WorldWideScience

Sample records for brain receptor imaging

  1. In vivo PET imaging of brain nicotinic cholinergic receptors

    International Nuclear Information System (INIS)

    Neuronal acetylcholine receptors (nAChRs) are widely distributed throughout the central nervous system where they modulate a number of CNS functions including neurotransmitter release, cognitive function, anxiety, analgesia and control of cerebral blood flow. In the brain, a major subtype is composed of the α4β2 subunit combination. Density of this subtype has been shown to be decreased in patients with neuro-degenerative disease such as Alzheimer and Parkinson's disease (AD and PD), and mutated receptors has been described in some familial epilepsy. Thus, in vivo mapping of the nicotinic nAChRs by Positron Emission Tomography (PET) are of great interest to monitor the evolution of these pathologies and changes in the neuronal biochemistry induced by therapeutic agents. Recently, a new compound, 3-[2(S)-2-azetidinyl-methoxy]pyridine (A-85380) has been synthesised and labelled with fluorine-18, [18F]fluoro-A-85380 (Dolle et al., 1999). The [18F]fluoro-A-85380 has been shown to bind with high affinity t o nAChRs in vitro (Saba et al., 2004), and its toxicity was low and compatible with it s use at tracer dose in human PET studies (Valette, 2002). PET studies in baboons showed that, after in vivo administration of [ 18F]fluoro-A-85380 at a tracer dose, the distribution of the radioactivity in the brain reflect the distribution of the 18F]fluoro-A-8538 0 combined with its low toxicity make possible the imaging of the nicotinic receptor s in human by PET (Bottlaender 2003). Studies were performed in healthy non-smoker volunteers to evaluate the brain kinetics of [18F]fluoro-A-85380 and to assess the quantification of its nAChRs binding in the human brain with PET (Gallezot et a., 2005). The [18F]fluoro-A-85380 was also used in epileptic patients to whom a mutation in the α4 or β2 nAChRs subunit have been identified. We found that, in these patients, the pattern of the brain distribution of the radiotracer was found different when compared to the healthy subjects

  2. In vivo PET imaging of brain nicotinic cholinergic receptors

    Energy Technology Data Exchange (ETDEWEB)

    Bottlaender, M.; Valette, H.; Saba, W.; Schollhorn-Peyronneau, M.A.; Dolle, F.; Syrota, A. [Service Hospitalier Frederic Joliot (CEA/DSV/DRM), 91 - Orsay (France)

    2006-07-01

    Neuronal acetylcholine receptors (nAChRs) are widely distributed throughout the central nervous system where they modulate a number of CNS functions including neurotransmitter release, cognitive function, anxiety, analgesia and control of cerebral blood flow. In the brain, a major subtype is composed of the {alpha}4{beta}2 subunit combination. Density of this subtype has been shown to be decreased in patients with neuro-degenerative disease such as Alzheimer and Parkinson's disease (AD and PD), and mutated receptors has been described in some familial epilepsy. Thus, in vivo mapping of the nicotinic nAChRs by Positron Emission Tomography (PET) are of great interest to monitor the evolution of these pathologies and changes in the neuronal biochemistry induced by therapeutic agents. Recently, a new compound, 3-[2(S)-2-azetidinyl-methoxy]pyridine (A-85380) has been synthesised and labelled with fluorine-18, [{sup 18}F]fluoro-A-85380 (Dolle et al., 1999). The [{sup 18}F]fluoro-A-85380 has been shown to bind with high affinity t o nAChRs in vitro (Saba et al., 2004), and its toxicity was low and compatible with it s use at tracer dose in human PET studies (Valette, 2002). PET studies in baboons showed that, after in vivo administration of [ {sup 18}F]fluoro-A-85380 at a tracer dose, the distribution of the radioactivity in the brain reflect the distribution of the < 4R2 nAChRs. Competition and pre-blocking studies, using nicotinic agonists, confirm that the radiotracer binds specifically to the heteromeric nAChRs in the brain (Valette et al., 1999). The in vivo, characteristics of the [{sup 18}F]fluoro-A-8538 0 combined with its low toxicity make possible the imaging of the nicotinic receptor s in human by PET (Bottlaender 2003). Studies were performed in healthy non-smoker volunteers to evaluate the brain kinetics of [{sup 18}F]fluoro-A-85380 and to assess the quantification of its nAChRs binding in the human brain with PET (Gallezot et a., 2005). The [{sup 18}F

  3. Radiochemical evaluation of a new brain receptor imaging agent

    International Nuclear Information System (INIS)

    We report about the radiochemical evaluation of a new serotonin-1A (5-HT1A) receptor imaging agent. The new derivative of WAY 100635, viz. C1-(2 methoxyphenyl)-(4- mercaptoethyl)-piperazine, was labelled with technetium-99m using thiocresol through 99mTc(V)-glucoheptonate precursor. The labelling was carried out at room temperature within 10 minutes using 370-740 MBq of 99mTc-pertechnetate. The specific activity of the '2+1+1' mixed ligand complex was about 40 GBq/ml. The labelling efficiency and the stability of the labelled compound were monitored by ITLC-SG, solvent extraction and reverse-phase HPLC. The labelling efficiency exceeded 95% and remained high about 4 hours if stored at room temperature or in a refrigerator at 4 deg C. The results give evidence of a high labelling efficiency and stability of the ligand used. The labelled ligand seems to hold promise within the family of existing radiopharmaceuticals

  4. Imaging dopamine and opiate receptors in the human brain in health and disease

    International Nuclear Information System (INIS)

    Chemical activity accompanies mental activity, but only recently has it been possible to begin to examine its nature. In 1983 the first imaging of a neuroreceptor in the human brain was accomplished with carbon-11 methyl spipeone, a ligand that binds preferentially to dopamine-2 receptors, 80% of which are located in the caudate nucleus and putamen. Quantitative imaging of serotonin-2, opiate, benzodiazapine and muscarinic cholinergic receptors has subsequently been accomplished. In studies of normal men and women, it has been found that dopamine and serotonin receptor activity decreases dramatically with age, such a decrease being more pronounced in men than in women and greater in the case of dopamine receptors than serotonin-2 receptors. Preliminary studies in patients with neuropsychiatric disorders suggests that dopamine-2 receptor activity is diminished in the caudate nucleus of patients with Huntington's disease. Positron tomography permits quantitative assay of picomolar quantities of neuroreceptors within the living human brain. Studies of patients with Parkinson's disease, Alzheimer's disease, depression, anxiety, schizophrenia, acute and chronic pain states and drug addiction are now in progress

  5. Quantitative Molecular Imaging of Neuronal Nicotinic Acetylcholine Receptors in the Human Brain with A-85380 Radiotracers

    OpenAIRE

    Lotfipour, Shahrdad; Mandelkern, Mark; Brody, Arthur L.

    2011-01-01

    Neuronal nicotinic acetylcholine receptors (nAChRs) have been implicated in a spectrum of cognitive functions as well as psychiatric and neurodegenerative disorders, including tobacco addiction and Alzheimer's Disease. The examination of neuronal nAChRs in living humans is a relatively new field. Researchers have developed brain-imaging radiotracers for nAChRs, with radiolabeled A-85380 compounds having the most widespread use. We provide a brief background on nAChRs, followed by a discussion...

  6. In vivo imaging of brain androgen receptors in rats: a [18F]FDHT PET study

    International Nuclear Information System (INIS)

    Introduction: Steroid hormones like androgens play an important role in the development and maintenance of several brain functions. Androgens can act through androgen receptors (AR) in the brain. This study aims to demonstrate the feasibility of positron emission tomography (PET) with 16β-[18F]fluoro-5α-dihydrotestosterone ([18F]FDHT) to image AR expression in the brain. Methods: Male Wistar rats were either orchiectomized to inhibit endogenous androgen production or underwent sham-surgery. Fifteen days after surgery, rats were subjected to a 90-min dynamic [18F]FDHT PET scan with arterial blood sampling. In a subset of orchiectomized rats, 1 mg/kg dihydrotestosterone was co-injected with the tracer in order to saturate the AR. Plasma samples were analyzed for the presence of radioactive metabolites by radio-TLC. Pharmacokinetic modeling was performed to quantify brain kinetics of the tracer. After the PET scan, the animals were terminated for ex-vivo biodistribution. Results: PET imaging and ex vivo biodistribution studies showed low [18F]FDHT uptake in all brain regions, except pituitary. [18F]FDHT uptake in the surrounding cranial bones was high and increased over time. [18F]FDHT was rapidly metabolized in rats. Metabolism was significantly faster in orchiectomized rats than in sham-orchiectomized rats. Quantitative analysis of PET data indicated substantial spill-over of activity from cranial bones into peripheral brain regions, which prevented further analysis of peripheral brain regions. Logan graphical analysis and kinetic modeling using 1- and 2-tissue compartment models showed reversible and homogenously distributed tracer uptake in central brain regions. [18F]FDHT uptake in the brain could not be blocked by endogenous androgens or administration of dihydrotestosterone. Conclusion: The results of this study indicate that imaging of AR availability in rat brain with [18F]FDHT PET is not feasible. The low AR expression in the brain, the rapid metabolism of

  7. Radiochemical and biological evaluation of a new brain serotonin1A receptor imaging agent

    International Nuclear Information System (INIS)

    Radiochemical and biological evaluations are made of a new bidentate radioligand as a potential brain serotonin1A (5-HT1A) receptor imaging agent. The bidentate part of the complex was a derivative of the well known serotonin1A receptor antagonist molecule, namely WAY 100635; the monodentate parts were thiocresol, thiosalicylic acid and thio-2-naphthol. The labelling procedure was performed through the 99mTc(V)-glucoheptonate precursor. The bidentate + monodentate complex formed during the reaction in the case of thiocresol was identified as 99TcO(o-CH3-C6H4-N(CH2-CH2)2N-CH2CH2S)( p-C6H4CH3)2 (99mTc-1). Its labelling efficiency and stability were determined by thin layer chromatography, the organic solvent extraction method and high performance liquid chromagraphy. The biodistribution of the labelled compound was found by using male Wistar rats. On the basis of these data, kinetic curves were constructed for different organs and the dosimetry for humans was calculated. The brain uptake and pharmacokinetics were followed by planar and single photon emission computed tomography (SPECT) imaging in rats. Average brain count density was calculated and different regional count densities (counts/gram tissue) were obtained for the hippocampus and other receptor-rich regions. A detailed SPECT study was carried out after administration of 99mTc-1 to a cynomolgus monkey (Macaca cynomolgus). The results found show that, of three investigated aromatic thiol compounds, the labelling efficiency was the highest in the case of thiocresol as the monodentate part. Therefore all further studies were carried out using thiocresol. The labelling efficiency of this bidentate complex was about 80%, and the molecule was stable for up to one hour. The biodistribution data show that more than 0.1% of the injected dose is present in the rat brains a few minutes after administration, and the metabolic pathway is through the hepatobiliary system. From the results obtained with the study of the

  8. Ligands for SPECT and PET imaging of muscarinic-cholinergic receptors of the heart and brain

    Energy Technology Data Exchange (ETDEWEB)

    Knapp, F.F. Jr.; McPherson, D.W.; Luo, H. [and others

    1995-06-01

    Interest in the potential use of cerebral SPECT and PET imaging for determination of the density and activity of muscarinic-cholinergic receptors (mAChR) has been stimulated by the changes in these receptors which occur in many neurological diseases. In addition, the important involvement of mAChR in modulating negative inotropic cardiac activity suggests that such receptor ligands may have important applications in evaluation of changes which may occur in cardiac disease. In this paper, the properties of several key muscarinic receptor ligands being developed or which have been used for clinical SPECT and PET are discussed. In addition, the ORNL development of the new iodinated IQNP ligand based on QNB and the results of in vivo biodistribution studies in rats, in vitro competitive binding studies and ex vivo autoradiographic experiments are described. The use of radioiodinated IQNP may offer several advantages in comparison to IQNB because of its easy and high yield preparation and high brain uptake and the potential usefulness of the {open_quotes}partial{close_quotes} subtype selective IONP isomers. We also describe the development of new IQNP-type analogues which offer the opportunity for radiolabeling with positron-emitting radioisotopes (carbon-11, fluorine-18 and bromine-76) for potential use with PET.

  9. Pet imaging of two monoaminergic neurotransmitter systems in brain : studies of the norepinephrine transporter and dopamine D©ü receptor

    OpenAIRE

    Seneca, Nicholas

    2006-01-01

    Positron emission tomography (PET) has been widely used to study non-invasively function of the brain, pathophysiology of disease and aid in the development of new drugs. PET and selective radiolabeled molecules allow imaging of certain critical components of neurotransmission, such as pre-synaptic transporters and post-synaptic receptors in living brain. The general aim of the present thesis was (i) to measure neuropharmacological interventions using PET (e.g., competition ...

  10. In vivo molecular imaging of the GABA/benzodiazepine receptor complex in the aged rat brain.

    Science.gov (United States)

    Hoekzema, Elseline; Rojas, Santiago; Herance, Raúl; Pareto, Deborah; Abad, Sergio; Jiménez, Xavier; Figueiras, Francisca P; Popota, Foteini; Ruiz, Alba; Flotats, Núria; Fernández, Francisco J; Rocha, Milagros; Rovira, Mariana; Víctor, Víctor M; Gispert, Juan D

    2012-07-01

    The GABA-ergic system, known to regulate neural tissue genesis during cortical development, has been postulated to play a role in cerebral aging processes. Using in vivo molecular imaging and voxel-wise quantification, we aimed to assess the effects of aging on the benzodiazepine (BDZ) recognition site of the GABA(A) receptor. To visualize BDZ site availability, [(11)C]-flumazenil microPET acquisitions were conducted in young and old rats. The data were analyzed and region of interest analyses were applied to validate the voxel-wise approach. We observed decreased [(11)C]-flumazenil binding in the aged rat brains in comparison with the young control group. More specifically, clusters of reduced radioligand uptake were detected in the bilateral hippocampus, cerebellum, midbrain, and bilateral frontal and parieto-occipital cortex. Our results support the pertinence of voxel-wise quantification in the analysis of microPET data. Moreover, these findings indicate that the aging process involves declines in neural BDZ recognition site availability, proposed to reflect alterations in GABA(A) receptor subunit polypeptide expression.

  11. Human brain imaging

    International Nuclear Information System (INIS)

    Just as there have been dramatic advances in the molecular biology of the human brain in recent years, there also have been remarkable advances in brain imaging. This paper reports on the development and broad application of microscopic imaging techniques which include the autoradiographic localization of receptors and the measurement of glucose utilization by autoradiography. These approaches provide great sensitivity and excellent anatomical resolution in exploring brain organization and function. The first noninvasive external imaging of receptor distributions in the living human brain was achieved by positron emission tomography (PET) scanning. Developments, techniques and applications continue to progress. Magnetic resonance imaging (MRI) is also becoming important. Its initial clinical applications were in examining the structure and anatomy of the brain. However, more recent uses, such as MRI spectroscopy, indicate the feasibility of exploring biochemical pathways in the brain, the metabolism of drugs in the brain, and also of examining some of these procedures at an anatomical resolution which is substantially greater than that obtainable by PET scanning. The issues will be discussed in greater detail

  12. Brain imaging of serotonin 4 receptors in humans with [11C]SB207145-PET

    DEFF Research Database (Denmark)

    Marner, Lisbeth; Gillings, Nic; Madsen, Karine;

    2010-01-01

    Pharmacological stimulation of the serotonin 4 (5-HT(4)) receptor has shown promise for treatment of Alzheimer's disease and major depression. A new selective radioligand, [(11)C]SB207145, for positron emission tomography (PET) was used to quantify brain 5-HT(4) receptors in sixteen healthy subje......-HT(4) receptor binding in human brain can be reliably assessed with [(11)C]SB207145, which is encouraging for future PET studies of drug occupancy or patients with neuropsychiatric disorders.......Pharmacological stimulation of the serotonin 4 (5-HT(4)) receptor has shown promise for treatment of Alzheimer's disease and major depression. A new selective radioligand, [(11)C]SB207145, for positron emission tomography (PET) was used to quantify brain 5-HT(4) receptors in sixteen healthy......(max) was in accordance with post-mortem brain studies (Spearman's r=0.83, p=0.04), and the regional binding potentials, BP(ND), were on average 2.6 in striatum, 0.42 in prefrontal cortex, and 0.91 in hippocampus. We found no effect of sex but a decreased binding with age (p=0.046). A power analysis showed that, given...

  13. Uncertainty analysis for absorbed dose from a brain receptor imaging agent

    Energy Technology Data Exchange (ETDEWEB)

    Aydogan, B.; Miller, L.F. [Univ. of Tennessee, Knoxville, TN (United States). Nuclear Engineering Dept.; Sparks, R.B. [Oak Ridge Inst. for Science and Education, TN (United States); Stubbs, J.B. [Radiation Dosimetry Systems of Oak Ridge, Inc., Knoxville, TN (United States)

    1999-01-01

    Absorbed dose estimates are known to contain uncertainties. A recent literature search indicates that prior to this study no rigorous investigation of uncertainty associated with absorbed dose has been undertaken. A method of uncertainty analysis for absorbed dose calculations has been developed and implemented for the brain receptor imaging agent {sup 123}I-IPT. The two major sources of uncertainty considered were the uncertainty associated with the determination of residence time and that associated with the determination of the S values. There are many sources of uncertainty in the determination of the S values, but only the inter-patient organ mass variation was considered in this work. The absorbed dose uncertainties were determined for lung, liver, heart and brain. Ninety-five percent confidence intervals of the organ absorbed dose distributions for each patient and for a seven-patient population group were determined by the ``Latin Hypercube Sampling`` method. For an individual patient, the upper bound of the 95% confidence interval of the absorbed dose was found to be about 2.5 times larger than the estimated mean absorbed dose. For the seven-patient population the upper bound of the 95% confidence interval of the absorbed dose distribution was around 45% more than the estimated population mean. For example, the 95% confidence interval of the population liver dose distribution was found to be between 1.49E+0.7 Gy/MBq and 4.65E+07 Gy/MBq with a mean of 2.52E+07 Gy/MBq. This study concluded that patients in a population receiving {sup 123}I-IPT could receive absorbed doses as much as twice as large as the standard estimated absorbed dose due to these uncertainties.

  14. Metabolism of [123I]epidepride may affect brain dopamine D2 receptor imaging with single-photon emission tomography

    International Nuclear Information System (INIS)

    Iodine-123 labelled epidepride is a novel radiopharmaceutical for the study of cerebral dopamine D2 receptors using single-photon emission tomography (SPET). A lipophilic labelled metabolite of [123I]epidepride which may enter the brain and hamper the quantitation of receptors has been observed in human plasma. In the present study, gradient high-performance liquid chromatography (HPLC) was used to investigate the plasma concentration of the lipophilic labelled metabolite and its correlation to SPET imaging of striatal dopamine D2 receptors. A linear regression fit showed a negative correlation between the amount of the lipophilic labelled metabolite and the striatum to cerebellum ratio (n=16, R=-0.58, P2 receptors with SPET using [123I]epidepride. (orig.)

  15. Metabolism of [123I]epidepride may affect brain dopamine D2 receptor imaging with single-photon emission tomography.

    Science.gov (United States)

    Bergström, K A; Yu, M; Kuikka, J T; Akerman, K K; Hiltunen, J; Lehtonen, J; Halldin, C; Tiihonen, J

    2000-02-01

    Iodine-123 labelled epidepride is a novel radiopharmaceutical for the study of cerebral dopamine D2 receptors using single-photon emission tomography (SPET). A lipophilic labelled metabolite of [123I]epidepride which may enter the brain and hamper the quantitation of receptors has been observed in human plasma. In the present study, gradient high-performance liquid chromatography (HPLC) was used to investigate the plasma concentration of the lipophilic labelled metabolite and its correlation to SPET imaging of striatal dopamine D2 receptors. A linear regression fit showed a negative correlation between the amount of the lipophilic labelled metabolite and the striatum to cerebellum ratio (n=16, R=-0.58, Pepidepride. PMID:10755727

  16. Application of 5-hydroxytryptamine receptor imaging for study of neuropsychiatric disorders and brain functions

    International Nuclear Information System (INIS)

    In the central nervous system, the widely distributed 5-hydroxytryptamine (5-HT)receptors are involved in regulating a large number of psychological and physiological functions, including mood, sleep, endocrine and autonomic nervous system. Abnormal 5-HT transmission has been implicated in a variety of neuropsychiatric disorders, such as pain, depression and epilepsy. With the development of radioligands, non-invasive nuclear imaging technique with exquisite sensitivity and specificity has been applied for delineation of neurotransmitter function in vivo. It does great benefit for researches of these diseases and development of drugs. This review provided an overview of 5-HT receptors radioligands and recent findings. (authors)

  17. Imaging for metabotropic glutamate receptor subtype 1 in rat and monkey brains using PET with [{sup 18}F]FITM

    Energy Technology Data Exchange (ETDEWEB)

    Yamasaki, Tomoteru [National Institute of Radiological Sciences, Molecular Imaging Centre, Chiba (Japan); Tohoku University, Graduate School of Pharmaceutical Sciences, Sendai (Japan); Fujinaga, Masayuki; Maeda, Jun; Kawamura, Kazunori; Yui, Joji; Hatori, Akiko; Nagai, Yuji; Tokunaga, Masaki; Higuchi, Makoto; Suhara, Tetsuya; Fukumura, Toshimitsu [National Institute of Radiological Sciences, Molecular Imaging Centre, Chiba (Japan); Yoshida, Yuichiro [SHI Accelerator Service Co. Ltd., Tokyo (Japan); Zhang, Ming-Rong [National Institute of Radiological Sciences, Molecular Imaging Centre, Chiba (Japan); National Institute of Radiological Sciences, Department of Molecular Probes, Molecular Imaging Centre, Chiba (Japan)

    2012-04-15

    In this study, we evaluate the utility of 4-[{sup 18}F]fluoro-N-[4-[6-(isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-N-methylbenzamide ([{sup 18}F]FITM) as a positron emission tomography (PET) ligand for imaging of the metabotropic glutamate receptor subtype 1 (mGluR1) in rat and monkey brains. In vivo distribution of [{sup 18}F]FITM in brains was evaluated by PET scans with or without the mGluR1-selective antagonist (JNJ16259685). Kinetic parameters of monkey PET data were obtained using the two-tissue compartment model with arterial blood sampling. In PET studies in rat and monkey brains, the highest uptake of radioactivity was in the cerebellum, followed by moderate uptake in the thalamus, hippocampus and striatum. The lowest uptake of radioactivity was detected in the pons. These uptakes in all brain regions were dramatically decreased by pre-administration of JNJ16259685. In kinetic analysis of monkey PET, the highest volume of distribution (V{sub T}) was detected in the cerebellum (V{sub T} = 11.5). [{sup 18}F ]FITM has an excellent profile as a PET ligand for mGluR1 imaging. PET with [{sup 18}F ]FITM may prove useful for determining the regional distribution and density of mGluR1 and the mGluR1 occupancy of drugs in human brains. (orig.)

  18. [sup 123]I-SCH 23982 is not suitable for dopamine D1 receptor imaging in vivo in the human brain

    Energy Technology Data Exchange (ETDEWEB)

    Verhoeff, N.P.L.G.; Fennema, P.; Royen, E.A. van (Academic Medical Centre, Amsterdam (Netherlands). Dept. of Nuclear Medicine); Bekier, A. (Kantonsspital, St Gallen (Switzerland). Inst. for Nuclear Medicine); Beer, H.-F.; Schubiger, P.A. (Paul Scherrer Inst. (PSI), Villigen (Switzerland))

    1993-02-01

    The tracer [sup 123]I-SCH 23982 was tested with regard to its ability to image dopamine D1 receptor in the human brain in vivo with single photon emission computed tomography (SPECT). The tracer did not reach equilibrium with regard to its bindign to dopamine D1 receptors, presumably owing to fast metabolism to hydrophilic products and deiodination. It is concluded that [sup 123]I-SCH 23982 is not suitable for dopamine D1 receptor imaging with SPECT in the human brain. (author).

  19. Live imaging reveals a new role for the sigma-1 (σ1) receptor in allowing microglia to leave brain injuries.

    Science.gov (United States)

    Moritz, Christian; Berardi, Francesco; Abate, Carmen; Peri, Francesca

    2015-03-30

    Microglial cells are responsible for clearing and maintaining the central nervous system (CNS) microenvironment. Upon brain damage, they move toward injuries to clear the area by engulfing dying neurons. However, in the context of many neurological disorders chronic microglial responses are responsible for neurodegeneration. Therefore, it is important to understand how these cells can be "switched-off" and regain their ramified state. Current research suggests that microglial inflammatory responses can be inhibited by sigma (σ) receptor activation. Here, we take advantage of the optical transparency of the zebrafish embryo to study the role of σ1 receptor in microglia in an intact living brain. By combining chemical approaches with real time imaging we found that treatment with PB190, a σ1 agonist, blocks microglial migration toward injuries leaving cellular baseline motility and the engulfment of apoptotic neurons unaffected. Most importantly, by taking a reverse genetic approach, we discovered that the role of σ1in vivo is to "switch-off" microglia after they responded to an injury allowing for these cells to leave the site of damage. This indicates that pharmacological manipulation of σ1 receptor modulates microglial responses providing new approaches to reduce the devastating impact that microglia have in neurodegenerative diseases.

  20. STRATEGIES FOR QUANTIFYING PET IMAGING DATA FROM TRACER STUDIES OF BRAIN RECEPTORS AND ENZYMES.

    Energy Technology Data Exchange (ETDEWEB)

    Logan, J.

    2001-04-02

    A description of some of the methods used in neuroreceptor imaging to distinguish changes in receptor availability has been presented in this chapter. It is necessary to look beyond regional uptake of the tracer since uptake generally is affected by factors other than the number of receptors for which the tracer has affinity. An exception is the infusion method producing an equilibrium state. The techniques vary in complexity some requiring arterial blood measurements of unmetabolized tracer and multiple time uptake data. Others require only a few plasma and uptake measurements and those based on a reference region require no plasma measurements. We have outlined some of the limitations of the different methods. Laruelle (1999) has pointed out that test/retest studies to which various methods can be applied are crucial in determining the optimal method for a particular study. The choice of method will also depend upon the application. In a clinical setting, methods not involving arterial blood sampling are generally preferred. In the future techniques for externally measuring arterial plasma radioactivity with only a few blood samples for metabolite correction will extend the modeling options of clinical PET. Also since parametric images can provide information beyond that of ROI analysis, improved techniques for generating such images will be important, particularly for ligands requiring more than a one-compartment model. Techniques such as the wavelet transform proposed by Turkheimer et al. (2000) may prove to be important in reducing noise and improving quantitation.

  1. Development of radioactive agent for image diagnosis of brain dopamine receptor

    International Nuclear Information System (INIS)

    Recently, MRI is often used to examine pathological degeneration of intracerebellar neurons of patients with Parkinson's disease, Huntington's chorea, spinocerebellar degeneration, etc. However, the efficacy of MRI is still unsatisfactory at present. In this project, the efficacy of SPECT was examined to evaluate the cerebellar functions in the previous year and it was found that the benzodiazepin receptor in CNS was detectable using SPECT with 125I iomazenil. In this year, ocular movements as one of cerebellar functions was attempted using functional MRI and patients' ocular movements were analyzed on the basis of the saccade during functional MRI imaging by Ober2 (Permobil Sweden). Image of an activated region in the frontal eye field (FEF), supplementary eye field (SEF), parietal eye field (PEF), posterior lobe or cerebellum was obtainable by Ober2-attached functional MRI. Especially, vermis 5, 6 and 7 lobules in the cerebellum were activated and random saccade was much stronger than regular saccade in the cerebellum. These results indicated that functional MRI was usable for clinical evaluation of patients with central nervous degeneration. (M.N.)

  2. Cyclopentadienyl tricarbonyl complexes of 99mTc for the in vivo imaging of the serotonin 5-HT 1a receptor in the brain

    International Nuclear Information System (INIS)

    The present interest in the 5-HT 1a receptor is due to its implicated role in several major neuropsychiatric disorders such as depression, eating disorders and anxiety. For the diagnosis of these pathophysiological processes it is important to have radioligands in hand able to specifically bind on the 5-HT 1a receptor in order to allow brain imaging. due to the optimal radiation properties of 99mTc there is a considerable interest in the development of 99mTc radiopharmaceuticals for imaging serotonergic CNS receptors using single-photon emission tomography (SPET). Here we introduce two cyclopentadienyl technitium tricarbonyl conjugates of piperidine derivatives which show high accumulation of radioactivity in brain areas rich in 5-HT 1a receptors

  3. Metabolism of [{sup 123}I]epidepride may affect brain dopamine D{sub 2} receptor imaging with single-photon emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Bergstroem, K.A.; Yu, M.; Kuikka, J.T.; Aakerman, K.K. [Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio (Finland); Hiltunen, J. [MAP Medical Technologies Oy, Tikkakoski (Finland); Lehtonen, J. [Department of Psychiatry, University of Kuopio (Finland); Halldin, C. [Karolinska Institute, Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, Stockholm (Sweden); Tiihonen, J. [Department of Forensic Psychiatry, University of Kuopio, Niuvanniemi Hospital, Kuopio (Finland)

    2000-02-01

    Iodine-123 labelled epidepride is a novel radiopharmaceutical for the study of cerebral dopamine D{sub 2} receptors using single-photon emission tomography (SPET). A lipophilic labelled metabolite of [{sup 123}I]epidepride which may enter the brain and hamper the quantitation of receptors has been observed in human plasma. In the present study, gradient high-performance liquid chromatography (HPLC) was used to investigate the plasma concentration of the lipophilic labelled metabolite and its correlation to SPET imaging of striatal dopamine D{sub 2} receptors. A linear regression fit showed a negative correlation between the amount of the lipophilic labelled metabolite and the striatum to cerebellum ratio (n=16, R=-0.58, P<0.02), suggesting that plasma metabolite analysis is essential when imaging dopamine D{sub 2} receptors with SPET using [{sup 123}I]epidepride. (orig.)

  4. Preclinical evaluation and quantification of [18F]MK-9470 as a radioligand for PET imaging of the type 1 cannabinoid receptor in rat brain

    International Nuclear Information System (INIS)

    [18F]MK-9470 is an inverse agonist for the type 1 cannabinoid (CB1) receptor allowing its use in PET imaging. We characterized the kinetics of [18F]MK-9470 and evaluated its ability to quantify CB1 receptor availability in the rat brain. Dynamic small-animal PET scans with [18F]MK-9470 were performed in Wistar rats on a FOCUS-220 system for up to 10 h. Both plasma and perfused brain homogenates were analysed using HPLC to quantify radiometabolites. Displacement and blocking experiments were done using cold MK-9470 and another inverse agonist, SR141716A. The distribution volume (VT) of [18F]MK-9470 was used as a quantitative measure and compared to the use of brain uptake, expressed as SUV, a simplified method of quantification. The percentage of intact [18F]MK-9470 in arterial plasma samples was 80 ± 23 % at 10 min, 38 ± 30 % at 40 min and 13 ± 14 % at 210 min. A polar radiometabolite fraction was detected in plasma and brain tissue. The brain radiometabolite concentration was uniform across the whole brain. Displacement and pretreatment studies showed that 56 % of the tracer binding was specific and reversible. VT values obtained with a one-tissue compartment model plus constrained radiometabolite input had good identifiability (≤10 %). Ignoring the radiometabolite contribution using a one-tissue compartment model alone, i.e. without constrained radiometabolite input, overestimated the [18F]MK-9470 VT, but was correlated. A correlation between [18F]MK-9470 VT and SUV in the brain was also found (R 2 = 0.26-0.33; p ≤ 0.03). While the presence of a brain-penetrating radiometabolite fraction complicates the quantification of [18F]MK-9470 in the rat brain, its tracer kinetics can be modelled using a one-tissue compartment model with and without constrained radiometabolite input. (orig.)

  5. SPECT imaging of dopamine receptors with [123I]epidepride: characterization of uptake in the human brain

    International Nuclear Information System (INIS)

    Summary. [123I]Epidepride is a new ligand for single photon emission computerized tomography (SPECT) that specifically labels D2-like dopamine receptors with very high affinity. Here, we report on the regional kinetic uptake of [123I]epidepride in the brain of 4 normal volunteers and 3 patients with choreatic movement disorders. In healthy subjects striatal activity peaked at 2.5 hours after injection of the tracer and decreased slowly thereafter. There were no significant differences between left and right brain hemispheres. Activity above background was also measurable in areas corresponding to the thalamus, temporal cortex and frontal cortex. The striatal to cerebellar ratio was about 14 after 2.5 hours and this ratio steadily increased with time. The striatal to cerebellar ratio was clearly reduced in all 3 patients with choreatic movement disorders (from about 14 in control subjects after 2.5 hours to about 7 in choreatic patients). [123I]Epidepride may be a useful SPECT ligand for studying D2 receptors in the living human brain because of its high target to background ratio, its high affinity and the possibility to investigate extrastriatal D2 receptors. (author)

  6. GABA receptor imaging

    International Nuclear Information System (INIS)

    GABA is primary an inhibitory neurotransmitter that is localized in inhibitory interneurons. GABA is released from presynaptic terminals and functions by binding to GABA receptors. There are two types of GABA receptors, GABAA-receptor that allows chloride to pass through a ligand gated ion channel and GABAB-receptor that uses G-proteins for signaling. The GABAA-receptor has a GABA binding site as well as a benzodiazepine binding sites, which modulate GABAA-receptor function. Benzodiazepine GABAA receptor imaging can be accomplished by radiolabeling derivates that activates benzodiazepine binding sites. There has been much research on flumazenil (FMZ) labeled with 11C-FMZ, a benzodiazepine derivate that is a selective, reversible antagonist to GABAA receptors. Recently, 18F-fluoroflumazenil (FFMZ) has been developed to overcome 11C's short half-life. 18F-FFMZ shows high selective affinity and good pharmacodynamics, and is a promising PET agent with better central benzodiazepine receptor imaging capabilities. In an epileptic focus, because the GABA/benzodiazepine receptor amount is decreased, using '11C-FMZ PET instead of 18F-FDG, PET, restrict the foci better and may also help find lesions better than high resolution MR. GABAA receptors are widely distributed in the cerebral cortex, and can be used as an viable neuronal marker. Therefore it can be used as a neuronal cell viability marker in cerebral ischemia. Also, GABA-receptors decrease in areas where neuronal plasticity develops, therefore, GABA imaging can be used to evaluate plasticity. Besides these usages, GABA receptors are related with psychological diseases, especially depression and schizophrenia as well as cerebral palsy, a motor-related disorder, so further in-depth studies are needed for these areas

  7. GABA receptor imaging

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jong Doo [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2007-04-15

    GABA is primary an inhibitory neurotransmitter that is localized in inhibitory interneurons. GABA is released from presynaptic terminals and functions by binding to GABA receptors. There are two types of GABA receptors, GABA{sub A}-receptor that allows chloride to pass through a ligand gated ion channel and GABA{sub B}-receptor that uses G-proteins for signaling. The GABA{sub A}-receptor has a GABA binding site as well as a benzodiazepine binding sites, which modulate GABA{sub A}-receptor function. Benzodiazepine GABAA receptor imaging can be accomplished by radiolabeling derivates that activates benzodiazepine binding sites. There has been much research on flumazenil (FMZ) labeled with {sup 11}C-FMZ, a benzodiazepine derivate that is a selective, reversible antagonist to GABAA receptors. Recently, {sup 18}F-fluoroflumazenil (FFMZ) has been developed to overcome {sup 11}C's short half-life. {sup 18}F-FFMZ shows high selective affinity and good pharmacodynamics, and is a promising PET agent with better central benzodiazepine receptor imaging capabilities. In an epileptic focus, because the GABA/benzodiazepine receptor amount is decreased, using '1{sup 1}C-FMZ PET instead of {sup 18}F-FDG, PET, restrict the foci better and may also help find lesions better than high resolution MR. GABA{sub A} receptors are widely distributed in the cerebral cortex, and can be used as an viable neuronal marker. Therefore it can be used as a neuronal cell viability marker in cerebral ischemia. Also, GABA-receptors decrease in areas where neuronal plasticity develops, therefore, GABA imaging can be used to evaluate plasticity. Besides these usages, GABA receptors are related with psychological diseases, especially depression and schizophrenia as well as cerebral palsy, a motor-related disorder, so further in-depth studies are needed for these areas.

  8. Functional Brain Imaging

    Directory of Open Access Journals (Sweden)

    K. Vessal

    2005-08-01

    Full Text Available Introduction & Background: The historical evolution of concepts of the mind has had a tremendous impact on human civilization. Aside from Smith’s surgical papyrus, there exists practically no documentation down to the era of Hippocrates. While in Corpus, the seat of all sensations is put in the brain, there is an amazing regression, for many centuries thereafter notably influenced by Aristotle, to displace it to the heart. This erroneous diversion promulgated in De Anima with minor corrections by Galen, has per-petuated to our time when we say, for example, that we love something with our very hearts or “knowing by heart” when we mean to memorize something. Avicenna challenged many of Aristotle’s ideas in El-monnafs (psychology section of Al Shafa, paving the road for the later European Renaissance. Cartesian choice of pineal body as the seat of soul in the first half of the 7th century was a fundamental departure from brain-soul dichotomy. It was followed by Gall’s pseudo-science, phrenology, as the first attempt of brain mapping in ascribing “mental faculties” to the speculative “organs” of the brain. Brain mapping through Functional Brain Imaging has flourished ex-tensively in the past decades -starting from PET with later substitution by fMRI- as robust tools for interro-gating mysteries of the brain. With a surprising pace of development, Functional Brain Imaging heralds a welcome adjunct to the science of radiology in ex-ploring mind and human behavior. Given the multi-tude of appropriate MRI machines operating across the country, attention to this aspect of imaging can invigorate research in radiology and boost generation of knowledge in this rapidly growing field. Recent advances in MRI fast imaging, fMRI, as well as clini-cal and spectroscopic imaging with present clinical application and future trends are discussed.

  9. Quantitative imaging of brain chemistry

    International Nuclear Information System (INIS)

    We can now measure how chemicals affect different regions of the human brain. One area involves the study of drugs - in-vivo neuro-pharmacology; another involves the study of toxic chemical effects - in vivo neurotoxicology. The authors approach is to label drugs with positron-emitting radioactive tracers - chiefly carbon-11 with a half-life of 20 minutes and fluorine-18 with a half-life of 110 minutes. The labeled drugs are injected intravenously and a positron emission tomography (PET) scanner is used to map out the distribution of the radioactivity within the brain from the moment of injection until about 90 minutes later. Mathematical models are used to calculate receptor concentrations and the affinity of the receptors for the injected radioactive tracer. By means of PET scanning, they look at cross sections or visual slices throughout the human brain, obtaining computer-generated images in any plane. The authors are investigating the functions of specific drugs or specific receptors, as well as looking at the metabolic activity in different parts of the brain as revealed in glucose metabolism. For example, the authors are studying opiate receptors in patients with a variety of conditions: those who suffer from chronic pain, those who are congenitally insensitive to pain and drug addicts. They are studying patients with schizophrenia, tardive dyskinesia, Parkinson's disease, Huntington's disease, depressed patients and sex-offenders. They are relating the state of the neurotransmitter/neuroreceptor systems to behavior. In essence, they believe that they can now examine in living human beings what relates the structure of the brain to the function of the mind that is chemistry

  10. Brain Image Motion Correction

    DEFF Research Database (Denmark)

    Jensen, Rasmus Ramsbøl; Benjaminsen, Claus; Larsen, Rasmus;

    2015-01-01

    The application of motion tracking is wide, including: industrial production lines, motion interaction in gaming, computer-aided surgery and motion correction in medical brain imaging. Several devices for motion tracking exist using a variety of different methodologies. In order to use such devices...... offset and tracking noise in medical brain imaging. The data are generated from a phantom mounted on a rotary stage and have been collected using a Siemens High Resolution Research Tomograph for positron emission tomography. During acquisition the phantom was tracked with our latest tracking prototype...

  11. Functional brain imaging

    International Nuclear Information System (INIS)

    Functional magnetic resonance imaging (fMRI) is a non-invasive method that has become one of the major tools for understanding human brain function and in recent years has also been developed for clinical applications. Changes in hemodynamic signals correspond to changes in neuronal activity with good spatial and temporal resolution in fMRI. Using high-field MR systems and increasingly dedicated statistics and postprocessing, activated brain areas can be detected and superimposed on anatomical images. Currently, fMRI data are often combined in multimodal imaging, e. g. with diffusion tensor imaging (DTI) sequences. This method is helping to further understand the physiology of cognitive brain processes and is also being used in a number of clinical applications. In addition to the blood oxygenation level-dependent (BOLD) signals, this article deals with the construction of fMRI investigations, selection of paradigms and evaluation in the clinical routine. Clinically, this method is mainly used in the planning of brain surgery, analyzing the location of brain tumors in relation to eloquent brain areas and the lateralization of language processing. As the BOLD signal is dependent on the strength of the magnetic field as well as other limitations, an overview of recent developments is given. Increases of magnetic field strength (7 T), available head coils and advances in MRI analytical methods have led to constant improvement in fMRI signals and experimental design. Especially the depiction of eloquent brain regions can be done easily and quickly and has become an essential part of presurgical planning. (orig.)

  12. MRI brain imaging.

    Science.gov (United States)

    Skinner, Sarah

    2013-11-01

    General practitioners (GPs) are expected to be allowed to request MRI scans for adults for selected clinically appropriate indications from November 2013 as part of the expansion of Medicare-funded MRI services announced by the Federal Government in 2011. This article aims to give a brief overview of MRI brain imaging relevant to GPs, which will facilitate explanation of scan findings and management planning with their patients. Basic imaging techniques, common findings and terminology are presented using some illustrative case examples.

  13. Striatal and extrastriatal imaging of dopamine D{sub 2}receptors in the living human brain with [ {sup 123}I]epidepride single-photon emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Kuikka, J.T. [Department of Clinical Physiology, Kuopio University Hospital, Kuopio (Finland); Aakerman, K.K. [Department of Clinical Physiology, Kuopio University Hospital, Kuopio (Finland); Hiltunen, J. [MAP Medical Technologies Inc., Tikkakoski (Finland); Bergstroem, K.A. [Department of Clinical Physiology, Kuopio University Hospital, Kuopio (Finland); Raesaenen, P. [Department of Forensic Psychiatry, University of Kuopio and Niuvanniemi Hospital, Kuopio (Finland); Vanninen, E. [Department of Clinical Physiology, Kuopio University Hospital, Kuopio (Finland); Halldin, C. [Karolinska Institutet, Department of Clinical Neuroscience, Karolinska Hospital, Stockholm (Sweden); Tiihonen, J. [Department of Forensic Psychiatry, University of Kuopio and Niuvanniemi Hospital, Kuopio (Finland)

    1997-05-01

    The iodine-123 labelled ligand benzamide epidepride was evaluated as a probe for in vivo imaging of striatal and extrastriatal dopamine D{sub 2}receptor sites in the human brain. Four healthy males were imaged with a high-resolution single-photon emission tomography scanner. Striatal radioactivity peaked at 3 h after injection. The specific binding in the striatum was 0.91 {+-}0.03 at 3 h and this ratio steadily increased with time. Extrastriatal radioactivity was highest in the thalamus, in the midbrain and in the temporal cortex, and peaked at 45-60 min after injection of tracer. A smaller amount of radioactivity was found in the parietal, frontal and occipital cortices. Two radioactive metabolites were observed, of which one was more lipophilic than the parent compound. The radiation burden to the patient was 0.035 mSv/MBq (effective dose equivalent). The preliminary results showed that [ {sup 123}I]epidepride can be used for imaging striatal and extrastriatal dopamine D {sub 2}receptor sites in the living human brain. (orig.). With 5 figs., 1 tab.

  14. Striatal and extrastriatal imaging of dopamine D2 receptors in the living human brain with [123I]epidepride single-photon emission tomography.

    Science.gov (United States)

    Kuikka, J T; Akerman, K K; Hiltunen, J; Bergström, K A; Räsänen, P; Vanninen, E; Halldin, C; Tiihonen, J

    1997-05-01

    The iodine-123 labelled ligand benzamide epidepride was evaluated as a probe for in vivo imaging of striatal and extrastriatal dopamine D2 receptor sites in the human brain. Four healthy males were imaged with a high-resolution single-photon emission tomography scanner. Striatal radioactivity peaked at 3 h after injection. The specific binding in the striatum was 0.91+/-0.03 at 3 h and this ratio steadily increased with time. Extrastriatal radioactivity was highest in the thalamus, in the midbrain and in the temporal cortex, and peaked at 45-60 min after injection of tracer. A smaller amount of radioactivity was found in the parietal, frontal and occipital cortices. Two radioactive metabolites were observed, of which one was more lipophilic than the parent compound. The radiation burden to the patient was 0.035 mSv/MBq (effective dose equivalent). The preliminary results showed that [123I]epidepride can be used for imaging striatal and extrastriatal dopamine D2 receptor sites in the living human brain. PMID:9142727

  15. Striatal and extrastriatal imaging of dopamine D2receptors in the living human brain with [ 123I[epidepride single-photon emission tomography

    International Nuclear Information System (INIS)

    The iodine-123 labelled ligand benzamide epidepride was evaluated as a probe for in vivo imaging of striatal and extrastriatal dopamine D2receptor sites in the human brain. Four healthy males were imaged with a high-resolution single-photon emission tomography scanner. Striatal radioactivity peaked at 3 h after injection. The specific binding in the striatum was 0.91 ±0.03 at 3 h and this ratio steadily increased with time. Extrastriatal radioactivity was highest in the thalamus, in the midbrain and in the temporal cortex, and peaked at 45-60 min after injection of tracer. A smaller amount of radioactivity was found in the parietal, frontal and occipital cortices. Two radioactive metabolites were observed, of which one was more lipophilic than the parent compound. The radiation burden to the patient was 0.035 mSv/MBq (effective dose equivalent). The preliminary results showed that [ 123I[epidepride can be used for imaging striatal and extrastriatal dopamine D 2receptor sites in the living human brain. (orig.). With 5 figs., 1 tab

  16. Opioid receptor imaging and displacement studies with [6-O-[{sup 11}C]methyl]buprenorphine in baboon brain

    Energy Technology Data Exchange (ETDEWEB)

    Galynker, Igor; Schlyer, David J.; Dewey, Stephen L.; Fowler, Joanna S.; Logan, Jean; Gatley, S. John; MacGregor, Robert R.; Ferrieri, Richard A.; Holland, M. J.; Brodie, Jonathan; Simon, Eric; Wolf, Alfred P

    1996-04-01

    Buprenorphine (BPN) is a mixed opiate agonist-antagonist used as an analgesic and in the treatment of opiate addiction. We have used [6-O-[{sup 11}C]methyl]buprenorphine ([{sup 11}C]BPN) to measure the regional distribution in baboon brain, the test-retest stability of repeated studies in the same animal, the displacement of the labeled drug by naloxone in vivo, and the tissue distribution in mice. The regional distribution of radioactivity in baboon brain determined with PET was striatum > thalamus > cingulate gyrus > frontal cortex > parietal cortex > occipital cortex > cerebellum. This distribution corresponded to opiate receptor density and to previously published data (37). The tracer uptake in adult female baboons showed no significant variation in serial scans in the same baboon with no intervention in the same scanning session. HPLC analysis of baboon plasma showed the presence of labeled metabolites with 92% {+-} 2.2% and 43% {+-} 14.4% of the intact tracer remaining at 5 and 30 min, respectively. Naloxone, an opiate receptor antagonist, administered 30-40 min after tracer injection at a dose of 1.0 mg/kg i.v., reduced [{sup 11}C]BPN binding in thalamus, striatum, cingulate gyrus, and frontal cortex to values 0.25 to 0.60 of that with no intervention. There were minimal (< 15%) effects on cerebellum. Naloxone treatment significantly reduced the slope of the Patlak plot in receptor-containing regions. These results demonstrate that [{sup 11}C]BPN can be displaced by naloxone in vivo, and they affirm the feasibility of using this tracer and displacement methodology for short-term kinetics studies with PET. Mouse tissue distribution data were used to estimate the radiation dosimetry to humans. The critical organ was the small intestine, with a radiation dose estimate to humans of 117 nrad/mCi.

  17. Cannabinoid receptor localization in brain

    Energy Technology Data Exchange (ETDEWEB)

    Herkenham, M.; Lynn, A.B.; Little, M.D.; Johnson, M.R.; Melvin, L.S.; de Costa, B.R.; Rice, K.C. (National Institute of Mental Health, Bethesda, MD (USA))

    1990-03-01

    (3H)CP 55,940, a radiolabeled synthetic cannabinoid, which is 10-100 times more potent in vivo than delta 9-tetrahydrocannabinol, was used to characterize and localize a specific cannabinoid receptor in brain sections. The potencies of a series of natural and synthetic cannabinoids as competitors of (3H)CP 55,940 binding correlated closely with their relative potencies in several biological assays, suggesting that the receptor characterized in our in vitro assay is the same receptor that mediates behavioral and pharmacological effects of cannabinoids, including human subjective experience. Autoradiography of cannabinoid receptors in brain sections from several mammalian species, including human, reveals a unique and conserved distribution; binding is most dense in outflow nuclei of the basal ganglia--the substantia nigra pars reticulata and globus pallidus--and in the hippocampus and cerebellum. Generally high densities in forebrain and cerebellum implicate roles for cannabinoids in cognition and movement. Sparse densities in lower brainstem areas controlling cardiovascular and respiratory functions may explain why high doses of delta 9-tetrahydrocannabinol are not lethal.

  18. A Promising PET Tracer for Imaging of α7 Nicotinic Acetylcholine Receptors in the Brain: Design, Synthesis, and in Vivo Evaluation of a Dibenzothiophene-Based Radioligand

    Directory of Open Access Journals (Sweden)

    Rodrigo Teodoro

    2015-10-01

    Full Text Available Changes in the expression of α7 nicotinic acetylcholine receptors (α7 nAChRs in the human brain are widely assumed to be associated with neurological and neurooncological processes. Investigation of these receptors in vivo depends on the availability of imaging agents such as radioactively labelled ligands applicable in positron emission tomography (PET. We report on a series of new ligands for α7 nAChRs designed by the combination of dibenzothiophene dioxide as a novel hydrogen bond acceptor functionality with diazabicyclononane as an established cationic center. To assess the structure-activity relationship (SAR of this new basic structure, we further modified the cationic center systematically by introduction of three different piperazine-based scaffolds. Based on in vitro binding affinity and selectivity, assessed by radioligand displacement studies at different rat and human nAChR subtypes and at the structurally related human 5-HT3 receptor, we selected the compound 7-(1,4-diazabicyclo[3.2.2]nonan-4-yl-2-fluorodibenzo-[b,d]thiophene 5,5-dioxide (10a for radiolabeling and further evaluation in vivo. Radiosynthesis of [18F]10a was optimized and transferred to an automated module. Dynamic PET imaging studies with [18F]10a in piglets and a monkey demonstrated high uptake of radioactivity in the brain, followed by washout and target-region specific accumulation under baseline conditions. Kinetic analysis of [18F]10a in pig was performed using a two-tissue compartment model with arterial-derived input function. Our initial evaluation revealed that the dibenzothiophene-based PET radioligand [18F]10a ([18F]DBT-10 has high potential to provide clinically relevant information about the expression and availability of α7 nAChR in the brain.

  19. Brain hypoxia imaging

    Energy Technology Data Exchange (ETDEWEB)

    Song, Ho Chun [Chonnam National University Medical School, Gwangju (Korea, Republic of)

    2007-04-15

    The measurement of pathologically low levels of tissue pO{sub 2} is an important diagnostic goal for determining the prognosis of many clinically important diseases including cardiovascular insufficiency, stroke and cancer. The target tissues nowadays have mostly been tumors or the myocardium, with less attention centered on the brain. Radiolabelled nitroimidazole or derivatives may be useful in identifying the hypoxic cells in cerebrovascular disease or traumatic brain injury, and hypoxic-ischemic encephalopathy. In acute stroke, the target of therapy is the severely hypoxic but salvageable tissue. {sup 18}F-MISO PET and {sup 99m}Tc-EC-metronidazole SPECT in patients with acute ischemic stroke identified hypoxic tissues and ischemic penumbra, and predicted its outcome. A study using {sup 123}I-IAZA in patient with closed head injury detected the hypoxic tissues after head injury. Up till now these radiopharmaceuticals have drawbacks due to its relatively low concentration with hypoxic tissues associated with/without low blood-brain barrier permeability and the necessity to wait a long time to achieve acceptable target to background ratios for imaging in acute ischemic stroke. It is needed to develop new hypoxic marker exhibiting more rapid localization in the hypoxic region in the brain. And then, the hypoxic brain imaging with imidazoles or non-imidazoles may be very useful in detecting the hypoxic tissues, determining therapeutic strategies and developing therapeutic drugs in several neurological disease, especially, in acute ischemic stroke.

  20. Electromagnetic brain imaging

    International Nuclear Information System (INIS)

    Present imaging methods of cerebral neuro-activity like brain functional MRI and positron emission tomography (PET) secondarily measure only average activities within a time of the second-order (low time-resolution). In contrast, the electromagnetic brain imaging (EMBI) directly measures the faint magnetic field (10-12-10-13 T) yielded by the cerebral activity with use of multiple arrayed sensors equipped on the head surface within a time of sub-millisecond order (high time-resolution). The sensor array technology to find the signal source from the measured data is common in wide areas like signal procession for radar, sonar, and epicenter detection by seismic wave. For estimating and reconstructing the active region in the brain in EMBI, the efficient method must be developed and this paper describes the direct and inverse problems concerned in signal and image processions of EMBI. The direct problem involves the cerebral magnetic field/lead field matrix and inverse problem for reconstruction of signal source, the MUSIC (multiple signal classification) algorithm, GLRT (generalized likelihood ratio test) scan, and adaptive beamformer. As an example, given are results of magnetic intensity changes (unit, fT) in the somatosensory cortex vs time (msec) measured by 160 sensors and of images reconstructed from EMBI and MRI during electric muscle afferent input from the hand. The real-time imaging is thus possible with EMBI and extremely, the EMBI image, the real-time cerebral signals, can inversely operate a machine, of which application directs toward the brain/machine interface development. (R.T.)

  1. The discovery of epidepride and its analogs as high-affinity radioligands for imaging extrastriatal dopamine D(2) receptors in human brain.

    Science.gov (United States)

    de Paulis, Tomas

    2003-01-01

    [(123)I]Epidepride, [(18)F]fallypride, and [(76)Br]isoremoxipride (FLB-457) and their corresponding [(11)C]labeled derivatives belong to a class of high-affinity radioligands for SPECT or PET imaging of dopamine D(2) receptors in the human brain. In contrast to previously used imaging agents, these ligands are capable of identifying extrastriatal dopamine D(2) receptors. The design of these substituted benzamides derive its origin from the atypical antipsychotic agent, remoxipride. Starting in the late 1970's, halogenated analogs of (S)-sulpiride were evaluated in binding assays and behavioral studies, leading to the discovery of remoxipride. Remoxipride was 10 times weaker than sulpiride in vitro but 50 times more potent in vivo. Search for a putative active metabolite of remoxipride led to the discovery of raclopride and eticlopride, the former becoming a useful radioligand as tritium or carbon-11 labeled form for receptor binding and PET studies, respectively. In the US, the mono-iodine analog of raclopride, [(123)I]iodobenzamide (IBZM), was found to have moderate putamen-to-cerebellum ratio in rat and human brain. Continued search for metabolites of remoxipride led to the discovery of its 3,6-dihydroxy derivative, NCQ-344, with an extremely potent in vivo activity in the rat. SAR studies of the metabolites of remoxipride led to the discovery of the 3-methoxy isomer, isoremoxipride (FLB-457) and its corresponding 6-hydroxy analog, FLB-463, both having affinities for the dopamine D(2) receptor in the 20-30 pM range. Later, the 5-[(123)I]iodo analog of FLB-463, [(123)I]ioxipride ([(123)I]NCQ-298), became a potential SPECT imaging agent. In the mean time, the deshydroxy analog of IBZM, [(125)I]iodopride, showed binding potential in the rat similar to [(125)I]IBZM. Epidepride was designed by combining the structure of isoremoxipride with that of iodopride. In 1988, epidepride was independently prepared and radiolabeled in three separate laboratories in Stockholm

  2. Preclinical evaluation and quantification of [{sup 18}F]MK-9470 as a radioligand for PET imaging of the type 1 cannabinoid receptor in rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Casteels, Cindy [K.U. Leuven, University Hospital Leuven, Division of Nuclear Medicine, Leuven (Belgium); K.U. Leuven, MoSAIC, Molecular Small Animal Imaging Center, Leuven (Belgium); University Hospital Gasthuisberg, Division of Nuclear Medicine, Leuven (Belgium); Koole, Michel; Laere, Koen van [K.U. Leuven, University Hospital Leuven, Division of Nuclear Medicine, Leuven (Belgium); K.U. Leuven, MoSAIC, Molecular Small Animal Imaging Center, Leuven (Belgium); Celen, Sofie; Bormans, Guy [K.U. Leuven, MoSAIC, Molecular Small Animal Imaging Center, Leuven (Belgium); K.U. Leuven, Laboratory for Radiopharmacy, Leuven (Belgium)

    2012-09-15

    [{sup 18}F]MK-9470 is an inverse agonist for the type 1 cannabinoid (CB1) receptor allowing its use in PET imaging. We characterized the kinetics of [{sup 18}F]MK-9470 and evaluated its ability to quantify CB1 receptor availability in the rat brain. Dynamic small-animal PET scans with [{sup 18}F]MK-9470 were performed in Wistar rats on a FOCUS-220 system for up to 10 h. Both plasma and perfused brain homogenates were analysed using HPLC to quantify radiometabolites. Displacement and blocking experiments were done using cold MK-9470 and another inverse agonist, SR141716A. The distribution volume (V{sub T}) of [{sup 18}F]MK-9470 was used as a quantitative measure and compared to the use of brain uptake, expressed as SUV, a simplified method of quantification. The percentage of intact [{sup 18}F]MK-9470 in arterial plasma samples was 80 {+-} 23 % at 10 min, 38 {+-} 30 % at 40 min and 13 {+-} 14 % at 210 min. A polar radiometabolite fraction was detected in plasma and brain tissue. The brain radiometabolite concentration was uniform across the whole brain. Displacement and pretreatment studies showed that 56 % of the tracer binding was specific and reversible. V{sub T} values obtained with a one-tissue compartment model plus constrained radiometabolite input had good identifiability ({<=}10 %). Ignoring the radiometabolite contribution using a one-tissue compartment model alone, i.e. without constrained radiometabolite input, overestimated the [{sup 18}F]MK-9470 V{sub T}, but was correlated. A correlation between [{sup 18}F]MK-9470 V{sub T} and SUV in the brain was also found (R {sup 2} = 0.26-0.33; p {<=} 0.03). While the presence of a brain-penetrating radiometabolite fraction complicates the quantification of [{sup 18}F]MK-9470 in the rat brain, its tracer kinetics can be modelled using a one-tissue compartment model with and without constrained radiometabolite input. (orig.)

