordings seen during the dysrhythmic cycle.

  6. 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

  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. MR Susceptibility Weighted Imaging (SWI) Complements Conventional Contrast Enhanced T1 Weighted MRI in Characterizing Brain Abnormalities of Sturge-Weber Syndrome

    PubMed Central

    Hu, Jiani; Yu, Yingjian; Juhasz, Csaba; Kou, Zhifeng; Xuan, Yang; Latif, Zahid; Kudo, Kohsuke; Chugani, Harry T.; Haacke, E. Mark

    2009-01-01

    PURPOSE To evaluate the efficacy of susceptibility weighted imaging (SWI) in comparison to standard T1 weighted post gadolinium contrast (T1-Gd) MRI in patients with Sturge-Weber Syndrome (SWS). MATERIALS AND METHODS Twelve children (mean age 5.6 years) with the diagnosis of SWS and unilateral hemispheric involvement were recruited prospectively and examined with high resolution 3D SWI and conventional T1-Gd. Both SWI and T1-Gd images were evaluated using a four-grade scoring system according to six types of imaging findings (enlargement of transmedullary veins, periventricular veins and choroid plexus, as well as leptomeningeal abnormality, cortical gyriform abnormality, and gray matter/white matter junctional abnormality). The scores of SWI vs. T1-Gd images were then compared for each type of abnormality. RESULTS SWI was superior to T1-Gd in identifying the enlarged transmedullary veins (p=0.0020), abnormal periventricular veins (p=0.0078), cortical gyriform abnormalities (p=0.0020), and grey matter/white matter junction abnormalities (p=0.0078). Conversely, T1-Gd was better than SWI in identifying enlarged choroid plexus (p=0.0050) and leptomeningeal abnormalities (p=0.0050). CONCLUSION SWI can provide useful and unique information complementary to conventional contrast enhanced T1 weighted MRI for characterizing SWS. Therefore, SWI should be integrated into routine clinical MRI protocols for suspected SWS. PMID:18666142

  9. Leukocyte abnormalities.

    PubMed

    Gabig, T G

    1980-07-01

    Certain qualitative abnormalities in neutrophils and blood monocytes are associated with frequent, severe, and recurrent bacterial infections leading to fatal sepsis, while other qualitative defects demonstrated in vitro may have few or no clinical sequelae. These qualitative defects are discussed in terms of the specific functions of locomotion, phagocytosis, degranulation, and bacterial killing.

  10. Three-dimensional whole-brain perfusion quantification using pseudo-continuous arterial spin labeling MRI at multiple post-labeling delays: accounting for both arterial transit time and impulse response function.

    PubMed

    Qin, Qin; Huang, Alan J; Hua, Jun; Desmond, John E; Stevens, Robert D; van Zijl, Peter C M

    2014-02-01

    Measurement of the cerebral blood flow (CBF) with whole-brain coverage is challenging in terms of both acquisition and quantitative analysis. In order to fit arterial spin labeling-based perfusion kinetic curves, an empirical three-parameter model which characterizes the effective impulse response function (IRF) is introduced, which allows the determination of CBF, the arterial transit time (ATT) and T(1,eff). The accuracy and precision of the proposed model were compared with those of more complicated models with four or five parameters through Monte Carlo simulations. Pseudo-continuous arterial spin labeling images were acquired on a clinical 3-T scanner in 10 normal volunteers using a three-dimensional multi-shot gradient and spin echo scheme at multiple post-labeling delays to sample the kinetic curves. Voxel-wise fitting was performed using the three-parameter model and other models that contain two, four or five unknown parameters. For the two-parameter model, T(1,eff) values close to tissue and blood were assumed separately. Standard statistical analysis was conducted to compare these fitting models in various brain regions. The fitted results indicated that: (i) the estimated CBF values using the two-parameter model show appreciable dependence on the assumed T(1,eff) values; (ii) the proposed three-parameter model achieves the optimal balance between the goodness of fit and model complexity when compared among the models with explicit IRF fitting; (iii) both the two-parameter model using fixed blood T1 values for T(1,eff) and the three-parameter model provide reasonable fitting results. Using the proposed three-parameter model, the estimated CBF (46 ± 14 mL/100 g/min) and ATT (1.4 ± 0.3 s) values averaged from different brain regions are close to the literature reports; the estimated T(1,eff) values (1.9 ± 0.4 s) are higher than the tissue T1 values, possibly reflecting a contribution from the microvascular arterial blood compartment.

  11. Walking abnormalities

    MedlinePlus

    ... or head trauma Brain tumor Cerebrovascular accident (stroke) Cerebral palsy Cervical spondylosis with myelopathy (a problem with the ... 22. Read More Arthritis Bunions Central nervous system Cerebral palsy Dizziness Ingrown toenail Multiple sclerosis Muscular dystrophy Myositis ...