  3. Opioid receptor imaging and displacement studies with [6-O-[11C]methyl]buprenorphine in baboon brain

    International Nuclear Information System (INIS)

    Buprenorphine (BPN) is a mixed opiate agonist-antagonist used as an analgesic and in the treatment of opiate addiction. We have used [6-O-[11C]methyl]buprenorphine ([11C]BPN) to measure the regional distribution in baboon brain, the test-retest stability of repeated studies in the same animal, the displacement of the labeled drug by naloxone in vivo, and the tissue distribution in mice. The regional distribution of radioactivity in baboon brain determined with PET was striatum > thalamus > cingulate gyrus > frontal cortex > parietal cortex > occipital cortex > cerebellum. This distribution corresponded to opiate receptor density and to previously published data (37). The tracer uptake in adult female baboons showed no significant variation in serial scans in the same baboon with no intervention in the same scanning session. HPLC analysis of baboon plasma showed the presence of labeled metabolites with 92% ± 2.2% and 43% ± 14.4% of the intact tracer remaining at 5 and 30 min, respectively. Naloxone, an opiate receptor antagonist, administered 30-40 min after tracer injection at a dose of 1.0 mg/kg i.v., reduced [11C]BPN binding in thalamus, striatum, cingulate gyrus, and frontal cortex to values 0.25 to 0.60 of that with no intervention. There were minimal (11C]BPN can be displaced by naloxone in vivo, and they affirm the feasibility of using this tracer and displacement methodology for short-term kinetics studies with PET. Mouse tissue distribution data were used to estimate the radiation dosimetry to humans. The critical organ was the small intestine, with a radiation dose estimate to humans of 117 nrad/mCi

  4. Brain imaging and autism

    Energy Technology Data Exchange (ETDEWEB)

    Zilbovicius, M. [Service Hospitalier Frederic Joliot (CEA/DSV/DRM), INSERM CEA 0205, 91 - Orsay (France)

    2006-07-01

    Autism is a neuro-developmental disorder with a range of clinical presentations, from mild to severe, referred to as autism spectrum disorders (ASD). The most common clinical ASD sign is social interaction impairment, which is associated with verbal and non-verbal communication deficits and stereotyped and obsessive behaviors. Thanks to recent brain imaging studies, scientists are getting a better idea of the neural circuits involved in ASD. Indeed, functional brain imaging, such as positron emission tomography (PET), single positron emission tomograph y (SPECT) and functional MRI (fMRI) have opened a new perspective to study normal and pathological brain functions. Three independent studies have found anatomical and rest functional temporal abnormalities. These anomalies are localized in the superior temporal sulcus bilaterally which are critical for perception of key social stimuli. In addition, functional studies have shown hypo-activation of most areas implicated in social perception (face and voice perception) and social cognition (theory of mind). These data suggest an abnormal functioning of the social brain network. The understanding of such crucial abnormal mechanism may drive the elaboration of new and more adequate social re-educative strategies in autism. (author)

  5. Brain imaging and autism

    International Nuclear Information System (INIS)

    Autism is a neuro-developmental disorder with a range of clinical presentations, from mild to severe, referred to as autism spectrum disorders (ASD). The most common clinical ASD sign is social interaction impairment, which is associated with verbal and non-verbal communication deficits and stereotyped and obsessive behaviors. Thanks to recent brain imaging studies, scientists are getting a better idea of the neural circuits involved in ASD. Indeed, functional brain imaging, such as positron emission tomography (PET), single positron emission tomograph y (SPECT) and functional MRI (fMRI) have opened a new perspective to study normal and pathological brain functions. Three independent studies have found anatomical and rest functional temporal abnormalities. These anomalies are localized in the superior temporal sulcus bilaterally which are critical for perception of key social stimuli. In addition, functional studies have shown hypo-activation of most areas implicated in social perception (face and voice perception) and social cognition (theory of mind). These data suggest an abnormal functioning of the social brain network. The understanding of such crucial abnormal mechanism may drive the elaboration of new and more adequate social re-educative strategies in autism. (author)

  6. Somatostatin receptor imaging

    International Nuclear Information System (INIS)

    The intention of the meeting was to present: 1.Results from large-scale diagnositc imaging studies, carried out in various somatostatin receptorpositive tumors by Germany nuclear medicine specialists; 2. Potential clinical indications for somatostatin receptor scintigraphy in gastroenterology, endocrinology, and other clinical disciplines. These presentations were balanced by the reports of distinguished clinicians on their experience with somatostatin analogs in therapeutic settings and by the comments of a number of investigators on the basic mechanisms of somatostatin-receptor/ligand-system(s) and on peptide radiopharmacology. Separate entries are proposed for 8 of the 11 individual papers presented at the conference. (orig./MG). 48 figs., 22 tabs

  7. Imaging brain plasticity after trauma

    OpenAIRE

    Kou, Zhifeng; Iraji, Armin

    2014-01-01

    The brain is highly plastic after stroke or epilepsy; however, there is a paucity of brain plasticity investigation after traumatic brain injury (TBI). This mini review summarizes the most recent evidence of brain plasticity in human TBI patients from the perspective of advanced magnetic resonance imaging. Similar to other forms of acquired brain injury, TBI patients also demonstrated both structural reorganization as well as functional compensation by the recruitment of other brain regions. ...

  8. (11) C-labeled and (18) F-labeled PET ligands for subtype-specific imaging of histamine receptors in the brain.

    Science.gov (United States)

    Funke, Uta; Vugts, Danielle J; Janssen, Bieneke; Spaans, Arnold; Kruijer, Perry S; Lammertsma, Adriaan A; Perk, Lars R; Windhorst, Albert D

    2013-01-01

    The signaling molecule histamine plays a key role in the mediation of immune reactions, in gastric secretion, and in the sensory system. In addition, it has an important function as a neurotransmitter in the central nervous system, acting in pituitary hormone secretion, wakefulness, motor and cognitive functions, as well as in itch and nociception. This has raised interest in the role of the histaminergic system for the treatment and diagnosis of various pathologies such as allergy, sleeping and eating disorders, neurodegeneration, neuroinflammation, mood disorders, and pruritus. In the past 20 years, several ligands targeting the four different histamine receptor subtypes have been explored as potential radiotracers for positron emission tomography (PET). This contribution provides an overview of the developments of subtype-selective carbon-11-labeled and fluorine-18-labeled compounds for imaging in the brain. Using specific radioligands, the H1 R expression in human brain could be examined in diseases such as schizophrenia, depression, and anorexia nervosa. In addition, the sedative effects of antihistamines could be investigated in terms of H1 R occupancy. The H3 R is of special interest because of its regulatory role in the release of various other neurotransmitters, and initial H3 R PET imaging studies in humans have been reported. The H4 R is the youngest member of the histamine receptor family and is involved in neuroinflammation and various sensory pathways. To date, two H4 R-specific (11) C-labeled ligands have been synthesized, and the imaging of the H4 R in vivo is in the early stage.

  9. NMDA receptor function, memory, and brain aging

    OpenAIRE

    Newcomer, John W.; Farber, Nuri B.; Olney, John W.

    2000-01-01

    An increasing level of N-methyl-D-aspartate (NMDA) receptor hypofunction within the brain is associated with memory and learning impairments, with psychosis, and ultimately with excitotoxic brain injury. As the brain ages, the NMDA receptor system becomes progressively hypofunctional, contributing to decreases in memory and learning performance. In those individuals destined to develop Alzheimer's disease, other abnormalities (eg, amyloidopathy and oxidative stress) interact to increase the N...

  10. Synthesis and initial evaluation of [{sup 11}C](R)-RWAY in monkey - a new, simply labeled antagonist radioligand for imaging brain 5-HT{sub 1A} receptors with PET

    Energy Technology Data Exchange (ETDEWEB)

    McCarron, Julie A.; Zoghbi, Sami S.; Shetty, H.U.; Ichise, Masanori; Yasuno, Fumihiko; Innis, Robert B.; Pike, Victor W. [National Institutes of Health, Molecular Imaging Branch, National Institute of Mental Health, Bethesda, MD (United States); Vermeulen, Eric S.; Wikstroem, Haakan V. [University of Groningen, Department of Medicinal Chemistry, University Center for Pharmacy, Groningen (Netherlands); Halldin, Christer [Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry Section, Stockholm (Sweden)

    2007-10-15

    We aimed to fulfill a need for a radioligand that may be simply labeled with carbon-11 for effective positron emission tomography (PET) imaging of brain 5-HT{sub 1A} receptors. Racemic RWAY (2,3,4,5,6,7-hexahydro-1-[4-[1-[4-(2-methoxyphenyl)piperazinyl

  11. High-resolution imaging of brain 5-HT{sub 1B} receptors in the rhesus monkey using [{sup 11}C]P943

    Energy Technology Data Exchange (ETDEWEB)

    Nabulsi, Nabeel; Huang Yiyun; Weinzimmer, David; Ropchan, Jim; Frost, James J. [Yale PET Center, Department of Diagnostic Radiology and Psychiatry, Yale University School of Medicine, P.O. Box 208048, New Haven, CT 06520-8048 (United States); McCarthy, Timothy [Pfizer Global R and D, Groton, CT 06340 (United States); Carson, Richard E.; Ding Yushin [Yale PET Center, Department of Diagnostic Radiology and Psychiatry, Yale University School of Medicine, P.O. Box 208048, New Haven, CT 06520-8048 (United States)

    2010-02-15

    The serotonin 5-HT{sub 1B} receptors regulate the release of serotonin and are involved in various disease states, including depression and schizophrenia. The goal of the study was to evaluate a high affinity and high selectivity antagonist, [{sup 11}C]P943, as a positron emission tomography (PET) tracer for imaging the 5-HT{sub 1B} receptor. [{sup 11}C]P943 was synthesized via N-methylation of the precursor with [{sup 11}C]methyl iodide or [{sup 11}C]methyl triflate using automated modules. The average radiochemical yield was approx. 10% with radiochemical purity of >99% and specific activity of 8.8{+-}3.6 mCi/nmol at the end-of-synthesis (n=37). PET imaging was performed in non-human primates with a high-resolution research tomograph scanner with a bolus/infusion paradigm. Binding potential (BP{sub ND}) was calculated using the equilibrium ratios of regions to cerebellum. The tracer uptake was highest in the globus pallidus and occipital cortex, moderate in basal ganglia and thalamus, and lowest in the cerebellum, which is consistent with the known brain distribution of 5-HT{sub 1B} receptors. Infusion of tracer at different specific activities (by adding various amount of unlabeled P943) reduced BP{sub ND} values in a dose-dependent manner, demonstrating the saturability of the tracer binding. Blocking studies with GR127935 (2 mg/kg iv), a selective 5-HT{sub 1B}/5-HT{sub 1D} antagonist, resulted in reduction of BP{sub ND} values by 42-95% across regions; for an example, in occipital region from 0.71 to 0.03, indicating a complete blockade. These results demonstrate the saturability and specificity of [{sup 11}C]P943 for 5-HT{sub 1B} receptors, suggesting its suitability as a PET radiotracer for in vivo evaluations of the 5-HT{sub 1B} receptor system in humans.

  12. Whole-body biodistribution and dosimetry estimates of a novel radiotracer for imaging of serotonin 4 receptors in brain: [18F]MNI-698

    International Nuclear Information System (INIS)

    Introduction: A new radiotracer for imaging the serotonin 4 receptors (5-HT4) in brain, [18F]MNI-698, was recently developed by our group. Evaluation in nonhuman primates indicates the novel radiotracer holds promise as an imaging agent of 5-HT4 in brain. This paper aims to describe the whole-body biodistribution and dosimetry estimates of [18F]MNI-698. Methods: Whole-body positron emission tomography (PET) images were acquired over 240 minutes after intravenous bolus injection of [18F]MNI-698 in adult rhesus monkeys. Different models were investigated for quantification of radiation absorbed and effective doses using OLINDA/EXM 1.0 software. Results: The radiotracer main elimination route was found to be urinary and the critical organ was the urinary bladder. Modeling of the urinary bladder voiding interval had a considerable effect on the estimated effective dose. Normalization of rhesus monkeys’ organs and whole-body masses to human equivalent reduced the calculated dosimetry values. The effective dose ranged between 0.017 and 0.027 mSv/MBq. Conclusion: The dosimetry estimates, obtained when normalizing organ and whole-body weights and applying the urinary bladder model, indicate that the radiation doses from [18F]MNI-698 comply with limits and guidelines recommended by key regulatory authorities that govern the translation of radiotracers to human clinical trials. The timing of urinary bladder emptying should be considered when designing future clinical protocols with [18F]MNI-698, in order to minimize the subject absorbed doses

  13. Synthesis and evaluation of [{sup 125}I]I-TSA as a brain nicotinic acetylcholine receptor {alpha}{sub 7} subtype imaging agent

    Energy Technology Data Exchange (ETDEWEB)

    Ogawa, Mikako [Laboratory of Genome Bio-Photonics, Photon Medical Research Center, Hamamatsu Medical University, Hamamatsu 431-3192 (Japan); Tatsumi, Ryo [Pharmaceuticals Research Unit, Research and Development Division, Mitsubishi Pharma Corporation, Yokohama 227-0033 (Japan); Fujio, Masakazu [Pharmaceuticals Research Unit, Research and Development Division, Mitsubishi Pharma Corporation, Yokohama 227-0033 (Japan); Katayama, Jiro [Pharmaceuticals Research Unit, Research and Development Division, Mitsubishi Pharma Corporation, Yokohama 227-0033 (Japan); Magata, Yasuhiro [Laboratory of Genome Bio-Photonics, Photon Medical Research Center, Hamamatsu Medical University, Hamamatsu 431-3192 (Japan)]. E-mail: magata@hama-med.ac.jp

    2006-04-15

    Introduction: Some in vitro investigations have suggested that the nicotinic acetylcholine receptor (nAChR) {alpha}{sub 7} subtype is implicated in Alzheimer's disease, schizophrenia and others. Recently, we developed (R)-3'-(5-bromothiophen-2-yl)spiro[1-azabicyclo[2.2.2]octane-3,5'-[1',3'] oxazolidin]-2'-one (Br-TSA), which has a high affinity and selectivity for {alpha}{sub 7} nAChRs. Therefore we synthesized (R)-3'-(5-[{sup 125}I]iodothiophen-2-yl)spiro[1-azabicyclo[2.2.2]octane-3,5'- [1',3']oxazolidin]-2'-one ([{sup 125}I]I-TSA) and evaluated its potential for the in vivo detection of {alpha}{sub 7} nAChR in brain. Methods: In vitro binding affinity of I-TSA was measured in rat brain homogenates. Radioiodination was accomplished by a Br-I exchange reaction. Biodistribution studies were undertaken in mice by tail vein injection of [{sup 125}I]I-TSA. In vivo receptor blocking studies were carried out by treating mice with methyllycaconitine (MLA; 5 nmol/5 {mu}l, i.c.v.) or nonradioactive I-TSA (50 {mu}mol/kg, i.v.). Results: I-TSA exhibited a high affinity and selectivity for the {alpha}{sub 7} nAChR (K {sub i} for {alpha}{sub 7} nAChR=0.54 nM). Initial uptake in the brain was high (4.42 %dose/g at 5 min), and the clearance of radioactivity was relatively slow in the hippocampus ({alpha}{sub 7} nAChR-rich region) and was rather rapid in the cerebellum ({alpha}{sub 7} nAChR poor region). The hippocampus to cerebellum uptake ratio was 0.9 at 5 min postinjection, but it was increased to 1.8 at 60 min postinjection. Although the effect was not statistically significant, administration of I-TSA and MLA decreased the accumulation of radioactivity in hippocampus. Conclusion: Despite its high affinity and selectivity, [{sup 125}I]I-TSA does not appear to be a suitable tracer for in vivo {alpha}{sub 7} nAChR receptor imaging studies due to its high nonspecific binding. Further structural optimization is needed.

  14. Imaging brain inflammation with [(11)C]PK11195 by PET and induction of the peripheral-type benzodiazepine receptor after transient focal ischemia in rats.

    Science.gov (United States)

    Rojas, Santiago; Martín, Abraham; Arranz, Maria J; Pareto, Deborah; Purroy, Jesús; Verdaguer, Esther; Llop, Jordi; Gómez, Vanessa; Gispert, Joan D; Millán, Olga; Chamorro, Angel; Planas, Anna M

    2007-12-01

    [(11)C]PK11195 is used in positron emission tomography (PET) studies for imaging brain inflammation in vivo as it binds to the peripheral-type benzodiazepine receptor (PBR) expressed by reactive glia and macrophages. However, features of the cellular reaction required to induce a positive [(11)C]PK11195 signal are not well characterized. We performed [(11)C]PK11195 PET and autoradiography in rats after transient focal cerebral ischemia. We determined [(3)H]PK11195 binding and PBR expression in brain tissue and examined the lesion with several markers. [(11)C]PK11195 standard uptake value increased at day 4 and grew further at day 7 within the ischemic core. Accordingly, ex vivo [(3)H]PK11195 binding increased at day 4, and increases further at day 7. The PET signal also augmented in peripheral regions, but to a lesser extent than in the core. Binding in the region surrounding infarction was supported by [(11)C]PK11195 autoradiography at day 7 showing that the radioactive signal extended beyond the infarcted core. Enhanced binding was preceded by increases in PBR mRNA expression in the ipsilateral hemisphere, and a 18-kDa band corresponding to PBR protein was detected. Peripheral-type benzodiazepine receptor immunohistochemistry showed subsets of ameboid microglia/macrophages within the infarcted core showing a distinctive strong PBR expression from day 4. These cells were often located surrounding microhemorrhages. Reactive astrocytes forming a rim surrounding infarction at day 7 also showed some PBR immunostaining. These results show cellular heterogeneity in the level of PBR expression, supporting that PBR is not a simple marker of inflammation, and that the extent of [(11)C]PK11195 binding depends on intrinsic features of the inflammatory cells.

  15. Sigma-1 Receptor Imaging in the Brain: Cerebral sigma-1 receptors and cognition: Small-animal PET studies using 11C-SA4503

    OpenAIRE

    Kuzhuppilly Ramakrishnan, Nisha

    2014-01-01

    The sigma-1 receptor is a unique orphan receptor, strongly expressed in neurons and glia. Sigma-1 receptors are involved in several central nervous system (CNS) disorders like depression, anxiety, psychosis, schizophrenia, Parkinson’s disease, Alzheimer’s disease, addiction and neuropathic pain. Several CNS drugs like haloperidol, donepezil, rimcazole, fluvoxamine, sertraline and clorgyline have moderate to high sigma-1 receptor affinity. Pharmaceutical companies currently involved in R&D and...

  16. Sigma-1 Receptor Imaging in the Brain : Cerebral sigma-1 receptors and cognition: Small-animal PET studies using 11C-SA4503

    NARCIS (Netherlands)

    Kuzhuppilly Ramakrishnan, Nisha

    2014-01-01

    The sigma-1 receptor is a unique orphan receptor, strongly expressed in neurons and glia. Sigma-1 receptors are involved in several central nervous system (CNS) disorders like depression, anxiety, psychosis, schizophrenia, Parkinson’s disease, Alzheimer’s disease, addiction and neuropathic pain. Sev

  17. Imaging brain plasticity after trauma

    Institute of Scientific and Technical Information of China (English)

    Zhifeng Kou; Armin Iraji

    2014-01-01

    The brain is highly plastic after stroke or epilepsy;however, there is a paucity of brain plasticity investigation after traumatic brain injury (TBI). This mini review summarizes the most recent evidence of brain plasticity in human TBI patients from the perspective of advanced magnetic resonance imaging. Similar to other forms of acquired brain injury, TBI patients also demonstrat-ed both structural reorganization as well as functional compensation by the recruitment of other brain regions. However, the large scale brain network alterations after TBI are still unknown, and the ifeld is still short of proper means on how to guide the choice of TBI rehabilitation or treat-ment plan to promote brain plasticity. The authors also point out the new direction of brain plas-ticity investigation.

  18. Imaging brain plasticity after trauma

    Science.gov (United States)

    Kou, Zhifeng; Iraji, Armin

    2014-01-01

    The brain is highly plastic after stroke or epilepsy; however, there is a paucity of brain plasticity investigation after traumatic brain injury (TBI). This mini review summarizes the most recent evidence of brain plasticity in human TBI patients from the perspective of advanced magnetic resonance imaging. Similar to other forms of acquired brain injury, TBI patients also demonstrated both structural reorganization as well as functional compensation by the recruitment of other brain regions. However, the large scale brain network alterations after TBI are still unknown, and the field is still short of proper means on how to guide the choice of TBI rehabilitation or treatment plan to promote brain plasticity. The authors also point out the new direction of brain plasticity investigation. PMID:25206874

  19. Synthesis and characterization in monkey of [{sup 11}C]SP203 as a radioligand for imaging brain metabotropic glutamate 5 receptors

    Energy Technology Data Exchange (ETDEWEB)

    Simeon, Fabrice G.; Liow, Jeih-San; Zhang, Yi; Hong, Jinsoo; Gladding, Robert L.; Zoghbi, Sami S.; Innis, Robert B.; Pike, Victor W. [National Institutes of Health, Molecular Imaging Branch, National Institute of Mental Health, Bethesda, MD (United States)

    2012-12-15

    [{sup 18}F]SP203 (3-fluoro-5-(2-(2-([{sup 18}F]fluoromethyl)-thiazol-4-yl)ethynyl)benzonitrile) is an effective high-affinity and selective radioligand for imaging metabotropic 5 receptors (mGluR5) in human brain with PET. To provide a radioligand that may be used for more than one scanning session in the same subject in a single day, we set out to label SP203 with shorter-lived {sup 11}C (t{sub 1/2} = 20.4 min) and to characterize its behavior as a radioligand with PET in the monkey. Iodo and bromo precursors were obtained by cross-coupling 2-fluoromethyl-4-((trimethylsilyl)ethynyl)-1,3-thiazole with 3,5-diiodofluorobenzene and 3,5-dibromofluorobenzene, respectively. Treatment of either precursor with [{sup 11}C]cyanide ion rapidly gave [{sup 11}C]SP203, which was purified with high-performance liquid chromatography. PET was used to measure the uptake of radioactivity in brain regions after injecting [{sup 11}C]SP203 intravenously into rhesus monkeys at baseline and under conditions in which mGluR5 were blocked with 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine (MTEP). The emergence of radiometabolites in monkey blood in vitro and in vivo was assessed with radio-HPLC. The stability of [{sup 11}C]SP203 in human blood in vitro was also measured. The iodo precursor gave [{sup 11}C]SP203 in higher radiochemical yield (>98 %) than the bromo precursor (20-52 %). After intravenous administration of [{sup 11}C]SP203 into three rhesus monkeys, radioactivity peaked early in brain (average 12.5 min) with a regional distribution in rank order of expected mGluR5 density. Peak uptake was followed by a steady decline. No radioactivity accumulated in the skull. In monkeys pretreated with MTEP before [{sup 11}C]SP203 administration, radioactivity uptake in brain was again high but then declined more rapidly than in the baseline scan to a common low level. [{sup 11}C]SP203 was unstable in monkey blood in vitro and in vivo, and gave predominantly less lipophilic radiometabolites

  20. Dopamine D1 receptor imaging in the rodent and primate brain using the isoquinoline (+)-[{sup 11}C]A-69024 and positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Besret, L.; Herard, A.S.; Guillermier, M.; Hantraye, P. [CNRS, URA 2210, F-91406 Orsay (France); Dolle, F.; Demphel, S.; Hinnen, F.; Coulon, C.; Ottaviani, M.; Bottlaender, M. [CEA, DSV, I2BM, SHFJ, Lab Imagerie Mol Expt, F-91406 Orsay (France); Herard, A.S.; Guillermier, M.; Hantraye, P. [CEA, DSV, I2BM, Mol Imaging Res Ctr, F-92265 Fontenay Aux Roses (France); Kassiou, M. [Univ Sydney, Discipline Med Radiat Sci, Sydney, NSW 2006 (Australia); Kassiou, M. [Univ Sydney, Brain and Mind Res Inst, Sydney, NSW 2050 (Australia); Kassiou, M. [Univ Sydney, Sch Chem, Sydney, NSW 2006 (Australia)

    2008-07-01

    In vivo pharmacokinetic and brain binding characteristics of (+)-[{sup 11}C]A-69024, a high-affinity-D1-selective dopamine receptor antagonist, were assessed with micro-PET and {beta}-microprobes in the rat and PET in the baboon. The biodistribution of (+)-[{sup 11}C]A-69024 in rats and baboons showed a rapid brain uptake (reaching a maximal value at 5 and 15 min postinjection in rats and baboons, respectively), followed by a slow wash out. The region/cerebellum concentration ratio was characterized by a fourfold higher uptake in striatum and a twofold higher uptake in cortical regions, consistent with in vivo specific binding of the radiotracer in these cerebral regions. Furthermore, this specific (+)-[{sup 11}C]A-69024 binding significantly correlated with the reported in vitro distribution of dopamine D1-receptors. Finally, the specific uptake of the tracer in the striatum and cortical regions was completely prevented by either a pretreatment with large doses of nonradioactive {+-}A-69024 or of the D1-selective antagonist SCH23390, resulting in a similar uptake in the reference region (cerebellum) and in other brain regions. Thus, (+)-[{sup 11}C]A-69024 appears to be a specific and enantioselective radioligand to visualize and quantify brain dopamine D1 receptors in vivo using positron emission tomography. (authors)

  1. Dopamine D2-receptor imaging with [sup 123]I-iodobenzamide SPECT in migraine patients abusing ergotamine: does ergotamine cross the blood brain barrier

    Energy Technology Data Exchange (ETDEWEB)

    Verhoeff, N.P.; Visser, W.H.; Ferrari, M.D.; Saxena, P.R.; Royen, E.A. van (Erasmus Univ., Rotterdam (Netherlands))

    1993-10-01

    Two migraine patients were studied by in vivo SPECT using the dopamine D2-receptor specific radioligand [sup 123]I-3-iodo-6-methoxybenzamide ([sup 123]I-IBZM) during ergotamine abuse and after withdrawal. Results were compared with 15 healthy controls. Striatum/cerebellum and striatum/occipital cortex ratios of count rate density were calculated as a semiquantitative measurement for striatal dopamine D2-receptor binding potential. No differences were found in striatal uptake of [sup 123]I-IBZM between healthy controls and the patients when on or off ergotamine. Preliminary evidence suggests that ergotamine may not occupy striatal dopamine D2-receptors to a large extent and thus may not cross the blood brain barrier in large quantities. 23 refs., 3 figs.

  2. Dopamine D2-receptor imaging with 123I-iodobenzamide SPECT in migraine patients abusing ergotamine: does ergotamine cross the blood brain barrier?

    International Nuclear Information System (INIS)

    Two migraine patients were studied by in vivo SPECT using the dopamine D2-receptor specific radioligand 123I-3-iodo-6-methoxybenzamide (123I-IBZM) during ergotamine abuse and after withdrawal. Results were compared with 15 healthy controls. Striatum/cerebellum and striatum/occipital cortex ratios of count rate density were calculated as a semiquantitative measurement for striatal dopamine D2-receptor binding potential. No differences were found in striatal uptake of 123I-IBZM between healthy controls and the patients when on or off ergotamine. Preliminary evidence suggests that ergotamine may not occupy striatal dopamine D2-receptors to a large extent and thus may not cross the blood brain barrier in large quantities. 23 refs., 3 figs

  3. Functional Brain Imaging: A Comprehensive Survey

    CERN Document Server

    Sarraf, Saman

    2016-01-01

    Functional brain imaging allows measuring dynamic functionality in all brain regions. It is broadly used in clinical cognitive neuroscience as, well as in research. It will allow the observation of neural activities in the brain simultaneously. From the beginning when functional brain imaging was initiated by the mapping of brain functions proposed by phrenologists, many scientists were asking why we need to image brain functionality since we have already structural information. Simply, their important question was including a great answer. Functional information of the human brain would definitely complement structural information, helping to have a better understanding of what is happening in the brain. This paper, which could be useful to those who have an interest in functional brain imaging, such as engineers, will present a quick review of modalities used in functional brain imaging. We will concentrate on the most used techniques in functional imaging which are functional magnetic resonance imaging (fM...

  4. Imaging the Addicted Human Brain

    OpenAIRE

    Fowler, Joanna S.; Volkow, Nora D.; Kassed, Cheryl A; Chang, Linda

    2007-01-01

    Modern imaging techniques enable researchers to observe drug actions and consequences as they occur and persist in the brains of abusing and addicted individuals. This article presents the five most commonly used techniques, explains how each produces images, and describes how researchers interpret them. The authors give examples of key findings illustrating how each technique has extended and deepened our knowledge of the neurobiological bases of drug abuse and addiction, and they address po...

  5. Classification of Medical Brain Images

    Institute of Scientific and Technical Information of China (English)

    Pan Haiwei(潘海为); Li Jianzhong; Zhang Wei

    2003-01-01

    Since brain tumors endanger people's living quality and even their lives, the accuracy of classification becomes more important. Conventional classifying techniques are used to deal with those datasets with characters and numbers. It is difficult, however, to apply them to datasets that include brain images and medical history (alphanumeric data), especially to guarantee the accuracy. For these datasets, this paper combines the knowledge of medical field and improves the traditional decision tree. The new classification algorithm with the direction of the medical knowledge not only adds the interaction with the doctors, but also enhances the quality of classification. The algorithm has been used on real brain CT images and a precious rule has been gained from the experiments. This paper shows that the algorithm works well for real CT data.

  6. Minireview of Stereoselective Brain Imaging

    DEFF Research Database (Denmark)

    Smith, Donald F.; Jakobsen, Steen

    2014-01-01

    Stereoselectivity is a fundamental principle in living systems. Stereoselectivity reflects the dependence of molecular processes on the spatial orientation of constituent atoms. Stereoselective processes govern many aspects of brain function and direct the course of many psychotropic drugs. Today......, modern imaging techniques such as SPECT and PET provide a means for studying stereoselective processes in the living brain. Chemists have prepared numerous radiolabelled stereoisomers for use in SPECT and PET in order to explore various molecular processes in the living brain of anesthetized laboratory...... animals and awake humans. The studies have demonstrated how many aspects of neurotransmission consist of crucial stereoselective events that can affect brain function in health and disease. Here, we present a brief account of those findings in hope of stimulating further interest in the vital topic....

  7. Preclinical evaluation of [{sup 11}C]SA4503. Radiation dosimetry, in vivo selectivity and PET imaging of sigma{sub 1} receptors in the cat brain

    Energy Technology Data Exchange (ETDEWEB)

    Kawamura, Kazunori; Ishiwata, Kiichi; Shimada, Yuhei; Kimura, Yuichi; Senda, Michio [Tokyo Metropolitan Inst. of Gerontology (Japan). Positron Medical Center; Kobayashi, Tadayuki; Matsuno, Kiyoshi; Homma, Yoshio

    2000-08-01

    Our previous in vivo study with rats has demonstrated that {sup 11}C-labeled 1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine ([{sup 11}C]SA4503) is a potential radioligand for mapping central nervous system (CNS) sigma{sub 1} receptors by positron emission tomography (PET). In the present study, we further characterized this ligand. The radiation absorbed-dose of [{sup 11}C]SA4503 in humans estimated with the tissue distribution in mice, was higher in the liver, kidney and pancreas than in other organs studied, but was low enough for clinical use. The brain uptake of [{sup 11}C]SA4503 in mice was reduced to approximately 60-70% by co-injection of carrier SA4503 and haloperidol, but not by co-injection of any of six ligands for sigma{sub 2} or other receptors, for which SA4503 showed in vitro >100 times weaker affinity than for sigma{sub 1} receptor. In the cat brain, the uptake in the cortex was higher than that in the cerebellum. The radioactivity in the cortex and cerebellum accumulated for the first 10 min and then gradually decreased until 81.5 min in the baseline measurement, but rapidly decreased in the carrier-loading condition. The receptor-mediated uptake was estimated to be approximately 60-65% of the total radioactivity in the cortex and cerebellum at 76 min after tracer injection. We have concluded that [{sup 11}C]SA4503 has the potential for mapping sigma{sub 1} receptor by PET. (author)

  8. Brain dopaminergic systems : imaging with positron tomography

    International Nuclear Information System (INIS)

    Imaging of the dopaminergic system in the human brain with the in vivo use of Positron Emission Tomography emerged in the late 1980s as a tool of major importance in clinical neurosciences and pharmacology. The last few years have witnessed rapid development of new radiotracers specific to receptors, reuptake sites and enzymes of the dopamine system; the application of these radiotracers has led to major break-troughs in the pathophysiology and therapy of movement disorders and schizophrenic-like psychoses. This book is the first to collect, in a single volume, state-of-the-art contributions to the various aspects of this research. Its contents address methodological issues related to the design, labelling, quantitative imaging and compartmental modeli-sation of radioligands of the post-synaptic, pre-synaptic and enzyme sites of the dopamine system and to their use in clinical research in the fields of Parkinson's disease as well as other movement disorders, psychoses and neuroleptic receptor occupancy. The chapters were written by leading European scientists in the field of PET, gathered together in Caen (France, November 1990) under the aegis of the EEC Concerted Action on PET Investigations of Cellular Regeneration and Degeneration. This book provides a current and comprehensive overview on PET studies of the brain dopamine system which should aid and interest neurologists , psychiatrists, pharmacologists and medical imaging scientists. (author). refs.; figs.; tabs

  9. Distribution of melatonin receptor in human fetal brain

    Institute of Scientific and Technical Information of China (English)

    WANG Guo-quan; SHAO Fu-yuan; ZHAO Ying; LIU Zhi-min

    2001-01-01

    Objective: To study the distribution of 2 kinds of melatonin receptor subtypes (mtl and MT2) in human fetal brain. Methods: The fetal brain tissues were sliced and the distribution ofmelatonin receptors in human fetal brain were detected using immunohistochemistry and in situ hybridization. Results: Melatonin receptor mtl existed in the cerebellun and hypothalamus, melatonin receptor MT2 exists in hypothalamus, occipital and medulla. Conclusion: Two kinds of melatonin receptors, mtl and MT2 exist in the membrane and cytosol of brain cells, indicating that human fetal brain is a target organ of melatonin.

  10. Brain Imaging in Alzheimer Disease

    Science.gov (United States)

    Johnson, Keith A.; Fox, Nick C.; Sperling, Reisa A.; Klunk, William E.

    2012-01-01

    Imaging has played a variety of roles in the study of Alzheimer disease (AD) over the past four decades. Initially, computed tomography (CT) and then magnetic resonance imaging (MRI) were used diagnostically to rule out other causes of dementia. More recently, a variety of imaging modalities including structural and functional MRI and positron emission tomography (PET) studies of cerebral metabolism with fluoro-deoxy-d-glucose (FDG) and amyloid tracers such as Pittsburgh Compound-B (PiB) have shown characteristic changes in the brains of patients with AD, and in prodromal and even presymptomatic states that can help rule-in the AD pathophysiological process. No one imaging modality can serve all purposes as each have unique strengths and weaknesses. These modalities and their particular utilities are discussed in this article. The challenge for the future will be to combine imaging biomarkers to most efficiently facilitate diagnosis, disease staging, and, most importantly, development of effective disease-modifying therapies. PMID:22474610

  11. Advances in brain imaging of neuropathic pain

    Institute of Scientific and Technical Information of China (English)

    CHEN Fu-yong; TAO Wei; LI Yong-jie

    2008-01-01

    Objective To review the literature on the use of brain imaging,including functional magnetic resonance imaging(fMRI), positron emission tomography(PET),magnetic resonance spectroscopy(MRS)and voxel-based morphometry(VBM)in investigation of the activity in diverse brain regions that creates and modulates chronic neuropathic pain. Data sources English literatures from January 1,2000 to July 31,2007 that examined human brain activity in chronic neuropathic pain were accessed through MEDLINE/CD ROM,using PET,fMRI,VBM,MRS and receptor binding. Study selection Published articles about the application of fMRI,PET,VBM,MRS and chronic neuropathic pain were selected. Data extraction Data were mainly extracted from 40 representative articles as the research basis. Results The PET studies suggested that spontaneous neuropathic pain is associated with changes in thalamic activity. Both PET and fMRI have been used to investigate the substrate of allodynia.The VBM demonstrated that brain structural changes are involved in chronic neuropathic pain,which is not seen in a matched control group.However,the results obtained had a large variety,which may be due to different pain etiology,pain distribution,lesion tomography,symptoms and stimulation procedures. Conclusions Application of the techniques of brain imaging plays a very important role in the study of structural and functional reorganization In patients with neuropathic pain.However,a unique"pain matrix" has not been defined.Future studies should be conducted using a prospective longitudinal research design,which would guarantee the control for many confounding factors.

  12. Fueling and imaging brain activation

    Directory of Open Access Journals (Sweden)

    Gerald A Dienel

    2012-07-01

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

  13. Imaging opiate receptors with positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Frost, J.J.; Dannals, R.F.; Ravert, H.T.; Wilson, A.A.; Wong, D.F.; Links, J.M.; Burns, H.D.; Kuhar, M.J.; Snyder, S.H.; Wagner, H.N. Jr.

    1984-01-01

    Opiate receptors exist in the mammalian brain and are thought to meditate the diverse pharmacological actions of the opiates, such as analgesia, euphoria, and sedation. The 4-carbomethoxyl derivatives of fentanyl, such as lofentanil and R31833 (4-carbomethoxyfentanyl) bind to the opiate receptor with high affinity. C-11 R31833 was synthesized by reacting C-11 methyl iodide with the appropriate carboxylate. Male ICR mice were injected intravenously with C-11 R31833 (5..mu..g/kg), killed 30 minutes later, and the brains rapidly dissected. The thalami, striata, and cerebral cortex are rich in opiate receptors, but the cerebellum contains a very low concentration of opiate receptors. The thalamus/cerebellum and striatum/cerebellum activity ratios, calculated per mg of wet tissue, were 4.1 and 5.2 respectively. Coinjection of 5mg/kg naloxone reduced the ratios to 1.1, which indicates that the preferential localization of C-11 R31833 in the thalami and striata is due to binding to opiate is due to binding to opiate receptors. A 22 kg anesthetized male baboon was imaged using the NeuroECAT after injection of 18.9 mCi of C-11 R13833 (0.50 ..mu..g/kg, specific activity 616 Ci/mmole at time of injection). From 15-70 minutes after injection preferential accumulation of activity could be seen in the thalami, caudate nuclei, and cerebral cortex and, conversely, low activity was demonstrated in the cerebellum. At one hour postinjection the maximum measured caudate/cerebellum activity ratio per pixel was 2.9. For the NeuroECAT the recovery coefficient for the baboon caudate is ca. 0.2-0.3, and therefore the actual caudate/cerebellum ratio is ca. 10-15.

  14. Functional brain imaging; Funktionelle Hirnbildgebung

    Energy Technology Data Exchange (ETDEWEB)

    Gizewski, E.R. [Medizinische Universitaet Innsbruck, Universitaetsklinik fuer Neuroradiologie, Innsbruck (Austria)

    2016-02-15

    Functional magnetic resonance imaging (fMRI) is a non-invasive method that has become one of the major tools for understanding human brain function and in recent years has also been developed for clinical applications. Changes in hemodynamic signals correspond to changes in neuronal activity with good spatial and temporal resolution in fMRI. Using high-field MR systems and increasingly dedicated statistics and postprocessing, activated brain areas can be detected and superimposed on anatomical images. Currently, fMRI data are often combined in multimodal imaging, e. g. with diffusion tensor imaging (DTI) sequences. This method is helping to further understand the physiology of cognitive brain processes and is also being used in a number of clinical applications. In addition to the blood oxygenation level-dependent (BOLD) signals, this article deals with the construction of fMRI investigations, selection of paradigms and evaluation in the clinical routine. Clinically, this method is mainly used in the planning of brain surgery, analyzing the location of brain tumors in relation to eloquent brain areas and the lateralization of language processing. As the BOLD signal is dependent on the strength of the magnetic field as well as other limitations, an overview of recent developments is given. Increases of magnetic field strength (7 T), available head coils and advances in MRI analytical methods have led to constant improvement in fMRI signals and experimental design. Especially the depiction of eloquent brain regions can be done easily and quickly and has become an essential part of presurgical planning. (orig.) [German] Mittlerweile ist die funktionelle MRT (fMRT) eine Methode, die nicht mehr nur in der neurowissenschaftlichen Routine verwendet wird. Die fMRT ermoeglicht die nichtinvasive Darstellung der Hirnaktivitaet in guter raeumlicher und zeitlicher Aufloesung unter Ausnutzung der Durchblutungsaenderung aufgrund der erhoehten Nervenzellaktivitaet. Unter

  15. Automation of the radiosynthesis and purification procedures for [18F]Fluspidine preparation, a new radiotracer for clinical investigations in PET imaging of σ1 receptors in brain

    International Nuclear Information System (INIS)

    The radiosynthesis of [18F]Fluspidine, a potent σ1 receptor imaging probe for pre-clinical/clinical studies, was implemented on a TRACERlabTM FX F-N synthesizer. [18F]2 was synthesized in 15 min at 85 °C starting from its tosylate precursor. Purification via semi-preparative RP-HPLC was investigated using different columns and eluent compositions and was most successful on a polar RP phase with acetonitrile/water buffered with NH4OAc. After solid phase extraction, [18F]Fluspidine was formulated and produced within 59±4 min with an overall radiochemical yield of 37±8%, a radiochemical purity of 99.3±0.5% and high specific activity (176.6±52.0 GBq/µmol). - Highlights: • [18F]Fluspidine is a promising radiotracer for PET imaging of sigma1 receptors. • A fully automated CGMP-oriented radiosynthesis of [18F]Fluspidine is described. • The purification was investigated using different semi-preparative HPLC systems. • [18F]Fluspidine was produced within 59±4 min with a radiochemical yield of 37±8%

  16. Functional brain imaging to investigate the higher brain dysfunction induced by diffuse brain injury

    International Nuclear Information System (INIS)

    Higher brain dysfunction is the major problem of patients who recover from neurotrauma the prevents them from returning to their previous social life. Many such patients do not have focal brain damage detected with morphological imaging. We focused on studying the focal brain dysfunction that can be detected only with functional imaging with positron emission tomography (PET) in relation to the score of various cognition batteries. Patients who complain of higher brain dysfunction without apparent morphological cortical damage were recruited for this study. Thirteen patients with diffuse axonal injury (DAI) or cerebral concussion was included. They underwent a PET study to image glucose metabolism by 18F-fluorodeoxyglucose (FDG), and central benodiazepine receptor (cBZD-R) (marker of neuronal body) by 11C-flumazenil, together with cognition measurement by WAIS-R, WMS-R, and WCST etc. PET data were compared with age matched normal controls using statistical parametric mapping (SPM)2. DAI patients had a significant decrease in glucose matabolism and cBZD-R distribution in the cingulated cortex than normal controls. Patients diagnosed with concussion because of shorter consciousness disturbance also had abnormal FDG uptake and cBZD-R distribution. Cognition test scores were variable among patients. Degree of decreased glucose metabolism and cBZD-R distribution in the dominant hemishphere corresponded well to the severity of cognitive disturbance. PET molecular imaging was useful to depict focal cortical dysfunction of neurotrauma patients even when morphological change was not apparent. This method may be promising to clarify the pathophysiology of higher brain dysfunction of patients with diffuse axonal injury or chronic traumatic encephalopathy. (author)

  17. Brain imaging studies of sleep disorder

    International Nuclear Information System (INIS)

    Brain imaging studies of narcolepsy (NA)/cataplexy (CA), a typical sleep disorder, are summarized together with techniques of functional and structural imaging means. single photon emission CT (SPECT) is based on the distribution of tracers labeled by single photon emitters like 99mTc and 123I for seeing the blood flow and receptors. PET using positron emitters like 15O and 18F for blood flow and for glucose metabolism, respectively, is of higher resolution and more quantitative than SPECT. Functional MRI (fMRI) depicts the cerebral activity through signal difference by blood oxygenation level dependence (BOLD) effect, and MR spectroscopy (MRS) depicts and quantifies biomaterials through the difference of their nuclear chemical shifts in the magnetic field. Morphologic imaging studies involve the measurement of the volume of the region of interest by comparison with the reference region such as the whole brain volume. Voxel-based morphometry (VBM) has changed to its more advanced surface-based analysis (SBA) of T1-enhanced image. Diffusion tensor imaging (DTI) is based on the tissue water diffusion. Functional SPECT/PET studies have suggested the decrease of blood flow and metabolic activity in the hypothalamus (HT) and other related regions at the conscious resting state, and locally increased blood flow in cingulate gyrus (CG) and amygdaloid complex (AC) at affective CA/PA seizure. fMRI has suggested the hypoactivity of HT and hyperactivity of AC at the seizure. VBM-based studies have not given the consistent results, but DTI studies have suggested an important participation of AC at the seizure. (T.T.)

  18. Brain CB2 Receptors: Implications for Neuropsychiatric Disorders

    Directory of Open Access Journals (Sweden)

    Michelle Roche

    2010-08-01

    Full Text Available Although previously thought of as the peripheral cannabinoid receptor, it is now accepted that the CB2 receptor is expressed in the central nervous system on microglia, astrocytes and subpopulations of neurons. Expression of the CB2 receptor in the brain is significantly lower than that of the CB1 receptor. Conflicting findings have been reported on the neurological effects of pharmacological agents targeting the CB2 receptor under normal conditions. Under inflammatory conditions, CB2 receptor expression in the brain is enhanced and CB2 receptor agonists exhibit potent anti-inflammatory effects. These findings have prompted research into the CB2 receptor as a possible target for the treatment of neuroinflammatory and neurodegenerative disorders. Neuroinflammatory alterations are also associated with neuropsychiatric disorders and polymorphisms in the CB2 gene have been reported in depression, eating disorders and schizophrenia. This review will examine the evidence to date for a role of brain CB2 receptors in neuropsychiatric disorders.

  19. Adenosine A{sub 2A} receptor imaging with [{sup 11}C]KF18446 PET in the rat brain after quinolinic acid lesion. Comparison with the dopamine receptor imaging

    Energy Technology Data Exchange (ETDEWEB)

    Ishiwata, Kiichi; Ogi, Nobuo; Hayakawa, Nobutaka [Tokyo Metropolitan Inst. of Gerontology, Tokyo (Japan). Positron Medical Center] [and others

    2002-11-01

    We proposed [{sup 11}C]KF18446 as a selective radioligand for mapping the adenosine A{sub 2A} receptors being highly enriched in the striatum by positron emission tomography (PET). In the present study, we investigated whether [{sup 11}C]KF18446 PET can detect the change in the striatal adenosine A{sub 2A} receptors in the rat after unilateral injection of an excitotoxin quinolinic acid into the striatum, a Huntington's disease model, to demonstrate the usefulness of [{sup 11}C]KF18446. The extent of the striatal lesion was identified based on MRI, to which the PET was co-registered. The binding potential of [{sup 11}C]KF18446 significantly decreased in the quinolinic acid-lesioned striatum. The decrease was comparable to the decrease in the potential of [{sup 11}C] raclopride binding to dopamine D{sub 2} receptors in the lesioned striatum, but seemed to be larger than the decrease in the potential of [{sup 11}C]SCH23390 binding to dopamine D{sub 1} receptors. Ex vivo and in vitro autoradiography validated the PET signals. We concluded that [{sup 11}C]KF18446 PET can detect change in the adenosine A{sub 2A} receptors in the rat model, and will provide a new diagnostic tool for characterizing post-synaptic striatopallidal neurons in the stratum. (author)

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

    Science.gov (United States)

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

    2016-03-01

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

  1. Brain Image Representation and Rendering: A Survey

    Directory of Open Access Journals (Sweden)

    Mudassar Raza

    2012-09-01

    Full Text Available Brain image representation and rendering processes are basically used for evaluation, development and investigation consent experimental examination and formation of brain images of a variety of modalities that includes the major brain types like MEG, EEG, PET, MRI, CT or microscopy. So, there is a need to conduct a study to review the existing work in this area. This paper provides a review of different existing techniques and methods regarding the brain image representation and rendering. Image Rendering is the method of generating an image by means of a model, through computer programs. The basic purpose of brain image representation and rendering processes is to analyze the brain images precisely in order to effectively diagnose and examine the diseases and problems. The basic objective of this study is to evaluate and discuss different techniques and approaches proposed in order to handle different brain imaging types. The paper provides a short overview of different methods, in the form of advantages and limitations, presented in the prospect of brain image representation and rendering along with their sub categories proposed by different authors.

  2. Imaging of cerebritis, encephalitis, and brain abscess.

    Science.gov (United States)

    Rath, Tanya J; Hughes, Marion; Arabi, Mohammad; Shah, Gaurang V

    2012-11-01

    Imaging plays an important role in the diagnosis and treatment of brain abscess, pyogenic infection, and encephalitis. The role of CT and MRI in the diagnosis and management of pyogenic brain abscess and its complications is reviewed. The imaging appearances of several common and select uncommon infectious encephalitides are reviewed. Common causes of encephalitis in immunocompromised patients, and their imaging appearances, are also discussed. When combined with CSF, serologic studies and patient history, imaging findings can suggest the cause of encephalitis. PMID:23122258

  3. Permeability imaging in pediatric brain tumors

    OpenAIRE

    Lam, Sandi; Lin, Yimo; Warnke, Peter C.

    2014-01-01

    While traditional computed tomography (CT) and magnetic resonance (MR) imaging illustrate the structural morphology of brain pathology, newer, dynamic imaging techniques are able to show the movement of contrast throughout the brain parenchyma and across the blood-brain barrier (BBB). These data, in combination with pharmacokinetic models, can be used to investigate BBB permeability, which has wide-ranging applications in the diagnosis and management of central nervous system (CNS) tumors in ...

  4. GABAA receptor downregulation in brains of subjects with autism

    OpenAIRE

    Fatemi, S. Hossein; Reutiman, Teri J.; Folsom, Timothy D.; Thuras, Paul D.

    2008-01-01

    Gamma-aminobutyric acid A (GABAA) receptors are ligand-gated ion channels responsible for mediation of fast inhibitory action of GABA in the brain. Preliminary reports have demonstrated altered expression of GABA receptors in the brains of subjects with autism suggesting GABA/glutamate system dysregulation. We investigated the expression of four GABAA receptor subunits and observed significant reductions in GABRA1, GABRA2, GABRA3, and GABRB3 in parietal cortex (Brodmann's Area 40(BA40)), whil...

  5. Radiopharmaceuticals for single-photon emission computed tomography brain imaging.

    Science.gov (United States)

    Kung, Hank F; Kung, Mei-Ping; Choi, Seok Rye

    2003-01-01

    In the past 10 years, significant progress on the development of new brain-imaging agents for single-photon emission computed tomography has been made. Most of the new radiopharmaceuticals are designed to bind specific neurotransmitter receptor or transporter sites in the central nervous system. Most of the site-specific brain radiopharmaceuticals are labeled with (123)I. Results from imaging of benzodiazepine (gamma-aminobutyric acid) receptors by [(123)I]iomazenil are useful in identifying epileptic seizure foci and changes of this receptor in psychiatric disorders. Imaging of dopamine D2/D3 receptors ([(123)I]iodobenzamide and [(123)I]epidepride) and transporters [(123)I]CIT (2-beta-carboxymethoxy-3-beta(4-iodophenyl)tropane) and [(123)I]FP-beta-CIT (N-propyl-2-beta-carboxymethoxy-3-beta(4-iodophenyl)-nortropane has proven to be a simple but powerful tool for differential diagnosis of Parkinson's and other neurodegenerative diseases. A (99m)Tc-labeled agent, [(99m)Tc]TRODAT (technetium, 2-[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo [3,2,1]oct-2-yl]methyl](2-mercaptoethyl)amino]ethyl]amino] ethanethiolato(3-)]oxo-[1R-(exo-exo)]-), for imaging dopamine transporters in the brain has been successfully applied in the diagnosis of Parkinson's disease. Despite the fact that (123)I radiopharmaceuticals have been widely used in Japan and in Europe, clinical application of (123)I-labeled brain radiopharmaceuticals in the United States is limited because of the difficulties in supplying such agents. Development of (99m)Tc agents will likely extend the application of site-specific brain radiopharmaceuticals for routine applications in aiding the diagnosis and monitoring treatments of various neurologic and psychiatric disorders. PMID:12605353

  6. Positron Emission Tomography (PET Quantification of GABAA Receptors in the Brain of Fragile X Patients.

    Directory of Open Access Journals (Sweden)

    Charlotte D'Hulst

    Full Text Available Over the last several years, evidence has accumulated that the GABAA receptor is compromised in animal models for fragile X syndrome (FXS, a common hereditary form of intellectual disability. In mouse and fly models, agonists of the GABAA receptor were able to rescue specific consequences of the fragile X mutation. Here, we imaged and quantified GABAA receptors in vivo in brain of fragile X patients using Positron Emission Topography (PET and [11C]flumazenil, a known high-affinity and specific ligand for the benzodiazepine site of GABAA receptors. We measured regional GABAA receptor availability in 10 fragile X patients and 10 control subjects. We found a significant reduction of on average 10% in GABAA receptor binding potential throughout the brain in fragile X patients. In the thalamus, the brain region showing the largest difference, the GABAA receptor availability was even reduced with 17%. This is one of the first reports of a PET study of human fragile X brain and directly demonstrates that the GABAA receptor availability is reduced in fragile X patients. The study reinforces previous hypotheses that the GABAA receptor is a potential target for rational pharmacological treatment of fragile X syndrome.

  7. Linking brain imaging signals to visual perception.

    Science.gov (United States)

    Welchman, Andrew E; Kourtzi, Zoe

    2013-11-01

    The rapid advances in brain imaging technology over the past 20 years are affording new insights into cortical processing hierarchies in the human brain. These new data provide a complementary front in seeking to understand the links between perceptual and physiological states. Here we review some of the challenges associated with incorporating brain imaging data into such "linking hypotheses," highlighting some of the considerations needed in brain imaging data acquisition and analysis. We discuss work that has sought to link human brain imaging signals to existing electrophysiological data and opened up new opportunities in studying the neural basis of complex perceptual judgments. We consider a range of approaches when using human functional magnetic resonance imaging to identify brain circuits whose activity changes in a similar manner to perceptual judgments and illustrate these approaches by discussing work that has studied the neural basis of 3D perception and perceptual learning. Finally, we describe approaches that have sought to understand the information content of brain imaging data using machine learning and work that has integrated multimodal data to overcome the limitations associated with individual brain imaging approaches. Together these approaches provide an important route in seeking to understand the links between physiological and psychological states.

  8. Brain MR imaging in dietarily treated phenylketonuria

    Energy Technology Data Exchange (ETDEWEB)

    Breysem, L. [Dept. of Radiology, University Hospitals, Leuven (Belgium); Smet, M.H. [Dept. of Radiology, University Hospitals, Leuven (Belgium); Johannik, K. [Dept. of Radiology, University Hospitals, Leuven (Belgium); Hecke, P. van [Dept. of Radiology, University Hospitals, Leuven (Belgium); Francois, B. [L. Willems Inst., Diepenbeek (Belgium); Wilms, G. [Dept. of Radiology, University Hospitals, Leuven (Belgium); Bosmans, H. [Dept. of Radiology, University Hospitals, Leuven (Belgium); Marchal, G. [Dept. of Radiology, University Hospitals, Leuven (Belgium); Jaeken, J. [Dept. of Pediatrics, University Hospitals, Leuven (Belgium); Demaerel, P. [Dept. of Radiology, University Hospitals, Leuven (Belgium)

    1994-08-01

    Magnetic resonance imaging is the most efficient imaging modality to evaluate brain gray and white matter of patients with metabolic diseases. The main purpose of our study was to investigate the relation between brain MRI abnormalities and the phenylalanine (phe) and tyrosine (tyr) blood levels in 38 phenylketonuria (PKU) patients. Increased periventricular white matter intensity on T2-weighted brain images was the only pathologic finding in 24 patients. Brain MRI abnormalities were scored (4) and correlated with the individual mean phe and phe/tyr levels during 1 year preceding MR examination and with phe tolerance. The residual activity of phenylalanine hydroxylase was defined for each patient by an oral phe tolerance. The appearance of MRI abnormalities on brain T2-weighted images correlates with a threshold mean phe level (averaged over the year preceding the examination). (orig.)

  9. 5-HT radioligands for human brain imaging with PET and SPECT

    DEFF Research Database (Denmark)

    Paterson, Louise M; Kornum, Birgitte R; Nutt, David J;

    2013-01-01

    The serotonergic system plays a key modulatory role in the brain and is the target for many drug treatments for brain disorders either through reuptake blockade or via interactions at the 14 subtypes of 5-HT receptors. This review provides the history and current status of radioligands used...... for positron emission tomography (PET) and single photon emission computerized tomography (SPECT) imaging of human brain serotonin (5-HT) receptors, the 5-HT transporter (SERT), and 5-HT synthesis rate. Currently available radioligands for in vivo brain imaging of the 5-HT system in humans include antagonists...... to image serotonergic targets is of high interest, and successful evaluation in humans is leading to invaluable insight into normal and abnormal brain function, emphasizing the need for continued development of both SPECT and PET radioligands for human brain imaging....

  10. Image Processing Technique for Brain Abnormality Detection

    Directory of Open Access Journals (Sweden)

    Ashraf Anwar

    2013-02-01

    Full Text Available Medical imaging is expensive and very much sophisticated because of proprietary software and expert personalities. This paper introduces an inexpensive, user friendly general-purpose image processing tool and visualization program specifically designed in MATLAB to detect much of the brain disorders as early as possible. The application provides clinical and quantitative analysis of medical images. Minute structural difference of brain gradually results in major disorders such as schizophrenia, Epilepsy, inherited speech and language disorder, Alzheimer's dementia etc. Here the main focusing is given to diagnose the disease related to the brain and its psychic nature (Alzheimer’s disease.

  11. PET imaging reveals brain functional changes in internet gaming disorder

    International Nuclear Information System (INIS)

    Internet gaming disorder is an increasing problem worldwide, resulting in critical academic, social, and occupational impairment. However, the neurobiological mechanism of internet gaming disorder remains unknown. The aim of this study is to assess brain dopamine D2 (D2)/Serotonin 2A (5-HT2A) receptor function and glucose metabolism in the same subjects by positron emission tomography (PET) imaging approach, and investigate whether the correlation exists between D2 receptor and glucose metabolism. Twelve drug-naive adult males who met criteria for internet gaming disorder and 14 matched controls were studied with PET and 11C-N-methylspiperone (11C-NMSP) to assess the availability of D2/5-HT2A receptors and with 18F-fluoro-D-glucose (18F-FDG) to assess regional brain glucose metabolism, a marker of brain function. 11C-NMSP and 18F-FDG PET imaging data were acquired in the same individuals under both resting and internet gaming task states. In internet gaming disorder subjects, a significant decrease in glucose metabolism was observed in the prefrontal, temporal, and limbic systems. Dysregulation of D2 receptors was observed in the striatum, and was correlated to years of overuse. A low level of D2 receptors in the striatum was significantly associated with decreased glucose metabolism in the orbitofrontal cortex. For the first time, we report the evidence that D2 receptor level is significantly associated with glucose metabolism in the same individuals with internet gaming disorder, which indicates that D2/5-HT2A receptor-mediated dysregulation of the orbitofrontal cortex could underlie a mechanism for loss of control and compulsive behavior in internet gaming disorder subjects. (orig.)

  12. PET imaging reveals brain functional changes in internet gaming disorder

    Energy Technology Data Exchange (ETDEWEB)

    Tian, Mei; Zhang, Ying; Du, Fenglei; Hou, Haifeng; Chao, Fangfang; Zhang, Hong [The Second Hospital of Zhejiang University School of Medicine, Department of Nuclear Medicine, Hangzhou, Zhejiang (China); Key Laboratory of Medical Molecular Imaging of Zhejiang Province, Hangzhou (China); Chen, Qiaozhen [The Second Hospital of Zhejiang University School of Medicine, Department of Nuclear Medicine, Hangzhou, Zhejiang (China); The Second Affiliated Hospital of Zhejiang University School of Medicine, Department of Psychiatry, Hangzhou (China)

    2014-07-15

    Internet gaming disorder is an increasing problem worldwide, resulting in critical academic, social, and occupational impairment. However, the neurobiological mechanism of internet gaming disorder remains unknown. The aim of this study is to assess brain dopamine D{sub 2} (D{sub 2})/Serotonin 2A (5-HT{sub 2A}) receptor function and glucose metabolism in the same subjects by positron emission tomography (PET) imaging approach, and investigate whether the correlation exists between D{sub 2} receptor and glucose metabolism. Twelve drug-naive adult males who met criteria for internet gaming disorder and 14 matched controls were studied with PET and {sup 11}C-N-methylspiperone ({sup 11}C-NMSP) to assess the availability of D{sub 2}/5-HT{sub 2A} receptors and with {sup 18}F-fluoro-D-glucose ({sup 18}F-FDG) to assess regional brain glucose metabolism, a marker of brain function. {sup 11}C-NMSP and {sup 18}F-FDG PET imaging data were acquired in the same individuals under both resting and internet gaming task states. In internet gaming disorder subjects, a significant decrease in glucose metabolism was observed in the prefrontal, temporal, and limbic systems. Dysregulation of D{sub 2} receptors was observed in the striatum, and was correlated to years of overuse. A low level of D{sub 2} receptors in the striatum was significantly associated with decreased glucose metabolism in the orbitofrontal cortex. For the first time, we report the evidence that D{sub 2} receptor level is significantly associated with glucose metabolism in the same individuals with internet gaming disorder, which indicates that D{sub 2}/5-HT{sub 2A} receptor-mediated dysregulation of the orbitofrontal cortex could underlie a mechanism for loss of control and compulsive behavior in internet gaming disorder subjects. (orig.)

  13. Brain imaging in type 2 diabetes.

    Science.gov (United States)

    Brundel, Manon; Kappelle, L Jaap; Biessels, Geert Jan

    2014-12-01

    Type 2 diabetes mellitus (T2DM) is associated with cognitive dysfunction and dementia. Brain imaging may provide important clues about underlying processes. This review focuses on the relationship between T2DM and brain abnormalities assessed with different imaging techniques: both structural and functional magnetic resonance imaging (MRI), including diffusion tensor imaging and magnetic resonance spectroscopy, as well as positron emission tomography and single-photon emission computed tomography. Compared to people without diabetes, people with T2DM show slightly more global brain atrophy, which increases gradually over time compared with normal aging. Moreover, vascular lesions are seen more often, particularly lacunar infarcts. The association between T2DM and white matter hyperintensities and microbleeds is less clear. T2DM has been related to diminished cerebral blood flow and cerebrovascular reactivity, particularly in more advanced disease. Diffusion tensor imaging is a promising technique with respect to subtle white matter involvement. Thus, brain imaging studies show that T2DM is associated with both degenerative and vascular brain damage, which develops slowly over the course of many years. The challenge for future studies will be to further unravel the etiology of brain damage in T2DM, and to identify subgroups of patients that will develop distinct progressive brain damage and cognitive decline.

  14. Brain MR imaging in child abuse

    International Nuclear Information System (INIS)

    Intracranial injuries represent the most severe manifestation of child abuse. CT of the brain is the current standard for evaluation of these infants; however, MR imaging offers several potential advantages. MR imaging and CT were performed in ten infants who suffered intracranial trauma owing to child abuse. CT was slightly better at demonstrating subarachnoid hemorrhage and had definite advantages for defining fractures. MR imaging was superior in the demonstration of subacute extraaxial hemorrhage, deep brain injuries owing to shearing effects from shaking, and anoxic injuries. MR imaging has a definite complementary role in the evaluation of acute intracranial trauma in child abuse victims

  15. Imaging neuroreceptors in the human brain in health and disease

    International Nuclear Information System (INIS)

    For nearly a century it has been known that chemical activity accompanies mental activity, but only recently has it been possible to begin to examine its exact nature. Positron-emitting radioactive tracers have made it possible to study the chemistry of the human brain in health and disease, using chiefly cyclotron-produced radionuclides, carbon-11, fluorine-18 and oxygen-15. It is now well established that measurable increases in regional cerebral blood flow, and glucose and oxygen metabolism accompany the mental functions of perception, cognition, emotion and motion. On 25 May 1983 the first imaging of a neuroreceptor in the human brain was accomplished with carbon-11 N-methyl spiperone, a ligand that binds preferentially to dopamine-2 receptors, 80% of which are located in the caudate nucleus and putamen. Quantitative imaging of serotonin-2, opiate, benzodiazapine and muscarinic cholinergic receptors has subsequently been accomplished. In studies of normal men and women, it has been found that dopamine and serotonin receptor activity decreases dramatically with age, such a decrease being more pronounced in men than in women and greater in the case of dopamine-2 receptors than in serotonin-2 receptors. Preliminary studies of patients with neuropsychiatric disorders suggest that dopamine-2 receptor activity is diminished in the caudate nucleus of patients with Huntington's disease. Positron tomography permits a quantitative assay of picomolar quantities of neuroreceptors within the living human brain. Studies of patients with Parkinson's disease, Alzheimer's disease, depression, anxiety, schizophrenia, acute and chronic pain states and drug addiction are now in progress. (author)

  16. Novel optical system for neonatal brain imaging

    Science.gov (United States)

    Chen, Yu; Zhou, Shuoming; Nioka, Shoko; Chance, Britton; Anday, Endla; Ravishankar, Sudha; Delivoria-Papadopoulos, Maria

    1999-03-01

    A highly portable, fast, safe and affordable imaging system that provides interpretable images of brain function in full- and pre-term neonates within a few seconds has been applied to neonates with normal and pathological states. We have used a uniquely sensitive optical tomography system, termed phased array, which has revealed significant functional responses, particularly to parietal stimulation in neonate brain. This system can indicate the blood concentration and oxygenation change during the parietal brain activation in full- and pre-term neonates. The preliminary clinical results, especially a longitudinal study of a cardiac arrest neonate, suggest a variety of future applications.

  17. Risperidone treatment increases CB1 receptor binding in rat brain

    DEFF Research Database (Denmark)

    Secher, Anna; Husum, Henriette; Holst, Birgitte;

    2010-01-01

    BACKGROUND/AIMS: Body weight gain is a common side effect of treatment with antipsychotics, but the mechanisms underlying this weight gain are unknown. Several factors may be involved in antipsychotic-induced body weight gain including the cannabinoid receptor 1 (CB(1)), the serotonin receptor 2C...... positively correlated with visceral fat mass. Risperidone treatment increased CB(1) receptor binding in the arcuate nucleus (40%), hippocampus (25-30%) and amygdala (35%) without concurrent alterations in the CB(1) receptor mRNA. Risperidone treatment increased adiponectin mRNA. CONCLUSION: The present study...... showed that risperidone treatment altered CB(1) receptor binding in the rat brain. Risperidone-induced adiposity and metabolic dysfunction in the clinic may be explained by increased CB(1) receptor density in brain regions involved in appetite and regulation of metabolic function....

  18. Cysteinyl leukotriene receptor 1 partially mediates brain cryoinjury in mice

    Institute of Scientific and Technical Information of China (English)

    Qian DING; San-hua FANG; Yu ZHOU; Li-hui ZHANG; Wei-ping ZHANG; Zhong CHEN; Er-qing WEI

    2007-01-01

    Aim: To determine whether the cysteinyl leukotriene receptor 1 (CysLT1 receptor) modulates brain cryoinjury and whether the CysLT1 receptor antagonist pranlukast exerts a time-dependent protective effect on cryoinjury in mice. Methods: Brain cryoinjury was induced by applying a liquid nitrogen-cooled metal probe to the surface of the skull for 30 s. Brain lesion, neuron density, and endogenous IgG exudation were observed 24 h after cryoinjury. Transcription and the expression of the CysLT1 receptor were detected by RT-PCR and immunoblotting, and the localization of the receptor protein by double immunofluorescence. Results: The mRNA and protein expressions of the CysLT1 receptor were upregulated in the brain 6-24 h after cryoinjury, and the CysLT1 receptor protein was primarily local-ized in the neurons, not in the astrocytes or microglia. Pre-injury treatments with multi-doses and a single dose of pranlukast (0.1 mg/kg) attenuated cryoinjury; postinjury single dose (0.1 mg/kg) at 30 min (not 1 h) after cryoinjury was also effective. Conclusion: The CysLT1 receptor modulates cryoinjury in mice at least partly, and postinjury treatment with its antagonist pranlukast exerts the protec-tive effect with a therapeutic window of 30 min.

  19. Magnetic resonance imaging of brain death

    Energy Technology Data Exchange (ETDEWEB)

    Lee, D.H.; Nathanson, J.A.; Fox, A.J.; Pelz, D.M.; Lownie, S.P.

    1995-06-01

    In order to demonstrate the magnetic resonance imaging (MRI) appearance of the brain in patients with clinical brain death, high-field MRI was performed on 5 patients using conventional T1-weighted and T2-weighted imaging. The study showed MRI exhibited similar features for all of the patients, features which were not found in MRI of comatose patients who were not clinically brain dead. It was stated that up to now the most important limitation in MRI of patients with suspected brain death has been the extreme difficulty of moving them out of the intensive care setting. If this problem can be overcome, and it appears possible with with the advent of MRI-compatible ventilators and noninvasive monitoring, MRI could become an excellent alternative for confirming clinical diagnosis of brain death for such patients. 15 refs., 3 figs.

  20. MRI Brain Image Segmentation based on Thresholding

    Directory of Open Access Journals (Sweden)

    G. Evelin Sujji, Y.V.S. Lakshmi, G. Wiselin Jiji

    2013-03-01

    Full Text Available Medical Image processing is one of the mostchallenging topics in research field. The mainobjective of image segmentation is to extract variousfeatures of the image that are used foranalysing,interpretation and understanding of images.Medical Resonance Image plays a major role inMedical diagnostics. Image processing in MRI ofbrain is highlyessential due to accurate detection ofthe type of brain abnormality which can reduce thechance of fatal result. This paper outlines anefficient image segmentation technique that candistinguish the pathological tissues such asedemaandtumourfrom thenormal tissues such as WhiteMatter(WM,GreyMatter(GM, andCerebrospinal Fluid(CSF. Thresholding is simplerand most commonly used techniques in imagesegmentation. This technique can be used to detectthe contour of thetumourin brain.

  1. Brain and nervous system (image)

    Science.gov (United States)

    ... complicated and interconnected functions of the body and mind. Motor, sensory cognitive and autonomic function are all coordinated and driven by the brain and nerves. As people age, nerve cells deteriorated ...

  2. NIH Conference. Brain imaging: aging and dementia

    International Nuclear Information System (INIS)

    The brain imaging techniques of positron emission tomography using [18F]-fluoro-2-deoxy-D-glucose, and computed tomography, together with neuropsychological tests, were used to examine overall brain function and anatomy in three study populations: healthy men at different ages, patients with presumptive Alzheimer's disease, and adults with Down's syndrome. Brain glucose use did not differ with age, whereas an age-related decrement in gray matter volume was found on computed tomographic assessment in healthy subjects. Memory deficits were found to precede significant reductions in brain glucose utilization in mild to moderate Alzheimer's dementia. Furthermore, differences between language and visuoconstructive impairments in patients with mild to moderate Alzheimer's disease were related to hemispheric asymmetry of brain metabolism. Brain glucose utilization was found to be significantly elevated in young adults with Down's syndrome, compared with controls. The importance of establishing strict criteria for selecting control subjects and patients is explained in relation to the findings

  3. Prolactin transport into mouse brain is independent of prolactin receptor.

    Science.gov (United States)

    Brown, Rosemary S E; Wyatt, Amanda K; Herbison, Ryan E; Knowles, Penelope J; Ladyman, Sharon R; Binart, Nadine; Banks, William A; Grattan, David R

    2016-02-01

    The anterior pituitary hormone prolactin exerts important physiologic actions in the brain. However, the mechanism by which prolactin crosses the blood-brain barrier and enters the brain is not completely understood. On the basis of high expression of the prolactin receptor in the choroid plexus, it has been hypothesized that the receptor may bind to prolactin in the blood and translocate it into the cerebrospinal fluid (CSF). This study aimed to test this hypothesis by investigating transport of (125)I-labeled prolactin ((125)I-prolactin) into the brain of female mice in the presence and absence of the prolactin receptor (PRLR(-/-)). Peripherally administered prolactin rapidly activates brain neurons, as evidenced by prolactin-induced phosphorylation of signal transducer and activator of transcription 5 (pSTAT5) in neurons within 30 min of administration. The transport of prolactin into the brain was saturable, with transport effectively blocked only by a very high dose of unlabeled ovine prolactin. Transport was regulated, as in lactating mice with chronically elevated levels of prolactin, the rate of (125)I-prolactin transport into the brain was significantly increased compared to nonlactating controls. There was no change in the rate of (125)I-prolactin transport into the brain in PRLR(-/-) mice lacking functional prolactin receptors compared to control mice, indicating transport is independent of the prolactin receptor. These data suggest that prolactin transport into the brain involves another as yet unidentified transporter molecule. Because CSF levels of (125)I-prolactin were very low, even up to 90 min after administration, the data suggest that CSF is not the major route by which blood prolactin gains access to neurons in the brain.

  4. Brain Morphometry Using Anatomical Magnetic Resonance Imaging

    Science.gov (United States)

    Bansal, Ravi; Gerber, Andrew J.; Peterson, Bradley S.

    2008-01-01

    The efficacy of anatomical magnetic resonance imaging (MRI) in studying the morphological features of various regions of the brain is described, also providing the steps used in the processing and studying of the images. The ability to correlate these features with several clinical and psychological measures can help in using anatomical MRI to…

  5. New developments in the imaging of brains

    International Nuclear Information System (INIS)

    A review is given for the imaging techniques of brains. Separate paragraphs are devoted to echography, computerized tomography and magnetic resonance imaging. Special attention is payed to new developments such as magnetic resonance spectroscopy used for metabolic processes. (R.B.) 11 refs

  6. Advantages in functional imaging of the brain

    Directory of Open Access Journals (Sweden)

    Walter eMier

    2015-05-01

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

  7. Design, synthesis, radiolabeling and in vivo evaluation of potential positron emission tomography (PET) radioligands for brain imaging of the 5-HT7 receptor

    DEFF Research Database (Denmark)

    Lacivita, Enza; Niso, Mauro; Hansen, Hanne D.;

    2014-01-01

    considered optimal for brain penetration and low non-specific binding. 4-[2-(4-Methoxyphenyl)phenyl]-N-(pyridin-4-ylmethyl)piperazinehexanamide (23a) and N-pyridin-4-ylmethyl-3-[4-[2-(4-methoxyphenyl)phenyl]piperazin-1-yl]ethoxy]propanamide (26a) were radiolabeled on the methoxy group with carbon-11....... Positron emission tomography (PET) analysis revealed that [(11)C]-23a and [(11)C]-26a were P-glycoprotein (P-gp) substrates and rapidly metabolized, resulting in poor brain uptake. These features were not predicted by in vitro tests....

  8. New perspectives on using brain imaging to study CNS stimulants.

    Science.gov (United States)

    Lukas, Scott E

    2014-12-01

    While the recent application of brain imaging to study CNS stimulants has offered new insights into the fundamental factors that contribute to their use and abuse, many gaps remain. Brain circuits that mediate pleasure, dependence, craving and relapse are anatomically, neurophysiologically and neurochemically distinct from one another, which has guided the search for correlates of stimulant-seeking and taking behavior. However, unlike other drugs of abuse, metrics for tolerance and physical dependence on stimulants are not obvious. The dopamine theory of stimulant abuse does not sufficiently explain this disorder as serotonergic, GABAergic and glutamagergic circuits are clearly involved in stimulant pharmacology and so tracking the source of the "addictive" processes must adopt a more multimodal, multidisciplinary approach. To this end, both anatomical and functional magnetic resonance imaging (MRI), MR spectroscopy (MRS) and positron emission tomography (PET) are complementary and have equally contributed to our understanding of how stimulants affect the brain and behavior. New vistas in this area include nanotechnology approaches to deliver small molecules to receptors and use MRI to resolve receptor dynamics. Anatomical and blood flow imaging has yielded data showing that cognitive enhancers might be useful adjuncts in treating CNS stimulant dependence, while MRS has opened opportunities to examine the brain's readiness to accept treatment as GABA tone normalizes after detoxification. A desired outcome of the above approaches is being able to offer evidence-based rationales for treatment approaches that can be implemented in a more broad geographic area, where access to brain imaging facilities may be limited. This article is part of the Special Issue entitled 'CNS Stimulants'.

  9. Perfusion harmonic imaging of the human brain

    Science.gov (United States)

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

    2003-05-01

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

  10. Magnetic resonance imaging of a brain abscess

    International Nuclear Information System (INIS)

    Magnetic resonance imaging (MRI) was performed on 13 patients with brain abscesses, and the alternation of MRI findings, as correlated with the progression of brain-abscess formation, was reviewed. In the cerebritis stage, spin-echo images showed a high intensity, and inversion-recovery images, a low intensity, due to inflammation and edema. The spin-echo images were very sensitive in delineating the brain edema; however, it was difficult to distinguish the inflammation from the surrounding edema. In the capsule stage, due to the accumulation of purulent material, the central necrotic area was demonstrated as a low-intensity area, while the capsule of the abscess was revealed as an iso-intensity ring on the inversion-recovery images. The central necrotic area also decreased in intensity on spin-echo images in the later period of this stage. With contrast enhancement (Gd-DTPA), the SR image showed the capsule as a high-intensity ring. MRI was found to be a useful method for estimating the process of the formation of a brain abscess. (author)

  11. Magnetic resonance imaging of a brain abscess

    Energy Technology Data Exchange (ETDEWEB)

    Oikawa, Akihiro; Kagawa, Mizuo; Yatoh, Seiji; Izawa, Masahiro; Ujiie, Hiroshi; Sakaguchi, Jun; Onda, Hideaki; Kitamura, Kohichi

    1988-06-01

    Magnetic resonance imaging (MRI) was performed on 13 patients with brain abscesses, and the alternation of MRI findings, as correlated with the progression of brain-abscess formation, was reviewed. In the cerebritis stage, spin-echo images showed a high intensity, and inversion-recovery images, a low intensity, due to inflammation and edema. The spin-echo images were very sensitive in delineating the brain edema; however, it was difficult to distinguish the inflammation from the surrounding edema. In the capsule stage, due to the accumulation of purulent material, the central necrotic area was demonstrated as a low-intensity area, while the capsule of the abscess was revealed as an iso-intensity ring on the inversion-recovery images. The central necrotic area also decreased in intensity on spin-echo images in the later period of this stage. With contrast enhancement (Gd-DTPA), the SR image showed the capsule as a high-intensity ring. MRI was found to be a useful method for estimating the process of the formation of a brain abscess.

  12. Brain imaging, genetics and emotion

    NARCIS (Netherlands)

    Aleman, Andre; Swart, Marte; van Rijn, Sophie

    2008-01-01

    This paper reviews the published evidence on genetically driven variation in neurotransmitter function and brain circuits involved in emotion. Several studies point to a role of the serotonin transporter promoter polymorphism in amygdala activation during emotion perception. We also discuss other po

  13. Proton MRS imaging in pediatric brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Zarifi, Maria [Aghia Sophia Children' s Hospital, Department of Radiology, Athens (Greece); Tzika, A.A. [Harvard Medical School, Department of Surgery, Massachusetts General Hospital, Boston, MA (United States); Shriners Burn Hospital, Boston, MA (United States)

    2016-06-15

    Magnetic resonance (MR) techniques offer a noninvasive, non-irradiating yet sensitive approach to diagnosing and monitoring pediatric brain tumors. Proton MR spectroscopy (MRS), as an adjunct to MRI, is being more widely applied to monitor the metabolic aspects of brain cancer. In vivo MRS biomarkers represent a promising advance and may influence treatment choice at both initial diagnosis and follow-up, given the inherent difficulties of sequential biopsies to monitor therapeutic response. When combined with anatomical or other types of imaging, MRS provides unique information regarding biochemistry in inoperable brain tumors and can complement neuropathological data, guide biopsies and enhance insight into therapeutic options. The combination of noninvasively acquired prognostic information and the high-resolution anatomical imaging provided by conventional MRI is expected to surpass molecular analysis and DNA microarray gene profiling, both of which, although promising, depend on invasive biopsy. This review focuses on recent data in the field of MRS in children with brain tumors. (orig.)

  14. The role of the serotonergic system and the effects of antidepressants during brain development examined using in vivo PET imaging and in vitro receptor binding

    OpenAIRE

    Shrestha, Stal Saurav

    2014-01-01

    Serotonin (5-HT) and the serotonergic system, which includes the serotonin transporter (SERT) and the two G protein-coupled 5-HT1A and 5-HT1B receptors, are implicated in the pathophysiology and treatment of several neuropsychiatric disorders including major depressive disorder (MDD) and anxiety. Two classes of antidepressants—selective serotonin reuptake inhibitors (SSRIs), which block SERT, and tricyclic antidepressants (TCAs), which block several monoamine transporters...

  15. Generating text from functional brain images

    Directory of Open Access Journals (Sweden)

    Francisco ePereira

    2011-08-01

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

  16. MR imaging of regional late brain development

    International Nuclear Information System (INIS)

    This paper reports, to complement current knowledge on brain development, late regional brain maturation assessed with quantitative MR imaging. Axial and coronal head spin-echo (SE) images were obtained in 60 healthy individuals aged 5--56 years, with a double-echo, flow compensated imaging sequence obtained with a 1.5-T Magnetom spectroscopy and imaging system. T2-weighted images were calculated from the intensity differences in SE images at echo times (TEs) of 15 and 90 msec (TR = 2.5 second). The mean T2 values were determined at 16 sites in each cerebral hemisphere. T2 values of the six frontal subcortical white matter (FSCWM) sites and of the internal capsule (IC) were evaluated. Mean T2 values in the IC decreased until age 10 years, whereas this decrease continued in the FSCWM past age 15 years before reaching a plateau. Differential age-dependent patterns of mean T2 values emerged between the six FSCWM sites. The spread of T2 values varied at different sites independent of the age of the individuals. T2- values have previously been shown to reflect the status of brain development. The authors' data on the six FSCWM sites and the IC extend these findings to specific substructures of the brain. Interindividual variations and technical issues are responsible for the observed spread of data

  17. IMAGING THE BRAIN AS SCHIZOPHRENIA DEVELOPS: DYNAMIC & GENETIC BRAIN MAPS.

    Science.gov (United States)

    Thompson, Paul; Rapoport, Judith L; Cannon, Tyrone D; Toga, Arthur W

    2002-01-01

    Schizophrenia is a chronic, debilitating psychiatric disorder that affects 0.2-2% of the population worldwide. Often striking without warning in the late teens or early twenties, its symptoms include auditory and visual hallucinations, psychotic outbreaks, bizarre or disordered thinking, depression and social withdrawal. To combat the disease, new antipsychotic drugs are emerging; these atypical neuroleptics target dopamine and serotonin pathways in the brain, offering increased therapeutic efficacy with fewer side effects. Despite their moderate success in controlling some patients' symptoms, little is known about the causes of schizophrenia, and what triggers the disease. Its peculiar age of onset raises key questions: What physical changes occur in the brain as a patient develops schizophrenia? Do these deficits spread in the brain, and can they be opposed? How do they relate to psychotic symptoms? As risk for the disease is genetically transmitted, do a patient's relatives exhibit similar brain changes? Recent advances in brain imaging and genetics provide exciting insight on these questions. Neuroimaging can now chart the emergence and progression of deficits in the brain, providing an exceptionally sharp scalpel to dissect the effects of genetic risk, environmental triggers, and susceptibility genes. Visualizing the dynamics of the disease, these techniques also offer new strategies to evaluate drugs that combat the unrelenting symptoms of schizophrenia.

  18. Four-view spect brain imaging detector

    International Nuclear Information System (INIS)

    This paper reports that with increasing use of single photon radiopharmaceuticals for brain imaging, there is a growing demand for efficient, economical SPECT brain imaging instrumentation. This new multiple view imaging detector design has the sensitivity advantages of an array of four discrete cameras, but functions essentially like a single camera head. Four separate flat crystals are surrounded with PMT's which perform as a single array for photon event detection. Unique windows on adjoining crystal edges are coupled to corner light pipe/PMT assemblies. Reduced edge packing range, and sharing of corner PMT's allows a compact assembly volume, even with 3 inch PMT's. The imaging volume is approximately a 23 centimeter cube, and the imaging electronics are nearly the same as used in a single 64 PMT gamma camera

  19. Nicotinic α4β2 receptor imaging agents

    International Nuclear Information System (INIS)

    The α4β2 nicotinic acetylcholine receptor (nAChR) has been implicated in various neurodegenerative diseases. Optimal positron emission tomography (PET) imaging agents are therefore highly desired for this receptor. We report here the development and initial evaluation of 2-fluoro-3-[2-((S)-3-pyrrolinyl)methoxy]pyridine (nifene). In vitro binding affinity of nifene in rat brain homogenate using 3H-cytisine exhibited a K i=0.50 nM for the α4β2 sites. The radiosynthesis of 2-18F-fluoro-3-[2-((S)-3-pyrrolinyl)methoxy]pyridine (18F-nifene) was accomplished in 2.5 h with an overall radiochemical yield of 40-50%, decay corrected. The specific activity was estimated to be approx. 37-185 GBq/μmol. In vitro autoradiography in rat brain slices indicated selective binding of 18F-nifene to anteroventral thalamic (AVT) nucleus, thalamus, subiculum, striata, cortex and other regions consistent with α4β2 receptor distribution. Rat cerebellum showed some binding, whereas regions in the hippocampus had the lowest binding. The highest ratio of >13 between AVT and cerebellum was measured for 18F-nifene in rat brain slices. The specific binding was reduced (>95%) by 300 μM nicotine in these brain regions. Positron emission tomography imaging study of 18F-nifene (130 MBq) in anesthetized rhesus monkey was carried out using an ECAT EXACT HR+ scanner. PET study showed selective maximal uptake in the regions of the anterior medial thalamus, ventro-lateral thalamus, lateral geniculate, cingulate gyrus, temporal cortex including the subiculum. The cerebellum in the monkeys showed lower binding than the other regions. Thalamus-to-cerebellum ratio peaked at 30-35 min postinjection to a value of 2.2 and subsequently reduced. The faster binding profile of 18F-nifene indicates promise as a PET imaging agent and thus needs further evaluation

  20. Brain 'imaging' in the Renaissance.

    Science.gov (United States)

    Paluzzi, Alessandro; Belli, Antonio; Bain, Peter; Viva, Laura

    2007-12-01

    During the Renaissance, a period of 'rebirth' for humanities and science, new knowledge and speculation began to emerge about the function of the human body, replacing ancient religious and philosophical dogma. The brain must have been a fascinating mystery to a Renaissance artist, but some speculation existed at that time on the function of its parts. Here we show how revived interest in anatomy and life sciences may have influenced the figurative work of Italian and Flemish masters, such as Rafael, Michelangelo and David. We present a historical perspective on the artists and the period in which they lived, their fascination for human anatomy and its symbolic use in their art. Prior to the 16th century, knowledge of the brain was limited and influenced in a dogmatic way by the teachings of Galen(1) who, as we now know, conducted his anatomical studies not on humans but on animals.(2) Nemesus, Bishop of Emesa, in around the year 400 was one of the first to attribute mental faculties to the brain, specifically to the ventricles. He identified two anterior (lateral) ventricles, to which he assigned perception, a middle ventricle responsible for cognition and a posterior ventricle for memory.(2,3) After a long period of stasis in the Middle Ages, Renaissance scholars realized the importance of making direct observations on dissected cadavers. Between 1504 and 1507, Leonardo da Vinci conducted experiments to reveal the anatomy of the ventricular system in the brain. He injected hot wax through a tube thrust into the ventricular cavities of an ox and then scraped the overlying brain off, thus obtaining, in a simple but ingenious way, an accurate cast of the ventricles.(2,4) Leonardo shared the belief promoted by scholarly Christians that the ventricles were the abode of rational soul. We have several examples of hidden symbolism in Renaissance paintings, but the influence of phrenology and this rudimentary knowledge of neuroanatomy on artists of that period is under

  1. Functional brain imaging - baric and clinical questions

    International Nuclear Information System (INIS)

    The advancing biological knowledge of disease processes plays a central part in the progress of modern psychiatry. An essential contribution comes from the functional and structural brain imaging techniques (CT, MRI, SPECT, PET). Their application is important for biological oriented research in psychiatry and there is also a growing relevance in clinical aspects. This development is taken into account by recent diagnostic classification systems in psychiatry. The capabilities and limitations of functional brain imaging in the context of research and clinic will be presented and discussed by examples and own investigations. (orig.)

  2. Somatostatin receptor imaging in patients with sarcoidosis

    International Nuclear Information System (INIS)

    Granulomatous diseases can be visualized in vivo after the injection of indium-111-DTPA-octreotide (111In-pentetreotide), a radiolabelled somatostatin analogue. We evaluated whether somatostatin receptor imaging reflects disease activity, whether certain scintigraphic characteristics can predict the disease prognosis and whether repeat scintigraphy correlates with the clinical course in patients with sarcoidosis. 111In-pentetreotide was injected in 46 patients and images were obtained 24 h later. Known mediastinal, hilar and interstitial disease was recognized in 36 of 37 patients. Also, such pathology was found in seven other patients who had normal chest X-rays. In five of these, somatostatin receptor imaging pointed to interstitial disease. Frequently, accumulation of radioactivity in parotid glands and supraclavicular lymph nodes was found. Neither the degree of radioactive accumulation in the thorax nor a specific pattern of pathological uptake was correlated with disease severity or clinical course. The degree of uptake of radioactivity in the parotid glands was correlated with significantly higher serum angiotensin-converting enzyme (ACE) levels. Somatostatin receptor imaging was repeated in 13 patients. In five of six patients in whom chest X-ray monitored improvement of disease activity, the pentetreotide scintigram also showed a decrease in pathological uptake. In two of five patients in whom the chest X-ray was unchanged, but serum ACE concentrations had decreased and lung function improved, normalization on pentetreotide scintigrams was found. It is concluded that: (1) somatostatin receptor imaging can demonstrate active granulomatous disease in patients with sarcoidosis; (2) pathological uptake of radioactivity in the parotid glands during somatostatin receptor imaging is correlated with higher serum ACE concentrations; (3) the value of somatostatin receptor imaging in the follow-up of patients with sarcoidosis will have to be determined in a

  3. Single nanoparticle tracking of [Formula: see text]-methyl-d-aspartate receptors in cultured and intact brain tissue.

    Science.gov (United States)

    Varela, Juan A; Ferreira, Joana S; Dupuis, Julien P; Durand, Pauline; Bouchet, Delphine; Groc, Laurent

    2016-10-01

    Recent developments in single-molecule imaging have revealed many biological mechanisms, providing high spatial and temporal resolution maps of molecular events. In neurobiology, these techniques unveiled that plasma membrane neurotransmitter receptors and transporters laterally diffuse at the surface of cultured brain cells. The photostability of bright nanoprobes, such as quantum dots (QDs), has given access to neurotransmitter receptor tracking over long periods of time with a high spatial resolution. However, our knowledge has been restricted to cultured systems, i.e., neurons and organotypic slices, therefore lacking several aspects of the intact brain rheology and connectivity. Here, we used QDs to track single glutamatergic [Formula: see text]-methyl-d-aspartate receptors (NMDAR) in acute brain slices. By delivering functionalized nanoparticles in vivo through intraventricular injections to rats expressing genetically engineered-tagged NMDAR, we successfully tracked the receptors in native brain tissue. Comparing NMDAR tracking to different classical brain preparations (acute brain slices, cultured organotypic brain slices, and cultured neurons) revealed that the surface diffusion properties shared several features and are also influenced by the nature of the extracellular environment. Together, we describe the experimental procedures to track plasma membrane NMDAR in dissociated and native brain tissue, paving the way for investigations aiming at characterizing receptor diffusion biophysics in intact tissue and exploring the physiopathological roles of receptor surface dynamics. PMID:27429996

  4. Positron emission tomography imaging studies of dopamine receptors in primate models of addiction

    OpenAIRE

    Nader, Michael A.; Czoty, Paul W; Gould, Robert W.; Riddick, Natallia V.

    2008-01-01

    Animal models have provided valuable information related to trait and state variables associated with vulnerability to drug addiction. Our brain imaging studies in monkeys have implicated D2 receptors in cocaine addiction. For example, an inverse relationship between D2 receptor availability and rates of cocaine self-administration has been documented. Moreover, environmental variables, such as those associated with formation of the social hierarchy, can impact receptor availability and sensi...

  5. Transferrin receptor-targeted theranostic gold nanoparticles for photosensitizer delivery in brain tumors

    Science.gov (United States)

    Dixit, Suraj; Novak, Thomas; Miller, Kayla; Zhu, Yun; Kenney, Malcolm E.; Broome, Ann-Marie

    2015-01-01

    Therapeutic drug delivery across the blood-brain barrier (BBB) is not only inefficient, but also nonspecific to brain stroma. These are major limitations in the effective treatment of brain cancer. Transferrin peptide (Tfpep) targeted gold nanoparticles (Tfpep-Au NPs) loaded with the photodynamic pro-drug, Pc 4, have been designed and compared with untargeted Au NPs for delivery of the photosensitizer to brain cancer cell lines. In vitro studies of human glioma cancer lines (LN229 and U87) overexpressing the transferrin receptor (TfR) show a significant increase in cellular uptake for targeted conjugates as compared to untargeted particles. Pc 4 delivered from Tfpep-Au NPs clusters within vesicles after targeting with the Tfpep. Pc 4 continues to accumulate over a 4 hour period. Our work suggests that TfR-targeted Au NPs may have important therapeutic implications for delivering brain tumor therapies and/or providing a platform for noninvasive imaging.

  6. Image reconstruction for brain CT slices

    Institute of Scientific and Technical Information of China (English)

    吴建明; 施鹏飞

    2004-01-01

    Different modalities in biomedical images, like CT, MRI and PET scanners, provide detailed cross-sectional views of human anatomy. This paper introduces three-dimensional brain reconstruction based on CT slices. It contains filtering, fuzzy segmentation, matching method of contours, cell array structure and image animation. Experimental results have shown its validity. The innovation is matching method of contours and fuzzy segmentation algorithm of CT slices.

  7. Simultaneous imaging of MR angiographic image and brain surface image using steady-state free precession

    Energy Technology Data Exchange (ETDEWEB)

    Takane, Atsushi; Tsuda, Munetaka (Hitachi Ltd., Katsuta, Ibaraki (Japan)); Koizumi, Hideaki; Koyama, Susumu; Yoshida, Takeyuki

    1993-09-01

    Synthesis of a brain surface image and an angiographic image representing brain surface vasculatures can be useful for pre-operational contemplation of brain surgery. Both brain surface images and brain surface vasculature images were successfully acquired simultaneously utilizing both FID signals and time-reversed FID signals created under steady-state free precession (SSFP). This simultaneous imaging method has several advantages. No positional discrepancies between both images and prolongation of scan time are anticipated because of concurrent acquisition of the two kinds of image data. Superimposition and stereo-display of both images enable understanding of their spatial relationship, and therefore afford a useful means for pre-operational simulation of brain surgery. (author).

  8. Imaging receptor changes in human drug abusers.

    Science.gov (United States)

    Cosgrove, Kelly P

    2010-01-01

    This chapter will review the literature on differences in the brain chemistry of alcohol- and drug-dependent individuals compared to healthy controls as measured with positron emission tomography and single photon emission computed tomography. Specifically, alterations in dopamine, serotonin, opioid, and GABA systems in cocaine, alcohol, nicotine, and heroin dependence have been examined. These neurochemical systems are integrated and play significant roles in a final common pathway mediating addiction in the brain. One recurrent finding is that dopaminergic dysfunction is prevalent in both alcohol and drug dependent populations, and specifically there is a lower availability of dopamine type 2/3 receptors in cocaine-, alcohol-, nicotine-, and heroin-dependent individuals compared to healthy controls. The development of novel radiotracers that target additional receptor systems will further our understanding of the neurochemical basis of addiction. PMID:21161754

  9. Kappa-opioid receptor signaling and brain reward function

    OpenAIRE

    Bruijnzeel, Adrie W.

    2009-01-01

    The dynorphin-like peptides have profound effects on the state of the brain reward system and human and animal behavior. The dynorphin-like peptides affect locomotor activity, food intake, sexual behavior, anxiety-like behavior, and drug intake. Stimulation of kappa-opioid receptors, the endogenous receptor for the dynorphin-like peptides, inhibits dopamine release in the striatum (nucleus accumbens and caudate putamen) and induces a negative mood state in humans and animals. The administrati...

  10. Imaging biomarkers in primary brain tumours

    Energy Technology Data Exchange (ETDEWEB)

    Lopci, Egesta; Chiti, Arturo [Humanitas Clinical and Research Center, Nuclear Medicine Department, Rozzano, MI (Italy); Franzese, Ciro; Navarria, Pierina; Scorsetti, Marta [Humanitas Clinical and Research Center, Radiosurgery and Radiotherapy, Rozzano, MI (Italy); Grimaldi, Marco [Humanitas Clinical and Research Center, Radiology, Rozzano, MI (Italy); Zucali, Paolo Andrea; Simonelli, Matteo [Humanitas Clinical and Research Center, Medical Oncology, Rozzano, MI (Italy); Bello, Lorenzo [Humanitas Clinical and Research Center, Neurosurgery, Rozzano, MI (Italy)

    2015-04-01

    We are getting used to referring to instrumentally detectable biological features in medical language as ''imaging biomarkers''. These two terms combined reflect the evolution of medical imaging during recent decades, and conceptually comprise the principle of noninvasive detection of internal processes that can become targets for supplementary therapeutic strategies. These targets in oncology include those biological pathways that are associated with several tumour features including independence from growth and growth-inhibitory signals, avoidance of apoptosis and immune system control, unlimited potential for replication, self-sufficiency in vascular supply and neoangiogenesis, acquired tissue invasiveness and metastatic diffusion. Concerning brain tumours, there have been major improvements in neurosurgical techniques and radiotherapy planning, and developments of novel target drugs, thus increasing the need for reproducible, noninvasive, quantitative imaging biomarkers. However, in this context, conventional radiological criteria may be inappropriate to determine the best therapeutic option and subsequently to assess response to therapy. Integration of molecular imaging for the evaluation of brain tumours has for this reason become necessary, and an important role in this setting is played by imaging biomarkers in PET and MRI. In the current review, we describe most relevant techniques and biomarkers used for imaging primary brain tumours in clinical practice, and discuss potential future developments from the experimental context. (orig.)

  11. Imaging biomarkers in primary brain tumours

    International Nuclear Information System (INIS)

    We are getting used to referring to instrumentally detectable biological features in medical language as ''imaging biomarkers''. These two terms combined reflect the evolution of medical imaging during recent decades, and conceptually comprise the principle of noninvasive detection of internal processes that can become targets for supplementary therapeutic strategies. These targets in oncology include those biological pathways that are associated with several tumour features including independence from growth and growth-inhibitory signals, avoidance of apoptosis and immune system control, unlimited potential for replication, self-sufficiency in vascular supply and neoangiogenesis, acquired tissue invasiveness and metastatic diffusion. Concerning brain tumours, there have been major improvements in neurosurgical techniques and radiotherapy planning, and developments of novel target drugs, thus increasing the need for reproducible, noninvasive, quantitative imaging biomarkers. However, in this context, conventional radiological criteria may be inappropriate to determine the best therapeutic option and subsequently to assess response to therapy. Integration of molecular imaging for the evaluation of brain tumours has for this reason become necessary, and an important role in this setting is played by imaging biomarkers in PET and MRI. In the current review, we describe most relevant techniques and biomarkers used for imaging primary brain tumours in clinical practice, and discuss potential future developments from the experimental context. (orig.)

  12. Modelling Brain Tissue using Magnetic Resonance Imaging

    DEFF Research Database (Denmark)

    Dyrby, Tim Bjørn

    2008-01-01

    Diffusion MRI, or diffusion weighted imaging (DWI), is a technique that measures the restricted diffusion of water molecules within brain tissue. Different reconstruction methods quantify water-diffusion anisotropy in the intra- and extra-cellular spaces of the neural environment. Fibre tracking...... be used. Within a two year period, no statistical inter- or intra-brain difference in the diffusion coefficient was found in perfusion fixated minipig brains. However, a decreasing tendency in the diffusion coefficient was found at the last time points about 24 months post mortem and might be explained...... experiment. This includes the selection of independent anatomical data to be used to derive a gold standard, the selection of a gyrated animal model in place of the human brain, objective selection of the seed region to initiate, and a waypoint region to constrain the tractography results....

  13. Brain Imaging Studies of Developmental Stuttering.

    Science.gov (United States)

    Ingham, Roger J.

    2001-01-01

    A review of research on brain imaging of developmental stuttering concludes that findings increasingly point to a failure of normal temporal lobe activation during speech that may either contribute to (or is the result of) a breakdown in the sequencing of processing among premotor regions implicated in phonologic planning. (Contains references.)…

  14. Analysis of Dynamic Brain Imaging Data

    CERN Document Server

    Mitra, P

    1998-01-01

    Modern imaging techniques for probing brain function, including functional Magnetic Resonance Imaging, intrinsic and extrinsic contrast optical imaging, and magnetoencephalography, generate large data sets with complex content. In this paper we develop appropriate techniques of analysis and visualization of such imaging data, in order to separate the signal from the noise, as well as to characterize the signal. The techniques developed fall into the general category of multivariate time series analysis, and in particular we extensively use the multitaper framework of spectral analysis. We develop specific protocols for the analysis of fMRI, optical imaging and MEG data, and illustrate the techniques by applications to real data sets generated by these imaging modalities. In general, the analysis protocols involve two distinct stages: `noise' characterization and suppression, and `signal' characterization and visualization. An important general conclusion of our study is the utility of a frequency-based repres...

  15. MR imaging of acute hemorrhagic brain infarction

    International Nuclear Information System (INIS)

    Six patients with acute hemorrhagic brain infarct were imaged using spin-echo (SE) pulse sequences on a 1.5 Tesla MR scanner. Including two patients with repeated MR imaging, a total of eight examinations, all performed within 15 days after stroke, were analyzed retrospectively. Four patients revealed massive hemorrhages in the basal ganglia or cerebellum and three cases demonstrated multiple linear hemorrhages in the cerebral cortex. On T1-weighted images, hemorrhages were either mildly or definitely hyperintense relative to gray matter, while varied from mildly hypointense to hyperintense on T2-weighted images. T1-weighted images were superior to T2-weighted images in detection of hemorrhgage. CT failed to detect hemorrhage in two of five cases: indicative of MR superiority to CT in the diagnosis of acute hemorrhagic infarcts. (author)

  16. MR imaging of acute hemorrhagic brain infarction

    Energy Technology Data Exchange (ETDEWEB)

    Uchino, Akira; Ohnari, Norihiro; Ohno, Masato (Kyushu Rosai Hospital, Fukuoka (Japan))

    1989-11-01

    Six patients with acute hemorrhagic brain infarct were imaged using spin-echo (SE) pulse sequences on a 1.5 Tesla MR scanner. Including two patients with repeated MR imaging, a total of eight examinations, all performed within 15 days after stroke, were analyzed retrospectively. Four patients revealed massive hemorrhages in the basal ganglia or cerebellum and three cases demonstrated multiple linear hemorrhages in the cerebral cortex. On T1-weighted images, hemorrhages were either mildly or definitely hyperintense relative to gray matter, while varied from mildly hypointense to hyperintense on T2-weighted images. T1-weighted images were superior to T2-weighted images in detection of hemorrhgage. CT failed to detect hemorrhage in two of five cases: indicative of MR superiority to CT in the diagnosis of acute hemorrhagic infarcts. (author).

  17. Three-dimensional reconstruction of functional brain images

    International Nuclear Information System (INIS)

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

  18. Three-dimensional reconstruction of functional brain images

    Energy Technology Data Exchange (ETDEWEB)

    Inoue, Masato; Shoji, Kazuhiko; Kojima, Hisayoshi; Hirano, Shigeru; Naito, Yasushi; Honjo, Iwao [Kyoto Univ. (Japan)

    1999-08-01

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

  19. Fast optical imaging of human brain function

    Directory of Open Access Journals (Sweden)

    Gabriele Gratton

    2010-06-01

    Full Text Available Great advancements in brain imaging during the last few decades have opened a large number of new possibilities for neuroscientists. The most dominant methodologies (electrophysiological and magnetic resonance-based methods emphasize temporal and spatial information, respectively. However, theorizing about brain function has recently emphasized the importance of rapid (within 100 ms or so interactions between different elements of complex neuronal networks. Fast optical imaging, and in particular the event-related optical signal (EROS, a technology that has emerged over the last 15 years may provide descriptions of localized (to sub-cm level brain activity with a temporal resolution of less than 100 ms. The main limitations of EROS are its limited penetration, which allows us to image cortical structures not deeper than 3 cm from the surface of the head, and its low signal-to-noise ratio. Advantages include the fact that EROS is compatible with most other imaging methods, including electrophysiological, magnetic resonance, and trans-cranial magnetic stimulation techniques, with which can be recorded concurrently. In this paper we present a summary of the research that has been conducted so far on fast optical imaging, including evidence for the possibility of recording neuronal signals with this method, the properties of the signals, and various examples of applications to the study of human cognitive neuroscience. Extant issues, controversies, and possible future developments are also discussed.

  20. Profiling neurotransmitter receptor expression in the Ambystoma mexicanum brain.

    Science.gov (United States)

    Reyes-Ruiz, Jorge Mauricio; Limon, Agenor; Korn, Matthew J; Nakamura, Paul A; Shirkey, Nicole J; Wong, Jamie K; Miledi, Ricardo

    2013-03-22

    Ability to regenerate limbs and central nervous system (CNS) is unique to few vertebrates, most notably the axolotl (Ambystoma sp.). However, despite the fact the neurotransmitter receptors are involved in axonal regeneration, little is known regarding its expression profile. In this project, RT-PCR and qPCR were performed to gain insight into the neurotransmitter receptors present in Ambystoma. Its functional ability was studied by expressing axolotl receptors in Xenopus laevis oocytes by either injection of mRNA or by direct microtransplantation of brain membranes. Oocytes injected with axolotl mRNA expressed ionotropic receptors activated by GABA, aspartate+glycine and kainate, as well as metabotropic receptors activated by acetylcholine and glutamate. Interestingly, we did not see responses following the application of serotonin. Membranes from the axolotl brain were efficiently microtransplanted into Xenopus oocytes and two types of native GABA receptors that differed in the temporal course of their responses and affinities to GABA were observed. Results of this study are necessary for further characterization of axolotl neurotransmitter receptors and may be useful for guiding experiments aimed at understanding activity-dependant limb and CNS regeneration.

  1. Thresholding magnetic resonance images of human brain

    Institute of Scientific and Technical Information of China (English)

    Qing-mao HU; Wieslaw L NOWINSKI

    2005-01-01

    In this paper, methods are proposed and validated to determine low and high thresholds to segment out gray matter and white matter for MR images of different pulse sequences of human brain. First, a two-dimensional reference image is determined to represent the intensity characteristics of the original three-dimensional data. Then a region of interest of the reference image is determined where brain tissues are present. The non-supervised fuzzy c-means clustering is employed to determine: the threshold for obtaining head mask, the low threshold for T2-weighted and PD-weighted images, and the high threshold for T1-weighted, SPGR and FLAIR images. Supervised range-constrained thresholding is employed to determine the low threshold for T1-weighted, SPGR and FLAIR images. Thresholding based on pairs of boundary pixels is proposed to determine the high threshold for T2- and PD-weighted images. Quantification against public data sets with various noise and inhomogeneity levels shows that the proposed methods can yield segmentation robust to noise and intensity inhomogeneity. Qualitatively the proposed methods work well with real clinical data.

  2. Visceral Afferent Pathways and Functional Brain Imaging

    Directory of Open Access Journals (Sweden)

    Stuart W.G. Derbyshire

    2003-01-01

    Full Text Available The application of functional imaging to study painful sensations has generated considerable interest regarding insight into brain dysfunction that may be responsible for functional pain such as that suffered in patients with irritable bowel syndrome (IBS. This review provides a brief introduction to the development of brain science as it relates to pain processing and a snapshot of recent functional imaging results with somatic and visceral pain. Particular emphasis is placed on current hypotheses regarding dysfunction of the brain-gut axis in IBS patients. There are clear and interpretable differences in brain activation following somatic as compared with visceral noxious sensation. Noxious visceral distension, particularly of the lower gastrointestinal tract, activates regions associated with unpleasant affect and autonomic responses. Noxious somatic sensation, in contrast, activates regions associated with cognition and skeletomotor responses. Differences between IBS patients and control subjects, however, were far less clear and interpretable. While this is in part due to the newness of this field, it also reflects weaknesses inherent within the current understanding of IBS. Future use of functional imaging to examine IBS and other functional disorders will be more likely to succeed by describing clear theoretical and clinical endpoints.

  3. MR imaging of the fetal brain

    Energy Technology Data Exchange (ETDEWEB)

    Glenn, Orit A. [University of California, San Francisco, Department of Radiology, Neuroradiology Section, San Francisco, CA (United States)

    2010-01-15

    Fetal MRI is clinically performed to evaluate the brain in cases where an abnormality is detected by prenatal sonography. These most commonly include ventriculomegaly, abnormalities of the corpus callosum, and abnormalities of the posterior fossa. Fetal MRI is also increasingly performed to evaluate fetuses who have normal brain findings on prenatal sonogram but who are at increased risk for neurodevelopmental abnormalities, such as complicated monochorionic twin pregnancies. This paper will briefly discuss the common clinical conditions imaged by fetal MRI as well as recent advances in fetal MRI research. (orig.)

  4. Characteristics of muscarinic acetylcholine receptors in rat brain.

    Directory of Open Access Journals (Sweden)

    Nukina,Itaru

    1983-06-01

    Full Text Available Characteristics of muscarinic acetylcholine (ACh receptors were studied in the rat central nervous system (CNS using 3H-quinuclidinyl benzilate (QNB, an antagonist of muscarinic ACh receptors. Scatchard analysis indicated that the rat CNS had a single 3H-QNB binding site with an apparent dissociation constant (Kd of 5.0 X 10(-10 M. Li+, Zn++ and Cu++ had strong effects on 3H-QNB binding which indicates that these metal ions might play important roles at muscarinic ACh receptor sites in the brain. Since antidepressants and antischizophrenic drugs displaced the binding of 3H-QNB, the anticholinergic effects of these drugs need to be taken into account when they are applied clinically. The muscarinic ACh receptor was successfully solubilized with lysophosphatidylcholine. By gel chromatography, with a Sepharose 6B column, the solubilized muscarinic ACh receptor molecule eluted at the fraction corresponding to a Stokes' radius of 6.1 nm. With the use of sucrose-density-gradient centrifugation, the molecular weight of the solubilized muscarinic ACh receptor was determined to be about 90,000 daltons. The regional distribution of 3H-QNB binding in rat brain was examined, and the highest level of 3H-QNB binding was found to be in the striatum followed by cerebral cortex and hippocampus, indicating that muscarinic ACh mechanisms affect CNS function mainly through these areas.

  5. Repeated swim stress alters brain benzodiazepine receptors measured in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Weizman, R.; Weizman, A.; Kook, K.A.; Vocci, F.; Deutsch, S.I.; Paul, S.M.

    1989-06-01

    The effects of repeated swim stress on brain benzodiazepine receptors were examined in the mouse using both an in vivo and in vitro binding method. Specific in vivo binding of (/sup 3/H)Ro15-1788 to benzodiazepine receptors was decreased in the hippocampus, cerebral cortex, hypothalamus, midbrain and striatum after repeated swim stress (7 consecutive days of daily swim stress) when compared to nonstressed mice. In vivo benzodiazepine receptor binding was unaltered after repeated swim stress in the cerebellum and pons medulla. The stress-induced reduction in in vivo benzodiazepine receptor binding did not appear to be due to altered cerebral blood flow or to an alteration in benzodiazepine metabolism or biodistribution because there was no difference in (14C)iodoantipyrine distribution or whole brain concentrations of clonazepam after repeated swim stress. Saturation binding experiments revealed a change in both apparent maximal binding capacity and affinity after repeated swim stress. Moreover, a reduction in clonazepam's anticonvulsant potency was also observed after repeated swim stress (an increase in the ED50 dose for protection against pentylenetetrazol-induced seizures), although there was no difference in pentylenetetrazol-induced seizure threshold between the two groups. In contrast to the results obtained in vivo, no change in benzodiazepine receptor binding kinetics was observed using the in vitro binding method. These data suggest that environmental stress can alter the binding parameters of the benzodiazepine receptor and that the in vivo and in vitro binding methods can yield substantially different results.

  6. Repeated swim stress alters brain benzodiazepine receptors measured in vivo

    International Nuclear Information System (INIS)

    The effects of repeated swim stress on brain benzodiazepine receptors were examined in the mouse using both an in vivo and in vitro binding method. Specific in vivo binding of [3H]Ro15-1788 to benzodiazepine receptors was decreased in the hippocampus, cerebral cortex, hypothalamus, midbrain and striatum after repeated swim stress (7 consecutive days of daily swim stress) when compared to nonstressed mice. In vivo benzodiazepine receptor binding was unaltered after repeated swim stress in the cerebellum and pons medulla. The stress-induced reduction in in vivo benzodiazepine receptor binding did not appear to be due to altered cerebral blood flow or to an alteration in benzodiazepine metabolism or biodistribution because there was no difference in [14C]iodoantipyrine distribution or whole brain concentrations of clonazepam after repeated swim stress. Saturation binding experiments revealed a change in both apparent maximal binding capacity and affinity after repeated swim stress. Moreover, a reduction in clonazepam's anticonvulsant potency was also observed after repeated swim stress [an increase in the ED50 dose for protection against pentylenetetrazol-induced seizures], although there was no difference in pentylenetetrazol-induced seizure threshold between the two groups. In contrast to the results obtained in vivo, no change in benzodiazepine receptor binding kinetics was observed using the in vitro binding method. These data suggest that environmental stress can alter the binding parameters of the benzodiazepine receptor and that the in vivo and in vitro binding methods can yield substantially different results

  7. The 5-HT2A receptor binding pattern in the human brain is strongly genetically determined

    DEFF Research Database (Denmark)

    Pinborg, Lars H; Arfan, Haroon; Haugbol, Steven;

    2007-01-01

    variability in cortical 5-HT(2A) receptor binding as measured with [(18)F]altanserin PET imaging. The intraclass correlation coefficients were 0.67 for dizygotic and 0.87 for monozygotic twin pairs. For comparison, the intraclass correlation coefficient was 0.93 in a group of six male healthy subjects...... brain anatomy is largely genetically determined, it is currently unknown to what degree neuromodulatory markers are subjected to genetic and environmental influence. Changes in serotonin 2A (5-HT(2A)) receptors have been reported to occur in various neuropsychiatric disorders and an association between...

  8. PET imaging of human cardiac opioid receptors

    International Nuclear Information System (INIS)

    The presence of opioid peptides and receptors and their role in the regulation of cardiovascular function has been previously demonstrated in the mammalian heart. The aim of this study was to image μ and δ opioid receptors in the human heart using positron emission tomography (PET). Five subjects (three females, two males, 65±8 years old) underwent PET scanning of the chest with [11C]carfentanil ([11C]CFN) and [11C]-N-methyl-naltrindole ([11C]MeNTI) and the images were analyzed for evidence of opioid receptor binding in the heart. Either [11C]CFN or [11C]MeNTI (20 mCi) was injected i.v. with subsequent dynamic acquisitions over 90 min. For the blocking studies, either 0.2 mg/kg or 1 mg/kg of naloxone was injected i.v. 5 min prior to the injection of [11C]CFN and [11C]MeNTI, respectively. Regions of interest were placed over the left ventricle, left ventricular chamber, lung and skeletal muscle. Graphical analysis demonstrated average baseline myocardial binding potentials (BP) of 4.37±0.91 with [11C]CFN and 3.86±0.60 with [11C]MeNTI. Administration of 0.2 mg/kg naloxone prior to [11C]CFN produced a 25% reduction in BP in one subject in comparison with baseline values, and a 19% decrease in myocardial distribution volume (DV). Administration of 1 mg/kg of naloxone before [11C]MeNTI in another subject produced a 14% decrease in BP and a 21% decrease in the myocardial DV. These results demonstrate the ability to image these receptors in vivo by PET. PET imaging of cardiac opioid receptors may help to better understand their role in cardiovascular pathophysiology and the effect of abuse of opioids and drugs on heart function. (orig.)

  9. Optimized Discretization Schemes For Brain Images

    Directory of Open Access Journals (Sweden)

    USHA RANI.N,

    2011-02-01

    Full Text Available In medical image processing active contour method is the important technique in segmenting human organs. Geometric deformable curves known as levelsets are widely used in segmenting medical images. In this modeling , evolution of the curve is described by the basic lagrange pde expressed as a function of space and time. This pde can be solved either using continuous functions or discrete numerical methods.This paper deals with the application of numerical methods like finite diffefence and TVd-RK methods for brain scans. The stability and accuracy of these methods are also discussed. This paper also deals with the more accurate higher order non-linear interpolation techniques like ENO and WENO in reconstructing the brain scans like CT,MRI,PET and SPECT is considered.

  10. Modelling Brain Tissue using Magnetic Resonance Imaging

    OpenAIRE

    Dyrby, Tim Bjørn; Hansen, Lars Kai

    2008-01-01

    Diffusion MRI, or diffusion weighted imaging (DWI), is a technique that measures the restricted diffusion of water molecules within brain tissue. Different reconstruction methods quantify water-diffusion anisotropy in the intra- and extra-cellular spaces of the neural environment. Fibre tracking models then use the directions of greatest diffusion as estimates of white matter fibre orientation. Several fibre tracking algorithms have emerged in the last few years that provide reproducible visu...

  11. Thermoacoustic tomography arising in brain imaging

    CERN Document Server

    Stefanov, Plamen

    2010-01-01

    We study the mathematical model of thermoacoustic and photoacoustic tomography when the sound speed has a jump across a smooth surface. This models the change of the sound speed in the skull when trying to image the human brain. We derive an explicit inversion formula in the form of a convergent Neumann series under the assumptions that all singularities from the support of the source reach the boundary.

  12. Non-FDG PET imaging of brain tumors

    Institute of Scientific and Technical Information of China (English)

    HUANG Zemin; GUAN Yihui; ZUO Chuantao; ZHANG Zhengwei; XUE Fangping; LIN Xiangtong

    2007-01-01

    Due to relatively high uptake of glucose in the brain cortex, the use of FDG PET imaging is greatly limited in brain tumor imaging, especially for low-grade gliomas and some metastatic tumours. More and more tracers with higher specificity were developed lately for brain tumor imaging. There are 3 main types of non-FDG PET tracers:amino acid tracers, choline tracers and nucleic acid tracers. These tracers are now widely applied in many aspects of brain tumor imaging. This article summarized the general use of non-FDG PET in different aspects of brain tumor imaging.

  13. In vivo study of drug interaction with brain benzodiazepine receptor

    Energy Technology Data Exchange (ETDEWEB)

    Inoue, O.; Shinotoh, H.; Ito, T.; Suzuki, K.; Hashimoto, K.; Yamasaki, T.

    1985-05-01

    The possibility of direct estimation of in vivo Bz receptor occupancy in brain was evaluated using C-11, or H-3-flumazepil (Ro15-1788). In animal experiments, 1 ..mu..Ci of H-3-Ro15-1788 was injected at 0.5 or 20 hr after i.v. injection of various dosage of clonazepam. Then radioactivity in cerebral cortex, cerebellum and blood at 5 min. after injection of the tracer was compared. Competitive inhibition of in vivo binding was clearly observed when clonazepam was pretreated at 0.5 hr before injection of the tracer. On the other hand, brain radioactivity was increased when clonazepam was administered at 20 hr before injection of the tracer. This increase in binding of H-3-Ro15-1788 might be caused by rebound of Bz receptor function by treatment with Bz agonist, and this rebound may have an important role in physiological function. Clinical investigation concerning drug interaction with brain Bz receptor was performed in normal volunteer and patients with neurological disorders. The distribution of C-11-Ro15-1788 in the brain of patients chronically treated with clonazepam were significantly heterogeneous. However, cerebral blood flow estimated with N-13 NH3 of these patients were normal.