  12. 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.

  13. 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

    2015-12-08

    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.

  14. [Portable peristaltic perfusion pumps].

    PubMed

    Magallón Pedrera, I; Soto Torres, I

    1999-11-01

    Portable peristaltic perfusion pumps allow one to administer pharmaceuticals in hospitals as well as in primary health care centers and furthermore these pumps present multiple advantages for patients and their families since they make it possible to carry out treatment in a patient's home while at the same time lowering the costs involved. The authors analyze the most out standing aspects of portable peristaltic perfusion pumps along with their characteristics, installation, programming, and how to turn them on; in addition, the authors list the maintenance care which these pumps require.

  15. Anatomical Abnormalities in Autism?

    PubMed

    Haar, Shlomi; Berman, Sigal; Behrmann, Marlene; Dinstein, Ilan

    2016-04-01

    Substantial controversy exists regarding the presence and significance of anatomical abnormalities in autism spectrum disorders (ASD). The release of the Autism Brain Imaging Data Exchange (∼1000 participants, age 6-65 years) offers an unprecedented opportunity to conduct large-scale comparisons of anatomical MRI scans across groups and to resolve many of the outstanding questions. Comprehensive univariate analyses using volumetric, thickness, and surface area measures of over 180 anatomically defined brain areas, revealed significantly larger ventricular volumes, smaller corpus callosum volume (central segment only), and several cortical areas with increased thickness in the ASD group. Previously reported anatomical abnormalities in ASD including larger intracranial volumes, smaller cerebellar volumes, and larger amygdala volumes were not substantiated by the current study. In addition, multivariate classification analyses yielded modest decoding accuracies of individuals' group identity (<60%), suggesting that the examined anatomical measures are of limited diagnostic utility for ASD. While anatomical abnormalities may be present in distinct subgroups of ASD individuals, the current findings show that many previously reported anatomical measures are likely to be of low clinical and scientific significance for understanding ASD neuropathology as a whole in individuals 6-35 years old.

  16. Quantitative measurement of tissue perfusion and diffusion in vivo.

    PubMed

    Chenevert, T L; Pipe, J G; Williams, D M; Brunberg, J A

    1991-01-01

    Magnetic resonance imaging techniques designed for sensitivity to microscopic motions of water diffusion and blood flow in the capillary network are also exceptionally sensitive to bulk motion properties of the tissue, which may lead to contrast artifact and large quantitative errors. The magnitude of bulk motion error that exists in human brain perfusion/diffusion imaging and the inability of cardiac gating to adequately control this motion are demonstrated by direct measurement of phase stability of voxels localized in the brain. Two methods are introduced to reduce bulk motion phase error. The first, a postprocessing phase correction algorithm, reduces coarse phase error but is inadequate by itself for quantitative perfusion/diffusion MRI. The second method employs orthogonal slice selection gradients to define a column of tissue in the object, from which echoes may be combined in a phase-insensitive manner to measure more reliably the targeted signal attenuation. Applying this acquisition technique and a simplistic model of perfusion and diffusion signal attenuations yields an estimated perfusion fraction of 3.4 +/- 1.1% and diffusion coefficient of 1.1 +/- 0.2 x 10(-5) cm2/s in the white matter of one normal volunteer. Successful separation of perfusion and diffusion effects by this technique is supported in a dynamic study of calf muscle. Periods of normal blood flow, low flow, and reactive hyperemia are clearly distinguished in the quantitative perfusion results, whereas measured diffusion remained nearly constant.

  17. Postoperative luxury perfusion syndrome in patients with severe subarachnoid hemorrhage treated by early aneurysmal clipping.

    PubMed

    Ohta, H

    1990-01-01

    Cerebral blood flow (CBF) was measured in 90 patients who underwent early aneurysmal clipping after subarachnoid hemorrhage (SAH). Measurements were made by a noninvasive, two-dimensional method involving intravenous injection of 133Xe. Patients of Hunt and Hess grades I and II exhibited normal to slightly subnormal CBF, without significant changes, during the study period. Grades III-V patients had almost normal CBF in the early postoperative period, but their CBF gradually decreased, becoming significantly low after day 31. It is noteworthy that in grades IV and V patients, CBF was abnormally high in the acute stage, relative to their poor neurological condition; these patients were considered to have the "global luxury perfusion syndrome." The syndrome was not uncommon in patients with severe SAH. Possible causative or contributory factors are attempts to surgically reduce intracranial pressure, which leads to increased cerebral perfusion pressure, and concomitant global dysautoregulation. In patients with this syndrome, maneuvers intended to increase CBF should be avoided, as they may aggravate brain swelling or cause hemorrhagic events. Positron emission tomographic studies will provide more accurate and useful information concerning the management of SAH patients.