  14. In vivo study of drug interaction with brain benzodiazepine receptor

    International Nuclear Information System (INIS)

    The possibility of direct estimation of in vivo Bz receptor occupancy in brain was evaluated using C-11, or H-3-flumazepil (Ro15-1788). In animal experiments, 1 μCi of H-3-Ro15-1788 was injected at 0.5 or 20 hr after i.v. injection of various dosage of clonazepam. Then radioactivity in cerebral cortex, cerebellum and blood at 5 min. after injection of the tracer was compared. Competitive inhibition of in vivo binding was clearly observed when clonazepam was pretreated at 0.5 hr before injection of the tracer. On the other hand, brain radioactivity was increased when clonazepam was administered at 20 hr before injection of the tracer. This increase in binding of H-3-Ro15-1788 might be caused by rebound of Bz receptor function by treatment with Bz agonist, and this rebound may have an important role in physiological function. Clinical investigation concerning drug interaction with brain Bz receptor was performed in normal volunteer and patients with neurological disorders. The distribution of C-11-Ro15-1788 in the brain of patients chronically treated with clonazepam were significantly heterogeneous. However, cerebral blood flow estimated with N-13 NH3 of these patients were normal

  15. Brain dopamine D-2 receptors in senile dementia

    International Nuclear Information System (INIS)

    Brain dopamine D-2 receptors were analysed in the caudate nucleus, putamen and nucleus accumbens in 49 patients with different types of neuropathologically verified dementia and in 39 controls by the binding of 3H-spiroperidol. The binding was significantly decreased in all brain areas in patients with Alzheimer's disease (AD), while the changes in patients with multi-infarct dementia (MID) or combined dementia (CD) were non-significant. According to a Scatchard analysis, this decrease in binding was due to the reduced number of receptors. On the other hand, the binding of 3H-spiroperidol was significantly increased in those patients who had received neuroleptic drugs. Significant correlations between 3H-spiroperidol binding and neuropathological changes were seen only in AD patients in the nucleus accumbens. The nucleus accumbens was also the only brain area in which there was a significant correlation between dopamine D-2 and the number of muscarinic receptors in AD patients. The findings of this study on dopamine D-2 receptors suggest the involvement of the nigrostriatal dopaminergic system in AD but not in the other two major types of dementia. (Author)

  16. Fetal trauma: brain imaging in four neonates

    International Nuclear Information System (INIS)

    The purpose of this paper is to describe brain pathology in neonates after major traffic trauma in utero during the third trimester. Our patient cohort consisted of four neonates born by emergency cesarean section after car accident in the third trimester of pregnancy. The median gestational age (n=4) was 36 weeks (range: 30-38). Immediate post-natal and follow-up brain imaging consisted of cranial ultrasound (n=4), computed tomography (CT) (n=1) and post-mortem magnetic resonance imaging (MRI) (n=1). Pathology findings were correlated with the imaging findings (n=3). Cranial ultrasound demonstrated a huge subarachnoidal hemorrhage (n=1), subdural hematoma (n=1), brain edema with inversion of the diastolic flow (n=1) and severe ischemic changes (n=1). In one case, CT demonstrated the presence and extension of the subarachnoidal hemorrhage, a parietal fracture and a limited intraventricular hemorrhage. Cerebellar hemorrhage and a small cerebral frontal contusion were seen on post-mortem MRI in a child with a major subarachnoidal hemorrhage on ultrasound. None of these four children survived (three children died within 2 days and one child died after 1 month). Blunt abdominal trauma during pregnancy can cause fetal cranial injury. In our cases, skull fracture, intracranial hemorrhage and hypoxic-ischemic encephalopathy were encountered. (orig.)

  17. Fetal trauma: brain imaging in four neonates

    Energy Technology Data Exchange (ETDEWEB)

    Breysem, Luc; Mussen, E.; Demaerel, P.; Smet, M. [Department of Radiology, University Hospitals, Herestraat 49, 3000, Leuven (Belgium); Cossey, V. [Department of Pediatrics, University Hospitals, Leuven (Belgium); Voorde, W. van de [Department of Forensic Medicine, University Hospitals, Leuven (Belgium)

    2004-09-01

    The purpose of this paper is to describe brain pathology in neonates after major traffic trauma in utero during the third trimester. Our patient cohort consisted of four neonates born by emergency cesarean section after car accident in the third trimester of pregnancy. The median gestational age (n=4) was 36 weeks (range: 30-38). Immediate post-natal and follow-up brain imaging consisted of cranial ultrasound (n=4), computed tomography (CT) (n=1) and post-mortem magnetic resonance imaging (MRI) (n=1). Pathology findings were correlated with the imaging findings (n=3). Cranial ultrasound demonstrated a huge subarachnoidal hemorrhage (n=1), subdural hematoma (n=1), brain edema with inversion of the diastolic flow (n=1) and severe ischemic changes (n=1). In one case, CT demonstrated the presence and extension of the subarachnoidal hemorrhage, a parietal fracture and a limited intraventricular hemorrhage. Cerebellar hemorrhage and a small cerebral frontal contusion were seen on post-mortem MRI in a child with a major subarachnoidal hemorrhage on ultrasound. None of these four children survived (three children died within 2 days and one child died after 1 month). Blunt abdominal trauma during pregnancy can cause fetal cranial injury. In our cases, skull fracture, intracranial hemorrhage and hypoxic-ischemic encephalopathy were encountered. (orig.)

  18. Melanocortin 4 Receptor and Dopamine D2 Receptor Expression in Brain Areas Involved in Food Intake

    OpenAIRE

    Yoon, Ye Ran; Baik, Ja-Hyun

    2015-01-01

    Background The melanocortin 4 receptor (MC4R) is involved in the regulation of homeostatic energy balance by the hypothalamus. Recent reports showed that MC4R can also control the motivation for food in association with a brain reward system, such as dopamine. We investigated the expression levels of MC4R and the dopamine D2 receptor (D2R), which is known to be related to food rewards, in both the hypothalamus and brain regions involved in food rewards. Methods We examined the expression leve...

  19. Electroencephalographic imaging of higher brain function

    Science.gov (United States)

    Gevins, A.; Smith, M. E.; McEvoy, L. K.; Leong, H.; Le, J.

    1999-01-01

    High temporal resolution is necessary to resolve the rapidly changing patterns of brain activity that underlie mental function. Electroencephalography (EEG) provides temporal resolution in the millisecond range. However, traditional EEG technology and practice provide insufficient spatial detail to identify relationships between brain electrical events and structures and functions visualized by magnetic resonance imaging or positron emission tomography. Recent advances help to overcome this problem by recording EEGs from more electrodes, by registering EEG data with anatomical images, and by correcting the distortion caused by volume conduction of EEG signals through the skull and scalp. In addition, statistical measurements of sub-second interdependences between EEG time-series recorded from different locations can help to generate hypotheses about the instantaneous functional networks that form between different cortical regions during perception, thought and action. Example applications are presented from studies of language, attention and working memory. Along with its unique ability to monitor brain function as people perform everyday activities in the real world, these advances make modern EEG an invaluable complement to other functional neuroimaging modalities.

  20. Spatial normalization of brain images and beyond.

    Science.gov (United States)

    Mangin, J-F; Lebenberg, J; Lefranc, S; Labra, N; Auzias, G; Labit, M; Guevara, M; Mohlberg, H; Roca, P; Guevara, P; Dubois, J; Leroy, F; Dehaene-Lambertz, G; Cachia, A; Dickscheid, T; Coulon, O; Poupon, C; Rivière, D; Amunts, K; Sun, Z Y

    2016-10-01

    The deformable atlas paradigm has been at the core of computational anatomy during the last two decades. Spatial normalization is the variant endowing the atlas with a coordinate system used for voxel-based aggregation of images across subjects and studies. This framework has largely contributed to the success of brain mapping. Brain spatial normalization, however, is still ill-posed because of the complexity of the human brain architecture and the lack of architectural landmarks in standard morphological MRI. Multi-atlas strategies have been developed during the last decade to overcome some difficulties in the context of segmentation. A new generation of registration algorithms embedding architectural features inferred for instance from diffusion or functional MRI is on the verge to improve the architectural value of spatial normalization. A better understanding of the architectural meaning of the cortical folding pattern will lead to use some sulci as complementary constraints. Improving the architectural compliance of spatial normalization may impose to relax the diffeomorphic constraint usually underlying atlas warping. A two-level strategy could be designed: in each region, a dictionary of templates of incompatible folding patterns would be collected and matched in a way or another using rare architectural information, while individual subjects would be aligned using diffeomorphisms to the closest template. Manifold learning could help to aggregate subjects according to their morphology. Connectivity-based strategies could emerge as an alternative to deformation-based alignment leading to match the connectomes of the subjects rather than images. PMID:27344104

  1. Nuclear magnetic resonance imaging in brain tumors

    International Nuclear Information System (INIS)

    Full text: Magnetic resonance imaging (MRI) is a non-invasive imaging method based on the detecting signal from hydrogen nuclei of water molecules and fat. Performances of MRI are continuously increasing, and its domains of investigation of the human body are growing in both morphological and functional study. MRI also allows It also performing advanced management of tumours especially in the brain, by combining anatomical information (morphological MRI), functional (diffusion, perfusion and BOLD contrast) and metabolic (tissue composition in magnetic resonance spectroscopy (MRS)). The MRI techniques have an important role in cancerology. These techniques allow essential information for the diagnosis and answering therapist's questions before, during or after the treatment. The MR allows clarifying the localization of expanding processes, the differential diagnosis between brain tumour and a lesion confined by another structural aspect, the diagnosis of the tumoral aspect of a lesion, the histological ranking in case of glial tumour and the extension of its localization as well as the therapeutic follow-up (pre-therapeutic and post-therapeutics assessments). A better combination between the morphological, functional and metabolic studies, as well as integrating new technical developments, especially while using a multichannel bird cage coils the 3T magnet and suitable computing software, would allow significant improvements of the exploration strategies and management of brain tumors.

  2. Somatostatin-receptor positive brain stem glioma visualized by octreoscan.

    Science.gov (United States)

    Pichler, Robert; Pichler, Josef; Mustafa, Hamdy; Nussbaumer, Karin; Zaunmüller, Thomas; Topakian, Raffi

    2007-06-01

    In diffuse brainstem gliomas often surgical biopsies cannot be obtained. The diagnosis relies upon imaging criteria, first line being MRI. Gliomas generally express somatostatin receptors (SSTR), which might enable receptor imaging. We present the case of a female adolescent with acute onset of hallucinations, dysphagia and diplopia. MRI detected a suggestive large pontine glioma. This lesion presented with marked In-111-pentreotide tracer uptake. SSTR-scan provided information about SSTR-expression, tumour viability and extension. Radiopeptide therapy for selected patients might be discussed. PMID:17627256

  3. Angiotensin II AT1 receptor blockers as treatments for inflammatory brain disorders

    OpenAIRE

    Saavedra, Juan M.

    2012-01-01

    The effects of brain AngII (angiotensin II) depend on AT1 receptor (AngII type 1 receptor) stimulation and include regulation of cerebrovascular flow, autonomic and hormonal systems, stress, innate immune response and behaviour. Excessive brain AT1 receptor activity associates with hypertension and heart failure, brain ischaemia, abnormal stress responses, blood–brain barrier breakdown and inflammation. These are risk factors leading to neuronal injury, the incidence and progression of neurod...

  4. Multiple opiate receptors in the brain of spontaneously hypertensive rats

    Energy Technology Data Exchange (ETDEWEB)

    Das, S.; Bhargava, H.N.

    1986-03-01

    The characteristics of ..mu.., delta and kappa -opiate receptors in the brain of spontaneously hypertensive (SH) and normotensive Wistar-Kyoto (WKY) rats were determined using the receptor binding assays. The ligands used were /sup 3/H-naltrexone (..mu..), /sup 3/H-ethylketocyclazocine (EKC, kappa) and /sup 3/H-Tyr-D-Ser-Gly-Phe-Leu-Thr (DSTLE, delta). Since EKC binds to ..mu.. and delta receptors in addition to kappa, the binding was done in the presence of 100 nM each of DAGO and DADLE to suppress ..mu.. and delta sites, respectively. All three ligands bound to brain membranes of WKY rats at a single high affinity site with the following B/sub max/ (fmol/mg protein) and K/sub d/ (nM) values: /sup 3/H-naltrexone (130.5; 0.43) /sup 3/H-EKC (19.8, 1.7) and /sup 3/H-DSTLE (139, 2.5). The binding of /sup 3/H-naltrexone and /sup 3/H-DSTLE in the brain of WKY and SH did not differ. A consistent increase (22%) in B/sub max/ of /sup 3/H-EKC was found in SHR compared to WKY rats. However, the K/sub d/ values did not differ. The increase in B/sub max/ was due to increases in hypothalamus and cortex. It is concluded that SH rats have higher density of kappa-opiate receptors, particularly in hypothalamus and cortex, compared to WKY rats, and that kappa-opiate receptors may be involved in the pathophysiology of hypertension.

  5. Diffuse Optical Tomography for Brain Imaging: Theory

    Science.gov (United States)

    Yuan, Zhen; Jiang, Huabei

    Diffuse optical tomography (DOT) is a noninvasive, nonionizing, and inexpensive imaging technique that uses near-infrared light to probe tissue optical properties. Regional variations in oxy- and deoxy-hemoglobin concentrations as well as blood flow and oxygen consumption can be imaged by monitoring spatiotemporal variations in the absorption spectra. For brain imaging, this provides DOT unique abilities to directly measure the hemodynamic, metabolic, and neuronal responses to cells (neurons), and tissue and organ activations with high temporal resolution and good tissue penetration. DOT can be used as a stand-alone modality or can be integrated with other imaging modalities such as fMRI/MRI, PET/CT, and EEG/MEG in studying neurophysiology and pathology. This book chapter serves as an introduction to the basic theory and principles of DOT for neuroimaging. It covers the major aspects of advances in neural optical imaging including mathematics, physics, chemistry, reconstruction algorithm, instrumentation, image-guided spectroscopy, neurovascular and neurometabolic coupling, and clinical applications.

  6. Sex Differences in Serotonin 1 Receptor Binding in Rat Brain

    Science.gov (United States)

    Fischette, Christine T.; Biegon, Anat; McEwen, Bruce S.

    1983-10-01

    Male and female rats exhibit sex differences in binding by serotonin 1 receptors in discrete areas of the brain, some of which have been implicated in the control of ovulation and of gonadotropin release. The sex-specific changes in binding, which occur in response to the same hormonal (estrogenic) stimulus, are due to changes in the number of binding sites. Castration alone also affects the number of binding sites in certain areas. The results lead to the conclusion that peripheral hormones modulate binding by serotonin 1 receptors. The status of the serotonin receptor system may affect the reproductive capacity of an organism and may be related to sex-linked emotional disturbances in humans.

  7. Oxytocin and Estrogen Receptor β in the Brain: An Overview

    Directory of Open Access Journals (Sweden)

    Alexandra eAcevedo-Rodriguez

    2015-10-01

    Full Text Available Oxytocin is a neuropeptide synthesized primarily by neurons of the paraventricular and supraoptic nuclei of the hypothalamus. These neurons have axons that project into the posterior pituitary and release oxytocin into the bloodstream to promote labor and lactation; however, oxytocin neurons also project to other brain areas where it plays a role in numerous brain functions. Oxytocin binds to the widely expressed oxytocin receptor, and, in doing so, it regulates homeostatic processes, social recognition and fear conditioning. In addition to these functions, oxytocin decreases neuroendocrine stress signaling and anxiety-related and depression-like behaviors. Steroid hormones differentially modulate stress responses and alter oxytocin receptor expression. In particular, estrogen receptor β activation has been found to both reduce anxiety-related behaviors and increase oxytocin peptide transcription, suggesting a role for oxytocin in this estrogen receptor β mediated anxiolytic effect. Further research is needed to identify modulators of oxytocin signaling and the pathways utilized and to elucidate molecular mechanisms controlling oxytocin expression to allow better therapeutic manipulations of this system in patient populations.

  8. Distribution of cysteinyl leukotriene receptor 2 in human traumatic brain injury and brain tumors

    Institute of Scientific and Technical Information of China (English)

    Hua HU; Er-qing WEI; Gao CHEN; Jian-min ZHANG; Wei-ping ZHANG; Lei ZHANG; Qiu-fu GE; Hong-tian YAO; Wei DING; Zhong CHEN

    2005-01-01

    Aim: To determine the distribution of cysteinyl leukotriene receptor 2 (CysLT2),one of the cysteinyl leukotriene receptors, in human brains with traumatic injury and tumors. Methods: Brain specimens were obtained from patients who underwent brain surgery. CysLT2 in brain tissues was examined using immunohistochemical analysis. Results: CysLT2 was expressed in the smooth muscle cells (not in the endothelial cells) of arteries and veins. CysLT2 was also expressed in the granulocytes in both vessels and in the brain parenchyma. In addition, CysLT2 was detected in neuron- and glial-appearing cells in either the late stages of traumatic injury or in the area surrounding the tumors. Microvessels regenerated 8 d after trauma and CysLT2 expression was recorded in their endothelial cells.Conclusion: CysLT2 is distributed in vascular smooth muscle cells and granulocytes, and brain trauma and tumor can induce its expression in vascular endothelial cells and in a number of other cells.

  9. PET imaging of human cardiac opioid receptors

    Energy Technology Data Exchange (ETDEWEB)

    Villemagne, Patricia S.R.; Dannals, Robert F. [Department of Radiology, The Johns Hopkins University School of Medicine, 605 N Caroline St., Baltimore, Maryland (United States); Department of Environmental Health Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Ravert, Hayden T. [Department of Radiology, The Johns Hopkins University School of Medicine, 605 N Caroline St., Baltimore, Maryland (United States); Frost, James J. [Department of Radiology, The Johns Hopkins University School of Medicine, 605 N Caroline St., Baltimore, Maryland (United States); Department of Environmental Health Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States)

    2002-10-01

    The presence of opioid peptides and receptors and their role in the regulation of cardiovascular function has been previously demonstrated in the mammalian heart. The aim of this study was to image {mu} and {delta} opioid receptors in the human heart using positron emission tomography (PET). Five subjects (three females, two males, 65{+-}8 years old) underwent PET scanning of the chest with [{sup 11}C]carfentanil ([{sup 11}C]CFN) and [{sup 11}C]-N-methyl-naltrindole ([{sup 11}C]MeNTI) and the images were analyzed for evidence of opioid receptor binding in the heart. Either [{sup 11}C]CFN or [{sup 11}C]MeNTI (20 mCi) was injected i.v. with subsequent dynamic acquisitions over 90 min. For the blocking studies, either 0.2 mg/kg or 1 mg/kg of naloxone was injected i.v. 5 min prior to the injection of [{sup 11}C]CFN and [{sup 11}C]MeNTI, respectively. Regions of interest were placed over the left ventricle, left ventricular chamber, lung and skeletal muscle. Graphical analysis demonstrated average baseline myocardial binding potentials (BP) of 4.37{+-}0.91 with [{sup 11}C]CFN and 3.86{+-}0.60 with [{sup 11}C]MeNTI. Administration of 0.2 mg/kg naloxone prior to [{sup 11}C]CFN produced a 25% reduction in BP in one subject in comparison with baseline values, and a 19% decrease in myocardial distribution volume (DV). Administration of 1 mg/kg of naloxone before [{sup 11}C]MeNTI in another subject produced a 14% decrease in BP and a 21% decrease in the myocardial DV. These results demonstrate the ability to image these receptors in vivo by PET. PET imaging of cardiac opioid receptors may help to better understand their role in cardiovascular pathophysiology and the effect of abuse of opioids and drugs on heart function. (orig.)

  10. Quantitative autoradiography of (/sup 3/H)corticosterone receptors in rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Sapolsky, R.M.; McEwen, B.S. (Rockefeller Univ., New York (USA)); Rainbow, T.C. (Pennsylvania Univ., Philadelphia (USA). School of Medicine)

    1983-07-25

    The authors have quantified corticosterone receptors in rat brain by optical density measurements of tritium-film autoradiograms. Rats were injected i.v. with 500 ..mu..Ci (/sup 3/H)corticosterone to label brain receptors. Frozen sections of brain were cut with a cryostat and exposed for 2 months against tritium-sensitive sheet film (LKB Ultrofilm). Tritium standards were used to convert optical density readings into molar concentrations of receptor. High levels of corticosterone receptors were present throughout the pyramidal and granule cell layers of the hippocampus. Moderate levels of receptors were found in the neuropil of the hippocampus, the lateral septum, the cortical nucleus of the amygdala and the entorhinal cortex. All other brain regions had low levels of receptors. These results extend previous non-quantitative autoradiographic studies of corticosterone receptors and provide a general procedure for the quantitative autoradiography of steroid hormone receptors in brain tissue.

  11. Neurolight -astonishing advances in brain imaging.

    Science.gov (United States)

    Rojczyk-Gołębiewska, Ewa; Pałasz, Artur; Worthington, John J; Markowski, Grzegorz; Wiaderkiewicz, Ryszard

    2015-02-01

    In recent years, significant advances in basic neuroanatomical studies have taken place. Moreover, such classical, clinically-oriented human brain imaging methods such as MRI, PET and DTI have been applied to small laboratory animals allowing improvement in current experimental neuroscience. Contemporary structural neurobiology also uses various technologies based on fluorescent proteins. One of these is optogenetics, which integrates physics, genetics and bioengineering to enable temporal precise control of electrical activity of specific neurons. Another important challenge in the field is the accurate imaging of complicated neural networks. To address this problem, three-dimensional reconstruction techniques and retrograde labeling with modified viruses has been developed. However, a revolutionary step was the invention of the "Brainbow" system, utilizing gene constructs including the sequences of fluorescent proteins and the usage of Cre recombinase to create dozens of colour combinations, enabling visualization of neurons and their connections in extremely high resolution. Furthermore, the newly- introduced CLARITY method should make it possible to visualize three-dimensionally the structure of translucent brain tissue using the hydrogel polymeric network. This original technique is a big advance in neuroscience creating novel viewpoints completely different than standard glass slide immunostaining.

  12. Aromatase, estrogen receptors and brain development in fish and amphibians.

    Science.gov (United States)

    Coumailleau, Pascal; Pellegrini, Elisabeth; Adrio, Fátima; Diotel, Nicolas; Cano-Nicolau, Joel; Nasri, Ahmed; Vaillant, Colette; Kah, Olivier

    2015-02-01

    Estrogens affect brain development of vertebrates, not only by impacting activity and morphology of existing circuits, but also by modulating embryonic and adult neurogenesis. The issue is complex as estrogens can not only originate from peripheral tissues, but also be locally produced within the brain itself due to local aromatization of androgens. In this respect, teleost fishes are quite unique because aromatase is expressed exclusively in radial glial cells, which represent pluripotent cells in the brain of all vertebrates. Expression of aromatase in the brain of fish is also strongly stimulated by estrogens and some androgens. This creates a very intriguing positive auto-regulatory loop leading to dramatic aromatase expression in sexually mature fish with elevated levels of circulating steroids. Looking at the effects of estrogens or anti-estrogens in the brain of adult zebrafish showed that estrogens inhibit rather than stimulate cell proliferation and newborn cell migration. The functional meaning of these observations is still unclear, but these data suggest that the brain of fish is experiencing constant remodeling under the influence of circulating steroids and brain-derived neurosteroids, possibly permitting a diversification of sexual strategies, notably hermaphroditism. Recent data in frogs indicate that aromatase expression is limited to neurons and do not concern radial glial cells. Thus, until now, there is no other example of vertebrates in which radial progenitors express aromatase. This raises the question of when and why these new features were gained and what are their adaptive benefits. This article is part of a Special Issue entitled: Nuclear receptors in animal development.

  13. Animal imaging studies of potential brain damage

    Science.gov (United States)

    Gatley, S. J.; Vazquez, M. E.; Rice, O.

    To date, animal studies have not been able to predict the likelihood of problems in human neurological health due to HZE particle exposure during space missions outside the Earth's magnetosphere. In ongoing studies in mice, we have demonstrated that cocaine stimulated locomotor activity is reduced by a moderate dose (120 cGy) of 1 GeV 56Fe particles. We postulate that imaging experiments in animals may provide more sensitive and earlier indicators of damage due to HZE particles than behavioral tests. Since the small size of the mouse brain is not well suited to the spatial resolution offered by microPET, we are now repeating some of our studies in a rat model. We anticipate that this will enable us to identify imaging correlates of behavioral endpoints. A specific hypothesis of our studies is that changes in the metabolic rate for glucose in striatum of animals will be correlated with alterations in locomotor activity. We will also evaluate whether the neuroprotective drug L-deprenyl reduces the effect of radiation on locomotor activity. In addition, we will conduct microPET studies of brain monoamine oxidase A and monoamine oxidase B in rats before and at various times after irradiation with HZE particles. The hypothesis is that monoamine oxidase A, which is located in nerve terminals, will be unchanged or decreased after irradiation, while monoamine oxidase B, which is located in glial cells, will be increased after irradiation. Neurochemical effects that could be measured using PET could in principle be applied in astronauts, in terms of detecting and monitoring subtle neurological damage that might have occurred during long space missions. More speculative uses of PET are in screening candidates for prolonged space missions (for example, for adequate reserve in critical brain circuits) and in optimizing medications to treat impairments after missions.

  14. Brain MR imaging in systemic lupus erythematous

    International Nuclear Information System (INIS)

    To present MR imaging findings of intracranial lesions in systemic lupus erythematosus(SLE), a retrospective study was performed on MR images of 33 SLE patients with neurologic symptoms and signs. MR imaging was performed on either a 0.5 T (21 patients) or 2.0 T unit (12 patients), using T1-weighted, proton-density-weighted, and T2-weighted spin echo sequences in all patients. In seven patients, post-contrast T1-weighted images were also obtained after administration of gadopentetate dimeglumine. The main MR findings consisted of focal lesions suggesting ischemia/infarct (15 patients), diffuse brain atrophy (8), and findings associated with infection (4). The MR findings were normal in 11 patients (33%). The focal lesions suggesting ischemia/infarcts presumably secondary to vasculitis were distributed in the cortex or subcortical white matter (7 patients), deep periventricular white matter (3), or in both areas (5). Most of the focal lesions were multiple and small in size. The findings associated with infection were variable and included communicating hydrocephalus, meningeal enhancement, granuloma, etc. MR findings of SLE were non-specific and therefore clinical correlation is needed when evaluating SLE in MR

  15. Modulation of glutamate transport and receptor binding by glutamate receptor antagonists in EAE rat brain.

    Science.gov (United States)

    Sulkowski, Grzegorz; Dąbrowska-Bouta, Beata; Salińska, Elżbieta; Strużyńska, Lidia

    2014-01-01

    The etiology of multiple sclerosis (MS) is currently unknown. However, one potential mechanism involved in the disease may be excitotoxicity. The elevation of glutamate in cerebrospinal fluid, as well as changes in the expression of glutamate receptors (iGluRs and mGluRs) and excitatory amino acid transporters (EAATs), have been observed in the brains of MS patients and animals subjected to experimental autoimmune encephalomyelitis (EAE), which is the predominant animal model used to investigate the pathophysiology of MS. In the present paper, the effects of glutamatergic receptor antagonists, including amantadine, memantine, LY 367583, and MPEP, on glutamate transport, the expression of mRNA of glutamate transporters (EAATs), the kinetic parameters of ligand binding to N-methyl-D-aspartate (NMDA) receptors, and the morphology of nerve endings in EAE rat brains were investigated. The extracellular level of glutamate in the brain is primarily regulated by astrocytic glutamate transporter 1 (GLT-1) and glutamate-aspartate transporter (GLAST). Excess glutamate is taken up from the synaptic space and metabolized by astrocytes. Thus, the extracellular level of glutamate decreases, which protects neurons from excitotoxicity. Our investigations showed changes in the expression of EAAT mRNA, glutamate transport (uptake and release) by synaptosomal and glial plasmalemmal vesicle fractions, and ligand binding to NMDA receptors; these effects were partially reversed after the treatment of EAE rats with the NMDA antagonists amantadine and memantine. The antagonists of group I metabotropic glutamate receptors (mGluRs), including LY 367385 and MPEP, did not exert any effect on the examined parameters. These results suggest that disturbances in these mechanisms may play a role in the processes associated with glutamate excitotoxicity and the progressive brain damage in EAE.

  16. Compact and mobile high resolution PET brain imager

    Science.gov (United States)

    Majewski, Stanislaw; Proffitt, James

    2011-02-08

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

  17. Infrared Imaging System for Studying Brain Function

    Science.gov (United States)

    Mintz, Frederick; Mintz, Frederick; Gunapala, Sarath

    2007-01-01

    A proposed special-purpose infrared imaging system would be a compact, portable, less-expensive alternative to functional magnetic resonance imaging (fMRI) systems heretofore used to study brain function. Whereas a typical fMRI system fills a large room, and must be magnetically isolated, this system would fit into a bicycle helmet. The system would include an assembly that would be mounted inside the padding in a modified bicycle helmet or other suitable headgear. The assembly would include newly designed infrared photodetectors and data-acquisition circuits on integrated-circuit chips on low-thermal-conductivity supports in evacuated housings (see figure) arranged in multiple rows and columns that would define image coordinates. Each housing would be spring-loaded against the wearer s head. The chips would be cooled by a small Stirling Engine mounted contiguous to, but thermally isolated from, the portions of the assembly in thermal contact with the wearer s head. Flexible wires or cables for transmitting data from the aforementioned chips would be routed to an integrated, multichannel transmitter and thence through the top of the assembly to a patch antenna on the outside of the helmet. The multiple streams of data from the infrared-detector chips would be sent to a remote site, where they would be processed, by software, into a three-dimensional display of evoked potentials that would represent firing neuronal bundles and thereby indicate locations of neuronal activity associated with mental or physical activity. The 3D images will be analogous to current fMRI images. The data would also be made available, in real-time, for comparison with data in local or internationally accessible relational databases that already exist in universities and research centers. Hence, this system could be used in research on, and for the diagnosis of response from the wearer s brain to physiological, psychological, and environmental changes in real time. The images would also be

  18. FULLY AUTOMATIC FRAMEWORK FOR SEGMENTATION OF BRAIN MRI IMAGE

    Institute of Scientific and Technical Information of China (English)

    Lin Pan; Zheng Chongxun; Yang Yong; Gu Jianwen

    2005-01-01

    Objective To propose an automatic framework for segmentation of brain image in this paper. Methods The brain MRI image segmentation framework consists of three-step segmentation procedures. First, Non-brain structures removal by level set method. Then, the non-uniformity correction method is based on computing estimates of tissue intensity variation. Finally, it uses a statistical model based on Markov random filed for MRI brain image segmentation. The brain tissue can be classified into cerebrospinal fluid, white matter and gray matter. Results To evaluate the proposed our method, we performed two sets of experiments, one on simulated MR and another on real MR brain data. Conclusion The efficacy of the brain MRI image segmentation framework has been demonstrated by the extensive experiments. In the future, we are also planning on a large-scale clinical evaluation of this segmentation framework.

  19. FCM Clustering Algorithms for Segmentation of Brain MR Images

    Directory of Open Access Journals (Sweden)

    Yogita K. Dubey

    2016-01-01

    Full Text Available The study of brain disorders requires accurate tissue segmentation of magnetic resonance (MR brain images which is very important for detecting tumors, edema, and necrotic tissues. Segmentation of brain images, especially into three main tissue types: Cerebrospinal Fluid (CSF, Gray Matter (GM, and White Matter (WM, has important role in computer aided neurosurgery and diagnosis. Brain images mostly contain noise, intensity inhomogeneity, and weak boundaries. Therefore, accurate segmentation of brain images is still a challenging area of research. This paper presents a review of fuzzy c-means (FCM clustering algorithms for the segmentation of brain MR images. The review covers the detailed analysis of FCM based algorithms with intensity inhomogeneity correction and noise robustness. Different methods for the modification of standard fuzzy objective function with updating of membership and cluster centroid are also discussed.

  20. Relationship between changes of N-methyl-D-aspartate receptor activity and brain edema after brain injury in rats

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective: To investigate the relationship between the changes of N-methyl-D-aspartate (NMDA) receptor activity and brain edema after injury in rats.   Methods: The brain injury models were made by using a free-falling body. The treatment model was induced by means of injecting AP5 into lateral ventricle before brain injury; water contents in brain cortex were measured with dry-wet method; and NMDA receptor activity was detected with a radio ligand binding assay.   Results: The water contents began to increase at 30 minutes and reached the peak at 6 hours after brain injury. The maximal binding (Bmax) of NMDA receptor increased significantly at 15 minutes and reached the peak at 30 minutes, then decreased gradually and had the lowest value 6 hours after brain injury. Followed the treatment with AP5, NMDA receptor activity in the injured brain showed a normal value; and the water contents were lower than that of AP5-free injury group 24 hours after brain injury.   Conclusions: It suggests that excessive activation of NMDA receptor may be one of the most important factors to induce the secondary cerebral impairments, and AP5 may protect the brain from edema after brain injury.

  1. Exploring brain function with magnetic resonance imaging

    International Nuclear Information System (INIS)

    Since its invention in the early 1990s, functional magnetic resonance imaging (fMRI) has rapidly assumed a leading role among the techniques used to localize brain activity. The spatial and temporal resolution provided by state-of-the-art MR technology and its non-invasive character, which allows multiple studies of the same subject, are some of the main advantages of fMRI over the other functional neuroimaging modalities that are based on changes in blood flow and cortical metabolism. This paper describes the basic principles and methodology of fMRI and some aspects of its application to functional activation studies. Attention is focused on the physiology of the blood oxygenation level-dependent (BOLD) contrast mechanism and on the acquisition of functional time-series with echo planar imaging (EPI). We also provide an introduction to the current strategies for the correction of signal artefacts and other image processing techniques. In order to convey an idea of the numerous applications of fMRI, we will review some of the recent results in the fields of cognitive and sensorimotor psychology and physiology

  2. Imaging of brain activity by positron emission tomography

    International Nuclear Information System (INIS)

    Brain function is associated with regional energy metabolism and blood flow increase. Such brain activity is visualized by using external scintigraphy. Positron emission tomography (PET) is the currently available most superior technique, allowing three-dimensional imaging of subtle blood flow. In this article, imaging methods and application of PET are discussed in terms of the following items: (1) measurement of cerebral glucose consumption, (2) PET in persons with visual impairment, (3) association between brain function and regional cerebral blood flow, (4) measurement of cerebral blood flow, (5) method for decreasing noise in PET imaging, (6) anatomic standardization of PET images, and (7) speech load and regional cerebral activity images. (N.K.)

  3. Sex, the brain and hypertension: brain oestrogen receptors and high blood pressure risk factors.

    Science.gov (United States)

    Hay, Meredith

    2016-01-01

    Hypertension is a major contributor to worldwide morbidity and mortality rates related to cardiovascular disease. There are important sex differences in the onset and rate of hypertension in humans. Compared with age-matched men, premenopausal women are less likely to develop hypertension. However, after age 60, the incidence of hypertension increases in women and even surpasses that seen in older men. It is thought that changes in levels of circulating ovarian hormones as women age may be involved in the increase in hypertension in older women. One of the key mechanisms involved in the development of hypertension in both men and women is an increase in sympathetic nerve activity (SNA). Brain regions important for the regulation of SNA, such as the subfornical organ, the paraventricular nucleus and the rostral ventral lateral medulla, also express specific subtypes of oestrogen receptors. Each of these brain regions has also been implicated in mechanisms underlying risk factors for hypertension such as obesity, stress and inflammation. The present review brings together evidence that links actions of oestrogen at these receptors to modulate some of the common brain mechanisms involved in the ability of hypertensive risk factors to increase SNA and blood pressure. Understanding the mechanisms by which oestrogen acts at key sites in the brain for the regulation of SNA is important for the development of novel, sex-specific therapies for treating hypertension.

  4. Optical Methods and Instrumentation in Brain Imaging and Therapy

    CERN Document Server

    2013-01-01

    This book provides a comprehensive up-to-date review of optical approaches used in brain imaging and therapy. It covers a variety of imaging techniques including diffuse optical imaging, laser speckle imaging, photoacoustic imaging and optical coherence tomography. A number of laser-based therapeutic approaches are reviewed, including photodynamic therapy, fluorescence guided resection and photothermal therapy. Fundamental principles and instrumentation are discussed for each imaging and therapeutic technique. Represents the first publication dedicated solely to optical diagnostics and therapeutics in the brain Provides a comprehensive review of the principles of each imaging/therapeutic modality Reviews the latest advances in instrumentation for optical diagnostics in the brain Discusses new optical-based therapeutic approaches for brain diseases

  5. Cognitive disorder and changes in cholinergic receptors, N-methyl-D aspartate receptors, neural cell adhesion molecule, and brain-derived neurotrophic factor following brain injury

    Institute of Scientific and Technical Information of China (English)

    Weiliang Zhao; Dezhi Kang; Yuanxiang Lin

    2008-01-01

    BACKGROUND: Learning and memory damage is one of the most permanent and the severest symptoms of traumatic brain injury; it can seriously influence the normal life and work of patients. Some research has demonstrated that cognitive disorder is closely related to nicotine cholinergic receptors, N-methyl-D aspartate receptors, neural cell adhesion molecule, and brain-derived neurotrophic factor. OBJECTIVE: To summarize the cognitive disorder and changes in nicotine cholinergic receptors, N-methyl-D aspartate receptors, neural cell adhesion molecule, and brain-derived neurotrophic factor following brain injury. RETRIEVAL STRATEGY: A computer-based online search was conducted in PUBMED for English language publications containing the key words "brain injured, cognitive handicap, acetylcholine, N-methyl-D aspartate receptors, neural cell adhesion molecule, brain-derived neurotrophic factor" from January 2000 to December 2007. There were 44 papers in total. Inclusion criteria: ① articles about changes in nicotine cholinergic receptors, N-methyl-D aspartate receptors, neural cell adhesion molecule, and brain-derived neurotrophic factor following brain injury; ② articles in the same researching circle published in authoritative journals or recently published. Exclusion criteria: duplicated articles.LITERATURE EVALUATION: References were mainly derived from research on changes in these four factors following brain injury. The 20 included papers were clinical or basic experimental studies. DATA SYNTHESIS: After craniocerebral injury, changes in these four factors in brain were similar to those during recovery from cognitive disorder, to a certain degree. Some data have indicated that activation of nicotine cholinergic receptors, N-methyl-D aspartate receptors, neural cell adhesion molecule, and brain-derived neurotrophic factor could greatly improve cognitive disorder following brain injury. However, there are still a lot of questions remaining; for example, how do these

  6. A Novel Approach for MRI Brain Images Segmentation

    OpenAIRE

    Abo-Eleneen Z. A; Gamil Abdel-Azim

    2013-01-01

    Segmentation of brain from magnetic resonance (MR) images has important applications in neuroimaging, in particular it facilitates in extracting different brain tissues such as cerebrospinal fluids, white matter and gray matter. That helps in determining the volume of the tissues in three-dimensional brain MR images, which yields in analyzing many neural disorders such as epilepsy and Alzheimer disease. The Fisher information is a measure of the fluctuations in the observations. In a sense, ...

  7. Whole-brain dynamic CT angiography and perfusion imaging

    Energy Technology Data Exchange (ETDEWEB)

    Orrison, W.W. [CHW Nevada Imaging Company, Nevada Imaging Centers, Spring Valley, Las Vegas, NV (United States); College of Osteopathic Medicine, Touro University Nevada, Henderson, NV (United States); Department of Health Physics and Diagnostic Sciences, University of Nevada Las Vegas, Las Vegas, NV (United States); Department of Medical Education, University of Nevada School of Medicine, Reno, NV (United States); Snyder, K.V.; Hopkins, L.N. [Department of Neurosurgery, Millard Fillmore Gates Circle Hospital, Buffalo, NY (United States); Roach, C.J. [School of Life Sciences, University of Nevada Las Vegas, Las Vegas, NV (United States); Advanced Medical Imaging and Genetics (Amigenics), Las Vegas, NV (United States); Ringdahl, E.N. [Department of Psychology, University of Nevada Las Vegas, Las Vegas, NV (United States); Nazir, R. [Shifa International Hospital, Islamabad (Pakistan); Hanson, E.H., E-mail: eric.hanson@amigenics.co [College of Osteopathic Medicine, Touro University Nevada, Henderson, NV (United States); Department of Health Physics and Diagnostic Sciences, University of Nevada Las Vegas, Las Vegas, NV (United States); Advanced Medical Imaging and Genetics (Amigenics), Las Vegas, NV (United States)

    2011-06-15

    The availability of whole brain computed tomography (CT) perfusion has expanded the opportunities for analysing the haemodynamic parameters associated with varied neurological conditions. Examples demonstrating the clinical utility of whole-brain CT perfusion imaging in selected acute and chronic ischaemic arterial neurovascular conditions are presented. Whole-brain CT perfusion enables the detection and focused haemodynamic analyses of acute and chronic arterial conditions in the central nervous system without the limitation of partial anatomical coverage of the brain.

  8. Whole-brain dynamic CT angiography and perfusion imaging

    International Nuclear Information System (INIS)

    The availability of whole brain computed tomography (CT) perfusion has expanded the opportunities for analysing the haemodynamic parameters associated with varied neurological conditions. Examples demonstrating the clinical utility of whole-brain CT perfusion imaging in selected acute and chronic ischaemic arterial neurovascular conditions are presented. Whole-brain CT perfusion enables the detection and focused haemodynamic analyses of acute and chronic arterial conditions in the central nervous system without the limitation of partial anatomical coverage of the brain.

  9. Functional brain imaging of gastrointestinal sensation in health and disease

    Institute of Scientific and Technical Information of China (English)

    Lukas Van Oudenhove; Steven J Coen; Qasim Aziz

    2007-01-01

    It has since long been known, from everyday experience as well as from animal and human studies, that psychological processes-both affective and cognitiveexert an influence on gastrointestinal sensorimotor function. More specifically, a link between psychological factors and visceral hypersensitivity has been suggested,mainly based on research in functional gastrointestinal disorder patients. However, until recently, the exact nature of this putative relationship remained unclear,mainly due to a lack of non-invasive methods to study the (neurobiological) mechanisms underlying this relationship in non-sleeping humans. As functional brain imaging, introduced in visceral sensory neuroscience some 10 years ago, does provide a method for in vivo study of brain-gut interactions, insight into the neurobiological mechanisms underlying visceral sensation in general and the influence of psychological factors more particularly,has rapidly grown. In this article, an overview of brain imaging evidence on gastrointestinal sensation will be given, with special emphasis on the brain mechanisms underlying the interaction between affective & cognitive processes and visceral sensation. First, the reciprocal neural pathways between the brain and the gut (braingut axis) will be briefly outlined, including brain imaging evidence in healthy volunteers. Second, functional brain imaging studies assessing the influence of psychological factors on brain processing of visceral sensation in healthy humans will be discussed in more detail.Finally, brain imaging work investigating differences in brain responses to visceral distension between healthy volunteers and functional gastrointestinal disorder patients will be highlighted.

  10. Automated segmentation of three-dimensional MR brain images

    Science.gov (United States)

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

    2006-03-01

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

  11. Direct imaging of lateral movements of AMPA receptors inside synapses

    CERN Document Server

    Tardin, Catherine; Bats, Cécile; Lounis, Brahim; Choquet, Daniel

    2003-01-01

    Trafficking of AMPA receptors in and out of synapses is crucial for synaptic plasticity. Previous studies have focused on the role of endo/exocytosis processes or that of lateral diffusion of extra-synaptic receptors. We have now directly imaged AMPAR movements inside and outside synapses of live neurons using single-molecule fluorescence microscopy. Inside individual synapses, we found immobile and mobile receptors, which display restricted diffusion. Extra-synaptic receptors display free diffusion. Receptors could also exchange between these membrane compartments through lateral diffusion. Glutamate application increased both receptor mobility inside synapses and the fraction of mobile receptors present in a juxtasynaptic region. Block of inhibitory transmission to favor excitatory synaptic activity induced a transient increase in the fraction of mobile receptors and a decrease in the proportion of juxtasynaptic receptors. Altogether, our data show that rapid exchange of receptors between a synaptic and ext...

  12. Intracranial Hemorrhage Annotation for CT Brain Images

    Directory of Open Access Journals (Sweden)

    Tong Hau Lee

    2011-01-01

    Full Text Available In this paper, we created a decision-making model to detect intracranial hemorrhage and adopted Expectation Maximization(EM segmentation to segment the Computed Tomography (CT images. In this work, basically intracranial hemorrhage is classified into two main types which are intra-axial hemorrhage and extra-axial hemorrhage. In order to ease classification, contrast enhancement is adopted to finetune the contrast of the hemorrhage. After that, k-means is applied to group the potential and suspicious hemorrhagic regions into one cluster. The decision-making process is to identify whether the suspicious regions are hemorrhagic regions or non-regions of interest. After the hemorrhagic detection, the images are segmented into brain matter and cerebrospinal fluid (CSF by using expectation-maximization (EM segmentation. The acquired experimental results are evaluated in terms of recall and precision. The encouraging results have been attained whereby the proposed system has yielded 0.9333 and 0.8880 precision for extra-axial and intra-axial hemorrhagic detection respectively, whereas recall rate obtained is 0.9245 and 0.8043 for extra-axial and intra-axial hemorrhagic detection respectively.

  13. Experimental research for tumor VIP receptor imaging

    International Nuclear Information System (INIS)

    To study the possibility of radioactive labelled vasoactive intestinal peptide (VIP) for tumor VIP receptor imaging. 125I-VIP was prepared by chloramine-T method, and purified by Sephadex G-50 column chromatography. The bioactivity and stability of 125I-VIP were measured by silica 60 F254 TLC and competition test to SGC7901 cell in vitro. The biodistribution of 125I-VIP was studied in the nude mice bearing tumor. The results showed that labelled rate of 125I was 73.8%, the specific activity was 18.2 PBq/mol, the radiochemical purity (RCP) was over 98% and remained 96.3% after 48 days stored at -80 degree C. The specific binding of 125I-VIP to the SGC7901 cell was inhibited by VIP in dose dependence in the competition experiment. The radioactivity of tumor was higher than that of muscles in all phases (P<0.05-0.01), the peak activity of tumor occurred at 30 min (3.58 +- 0.48ID%/g) and the peak ratio of T/N occurred at 60 min after the injection. The activity of lungs was obviously higher than that of blood, the intestine was always in low level. Most of the activity in the body was mainly eliminated from kidney. The present study demonstrated that the radioactive labelled VIP is a promising agent for tumor VIP receptor scintigraphy

  14. Blockade of brain angiotensin II AT1 receptors ameliorates stress, anxiety, brain inflammation and ischemia: Therapeutic implications.

    Science.gov (United States)

    Saavedra, Juan M; Sánchez-Lemus, Enrique; Benicky, Julius

    2011-01-01

    Poor adaptation to stress, alterations in cerebrovascular function and excessive brain inflammation play critical roles in the pathophysiology of many psychiatric and neurological disorders such as major depression, schizophrenia, post traumatic stress disorder, Parkinson's and Alzheimer's diseases and traumatic brain injury. Treatment for these highly prevalent and devastating conditions is at present very limited and many times inefficient, and the search for novel therapeutic options is of major importance. Recently, attention has been focused on the role of a brain regulatory peptide, Angiotensin II, and in the translational value of the blockade of its physiological AT(1) receptors. In addition to its well-known cardiovascular effects, Angiotensin II, through AT(1) receptor stimulation, is a pleiotropic brain modulatory factor involved in the control of the reaction to stress, in the regulation of cerebrovascular flow and the response to inflammation. Excessive brain AT(1) receptor activity is associated with exaggerated sympathetic and hormonal response to stress, vulnerability to cerebrovascular ischemia and brain inflammation, processes leading to neuronal injury. In animal models, inhibition of brain AT(1) receptor activity with systemically administered Angiotensin II receptor blockers is neuroprotective; it reduces exaggerated stress responses and anxiety, prevents stress-induced gastric ulcerations, decreases vulnerability to ischemia and stroke, reverses chronic cerebrovascular inflammation, and reduces acute inflammatory responses produced by bacterial endotoxin. These effects protect neurons from injury and contribute to increase the lifespan. Angiotensin II receptor blockers are compounds with a good margin of safety widely used in the treatment of hypertension and their anti-inflammatory and vascular protective effects contribute to reduce renal and cardiovascular failure. Inhibition of brain AT(1) receptors in humans is also neuroprotective

  15. Automated in situ brain imaging for mapping the Drosophila connectome.

    Science.gov (United States)

    Lin, Chi-Wen; Lin, Hsuan-Wen; Chiu, Mei-Tzu; Shih, Yung-Hsin; Wang, Ting-Yuan; Chang, Hsiu-Ming; Chiang, Ann-Shyn

    2015-01-01

    Mapping the connectome, a wiring diagram of the entire brain, requires large-scale imaging of numerous single neurons with diverse morphology. It is a formidable challenge to reassemble these neurons into a virtual brain and correlate their structural networks with neuronal activities, which are measured in different experiments to analyze the informational flow in the brain. Here, we report an in situ brain imaging technique called Fly Head Array Slice Tomography (FHAST), which permits the reconstruction of structural and functional data to generate an integrative connectome in Drosophila. Using FHAST, the head capsules of an array of flies can be opened with a single vibratome sectioning to expose the brains, replacing the painstaking and inconsistent brain dissection process. FHAST can reveal in situ brain neuroanatomy with minimal distortion to neuronal morphology and maintain intact neuronal connections to peripheral sensory organs. Most importantly, it enables the automated 3D imaging of 100 intact fly brains in each experiment. The established head model with in situ brain neuroanatomy allows functional data to be accurately registered and associated with 3D images of single neurons. These integrative data can then be shared, searched, visualized, and analyzed for understanding how brain-wide activities in different neurons within the same circuit function together to control complex behaviors.

  16. Interleukin-1 receptors in mouse brain: Characterization and neuronal localization

    International Nuclear Information System (INIS)

    The cytokine interleukin-1 (IL-1) has a variety of effects in brain, including induction of fever, alteration of slow wave sleep, and alteration of neuroendocrine activity. To examine the potential sites of action of IL-1 in brain, we used iodine-125-labeled recombinant human interleukin-1 [( 125I]IL-1) to identify and characterize IL-1 receptors in crude membrane preparations of mouse (C57BL/6) hippocampus and to study the distribution of IL-1-binding sites in brain using autoradiography. In preliminary homogenate binding and autoradiographic studies, [125I]IL-1 alpha showed significantly higher specific binding than [125I]IL-1 beta. Thus, [125I]IL-1 alpha was used in all subsequent assays. The binding of [125I]IL-1 alpha was linear over a broad range of membrane protein concentrations, saturable, reversible, and of high affinity, with an equilibrium dissociation constant value of 114 +/- 35 pM and a maximum number of binding sites of 2.5 +/- 0.4 fmol/mg protein. In competition studies, recombinant human IL-1 alpha, recombinant human IL-1 beta, and a weak IL-1 beta analog. IL-1 beta +, inhibited [125I]IL-1 alpha binding to mouse hippocampus in parallel with their relative bioactivities in the T-cell comitogenesis assay, with inhibitory binding affinity constants of 55 +/- 18, 76 +/- 20, and 2940 +/- 742 pM, respectively; rat/human CRF and human tumor necrosis factor showed no effect on [125I]IL-1 alpha binding. Autoradiographic localization studies revealed very low densities of [125I]IL-1 alpha-binding sites throughout the brain, with highest densities present in the molecular and granular layers of the dentate gyrus of the hippocampus and in the choroid plexus. Quinolinic acid lesion studies demonstrated that the [125I]IL-1 alpha-binding sites in the hippocampus were localized to intrinsic neurons

  17. Selective oestrogen receptor modulators differentially potentiate brain mitochondrial function.

    Science.gov (United States)

    Irwin, R W; Yao, J; To, J; Hamilton, R T; Cadenas, E; Brinton, R D

    2012-01-01

    The mitochondrial energy-transducing capacity of the brain is important for long-term neurological health and is influenced by endocrine hormone responsiveness. The present study aimed to determine the role of oestrogen receptor (ER) subtypes in regulating mitochondrial function using selective agonists for ERα (propylpyrazoletriol; PPT) and ERβ (diarylpropionitrile; DPN). Ovariectomised female rats were treated with 17β-oestradiol (E(2) ), PPT, DPN or vehicle control. Both ER selective agonists significantly increased the mitochondrial respiratory control ratio and cytochrome oxidase (COX) activity relative to vehicle. Western blots of purified whole brain mitochondria detected ERα and, to a greater extent, ERβ localisation. Pre-treatment with DPN, an ERβ agonist, significantly increased ERβ association with mitochondria. In the hippocampus, DPN activated mitochondrial DNA-encoded COX I expression, whereas PPT was ineffective, indicating that mechanistically ERβ, and not ERα, activated mitochondrial transcriptional machinery. Both selective ER agonists increased protein expression of nuclear DNA-encoded COX IV, suggesting that activation of ERβ or ERα is sufficient. Selective ER agonists up-regulated a panel of bioenergetic enzymes and antioxidant defence proteins. Up-regulated proteins included pyruvate dehydrogenase, ATP synthase, manganese superoxide dismutase and peroxiredoxin V. In vitro, whole cell metabolism was assessed in live primary cultured hippocampal neurones and mixed glia. The results of analyses conducted in vitro were consistent with data obtained in vivo. Furthermore, lipid peroxides, accumulated as a result of hormone deprivation, were significantly reduced by E(2) , PPT and DPN. These findings suggest that the activation of both ERα and ERβ is differentially required to potentiate mitochondrial function in brain. As active components in hormone therapy, synthetically designed oestrogens as well as natural phyto-oestrogen cocktails

  18. Imaging of a glioma using peripheral benzodiazepine receptor ligands

    Energy Technology Data Exchange (ETDEWEB)

    Starosta-Rubinstein, S.; Ciliax, B.J.; Penney, J.B.; McKeever, P.; Young, A.B.

    1987-02-01

    Two types of benzodiazepine receptors have been demonstrated in mammalian tissues, one which is localized on neuronal elements in brain and the other, on glial cells and in peripheral tissues such as kidney. In vivo administration of /sup 3/H-labeled PK 11195 (1-(2-chlorophenyl-N-methyl-N-(1-methylpropyl)-3-isoquinoline carboxamide) or (/sup 3/H)flunitrazepam with 5 mg of clonazepam per kg to rats with intracranial C6 gliomas resulted in high levels of tritiated-drug binding to the tumor as shown by quantitative autoradiography. Pharmacological studies indicated that the bound drugs labeled the peripheral benzodiazepine binding site. Binding to the peripheral benzodiazepine site was confirmed primarily to malignant cells with little binding to adjacent normal brain tissue or to necrotic tissue. Tumor cell binding was completely inhibited by preadministration of the peripheral benzodiazepine blocking agent PK 11195 at 5 mg/kg. The centrally selective benzodiazepine ligand clonazepam had no effect on PK 11195 binding to the tumor cells. When binding to other tumor cell lines grown in nude mice and nude athymic rats was evaluated, little or no peripheral benzodiazepine binding was detected on human pheochromocytoma (RN1) and neuroblastoma (SK-N-MC, SK-N-SH) tumor cells, respectively. However, high densities of peripheral benzodiazepine binding sites were observed on tumors derived from a human glioma cell line (ATCC HTB 14, U-87 MG). The presence of high concentrations of specific peripheral benzodiazepine receptors on glial tumors suggests that human primary central nervous system tumors could be imaged and diagnosed using peripheral benzodiazepine ligands labeled with positron- or gamma-emitting isotopes.

  19. Imaging of a glioma using peripheral benzodiazepine receptor ligands

    International Nuclear Information System (INIS)

    Two types of benzodiazepine receptors have been demonstrated in mammalian tissues, one which is localized on neuronal elements in brain and the other, on glial cells and in peripheral tissues such as kidney. In vivo administration of 3H-labeled PK 11195 [1-(2-chlorophenyl-N-methyl-N-(1-methylpropyl)-3-isoquinoline carboxamide] or [3H]flunitrazepam with 5 mg of clonazepam per kg to rats with intracranial C6 gliomas resulted in high levels of tritiated-drug binding to the tumor as shown by quantitative autoradiography. Pharmacological studies indicated that the bound drugs labeled the peripheral benzodiazepine binding site. Binding to the peripheral benzodiazepine site was confirmed primarily to malignant cells with little binding to adjacent normal brain tissue or to necrotic tissue. Tumor cell binding was completely inhibited by preadministration of the peripheral benzodiazepine blocking agent PK 11195 at 5 mg/kg. The centrally selective benzodiazepine ligand clonazepam had no effect on PK 11195 binding to the tumor cells. When binding to other tumor cell lines grown in nude mice and nude athymic rats was evaluated, little or no peripheral benzodiazepine binding was detected on human pheochromocytoma (RN1) and neuroblastoma (SK-N-MC, SK-N-SH) tumor cells, respectively. However, high densities of peripheral benzodiazepine binding sites were observed on tumors derived from a human glioma cell line (ATCC HTB 14, U-87 MG). The presence of high concentrations of specific peripheral benzodiazepine receptors on glial tumors suggests that human primary central nervous system tumors could be imaged and diagnosed using peripheral benzodiazepine ligands labeled with positron- or gamma-emitting isotopes

  20. Improved tumor identification using dual tracer molecular imaging in fluorescence guided brain surgery

    Science.gov (United States)

    Xu, Xiaochun; Torres, Veronica; Straus, David; Brey, Eric M.; Byrne, Richard W.; Tichauer, Kenneth M.

    2015-03-01

    Brain tumors represent a leading cause of cancer death for people under the age of 40 and the probability complete surgical resection of brain tumors remains low owing to the invasive nature of these tumors and the consequences of damaging healthy brain tissue. Molecular imaging is an emerging approach that has the potential to improve the ability for surgeons to correctly discriminate between healthy and cancerous tissue; however, conventional molecular imaging approaches in brain suffer from significant background signal in healthy tissue or an inability target more invasive sections of the tumor. This work presents initial studies investigating the ability of novel dual-tracer molecular imaging strategies to be used to overcome the major limitations of conventional "single-tracer" molecular imaging. The approach is evaluated in simulations and in an in vivo mice study with animals inoculated orthotopically using fluorescent human glioma cells. An epidermal growth factor receptor (EGFR) targeted Affibody-fluorescent marker was employed as a targeted imaging agent, and the suitability of various FDA approved untargeted fluorescent tracers (e.g. fluorescein & indocyanine green) were evaluated in terms of their ability to account for nonspecific uptake and retention of the targeted imaging agent. Signal-to-background ratio was used to measure and compare the amount of reporter in the tissue between targeted and untargeted tracer. The initial findings suggest that FDA-approved fluorescent imaging agents are ill-suited to act as untargeted imaging agents for dual-tracer fluorescent guided brain surgery as they suffer from poor delivery to the healthy brain tissue and therefore cannot be used to identify nonspecific vs. specific uptake of the targeted imaging agent where current surgery is most limited.

  1. GABA[subscript A] Receptor Downregulation in Brains of Subjects with Autism

    Science.gov (United States)

    Fatemi, S. Hossein; Reutiman, Teri J.; Folsom, Timothy D.; Thuras, Paul D.

    2009-01-01

    Gamma-aminobutyric acid A (GABA[subscript A]) receptors are ligand-gated ion channels responsible for mediation of fast inhibitory action of GABA in the brain. Preliminary reports have demonstrated altered expression of GABA receptors in the brains of subjects with autism suggesting GABA/glutamate system dysregulation. We investigated the…

  2. Dopamine D1, D2, D3 receptors, vesicular monoamine transporter type-2 (VMAT2 and dopamine transporter (DAT densities in aged human brain.

    Directory of Open Access Journals (Sweden)

    Jianjun Sun

    Full Text Available The dopamine D(1, D(2, D(3 receptors, vesicular monoamine transporter type-2 (VMAT2, and dopamine transporter (DAT densities were measured in 11 aged human brains (aged 77-107.8, mean: 91 years by quantitative autoradiography. The density of D(1 receptors, VMAT2, and DAT was measured using [(3H]SCH23390, [(3H]dihydrotetrabenazine, and [(3H]WIN35428, respectively. The density of D(2 and D(3 receptors was calculated using the D(3-preferring radioligand, [(3H]WC-10 and the D(2-preferring radioligand [(3H]raclopride using a mathematical model developed previously by our group. Dopamine D(1, D(2, and D(3 receptors are extensively distributed throughout striatum; the highest density of D(3 receptors occurred in the nucleus accumbens (NAc. The density of the DAT is 10-20-fold lower than that of VMAT2 in striatal regions. Dopamine D(3 receptor density exceeded D(2 receptor densities in extrastriatal regions, and thalamus contained a high level of D(3 receptors with negligible D(2 receptors. The density of dopamine D(1 linearly correlated with D(3 receptor density in the thalamus. The density of the DAT was negligible in the extrastriatal regions whereas the VMAT2 was expressed in moderate density. D(3 receptor and VMAT2 densities were in similar level between the aged human and aged rhesus brain samples, whereas aged human brain samples had lower range of densities of D(1 and D(2 receptors and DAT compared with the aged rhesus monkey brain. The differential density of D(3 and D(2 receptors in human brain will be useful in the interpretation of PET imaging studies in human subjects with existing radiotracers, and assist in the validation of newer PET radiotracers having a higher selectivity for dopamine D(2 or D(3 receptors.

  3. A Novel Approach for MRI Brain Images Segmentation

    Directory of Open Access Journals (Sweden)

    Abo-Eleneen Z. A

    2013-03-01

    Full Text Available Segmentation of brain from magnetic resonance (MR images has important applications in neuroimaging, in particular it facilitates in extracting different brain tissues such as cerebrospinal fluids, white matter and gray matter. That helps in determining the volume of the tissues in three-dimensional brain MR images, which yields in analyzing many neural disorders such as epilepsy and Alzheimer disease. The Fisher information is a measure of the fluctuations in the observations. In a sense, the Fisher information of an image specifies the quality of the image. In this paper, we developed a new thresholding method using the Fisher information measure and intensity contrast to segment medical images. It is the weighted sum of the Fisher information measure and intensity contrast between the object and background. This technique is a powerful method for noisy image segmentation. The method applied on a normal MR brain images and a glioma MR brain images. Experimental results show that the use of the Fisher information effectively segmented MR brain images.

  4. Pattern recognition on brain magnetic resonance imaging in alpha dystroglycanopathies

    Directory of Open Access Journals (Sweden)

    Bindu Parayil

    2010-01-01

    Full Text Available Alpha dystroglycanopathies are heterogeneous group of disorders both phenotypically and genetically. A subgroup of these patients has characteristic brain imaging findings. Four patients with typical imaging findings of alpha dystroglycanopathy are reported. Phenotypic features included: global developmental delay, contractures, hypotonia and oculomotor abnormalities in all. Other manifestations were consanguinity (3, seizures (3, macrocephaly (1, microcephaly (3, retinal changes (2 and hypogenitalism (2. Magnetic resonance imaging (MRI of the brain revealed polymicrogyria, white matter changes, pontine hypoplasia, and subcortical cerebellar cysts in all the patients, ventriculomegaly, callosal abnormalities, and absent septum pellucidum in two and Dandy -Walker variant malformation in three. Magnetic resonace imaging of the first cousin of one the patient had the same characteristic imaging features. Brain imaging findings were almost identical despite heterogeneity in clinical presentation and histopathological features. Pattern recognition of MR imaging features may serve as a clue to the diagnosis of alpha dystroglycanopathy.

  5. Role of Hybrid Brain Imaging in Neuropsychiatric Disorders

    Directory of Open Access Journals (Sweden)

    Amer M. Burhan

    2015-12-01

    Full Text Available This is a focused review of imaging literature to scope the utility of hybrid brain imaging in neuropsychiatric disorders. The review focuses on brain imaging modalities that utilize hybrid (fusion techniques to characterize abnormal brain molecular signals in combination with structural and functional changes that have been observed in neuropsychiatric disorders. An overview of clinical hybrid brain imaging technologies for human use is followed by a selective review of the literature that conceptualizes the use of these technologies in understanding basic mechanisms of major neuropsychiatric disorders and their therapeutics. Neuronal network abnormalities are highlighted throughout this review to scope the utility of hybrid imaging as a potential biomarker for each disorder.

  6. Identifying brain neoplasms using dye-enhanced multimodal confocal imaging

    Science.gov (United States)

    Wirth, Dennis; Snuderl, Matija; Sheth, Sameer; Kwon, Churl-Su; Frosch, Matthew P.; Curry, William; Yaroslavsky, Anna N.

    2012-02-01

    Brain tumors cause significant morbidity and mortality even when benign. Completeness of resection of brain tumors improves quality of life and survival; however, that is often difficult to accomplish. The goal of this study was to evaluate the feasibility of using multimodal confocal imaging for intraoperative detection of brain neoplasms. We have imaged different types of benign and malignant, primary and metastatic brain tumors. We correlated optical images with histopathology and evaluated the possibility of interpreting confocal images in a manner similar to pathology. Surgical specimens were briefly stained in 0.05 mg/ml aqueous solution of methylene blue (MB) and imaged using a multimodal confocal microscope. Reflectance and fluorescence signals of MB were excited at 642 nm. Fluorescence emission of MB was registered between 670 and 710 nm. After imaging, tissues were processed for hematoxylin and eosin (H&E) histopathology. The results of comparison demonstrate good correlation between fluorescence images and histopathology. Reflectance images provide information about morphology and vascularity of the specimens, complementary to that provided by fluorescence images. Multimodal confocal imaging has the potential to aid in the intraoperative detection of microscopic deposits of brain neoplasms. The application of this technique may improve completeness of resection and increase patient survival.

  7. Fuzzy object models for newborn brain MR image segmentation

    Science.gov (United States)

    Kobashi, Syoji; Udupa, Jayaram K.

    2013-03-01

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

  8. Design of brain imaging agents for positron emission tomography: do large bioconjugates provide an opportunity for in vivo brain imaging?

    Science.gov (United States)

    Schirrmacher, Ralf; Bernard-Gauthier, Vadim; Reader, Andrew; Soucy, Jean-Paul; Schirrmacher, Esther; Wängler, Björn; Wängler, Carmen

    2013-09-01

    The development of brain imaging agents for positron emission tomography and other in vivo imaging modalities mostly relies on small compounds of low MW as a result of the restricted transport of larger molecules, such as peptides and proteins, across the blood-brain barrier. Besides passive transport, only a few active carrier mechanisms, such as glucose transporters and amino acid transporters, have so far been exploited to mediate the accumulation of imaging probes in the brain. An important question for the future is whether some of the abundant active carrier systems located at the blood-brain barrier can be used to shuttle potential, but non-crossing, imaging agents into the brain. What are the biological and chemical constrictions toward such bioconjugates and is it worthwhile to persue such a delivery strategy?

  9. Appropriate Contrast Enhancement Measures for Brain and Breast Cancer Images

    Directory of Open Access Journals (Sweden)

    Suneet Gupta

    2016-01-01

    Full Text Available Medical imaging systems often produce images that require enhancement, such as improving the image contrast as they are poor in contrast. Therefore, they must be enhanced before they are examined by medical professionals. This is necessary for proper diagnosis and subsequent treatment. We do have various enhancement algorithms which enhance the medical images to different extents. We also have various quantitative metrics or measures which evaluate the quality of an image. This paper suggests the most appropriate measures for two of the medical images, namely, brain cancer images and breast cancer images.

  10. A mu–delta opioid receptor brain atlas reveals neuronal co-occurrence in subcortical networks

    OpenAIRE

    Erbs, Eric; Faget, Lauren; Scherrer, Gregory; Matifas, Audrey; Filliol, Dominique; Vonesch, Jean-Luc; Koch, Marc; Kessler, Pascal; Hentsch, Didier; Birling, Marie-Christine; Koutsourakis, Manoussos; Vasseur, Laurent; Veinante, Pierre; Kieffer, Brigitte L.; Massotte, Dominique

    2014-01-01

    Opioid receptors are G protein-coupled receptors (GPCRs) that modulate brain function at all levels of neural integration, including autonomic, sensory, emotional and cognitive processing. Mu (MOR) and delta (DOR) opioid receptors functionally interact in vivo, but whether interactions occur at circuitry, cellular or molecular levels remains unsolved. To challenge the hypothesis of MOR/DOR heteromerization in the brain, we generated redMOR/greenDOR double knock-in mice and report dual recepto...

  11. Mechanism of Chronic Pain in Rodent Brain Imaging

    Science.gov (United States)

    Chang, Pei-Ching

    Chronic pain is a significant health problem that greatly impacts the quality of life of individuals and imparts high costs to society. Despite intense research effort in understanding of the mechanism of pain, chronic pain remains a clinical problem that has few effective therapies. The advent of human brain imaging research in recent years has changed the way that chronic pain is viewed. To further extend the use of human brain imaging techniques for better therapies, the adoption of imaging technique onto the animal pain models is essential, in which underlying brain mechanisms can be systematically studied using various combination of imaging and invasive techniques. The general goal of this thesis is to addresses how brain develops and maintains chronic pain in an animal model using fMRI. We demonstrate that nucleus accumbens, the central component of mesolimbic circuitry, is essential in development of chronic pain. To advance our imaging technique, we develop an innovative methodology to carry out fMRI in awake, conscious rat. Using this cutting-edge technique, we show that allodynia is assoicated with shift brain response toward neural circuits associated nucleus accumbens and prefrontal cortex that regulate affective and cognitive component of pain. Taken together, this thesis provides a deeper understanding of how brain mediates pain. It builds on the existing body of knowledge through maximizing the depth of insight into brain imaging of chronic pain.

  12. Endothelium in brain: Receptors, mitogenesis, and biosynthesis in glial cells

    Energy Technology Data Exchange (ETDEWEB)

    MacCumber, M.W.; Ross, C.A.; Snyder, S.H. (Johns Hopkins Univ. School of Medicine, Baltimore, MD (USA))

    1990-03-01

    The authors have explored the cellular loci of endothelin (ET) actions and formation in the brain, using cerebellar mutant mice was well as primary and continuous cell cultures. A glial role is favored by several observations: (1) mutant mice lacking neuronal Purkinje cells display normal ET receptor binding and enhanced stimulation by ET of inositolphospholipid turnover; (ii) in weaver mice lacking neuronal granule cells, ET stimulation of inositolphospholipid turnover is not significantly diminished; (iii) C{sub 6} glioma cells and primary cultures of cerebellar astroglia exhibit substantial ET receptor binding and ET-induced stimulation of inositolphospholipid turnover; (iv) ET promotes mitogenesis of C{sub 6} glioma cells and primary cerebellar astroglia; and (v) primary cultures of cerebellar astroglia contain ET mRNA. ET also appears to have a neuronal role, since it stimulates inositolphospholipid turnover in primary cultures of cerebellar granule cells, and ET binding declines in granule cell-deficient mice. Thus, ET can be produced by glia and act upon both glia and neurons in a paracrine fashion.

  13. [11C]-MeJDTic: a novel radioligand for κ-opioid receptor positron emission tomography imaging

    International Nuclear Information System (INIS)

    Introduction: Radiopharmaceuticals that can bind selectively the κ-opioid receptor may present opportunities for staging clinical brain disorders and evaluating the efficiency of new therapies related to stroke, neurodegenerative diseases or opiate addiction. The N-methylated derivative of JDTic (named MeJDTic), which has been recently described as a potent and selective antagonist of κ-opioid receptor in vitro, was labeled with carbon-11 and evaluated for in vivo imaging the κ-opioid receptor in mice. Methods: [11C]-MeJDTic was prepared by methylation of JDTic with [11C]-methyl triflate. The binding of [11C]-MeJDTic to κ-opioid receptor was investigated ex vivo by biodistribution and competition studies using nonfasted male CD1 mice. Results: [11C]-MeJDTic exhibited a high and rapid distribution in peripheral organs. The uptake was maximal in lung where the κ receptor is largely expressed. [11C]-MeJDTic rapidly crossed the blood-brain barrier and accumulated in the brain regions of interest (hypothalamus). The parent ligand remained the major radioactive compound in brain during the experiment. Chase studies with U50,488 (a κ referring agonist), morphine (a μ agonist) and naltrindole (a δ antagonist) demonstrated that this uptake was the result of specific binding to the κ-opioid receptor. Conclusion: These findings suggested that [11C]-MeJDTic appeared to be a promising selective 'lead' radioligand for κ-opioid receptor PET imaging

  14. Functional brain imaging studies on specificity of meridian and acupoints

    Institute of Scientific and Technical Information of China (English)

    Xuezhi Li; Xuguang Liu; Fanrong Liang

    2008-01-01

    At present,the specificity of meridians and acupoints has been studied using functional brain imaging techniques from many standpoints.including meridians,acupoints,and sham acupoints,as well as different meridians and acupoints,coordination of acupoints,and factors influencing meridian and acupoint specificity.Preliminary experimental data have demonstrated that acupuncture at meridians and acupoints is specific with regard to brain neural information.However,research findings are contradictory,which may be related to brain functional complexity,resolution of functional brain imaging techniques,and experimental design.Future studies should further improve study method,and should strictly control experimental conditions to better analyze experimental data and acquire more beneficial data.Because of its many advantages.the functional brain imaging technique is a promising method for studying meridian and acupoint specificity.

  15. Antibodies to the α1-adrenergic receptor cause vascular impairments in rat brain as demonstrated by magnetic resonance angiography.

    Directory of Open Access Journals (Sweden)

    Peter Karczewski

    Full Text Available BACKGROUND: Circulating agonistic autoantibodies acting at G protein-coupled receptors have been associated with numerous sever pathologies in humans. Antibodies directed predominantly against the α(1-adrenergig receptor were detected in patients suffering from widespread diseases such as hypertension and type 2 diabetes. Their deleterious action has been demonstrated for peripheral organs. We postulate that antibodies to the α(1-adrenergig receptor are relevant pathomolecules in diseases of the central nervous system associated with vascular impairments. METHODOLOGY/PRINCIPAL FINDINGS: Using a rat model we studied the long-term action of antibodies against the α(1-adrenergig receptor either induced by immunization with a receptor peptide or applied by intravenous injection. The vasculature in the rat brains was investigated by time-of-flight magnetic resonance angiography using a 9.4 Tesla small animal MR imaging system. Visual examination of maximum-intensity-projections (MIPs of brain angiographs revealed the development of vascular defects in antibody- exposed animals between three and eight months of treatment. Relative vascular areas were derived from representative MIP image sections by grayscale analysis and used to form an index of vascular circulation. Animals exposed to the action of α(1-adrenergig receptor antibodies showed significantly reduced vascular areas (p<0.05. Calculated index values indicated attenuated blood flow in both antibody-treated cohorts compared to their respective controls reaching with (relative units ± standard error, n = 10 0.839 ± 0.026 versus 0.919 ± 0.026 statistical significance (p<0.05 for peptide-immunized rats. CONCLUSION/SIGNIFICANCE: We present evidence that antibodies to the α(1-adrenergig receptor cause cerebrovascular impairments in the rat. Our findings suggest the pathological significance of these antibodies in pathologies of the human central nervous system linked to impairments of

  16. Skull-stripping for Tumor-bearing Brain Images

    CERN Document Server

    Bauer, Stefan; Reyes, Mauricio

    2012-01-01

    Skull-stripping separates the skull region of the head from the soft brain tissues. In many cases of brain image analysis, this is an essential preprocessing step in order to improve the final result. This is true for both registration and segmentation tasks. In fact, skull-stripping of magnetic resonance images (MRI) is a well-studied problem with numerous publications in recent years. Many different algorithms have been proposed, a summary and comparison of which can be found in [Fennema-Notestine, 2006]. Despite the abundance of approaches, we discovered that the algorithms which had been suggested so far, perform poorly when dealing with tumor-bearing brain images. This is mostly due to additional difficulties in separating the brain from the skull in this case, especially when the lesion is located very close to the skull border. Additionally, images acquired according to standard clinical protocols, often exhibit anisotropic resolution and only partial coverage, which further complicates the task. There...

  17. The Center for Integrated Molecular Brain Imaging (Cimbi) database

    DEFF Research Database (Denmark)

    Knudsen, Gitte M.; Jensen, Peter S.; Erritzoe, David;

    2016-01-01

    We here describe a multimodality neuroimaging containing data from healthy volunteers and patients, acquired within the Lundbeck Foundation Center for Integrated Molecular Brain Imaging (Cimbi) in Copenhagen, Denmark. The data is of particular relevance for neurobiological research questions...

  18. Imaging of brain tumors with histological correlations. 2. ed.

    Energy Technology Data Exchange (ETDEWEB)

    Drevelegas, Antonios (ed.)

    2011-07-01

    This volume provides a deeper understanding of the diagnosis of brain tumors by correlating radiographic imaging features with the underlying pathological abnormalities. All modern imaging modalities are used to complete a diagnostic overview of brain tumors with emphasis on recent advances in diagnostic neuroradiology. High-quality illustrations depicting common and uncommon imaging characteristics of a wide range of brain tumors are presented and analysed, drawing attention to the ways in which these characteristics reflect different aspects of pathology. Important theoretical considerations are also discussed. Since the first edition, chapters have been revised and updated and new material has been added, including detailed information on the clinical application of functional MRI and diffusion tensor imaging. Radiologists and other clinicians interested in the current diagnostic approach to brain tumors will find this book to be an invaluable and enlightening clinical tool. (orig.)

  19. Automated morphometry of transgenic mouse brains in MR images

    NARCIS (Netherlands)

    Scheenstra, Alize Elske Hiltje

    2011-01-01

    Quantitative and local morphometry of mouse brain MRI is a relatively new field of research, where automated methods can be exploited to rapidly provide accurate and repeatable results. In this thesis we reviewed several existing methods and applications of quantitative morphometry to brain MR image

  20. Quantitative assessment of brain perfusion with magnetic resonance imaging

    NARCIS (Netherlands)

    Bleeker, Egbert Jan Willem

    2011-01-01

    This thesis focuses on assessing blood supply to brain tissue using MRI. For Dynamic Susceptibility Contrast-MRI a series of images is acquired during the passage of a bolus contrast agent through the brain up to the point that the contrast agent is equally mixed within the total blood pool. The tis

  1. Structural brain imaging in diabetes : A methodological perspective

    NARCIS (Netherlands)

    Jongen, Cynthia; Biessels, Geert Jan

    2008-01-01

    Brain imaging provides information on brain anatomy and function and progression of cerebral abnormalities can be monitored. This may provide insight into the aetiology of diabetes related cerebral disorders. This paper focuses on the methods for the assessment of white matter hyperintensities and b

  2. Rapid and automatic detection of brain tumors in MR images

    Science.gov (United States)

    Wang, Zhengjia; Hu, Qingmao; Loe, KiaFock; Aziz, Aamer; Nowinski, Wieslaw L.

    2004-04-01

    An algorithm to automatically detect brain tumors in MR images is presented. The key concern is speed in order to process efficiently large brain image databases and provide quick outcomes in clinical setting. The method is based on study of asymmetry of the brain. Tumors cause asymmetry of the brain, so we detect brain tumors in 3D MR images using symmetry analysis of image grey levels with respect to the midsagittal plane (MSP). The MSP, separating the brain into two hemispheres, is extracted using our previously developed algorithm. By removing the background pixels, the normalized grey level histograms are calculated for both hemispheres. The similarity between these two histograms manifests the symmetry of the brain, and it is quantified by using four symmetry measures: correlation coefficient, root mean square error, integral of absolute difference (IAD), and integral of normalized absolute difference (INAD). A quantitative analysis of brain normality based on 42 patients with tumors and 55 normals is presented. The sensitivity and specificity of IAD and INAD were 83.3% and 89.1%, and 85.7% and 83.6%, respectively. The running time for each symmetry measure for a 3D 8bit MR data was between 0.1 - 0.3 seconds on a 2.4GHz CPU PC.

  3. {sup 18}F-labeled RGD peptide: initial evaluation for imaging brain tumor angiogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Chen Xiaoyuan; Park, Ryan; Shahinian, Anthony H.; Tohme, Michel; Khankaldyyan, Vazgen; Bozorgzadeh, Mohammed H.; Bading, James R.; Moats, Rex; Laug, Walter E.; Conti, Peter S. E-mail: pconti@usc.edu

    2004-02-01

    Brain tumors are highly angiogenesis dependent. The cell adhesion receptor integrin {alpha}{sub v}{beta}{sub 3} is overexpressed in glioma and activated endothelial cells and plays an important role in brain tumor growth, spread and angiogenesis. Suitably labeled {alpha}{sub v}{beta}{sub 3}-integrin antagonists may therefore be useful for imaging brain tumor associated angiogenesis. Cyclic RGD peptide c(RGDyK) was labeled with {sup 18}F via N-succinimidyl-4-[{sup 18}F]fluorobenzoate through the side-chain {epsilon}-amino group of the lysine residue. The radiotracer was evaluated in vivo for its tumor targeting efficacy and pharmacokinetics in subcutaneously implanted U87MG and orthotopically implanted U251T glioblastoma nude mouse models by means of microPET, quantitative autoradiography and direct tissue sampling. The N-4-[{sup 18}F]fluorobenzoyl-RGD ([{sup 18}F]FB-RGD) was produced in less than 2 h with 20-25% decay-corrected yields and specific activity of 230 GBq/{mu}mol at end of synthesis. The tracer showed very rapid blood clearance and both hepatobiliary and renal excretion. Tumor-to-muscle uptake ratio at 30 min was approximately 5 in the subcutaneous U87MG tumor model. MicroPET imaging with the orthotopic U251T brain tumor model revealed very high tumor-to-brain ratio, with virtually no uptake in the normal brain. Successful blocking of tumor uptake of [{sup 18}F]FB-RGD in the presence of excess amount of c(RGDyK) revealed receptor specific activity accumulation. Hence, N-4-[{sup 18}F]fluorobenzoyl labeled cyclic RGD peptide [{sup 18}F]FB-RGD is a potential tracer for imaging {alpha}{sub v}{beta}{sub 3}-integrin positive tumors in brain and other anatomic locations.

  4. Do brain image databanks support understanding of normal ageing brain structure? A systematic review

    Energy Technology Data Exchange (ETDEWEB)

    Dickie, David Alexander; Job, Dominic E.; Wardlaw, Joanna M. [University of Edinburgh, Division of Clinical Neurosciences, Western General Hospital, Brain Research Imaging Centre (BRIC), Edinburgh (United Kingdom); Scottish Imaging Network, A Platform for Scientific Excellence (SINAPSE), Edinburgh (United Kingdom); Poole, Ian [Toshiba Medical Visualisation Systems Europe, Ltd., Edinburgh (United Kingdom); Ahearn, Trevor S.; Staff, Roger T.; Murray, Alison D. [University of Aberdeen, Aberdeen Biomedical Imaging Centre, Aberdeen (United Kingdom); Scottish Imaging Network, A Platform for Scientific Excellence (SINAPSE), Edinburgh (United Kingdom)

    2012-07-15

    To document accessible magnetic resonance (MR) brain images, metadata and statistical results from normal older subjects that may be used to improve diagnoses of dementia. We systematically reviewed published brain image databanks (print literature and Internet) concerned with normal ageing brain structure. From nine eligible databanks, there appeared to be 944 normal subjects aged {>=}60 years. However, many subjects were in more than one databank and not all were fully representative of normal ageing clinical characteristics. Therefore, there were approximately 343 subjects aged {>=}60 years with metadata representative of normal ageing, but only 98 subjects were openly accessible. No databank had the range of MR image sequences, e.g. T2*, fluid-attenuated inversion recovery (FLAIR), required to effectively characterise the features of brain ageing. No databank supported random subject retrieval; therefore, manual selection bias and errors may occur in studies that use these subjects as controls. Finally, no databank stored results from statistical analyses of its brain image and metadata that may be validated with analyses of further data. Brain image databanks require open access, more subjects, metadata, MR image sequences, searchability and statistical results to improve understanding of normal ageing brain structure and diagnoses of dementia. (orig.)

  5. STEREOLOGICAL EVALUATION OF BRAIN MAGNETIC RESONANCE IMAGES OF SCHIZOPHRENIC PATIENTS

    Directory of Open Access Journals (Sweden)

    Amani Abdelrazag Elfaki

    2013-11-01

    Full Text Available Advances in neuroimaging have enabled studies of specific neuroanatomical abnormalities with relevance to schizophrenia. This study quantified structural alterations on brain magnetic resonance (MR images of patients with schizophrenia. MR brain imaging was done on 88 control and 57 schizophrenic subjects and Dicom images were analyzed with ImageJ software. The brain volume was estimated with the planimetric stereological technique. The volume fraction of brain structures was also estimated. The results showed that, the mean volume of right, left, and total hemispheres in controls were 551, 550, and 1101 cm³, respectively. The mean volumes of right, left, and total hemispheres in schizophrenics were 513, 512, and 1026 cm³, respectively. The schizophrenics’ brains were smaller than the controls (p < 0.05. The mean volume of total white matter of controls (516 cm³ was bigger than the schizophrenics’ volume (451 cm³, (p < 0.05. The volume fraction of total white matter was also lower in schizophrenics (p < 0.05. Volume fraction of the lateral ventricles was higher in schizophrenics (p < 0.05. According to the findings, the volumes of schizophrenics’ brain were smaller than the controls and the volume fractional changes in schizophrenics showed sex dependent differences. We conclude that stereological analysis of MR brain images is useful for quantifying schizophrenia related structural changes.

  6. Brain Imaging, Forward Inference, and Theories of Reasoning

    OpenAIRE

    Evan Heit

    2015-01-01

    This review focuses on the issue of how neuroimaging studies address theoretical accounts of reasoning, through the lens of the method of forward inference (Henson, 2005, 2006). After theories of deductive and inductive reasoning are briefly presented, the method of forward inference for distinguishing between psychological theories based on brain imaging evidence is critically reviewed. Brain imaging studies of reasoning, comparing deductive and inductive arguments, comparing meaningful ve...

  7. Unsupervised Neural Techniques Applied to MR Brain Image Segmentation

    Directory of Open Access Journals (Sweden)

    A. Ortiz

    2012-01-01

    Full Text Available The primary goal of brain image segmentation is to partition a given brain image into different regions representing anatomical structures. Magnetic resonance image (MRI segmentation is especially interesting, since accurate segmentation in white matter, grey matter and cerebrospinal fluid provides a way to identify many brain disorders such as dementia, schizophrenia or Alzheimer’s disease (AD. Then, image segmentation results in a very interesting tool for neuroanatomical analyses. In this paper we show three alternatives to MR brain image segmentation algorithms, with the Self-Organizing Map (SOM as the core of the algorithms. The procedures devised do not use any a priori knowledge about voxel class assignment, and results in fully-unsupervised methods for MRI segmentation, making it possible to automatically discover different tissue classes. Our algorithm has been tested using the images from the Internet Brain Image Repository (IBSR outperforming existing methods, providing values for the average overlap metric of 0.7 for the white and grey matter and 0.45 for the cerebrospinal fluid. Furthermore, it also provides good results for high-resolution MR images provided by the Nuclear Medicine Service of the “Virgen de las Nieves” Hospital (Granada, Spain.

  8. AN ANN BASED BRAIN ABNORMALITY DETECTION USING MR IMAGES

    Directory of Open Access Journals (Sweden)

    K.V. Kulhalli

    2013-02-01

    Full Text Available The Main purpose of this paper is to design, implement and evaluate a strong automatic diagnostic system that increases the accuracy of tumor diagnosis in brain using MR images. This presented work classifies the brain tissues as normal or abnormal automatically, using computer vision. This saves lot of radiologist time to carryout monotonous repeated job. The acquired MR images are processed using image preprocessing techniques. The preprocessed images are then segmented, and the various features are extracted. The extracted features are fed to the artificial neural network as input that trains the network using error back propagation algorithm for correct decision making.

  9. The potential of using brain images for authentication.

    Science.gov (United States)

    Chen, Fanglin; Zhou, Zongtan; Shen, Hui; Hu, Dewen

    2014-01-01

    Biometric recognition (also known as biometrics) refers to the automated recognition of individuals based on their biological or behavioral traits. Examples of biometric traits include fingerprint, palmprint, iris, and face. The brain is the most important and complex organ in the human body. Can it be used as a biometric trait? In this study, we analyze the uniqueness of the brain and try to use the brain for identity authentication. The proposed brain-based verification system operates in two stages: gray matter extraction and gray matter matching. A modified brain segmentation algorithm is implemented for extracting gray matter from an input brain image. Then, an alignment-based matching algorithm is developed for brain matching. Experimental results on two data sets show that the proposed brain recognition system meets the high accuracy requirement of identity authentication. Though currently the acquisition of the brain is still time consuming and expensive, brain images are highly unique and have the potential possibility for authentication in view of pattern recognition. PMID:25126604

  10. PPG neurons of the lower brain stem and their role in brain GLP-1 receptor activation.

    Science.gov (United States)

    Trapp, Stefan; Cork, Simon C

    2015-10-15

    Within the brain, glucagon-like peptide-1 (GLP-1) affects central autonomic neurons, including those controlling the cardiovascular system, thermogenesis, and energy balance. Additionally, GLP-1 influences the mesolimbic reward system to modulate the rewarding properties of palatable food. GLP-1 is produced in the gut and by hindbrain preproglucagon (PPG) neurons, located mainly in the nucleus tractus solitarii (NTS) and medullary intermediate reticular nucleus. Transgenic mice expressing glucagon promoter-driven yellow fluorescent protein revealed that PPG neurons not only project to central autonomic control regions and mesolimbic reward centers, but also strongly innervate spinal autonomic neurons. Therefore, these brain stem PPG neurons could directly modulate sympathetic outflow through their spinal inputs to sympathetic preganglionic neurons. Electrical recordings from PPG neurons in vitro have revealed that they receive synaptic inputs from vagal afferents entering via the solitary tract. Vagal afferents convey satiation to the brain from signals like postprandial gastric distention or activation of peripheral GLP-1 receptors. CCK and leptin, short- and long-term satiety peptides, respectively, increased the electrical activity of PPG neurons, while ghrelin, an orexigenic peptide, had no effect. These findings indicate that satiation is a main driver of PPG neuronal activation. They also show that PPG neurons are in a prime position to respond to both immediate and long-term indicators of energy and feeding status, enabling regulation of both energy balance and general autonomic homeostasis. This review discusses the question of whether PPG neurons, rather than gut-derived GLP-1, are providing the physiological substrate for the effects elicited by central nervous system GLP-1 receptor activation.

  11. MR image-guided portal verification for brain treatment field

    International Nuclear Information System (INIS)

    Purpose: To investigate a method for the generation of digitally reconstructed radiographs directly from MR images (DRR-MRI) to guide a computerized portal verification procedure. Methods and Materials: Several major steps were developed to perform an MR image-guided portal verification procedure. Initially, a wavelet-based multiresolution adaptive thresholding method was used to segment the skin slice-by-slice in MR brain axial images. Some selected anatomical structures, such as target volume and critical organs, were then manually identified and were reassigned to relatively higher intensities. Interslice information was interpolated with a directional method to achieve comparable display resolution in three dimensions. Next, a ray-tracing method was used to generate a DRR-MRI image at the planned treatment position, and the ray tracing was simply performed on summation of voxels along the ray. The skin and its relative positions were also projected to the DRR-MRI and were used to guide the search of similar features in the portal image. A Canny edge detector was used to enhance the brain contour in both portal and simulation images. The skin in the brain portal image was then extracted using a knowledge-based searching technique. Finally, a Chamfer matching technique was used to correlate features between DRR-MRI and portal image. Results: The MR image-guided portal verification method was evaluated using a brain phantom case and a clinical patient case. Both DRR-CT and DRR-MRI were generated using CT and MR phantom images with the same beam orientation and then compared. The matching result indicated that the maximum deviation of internal structures was less than 1 mm. The segmented results for brain MR slice images indicated that a wavelet-based image segmentation technique provided a reasonable estimation for the brain skin. For the clinical patient case with a given portal field, the MR image-guided verification method provided an excellent match between

  12. Molecular cloning, chromosomal mapping, and functional expression of human brain glutamate receptors

    Energy Technology Data Exchange (ETDEWEB)

    Sun, W.; Ferrer-Montiel, A.V.; Schinder, A.F.; Montal, M. (Univ. of California, San Diego, La Jolla (United States)); McPherson, J.P. (Univ. of California, Irvine (United States)); Evans, G.A. (Salk Inst. for Biological Studies, La Jolla, CA (United States))

    1992-02-15

    A full-length cDNA clone encoding a glutamate receptor was isolated from a human brain cDNA library, and the gene product was characterized after expression in Xenopus oocytes. Degenerate PCR primers to conserved regions of published rat brain glutamate receptor sequences amplified a 1-kilobase fragment from a human brain cDNA library. This fragment was used as a probe for subsequent hybridization screening. Two clones were isolated that, based on sequence information, code for different receptors: a 3-kilobase clone, HBGR1, contains a full-length glutamate receptor cDNA highly homologous to the rat brain clone GluR1, and a second clone, HBGR2, contains approximately two-thirds of the coding region of a receptor homologous to rat brain clone GluR2. Southern and PCr analysis of a somatic cell-hybrid panel mapped HBGR1 to human chromosome 5q31.3-33.3 and mapped HBGR2 to chromosome 4q25-34.3. Xenopus oocytes injected with in vitro-synthesized HBGR1 cRNA expressed currents activated by glutamate receptor agonists. These results indicate that clone HBGR1 codes for a glutamate receptor of the kainate subtype cognate to members of the glutamate receptor family from rodent brain.

  13. Age, sex and NK1 receptors in the human brain -- a positron emission tomography study with [¹¹C]GR205171.

    Science.gov (United States)

    Engman, Jonas; Åhs, Fredrik; Furmark, Tomas; Linnman, Clas; Pissiota, Anna; Appel, Lieuwe; Frans, Örjan; Långström, Bengt; Fredrikson, Mats

    2012-08-01

    The substance P/neurokinin 1 (SP/NK1) system has been implicated in the processing of negative affect. Its role seems complex and findings from animal studies have not been easily translated to humans. Brain imaging studies on NK1 receptor distribution in humans have revealed an abundance of receptors in cortical, striatal and subcortical areas, including the amygdala. A reduction in NK1 receptors with increasing age has been reported in frontal, temporal, and parietal cortices, as well as in hippocampal areas. Also, a previous study suggests sex differences in cortical and subcortical areas, with women displaying fewer NK1 receptors. The present PET study explored NK1 receptor availability in men (n=9) and women (n=9) matched for age varying between 20 and 50years using the highly specific NK1 receptor antagonist [¹¹C]GR205171 and a reference tissue model with cerebellum as the reference region. Age by sex interactions in the amygdala and the temporal cortex reflected a lower NK1 receptor availability with increasing age in men, but not in women. A general age-related decline in NK1 receptor availability was evident in the frontal, temporal, and occipital cortices, as well as in the brainstem, caudate nucleus, and thalamus. Women had lower NK1 receptor availability in the thalamus. The observed pattern of NK1 receptor distribution in the brain might have functional significance for brain-related disorders showing age- and sex-related differences in prevalence. PMID:22225860

  14. Natural image classification driven by human brain activity

    Science.gov (United States)

    Zhang, Dai; Peng, Hanyang; Wang, Jinqiao; Tang, Ming; Xue, Rong; Zuo, Zhentao

    2016-03-01

    Natural image classification has been a hot topic in computer vision and pattern recognition research field. Since the performance of an image classification system can be improved by feature selection, many image feature selection methods have been developed. However, the existing supervised feature selection methods are typically driven by the class label information that are identical for different samples from the same class, ignoring with-in class image variability and therefore degrading the feature selection performance. In this study, we propose a novel feature selection method, driven by human brain activity signals collected using fMRI technique when human subjects were viewing natural images of different categories. The fMRI signals associated with subjects viewing different images encode the human perception of natural images, and therefore may capture image variability within- and cross- categories. We then select image features with the guidance of fMRI signals from brain regions with active response to image viewing. Particularly, bag of words features based on GIST descriptor are extracted from natural images for classification, and a sparse regression base feature selection method is adapted to select image features that can best predict fMRI signals. Finally, a classification model is built on the select image features to classify images without fMRI signals. The validation experiments for classifying images from 4 categories of two subjects have demonstrated that our method could achieve much better classification performance than the classifiers built on image feature selected by traditional feature selection methods.

  15. Atypical pyogenic brain abscess evaluation by diffusion-weighted imaging: diagnosis with multimodality MR imaging.

    Science.gov (United States)

    Ozbayrak, Mustafa; Ulus, Ozden Sila; Berkman, Mehmet Zafer; Kocagoz, Sesin; Karaarslan, Ercan

    2015-10-01

    Whether a brain abscess is apparent by imaging depends on the stage of the abscess at the time of imaging, as well as the etiology of the infection. Because conventional magnetic resonance imaging (MRI) is limited in its ability to distinguish brain abscesses from necrotic tumors, advanced techniques are required. The management of these two disease entities differs and can potentially affect the clinical outcome. We report a case having atypical imaging features of a pyogenic brain abscess on advanced MRI, in particular, on diffusion-weighted and perfusion imaging, in a patient with osteosarcoma undergoing chemotherapy.

  16. Computed tomographic imaging of the brain of normal neonatal foals

    Directory of Open Access Journals (Sweden)

    L Cabrera

    2015-01-01

    Full Text Available The aim of this study was to provide a more complete description of normal cross-sectional anatomy of the neonatal brain of the foal and associated structures by computed tomography (CT and gross anatomical sections. Using a fourth-generation CT scanner, 2-mm contiguous transverse images were acquired from two neonatal 5-days-old Quarter horse foals. After the study the animals were euthanised for reasons unrelated to head pathology. To assist in the accurate identification of brain and associated structures, transverse CT images were obtained and compared with the corresponding frozen cross-sections of the head. CT images matched well with their corresponding transverse gross sections and provided good differentiation between the bones and the soft tissues of the head. These CT images are intended to be a useful initial anatomic reference in the interpretation for clinical CT imaging studies of the brain and associated structures in live neonatal foals.

  17. In vivo calcium imaging of the aging and diseased brain

    Energy Technology Data Exchange (ETDEWEB)

    Eichhoff, Gerhard; Busche, Marc A.; Garaschuk, Olga [Technical University of Munich, Institute of Neuroscience, Munich (Germany)

    2008-03-15

    Over the last decade, in vivo calcium imaging became a powerful tool for studying brain function. With the use of two-photon microscopy and modern labelling techniques, it allows functional studies of individual living cells, their processes and their interactions within neuronal networks. In vivo calcium imaging is even more important for studying the aged brain, which is hard to investigate in situ due to the fragility of neuronal tissue. In this article, we give a brief overview of the techniques applicable to image aged rodent brain at cellular resolution. We use multicolor imaging to visualize specific cell types (neurons, astrocytes, microglia) as well as the autofluorescence of the ''aging pigment'' lipofuscin. Further, we illustrate an approach for simultaneous imaging of cortical cells and senile plaques in mouse models of Alzheimer's disease. (orig.)

  18. Three-dimensional microtomographic imaging of human brain cortex

    CERN Document Server

    Mizutania, Ryuta; Uesugi, Kentaro; Ohyama, Masami; Takekoshi, Susumu; Osamura, R Yoshiyuki; Suzuki, Yoshio

    2016-01-01

    This paper describes an x-ray microtomographic technique for imaging the three-dimensional structure of the human cerebral cortex. Neurons in the brain constitute a neural circuit as a three-dimensional network. The brain tissue is composed of light elements that give little contrast in a hard x-ray transmission image. The contrast was enhanced by staining neural cells with metal compounds. The obtained structure revealed the microarchitecture of the gray and white matter regions of the frontal cortex, which is responsible for the higher brain functions.

  19. The Center for Integrated Molecular Brain Imaging (Cimbi) database.

    Science.gov (United States)

    Knudsen, Gitte M; Jensen, Peter S; Erritzoe, David; Baaré, William F C; Ettrup, Anders; Fisher, Patrick M; Gillings, Nic; Hansen, Hanne D; Hansen, Lars Kai; Hasselbalch, Steen G; Henningsson, Susanne; Herth, Matthias M; Holst, Klaus K; Iversen, Pernille; Kessing, Lars V; Macoveanu, Julian; Madsen, Kathrine Skak; Mortensen, Erik L; Nielsen, Finn Årup; Paulson, Olaf B; Siebner, Hartwig R; Stenbæk, Dea S; Svarer, Claus; Jernigan, Terry L; Strother, Stephen C; Frokjaer, Vibe G

    2016-01-01

    We here describe a multimodality neuroimaging containing data from healthy volunteers and patients, acquired within the Lundbeck Foundation Center for Integrated Molecular Brain Imaging (Cimbi) in Copenhagen, Denmark. The data is of particular relevance for neurobiological research questions related to the serotonergic transmitter system with its normative data on the serotonergic subtype receptors 5-HT1A, 5-HT1B, 5-HT2A, and 5-HT4 and the 5-HT transporter (5-HTT), but can easily serve other purposes. The Cimbi database and Cimbi biobank were formally established in 2008 with the purpose to store the wealth of Cimbi-acquired data in a highly structured and standardized manner in accordance with the regulations issued by the Danish Data Protection Agency as well as to provide a quality-controlled resource for future hypothesis-generating and hypothesis-driven studies. The Cimbi database currently comprises a total of 1100 PET and 1000 structural and functional MRI scans and it holds a multitude of additional data, such as genetic and biochemical data, and scores from 17 self-reported questionnaires and from 11 neuropsychological paper/computer tests. The database associated Cimbi biobank currently contains blood and in some instances saliva samples from about 500 healthy volunteers and 300 patients with e.g., major depression, dementia, substance abuse, obesity, and impulsive aggression. Data continue to be added to the Cimbi database and biobank. PMID:25891375

  20. Brain-specific interleukin-1 receptor accessory protein in sleep regulation

    OpenAIRE

    Taishi, Ping; Davis, Christopher J.; Bayomy, Omar; Zielinski, Mark R.; Liao, Fan; Clinton, James M.; Smith, Dirk E.; Krueger, James M.

    2011-01-01

    Interleukin (IL)-1β is involved in several brain functions, including sleep regulation. It promotes non-rapid eye movement (NREM) sleep via the IL-1 type I receptor. IL-1β/IL-1 receptor complex signaling requires adaptor proteins, e.g., the IL-1 receptor brain-specific accessory protein (AcPb). We have cloned and characterized rat AcPb, which shares substantial homologies with mouse AcPb and, compared with AcP, is preferentially expressed in the brain. Furthermore, rat somatosensory cortex Ac...

  1. Autoradiographic analysis of alpha 1-noradrenergic receptors in the human brain postmortem. Effect of suicide

    International Nuclear Information System (INIS)

    In vitro quantitative autoradiography of alpha 1-noradrenergic receptors, using tritiated prazosin as a ligand, was performed on 24 human brains postmortem. Twelve brains were obtained from suicide victims and 12 from matched controls. We found significant lower binding to alpha 1 receptors in several brain regions of the suicide group as compared with matched controls. This decrease in receptor density was evident in portions of the prefrontal cortex, as well as the temporal cortex and in the caudate nucleus. Age, sex, presence of alcohol, and time of death to autopsy did not affect prazosin binding, in our sample, as measured by autoradiography

  2. Brain imaging of pain: state of the art

    Science.gov (United States)

    Morton, Debbie L; Sandhu, Javin S; Jones, Anthony KP

    2016-01-01

    Pain is a complex sensory and emotional experience that is heavily influenced by prior experience and expectations of pain. Before the development of noninvasive human brain imaging, our grasp of the brain’s role in pain processing was limited to data from postmortem studies, direct recording of brain activity, patient experience and stimulation during neurosurgical procedures, and animal models of pain. Advances made in neuroimaging have bridged the gap between brain activity and the subjective experience of pain and allowed us to better understand the changes in the brain that are associated with both acute and chronic pain. Additionally, cognitive influences on pain such as attention, anticipation, and fear can now be directly observed, allowing for the interpretation of the neural basis of the psychological modulation of pain. The use of functional brain imaging to measure changes in endogenous neurochemistry has increased our understanding of how states of increased resilience and vulnerability to pain are maintained. PMID:27660488

  3. Whole brain imaging with Serial Two-Photon Tomography

    Directory of Open Access Journals (Sweden)

    Stephen P Amato

    2016-03-01

    Full Text Available Imaging entire mouse brains at submicron resolution has historically been a challenging undertaking and largely confined to the province of dedicated atlasing initiatives. The has limited systematic investigations into important areas of neuroscience, such as neural circuits, brain mapping and neurodegeneration. In this paper, we describe in detail Serial Two-Photon (STP tomography, a robust, reliable method for imaging entire brains with histological detail. We provide examples of how the basic methodology can be extended to other imaging modalities, such as optical coherence tomography, in order to provide unique contrast mechanisms. Furthermore we provide a survey of the research that STP tomography has enabled in the field of neuroscience, provide examples of how this technology enables quantitative whole brain studies, and discuss the current limitations of STP tomography-based approaches

  4. Brain SPECT imaging in temporal lobe epilepsy

    International Nuclear Information System (INIS)

    Temporal lobe epilepsy is diagnosed by clinical symptoms and signs and by localization of an epileptogenic focus. A brain SPECT study of two patients with temporal lobe epilepsy, using 99mTc-HMPAO, was used to demonstrate a perfusion abnormality in the temporal lobe, while brain CT and MRI were non-contributory. The electroencephalogram, though abnormal, did not localize the diseased area. The potential role of the SPECT study in diagnosis and localization of temporal lobe epilepsy is discussed. (orig.)

  5. Photoacoustic imaging for transvascular drug delivery to the rat brain

    Science.gov (United States)

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

    2015-03-01

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

  6. Evaluation of 7 {alpha}-O-IADPN as a new potential SPECT opioid receptor imaging agent

    Energy Technology Data Exchange (ETDEWEB)

    Wang, R.F.; Mao, S.Y. [Fujian Medical College, Fuzhou (China). Dept. of Nuclear Medicine; Tafani, J.A.M.; Coulais, Y.; Guiraud, R. [Hospital Purpan, Toulouse (France). Service Central de medicine Nucleaire; Zajac, J.M. [LPTF-CNRS, Toulouse (France)

    1998-03-01

    Full text: A new iodinated diprenorphine antagonist analogue, [{sup 123}I]7 {alpha}.-O-IADPN, [E] - 17-(cyclopropylmethyl) -4,5 (x-epoxy- 18,19-dihydro-3-hydroxy-6-methoxy-7 {alpha}-[1-(3-iodoallyl)oxy-1-methylethyl]-6,14-endo-ethenomorphinan for in vivo and in vitro studies as a potential central nervous system (CNS) opioid receptor imaging agent was developed. In vivo biodistribution and metabolism of 7 {alpha}-O-lADPN in rat demonstrated that 0.16% of the iodinated compound was presented in mouse brain with a degradation-resistant at the first 60 min, and that 36% of the total cerebral radioactivity and 63% of its specific binding to opioid receptors were observed 20 min after i.v. injection. The cerebral radioactivity in mouse brain concentrated in the basal ganglion and cortex, and displayed a remarkably high target-to-non-target ratio (cortex/cerebellum = 60 min post-injection). The in vitro binding studies showed that [{sup 123}I]7 {alpha}-O-IADPN binds non selectively to multiple opioid receptors {mu} = 8 K) with a very high affinity (Ki = 0.4 + 0.2 nM). Ex vivo autoradiography results in mouse further confirmed the high uptake and retention of this agent in basal ganglion region and cortex. The planar imaging of monkey brains after i.v. injection of [{sup 123}I]7 {alpha}-O-IADPN clearly displayed that multiple opioid receptors can be visualized. With the excellent in vitro affinity and in vivo stability to deiodination and high target-to-nontarget ratio, [{sup 123}I]7 {alpha}- O-IADPN appears to be useful as a CNS opioid receptor imaging probe for SPECT in primate and non-primate.

  7. Wavelet Based Image Fusion for Detection of Brain Tumor

    Directory of Open Access Journals (Sweden)

    CYN Dwith

    2013-01-01

    Full Text Available Brain tumor, is one of the major causes for the increase in mortality among children and adults. Detecting the regions of brain is the major challenge in tumor detection. In the field of medical image processing, multi sensor images are widely being used as potential sources to detect brain tumor. In this paper, a wavelet based image fusion algorithm is applied on the Magnetic Resonance (MR images and Computed Tomography (CT images which are used as primary sources to extract the redundant and complementary information in order to enhance the tumor detection in the resultant fused image. The main features taken into account for detection of brain tumor are location of tumor and size of the tumor, which is further optimized through fusion of images using various wavelet transforms parameters. We discuss and enforce the principle of evaluating and comparing the performance of the algorithm applied to the images with respect to various wavelets type used for the wavelet analysis. The performance efficiency of the algorithm is evaluated on the basis of PSNR values. The obtained results are compared on the basis of PSNR with gradient vector field and big bang optimization. The algorithms are analyzed in terms of performance with respect to accuracy in estimation of tumor region and computational efficiency of the algorithms.

  8. Preclinical study of dopamine D2 receptor imaging agent 131I-epidepride

    International Nuclear Information System (INIS)

    Objective: To study the radioactivity distribution and the characteristic of imaging with dopamine D2 receptor imaging agent-epidepride. Methods: 131I-epidepride was prepared using hydrogen peroxide as the oxidant. The authors chose SD rats to study the characteristics of 131I-epidepride distribution in vivo and in brain. Two rabbits were used in SPECT imaging. Dynamic acquisition was performed in one rabbit after rapid injection of 370 MBq 131I-epidepride, and time-activity curve was obtained with Region of Interesting (ROI) technique. The other rabbit had brain tomography imaging and whole body imaging according to the result of time-activity curve. Results: The radiolabeling yield (RLY) of 131I-epidepride with hydrogen peroxide was over 95%. In vivo, the uptake of heart and lung was the fastest, so was the clearance of the two organs. The clearance of 131I-epidepride from the body was mainly through liver, stomach and intestines. The striatum uptake was concentrated and stable, while the cerebellum clearance was rapid. Conclusion: The hydrogen peroxide method is simple and fast with high RLY. The striatum uptake is concentrated and stable. 131I-epidepride is an effective agent suitable for dopamine D2 receptor imaging and may be a promising agent for clinical application

  9. Imaging Findings of Brain Death on 3-Tesla MRI

    International Nuclear Information System (INIS)

    To demonstrate the usefulness of 3-tesla (3T) magnetic resonance imaging (MRI) including T2-weighted imaging (T2WI), diffusion weighted imaging (DWI), time-of-flight (TOF) magnetic resonance angiography (MRA), T2*-weighted gradient recalled echo (GRE), and susceptibility weighted imaging (SWI) in diagnosing brain death. Magnetic resonance imaging findings for 10 patients with clinically verified brain death (group I) and seven patients with comatose or stuporous mentality who did not meet the clinical criteria of brain death (group II) were retrospectively reviewed. Tonsilar herniation and loss of intraarterial flow signal voids (LIFSV) on T2WI were highly sensitive and specific findings for the diagnosis of brain death (p < 0.001 and < 0.001, respectively). DWI, TOF-MRA, and GRE findings were statistically different between the two groups (p = 0.015, 0.029, and 0.003, respectively). However, cortical high signal intensities in T2WI and SWI findings were not statistically different between the two group (p = 0.412 and 1.0, respectively). T2-weighted imaging, DWI, and MRA using 3T MRI may be useful for diagnosing brain death. However, SWI findings are not specific due to high false positive findings.

  10. Imaging Findings of Brain Death on 3-Tesla MRI

    Energy Technology Data Exchange (ETDEWEB)

    Sohn, Chul Ho [Dept. of Radiology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul (Korea, Republic of); Lee, Hwa Pyung [Dept. of Occupational and Environmental Medicine, CHA Gumi Medical Center, CHA University, Gumi (Korea, Republic of); Park, Jun Beom [Dept. of Radiology, Korean Armed Force Daejeon Hospital, Daejeon (Korea, Republic of); Chang, Hyuk Won; Kim, Easlmaan; Park, Ui Jun; Kim, Hyoung Tae [Keimyung University College of Medicine, Dongsan Medical Center, Daegu (Korea, Republic of); Kim, Eun Hee [Dept. of Radiology, Seoul National University Bundang Hospital, Seongnam (Korea, Republic of); Ku, Jeong Hun [Dept. of Biomedical Engineering, Keimyung University College of Medicine, Daegu (Korea, Republic of)

    2012-09-15

    To demonstrate the usefulness of 3-tesla (3T) magnetic resonance imaging (MRI) including T2-weighted imaging (T2WI), diffusion weighted imaging (DWI), time-of-flight (TOF) magnetic resonance angiography (MRA), T2*-weighted gradient recalled echo (GRE), and susceptibility weighted imaging (SWI) in diagnosing brain death. Magnetic resonance imaging findings for 10 patients with clinically verified brain death (group I) and seven patients with comatose or stuporous mentality who did not meet the clinical criteria of brain death (group II) were retrospectively reviewed. Tonsilar herniation and loss of intraarterial flow signal voids (LIFSV) on T2WI were highly sensitive and specific findings for the diagnosis of brain death (p < 0.001 and < 0.001, respectively). DWI, TOF-MRA, and GRE findings were statistically different between the two groups (p = 0.015, 0.029, and 0.003, respectively). However, cortical high signal intensities in T2WI and SWI findings were not statistically different between the two group (p = 0.412 and 1.0, respectively). T2-weighted imaging, DWI, and MRA using 3T MRI may be useful for diagnosing brain death. However, SWI findings are not specific due to high false positive findings.

  11. Fuzzy local Gaussian mixture model for brain MR image segmentation.

    Science.gov (United States)

    Ji, Zexuan; Xia, Yong; Sun, Quansen; Chen, Qiang; Xia, Deshen; Feng, David Dagan

    2012-05-01

    Accurate brain tissue segmentation from magnetic resonance (MR) images is an essential step in quantitative brain image analysis. However, due to the existence of noise and intensity inhomogeneity in brain MR images, many segmentation algorithms suffer from limited accuracy. In this paper, we assume that the local image data within each voxel's neighborhood satisfy the Gaussian mixture model (GMM), and thus propose the fuzzy local GMM (FLGMM) algorithm for automated brain MR image segmentation. This algorithm estimates the segmentation result that maximizes the posterior probability by minimizing an objective energy function, in which a truncated Gaussian kernel function is used to impose the spatial constraint and fuzzy memberships are employed to balance the contribution of each GMM. We compared our algorithm to state-of-the-art segmentation approaches in both synthetic and clinical data. Our results show that the proposed algorithm can largely overcome the difficulties raised by noise, low contrast, and bias field, and substantially improve the accuracy of brain MR image segmentation.