  18. 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, ...

  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. 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

  1. 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

  2. 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.

  3. Monitoring tissue perfusion, oxygenation, and metabolism in critically ill patients.

    PubMed

    Ekbal, Nasirul J; Dyson, Alex; Black, Claire; Singer, Mervyn

    2013-06-01

    Alterations in oxygen transport and use are integral to the development of multiple organ failure; therefore, the ultimate goal of resuscitation is to restore effective tissue oxygenation and cellular metabolism. Hemodynamic monitoring is the cornerstone of management to promptly identify and appropriately manage (impending) organ dysfunction. Prospective randomized trials have confirmed outcome benefit when preemptive or early treatment is directed toward maintaining or restoring adequate tissue perfusion. However, treatment end points remain controversial, in large part because of current difficulties in determining what constitutes "optimal." Information gained from global whole-body monitoring may not detect regional organ perfusion abnormalities until they are well advanced. Conversely, the ideal "canary" organ that is readily accessible for monitoring, yet offers an early and sensitive indicator of tissue "unwellness," remains to be firmly identified. This review describes techniques available for real-time monitoring of tissue perfusion and metabolism and highlights novel developments that may complement or even supersede current tools.

  4. 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

  5. Iofetamine HCI I-123 brain scanning in stroke: a comparison with transmission CT

    SciTech Connect

    Park, C.H.; Madsen, M.T.; McLellan, T.; Schwartzman, R.J.

    1988-03-01

    Although IMP scans fail to show fine anatomical details of the brain, because of poor resolution of a single head rotational system, adequate information is offered by the scans to localize most perfusion defects caused by stroke. The following conclusions can be drawn from our study: 1. The planar IMP brain scans processed through the computer are sensitive in the early diagnosis of acute stroke except for small and deeply localized lesions. 2. The SPECT IMP imaging is more sensitive than the planar or transmission CT scans in the early diagnosis of stroke. Semiquantitative evaluations are feasible with IMP SPECT. 3. Neither transmission CT nor IMP SPECT are sensitive in the detection of acute lacunar infarcts. 4. In acute infarction, the transmission CT is usually negative or minimally positive in the early stages, while impaired uptake of IMP occurs immediately after the onset of the stroke. In acute stroke, the extent of the perfusion defect on IMP is usually greater than the abnormality seen on the transmission CT. 5. On followup studies, IMP scans show improved perfusion reflecting physiologic changes, while transmission CT scans show further dense anatomical changes when compared to the initial studies. 6. Hyperemic changes are likely due to collateral circulation or luxury perfusion. This finding suggests that the IMP reflects local cerebral blood flow in strokes.

  6. Scaling of cerebral blood perfusion in primates and marsupials.

    PubMed

    Seymour, Roger S; Angove, Sophie E; Snelling, Edward P; Cassey, Phillip

    2015-08-01

    The evolution of primates involved increasing body size, brain size and presumably cognitive ability. Cognition is related to neural activity, metabolic rate and rate of blood flow to the cerebral cortex. These parameters are difficult to quantify in living animals. This study shows that it is possible to determine the rate of cortical brain perfusion from the size of the internal carotid artery foramina in skulls of certain mammals, including haplorrhine primates and diprotodont marsupials. We quantify combined blood flow rate in both internal carotid arteries as a proxy of brain metabolism in 34 species of haplorrhine primates (0.116-145 kg body mass) and compare it to the same analysis for 19 species of diprotodont marsupials (0.014-46 kg). Brain volume is related to body mass by essentially the same exponent of 0.70 in both groups. Flow rate increases with haplorrhine brain volume to the 0.95 power, which is significantly higher than the exponent (0.75) expected for most organs according to 'Kleiber's Law'. By comparison, the exponent is 0.73 in marsupials. Thus, the brain perfusion rate increases with body size and brain size much faster in primates than in marsupials. The trajectory of cerebral perfusion in primates is set by the phylogenetically older groups (New and Old World monkeys, lesser apes) and the phylogenetically younger groups (great apes, including humans) fall near the line, with the highest perfusion. This may be associated with disproportionate increases in cortical surface area and mental capacity in the highly social, larger primates.

  7. Detection of the abnormal isoform of the prion protein associated with chronic wasting disease in the optic pathways of the brain and retina of Rocky Mountain elk (Cervus elaphus nelsoni).

    PubMed

    Spraker, T R; O'Rour