  12. Nonneural Androgen Receptors Affect Sexual Differentiation of Brain and Behavior.

    Science.gov (United States)

    Swift-Gallant, Ashlyn; Coome, Lindsay A; Ramzan, Firyal; Monks, D Ashley

    2016-02-01

    Testosterone, acting via estrogenic and androgenic pathways, is the major endocrine mechanism promoting sexual differentiation of the mammalian nervous system and behavior, but we have an incomplete knowledge of which cells and tissues mediate these effects. To distinguish between neural and nonneural actions of androgens in sexual differentiation of brain and behavior, we generated a loxP-based transgenic mouse, which overexpresses androgen receptors (ARs) when activated by Cre. We used this transgene to overexpress AR globally in all tissues using a cytomegalovirus (CMV)-Cre driver (CMV-AR), and we used a Nestin-Cre driver to overexpress AR only in neural tissue (Nes-AR). We then examined whether neural or global AR overexpression can affect socio-sexual behaviors using a resident-intruder paradigm. We found that both neural and global AR overexpression resulted in decreased aggressive behaviors and increased thrusting during mounting of intruders, consistent with a neural site of action. Global, but not neural, AR overexpression in males led to an increase in same-sex anogenital investigation. Together, these results suggest novel roles for nonneural AR in sexual differentiation of mice, and indicate that excess AR can lead to a paradoxical reduction of male-typical behavior. PMID:26636184

  13. Evaluation of MRI and cannabinoid type 1 receptor PET templates constructed using DARTEL for spatial normalization of rat brains

    Energy Technology Data Exchange (ETDEWEB)

    Kronfeld, Andrea; Müller-Forell, Wibke [Institute of Neuroradiology, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstraße 1, Mainz 55131 (Germany); Buchholz, Hans-Georg; Maus, Stephan; Reuss, Stefan; Schreckenberger, Mathias; Miederer, Isabelle, E-mail: isabelle.miederer@unimedizin-mainz.de [Department of Nuclear Medicine, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstraße 1, Mainz 55131 (Germany); Lutz, Beat [Institute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University Mainz, Duesbergweg 6, Mainz 55128 (Germany)

    2015-12-15

    Purpose: Image registration is one prerequisite for the analysis of brain regions in magnetic-resonance-imaging (MRI) or positron-emission-tomography (PET) studies. Diffeomorphic anatomical registration through exponentiated Lie algebra (DARTEL) is a nonlinear, diffeomorphic algorithm for image registration and construction of image templates. The goal of this small animal study was (1) the evaluation of a MRI and calculation of several cannabinoid type 1 (CB1) receptor PET templates constructed using DARTEL and (2) the analysis of the image registration accuracy of MR and PET images to their DARTEL templates with reference to analytical and iterative PET reconstruction algorithms. Methods: Five male Sprague Dawley rats were investigated for template construction using MRI and [{sup 18}F]MK-9470 PET for CB1 receptor representation. PET images were reconstructed using the algorithms filtered back-projection, ordered subset expectation maximization in 2D, and maximum a posteriori in 3D. Landmarks were defined on each MR image, and templates were constructed under different settings, i.e., based on different tissue class images [gray matter (GM), white matter (WM), and GM + WM] and regularization forms (“linear elastic energy,” “membrane energy,” and “bending energy”). Registration accuracy for MRI and PET templates was evaluated by means of the distance between landmark coordinates. Results: The best MRI template was constructed based on gray and white matter images and the regularization form linear elastic energy. In this case, most distances between landmark coordinates were <1 mm. Accordingly, MRI-based spatial normalization was most accurate, but results of the PET-based spatial normalization were quite comparable. Conclusions: Image registration using DARTEL provides a standardized and automatic framework for small animal brain data analysis. The authors were able to show that this method works with high reliability and validity. Using DARTEL

  14. Evaluation of MRI and cannabinoid type 1 receptor PET templates constructed using DARTEL for spatial normalization of rat brains

    International Nuclear Information System (INIS)

    Purpose: Image registration is one prerequisite for the analysis of brain regions in magnetic-resonance-imaging (MRI) or positron-emission-tomography (PET) studies. Diffeomorphic anatomical registration through exponentiated Lie algebra (DARTEL) is a nonlinear, diffeomorphic algorithm for image registration and construction of image templates. The goal of this small animal study was (1) the evaluation of a MRI and calculation of several cannabinoid type 1 (CB1) receptor PET templates constructed using DARTEL and (2) the analysis of the image registration accuracy of MR and PET images to their DARTEL templates with reference to analytical and iterative PET reconstruction algorithms. Methods: Five male Sprague Dawley rats were investigated for template construction using MRI and [18F]MK-9470 PET for CB1 receptor representation. PET images were reconstructed using the algorithms filtered back-projection, ordered subset expectation maximization in 2D, and maximum a posteriori in 3D. Landmarks were defined on each MR image, and templates were constructed under different settings, i.e., based on different tissue class images [gray matter (GM), white matter (WM), and GM + WM] and regularization forms (“linear elastic energy,” “membrane energy,” and “bending energy”). Registration accuracy for MRI and PET templates was evaluated by means of the distance between landmark coordinates. Results: The best MRI template was constructed based on gray and white matter images and the regularization form linear elastic energy. In this case, most distances between landmark coordinates were <1 mm. Accordingly, MRI-based spatial normalization was most accurate, but results of the PET-based spatial normalization were quite comparable. Conclusions: Image registration using DARTEL provides a standardized and automatic framework for small animal brain data analysis. The authors were able to show that this method works with high reliability and validity. Using DARTEL templates

  15. Clinical anatomy of the canine brain using magnetic resonance imaging.

    Science.gov (United States)

    Leigh, Edmund J; Mackillop, Edward; Robertson, Ian D; Hudson, Lola C

    2008-01-01

    The purpose of this study was to produce an magnetic resonsnce (MR) image atlas of clinically relevant brain anatomy and to relate this neuroanatomy to clinical signs. The brain of a large mixed breed dog was imaged in transverse, sagittal, and dorsal planes using a 1.5 T MR unit and the following pulse sequences: Turbo (fast) spin echo (TSE) T2, T1, and T2- weighted spatial and chemical shift-encoded excitation sequence. Relevant neuroanatomic structures were identified using anatomic texts, sectioned cadaver heads, and previously published atlases. Major subdivisions of the brain were mapped and the neurologic signs of lesions in these divisions were described. TSE T2-weighted images were found to be the most useful for identifying clinically relevant neuroanatomy. Relating clinical signs to morphology as seen on MR will assist veterinarians to better understand clinically relevant neuroanatomy in MR images. PMID:18418990

  16. Differential MRI Diagnosis Between Brain Abscess and Necrotic or Cystic Brain Tumors Using Diffusion Weighted Images

    Directory of Open Access Journals (Sweden)

    Zinat Miabi

    2009-01-01

    Full Text Available "nIntroduction: Differentiating brain abscesses from cystic or necrotic tumors by CT or MR imaging can be difficult. Difficulties in the diagnosis of intracranial abscess are mainly due to the combination of often unspecified clinical findings and similarities in the morphologic appearance of some intracranial mass lesions, such as cystic gliomas, metastases, and brain abscesses. Diffusion-weighted imaging provides a way to evaluate the diffusion properties of water molecules in tissue and has been used for diseases such as ischemia, tumors, epilepsy, and white matter disorders. The goal of this study was to evaluate the diagnostic utility of diffusion MRI to differentiate between brain abscesses and necrotic or cystic brain tumors. "nMaterials and Methods: MRI was performed in 17 patients (12 men and five women; age range, 19–74 years [mean, 55 years] with necrotic lesions and MR imaging evidence of ring-shaped enhancement after the injection of contrast material .In addition to standard MR sequences diffusion weighted MRI with apparent coefficient (ADC maps. "nResults: Eleven patients had tumors, and six had pyogenic abscesses. The tumors were glioblastomas (five patients, anaplastic astrocytoma (three patients, metastases (three patients, and primary malignancy, including lung (2 and breast (1 cancer. Surgical or stereotactic biopsies were obtained, and histologic studies were performed in all except one case (case 5. In the cases of abscess, bacteriologic analysis was also conducted. None of these lesions appeared hemorrhagic on T1-weighted images. "nConclusion: Diffusion-weighted imaging is useful for differentiating brain abscess from cystic or necrotic brain tumor, which is often difficult with conventional MR imaging. Diffusion-weighted imaging is useful as an additional imaging technique for establishing the differential diagnosis between brain abscesses and cystic or necrotic brain tumors. It requires less imaging time and is more

  17. Technical advances of interventional fluoroscopy and flat panel image receptor.

    Science.gov (United States)

    Lin, Pei-Jan Paul

    2008-11-01

    In the past decade, various radiation reducing devices and control circuits have been implemented on fluoroscopic imaging equipment. Because of the potential for lengthy fluoroscopic procedures in interventional cardiovascular angiography, these devices and control circuits have been developed for the cardiac catheterization laboratories and interventional angiography suites. Additionally, fluoroscopic systems equipped with image intensifiers have benefited from technological advances in x-ray tube, x-ray generator, and spectral shaping filter technologies. The high heat capacity x-ray tube, the medium frequency inverter generator with high performance switching capability, and the patient dose reduction spectral shaping filter had already been implemented on the image intensified fluoroscopy systems. These three underlying technologies together with the automatic dose rate and image quality (ADRIQ) control logic allow patients undergoing cardiovascular angiography procedures to benefit from "lower patient dose" with "high image quality." While photoconductor (or phosphor plate) x-ray detectors and signal capture thin film transistor (TFT) and charge coupled device (CCD) arrays are analog in nature, the advent of the flat panel image receptor allowed for fluoroscopy procedures to become more streamlined. With the analog-to-digital converter built into the data lines, the flat panel image receptor appears to become a digital device. While the transition from image intensified fluoroscopy systems to flat panel image receptor fluoroscopy systems is part of the on-going "digitization of imaging," the value of a flat panel image receptor may have to be evaluated with respect to patient dose, image quality, and clinical application capabilities. The advantage of flat panel image receptors has yet to be fully explored. For instance, the flat panel image receptor has its disadvantages as compared to the image intensifiers; the cost of the equipment is probably the most

  18. Review: magnetic resonance imaging of male/female differences in human adolescent brain anatomy

    Directory of Open Access Journals (Sweden)

    Giedd Jay N

    2012-08-01

    Full Text Available Abstract Improvements in neuroimaging technologies, and greater access to their use, have generated a plethora of data regarding male/female differences in the developing brain. Examination of these differences may shed light on the pathophysiology of the many illnesses that differ between the sexes and ultimately lead to more effective interventions. In this review, we attempt to synthesize the anatomic magnetic resonance imaging (MRI literature of male/female brain differences with emphasis on studies encompassing adolescence – a time of divergence in physical and behavioral characteristics. Across all ages total brain size is consistently reported to be about 10% larger in males. Structures commonly reported to be different between sexes include the caudate nucleus, amygdala, hippocampus, and cerebellum – all noted to have a relatively high density of sex steroid receptors. The direction and magnitude of reported brain differences depends on the methodology of data acquisition and analysis, whether and how the subcomponents are adjusted for the total brain volume difference, and the age of the participants in the studies. Longitudinal studies indicate regional cortical gray matter volumes follow inverted U shaped developmental trajectories with peak size occurring one to three years earlier in females. Cortical gray matter differences are modulated by androgen receptor genotyope and by circulating levels of hormones. White matter volumes increase throughout childhood and adolescence in both sexes but more rapidly in adolescent males resulting in an expanding magnitude of sex differences from childhood to adulthood.

  19. Identifying Brain Image Level Endophenotypes in Epilepsy

    CERN Document Server

    Cheng, Wei; Tian, Ge; Feng, Jianfeng; Wang, Zhengge; Zhang, Zhiqiang; Lu, GuangMing

    2012-01-01

    A brain wide association study (BWAS) based on the logistic regression was first developed and applied to a large population of epilepsy patients (168) and healthy controls (136). It was found that the most significant links associated with epilepsy are those bilateral links with regions mainly belonging to the default mode network and subcortex, such as amygdala, fusiform gyrus, inferior temporal gyrus, hippocampus, temporal pole, parahippocampal gyrus, insula, middle occipital gyrus, cuneus. These links were found to have much higher odd ratios than other links, and all of them showed reduced functional couplings in patients compared with controls. Interestingly, with the increasing of the seizure onset frequency or duration of illness, the functional connection between these bilateral regions became further reduced. On the other hand, as a functional compensation and brain plasticity, connections of these bilateral regions to other brain regions were abnormally enhanced and became even much stronger with t...

  20. Scaffolding of Fyn Kinase to the NMDA Receptor Determines Brain Region Sensitivity to Ethanol

    OpenAIRE

    Yaka, Rami; Phamluong, Khanhky; Ron, Dorit

    2003-01-01

    Alcohol (ethanol) abuse is a major societal problem. Although ethanol is a structurally simple, diffusible molecule, its sites of action are surprisingly selective, and the molecular mechanisms underlying specificity in ethanol actions are not understood. The NMDA receptor channel is one of the main targets for ethanol in the brain. We report here that the brain region-specific compartmentalization of Fyn kinase determines NMDA receptor sensitivity to ethanol. We demonstrate that, in the hipp...

  1. Eph Receptor and Ephrin Signaling in Developing and Adult Brain of the Honeybee (Apis mellifera)

    OpenAIRE

    Vidovic, Maria; Nighorn, Alan; Koblar, Simon; Maleszka, Ryszard

    2007-01-01

    Roles for Eph receptor tyrosine kinase and ephrin signaling in vertebrate brain development are well established. Their involvement in the modulation of mammalian synaptic structure and physiology is also emerging. However, less is known of their effects on brain development and their function in adult invertebrate nervous systems. Here, we report on the characterization of Eph receptor and ephrin orthologs in the honeybee, Apis mellifera (Am), and their role in learning and memory. In situ h...

  2. The sigma-1 receptor enhances brain plasticity and functional recovery after experimental stroke

    DEFF Research Database (Denmark)

    Ruscher, Karsten; Shamloo, Mehrdad; Rickhag, Karl Mattias;

    2011-01-01

    in an enriched environment for two weeks after permanent middle cerebral artery occlusion, we found increased sigma-1 receptor expression in peri-infarct areas. Treatment of rats subjected to permanent or transient middle cerebral artery occlusion with 1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl...... of biomolecules required for brain repair, thereby stimulating brain plasticity. Pharmacological targeting of the sigma-1 receptor provides new opportunities for stroke treatment beyond the therapeutic window of neuroprotection....

  3. MR imaging of the neonatal brain: Pathologic features

    International Nuclear Information System (INIS)

    Seventy-three neonates, aged 29-43 weeks since conception, were studied. US and/or CT correlations were obtained in most infants with pathology. In the first 4-5 days after hemorrhage, US and CT were superior to MR imaging, but after that time MR imaging was the single best modality for imaging blood. In early premature infants with very watery white matter, US detected infarction and brain edema that were poorly seen on both MR imaging and CT. However, in late premature and full-term infants, MR imaging was better than CT in distinguishing between normal white matter and infarction. Only MR imaging disclosed delayed myelination in 13 term infants with hydrocephalus and severe asphyxia. MR imaging with play an important role in imaging neonates once MR imaging-compatible monitors and neonatal head coils become widely available

  4. Brain imaging in lung cancer patients without symptoms of brain metastases: a national survey of current practice in England

    International Nuclear Information System (INIS)

    Aim: To determine current practice regarding brain imaging for newly diagnosed lung cancer patients without symptoms of brain metastases. Materials and methods: A survey questionnaire was sent by e-mail to all the lung cancer lead clinicians in England currently on the National Cancer Intelligence Network database. The survey asked whether brain imaging was used in new lung cancer patients without symptoms or signs to suggest brain metastases; and if so, which patient subgroups were imaged according to cell type, stage of disease, and intention to treat, and which techniques were used to image these patients. Responses were received between February and May 2014. Results: Fifty-nine of 154 centres replied to the survey (38%). Thirty of the 59 centres (51%) did not image the brain in these patients. Twenty-nine of the 59 (49%) centres imaged the brain in at least certain subgroups. Of those centres that did image the brain 21 (72%) used CT as the first-line imaging technique and six (20%) used MRI. Twenty-five of 59 (42%) centres stated that the 2011 NICE guidelines had led to a change in their practice. Conclusion: There is wide variation in practice regarding brain imaging in this patient group in England, with no brain imaging at all in approximately half of centres and a spectrum of imaging in the other half. When the brain is imaged, CT is the technique most commonly used. The 2011 NICE guidelines have led to some change in practice but not to national uniformity. - Highlights: • Ascertain current practice in brain imaging for staging asymptomatic lung cancer patients. • Survey questionnaire sent to all the lung cancer lead clinicians in England. • Wide variation in practice with regard to brain imaging in this patient group. • No brain imaging at all in approximately half of centres and a spectrum of imaging in the other half • The 2011 NICE guidelines have led to some change in practice but not to national uniformity

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

    Science.gov (United States)

    Studholme, Colin

    2011-08-15

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

  6. Metabolic Syndrome, Brain Magnetic Resonance Imaging, and Cognition

    OpenAIRE

    Cavalieri, Margherita; Ropele, Stefan; Petrovic, Katja; Pluta-Fuerst, Aga; Homayoon, Nina; Enzinger, Christian; Grazer, Anja; Katschnig, Petra; Schwingenschuh, Petra; Berghold, Andrea; Schmidt, Reinhold

    2010-01-01

    OBJECTIVE We explored cognitive impairment in metabolic syndrome in relation to brain magnetic resonance imaging (MRI) findings. RESEARCH DESIGN AND METHODS We studied 819 participants free of clinical stroke and dementia of the population-based Austrian Stroke Prevention Study who had undergone brain MRI, neuropsychological testing, and a risk factor assessment relevant to National Cholesterol Education Program Adult Treatment Panel III criteria–defined metabolic syndrome. High-sensitivity C...

  7. Brain magnetic resonance imaging of infants exposed prenatally to buprenorphine

    International Nuclear Information System (INIS)

    Purpose: To evaluate the brains of newborns exposed to buprenorphine prenatally. Material and Methods: Seven neonates followed up antenatally in connection with their mothers' buprenorphine replacement therapy underwent 1.5T magnetic resonance imaging (MRI) of the brain before the age of 2 months. The infants were born to heavy drug abusers. Four mothers were hepatitis C positive, and all were HIV negative. All mothers smoked tobacco and used benzodiazepines. All pregnancies were full term, and no perinatal asphyxia occurred. All but one neonate had abstinence syndrome and needed morphine replacement therapy. Results: Neither structural abnormalities nor abnormalities in signal intensity were recorded. Conclusion: Buprenorphine replacement therapy does not seem to cause any major structural abnormalities of the brain, and it may prevent known hypoxic-ischemic brain changes resulting from uncontrolled drug abuse. Longitudinal studies are needed to assess possible abnormalities in the brain maturation process

  8. Cerenkov and radioluminescence imaging of brain tumor specimens during neurosurgery

    Science.gov (United States)

    Spinelli, Antonello Enrico; Schiariti, Marco P.; Grana, Chiara M.; Ferrari, Mahila; Cremonesi, Marta; Boschi, Federico

    2016-05-01

    We presented the first example of Cerenkov luminescence imaging (CLI) and radioluminescence imaging (RLI) of human tumor specimens. A patient with a brain meningioma localized in the left parietal region was injected with 166 MBq of Y90-DOTATOC the day before neurosurgery. The specimens of the tumor removed during surgery were imaged using both CLI and RLI using an optical imager prototype developed in our laboratory. The system is based on a cooled electron multiplied charge coupled device coupled with an f/0.95 17-mm C-mount lens. We showed for the first time the possibility of obtaining CLI and RLI images of fresh human brain tumor specimens removed during neurosurgery.

  9. 123I-iomazenil brain receptor SPECT in focal epilepsy. In comparison with 99mTc-HMPAO brain SPECT, MRI and Video/EEG monitoring

    International Nuclear Information System (INIS)

    Purpose: To evaluate the clinical value of 123I-Iomazenil brain receptor SPECT in diagnosis of focal epilepsy in comparison with 99mTc-HMPAO brain SPECT, MRI and Video/EEG monitoring. Methods 123I-Iomazenil brain receptor SPECT was performed on 40 patients with focal epilepsy. The results were compared with those obtained by 99mTc-HMPAO brain SPECT, MRI and Video/EEG monitoring. Results: In 40 patients, the sensitivity of Video/EEG monitoring for localization of epileptogenic area was 95% (38/40). The sensitivity of 123I-iomazenil brain receptor SPECT, 99mTc-HMPAO brain SPECT and MRI for localization of epileptogenic area compared with Video/EEG monitoring ('gold standard') was 65.8%(25/38), 55.3%(21/38) and 47.4%(18/38), respectively. The localization of epileptogenic area with 123I-Iomazenil brain receptor SPECT was in concordance with Video/EEG monitoring in 20 patients, 99mTc-HMPAO brain SPECT in 15 patients and MRI in 16 patients, respectively. The sensitivity of 123I-Iomazenil brain receptor SPECT combined with MRI for localization of epileptogenic area was 84.2%(32/38). Conclusions: 123I-Iomazenil brain receptor SPECT is a useful method in detecting and localizing epileptogenic area. The combination of 123I-Iomazenil brain receptor SPECT and MRI has a high sensitivity for detecting epileptogenic area

  10. Use of automated image registration to generate mean brain SPECT image of Alzheimer's patients

    International Nuclear Information System (INIS)

    The purpose of this study was to compute and compare the group mean HMPAO brain SPECT images of patients with senile dementia of Alzheimer's type (SDAT) and age matched control subjects after transformation of the individual images to a standard size and shape. Ten patients with Alzheimer's disease (age 71.6±5.0 yr) and ten age matched normal subjects (age 71.0±6.1 yr) participated in this study. Tc-99m HMPAO brain SPECT and X-ray CT scans were acquired for each subject. SPECT images were normalized to an average activity of 100 counts/pixel. Individual brain images were transformed to a standard size and shape with the help of Automated Image Registration (AIR). Realigned brain SPECT images of both groups were used to generate mean and standard deviation images by arithmetic operations on voxel based numerical values. Mean images of both groups were compared by applying the unpaired t-test on a voxel by voxel basis to generate three dimensional T-maps. X-ray CT images of individual subjects were evaluated by means of a computer program for brain atrophy. A significant decrease in relative radioisotope (RI) uptake was present in the bilateral superior and inferior parietal lobules (p<0.05), bilateral inferior temporal gyri, and the bilateral superior and middle frontal gyri (p<0.001). The mean brain atrophy indices for patients and normal subjects were 0.853±0.042 and 0.933±0.017 respectively, the difference being statistically significant (p<0.001). The use of a brain image standardization procedure increases the accuracy of voxel based group comparisons. Thus, intersubject averaging enhances the capacity for detection of abnormalities in functional brain images by minimizing the influence of individual variation. (author)

  11. Normal feline brain: clinical anatomy using magnetic resonance imaging.

    Science.gov (United States)

    Mogicato, G; Conchou, F; Layssol-Lamour, C; Raharison, F; Sautet, J

    2012-04-01

    The purpose of this study was to provide a clinical anatomy atlas of the feline brain using magnetic resonance imaging (MRI). Brains of twelve normal cats were imaged using a 1.5 T magnetic resonance unit and an inversion/recovery sequence (T1). Fourteen relevant MRI sections were chosen in transverse, dorsal, median and sagittal planes. Anatomic structures were identified and labelled using anatomical texts and Nomina Anatomica Veterinaria, sectioned specimen heads, and previously published articles. The MRI sections were stained according to the major embryological and anatomical subdivisions of the brain. The relevant anatomical structures seen on MRI will assist clinicians to better understand MR images and to relate this neuro-anatomy to clinical signs.

  12. The psychopath magnetized: insights from brain imaging

    OpenAIRE

    Anderson, Nathaniel E.; Kiehl, Kent A.

    2011-01-01

    Psychopaths commit a disproportionate amount of violent crime, and this places a substantial economic and emotional burden on society. Elucidation of the neural correlates of psychopathy may lead to improved management and treatment of the condition. Although some methodological issues remain, the neuroimaging literature is generally converging on a set of brain regions and circuits that are consistently implicated in the condition: the orbitofrontal cortex, amygdala, and the anterior and pos...

  13. Advanced MR brain imaging in preterm infants

    OpenAIRE

    Bruine, Francisca Teresa de

    2013-01-01

    The aim of the thesis is to investigate the diagnostic value of MRI performed around term equivalent age in evaluating brain injury and predicting neurodevelopmental outcome at two years corrected age in very preterm infants with a gestational age of less than 32 weeks. MRI is a powerful tool to diagnose all types of white matter injury and is more sensitive than ultrasound in detecting punctate white matter lesions which are associated with developmental delay and cerebral palsy. The positiv...

  14. Imaging Monoamine Oxidase in the Human Brain

    International Nuclear Information System (INIS)

    Positron emission tomography (PET) studies mapping monoamine oxidase in the human brain have been used to measure the turnover rate for MAO B; to determine the minimum effective dose of a new MAO inhibitor drug lazabemide and to document MAO inhibition by cigarette smoke. These studies illustrate the power of PET and radiotracer chemistry to measure normal biochemical processes and to provide information on the effect of drug exposure on specific molecular targets

  15. Imaging Monoamine Oxidase in the Human Brain

    Energy Technology Data Exchange (ETDEWEB)

    Fowler, J. S.; Volkow, N. D.; Wang, G-J.; Logan, Jean

    1999-11-10

    Positron emission tomography (PET) studies mapping monoamine oxidase in the human brain have been used to measure the turnover rate for MAO B; to determine the minimum effective dose of a new MAO inhibitor drug lazabemide and to document MAO inhibition by cigarette smoke. These studies illustrate the power of PET and radiotracer chemistry to measure normal biochemical processes and to provide information on the effect of drug exposure on specific molecular targets.

  16. Vocal area-related expression of the androgen receptor in the budgerigar (Melopsittacus undulatus) brain.

    Science.gov (United States)

    Matsunaga, Eiji; Okanoya, Kazuo

    2008-05-01

    The androgen receptor is a steroid hormone receptor widely expressed in the vocal control nuclei in songbirds. Here, we analysed androgen receptor expression in the brains of juvenile and adult budgerigars. With a species-specific probe for budgerigar androgen receptor mRNA, we found that the androgen receptor was expressed in the vocal areas, such as the central nucleus of the lateral nidopallium, the anterior arcopallium, the oval nucleus of the mesopallium, the oval nucleus of the anterior nidopallium and the tracheosyringeal hypoglossal nucleus. With the present data, together with previous reports, it turned out that the androgen receptor expression in telencephalic vocal control areas is similar amongst three groups of vocal learners--songbirds, hummingbirds and parrots, suggesting the possibility that the androgen receptor might play a role in vocal development and that the molecular mechanism regulating the androgen receptor expression in the vocal areas might be important in the evolution of vocal learning.

  17. Development of novel mixed ligand technetium complexes (3 + 1 combination) for imaging central neural system receptors

    International Nuclear Information System (INIS)

    A series of mixed ligand oxotechnetium-99m complexes carrying the 1-(2-methoxyphenyl) piperazine moiety has been synthesized. For structural characterization, and for in vitro binding assays, the analogous oxorhenium or oxotechnetium-99 complexes were prepared. As demonstrated by appropriate competition binding tests in rat hippocampal preparations, all oxorhenium analogues showed affinity for the 5-HT1A receptor binding sites with 50% inhibitory concentration values in the nanomolar range (IC50=6-106nM). All 99mTcO[SN(R)S]/[S] complexes showed a significant brain uptake in rats at 2 min post-injection (0.24-1.31 dose/organ). The regional distribution is inhomogeneous but the ratio between areas rich and poor in 5-HT1A receptor was not high. Structural modifications to this system may further improve the biological profile of these compounds and eventually provide efficient 99mTc receptor imaging agents. (author)

  18. Angiotensin II AT(1) receptor blockers as treatments for inflammatory brain disorders.

    Science.gov (United States)

    Saavedra, Juan M

    2012-11-01

    The effects of brain AngII (angiotensin II) depend on AT(1) receptor (AngII type 1 receptor) stimulation and include regulation of cerebrovascular flow, autonomic and hormonal systems, stress, innate immune response and behaviour. Excessive brain AT(1) receptor activity associates with hypertension and heart failure, brain ischaemia, abnormal stress responses, blood-brain barrier breakdown and inflammation. These are risk factors leading to neuronal injury, the incidence and progression of neurodegerative, mood and traumatic brain disorders, and cognitive decline. In rodents, ARBs (AT(1) receptor blockers) ameliorate stress-induced disorders, anxiety and depression, protect cerebral blood flow during stroke, decrease brain inflammation and amyloid-β neurotoxicity and reduce traumatic brain injury. Direct anti-inflammatory protective effects, demonstrated in cultured microglia, cerebrovascular endothelial cells, neurons and human circulating monocytes, may result not only in AT(1) receptor blockade, but also from PPARγ (peroxisome-proliferator-activated receptor γ) stimulation. Controlled clinical studies indicate that ARBs protect cognition after stroke and during aging, and cohort analyses reveal that these compounds significantly reduce the incidence and progression of Alzheimer's disease. ARBs are commonly used for the therapy of hypertension, diabetes and stroke, but have not been studied in the context of neurodegenerative, mood or traumatic brain disorders, conditions lacking effective therapy. These compounds are well-tolerated pleiotropic neuroprotective agents with additional beneficial cardiovascular and metabolic profiles, and their use in central nervous system disorders offers a novel therapeutic approach of immediate translational value. ARBs should be tested for the prevention and therapy of neurodegenerative disorders, in particular Alzheimer's disease, affective disorders, such as co-morbid cardiovascular disease and depression, and traumatic

  19. In-vivo human brain molecular imaging with a brain-dedicated PET/MRI system.

    Science.gov (United States)

    Cho, Zang Hee; Son, Young Don; Choi, Eun Jung; Kim, Hang Keun; Kim, Jeong Hee; Lee, Sang Yoon; Ogawa, Seiji; Kim, Young Bo

    2013-02-01

    Advances in the new-generation of ultra-high-resolution, brain-dedicated positron emission tomography-magnetic resonance imaging (PET/MRI) systems have begun to provide many interesting insights into the molecular dynamics of the brain. First, the finely delineated structural information from ultra-high-field MRI can help us to identify accurate landmark structures, thereby making it easier to locate PET activation sites that are anatomically well-correlated with metabolic or ligand-specific organs in the neural structures in the brain. This synergistic potential of PET/MRI imaging is discussed in terms of neuroscience and neurological research from both translational and basic research perspectives. Experimental results from the hippocampus, thalamus, and brainstem obtained with (18)F-fluorodeoxyglucose and (11)C-3-amino-4-(2-dimethylaminomethylphenylsulfanyl)benzonitrile are used to demonstrate the potential of this new brain PET/MRI system.

  20. Brain Imaging, Forward Inference, and Theories of Reasoning

    Directory of Open Access Journals (Sweden)

    Evan eHeit

    2015-01-01

    Full Text Available This review focuses on the issue of how neuroimaging studies address theoretical accounts of reasoning, through the lens of the method of forward inference (Henson, 2005, 2006. After theories of deductive and inductive reasoning are briefly presented, the method of forward inference for distinguishing between psychological theories based on brain imaging evidence is critically reviewed. Brain imaging studies of reasoning, comparing deductive and inductive arguments, comparing meaningful versus non-meaningful material, investigating hemispheric localization, and comparing conditional and relational arguments, are assessed in light of the method of forward inference. Finally, conclusions are drawn with regard to future research opportunities.

  1. Brain imaging, forward inference, and theories of reasoning.

    Science.gov (United States)

    Heit, Evan

    2014-01-01

    This review focuses on the issue of how neuroimaging studies address theoretical accounts of reasoning, through the lens of the method of forward inference (Henson, 2005, 2006). After theories of deductive and inductive reasoning are briefly presented, the method of forward inference for distinguishing between psychological theories based on brain imaging evidence is critically reviewed. Brain imaging studies of reasoning, comparing deductive and inductive arguments, comparing meaningful versus non-meaningful material, investigating hemispheric localization, and comparing conditional and relational arguments, are assessed in light of the method of forward inference. Finally, conclusions are drawn with regard to future research opportunities. PMID:25620926

  2. Lesion detection in magnetic resonance brain images by hyperspectral imaging algorithms

    Science.gov (United States)

    Xue, Bai; Wang, Lin; Li, Hsiao-Chi; Chen, Hsian Min; Chang, Chein-I.

    2016-05-01

    Magnetic Resonance (MR) images can be considered as multispectral images so that MR imaging can be processed by multispectral imaging techniques such as maximum likelihood classification. Unfortunately, most multispectral imaging techniques are not particularly designed for target detection. On the other hand, hyperspectral imaging is primarily developed to address subpixel detection, mixed pixel classification for which multispectral imaging is generally not effective. This paper takes advantages of hyperspectral imaging techniques to develop target detection algorithms to find lesions in MR brain images. Since MR images are collected by only three image sequences, T1, T2 and PD, if a hyperspectral imaging technique is used to process MR images it suffers from the issue of insufficient dimensionality. To address this issue, two approaches to nonlinear dimensionality expansion are proposed, nonlinear correlation expansion and nonlinear band ratio expansion. Once dimensionality is expanded hyperspectral imaging algorithms are readily applied. The hyperspectral detection algorithm to be investigated for lesion detection in MR brain is the well-known subpixel target detection algorithm, called Constrained Energy Minimization (CEM). In order to demonstrate the effectiveness of proposed CEM in lesion detection, synthetic images provided by BrainWeb are used for experiments.

  3. 3T MR imaging of the brain.

    Science.gov (United States)

    DeLano, Mark C; Fisher, Charles

    2006-02-01

    The advent of very high field clinical scanners that operate at 3T is taking structural and functional imaging to new levels and is reinvigorating clinical spectroscopy, fMR imaging, and noncontrast-enhanced methods of MRA. Most of the challenges that are related to 3T imaging have been addressed to facilitate routine clinical imaging. An awareness of the complexities that underlie the solutions to these challenges is important to the continued improvements to the 3T platform so that its maximal potential can be reached. The development of the multichannel-head coils and the improvement in the design of body coils, concurrently with the development of multichannel capabilities that enable parallel imaging, have benefited all field platforms. Perhaps the added value of parallel imaging has been greatest at 3T where the additional signal can be exploited. The definition of very high field is a moving target, and may be well on its way to 7.0 T, although in terms of the current clinical state of the art, 3T is our current reference. PMID:16530636

  4. Brain damages in ketamine addicts as revealed by magnetic resonance imaging

    Directory of Open Access Journals (Sweden)

    Chunmei eWang

    2013-07-01

    Full Text Available Ketamine, a known antagonist of N-methyl-D-aspartic (NMDA glutamate receptors, had been used as an anesthetic particularly for pediatric or for cardiac patients. Unfortunately, ketamine has become an abusive drug in many parts of the world while chronic and prolonged usage led to damages of many organs including the brain. However, no studies on possible damages in the brains induced by chronic ketamine abuse have been documented in the human via neuroimaging. This paper described for the first time via employing magnetic resonance imaging (MRI the changes in ketamine addicts of 0.5 to 12 years and illustrated the possible brain regions susceptible to ketamine abuse. Twenty-one ketamine addicts were recruited and the results showed that the lesions in the brains of ketamine addicts were located in many regions which appeared 2-4 years after ketamine addiction. Cortical atrophy was usually evident in the frontal, parietal or occipital cortices of addicts. Such study confirmed that many brain regions in the human were susceptible to chronic ketamine injury and presented a diffuse effect of ketamine on the brain which might differ from other central nervous system (CNS drugs, such as cocaine, heroin and methamphetamine.

  5. Obsessive-compulsive disorder: advances in brain imaging

    International Nuclear Information System (INIS)

    In the past twenty years functional brain imaging has advanced to the point of tackling the differential diagnosis, prognosis and therapeutic response in Neurology and Psychiatry. Psychiatric disorders were rendered 'functional' a century ago; however nowadays they can be seen by means of brain imaging. Functional images in positron emission tomography (PET) and single photon emission tomography (NEUROSPET) show in non-invasive fashion the state of brain functioning. PET does this assessing glucose metabolism and NEUROSPET by putting cerebral blood flow in images. Prevalence of OCD is clearly low (2 to 3%), but comorbidity with depression, psychoses, bipolar disorder and schizophrenia is high. Furthermore, it is not infrequent with autism, attention disorder, tichotillomany, borderline personality disorders, in pathological compulsive spending, sexual compulsion and in pathological gambling, in tics, and in Gilles de la Tourette disorder, NEUROSPET and PET show hypoperfusion in both frontal lobes, in their prefrontal dorsolateral aspects, in their inferior zone and premotor cortex, with hyperperfusion in the posterior cingulum and hypoperfusion in basal ganglia (caudate nucleus). Cummings states that hyperactivity of the limbic system might be involved in OCD. Thus, brain imaging in OCD is a diagnostic aid, allows us to see clinical imagenological evolution and therapeutic response and, possibly, it is useful predict therapeutic response (Au)

  6. 99Tcm-Neurolite brain SPECT imaging as an outcome predictor after brain trauma: initial experience

    International Nuclear Information System (INIS)

    Full text: The aim of this study was to use semi-quantitative 99Tcm-ethylene cysteine dimer (Neurolite) cerebral blood flow (CBF) SPET brain imaging to assess its role in predicting outcome after brain trauma. Twelve adult patients (9 males, 3 females) who sustained moderate to severe brain trauma were studied by CBF/SPET within 4 weeks of the injury (scan A) and again after 1 year (scan B). Clinical assessment was also performed at these times and included extensive neuropsychometric testing. Patients received 800-850 MBq 99Tcm-Neurolite intravenously, and were imaged using a triple-headed gamma camera with LEUHR fan beam collimators. Processing, filtering, reconstruction and data set selection were identical for scans A and B. Semi-quantitative analysis was performed using 25 regions of interest in the cerebral cortex and deep structures in 2 coronal, 2 sagittal and 3 oblique planes. Normalized mean counts per pixel for the whole brain, and regional brain ratios were calculated. Scans A and B were compared and correlated to the clinical outcome data. Two patients with minimal CBF abnormalities made full recoveries. The remaining 10 had moderate to severe focal CBF defects, which showed no significant improvement at 12 months. Of these patients, 2 had moderate disability, 3 had severe to moderate disability and 2 had severe disability at 12 months. Patients with persisting focal abnormal CBF showed persisting neurological deficits. Neurolite brain CBF imaging is a useful method of predicting outcome after moderate to severe head injury

  7. Brain magnetic resonance imaging with contrast dependent on blood oxygenation

    Energy Technology Data Exchange (ETDEWEB)

    Ogawa, S.; Lee, T.M.; Kay, A.R.; Tank, D.W. (AT and T Bell Laboratories, Murray Hill, NJ (United States))

    1990-12-01

    Paramagnetic deoxyhemoglobin in venous blood is a naturally occurring contrast agent for magnetic resonance imaging (MRI). By accentuating the effects of this agent through the use of gradient-echo techniques in high yields, the authors demonstrate in vivo images of brain microvasculature with image contrast reflecting the blood oxygen level. This blood oxygenation level-dependent (BOLD) contrast follows blood oxygen changes induced by anesthetics, by insulin-induced hypoglycemia, and by inhaled gas mixtures that alter metabolic demand or blood flow. The results suggest that BOLD contrast can be used to provide in vivo real-time maps of blood oxygenation in the brain under normal physiological conditions. BOLD contrast adds an additional feature to magnetic resonance imaging and complement other techniques that are attempting to provide position emission tomography-like measurements related to regional neural activity.

  8. Brain magnetic resonance imaging with contrast dependent on blood oxygenation

    International Nuclear Information System (INIS)

    Paramagnetic deoxyhemoglobin in venous blood is a naturally occurring contrast agent for magnetic resonance imaging (MRI). By accentuating the effects of this agent through the use of gradient-echo techniques in high yields, the authors demonstrate in vivo images of brain microvasculature with image contrast reflecting the blood oxygen level. This blood oxygenation level-dependent (BOLD) contrast follows blood oxygen changes induced by anesthetics, by insulin-induced hypoglycemia, and by inhaled gas mixtures that alter metabolic demand or blood flow. The results suggest that BOLD contrast can be used to provide in vivo real-time maps of blood oxygenation in the brain under normal physiological conditions. BOLD contrast adds an additional feature to magnetic resonance imaging and complement other techniques that are attempting to provide position emission tomography-like measurements related to regional neural activity

  9. Imaging Receptor Changes in Human Drug Abusers

    OpenAIRE

    Cosgrove, Kelly P

    2010-01-01

    This chapter will review the literature on differences in the brain chemistry of alcohol- and drug-dependent individuals compared to healthy controls as measured with positron emission tomography and single photon emission computed tomography. Specifically, alterations in dopamine, serotonin, opioid, and GABA systems in cocaine, alcohol, nicotine, and heroin dependence have been examined. These neurochemical systems are integrated and play significant roles in a final common pathway mediating...

  10. MR imaging of brain metastases. Pt. 1

    International Nuclear Information System (INIS)

    Sensitifity and specificity of plain T2-WI and Gd-DTPA enhanced T1-WI were compared by evaluating MR exams of 30 patients with brain metastases. Large lesions with high signal on T2-WI always enhanced (43/43) when a structure (perifocal edema, tumor tissue, centralnecrosis) was found. Large lesions nearly always enhanced (53/55) even if no such structure was found. 65% of small unstructured white matter lesions with high signal on T2-WI, which are generally considered vascular, did not enhance. Surprisingly, 35% did enhance. Demonstration of blood brain barrier disturbance in these lesions suggested a metastatic origin. In 3 patients with multiple metastases, Gd-DTPA enhanced T1-WI disclosed more than 140 lesions not seen on T2-WI. All of them were located in or adjacent to grey matter. Our results indicate that enhanced T1-WI should be obtained even if T1-WI are normal or show only small white matter lesions. (orig.)

  11. CT versus MR in neonatal brain imaging at term

    Energy Technology Data Exchange (ETDEWEB)

    Robertson, Richard L.; Robson, Caroline D.; Zurakowski, David; Antiles, Sharon; Strauss, Keith; Mulkern, Robert V. [Department of Radiology, Children' s Hospital Medical Center, Harvard Medical School, 300 Longwood Avenue, MA 02115, Boston (United States)

    2003-07-01

    Recent reports have highlighted the lifetime risk of malignancy from using ionizing radiation in pediatric imaging. Computed tomography (CT), which uses ionizing radiation, is employed extensively for neonatal brain imaging of term infants. Magnetic resonance (MR) provides an alternative that does not use ionizing radiation. The purpose of this study was to assess the cross-modality agreement and interobserver agreement of CT and MR brain imaging of the term or near-term neonate. Brain CT and MR images of 48 neonates were retrospectively reviewed by two pediatric neuroradiologists. CT and MR examinations had been obtained within 72 h of one another in all patients. CT was obtained with 5 mm collimation (KV=120, mAs=340). MR consisted of T1-weighted imaging (TR/TE=300/14; 4-mm slice thickness/1-mm gap), T2-weighted imaging (TR/TE/etl= 3000/126/16; 4-mm slice thickness/1-mm gap), and line scan diffusion imaging (LSDI) (TR/TE/b factor=1258/63/750; nominal 4-mm slice thickness/3-mm gap). The brain was categorized as normal or abnormal on both CT and MR. Ischemic injury was the most common brain abnormality demonstrated. McNemar's test indicated no significant difference between CT and MR test results for reader 1 (P=0.22) or reader 2 (P=0.45). The readers agreed on the presence or absence of abnormality on CT in 40 patients (83.3%) and on MR in 45 patients (93.8%). For CT, the kappa coefficient indicated excellent interobserver agreement ({kappa}=0.68), although the lower limit of the 95% confidence interval extends to {kappa}=0.55, which indicates only good-to-moderate agreement. For MR, the kappa coefficient indicated almost perfect interobserver agreement ({kappa}=0.88) with the 95% confidence interval extending to a lower limit of {kappa}=0.76, which represents excellent agreement. Because MR demonstrates findings similar to CT and has greater interobserver agreement, it appears that MR is a superior test to CT in determining brain abnormalities in the term

  12. Biochemical imaging of the human brain in development and disease

    International Nuclear Information System (INIS)

    The authors used positron emission tomography (PET) to image cerebral glucose metabolism in more than 140 children aged 5 days to 15 years. Twenty-nine children were studied during normal development and the remainder because of infantile spasm, seizure, Lennox-Gastaut syndrome, or cerebral palsy. This exhibit demonstrates the temporal course of normal function (metabolic) development of the brain, and compares the relative value of PET, MR imaging, and x-ray CT in abnormal cases

  13. MR to CT Registration of Brains using Image Synthesis

    OpenAIRE

    Roy, Snehashis; Carass, Aaron; Jog, Amod; Prince, Jerry L.; Lee, Junghoon

    2014-01-01

    Computed tomography (CT) is the standard imaging modality for patient dose calculation for radiation therapy. Magnetic resonance (MR) imaging (MRI) is used along with CT to identify brain structures due to its superior soft tissue contrast. Registration of MR and CT is necessary for accurate delineation of the tumor and other structures, and is critical in radiotherapy planning. Mutual information (MI) or its variants are typically used as a similarity metric to register MRI to CT. However, u...

  14. Ethanol, not metabolized in brain, significantly reduces brain metabolism, probably via specific GABA(A) receptors

    Science.gov (United States)

    Rae, Caroline D.; Davidson, Joanne E.; Maher, Anthony D.; Rowlands, Benjamin D.; Kashem, Mohammed A.; Nasrallah, Fatima A.; Rallapalli, Sundari K.; Cook, James M; Balcar, Vladimir J.

    2014-01-01

    Ethanol is a known neuromodulatory agent with reported actions at a range of neurotransmitter receptors. Here, we used an indirect approach, measuring the effect of alcohol on metabolism of [3-13C]pyruvate in the adult Guinea pig brain cortical tissue slice and comparing the outcomes to those from a library of ligands active in the GABAergic system as well as studying the metabolic fate of [1,2-13C]ethanol. Ethanol (10, 30 and 60 mM) significantly reduced metabolic flux into all measured isotopomers and reduced all metabolic pool sizes. The metabolic profiles of these three concentrations of ethanol were similar and clustered with that of the α4β3δ positive allosteric modulator DS2 (4-Chloro-N-[2-(2-thienyl)imidazo[1,2a]-pyridin-3-yl]benzamide). Ethanol at a very low concentration (0.1 mM) produced a metabolic profile which clustered with those from inhibitors of GABA uptake, and ligands showing affinity for α5, and to a lesser extent, α1-containing GABA(A)R. There was no measureable metabolism of [1,2-13C]ethanol with no significant incorporation of 13C from [1,2-13C]ethanol into any measured metabolite above natural abundance, although there were measurable effects on total metabolite sizes similar to those seen with unlabeled ethanol. The reduction in metabolism seen in the presence of ethanol is therefore likely to be due to its actions at neurotransmitter receptors, particularly α4β3δ receptors, and not because ethanol is substituting as a substrate or because of the effects of ethanol catabolites acetaldehyde or acetate. We suggest that the stimulatory effects of very low concentrations of ethanol are due to release of GABA via GAT1 and the subsequent interaction of this GABA with local α5-containing, and to a lesser extent, α1-containing GABA(A)R. PMID:24313287

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

    Science.gov (United States)

    Bigler, Erin D

    2015-09-01

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

  16. Brain size and brain organization of the whale shark, Rhincodon typus, using magnetic resonance imaging.

    Science.gov (United States)

    Yopak, Kara E; Frank, Lawrence R

    2009-01-01

    Very little is known about the brain organization of the suction filter feeder, Rhincodon typus, and how it compares to other orectolobiforms in light of its specialization as a plankton-feeder. Brain size and overall brain organization was assessed in two specimens of R. typus in relation to both phylogeny and ecology, using magnetic resonance imaging (MRI). In comparison to over 60 other chondrichthyan species, R. typus demonstrated a relatively small brain for its body size (expressed in terms of encephalization quotients and residuals), similar to the lamniforms Carcharodon carcharias, Cetorhinus maximus, and Carcharias taurus. R. typus possessed a relatively small telencephalon with some development of the dorsal pallium, which was suggestive of moderate social behavior, in addition to a relatively large diencephalon and a relatively reduced mesencephalon. The most notable characteristic of the brain of Rhincodon was a large and highly foliated cerebellum, one of the largest cerebellums within the chondrichthyan clade. Early development of the brain was qualitatively assessed using an in situ MRI scan of the brain and chondrocranium of a neonate specimen of R. typus. There was evidence that folding of the cerebellar corpus appeared in early development, although the depth and number of folds might vary ontogenetically in this species. Hierarchical cluster analysis and multidimensional scaling ordinations showed evidence of convergent evolution with the basking shark, Cetorhinus maximus, another large-bodied filter feeding elasmobranch, supporting the claim that organization of the brain is more similar in species with analogous but independently evolved lifestyles than those that share taxonomic classification.

  17. Quantitative imaging of protein targets in the human brain with PET

    International Nuclear Information System (INIS)

    PET imaging of proteins in the human brain with high affinity radiolabelled molecules has a history stretching back over 30 years. During this period the portfolio of protein targets that can be imaged has increased significantly through successes in radioligand discovery and development. This portfolio now spans six major categories of proteins; G-protein coupled receptors, membrane transporters, ligand gated ion channels, enzymes, misfolded proteins and tryptophan-rich sensory proteins. In parallel to these achievements in radiochemical sciences there have also been significant advances in the quantitative analysis and interpretation of the imaging data including the development of methods for image registration, image segmentation, tracer compartmental modeling, reference tissue kinetic analysis and partial volume correction. In this review, we analyze the activity of the field around each of the protein targets in order to give a perspective on the historical focus and the possible future trajectory of the field. The important neurobiology and pharmacology is introduced for each of the six protein classes and we present established radioligands for each that have successfully transitioned to quantitative imaging in humans. We present a standard quantitative analysis workflow for these radioligands which takes the dynamic PET data, associated blood and anatomical MRI data as the inputs to a series of image processing and bio-mathematical modeling steps before outputting the outcome measure of interest on either a regional or parametric image basis. The quantitative outcome measures are then used in a range of different imaging studies including tracer discovery and development studies, cross sectional studies, classification studies, intervention studies and longitudinal studies. Finally we consider some of the confounds, challenges and subtleties that arise in practice when trying to quantify and interpret PET neuroimaging data including motion artifacts

  18. Quantitative imaging of protein targets in the human brain with PET

    Science.gov (United States)

    Gunn, Roger N.; Slifstein, Mark; Searle, Graham E.; Price, Julie C.

    2015-11-01

    PET imaging of proteins in the human brain with high affinity radiolabelled molecules has a history stretching back over 30 years. During this period the portfolio of protein targets that can be imaged has increased significantly through successes in radioligand discovery and development. This portfolio now spans six major categories of proteins; G-protein coupled receptors, membrane transporters, ligand gated ion channels, enzymes, misfolded proteins and tryptophan-rich sensory proteins. In parallel to these achievements in radiochemical sciences there have also been significant advances in the quantitative analysis and interpretation of the imaging data including the development of methods for image registration, image segmentation, tracer compartmental modeling, reference tissue kinetic analysis and partial volume correction. In this review, we analyze the activity of the field around each of the protein targets in order to give a perspective on the historical focus and the possible future trajectory of the field. The important neurobiology and pharmacology is introduced for each of the six protein classes and we present established radioligands for each that have successfully transitioned to quantitative imaging in humans. We present a standard quantitative analysis workflow for these radioligands which takes the dynamic PET data, associated blood and anatomical MRI data as the inputs to a series of image processing and bio-mathematical modeling steps before outputting the outcome measure of interest on either a regional or parametric image basis. The quantitative outcome measures are then used in a range of different imaging studies including tracer discovery and development studies, cross sectional studies, classification studies, intervention studies and longitudinal studies. Finally we consider some of the confounds, challenges and subtleties that arise in practice when trying to quantify and interpret PET neuroimaging data including motion artifacts

  19. PET and SPECT imaging of the opioid system: receptors, radioligands and avenues for drug discovery and development.

    Science.gov (United States)

    Lever, John R

    2007-01-01

    As we celebrate the bicentennial of the isolation of morphine by Sertürner, opioids continue to dominate major sectors of the analgesic market worldwide. The pharmaceutical industry stands to benefit greatly from molecular imaging in preclinical and early clinical trials of new or improved opioid drugs. At this juncture, it seems fitting to summarize the past twenty or so years of research on molecular imaging of the opioid system from the viewpoint of drug discovery and development. Opioid receptors were first imaged in human volunteers by positron emission tomography (PET) in 1984. Now, quantitative PET imaging of the major opioid receptor types (micro, delta , kappa) is possible in the brain and peripheral organs of healthy persons and patient populations. Radioligands are under development for single photon emission computed tomography (SPECT) of opioid receptors as well. These functional, nuclear imaging techniques can trace the fate of radiolabeled molecules directly, but non-invasively, and allow precise pharmacokinetic and pharmacodynamic measurements. Molecular imaging provides unique data that can aid in selecting the best drug candidates, determining optimal dosing regimens, clearing regulatory hurdles and lowering risks of failure. Using a historical perspective, this review touches on opioid receptors as drug targets, and focuses on the status and use of radiotracers for opioid receptor PET and SPECT. Selected studies are discussed to illustrate the power of molecular imaging for facilitating opioid drug discovery and development. PMID:17266587

  20. Data-driven forward model inference for EEG brain imaging

    DEFF Research Database (Denmark)

    Hansen, Sofie Therese; Hauberg, Søren; Hansen, Lars Kai

    2016-01-01

    . Combined with only a recorded EEG signal, we are able to estimate both the brain sources and a person-specific forward model by optimizing this parametrization. We thus not only solve an inverse problem, but also optimize over its specification. Our work demonstrates that personalized EEG brain imaging......Electroencephalography (EEG) is a flexible and accessible tool with excellent temporal resolution but with a spatial resolution hampered by volume conduction. Reconstruction of the cortical sources of measured EEG activity partly alleviates this problem and effectively turns EEG into a brain...... imaging device. The quality of the source reconstruction depends on the forward model which details head geometry and conductivities of different head compartments. These person-specific factors are complex to determine, requiring detailed knowledge of the subject’s anatomy and physiology. In this proof...

  1. Apparatus and method for motion tracking in brain imaging

    DEFF Research Database (Denmark)

    2013-01-01

    Disclosed is apparatus and method for motion tracking of a subject in medical brain imaging. The method comprises providing a light projector and a first camera; projecting a first pattern sequence (S1) onto a surface region of the subject with the light projector, wherein the subject is positioned...

  2. Reliability and Accuracy of Brain Volume Measurement on MR Imaging

    DEFF Research Database (Denmark)

    Yamagchii, Kechiro; Lassen, Anders; Ring, Poul

    1998-01-01

    Yamaguchi, K., Lassen, A. And Ring, P. Reliability and Accuracy of Brain Volume Measurement on MR Imaging. Abstract at ESMRMB98 European Society for Magnetic Resonance in Medicine and Biology, Geneva, Sept 17-20, 1998 Danish Research Center for Magnetic Resonance, Hvidovre University Hospital...

  3. Power of the metaphor: forty signs on brain imaging.

    Science.gov (United States)

    Gocmen, Rahsan; Guler, Ezgi; Kose, Ilgaz Cagatay; Oguz, Kader K

    2015-01-01

    We retrospectively reviewed neuroradiology database at our tertiary-care hospital to search for patients with metaphoric or descriptive signs on brain computed tomography or magnetic resonance imaging. Only patients who had clinical or pathological definitive diagnosis were included in this review.

  4. ( sup 125 I)(+)FISCH: A new CNS D-1 dopamine receptor imaging ligand

    Energy Technology Data Exchange (ETDEWEB)

    Billings, J.; Kung, M.P.; Chumpradit, S.; Pan, S.; Kung, H.F. (Univ. of Pennsylvania, Philadelphia (USA))

    1989-01-01

    Radiolabeling and in vitro and in vivo evaluation of an iodinated benzazepine: ({sup 125}I)FISCH 7-Chloro-8-hydroxy-1-(4{prime}-iodophenyl)-3-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine, as a potential imaging agent for CNS D-1 dopamine receptors in animals, were investigated. After an iv injection, this benzazepine derivative showed good brain uptake in rats. The striatum/cerebellum ratio was 2.50 at 60 min after the injection. The regional distribution in rat brain, as measured by ex vivo autoradiography, displayed highest uptake in the regions of the striatal complex and the substantia nigra, regions known to have a high concentration of D-1 dopamine receptors. Furthermore, this localized regional cerebral distribution was blocked by pretreatment with SCH-23390, a selective D-1 dopamine receptor antagonist. The in vitro binding affinity of this agent in rat striatum tissue preparation displayed a Kd of 1.43 {plus minus} 0.15 nM. Competition data (in vitro) showed the following rank order of potency: SCH-23390 > ({plus minus})IBZP >> apomorphine > WB 4101 > ketanserin {approximately} spiperone. The preliminary data suggest that this analog of SCH-23390 shows similar selectivity for the CNS D-1 receptor.

  5. Assessment of vessel diameters for MR brain angiography processed images

    Science.gov (United States)

    Moraru, Luminita; Obreja, Cristian-Dragos; Moldovanu, Simona

    2015-12-01

    The motivation was to develop an assessment method to measure (in)visible differences between the original and the processed images in MR brain angiography as a method of evaluation of the status of the vessel segments (i.e. the existence of the occlusion or intracerebral vessels damaged as aneurysms). Generally, the image quality is limited, so we improve the performance of the evaluation through digital image processing. The goal is to determine the best processing method that allows an accurate assessment of patients with cerebrovascular diseases. A total of 10 MR brain angiography images were processed by the following techniques: histogram equalization, Wiener filter, linear contrast adjustment, contrastlimited adaptive histogram equalization, bias correction and Marr-Hildreth filter. Each original image and their processed images were analyzed into the stacking procedure so that the same vessel and its corresponding diameter have been measured. Original and processed images were evaluated by measuring the vessel diameter (in pixels) on an established direction and for the precise anatomic location. The vessel diameter is calculated using the plugin ImageJ. Mean diameter measurements differ significantly across the same segment and for different processing techniques. The best results are provided by the Wiener filter and linear contrast adjustment methods and the worst by Marr-Hildreth filter.

  6. Development of the glucocorticoid receptor system in the rat limbic brain. 2. An autoradiographic study

    Energy Technology Data Exchange (ETDEWEB)

    Meaney, M.J.; Sapolsky, R.M.; McEwen, B.S. (Rockefeller Univ., New York (USA))

    1985-02-01

    The authors report the results of an autoradiographic analysis of the postnatal development of the hippocampal glucocorticoid receptor system in the rat brain. Quantitative analysis of the autoradiograms revealed a varied pattern of gradual development towards adult receptor concentrations during the second week of life. Receptor concentrations in the dentate gyrus increased dramatically between Days 9 and 15, while the changes during this period in the pyramidal layers of Ammon's horn seemed to reflect both structural changes in these regions as well as increases in receptor concentrations.

  7. Faster permutation inference in brain imaging.

    OpenAIRE

    Winkler, AM; Ridgway, GR; Douaud, G; Nichols, TE; Smith, SM

    2016-01-01

    Permutation tests are increasingly being used as a reliable method for inference in neuroimaging analysis. However, they are computationally intensive. For small, non-imaging datasets, recomputing a model thousands of times is seldom a problem, but for large, complex models this can be prohibitively slow, even with the availability of inexpensive computing power. Here we exploit properties of statistics used with the general linear model (GLM) and their distributions to obtain accelerations i...

  8. Intracranial Hemorrhage Annotation for CT Brain Images

    OpenAIRE

    Tong Hau Lee; Mohammad Faizal Ahmad Fauzi; Su-Cheng Haw

    2011-01-01

    In this paper, we created a decision-making model to detect intracranial hemorrhage and adopted Expectation Maximization(EM) segmentation to segment the Computed Tomography (CT) images. In this work, basically intracranial hemorrhage is classified into two main types which are intra-axial hemorrhage and extra-axial hemorrhage. In order to ease classification, contrast enhancement is adopted to finetune the contrast of the hemorrhage. After that, k-means is applied to group the potential and s...

  9. Quantification of human brain benzodiazepine receptors using [{sup 18}F]fluoroethylflumazenil: a first report in volunteers and epileptic patients

    Energy Technology Data Exchange (ETDEWEB)

    Leveque, Philippe [Unite de Tomographie par Positrons, Universite Catholique de Louvain, Louvain-la-Neuve (Belgium); Unite de Chimie Pharmaceutique et de Radiopharmacie, CMFA/REMA, Universite Catholique de Louvain, 73-40 Avenue Mounier, 1200, Bruxelles (Belgium); Sanabria-Bohorquez, Sandra [Imaging Research, Merck Research Laboratories, West Point, Philadelphia (United States); Bol, Anne; Volder, Anne de; Labar, Daniel [Unite de Tomographie par Positrons, Universite Catholique de Louvain, Louvain-la-Neuve (Belgium); Rijckevorsel, K. van [Service de Neurologie, Cliniques Universitaires Saint-Luc, Bruxelles (Belgium); Gallez, Bernard [Unite de Chimie Pharmaceutique et de Radiopharmacie, CMFA/REMA, Universite Catholique de Louvain, 73-40 Avenue Mounier, 1200, Bruxelles (Belgium); Unite de Resonance Magnetique Biomedicale, Universite Catholique de Louvain, Bruxelles (Belgium)

    2003-12-01

    Fluorine-18 fluoroethylflumazenil ([{sup 18}F]FEF) is a tracer for central benzodiazepine (BZ) receptors which is proposed as an alternative to carbon-11 flumazenil for in vivo imaging using positron emission tomography (PET) in humans. In this study, [{sup 18}F]FEF kinetic data were acquired using a 60-min two-injection protocol on three normal subjects and two patients suffering from mesiotemporal epilepsy as demonstrated by abnormal magnetic resonance imaging and [{sup 18}F]fluorodeoxyglucose positron emission tomography. First, a tracer bolus injection was performed and [{sup 18}F]FEF rapidly distributed in the brain according to the known BZ receptor distribution. Thirty minutes later a displacement injection of 0.01 mg/kg of unlabelled flumazenil was performed. Activity was rapidly displaced from all BZ receptor regions demonstrating the specific binding of [{sup 18}F]FEF. No displacement was observed in the pons. Plasma input function was obtained from arterial blood sampling, and metabolite analysis was performed by high-performance liquid chromatography. Metabolite quantification revealed a fast decrease in tracer plasma concentration, such that at 5 min post injection about 70% of the total radioactivity in plasma corresponded to [{sup 18}F]FEF, reaching 24% at 30 min post injection. The interactions between [{sup 18}F]FEF and BZ receptors were described using linear compartmental models with plasma input and reference tissue approaches. Binding potential values were in agreement with the known distribution of BZ receptors in human brain. Finally, in two patients with mesiotemporal sclerosis, reduced uptake of [{sup 18}F]FEF was clearly observed in the implicated left hippocampus. (orig.)

  10. GABA(A) receptor downregulation in brains of subjects with autism.

    Science.gov (United States)

    Fatemi, S Hossein; Reutiman, Teri J; Folsom, Timothy D; Thuras, Paul D

    2009-02-01

    Gamma-aminobutyric acid A (GABA(A)) receptors are ligand-gated ion channels responsible for mediation of fast inhibitory action of GABA in the brain. Preliminary reports have demonstrated altered expression of GABA receptors in the brains of subjects with autism suggesting GABA/glutamate system dysregulation. We investigated the expression of four GABA(A) receptor subunits and observed significant reductions in GABRA1, GABRA2, GABRA3, and GABRB3 in parietal cortex (Brodmann's Area 40 (BA40)), while GABRA1 and GABRB3 were significantly altered in cerebellum, and GABRA1 was significantly altered in superior frontal cortex (BA9). The presence of seizure disorder did not have a significant impact on GABA(A) receptor subunit expression in the three brain areas. Our results demonstrate that GABA(A) receptors are reduced in three brain regions that have previously been implicated in the pathogenesis of autism, suggesting widespread GABAergic dysfunction in the brains of subjects with autism. PMID:18821008

  11. Molecular imaging of the brain. Using multi-quantum coherence and diagnostics of brain disorders

    Energy Technology Data Exchange (ETDEWEB)

    Kaila, M.M. [New South Wales Univ., Sydney, NSW (Australia). School of Physics; Kaila, Rakhi [Univ. of New South Wales, Sydney (Australia). School of Medicine

    2013-11-01

    Explains the basics of the MRI and its use in the diagnostics and the treatment of the human brain disorders. Examines multi-quantum magnetic resonance imaging methods and the diagnostics of brain disorders. Covers how in a non-invasive manner one can diagnose diseases of the brain. This book examines multi-quantum magnetic resonance imaging methods and the diagnostics of brain disorders. It consists of two Parts. The part I is initially devoted towards the basic concepts of the conventional single quantum MRI techniques. It is supplemented by the basic knowledge required to understand multi-quantum MRI. Practical illustrations are included both on recent developments in conventional MRI and the MQ-MRI. This is to illustrate the connection between theoretical concepts and their scope in the clinical applications. The Part II initially sets out the basic details about quadrupole charge distribution present in certain nuclei and their importance about the functions they perform in our brain. Some simplified final mathematical expressions are included to illustrate facts about the basic concepts of the quantum level interactions between magnetic dipole and the electric quadrupole behavior of useful nuclei present in the brain. Selected practical illustrations, from research and clinical practices are included to illustrate the newly emerging ideas and techniques. The reader should note that the two parts of the book are written with no interdependence. One can read them quite independently.

  12. Simulation of brain tumor resection in image-guided neurosurgery

    Science.gov (United States)

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

    2011-03-01

    Preoperative magnetic resonance images are typically used for neuronavigation in image-guided neurosurgery. However, intraoperative brain deformation (e.g., as a result of gravitation, loss of cerebrospinal fluid, retraction, resection, etc.) significantly degrades the accuracy in image guidance, and must be compensated for in order to maintain sufficient accuracy for navigation. Biomechanical finite element models are effective techniques that assimilate intraoperative data and compute whole-brain deformation from which to generate model-updated MR images (uMR) to improve accuracy in intraoperative guidance. To date, most studies have focused on early surgical stages (i.e., after craniotomy and durotomy), whereas simulation of more complex events at later surgical stages has remained to be a challenge using biomechanical models. We have developed a method to simulate partial or complete tumor resection that incorporates intraoperative volumetric ultrasound (US) and stereovision (SV), and the resulting whole-brain deformation was used to generate uMR. The 3D ultrasound and stereovision systems are complimentary to each other because they capture features deeper in the brain beneath the craniotomy and at the exposed cortical surface, respectively. In this paper, we illustrate the application of the proposed method to simulate brain tumor resection at three temporally distinct surgical stages throughout a clinical surgery case using sparse displacement data obtained from both the US and SV systems. We demonstrate that our technique is feasible to produce uMR that agrees well with intraoperative US and SV images after dural opening, after partial tumor resection, and after complete tumor resection. Currently, the computational cost to simulate tumor resection can be up to 30 min because of the need for re-meshing and the trial-and-error approach to refine the amount of tissue resection. However, this approach introduces minimal interruption to the surgical workflow

  13. Registration of dynamic dopamine D2receptor images using principal component analysis

    International Nuclear Information System (INIS)

    This paper describes a novel technique for registering a dynamic sequence of single-photon emission tomography (SPET) dopamine D2receptor images, using principal component analysis (PCA). Conventional methods for registering images, such as count difference and correlation coefficient algorithms, fail to take into account the dynamic nature of the data, resulting in large systematic errors when registering time-varying images. However, by using principal component analysis to extract the temporal structure of the image sequence, misregistration can be quantified by examining the distribution of eigenvalues. The registration procedures were tested using a computer-generated dynamic phantom derived from a high-resolution magnetic resonance image of a realistic brain phantom. Each method was also applied to clinical SPET images of dopamine D 2receptors, using the ligands iodine-123 iodobenzamide and iodine-123 epidepride, to investigate the influence of misregistration on kinetic modelling parameters and the binding potential. The PCA technique gave highly significant (P 123I-epidepride scans. The PCA method produced data of much greater quality for subsequent kinetic modelling, with an improvement of nearly 50% in the χ2of the fit to the compartmental model, and provided superior quality registration of particularly difficult dynamic sequences. (orig.)

  14. Registration of dynamic dopamine D2 receptor images using principal component analysis.

    Science.gov (United States)

    Acton, P D; Pilowsky, L S; Suckling, J; Brammer, M J; Ell, P J

    1997-11-01

    This paper describes a novel technique for registering a dynamic sequence of single-photon emission tomography (SPET) dopamine D2 receptor images, using principal component analysis (PCA). Conventional methods for registering images, such as count difference and correlation coefficient algorithms, fail to take into account the dynamic nature of the data, resulting in large systematic errors when registering time-varying images. However, by using principal component analysis to extract the temporal structure of the image sequence, misregistration can be quantified by examining the distribution of eigenvalues. The registration procedures were tested using a computer-generated dynamic phantom derived from a high-resolution magnetic resonance image of a realistic brain phantom. Each method was also applied to clinical SPET images of dopamine D2 receptors, using the ligands iodine-123 iodobenzamide and iodine-123 epidepride, to investigate the influence of misregistration on kinetic modelling parameters and the binding potential. The PCA technique gave highly significant (Pepidepride scans. The PCA method produced data of much greater quality for subsequent kinetic modelling, with an improvement of nearly 50% in the chi2 of the fit to the compartmental model, and provided superior quality registration of particularly difficult dynamic sequences. PMID:9371874

  15. MR-based automatic delineation of volumes of interest in human brain PET images using probability maps

    DEFF Research Database (Denmark)

    Svarer, Claus; Madsen, Karina; Hasselbalch, Steen G.;

    2005-01-01

    delineation of the VOI set. The approach was also shown to work equally well in individuals with pronounced cerebral atrophy. Probability-map-based automatic delineation of VOIs is a fast, objective, reproducible, and safe way to assess regional brain values from PET or SPECT scans. In addition, the method......The purpose of this study was to develop and validate an observer-independent approach for automatic generation of volume-of-interest (VOI) brain templates to be used in emission tomography studies of the brain. The method utilizes a VOI probability map created on the basis of a database of several...... subjects' MR-images, where VOI sets have been defined manually. High-resolution structural MR-images and 5-HT(2A) receptor binding PET-images (in terms of (18)F-altanserin binding) from 10 healthy volunteers and 10 patients with mild cognitive impairment were included for the analysis. A template including...

  16. Radiosynthesis and initial evaluation of [18F]-FEPPA for PET imaging of peripheral benzodiazepine receptors

    International Nuclear Information System (INIS)

    Introduction: A novel [18F]-radiolabelled phenoxyanilide, [18F]-FEPPA, has been synthesized and evaluated, in vitro and ex vivo, as a potential positron emission tomography imaging agent for the peripheral benzodiazepine receptor (PBR). Methods: [18F]-FEPPA and two other radiotracers for imaging PBR, namely [11C]-PBR28 and [11C]-PBR28-d3, were synthesised and evaluated in vitro and ex vivo as potential PBR imaging agents. Results: [18F]-FEPPA is efficiently prepared in one step from its tosylate precursor and [18F]-fluoride in high radiochemical yields and at high specific activity. FEPPA displayed a Ki of 0.07 nM for PBR in rat mitochondrial membrane preparations and a suitable lipophilicity for brain penetration (log P of 2.99 at pH 7.4). Upon intravenous injection into rats, [18F]-FEPPA showed moderate brain uptake [standard uptake value (SUV) of 0.6 at 5 min] and a slow washout (SUV of 0.35 after 60 min). Highest uptake of radioactivity was seen in the hypothalamus and olfactory bulb, regions previously reported to be enriched in PBR in rat brain. Analysis of plasma and brain extracts demonstrated that [18F]-FEPPA was rapidly metabolized, but no lipophilic metabolites were observed in either preparation and only 5% radioactive metabolites were present in brain tissue extracts. Blocking studies to determine the extent of specific binding of [18F]-FEPPA in rat brain were problematic due to large perturbations in circulating radiotracer and the lack of a reference region. Conclusions: Further evaluation of the potential of [18F]-FEPPA will require the employment of rigorous kinetic models and/or appropriate animal models

  17. CB2 Receptor Activation Inhibits Melanoma Cell Transmigration through the Blood-Brain Barrier

    Directory of Open Access Journals (Sweden)

    János Haskó

    2014-05-01

    Full Text Available During parenchymal brain metastasis formation tumor cells need to migrate through cerebral endothelial cells, which form the morphological basis of the blood-brain barrier (BBB. The mechanisms of extravasation of tumor cells are highly uncharacterized, but in some aspects recapitulate the diapedesis of leukocytes. Extravasation of leukocytes through the BBB is decreased by the activation of type 2 cannabinoid receptors (CB2; therefore, in the present study we sought to investigate the role of CB2 receptors in the interaction of melanoma cells with the brain endothelium. First, we identified the presence of CB1, CB2(A, GPR18 (transcriptional variant 1 and GPR55 receptors in brain endothelial cells, while melanoma cells expressed CB1, CB2(A, GPR18 (transcriptional variants 1 and 2, GPR55 and GPR119. We observed that activation of CB2 receptors with JWH-133 reduced the adhesion of melanoma cells to the layer of brain endothelial cells. JWH-133 decreased the transendothelial migration rate of melanoma cells as well. Our results suggest that changes induced in endothelial cells are critical in the mediation of the effect of CB2 agonists. Our data identify CB2 as a potential target in reducing the number of brain metastastes originating from melanoma.

  18. Repeated stressful experiences differently affect brain dopamine receptor subtypes

    Energy Technology Data Exchange (ETDEWEB)

    Puglisi-Allegra, S.; Cabib, S. (Istituto di Psicobiologia e Psicofarmacologia (CNR), Roma (Italy)); Kempf, E.; Schleef, C. (Centre de Neurochimi, Strasbourg (Italy))

    1991-01-01

    The binding of tritiated spiperone (D2 antagonist) and tritiated SCH 23390 (D1 antagonist), in vivo, was investigated in the caudatus putamen (CP) and nucleus accumbens septi (NAS) of mice submitted to ten daily restraint stress sessions. Mice sacrificed 24 hr after the last stressful experience presented a 64% decrease of D2 receptor density (Bmax) but no changes in D1 receptor density in the NAS. In the CP a much smaller (11%) reduction of D2 receptor density was accompanied by a 10% increase of D1 receptors. These results show that the two types of dopamine (DA) receptors adapt in different or even opposite ways to environmental pressure, leading to imbalance between them.

  19. Brain imaging of mild cognitive impairment and Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    Changhao Yin; Siou Li; Weina Zhao; Jiachun Feng

    2013-01-01

    The rapidly increasing prevalence of cognitive impairment and Alzheimer's disease has the potential to create a major worldwide healthcare crisis. Structural MRI studies in patients with Alzheimer's disease and mild cognitive impairment are currently attracting considerable interest. It is extremely important to study early structural and metabolic changes, such as those in the hippocampus, entorhinal cortex, and gray matter structures in the medial temporal lobe, to allow the early detection of mild cognitive impairment and Alzheimer's disease. The microstructural integrity of white matter can be studied with diffusion tensor imaging. Increased mean diffusivity and decreased fractional anisotropy are found in subjects with white matter damage. Functional imaging studies with positron emission tomography tracer compounds enable detection of amyloid plaques in the living brain in patients with Alzheimer's disease. In this review, we will focus on key findings from brain imaging studies in mild cognitive impairment and Alzheimer's disease, including structural brain changes studied with MRI and white matter changes seen with diffusion tensor imaging, and other specific imaging methodologies will also be discussed.

  20. Arginine-Vasopressin Receptor Blocker Conivaptan Reduces Brain Edema and Blood-Brain Barrier Disruption after Experimental Stroke in Mice.

    Directory of Open Access Journals (Sweden)

    Emil Zeynalov

    Full Text Available Stroke is a major cause of morbidity and mortality. Stroke is complicated by brain edema and blood-brain barrier (BBB disruption, and is often accompanied by increased release of arginine-vasopressin (AVP. AVP acts through V1a and V2 receptors to trigger hyponatremia, vasospasm, and platelet aggregation which can exacerbate brain edema. The AVP receptor blockers conivaptan (V1a and V2 and tolvaptan (V2 are used to correct hyponatremia, but their effect on post-ischemic brain edema and BBB disruption remains to be elucidated. Therefore, we conducted this study to investigate if these drugs can prevent brain edema and BBB disruption in mice after stroke.Experimental mice underwent the filament model of middle cerebral artery occlusion (MCAO with reperfusion. Mice were treated with conivaptan, tolvaptan, or vehicle. Treatments were initiated immediately at reperfusion and administered IV (conivaptan or orally (tolvaptan for 48 hours. Physiological variables, neurological deficit scores (NDS, plasma and urine sodium and osmolality were recorded. Brain water content (BWC and Evans Blue (EB extravasation index were evaluated at the end point.Both conivaptan and tolvaptan produced aquaresis as indicated by changes in plasma and urine sodium levels. However plasma and urine osmolality was changed only by conivaptan. Unlike tolvaptan, conivaptan improved NDS and reduced BWC in the ipsilateral hemisphere: from 81.66 ± 0.43% (vehicle to 78.28 ± 0.48% (conivaptan, 0.2 mg, p < 0.05 vs vehicle. Conivaptan also attenuated the EB extravasation from 1.22 ± 0.08 (vehicle to 1.01 ± 0.02 (conivaptan, 0.2 mg, p < 0.05.Continuous IV infusion with conivaptan for 48 hours after experimental stroke reduces brain edema, and BBB disruption. Conivaptan but not tolvaptan may potentially be used in patients to prevent brain edema after stroke.

  1. 124I-Epidepride: A PET radiotracer for extended imaging of dopamine D2/D3 receptors

    International Nuclear Information System (INIS)

    Objectives: A new radiotracer, 124I-epidepride, has been developed for the imaging of dopamine D2/3 receptors (D2/3Rs). 124I-Epidepride (half-life of 124I = 4.2 days) allows imaging over extended periods compared to 18 F-fallypride (half-life of 18 F = 0.076 days) and may maximize visualization of D2/3Rs in the brain and pancreas (allowing clearance from adjacent organs). D2/3Rs are also present in pancreatic islets where they co-localize with insulin to produce granules and may serve as a surrogate marker for imaging diabetes. Methods: 124I-Epidepride was synthesized using N-[[(2S)-1-ethylpyrrolidin-2-yl]methyl]-5-tributyltin-2, 3-dimethoxybenzamide and 124I-iodide under no carrier added condition. Rats were used for in vitro and in vivo imaging. Brain slices were incubated with 124I-epidepride (0.75 μCi/cc) and nonspecific binding measured with 10 μM haloperidol. Autoradiograms were analyzed by OptiQuant. 124I-Epidepride (0.2 to 0.3 mCi, iv) was administered to rats and brain uptake at 3 hours, 24 hours, and 48 hours post injection was evaluated. Results: 124I-Epidepride was obtained with 50% radiochemical yield and high radiochemical purity (> 95%). 124I-Epidepride localized in the striatum with a striatum to cerebellum ratio of 10. Binding was displaced by dopamine and haloperidol. Brain slices demonstrated localization of 124I-epidepride up until 48 hours in the striatum. However, the extent of binding was reduced significantly. Conclusions: 124I-Epidepride is a new radiotracer suitable for extended imaging of dopamine D2/3 receptors and may have applications in imaging of receptors in the brain and monitoring pancreatic islet cell grafting

  2. 124I-Epidepride: A PET Radiotracer for Extended Imaging of Dopamine D2/D3 Receptors

    Science.gov (United States)

    Pandey, Suresh; Venugopal, Archana; Kant, Ritu; Coleman, Robert; Mukherjee, Jogeshwar

    2014-01-01

    Objectives A new radiotracer, 124I-epidepride, has been developed for the imaging of dopamine D2/3 receptors (D2/3Rs). 124I-epidepride (half-life of 124I = 4.2days) allows imaging over extended periods compared to 18F-fallypride (half-life of 18F = 0.076days) and may maximize visualization of D2/3Rs in the brain and pancreas (allowing clearance from adjacent organs). D2/3Rs are also present in pancreatic islets where they co-localize with insulin to produce granules and may serve as a surrogate marker for imaging diabetes. Methods 124I-Epidepride was synthesized using N-[[(2S)-1-ethylpyrrolidin-2-yl]methyl]-5-tributyltin-2,3-dimethoxybenzamide and 124I-iodide under no carrier added condition. Rats were used for in vitro and in vivo imaging. Brain slices were incubated with 124I-epidepride (0.75μCi/cc) and nonspecific binding measured with 10 μM haloperidol. Autoradiograms were analyzed by OptiQuant. 124I-Epidepride (0.2 to 0.3 mCi, iv) was administered to rats and brain uptake at 3 hours, 24 hours, and 48 hours post injection was evaluated. Results 124I-Epidepride was synthesized with 50% radiochemical yield and high radiochemical purity (>95%). 124I-Epidepride localized in the striatum with a striatum to cerebellum ratio of 10. Binding was displaced by dopamine and haloperidol. Brain slices demonstrated localization of 124I-epidepride up until 48 hr in the striatum. However, the extent of binding was reduced significantly. Conclusions 124I-Epidepride is a new radiotracer suitable for extended imaging of dopamine D2/3 receptors and may have applications in imaging of receptors in the brain and monitoring pancreatic islet cell grafting. PMID:24602412

  3. Transport, monitoring, and successful brain MR imaging in unsedated neonates

    Energy Technology Data Exchange (ETDEWEB)

    Mathur, Amit M. [St. Louis Children' s Hospital at the Washington University School of Medicine, Department of Pediatrics and Newborn Medicine, St. Louis, MO (United States); St. Louis Children' s Hospital, Division of Newborn Medicine, St. Louis, MO (United States); Neil, Jeffrey J. [St. Louis Children' s Hospital at the Washington University School of Medicine, Department of Neurology, St. Louis, MO (United States); Mallinckrodt Institute of Radiology, St. Louis, MO (United States); McKinstry, Robert C. [Mallinckrodt Institute of Radiology, St. Louis, MO (United States); Inder, Terrie E. [St. Louis Children' s Hospital at the Washington University School of Medicine, Department of Pediatrics and Newborn Medicine, St. Louis, MO (United States); St. Louis Children' s Hospital at the Washington University School of Medicine, Department of Neurology, St. Louis, MO (United States); Mallinckrodt Institute of Radiology, St. Louis, MO (United States)

    2008-03-15

    Neonatal cerebral MR imaging is a sensitive technique for evaluating brain injury in the term and preterm infant. In term encephalopathic infants, MR imaging reliably detects not only the pattern of brain injury but might also provide clues about the timing of injury. In premature infants, MR imaging has surpassed US in the detection of white matter injury, a common lesion in this population. Concerns remain about the safety and transport of sedated neonates for MR examination to radiology suites, which are usually located at a distance from neonatal intensive care units. We present our own institutional experience and guidelines used to optimize the performance of cerebral MR examinations in neonates without sedation or anesthesia. (orig.)

  4. Localization and characterization of brain somatostatin receptors as studied with somatostatin-14 and somatostatin-28 receptor radioautography

    International Nuclear Information System (INIS)

    The localization and characterization of receptors for somatostatin-14 (S-14) and somatostatin-28 (S-28) were studied in the rat brain using the iodinated agonists [Tyr0,D-Trp8]S-14 and [Leu8,D-Trp22,Tyr25]S-28 as tracers. By radioautography, the distribution of receptors for both S-14 and S-28 appeared very similar with high levels of binding in the deep layers of the cortex, the cingulate cortex, the claustrum, the locus coeruleus and most structures of the limbic system. Generally, there was a correlation between the localization of somatostatin receptors and that of immunoreactive somatostatin, as evaluated by immunocytochemistry. However, in some areas, an inverse correlation between receptor and peptide concentrations was observed. (Auth.)

  5. [{sup 11}C]-MeJDTic: a novel radioligand for {kappa}-opioid receptor positron emission tomography imaging

    Energy Technology Data Exchange (ETDEWEB)

    Poisnel, Geraldine; Oueslati, Farhana; Dhilly, Martine; Delamare, Jerome [Groupe de Developpements Methodologiques en Tomographie par Emission de Positons, DSV/DRM UMR CEA 2E, Universite de Caen-Basse Normandie, Centre Cyceron, 14074 Caen Cedex (France); Perrio, Cecile [Groupe de Developpements Methodologiques en Tomographie par Emission de Positons, DSV/DRM UMR CEA 2E, Universite de Caen-Basse Normandie, Centre Cyceron, 14074 Caen Cedex (France)], E-mail: perrio@cyceron.fr; Debruyne, Daniele [Groupe de Developpements Methodologiques en Tomographie par Emission de Positons, DSV/DRM UMR CEA 2E, Universite de Caen-Basse Normandie, Centre Cyceron, 14074 Caen Cedex (France)], E-mail: debruyne@cyceron.fr; Barre, Louisa [Groupe de Developpements Methodologiques en Tomographie par Emission de Positons, DSV/DRM UMR CEA 2E, Universite de Caen-Basse Normandie, Centre Cyceron, 14074 Caen Cedex (France)

    2008-07-15

    Introduction: Radiopharmaceuticals that can bind selectively the {kappa}-opioid receptor may present opportunities for staging clinical brain disorders and evaluating the efficiency of new therapies related to stroke, neurodegenerative diseases or opiate addiction. The N-methylated derivative of JDTic (named MeJDTic), which has been recently described as a potent and selective antagonist of {kappa}-opioid receptor in vitro, was labeled with carbon-11 and evaluated for in vivo imaging the {kappa}-opioid receptor in mice. Methods: [{sup 11}C]-MeJDTic was prepared by methylation of JDTic with [{sup 11}C]-methyl triflate. The binding of [{sup 11}C]-MeJDTic to {kappa}-opioid receptor was investigated ex vivo by biodistribution and competition studies using nonfasted male CD1 mice. Results: [{sup 11}C]-MeJDTic exhibited a high and rapid distribution in peripheral organs. The uptake was maximal in lung where the {kappa} receptor is largely expressed. [{sup 11}C]-MeJDTic rapidly crossed the blood-brain barrier and accumulated in the brain regions of interest (hypothalamus). The parent ligand remained the major radioactive compound in brain during the experiment. Chase studies with U50,488 (a {kappa} referring agonist), morphine (a {mu} agonist) and naltrindole (a {delta} antagonist) demonstrated that this uptake was the result of specific binding to the {kappa}-opioid receptor. Conclusion: These findings suggested that [{sup 11}C]-MeJDTic appeared to be a promising selective 'lead' radioligand for {kappa}-opioid receptor PET imaging.

  6. Comparison of Hybrid Codes for MRI Brain Image Compression

    Directory of Open Access Journals (Sweden)

    G. Soundarya

    2012-12-01

    Full Text Available In general, medical images are compressed in a lossless manner in order to preserve details and to avoid wrong diagnosis. But this leads to a lower compression rate. Therefore, our aim is to improve the compression ratio by means of hybrid coding the MRI brain (tumor images. Hence we consider Region of Interest (ROI normally the abnormal region in the image and compress it without loss to achieve high compression ratio in par with maintaining high image quality and the Non-Region of Interest (Non-ROI of the image is compressed in a lossy manner. This study discusses two simple hybrid coding techniques (Hybrid A and Hybrid B on MRI human brain tumor image datasets. Also we evaluate their performance by comparing them with the standard lossless technique JPEG 2000 in terms of Compression Ratio (CR and Peak to Signal Noise Ratio (PSNR. Both hybrid codes have resulted in computationally economical scheme producing higher compression ratio than existing JPEG2000 and also meets the legal requirement of medical image archiving. The results obtained prove that our proposed hybrid schemes outperform existing schemes.

  7. Genetic Imaging of the Association of Oxytocin Receptor Gene (OXTR Polymorphisms with Positive Maternal Parenting

    Directory of Open Access Journals (Sweden)

    Kalina J. Michalska

    2014-02-01

    Full Text Available Background: Well-validated models of maternal behavior in small-brain mammals posit a central role of oxytocin in parenting, by reducing stress and enhancing the reward value of social interactions with offspring. In contrast, human studies are only beginning to gain insights into how oxytocin modulates maternal behavior and affiliation. Methods: To explore associations between oxytocin receptor genes and maternal parenting behavior in humans, we conducted a genetic imaging study of women selected to exhibit a wide range of observed parenting when their children were 4-6 years old. Results: In response to child stimuli during functional magnetic resonance imaging, hemodynamic responses in brain regions that mediate affect, reward, and social behavior were significantly correlated with observed positive parenting. Furthermore, single nucleotide polymorphisms (rs53576 and rs1042778 in the gene encoding the oxytocin receptor were significantly associated with both positive parenting and hemodynamic responses to child stimuli in orbitofrontal cortex, anterior cingulate cortex and hippocampus. Conclusions: These findings contribute to the emerging literature on the role of oxytocin in human social behavior and support the feasibility of tracing biological pathways from genes to neural regions to positive maternal parenting behaviors in humans using genetic imaging methods.

  8. Reversible acute methotrexate leukoencephalopathy: atypical brain MR imaging features

    Energy Technology Data Exchange (ETDEWEB)

    Ziereisen, France; Damry, Nash; Christophe, Catherine [Queen Fabiola Children' s University Hospital, Department of Radiology, Brussels (Belgium); Dan, Bernard [Queen Fabiola Children' s University Hospital, Department of Neurology, Brussels (Belgium); Azzi, Nadira; Ferster, Alina [Queen Fabiola Children' s University Hospital, Department of Paediatrics, Brussels (Belgium)

    2006-03-15

    Unusual acute symptomatic and reversible early-delayed leukoencephalopathy has been reported to be induced by methotrexate (MTX). We aimed to identify the occurrence of such atypical MTX neurotoxicity in children and document its MR presentation. We retrospectively reviewed the clinical findings and brain MRI obtained in 90 children treated with MTX for acute lymphoblastic leukaemia or non-B malignant non-Hodgkin lymphoma. All 90 patients had normal brain imaging before treatment. In these patients, brain imaging was performed after treatment completion and/or relapse and/or occurrence of neurological symptoms. Of the 90 patients, 15 (16.7%) showed signs of MTX neurotoxicity on brain MRI, 9 (10%) were asymptomatic, and 6 (6.7%) showed signs of acute leukoencephalopathy. On the routine brain MRI performed at the end of treatment, all asymptomatic patients had classical MR findings of reversible MTX neurotoxicity, such as abnormal high-intensity areas localized in the deep periventricular white matter on T2-weighted images. In contrast, the six symptomatic patients had atypical brain MRI characterized by T2 high-intensity areas in the supratentorial cortex and subcortical white matter (n=6), cerebellar cortex and white matter (n=4), deep periventricular white matter (n=2) and thalamus (n=1). MR normalization occurred later than clinical recovery in these six patients. In addition to mostly asymptomatic classical MTX neurotoxicity, MTX may induce severe but reversible unusual leukoencephalopathy. It is important to recognize this clinicoradiological presentation in the differential diagnosis of acute neurological deterioration in children treated with MTX. (orig.)

  9. A new versatile clearing method for brain imaging

    Science.gov (United States)

    Costantini, Irene; Di Giovanna, Antonino Paolo; Allegra Mascaro, Anna Letizia; Silvestri, Ludovico; Müllenbroich, Marie Caroline; Sacconi, Leonardo; Pavone, Francesco S.

    2015-03-01

    Light scattering inside biological tissue is a limitation for large volumes imaging with microscopic resolution. Based on refractive index matching, different approaches have been developed to reduce scattering in fixed tissue. High refractive index organic solvents and water-based optical clearing agents, such as Sca/e, SeeDB and CUBIC have been used for optical clearing of entire mouse brain. Although these methods guarantee high transparency and preservation of the fluorescence, though present other non-negligible limitations. Tissue transformation by CLARITY allows high transparency, whole brain immunolabelling and structural and molecular preservation. This method however requires a highly expensive refractive index matching solution limiting practical applicability to large volumes. In this work we investigate the effectiveness of a water-soluble clearing agent, the 2,2'-thiodiethanol (TDE) to clear mouse and human brain. TDE does not quench the fluorescence signal, is compatible with immunostaining and does not introduce any deformation at sub-cellular level. The not viscous nature of the TDE make it a suitable agent to perform brain slicing during serial two-photon (STP) tomography. In fact, by improving penetration depth it reduces tissue slicing, decreasing the acquisition time and cutting artefacts. TDE can also be used as a refractive index medium for CLARITY. The potential of this method has been explored by imaging blocks of dysplastic human brain transformed with CLARITY, immunostained and cleared with the TDE. This clearing approach significantly expands the application of single and two-photon imaging, providing a new useful method for quantitative morphological analysis of structure in mouse and human brain.

  10. Diffusion tensor imaging and fiber tractography in brain malformations

    Energy Technology Data Exchange (ETDEWEB)

    Poretti, Andrea; Meoded, Avner; Huisman, Thierry A.G.M. [The Johns Hopkins University School of Medicine, Division of Pediatric Radiology, The Russell H. Morgan Department of Radiology and Radiological Science, Baltimore, MD (United States); Rossi, Andrea [G. Gaslini Institue, Pediatric Neuroradiology, Genova (Italy); Raybaud, Charles [University of Toronto, Department of Neuroradiology, Hospital for Sick Children, Toronto, ON (Canada)

    2013-01-15

    Diffusion tensor imaging (DTI) is an advanced MR technique that provides qualitative and quantitative information about the micro-architecture of white matter. DTI and its post-processing tool fiber tractography (FT) have been increasingly used in the last decade to investigate the microstructural neuroarchitecture of brain malformations. This article aims to review the use of DTI and FT in the evaluation of a variety of common, well-described brain malformations, in particular by pointing out the additional information that DTI and FT renders compared with conventional MR sequences. In addition, the relevant existing literature is summarized. (orig.)

  11. Dental image receptors - the changing scenario

    International Nuclear Information System (INIS)

    Dental radiology has made rapid changes in the recent years. There is overall improvement in quality of the images and reduction in imaging time. But the most important milestone that has been achieved is the reduction in the radiation dose to the patient. There has been a constant effort to reduce the patient dose during dental radiography by several methods. A key challenge is to develop films that require lesser exposure to the radiation. A constant change has been witnessed in the properties of the dental X-ray film to make it more sensitive to X-ray which literally means to achieve a reasonably good image with a minimum possible exposure. A lot of scientific papers in the past decades have highlighted on the importance of film speed and radiation dosage. Western countries have consistently upgraded their dental radiographic films over the years. This has led to high speed films being used in general practice. We have been more slow to react to these changes and have not consistently upgraded to these films. The current paper highlights the importance of film speed in reducing the radiation dosage to the patient in dental radiology. (author)

  12. Radioiodinated tracers for the evaluation of dopamine receptors in the neonatal rat brain after hypoxic-ischemic injury

    Energy Technology Data Exchange (ETDEWEB)

    Zouakia, A. (INSERM U316, Lab. de Biophysique Medicale et Pharmaceutique, 37 - Tours (France)); Chalon, S. (INSERM U316, Lab. de Biophysique Medicale et Pharmaceutique, 37 - Tours (France)); Kung, H.F. (Hospital of the Univ. of Pennsylvania, Dept. of Radiology, Philadelphia, PA (United States)); Dognon, A.M. (INSERM U316, Lab. de Biophysique Medicale et Pharmaceutique, 37 - Tours (France)); Saliba, E. (INSERM U316, Lab. de Biophysique Medicale et Pharmaceutique, 37 - Tours (France)); Besnard, J.C. (INSERM U316, Lab. de Biophysique Medicale et Pharmaceutique, 37 - Tours (France)); Guilloteau, D. (INSERM U316, Lab. de Biophysique Medicale et Pharmaceutique, 37 - Tours (France))

    1994-06-01

    In order to evaluate in vivo SPET for assessing cerebral function after hypoxic-ischemic injury in human neonates, we studied D[sub 1] and D[sub 2] dopamine receptors in a rat model. Seven-day-old rats underwent permanent unilateral common carotid ligation followed by exposure to 8% O[sub 2]. Two weeks later, in brains with no visible loss of hemispheric volume, striatal dopaminergic receptors were studied, with [[sup 125]I]TISCH and [[sup 125]I]IBZM for the D[sub 1] and D[sub 2] dopamine receptors, respectively. Using [[sup 125]I]TISCH, we observed no modifications of D[sub 1] receptors, but in contrast, ex vivo and in vitro autoradiographic experiments showed a 40% decrease in the striatal binding of [[sup 125]I]IBZM on both the ipsilateral and the contralateral side to the carotid ligation. These alterations were detected with IBZM, a D[sub 2] dopamine receptor ligand usable for SPET imaging. (orig./MG)

  13. Mapping pharmaceuticals in rat brain sections using MALDI imaging mass spectrometry.

    Science.gov (United States)

    Hsieh, Yunsheng; Li, Fangbiao; Korfmacher, Walter A

    2010-01-01

    Matrix-assisted laser desorption/ionization-tandem mass spectrometric method (MALDI-MS/MS) has proven to be a reliable tool for direct measurement of the disposition of small molecules in animal tissue sections. As example, MALDI-MS/MS imaging system was employed for visualizing the spatial distribution of astemizole and its primary metabolite in rat brain tissues. Astemizole is a second-generation antihistamine, a block peripheral H1 receptor, which was introduced to provide comparable therapeutic benefit but was withdrawn in most countries due to toxicity risks. Astemizole was observed to be heterogeneously distributed to most parts of brain tissue slices including cortex, hippocampus, hypothalamic, thalamus, and ventricle regions while its major metabolite, desmethylastemizole, was only found around ventricle sites. We have shown that astemizole alone is likely to be responsible for the central nervous system (CNS) side effects when its exposures became elevated. PMID:20680589

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

    Science.gov (United States)

    Pine, Daniel S.

    2006-01-01

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

  15. Radionuclide brain imaging in acquired immunodeficiency syndrome (AIDS)

    Energy Technology Data Exchange (ETDEWEB)

    Costa, D.C.; Gacinovic, S.; Miller, R.F. [London University College Medical School, Middlesex Hospital, London (United Kingdom)

    1995-09-01

    Infection with the Human Immunodeficiency Virus type 1 (HIV-1) may produce a variety of central nervous system (CNS) symptoms and signs. CNS involvement in patients with the Acquired Immunodeficiency Syndrome (AIDS) includes AIDS dementia complex or HIV-1 associated cognitive/motor complex (widely known as HIV encephalopathy), progressive multifocal leucoencephalopathy (PML), opportunistic infections such as Toxoplasma gondii, TB, Cryptococcus and infiltration by non-Hodgkin`s B cell lymphoma. High resolution structural imaging investigations, either X-ray Computed Tomography (CT scan) or Magnetic Resonance Imaging (MRI) have contributed to the understanding and definition of cerebral damage caused by HIV encephalopathy. Atrophy and mainly high signal scattered white matter abnormalities are commonly seen with MRI. PML produces focal white matter high signal abnormalities due to multiple foci of demyelination. However, using structural imaging techniques there are no reliable parameters to distinguish focal lesions due to opportunistic infection (Toxoplasma gondii abscess) from neoplasm (lymphoma infiltration). It is studied the use of radionuclide brain imaging techniques in the investigation of HIV infected patients. Brain perfusion Single Photon Emission Tomography (SPET), neuroreceptor and Positron Emission Tomography (PET) studies are reviewed. Greater emphasis is put on the potential of some radiopharmaceuticals, considered to be brain tumour markers, to distinguish intracerebral lymphoma infiltration from Toxoplasma infection. SPET with {sup 201}Tl using quantification (tumour to non-tumour radioactivity ratios) appears a very promising technique to identify intracerebral lymphoma.

  16. Brain surface maps from 3-D medical images

    Science.gov (United States)

    Lu, Jiuhuai; Hansen, Eric W.; Gazzaniga, Michael S.

    1991-06-01

    The anatomic and functional localization of brain lesions for neurologic diagnosis and brain surgery is facilitated by labeling the cortical surface in 3D images. This paper presents a method which extracts cortical contours from magnetic resonance (MR) image series and then produces a planar surface map which preserves important anatomic features. The resultant map may be used for manual anatomic localization as well as for further automatic labeling. Outer contours are determined on MR cross-sectional images by following the clear boundaries between gray matter and cerebral-spinal fluid, skipping over sulci. Carrying this contour below the surface by shrinking it along its normal produces an inner contour that alternately intercepts gray matter (sulci) and white matter along its length. This procedure is applied to every section in the set, and the image (grayscale) values along the inner contours are radially projected and interpolated onto a semi-cylindrical surface with axis normal to the slices and large enough to cover the whole brain. A planar map of the cortical surface results by flattening this cylindrical surface. The projection from inner contour to cylindrical surface is unique in the sense that different points on the inner contour correspond to different points on the cylindrical surface. As the outer contours are readily obtained by automatic segmentation, cortical maps can be made directly from an MR series.

  17. Radionuclide brain imaging in acquired immunodeficiency syndrome (AIDS)

    International Nuclear Information System (INIS)

    Infection with the Human Immunodeficiency Virus type 1 (HIV-1) may produce a variety of central nervous system (CNS) symptoms and signs. CNS involvement in patients with the Acquired Immunodeficiency Syndrome (AIDS) includes AIDS dementia complex or HIV-1 associated cognitive/motor complex (widely known as HIV encephalopathy), progressive multifocal leucoencephalopathy (PML), opportunistic infections such as Toxoplasma gondii, TB, Cryptococcus and infiltration by non-Hodgkin's B cell lymphoma. High resolution structural imaging investigations, either X-ray Computed Tomography (CT scan) or Magnetic Resonance Imaging (MRI) have contributed to the understanding and definition of cerebral damage caused by HIV encephalopathy. Atrophy and mainly high signal scattered white matter abnormalities are commonly seen with MRI. PML produces focal white matter high signal abnormalities due to multiple foci of demyelination. However, using structural imaging techniques there are no reliable parameters to distinguish focal lesions due to opportunistic infection (Toxoplasma gondii abscess) from neoplasm (lymphoma infiltration). It is studied the use of radionuclide brain imaging techniques in the investigation of HIV infected patients. Brain perfusion Single Photon Emission Tomography (SPET), neuroreceptor and Positron Emission Tomography (PET) studies are reviewed. Greater emphasis is put on the potential of some radiopharmaceuticals, considered to be brain tumour markers, to distinguish intracerebral lymphoma infiltration from Toxoplasma infection. SPET with 201Tl using quantification (tumour to non-tumour radioactivity ratios) appears a very promising technique to identify intracerebral lymphoma

  18. Dye-Enhanced Multimodal Confocal Imaging of Brain Cancers

    Science.gov (United States)

    Wirth, Dennis; Snuderl, Matija; Sheth, Sameer; Curry, William; Yaroslavsky, Anna

    2011-04-01

    Background and Significance: Accurate high resolution intraoperative detection of brain tumors may result in improved patient survival and better quality of life. The goal of this study was to evaluate dye enhanced multimodal confocal imaging for discriminating normal and cancerous brain tissue. Materials and Methods: Fresh thick brain specimens were obtained from the surgeries. Normal and cancer tissues were investigated. Samples were stained in methylene blue and imaged. Reflectance and fluorescence signals were excited at 658nm. Fluorescence emission and polarization were registered from 670 nm to 710 nm. The system provided lateral resolution of 0.6 μm and axial resolution of 7 μm. Normal and cancer specimens exhibited distinctively different characteristics. H&E histopathology was processed from each imaged sample. Results and Conclusions: The analysis of normal and cancerous tissues indicated clear differences in appearance in both the reflectance and fluorescence responses. These results confirm the feasibility of multimodal confocal imaging for intraoperative detection of small cancer nests and cells.

  19. Bacterial brain abscesses: prognostic value of an imaging severity index

    International Nuclear Information System (INIS)

    Aim: To assess the correlation between imaging findings [computed tomography (CT) or magnetic resonance imaging (MRI)] and neurological status before and after the treatment of bacterial brain abscesses. Materials and methods: CT and MRI images of 96 patients with brain abscesses were retrospectively evaluated in terms of the number, location and size of lesions, and the presence and extent of perilesional oedema and midline shift. An imaging severity index (ISI) based on these different radiological parameters was calculated. Initial Glasgow Coma Scale (GCS) scores and ISI were assessed and the prognostic value of these two indices was calculated. The Pearson correlation test, Mann-Whitney test, Chi-square test, receiver-operating characteristic (ROC) analysis, together with comparison of ROC analyses and Fisher's exact test were used. Results: There was a negative correlation between ISI and the initial GCS values: ISI increased as the GCS score decreased, indicating an inverse relationship (r = -0.51, p < 0.0001). There was a significant difference between the ISI and GCS scores of patients with an adverse event compared with patients with good recovery. Outcome was significantly worse in patients with initial ISI over the calculated cut-off values of 8 points or GCS scores under the cut-off value of 13 points. Conclusion: ISI is a useful prognostic indicator for bacterial brain abscess patients and correlates strongly with the patient outcome for all parameters studied. ISI score had a better prognostic value than GCS

  20. Brain angiotensin AT1 receptors as specific regulators of cardiovascular reactivity to acute psychoemotional stress.

    Science.gov (United States)

    Mayorov, Dmitry N

    2011-02-01

    1. Cardiovascular reactivity, an abrupt rise in blood pressure (BP) and heart rate in response to psychoemotional stress, is a risk factor for heart disease. Pharmacological and molecular genetic studies suggest that brain angiotensin (Ang) II and AT(1) receptors are required for the normal expression of sympathetic cardiovascular responses to various psychological stressors. Moreover, overactivity of the brain AngII system may contribute to enhanced cardiovascular reactivity in hypertension. 2. Conversely, brain AT(1) receptors appear to be less important for the regulation of sympathetic cardiovascular responses to a range of stressors involving an immediate physiological threat (physical stressors) in animal models. 3. Apart from threatening events, appetitive stimuli can induce a distinct, central nervous system-mediated rise in BP. However, evidence indicates that brain AT(1) receptors are not essential for the regulation of cardiovascular arousal associated with positively motivated behaviour, such as anticipation and the consumption of palatable food. The role of central AT(1) receptors in regulating cardiovascular activation elicited by other types of appetitive stimuli remains to be determined. 4. Emerging evidence also indicates that brain AT(1) receptors play a limited role in the regulation of cardiovascular responses to non-emotional natural daily activities, sleep and exercise. 5. Collectively, these findings suggest that, with respect to cardiovascular arousal, central AT(1) receptors may be involved primarily in the regulation of the defence response. Therefore, these receptors could be a potential therapeutic target for selective attenuation of BP hyperreactivity to aversive stressors, without altering physiologically important cardiovascular adjustments to normal daily activities, sleep and exercise.

  1. Genome-wide coexpression of steroid receptors in the mouse brain: Identifying signaling pathways and functionally coordinated regions.

    Science.gov (United States)

    Mahfouz, Ahmed; Lelieveldt, Boudewijn P F; Grefhorst, Aldo; van Weert, Lisa T C M; Mol, Isabel M; Sips, Hetty C M; van den Heuvel, José K; Datson, Nicole A; Visser, Jenny A; Reinders, Marcel J T; Meijer, Onno C

    2016-03-01

    Steroid receptors are pleiotropic transcription factors that coordinate adaptation to different physiological states. An important target organ is the brain, but even though their effects are well studied in specific regions, brain-wide steroid receptor targets and mediators remain largely unknown due to the complexity of the brain. Here, we tested the idea that novel aspects of steroid action can be identified through spatial correlation of steroid receptors with genome-wide mRNA expression across different regions in the mouse brain. First, we observed significant coexpression of six nuclear receptors (NRs) [androgen receptor (Ar), estrogen receptor alpha (Esr1), estrogen receptor beta (Esr2), glucocorticoid receptor (Gr), mineralocorticoid receptor (Mr), and progesterone receptor (Pgr)] with sets of steroid target genes that were identified in single brain regions. These coexpression relationships were also present in distinct other brain regions, suggestive of as yet unidentified coordinate regulation of brain regions by, for example, glucocorticoids and estrogens. Second, coexpression of a set of 62 known NR coregulators and the six steroid receptors in 12 nonoverlapping mouse brain regions revealed selective downstream pathways, such as Pak6 as a mediator for the effects of Ar and Gr on dopaminergic transmission. Third, Magel2 and Irs4 were identified and validated as strongly responsive targets to the estrogen diethylstilbestrol in the mouse hypothalamus. The brain- and genome-wide correlations of mRNA expression levels of six steroid receptors that we provide constitute a rich resource for further predictions and understanding of brain modulation by steroid hormones. PMID:26811448

  2. Automatic segmentation of brain images: selection of region extraction methods

    Science.gov (United States)

    Gong, Leiguang; Kulikowski, Casimir A.; Mezrich, Reuben S.

    1991-07-01

    In automatically analyzing brain structures from a MR image, the choice of low level region extraction methods depends on the characteristics of both the target object and the surrounding anatomical structures in the image. The authors have experimented with local thresholding, global thresholding, and other techniques, using various types of MR images for extracting the major brian landmarks and different types of lesions. This paper describes specifically a local- binary thresholding method and a new global-multiple thresholding technique developed for MR image segmentation and analysis. The initial testing results on their segmentation performance are presented, followed by a comparative analysis of the two methods and their ability to extract different types of normal and abnormal brain structures -- the brain matter itself, tumors, regions of edema surrounding lesions, multiple sclerosis lesions, and the ventricles of the brain. The analysis and experimental results show that the global multiple thresholding techniques are more than adequate for extracting regions that correspond to the major brian structures, while local binary thresholding is helpful for more accurate delineation of small lesions such as those produced by MS, and for the precise refinement of lesion boundaries. The detection of other landmarks, such as the interhemispheric fissure, may require other techniques, such as line-fitting. These experiments have led to the formulation of a set of generic computer-based rules for selecting the appropriate segmentation packages for particular types of problems, based on which further development of an innovative knowledge- based, goal directed biomedical image analysis framework is being made. The system will carry out the selection automatically for a given specific analysis task.

  3. Optimization of Butterworth filter for brain SPECT imaging

    International Nuclear Information System (INIS)

    A method has been described to optimize the cutoff frequency of the Butterworth filter for brain SPECT imaging. Since a computer simulation study has demonstrated that separation between an object signal and the random noise in projection images in a spatial-frequency domain is influenced by the total number of counts, the cutoff frequency of the Butterworth filter should be optimized for individual subjects according to total counts in a study. To reveal the relationship between the optimal cutoff frequencies and total counts in brain SPECT study, we used a normal volunteer and 99mTc hexamethyl-propyleneamine oxime (HMPAO) to obtain projection sets with different total counts. High quality images were created from a projection set with an acquisition time of 300-seconds per projection. The filter was optimized by calculating mean square errors from high quality images visually inspecting filtered reconstructed images. Dependence between total counts and optimal cutoff frequencies was clearly demonstrated in a nomogram. Using this nomogram, the optimal cutoff frequency for each study can be estimated from total counts, maximizing visual image quality. The results suggest that the cutoff frequency of Butterworth filter should be determined by referring to total counts in each study. (author)

  4. Autoradiographic comparison of [125I]epidepride and [125I]NCQ 298 binding to human brain extrastriated dopamine receptors.

    Science.gov (United States)

    Hall, H; Halldin, C; Jerning, E; Osterlund, M; Farde, L; Sedvall, G

    1997-07-01

    Extrastriatal D2-dopamine receptors can be visualised in the monkey and human brain using the benzamides [11C]- and [76Br]FLB 457 in PET and [123I]epidepride in SPECT but not with the salicylamide analogues [76Br]FLB 463 and [123I]NCQ 298. To clarify the background for the differences in binding seen in vivo, we have compared the in vitro binding of [125I]epidepride and [123I]NCQ 298, using human whole hemisphere autoradiography. The images obtained with any radioligand showed detailed distribution with very dense binding in the putamen and the caudate nucleus and with the same detailed extrastriatal distribution. Thus, the divergent results obtained in vivo cannot be explained by different binding properties of the extrastriatal receptors. PMID:9290072

  5. Autoradiographic comparison of [125I]epidepride and [125I]NCQ 298 binding to human brain extrastriated dopamine receptors

    International Nuclear Information System (INIS)

    Extrastriatal D2-dopamine receptors can be visualized in the monkey and human brain using the benzamides [11C]- and [76Br]FLB 457 in PET and [123I]epidepride in SPECT but not with the salicylamide analogues [76Br]FLB 463 and [123I]NCQ 298. To clarify the background for the differences in binding seen in vivo, we have compared the in vitro binding of [125I]epidepride and [125I]NCQ 298, using human whole hemisphere autoradiography. The images obtained with any radioligand showed detailed distribution with very dense binding in the putamen and the caudate nucleus and with the same detailed extrastriatal distribution. Thus, the divergent results obtained in vivo cannot be explained by different binding properties of the extrastriatal receptors

  6. Brain regional differences in CB1 receptor adaptation and regulation of transcription

    OpenAIRE

    Lazenka, M.F.; Selley, D.E.; Sim-Selley, L.J.

    2012-01-01

    Cannabinoid CB1 receptors (CB1Rs) are expressed throughout the brain and mediate the central effects of cannabinoids, including Δ9-tetrahydrocannabinol (THC), the main psychoactive constituent of marijuana. Repeated THC administration produces tolerance to cannabinoid-mediated effects, although the magnitude of tolerance varies by effect. Consistent with this observation, CB1R desensitization and downregulation, as well induction of immediate early genes (IEGs), varies by brain region. Zif268...

  7. High abundance androgen receptor in goldfish brain: characteristics and seasonal changes

    International Nuclear Information System (INIS)

    Testosterone (T) exerts its actions in brain directly via androgen receptors or, after aromatization to estradiol, via estrogen receptors. Brain aromatase activity in teleost fish is 100-1000 times greater than in mammals and would be expected to significantly reduce the quantity of androgen available for receptor binding. Experiments were carried out on the goldfish Carassius auratus to determine if androgen receptors are present in teleost brain and whether their physicochemical properties reflect elevated aromatase. Cytosolic and nuclear extracts were assayed with the use of [3H]T and charcoal, Sephadex LH-20, or DNA-cellulose chromatography to separate bound and free steroids. Binding activity was saturable and had an equally high affinity for T and 5 alpha-dihydrotestosterone. Although mibolerone was a relatively weak competitor, the putative teleost androgen 11-ketotestosterone, methyltrienolone (R1881), estradiol, progesterone, and cortisol were poor ligands. Characteristics that distinguish this receptor from a steroid-binding protein in goldfish serum are the presence of binding activity in both nuclear and cytosolic extracts, a low rate of ligand-receptor dissociation, electrophoretic mobility, sedimentation properties in low vs. high salt, and tissue distribution. DNA cellulose-adhering and nonadhering forms were detected, but these did not differ in other variables measured. Although goldfish androgen receptors resembled those of mammals in all important physicochemical characteristics, they were unusually abundant compared to levels in rat brain, but comparable to levels in prostate and other male sex hormone target organs. Moreover, there were seasonal variations in total receptors, with a peak at spawning (April) 4- to 5-fold higher than values in reproductively inactive fish

  8. Memory consolidation and amnesia modify 5-HT6 receptors expression in rat brain: an autoradiographic study.

    Science.gov (United States)

    Meneses, A; Manuel-Apolinar, L; Castillo, C; Castillo, E

    2007-03-12

    Traditionally, the search for memory circuits has been centered on examinations of amnesic and AD patients, cerebral lesions and, neuroimaging. A complementary alternative might be the use of autoradiography with radioligands. Indeed, ex vivo autoradiographic studies offer the advantage to detect functionally active receptors altered by pharmacological tools and memory formation. Hence, herein the 5-HT(6) receptor antagonist SB-399885 and the amnesic drugs scopolamine or dizocilpine were used to manipulate memory consolidation and 5-HT(6) receptors expression was determined by using [(3)H]-SB-258585. Thus, memory consolidation was impaired in scopolamine and dizocilpine treated groups relative to control vehicle but improved it in SB-399885-treated animals. SB-399885 improved memory consolidation seems to be associated with decreased 5-HT(6) receptors expression in 15 out 17 brain areas. Scopolamine or dizocilpine decreased 5-HT(6) receptors expression in nine different brain areas and increased it in CA3 hippocampus or other eight areas, respectively. In brain areas thought to be in charge of procedural memory such basal ganglia (i.e., nucleus accumbens, caudate putamen, and fundus striate) data showed that relative to control animals amnesic groups showed diminished (scopolamine) or augmented (dizocilpine) 5-HT(6) receptor expression. SB-399885 showing improved memory displayed an intermediate expression in these same brain regions. A similar intermediate expression occurs with regard to amygdala, septum, and some cortical areas in charge of explicit memory storage. However, relative to control group amnesic and SB-399885 rats in the hippocampus, region where explicit memory is formed, showed a complex 5-HT(6) receptors expression. In conclusion, these results indicate neural circuits underlying the effects of 5-HT(6) receptor antagonists in autoshaping task and offer some general clues about cognitive processes in general. PMID:17267053

  9. A Cellular Perspective on Brain Energy Metabolism and Functional Imaging

    KAUST Repository

    Magistretti, Pierre J.

    2015-05-01

    The energy demands of the brain are high: they account for at least 20% of the body\\'s energy consumption. Evolutionary studies indicate that the emergence of higher cognitive functions in humans is associated with an increased glucose utilization and expression of energy metabolism genes. Functional brain imaging techniques such as fMRI and PET, which are widely used in human neuroscience studies, detect signals that monitor energy delivery and use in register with neuronal activity. Recent technological advances in metabolic studies with cellular resolution have afforded decisive insights into the understanding of the cellular and molecular bases of the coupling between neuronal activity and energy metabolism and pointat a key role of neuron-astrocyte metabolic interactions. This article reviews some of the most salient features emerging from recent studies and aims at providing an integration of brain energy metabolism across resolution scales. © 2015 Elsevier Inc.

  10. Bombesin receptor-mediated imaging and cytotoxicity: review and current status

    OpenAIRE

    Sancho, Veronica; Di Florio, Alessia; Moody, Terry W.; Jensen, Robert T.

    2011-01-01

    The three mammalian bombesin (Bn) receptors (gastrin-releasing peptide [GRP] receptor, neuromedin B [NMB] receptor, BRS-3) are one of the classes of G protein-coupled receptors that are most frequently over-express/ectopically expressed by common, important malignancies. Because of the clinical success of somatostatin receptor-mediated imaging and cytotoxicity with neuroendocrine...

  11. Volume transmission and receptor-receptor interactions in heteroreceptor complexes: understanding the role of new concepts for brain communication.

    Science.gov (United States)

    Fuxe, Kjell; Borroto-Escuela, Dasiel O

    2016-08-01

    The discovery of the central monoamine neurons not only demonstrated novel types of brain stem neurons forming global terminal networks all over the brain and the spinal cord, but also to a novel type of communication called volume transmission. It is a major mode of communication in the central nervous system that takes places in the extracellular fluid and the cerebral spinal fluid through diffusion and flow of molecules, like neurotransmitters and extracellular vesicles. The integration of synaptic and volume transmission takes place through allosteric receptor-receptor interactions in heteroreceptor complexes. These heterocomplexes represent major integrator centres in the plasma membrane and their protomers act as moonlighting proteins undergoing dynamic changes and their structure and function. In fact, we propose that the molecular bases of learning and memory can be based on the reorganization of multiples homo and heteroreceptor complexes into novel assembles in the post-junctional membranes of synapses.

  12. Volume transmission and receptor-receptor interactions in heteroreceptor complexes: understanding the role of new concepts for brain communication

    Science.gov (United States)

    Fuxe, Kjell; Borroto-Escuela, Dasiel O.

    2016-01-01

    The discovery of the central monoamine neurons not only demonstrated novel types of brain stem neurons forming global terminal networks all over the brain and the spinal cord, but also to a novel type of communication called volume transmission. It is a major mode of communication in the central nervous system that takes places in the extracellular fluid and the cerebral spinal fluid through diffusion and flow of molecules, like neurotransmitters and extracellular vesicles. The integration of synaptic and volume transmission takes place through allosteric receptor-receptor interactions in heteroreceptor complexes. These heterocomplexes represent major integrator centres in the plasma membrane and their protomers act as moonlighting proteins undergoing dynamic changes and their structure and function. In fact, we propose that the molecular bases of learning and memory can be based on the reorganization of multiples homo and heteroreceptor complexes into novel assembles in the post-junctional membranes of synapses. PMID:27651759

  13. Volume transmission and receptor-receptor interactions in heteroreceptor complexes: understanding the role of new concepts for brain communication.

    Science.gov (United States)

    Fuxe, Kjell; Borroto-Escuela, Dasiel O

    2016-08-01

    The discovery of the central monoamine neurons not only demonstrated novel types of brain stem neurons forming global terminal networks all over the brain and the spinal cord, but also to a novel type of communication called volume transmission. It is a major mode of communication in the central nervous system that takes places in the extracellular fluid and the cerebral spinal fluid through diffusion and flow of molecules, like neurotransmitters and extracellular vesicles. The integration of synaptic and volume transmission takes place through allosteric receptor-receptor interactions in heteroreceptor complexes. These heterocomplexes represent major integrator centres in the plasma membrane and their protomers act as moonlighting proteins undergoing dynamic changes and their structure and function. In fact, we propose that the molecular bases of learning and memory can be based on the reorganization of multiples homo and heteroreceptor complexes into novel assembles in the post-junctional membranes of synapses. PMID:27651759

  14. Volume transmission and receptor-receptor interactions in heteroreceptor complexes:understanding the role of new concepts for brain communication

    Institute of Scientific and Technical Information of China (English)

    Kjell Fuxe; Dasiel O Borroto-Escuela

    2016-01-01

    The discovery of the central monoamine neurons not only demonstrated novel types of brain stem neu-rons forming global terminal networks all over the brain and the spinal cord, but also to a novel type of communication called volume transmission. It is a major mode of communication in the central nervous system that takes places in the extracellular lfuid and the cerebral spinal lfuid through diffusion and lfow of molecules, like neurotransmitters and extracellular vesicles. The integration of synaptic and volume trans-mission takes place through allosteric receptor-receptor interactions in heteroreceptor complexes. These heterocomplexes represent major integrator centres in the plasma membrane and their protomers act as moonlighting proteins undergoing dynamic changes and their structure and function. In fact, we propose that the molecular bases of learning and memory can be based on the reorganization of multiples homo and heteroreceptor complexes into novel assembles in the post-junctional membranes of synapses.

  15. Imaging GABAc Receptors with Ligand-Conjugated Quantum Dots

    Directory of Open Access Journals (Sweden)

    Ian D. Tomlinson

    2007-01-01

    Full Text Available We report a methodology for labeling the GABAc receptor on the surface membrane of intact cells. This work builds upon our earlier work with serotonin-conjugated quantum dots and our studies with PEGylated quantum dots to reduce nonspecific binding. In the current approach, a PEGylated derivative of muscimol was synthesized and attached via an amide linkage to quantum dots coated in an amphiphilic polymer derivative of a modified polyacrylamide. These conjugates were used to image GABAC receptors heterologously expressed in Xenopus laevis oocytes.

  16. Robust Intensity Standardization in Brain Magnetic Resonance Images.

    Science.gov (United States)

    De Nunzio, Giorgio; Cataldo, Rosella; Carlà, Alessandra

    2015-12-01

    The paper is focused on a tiSsue-Based Standardization Technique (SBST) of magnetic resonance (MR) brain images. Magnetic Resonance Imaging intensities have no fixed tissue-specific numeric meaning, even within the same MRI protocol, for the same body region, or even for images of the same patient obtained on the same scanner in different moments. This affects postprocessing tasks such as automatic segmentation or unsupervised/supervised classification methods, which strictly depend on the observed image intensities, compromising the accuracy and efficiency of many image analyses algorithms. A large number of MR images from public databases, belonging to healthy people and to patients with different degrees of neurodegenerative pathology, were employed together with synthetic MRIs. Combining both histogram and tissue-specific intensity information, a correspondence is obtained for each tissue across images. The novelty consists of computing three standardizing transformations for the three main brain tissues, for each tissue class separately. In order to create a continuous intensity mapping, spline smoothing of the overall slightly discontinuous piecewise-linear intensity transformation is performed. The robustness of the technique is assessed in a post hoc manner, by verifying that automatic segmentation of images before and after standardization gives a high overlapping (Dice index >0.9) for each tissue class, even across images coming from different sources. Furthermore, SBST efficacy is tested by evaluating if and how much it increases intertissue discrimination and by assessing gaussianity of tissue gray-level distributions before and after standardization. Some quantitative comparisons to already existing different approaches available in the literature are performed.

  17. BRAIN FUNCTIONAL IMAGING BASED ON BRAIN TISSUE OXYGEN CONTENT VIA MAGNETIC RESONANCE

    Directory of Open Access Journals (Sweden)

    M.A OGHABIAN

    2003-03-01

    Full Text Available Introduction: FMRI is a new approach in MRI to provide functional data of human brain activities. Some methods such as BOLD contrast, perfusion imaging, diffusion imaging, and spectroscopy in MRI have used to yield functional images. Material and Methods: This research was performed in imaging center of IMAM KHOMEINI hospital in TEHRAN in 1997. The experiments were performed on a conventional 1.5- T picker MR instrument, using a standard head coil. CE – FAST gradient echo images were obtained (TR=100, TE = 35, 128*256 matrix, 10 mm slice, FOV = 250 mm, F.A =25 Degree, NEX = 1, 13 s per image. Images were obtained during sensory - motor stimulation by pressing fingers to each other, coronal oblique images were acquired through central sulcus (precentral gyrus where the related sensory cortex is. Then, the Images were transferred to personal computers in order to eliminate noise and highlight the functional differences. These images were processed by various mathematical methods such as subtraction and student T- test. Results: Although some changes were seen in functional area, there were not significant results by the conventional system protocols. Some new protocols were designed and implemented to increase the sensitivity of the system to functional changes. Discussion: However, more research needs to be done in the future to obtain faster and more efficient techniques and in regard to clinical applications of the method.

  18. The image of a brain stroke in a computed tomograph

    International Nuclear Information System (INIS)

    On the basis of 100 findings from patients who suffered brain strokes and by the use of 1500 ensured stroke images it was tested whether or not the stroke-predilection typologie outlined by Zuelch is based on a coincidental summation of individual cases. The radio-computed tomography with the possibility of evaluation of non-lethal cases proved itself as a suited method for confirmation or repudiation of this stroke theory. By means of the consistently achieved association of the frontal, respectively horizontal sectional image for the typology it could be proven and - with the exception of a few rather seldom types - also demonstrated that the basic and predilection types of brain stroke repeated themselves in their pattern. In individual cases a specification of lower types could also be undertaken. (orig./TRV)

  19. Mixture Segmentation of Multispectral MR Brain Images for Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Lihong Li

    2005-04-01

    Full Text Available We present a fully automatic mixture model-based tissue classification of multispectral (T1- and T2-weighted magnetic resonance (MR brain images. Unlike the conventional hard classification with a unique label for each voxel, our method models a mixture to estimate the partial volumes (PV of multiple tissue types within a voxel. A new Markov random field (MRF model is proposed to reflect the spatial information of tissue mixtures. A mixture classification algorithm is performed by the maximum a posterior (MAP criterion, where the expectation maximization (EM algorithm is utilized to estimate model parameters. The algorithm interleaves segmentation with parameter estimation and improves classification in an iterative manner. The presented method is evaluated by clinical MR image datasets for quantification of brain volumes and multiple sclerosis (MS.

  20. Functional imaging of single synapses in brain slices.

    Science.gov (United States)

    Oertner, Thomas G

    2002-11-01

    The strength of synaptic connections in the brain is not fixed, but can be modulated by numerous mechanisms. Traditionally, electrophysiology has been used to characterize connections between neurons. Electrophysiology typically reports the activity of populations of synapses, while most mechanisms of plasticity are thought to operate at the level of single synapses. Recently, two-photon laser scanning microscopy has enabled us to perform optical quantal analysis of individual synapses in intact brain tissue. Here we introduce the basic principle of the two-photon microscope and discuss its main differences compared to the confocal microscope. Using calcium imaging in dendritic spines as an example, we explain the advantages of simultaneous dual-dye imaging for quantitative calcium measurements and address two common problems, dye saturation and background fluorescence subtraction.

  1. PET/SPECT imaging: From carotid vulnerability to brain viability

    Energy Technology Data Exchange (ETDEWEB)

    Meerwaldt, Robbert [Department of Surgery, Isala Clinics, Zwolle (Netherlands); Slart, Riemer H.J.A. [Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, Groningen (Netherlands); Dam, Gooitzen M. van [Department of Surgery, University Medical Center Groningen, Groningen (Netherlands); Luijckx, Gert-Jan [Department of Neurology, University Medical Center Groningen, Groningen (Netherlands); Tio, Rene A. [Department of Cardiology, University Medical Center Groningen, Groningen (Netherlands); Zeebregts, Clark J. [Department of Surgery, University Medical Center Groningen, Groningen (Netherlands)], E-mail: czeebregts@hotmail.com

    2010-04-15

    Background: Current key issues in ischemic stroke are related to carotid plaque vulnerability, brain viability, and timing of intervention. The treatment of ischemic stroke has evolved into urgent active interventions, as 'time is brain'. Functional imaging such as positron emission tomography (PET)/single photon emission computed tomography (SPECT) could improve selection of patients with a vulnerable plaque and evaluation of brain viability in ischemic stroke. Objective: To describe the current applications of PET and SPECT as a diagnostic tool in relation to ischemic stroke. Methods: A literature search using PubMed identified articles. Manual cross-referencing was also performed. Results: Several papers, all observational studies, identified PET/SPECT to be used as a tool to monitor systemic atheroma modifying treatment and to select high-risk patients for surgery regardless of the degree of luminal stenosis in carotid lesions. Furthermore, PET/SPECT is able to quantify the penumbra region during ischemic stroke and in this way may identify those patients who may benefit from timely intervention. Discussion: Functional imaging modalities such as PET/SPECT may become important tools for risk-assessment and evaluation of treatment strategies in carotid plaque vulnerability and brain viability. Prospective clinical studies are needed to evaluate the diagnostic accuracy of PET/SPECT.

  2. Study of functional brain imaging for bilingual language cognition

    International Nuclear Information System (INIS)

    Bilingual and multilingual brain studies of language recognition is an interdisciplinary subject which needs to identify different levels involved in the neural representation of languages, such as neuroanatomical, neurofunctional, biochemical, psychological and linguistic levels. Furthermore, specific factor's such as age, manner of acquisition and environmental factors seem to affect the neural representation. Functional brain imaging, such as PET, SPECT and functional MRI can explore the neurolinguistics representation of bilingualism in the brain in subjects, and elucidate the neuronal mechanisms of bilingual language processing. Functional imaging methods show differences in the pattern of cerebral activation associated with a second language compared with the subject's native language. It shows that verbal memory processing in two unrelated languages is mediated by a common neural system with some distinct cortical areas. The different patterns of activation differ according to the language used. It also could be ascribed either to age of acquisition or to proficiency level. And attained proficiency is more important than age of acquisition as a determinant of the cortical representation of the second language. The study used PET and SPECT shows that sign and spoken language seem to be localized in the same brain areas, and elicit similar regional cerebral blood flow patterns. But for sign language perception, the functional anatomy overlaps that of language processing contain both auditory and visual components. And the sign language is dependent on spatial information too. (authors)

  3. Methods for processing and analysis functional and anatomical brain images: computerized tomography, emission tomography and nuclear resonance imaging

    International Nuclear Information System (INIS)

    The various methods for brain image processing and analysis are presented and compared. The following topics are developed: the physical basis of brain image comparison (nature and formation of signals intrinsic performance of the methods image characteristics); mathematical methods for image processing and analysis (filtering, functional parameter extraction, morphological analysis, robotics and artificial intelligence); methods for anatomical localization (neuro-anatomy atlas, proportional stereotaxic atlas, numerized atlas); methodology of cerebral image superposition (normalization, retiming); image networks

  4. Brain size and brain organization of the whale shark, Rhincodon typus, using magnetic resonance imaging.

    Science.gov (United States)

    Yopak, Kara E; Frank, Lawrence R

    2009-01-01

    Very little is known about the brain organization of the suction filter feeder, Rhincodon typus, and how it compares to other orectolobiforms in light of its specialization as a plankton-feeder. Brain size and overall brain organization was assessed in two specimens of R. typus in relation to both phylogeny and ecology, using magnetic resonance imaging (MRI). In comparison to over 60 other chondrichthyan species, R. typus demonstrated a relatively small brain for its body size (expressed in terms of encephalization quotients and residuals), similar to the lamniforms Carcharodon carcharias, Cetorhinus maximus, and Carcharias taurus. R. typus possessed a relatively small telencephalon with some development of the dorsal pallium, which was suggestive of moderate social behavior, in addition to a relatively large diencephalon and a relatively reduced mesencephalon. The most notable characteristic of the brain of Rhincodon was a large and highly foliated cerebellum, one of the largest cerebellums within the chondrichthyan clade. Early development of the brain was qualitatively assessed using an in situ MRI scan of the brain and chondrocranium of a neonate specimen of R. typus. There was evidence that folding of the cerebellar corpus appeared in early development, although the depth and number of folds might vary ontogenetically in this species. Hierarchical cluster analysis and multidimensional scaling ordinations showed evidence of convergent evolution with the basking shark, Cetorhinus maximus, another large-bodied filter feeding elasmobranch, supporting the claim that organization of the brain is more similar in species with analogous but independently evolved lifestyles than those that share taxonomic classification. PMID:19729899

  5. Noninvasive bioluminescence imaging of dengue virus infection in the brain of A129 mice.

    Science.gov (United States)

    Li, Xiao-Feng; Deng, Yong-Qiang; Zhao, Hui; Ye, Qing; Wang, Hong-Jiang; Li, Shi-Hua; Zhu, Shun-Ya; Shi, Pei-Yong; Qin, E-De; Zhang, Bo; Qin, Cheng-Feng

    2013-05-01

    Dengue virus (DENV) infection is one of the most important public health threats globally; however, no vaccines or effective antivirals are currently available. The bioluminescence imaging technique has emerged as a powerful tool for studies on viral pathogenesis in vitro and in vivo. In this study, using a recombinant DENV that stably expressed Renilla luciferase (Rluc-DENV), we used bioluminescence for imaging of DENV infection in the brain of A129 mice that lacked type I interferon receptors. Upon intracranial inoculation with Rluc-DENV, A129 mice developed typical neurological symptoms and rapidly succumbed to viral infection. Real-time bioluminescence intensity analysis revealed the replication kinetics of Rluc-DENV in the brain of A129 mice. Linear regression analyses showed a good correlation between photon flux and viral titers (R(2) = 0.9923). Finally, the bioluminescence model was validated using a known mouse monoclonal antibody, 2A10G6, and the therapeutic effects of this neutralizing antibody were readily monitored by live imaging in the same animal. The noninvasive bioluminescence imaging of DENV infection as described here shows distinct advantages over traditional animal models and provides a powerful tool for potential antiviral or vaccine assays against DENV infection in vivo.

  6. In vivo (/sup 3/H)flunitrazepam binding: imaging of receptor regulation

    Energy Technology Data Exchange (ETDEWEB)

    Ciliax, B.J.; Penney, J.B. Jr.; Young, A.B.

    1986-08-01

    The use of (/sup 3/H)flunitrazepam as a ligand to measure alterations in benzodiazepine receptors in vivo in rats was investigated. Animals were injected with (/sup 3/H)flunitrazepam i.v., arterial samples of (/sup 3/H)flunitrazepam were obtained and, later, the animals were sacrificed to assay brain binding. (/sup 3/H)flunitrazepam enters the brain rapidly and binds to benzodiazepine receptors. About two-thirds of this binding is blocked by predosing the animals with 5 mg/kg of clonazepam. The amount of remaining (nonspecific) binding correlates very well (r = 0.88) with the amount of radioactivity found in plasma at the time of death. A series of rats were lesioned unilaterally with kainic acid in the caudate-putamen several months before the infusion of (/sup 3/H)flunitrazepam. In vivo autoradiography in lesioned rats showed that benzodiazepine binding in globus pallidus and substantia nigra on the side of the lesion was increased significantly as compared to the intact side. The observed changes in benzodiazepine binding were similar to those observed previously in lesioned rats using in vitro techniques. Thus, benzodiazepine receptor regulation can be imaged quantitatively using in vivo binding techniques.

  7. In vivo [3H]flunitrazepam binding: imaging of receptor regulation

    International Nuclear Information System (INIS)

    The use of [3H]flunitrazepam as a ligand to measure alterations in benzodiazepine receptors in vivo in rats was investigated. Animals were injected with [3H]flunitrazepam i.v., arterial samples of [3H]flunitrazepam were obtained and, later, the animals were sacrificed to assay brain binding. [3H]flunitrazepam enters the brain rapidly and binds to benzodiazepine receptors. About two-thirds of this binding is blocked by predosing the animals with 5 mg/kg of clonazepam. The amount of remaining (nonspecific) binding correlates very well (r = 0.88) with the amount of radioactivity found in plasma at the time of death. A series of rats were lesioned unilaterally with kainic acid in the caudate-putamen several months before the infusion of [3H]flunitrazepam. In vivo autoradiography in lesioned rats showed that benzodiazepine binding in globus pallidus and substantia nigra on the side of the lesion was increased significantly as compared to the intact side. The observed changes in benzodiazepine binding were similar to those observed previously in lesioned rats using in vitro techniques. Thus, benzodiazepine receptor regulation can be imaged quantitatively using in vivo binding techniques

  8. Region-selective effects of neuroinflammation and antioxidant treatment on peripheral benzodiazepine receptors and NMDA receptors in the rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Biegon, A.; Alvarado, M.; Budinger, T.F.; Grossman, R.; Hensley, K.; West, M.S.; Kotake, Y.; Ono, M.; Floyd, R.A.

    2001-12-10

    Following induction of acute neuroinflammation by intracisternal injection of endotoxin (lipopolysaccharide) in rats, quantitative autoradiography was used to assess the regional level of microglial activation and glutamate (NMDA) receptor binding. The possible protective action of the antioxidant phenyl-tert-butyl nitrone in this model was tested by administering the drug in the drinking water for 6 days starting 24 hours after endotoxin injection. Animals were killed 7 days post-injection and consecutive cryostat brain sections labeled with [3H]PK11195 as a marker of activated microglia and [125I]iodoMK801 as a marker of the open-channel, activated state of NMDA receptors. Lipopolysaccharide increased [3H]PK11195 binding in the brain, with the largest increases (2-3 fold) in temporal and entorhinal cortex, hippocampus, and substantia innominata. A significant (>50 percent) decrease in [125I]iodoMK801 binding was found in the same brain regions. Phenyl-tert-butyl nitrone treatment resulted in a partial inhibition ({approx}25 percent decrease) of the lipopolysaccharide-induced increase in [3H]PK11195 binding but completely reversed the lipopolysaccharide-induced decrease in [125I]iodoMK80 binding in the entorhinal cortex, hippocampus, and substantia innominata. Loss of NMDA receptor function in cortical and hippocampal regions may contribute to the cognitive deficits observed in diseases with a neuroinflammatory component, such as meningitis or Alzheimer's disease.

  9. Imaging of Brain Dopamine Pathways: Implications for Understanding Obesity

    OpenAIRE

    Wang, Gene-Jack; Volkow, Nora D.; Panayotis K Thanos; Fowler, Joanna S.

    2009-01-01

    Obesity is typically associated with abnormal eating behaviors. Brain imaging studies in humans implicate the involvement of dopamine (DA)-modulated circuits in pathologic eating behavior(s). Food cues increase striatal extracellular DA, providing evidence for the involvement of DA in the nonhedonic motivational properties of food. Food cues also increase metabolism in the orbitofrontal cortex indicating the association of this region with the motivation for food consumption. Similar to drug-...

  10. Towards an hybrid system for annotating brain MRI images

    OpenAIRE

    Mechouche, Ammar; Golbreich, Christine; Gibaud, Bernard

    2006-01-01

    This paper describes a method combining symbolic and numerical techniques for annotating brain Magnetic Resonance images. The goal is to assist existing automatic labelling methods which are mostly statistical in nature and do not work very well in certain situations such as the presence of lesions. The system uses existing statistical methods for generating ABox facts that constitute a set of initial information sufficient for fruitful reasoning. The reasoning is supported by an OWL ontology...

  11. Multiplexed echo planar imaging for sub-second whole brain FMRI and fast diffusion imaging.

    Directory of Open Access Journals (Sweden)

    David A Feinberg

    Full Text Available Echo planar imaging (EPI is an MRI technique of particular value to neuroscience, with its use for virtually all functional MRI (fMRI and diffusion imaging of fiber connections in the human brain. EPI generates a single 2D image in a fraction of a second; however, it requires 2-3 seconds to acquire multi-slice whole brain coverage for fMRI and even longer for diffusion imaging. Here we report on a large reduction in EPI whole brain scan time at 3 and 7 Tesla, without significantly sacrificing spatial resolution, and while gaining functional sensitivity. The multiplexed-EPI (M-EPI pulse sequence combines two forms of multiplexing: temporal multiplexing (m utilizing simultaneous echo refocused (SIR EPI and spatial multiplexing (n with multibanded RF pulses (MB to achieve m×n images in an EPI echo train instead of the normal single image. This resulted in an unprecedented reduction in EPI scan time for whole brain fMRI performed at 3 Tesla, permitting TRs of 400 ms and 800 ms compared to a more conventional 2.5 sec TR, and 2-4 times reductions in scan time for HARDI imaging of neuronal fibertracks. The simultaneous SE refocusing of SIR imaging at 7 Tesla advantageously reduced SAR by using fewer RF refocusing pulses and by shifting fat signal out of the image plane so that fat suppression pulses were not required. In preliminary studies of resting state functional networks identified through independent component analysis, the 6-fold higher sampling rate increased the peak functional sensitivity by 60%. The novel M-EPI pulse sequence resulted in a significantly increased temporal resolution for whole brain fMRI, and as such, this new methodology can be used for studying non-stationarity in networks and generally for expanding and enriching the functional information.

  12. Label-free dopamine imaging in live rat brain slices.

    Science.gov (United States)

    Sarkar, Bidyut; Banerjee, Arkarup; Das, Anand Kant; Nag, Suman; Kaushalya, Sanjeev Kumar; Tripathy, Umakanta; Shameem, Mohammad; Shukla, Shubha; Maiti, Sudipta

    2014-05-21

    Dopaminergic neurotransmission has been investigated extensively, yet direct optical probing of dopamine has not been possible in live cells. Here we image intracellular dopamine with sub-micrometer three-dimensional resolution by harnessing its intrinsic mid-ultraviolet (UV) autofluorescence. Two-photon excitation with visible light (540 nm) in conjunction with a non-epifluorescent detection scheme is used to circumvent the UV toxicity and the UV transmission problems. The method is established by imaging dopamine in a dopaminergic cell line and in control cells (glia), and is validated by mass spectrometry. We further show that individual dopamine vesicles/vesicular clusters can be imaged in cultured rat brain slices, thereby providing a direct visualization of the intracellular events preceding dopamine release induced by depolarization or amphetamine exposure. Our technique opens up a previously inaccessible mid-ultraviolet spectral regime (excitation ~270 nm, emission free imaging of native molecules in live tissue.

  13. In vivo brain dopaminergic receptor site mapping using /sup 75/Se-labeled pergolide analogs: the effects of various dopamine receptor agonists and antagonists

    Energy Technology Data Exchange (ETDEWEB)

    Weaver, A.

    1986-01-01

    Perogolide mesylate is a new synthetic ergoline derivative which is reported to possess agonistic activity at central dopamine receptor sites in the brain. The authors have synthesized a (/sup 75/Se)-radiolabeled pergolide mesylate derivative, (/sup 75/Se)-pergolide tartrate, which, after i.v. administration to mature male rats, showed a time course differentiation in the uptake of this radiolabeled compound in isolated peripheral and central (brain) tissues that are known to be rich in dopamine receptor sites. Further studies were conducted in which the animals were preexposed to the dopamine receptor agonist SKF-38393, as well as the dopamine receptor antagonists (+)-butaclamol, (-)-butaclamol, (+/-)-butaclamol and (-)-chloroethylnorapomorphine, to substantiate the specific peripheral and central localization patterns of (/sup 75/Se)-pergolide tartrate. Further investigations were also conducted in which the animals received an i.v. administration of N-isopropyl-l-123-p-iodoamphetamine ((/sup 123/I)-iodoamphetamine). However, (/sup 123/I)-iodoamphetamine did not demonstrate a specific affinity for any type of receptor site in the brain. These investigations further substantiated the fact that (/sup 75/Se)-pergolide tartrate does cross the blood-brain barrier is quickly localized at specific dopamine receptor sites in the intact rat brain and that this localization pattern can be affected by preexposure to different dopamine receptor agonists and antagonists. Therefore, these investigations provided further evidence that (/sup 75/Se)-pergolide tartrate and other radiolabeled ergoline analogs might be useful as brain dopamine receptor localization radiopharmaceuticals.

  14. Distribution of androgen receptor in microdissected brain areas of the female baboon (Papio cynocephalus).

    Science.gov (United States)

    Handa, R J; Roselli, C E; Resko, J A

    1988-03-29

    We measured androgen receptors in the brain and pituitary of 4 female baboons (Papio cynocephalus) by the in vitro binding of methyltrienolone (R1881) to cytosols from 17 brain subregions as well as anterior and posterior pituitaries. High levels of AR were detected in anterior (22.1 +/- 7.1 (S.E.M.) fmol/mg protein) and posterior pituitary (12.6 +/- 3.3 fmol/mg protein). In brain tissue, the highest androgen receptor levels were found in the infundibular nucleus/median eminence (9.4 +/- 2.3 fmol/mg protein), ventromedial nucleus (6.3 +/- 1.7 fmol/mg protein) and periventricular area (4.9 +/- 1.3 fmol/mg protein). Saturation analysis of anterior pituitary and brain tissue (pool of hypothalamic, preoptic area, amygdala and septum remaining after microdissection of brain nuclei) showed that [3H]R1881 binds to the androgen receptor with high specificity and affinity (Kd = 1.25 x 10(-10) M, 0.45 x 10(-10) M, in anterior pituitary and HPA cytosol, respectively). Serum testosterone levels were low in all animals (0.59 +/- 0.26 ng/ml). With these data we described the quantitative distribution of androgen receptor in the pituitary and in specific brain nuclei in a species of nonhuman primate. The distribution is similar in many respects to that described in the male rat and the data suggest a conservation of androgen receptor distribution across species. PMID:3259151

  15. Round Randomized Learning Vector Quantization for Brain Tumor Imaging

    Science.gov (United States)

    2016-01-01

    Brain magnetic resonance imaging (MRI) classification into normal and abnormal is a critical and challenging task. Owing to that, several medical imaging classification techniques have been devised in which Learning Vector Quantization (LVQ) is amongst the potential. The main goal of this paper is to enhance the performance of LVQ technique in order to gain higher accuracy detection for brain tumor in MRIs. The classical way of selecting the winner code vector in LVQ is to measure the distance between the input vector and the codebook vectors using Euclidean distance function. In order to improve the winner selection technique, round off function is employed along with the Euclidean distance function. Moreover, in competitive learning classifiers, the fitting model is highly dependent on the class distribution. Therefore this paper proposed a multiresampling technique for which better class distribution can be achieved. This multiresampling is executed by using random selection via preclassification. The test data sample used are the brain tumor magnetic resonance images collected from Universiti Kebangsaan Malaysia Medical Center and UCI benchmark data sets. Comparative studies showed that the proposed methods with promising results are LVQ1, Multipass LVQ, Hierarchical LVQ, Multilayer Perceptron, and Radial Basis Function.

  16. Round Randomized Learning Vector Quantization for Brain Tumor Imaging

    Directory of Open Access Journals (Sweden)

    Siti Norul Huda Sheikh Abdullah

    2016-01-01

    Full Text Available Brain magnetic resonance imaging (MRI classification into normal and abnormal is a critical and challenging task. Owing to that, several medical imaging classification techniques have been devised in which Learning Vector Quantization (LVQ is amongst the potential. The main goal of this paper is to enhance the performance of LVQ technique in order to gain higher accuracy detection for brain tumor in MRIs. The classical way of selecting the winner code vector in LVQ is to measure the distance between the input vector and the codebook vectors using Euclidean distance function. In order to improve the winner selection technique, round off function is employed along with the Euclidean distance function. Moreover, in competitive learning classifiers, the fitting model is highly dependent on the class distribution. Therefore this paper proposed a multiresampling technique for which better class distribution can be achieved. This multiresampling is executed by using random selection via preclassification. The test data sample used are the brain tumor magnetic resonance images collected from Universiti Kebangsaan Malaysia Medical Center and UCI benchmark data sets. Comparative studies showed that the proposed methods with promising results are LVQ1, Multipass LVQ, Hierarchical LVQ, Multilayer Perceptron, and Radial Basis Function.

  17. Imaging synaptic density in the living human brain.

    Science.gov (United States)

    Finnema, Sjoerd J; Nabulsi, Nabeel B; Eid, Tore; Detyniecki, Kamil; Lin, Shu-Fei; Chen, Ming-Kai; Dhaher, Roni; Matuskey, David; Baum, Evan; Holden, Daniel; Spencer, Dennis D; Mercier, Joël; Hannestad, Jonas; Huang, Yiyun; Carson, Richard E

    2016-07-20

    Chemical synapses are the predominant neuron-to-neuron contact in the central nervous system. Presynaptic boutons of neurons contain hundreds of vesicles filled with neurotransmitters, the diffusible signaling chemicals. Changes in the number of synapses are associated with numerous brain disorders, including Alzheimer's disease and epilepsy. However, all current approaches for measuring synaptic density in humans require brain tissue from autopsy or surgical resection. We report the use of the synaptic vesicle glycoprotein 2A (SV2A) radioligand [(11)C]UCB-J combined with positron emission tomography (PET) to quantify synaptic density in the living human brain. Validation studies in a baboon confirmed that SV2A is an alternative synaptic density marker to synaptophysin. First-in-human PET studies demonstrated that [(11)C]UCB-J had excellent imaging properties. Finally, we confirmed that PET imaging of SV2A was sensitive to synaptic loss in patients with temporal lobe epilepsy. Thus, [(11)C]UCB-J PET imaging is a promising approach for in vivo quantification of synaptic density with several potential applications in diagnosis and therapeutic monitoring of neurological and psychiatric disorders. PMID:27440727

  18. Simultaneous MRI and PET imaging of a rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Raylman, Raymond R [Center for Advanced Imaging, Department of Radiology, Box 9236, West Virginia University, Morgantown, WV (United States); Majewski, Stan [Thomas Jefferson National Accelerator Facility, 12000 Jefferson Ave., Newport News, VA (United States); Lemieux, Susan K [Center for Advanced Imaging, Department of Radiology, Box 9236, West Virginia University, Morgantown, WV (United States); Velan, S Sendhil [Center for Advanced Imaging, Department of Radiology, Box 9236, West Virginia University, Morgantown, WV (United States); Kross, Brian [Thomas Jefferson National Accelerator Facility, 12000 Jefferson Ave., Newport News, VA (United States); Popov, Vladimir [Thomas Jefferson National Accelerator Facility, 12000 Jefferson Ave., Newport News, VA (United States); Smith, Mark F [Thomas Jefferson National Accelerator Facility, 12000 Jefferson Ave., Newport News, VA (United States); Weisenberger, Andrew G [Thomas Jefferson National Accelerator Facility, 12000 Jefferson Ave., Newport News, VA (United States); Zorn, Carl [Thomas Jefferson National Accelerator Facility, 12000 Jefferson Ave., Newport News, VA (United States); Marano, Gary D [Center for Advanced Imaging, Department of Radiology, Box 9236, West Virginia University, Morgantown, WV (United States)

    2006-12-21

    Multi-modality imaging is rapidly becoming a valuable tool in the diagnosis of disease and in the development of new drugs. Functional images produced with PET fused with anatomical structure images created by MRI will allow the correlation of form with function. Our group is developing a system to acquire MRI and PET images contemporaneously. The prototype device consists of two opposed detector heads, operating in coincidence mode. Each MRI-PET detector module consists of an array of LSO detector elements coupled through a long fibre optic light guide to a single Hamamatsu flat panel position-sensitive photomultiplier tube (PSPMT). The use of light guides allows the PSPMTs to be positioned outside the bore of a 3T MRI scanner where the magnetic field is relatively small. To test the device, simultaneous MRI and PET images of the brain of a male Sprague Dawley rat injected with FDG were successfully obtained. The images revealed no noticeable artefacts in either image set. Future work includes the construction of a full ring PET scanner, improved light guides and construction of a specialized MRI coil to permit higher quality MRI imaging.

  19. Molecular Imaging of the Brain Using Multi-Quantum Coherence and Diagnostics of Brain Disorders

    CERN Document Server

    Kaila, M M

    2013-01-01

    This book examines multi-quantum magnetic resonance imaging methods and the diagnostics of brain disorders. It consists of two Parts. The part I is initially devoted towards the basic concepts of the conventional single quantum MRI techniques. It is supplemented by the basic knowledge required to understand multi-quantum MRI. Practical illustrations are included both on recent developments in conventional MRI and the MQ-MRI. This is to illustrate the connection between theoretical concepts and their scope in the clinical applications. The Part II initially sets out the basic details about quadrupole charge distribution present in certain nuclei and their importance about the functions they perform in our brain. Some simplified final mathematical expressions are included to illustrate facts about the basic concepts of the quantum level interactions between magnetic dipole and the electric quadrupole behavior of useful nuclei present in the brain. Selected practical illustrations, from research and clinical pra...

  20. Brain mineralocorticoid receptors as resilience factor under adverse life conditions?

    NARCIS (Netherlands)

    Kanatsou, S.

    2016-01-01

    Studies in human cohorts have underlined the importance of gene-environment interactions for brain structure and function during development and in adulthood. Such interactions can make the difference between staying healthy or succumbing to disease, e.g. depression or posttraumatic stress disorder.

  1. Brain dopamine receptors in relation to clinical PET-studies

    International Nuclear Information System (INIS)

    A number of published PET Models are discussed with regard to their structure and some of the underlying assumptions. Results of experiments with spiperone and N-methylspiperone in the rat and human brain, which challenge some of these assumptions, are summarized. (author). 37 refs.; 6 figs.; 1 tab

  2. Toll-like receptors in brain development and homeostasis

    DEFF Research Database (Denmark)

    Larsen, Peter H; Holm, Thomas Hellesøe; Owens, Trevor

    2007-01-01

    Toll-like receptors (TLRs) are best known as initiators of the innate immune response to pathogens. Recent reports now reveal intriguing roles for TLRs in the central nervous system (CNS). These include the regulation of neuroinflammation and of neurite outgrowth. The archetypal Toll protein in...

  3. The Prorenin and (Prorenin Receptor: New Players in the Brain Renin-Angiotensin System?

    Directory of Open Access Journals (Sweden)

    Wencheng Li

    2012-01-01

    Full Text Available It is well known that the brain renin-angiotensin (RAS system plays an essential role in the development of hypertension, mainly through the modulation of autonomic activities and vasopressin release. However, how the brain synthesizes angiotensin (Ang II has been a debate for decades, largely due to the low renin activity. This paper first describes the expression of the vasoconstrictive arm of RAS components in the brain as well as their physiological and pathophysiological significance. It then focus on the (prorenin receptor (PRR, a newly discovered component of the RAS which has a high level in the brain. We review the role of prorenin and PRR in peripheral organs and emphasize the involvement of brain PRR in the pathogenesis of hypertension. Some future perspectives in PRR research are heighted with respect to novel therapeutic target for the treatment of hypertension and other cardiovascular diseases.

  4. Registration of dynamic dopamine D{sub 2}receptor images using principal component analysis

    Energy Technology Data Exchange (ETDEWEB)

    Acton, P.D.; Ell, P.J. [Institute of Nuclear Medicine, University College London Medical School, London (United Kingdom); Pilowsky, L.S.; Brammer, M.J. [Institute of Psychiatry, De Crespigny Park, London (United Kingdom); Suckling, J. [Clinical Age Research Unit, Kings College School of Medicine and Dentistry, London (United Kingdom)

    1997-11-01

    This paper describes a novel technique for registering a dynamic sequence of single-photon emission tomography (SPET) dopamine D{sub 2}receptor images, using principal component analysis (PCA). Conventional methods for registering images, such as count difference and correlation coefficient algorithms, fail to take into account the dynamic nature of the data, resulting in large systematic errors when registering time-varying images. However, by using principal component analysis to extract the temporal structure of the image sequence, misregistration can be quantified by examining the distribution of eigenvalues. The registration procedures were tested using a computer-generated dynamic phantom derived from a high-resolution magnetic resonance image of a realistic brain phantom. Each method was also applied to clinical SPET images of dopamine D {sub 2}receptors, using the ligands iodine-123 iodobenzamide and iodine-123 epidepride, to investigate the influence of misregistration on kinetic modelling parameters and the binding potential. The PCA technique gave highly significant (P <0.001) improvements in image registration, leading to alignment errors in x and y of about 25% of the alternative methods, with reductions in autocorrelations over time. It could also be applied to align image sequences which the other methods failed completely to register, particularly {sup 123}I-epidepride scans. The PCA method produced data of much greater quality for subsequent kinetic modelling, with an improvement of nearly 50% in the {chi}{sup 2}of the fit to the compartmental model, and provided superior quality registration of particularly difficult dynamic sequences. (orig.) With 4 figs., 2 tabs., 26 refs.

  5. Brain Extraction and Fuzzy Tissue Segmentation in Cerebral 2D T1-Weigthed Magnetic Resonance Images

    OpenAIRE

    Bouchaib Cherradi; Omar Bouattane; Mohamed Youssfi; Abdelhadi Raihani

    2011-01-01

    In medical imaging, accurate segmentation of brain MR images is of interest for many brain manipulations. In this paper, we present a method for brain Extraction and tissues classification. An application of this method to the segmentation of simulated MRI cerebral images in three clusters will be made. The studied method is composed with different stages, first Brain Extraction from T1-weighted 2D MRI slices (TMBE) is performed as pre-processing procedure, then Histogram based centroids init...

  6. Magnetic resonance imaging research progress on brain functional reorganization after peripheral nerve injury

    International Nuclear Information System (INIS)

    In the recent years, with the development of functional magnetic resonance imaging technology the brain plasticity and functional reorganization are hot topics in the central nervous system imaging studies. Brain functional reorganization and rehabilitation after peripheral nerve injury may have certain regularity. In this paper, the progress of brain functional magnetic resonance imaging technology and its applications in the world wide clinical and experimental researches of the brain functional reorganization after peripheral nerve injury is are reviewed. (authors)

  7. Expression of a novel D4 dopamine receptor in the lamprey brain. Evolutionary considerations about dopamine receptors.

    Directory of Open Access Journals (Sweden)

    Juan ePérez-Fernández

    2016-01-01

    Full Text Available Numerous data reported in lampreys, which belong to the phylogenetically oldest branch of vertebrates, show that the dopaminergic system was already well developed at the dawn of vertebrate evolution. The expression of dopamine in the lamprey brain is well conserved when compared to other vertebrates, and this is also true for the D2 receptor. Additionally, the key role of dopamine in the striatum, modulating the excitability in the direct and indirect pathways through the D1 and D2 receptors, has also been recently reported in these animals. The moment of divergence regarding the two whole genome duplications occurred in vertebrates suggests that additional receptors, apart from the D1 and D2 previously reported, could be present in lampreys. We used in situ hybridization to characterize the expression of a novel dopamine receptor, which we have identified as a D4 receptor according to the phylogenetic analysis. The D4 receptor shows in the sea lamprey a more restricted expression pattern than the D2 subtype, as reported in mammals. Its main expression areas are the striatum, lateral and ventral pallial sectors, several hypothalamic regions, habenula, and mesencephalic and rhombencephalic motoneurons. Some expression areas are well conserved through vertebrate evolution, as is the case of the striatum or the habenula, but the controversies regarding the D4 receptor expression in other vertebrates hampers for a complete comparison, especially in rhombencephalic regions. Our results further support that the dopaminergic system in vertebrates is well conserved and suggest that at least some functions of the D4 receptor were already present before the divergence of lampreys.

  8. In vitro blood-brain barrier permeability predictions for GABAA receptor modulating piperine analogs

    DEFF Research Database (Denmark)

    Eigenmann, Daniela Elisabeth; Dürig, Carmen; Jähne, Evelyn Andrea;

    2016-01-01

    The alkaloid piperine from black pepper (Piper nigrum L.) and several synthetic piperine analogs were recently identified as positive allosteric modulators of γ-aminobutyric acid type A (GABAA) receptors. In order to reach their target sites of action, these compounds need to enter the brain by c...

  9. Brain-derived neurotrophic factor in human subjects with function-altering melanocortin-4 receptor variants

    Science.gov (United States)

    In rodents, hypothalamic brain-derived neurotrophic factor (BDNF) expression appears to be regulated by melanocortin-4 receptor (MC4R) activity. The impact of MC4R genetic variation on circulating BDNF in humans is unknown. The objective of this study is to compare BDNF concentrations of subjects wi...

  10. Quantitative autoradiography of angiotensin II receptors in the brain and kidney

    Energy Technology Data Exchange (ETDEWEB)

    Gehlert, D.R.

    1985-01-01

    The renin-angiotensin system is an important component in the regulation of systemic blood pressure. Angiotensin II is the principal effector peptide of this system. Interaction of angiotensin II with specific receptors can produce in several organic systems. When administered into the brain this octa-peptide produces a variety of responses including a stimulation of drinking, increased systemic blood pressure and several neuroendocrine responses. Its effects on the kidney include alterations in arteriolar resistance, mesangial cell contraction and a feedback inhibition of the release of renin. Since this peptide produces profound effects on homeostatis by an interaction with specific receptors, the quantitative technique of in vitro autoradiography was applied to localize receptor populations for angiotensin II. Specific binding sites for a radiolabeled form of angiotensin II were localized in various brain and kidney regions. In the rat brain high densities of angiotensin II receptors were observed in the paraventricular and suprachiasmatic nuclei of the hypothalamus, supraoptic nucleus and the posterior lobe of the pituitary, brain areas in which angiotensin II modified neuroendocrine functions.

  11. A novel brain receptor is expressed in a distinct population of olfactory sensory neurons

    NARCIS (Netherlands)

    Conzelmann, S; Levai, O; Bode, B; Eisel, U; Raming, K; Breer, H; Strotmann, J

    2000-01-01

    Three novel G-protein-coupled receptor genes related to the previously described RA1c gene have been isolated from the mouse genome. Expression of these genes has been detected in distinct areas of the brain and also in the olfactory epithelium of the nose. Developmental studies revealed a different

  12. The dynamic dielectric at a brain functional site and an EM wave approach to functional brain imaging.

    Science.gov (United States)

    Li, X P; Xia, Q; Qu, D; Wu, T C; Yang, D G; Hao, W D; Jiang, X; Li, X M

    2014-11-04

    Functional brain imaging has tremendous applications. The existing methods for functional brain imaging include functional Magnetic Resonant Imaging (fMRI), scalp electroencephalography (EEG), implanted EEG, magnetoencephalography (MEG) and Positron Emission Tomography (PET), which have been widely and successfully applied to various brain imaging studies. To develop a new method for functional brain imaging, here we show that the dielectric at a brain functional site has a dynamic nature, varying with local neuronal activation as the permittivity of the dielectric varies with the ion concentration of the extracellular fluid surrounding neurons in activation. Therefore, the neuronal activation can be sensed by a radiofrequency (RF) electromagnetic (EM) wave propagating through the site as the phase change of the EM wave varies with the permittivity. Such a dynamic nature of the dielectric at a brain functional site provides the basis for an RF EM wave approach to detecting and imaging neuronal activation at brain functional sites, leading to an RF EM wave approach to functional brain imaging.

  13. Evidence that the EphA2 receptor exacerbates ischemic brain injury.

    Directory of Open Access Journals (Sweden)

    John Thundyil

    Full Text Available Ephrin (Eph signaling within the central nervous system is known to modulate axon guidance, synaptic plasticity, and to promote long-term potentiation. We investigated the potential involvement of EphA2 receptors in ischemic stroke-induced brain inflammation in a mouse model of focal stroke. Cerebral ischemia was induced in male C57Bl6/J wild-type (WT and EphA2-deficient (EphA2(-/- mice by middle cerebral artery occlusion (MCAO; 60 min, followed by reperfusion (24 or 72 h. Brain infarction was measured using triphenyltetrazolium chloride staining. Neurological deficit scores and brain infarct volumes were significantly less in EphA2(-/- mice compared with WT controls. This protection by EphA2 deletion was associated with a comparative decrease in brain edema, blood-brain barrier damage, MMP-9 expression and leukocyte infiltration, and higher expression levels of the tight junction protein, zona occludens-1. Moreover, EphA2(-/- brains had significantly lower levels of the pro-apoptotic proteins, cleaved caspase-3 and BAX, and higher levels of the anti-apoptotic protein, Bcl-2 as compared to WT group. We confirmed that isolated WT cortical neurons express the EphA2 receptor and its ligands (ephrin-A1-A3. Furthermore, expression of all four proteins was increased in WT primary cortical neurons following 24 h of glucose deprivation, and in the brains of WT mice following stroke. Glucose deprivation induced less cell death in primary neurons from EphA2(-/- compared with WT mice. In conclusion, our data provide the first evidence that the EphA2 receptor directly contributes to blood-brain barrier damage and neuronal death following ischemic stroke.

  14. Pitfalls and Limitations of PET/CT in Brain Imaging.

    Science.gov (United States)

    Salmon, Eric; Bernard Ir, Claire; Hustinx, Roland

    2015-11-01

    Neurologic applications were at the forefront of PET imaging when the technique was developed in the mid-1970s. Although oncologic indications have become prominent in terms of number of studies performed worldwide, neurology remains a major field in which functional imaging provides unique information, both for clinical and research purposes. The evaluation of glucose metabolism using FDG remains the most frequent exploration, but in recent years, alternative radiotracers have been developed, including fluorinated amino acid analogues for primary brain tumor imaging and fluorinated compounds for assessing the amyloid deposits in patients with suspected Alzheimer disease. As the brain is enclosed in the skull, which presents fixed landmarks, it is relatively easy to coregister images obtained with various cross-sectional imaging methods, either functional or anatomical, with a relatively high accuracy and robustness. Nevertheless, PET in neurology has fully benefited from the advent of hybrid imaging. Attenuation and scatter correction is now much faster and equally accurate, using CT as compared with the traditional transmission scan using an external radioactive source. The perfect coregistration with the CT data, which is now systematically performed, also provides its own set of valuable information, for instance regarding cerebral atrophy. However, hybrid imaging in neurology comes with pitfalls and limitations, in addition to those that are well known, for example, blood glucose levels or psychotropic drugs that greatly affect the physiological FDG uptake. Movements of the patient's head, either during the PET acquisition or between the PET and the CT acquisitions will generate artifacts that may be very subtle yet lead to erroneous interpretation of the study. Similarly, quantitative analysis, such as voxel-based analyses, may prove very helpful in improving the diagnostic accuracy and the reproducibility of the reading, but a wide variety of artifacts may

  15. Solvation effects on brain uptakes of isomers of 99mTc brain imaging agents

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Analysis of electrostatic hydration free energies of the isomers of the 99mTc-BAT and 99mTc-DADT complexes is carried out using the computer simulation technique. The results show that not only a correlation exists between the logarithm of the brain uptake and the electrostatic hydration free energy for the isomers of 99mTc-brain radiopharmaceuticals, but also a linear relationship exists between the logarithm of the ratio of the brain uptake of the syn isomer to that of the anti one and the difference between the electrostatic hydration free energy of the syn-isomer and that of the anti one. Furthermore, the investigation on the important factors influencing the brain uptakes of 99mTc-radiopharmaceuticals and the reasons of the different biodistribution of the isomers of the 99mTc-complexes is explored at the molecular level. The results may provide a reference for the rational drug design of brain imaging agents.

  16. Bioluminescence imaging of estrogen receptor activity during breast cancer progression.

    Science.gov (United States)

    Vantaggiato, Cristina; Dell'Omo, Giulia; Ramachandran, Balaji; Manni, Isabella; Radaelli, Enrico; Scanziani, Eugenio; Piaggio, Giulia; Maggi, Adriana; Ciana, Paolo

    2016-01-01

    Estrogen receptors (ER) are known to play an important regulatory role in mammary gland development as well as in its neoplastic transformation. Although several studies highlighted the contribution of ER signaling in the breast transformation, little is known about the dynamics of ER state of activity during carcinogenesis due to the lack of appropriate models for measuring the extent of receptor signaling in time, in the same animal. To this aim, we have developed a reporter mouse model for the non-invasive in vivo imaging of ER activity: the ERE-Luc reporter mouse. ERE-Luc is a transgenic mouse generated with a firefly luciferase (Luc) reporter gene driven by a minimal promoter containing an estrogen responsive element (ERE). This model allows to measure receptor signaling in longitudinal studies by bioluminescence imaging (BLI). Here, we have induced sporadic mammary cancers by treating systemically ERE-Luc reporter mice with DMBA (9,10-dimethyl 1,2-benzanthracene) and measured receptor signaling by in vivo imaging in individual animals from early stage until a clinically palpable tumor appeared in the mouse breast. We showed that DMBA administration induces an increase of bioluminescence in the whole abdominal area 6 h after treatment, the signal rapidly disappears. Several weeks later, strong bioluminescence is observed in the area corresponding to the mammary glands. In vivo and ex vivo imaging analysis demonstrated that this bioluminescent signal is localized in the breast area undergoing neoplastic transformation. We conclude that this non-invasive assay is a novel relevant tool to identify the activation of the ER signaling prior the morphological detection of the neoplastic transformation.

  17. Estrogen provides neuroprotection against brain edema and blood brain barrier disruption through both estrogen receptors α and β following traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Vida Naderi

    2015-02-01

    Full Text Available Objective(s:Estrogen (E2 has neuroprotective effects on blood-brain-barrier (BBB after traumatic brain injury (TBI. In order to investigate the roles of estrogen receptors (ERs in these effects, ER-α antagonist (MPP and, ER-β antagonist (PHTPP, or non-selective estrogen receptors antagonist (ICI 182780 were administered. Materials and Methods: Ovariectomized rats were divided into 10 groups, as follows: Sham, TBI, E2, oil, MPP+E2, PHTPP+E2, MPP+PHTPP+E2, ICI+E2, MPP, and DMSO. E2 (33.3 µg/Kg or oil were administered 30 min after TBI. 1 dose (150 µg/Kg of each of MPP, PHTPP, and (4 mg/kg ICI182780 was injected two times, 24 hr apart, before TBI and estrogen treatment. BBB disruption (Evans blue content and brain edema (brain water content evaluated 5 hr and 24 hr after the TBI were evaluated, respectively. Results: The results showed that E2 reduced brain edema after TBI compared to vehicle (P

  18. Measuring specific receptor binding of a PET radioligand in human brain without pharmacological blockade: The genomic plot.

    Science.gov (United States)

    Veronese, Mattia; Zanotti-Fregonara, Paolo; Rizzo, Gaia; Bertoldo, Alessandra; Innis, Robert B; Turkheimer, Federico E

    2016-04-15

    PET studies allow in vivo imaging of the density of brain receptor species. The PET signal, however, is the sum of the fraction of radioligand that is specifically bound to the target receptor and the non-displaceable fraction (i.e. the non-specifically bound radioligand plus the free ligand in tissue). Therefore, measuring the non-displaceable fraction, which is generally assumed to be constant across the brain, is a necessary step to obtain regional estimates of the specific fractions. The nondisplaceable binding can be directly measured if a reference region, i.e. a region devoid of any specific binding, is available. Many receptors are however widely expressed across the brain, and a true reference region is rarely available. In these cases, the nonspecific binding can be obtained after competitive pharmacological blockade, which is often contraindicated in humans. In this work we introduce the genomic plot for estimating the nondisplaceable fraction using baseline scans only. The genomic plot is a transformation of the Lassen graphical method in which the brain maps of mRNA transcripts of the target receptor obtained from the Allen brain atlas are used as a surrogate measure of the specific binding. Thus, the genomic plot allows the calculation of the specific and nondisplaceable components of radioligand uptake without the need of pharmacological blockade. We first assessed the statistical properties of the method with computer simulations. Then we sought ground-truth validation using human PET datasets of seven different neuroreceptor radioligands, where nonspecific fractions were either obtained separately using drug displacement or available from a true reference region. The population nondisplaceable fractions estimated by the genomic plot were very close to those measured by actual human blocking studies (mean relative difference between 2% and 7%). However, these estimates were valid only when mRNA expressions were predictive of protein levels (i

  19. Measuring specific receptor binding of a PET radioligand in human brain without pharmacological blockade: The genomic plot

    Science.gov (United States)

    Veronese, Mattia; Zanotti-Fregonara, Paolo; Rizzo, Gaia; Bertoldo, Alessandra; Innis, Robert B.; Turkheimer, Federico E.

    2016-01-01

    PET studies allow in vivo imaging of the density of brain receptor species. The PET signal, however, is the sum of the fraction of radioligand that is specifically bound to the target receptor and the non-displaceable fraction (i.e. the non-specifically bound radioligand plus the free ligand in tissue). Therefore, measuring the non-displaceable fraction, which is generally assumed to be constant across the brain, is a necessary step to obtain regional estimates of the specific fractions. The nondisplaceable binding can be directly measured if a reference region, i.e. a region devoid of any specific binding, is available. Many receptors are however widely expressed across the brain, and a true reference region is rarely available. In these cases, the nonspecific binding can be obtained after competitive pharmacological blockade, which is often contraindicated in humans. In this work we introduce the genomic plot for estimating the nondisplaceable fraction using baseline scans only. The genomic plot is a transformation of the Lassen graphical method in which the brain maps of mRNA transcripts of the target receptor obtained from the Allen brain atlas are used as a surrogate measure of the specific binding. Thus, the genomic plot allows the calculation of the specific and nondisplaceable components of radioligand uptake without the need of pharmacological blockade. We first assessed the statistical properties of the method with computer simulations. Then we sought ground-truth validation using human PET datasets of seven different neuroreceptor radioligands, where nonspecific fractions were either obtained separately using drug displacement or available from a true reference region. The population nondisplaceable fractions estimated by the genomic plot were very close to those measured by actual human blocking studies (mean relative difference between 2% and 7%). However, these estimates were valid only when mRNA expressions were predictive of protein levels (i

  20. PET tracers for somatostatin receptor imaging of neuroendocrine tumors

    DEFF Research Database (Denmark)

    Johnbeck, Camilla Bardram; Knigge, Ulrich; Kjær, Andreas

    2014-01-01

    Neuroendocrine tumors have shown rising incidence mainly due to higher clinical awareness and better diagnostic tools over the last 30 years. Functional imaging of neuroendocrine tumors with PET tracers is an evolving field that is continuously refining the affinity of new tracers in the search...... for the perfect neuroendocrine tumor imaging tracer. (68)Ga-labeled tracers coupled to synthetic somatostatin analogs with differences in affinity for the five somatostatin receptor subtypes are now widely applied in Europe. Comparison of sensitivity between the most used tracers - (68)Ga-DOTA-Tyr3-octreotide...

  1. The Transferrin Receptor at the Blood-Brain Barrier - exploring the possibilities for brain drug delivery

    NARCIS (Netherlands)

    Visser, Corine

    2005-01-01

    There are many diseases of the central nervous system (CNS), like Parkinson's disease, Alzheimer's disease, depression, schizophrenia, epilepsy, migraine headache, and HIV infection in the brain. However, treatment is difficult since many drugs cannot reach the brain in sufficient quantities due to

  2. Brain imaging in the assessment for epilepsy surgery.

    Science.gov (United States)

    Duncan, John S; Winston, Gavin P; Koepp, Matthias J; Ourselin, Sebastien

    2016-04-01

    Brain imaging has a crucial role in the presurgical assessment of patients with epilepsy. Structural imaging reveals most cerebral lesions underlying focal epilepsy. Advances in MRI acquisitions including diffusion-weighted imaging, post-acquisition image processing techniques, and quantification of imaging data are increasing the accuracy of lesion detection. Functional MRI can be used to identify areas of the cortex that are essential for language, motor function, and memory, and tractography can reveal white matter tracts that are vital for these functions, thus reducing the risk of epilepsy surgery causing new morbidities. PET, SPECT, simultaneous EEG and functional MRI, and electrical and magnetic source imaging can be used to infer the localisation of epileptic foci and assist in the design of intracranial EEG recording strategies. Progress in semi-automated methods to register imaging data into a common space is enabling the creation of multimodal three-dimensional patient-specific datasets. These techniques show promise for the demonstration of the complex relations between normal and abnormal structural and functional data and could be used to direct precise intracranial navigation and surgery for individual patients.

  3. Connecting combat-related mild traumatic brain injury with posttraumatic stress disorder symptoms through brain imaging.

    Science.gov (United States)

    Costanzo, Michelle E; Chou, Yi-Yu; Leaman, Suzanne; Pham, Dzung L; Keyser, David; Nathan, Dominic E; Coughlin, Mary; Rapp, Paul; Roy, Michael J

    2014-08-01

    Mild traumatic brain injury (mTBI) and posttraumatic stress disorder (PTSD) may share common symptom and neuropsychological profiles in military service members (SMs) following deployment; while a connection between the two conditions is plausible, the relationship between them has been difficult to discern. The intent of this report is to enhance our understanding of the relationship between findings on structural and functional brain imaging and symptoms of PTSD. Within a cohort of SMs who did not meet criteria for PTSD but were willing to complete a comprehensive assessment within 2 months of their return from combat deployment, we conducted a nested case-control analysis comparing those with combat-related mTBI to age/gender-matched controls with diffusion tensor imaging, resting state functional magnetic resonance imaging and a range of psychological measures. We report degraded white matter integrity in those with a history of combat mTBI, and a positive correlation between the white matter microstructure and default mode network (DMN) connectivity. Higher clinician-administered and self-reported subthreshold PTSD symptoms were reported in those with combat mTBI. Our findings offer a potential mechanism through which mTBI may alter brain function, and in turn, contribute to PTSD symptoms.

  4. Serotonin 2A receptor agonist binding in the human brain with [11C]Cimbi-36

    DEFF Research Database (Denmark)

    Ettrup, Anders; Svarer, Claus; McMahon, Brenda;

    2016-01-01

    ]Cimbi-36 and the 5-HT2A receptor antagonist [(18)F]altanserin. METHODS: Sixteen healthy volunteers (mean age 23.9 ± 6.4years, 6 males) were scanned twice with a high resolution research tomography PET scanner. All subjects were scanned after a bolus of [(11)C]Cimbi-36; eight were scanned twice to determine...... BPNDs measured with [(11)C]Cimbi-36 and [(18)F]altanserin (mean Pearson's r: 0.95 ± 0.04) suggesting similar cortical binding of the radioligands. Relatively higher binding with [(11)C]Cimbi-36 as compared to [(18)F]altanserin was found in the choroid plexus and hippocampus in the human brain....... CONCLUSIONS: Excellent test-retest reproducibility highlights the potential of [(11)C]Cimbi-36 for PET imaging of 5-HT2A receptor agonist binding in vivo. Our data suggest that Cimbi-36 and altanserin both bind to 5-HT2A receptors, but in regions with high 5-HT2C receptor density, choroid plexus...

  5. Automated delineation of stroke lesions using brain CT images

    Directory of Open Access Journals (Sweden)

    Céline R. Gillebert

    2014-01-01

    Full Text Available Computed tomographic (CT images are widely used for the identification of abnormal brain tissue following infarct and hemorrhage in stroke. Manual lesion delineation is currently the standard approach, but is both time-consuming and operator-dependent. To address these issues, we present a method that can automatically delineate infarct and hemorrhage in stroke CT images. The key elements of this method are the accurate normalization of CT images from stroke patients into template space and the subsequent voxelwise comparison with a group of control CT images for defining areas with hypo- or hyper-intense signals. Our validation, using simulated and actual lesions, shows that our approach is effective in reconstructing lesions resulting from both infarct and hemorrhage and yields lesion maps spatially consistent with those produced manually by expert operators. A limitation is that, relative to manual delineation, there is reduced sensitivity of the automated method in regions close to the ventricles and the brain contours. However, the automated method presents a number of benefits in terms of offering significant time savings and the elimination of the inter-operator differences inherent to manual tracing approaches. These factors are relevant for the creation of large-scale lesion databases for neuropsychological research. The automated delineation of stroke lesions from CT scans may also enable longitudinal studies to quantify changes in damaged tissue in an objective and reproducible manner.

  6. Metabolically stable bradykinin B2 receptor agonists enhance transvascular drug delivery into malignant brain tumors by increasing drug half-life

    Directory of Open Access Journals (Sweden)

    Glen Daniel

    2009-05-01

    Full Text Available Abstract Background The intravenous co-infusion of labradimil, a metabolically stable bradykinin B2 receptor agonist, has been shown to temporarily enhance the transvascular delivery of small chemotherapy drugs, such as carboplatin, across the blood-brain tumor barrier. It has been thought that the primary mechanism by which labradimil does so is by acting selectively on tumor microvasculature to increase the local transvascular flow rate across the blood-brain tumor barrier. This mechanism of action does not explain why, in the clinical setting, carboplatin dosing based on patient renal function over-estimates the carboplatin dose required for target carboplatin exposure. In this study we investigated the systemic actions of labradimil, as well as other bradykinin B2 receptor agonists with a range of metabolic stabilities, in context of the local actions of the respective B2 receptor agonists on the blood-brain tumor barrier of rodent malignant gliomas. Methods Using dynamic contrast-enhanced MRI, the pharmacokinetics of gadolinium-diethyltriaminepentaacetic acid (Gd-DTPA, a small MRI contrast agent, were imaged in rodents bearing orthotopic RG-2 malignant gliomas. Baseline blood and brain tumor tissue pharmacokinetics were imaged with the 1st bolus of Gd-DTPA over the first hour, and then re-imaged with a 2nd bolus of Gd-DTPA over the second hour, during which normal saline or a bradykinin B2 receptor agonist was infused intravenously for 15 minutes. Changes in mean arterial blood pressure were recorded. Imaging data was analyzed using both qualitative and quantitative methods. Results The decrease in systemic blood pressure correlated with the known metabolic stability of the bradykinin B2 receptor agonist infused. Metabolically stable bradykinin B2 agonists, methionine-lysine-bradykinin and labradimil, had differential effects on the transvascular flow rate of Gd-DTPA across the blood-brain tumor barrier. Both methionine

  7. Lactate Receptor Sites Link Neurotransmission, Neurovascular Coupling, and Brain Energy Metabolism

    DEFF Research Database (Denmark)

    Lauritzen, Knut H; Morland, Cecilie; Puchades, Maja;

    2013-01-01

    on subplasmalemmal vesicular organelles, suggesting trafficking of the protein to and from the plasma membrane. The results indicate roles of lactate in brain signaling, including a neuronal glucose and glycogen saving response to the supply of lactate. We propose that lactate, through activation of GPR81 receptors......The G-protein-coupled lactate receptor, GPR81 (HCA1), is known to promote lipid storage in adipocytes by downregulating cAMP levels. Here, we show that GPR81 is also present in the mammalian brain, including regions of the cerebral neocortex and hippocampus, where it can be activated...... by physiological concentrations of lactate and by the specific GPR81 agonist 3,5-dihydroxybenzoate to reduce cAMP. Cerebral GPR81 is concentrated on the synaptic membranes of excitatory synapses, with a postsynaptic predominance. GPR81 is also enriched at the blood-brain-barrier: the GPR81 densities at endothelial...

  8. Transferrin receptor expression and role in transendothelial transport of transferrin in cultured brain endothelial monolayers

    DEFF Research Database (Denmark)

    Hersom, Maria; Helms, Hans Christian; Pretzer, Natasia;

    2016-01-01

    across the endothelial cells by transcytosis. The aim of the present study was to investigate transferrin receptor expression and role in transendothelial transferrin transport in cultured bovine brain endothelial cell monolayers. Transferrin receptor mRNA and protein levels were investigated...... in endothelial mono-cultures and co-cultures with astrocytes, as well as in freshly isolated brain capillaries using qPCR, immunocytochemistry and Western blotting. Transendothelial transport and luminal association of holo-transferrin was investigated using [125I]holo-transferrin or [59Fe......]-transferrin. Transferrin receptor mRNA expression in all cell culture configurations was lower than in freshly isolated capillaries, but the expression slightly increased during six days of culture. The mRNA expression levels were similar in mono-cultures and co-cultures. Immunostaining demonstrated comparable transferrin...

  9. 3D Reconstructed Cyto-, Muscarinic M2 Receptor, and Fiber Architecture of the Rat Brain Registered to the Waxholm Space Atlas.

    Science.gov (United States)

    Schubert, Nicole; Axer, Markus; Schober, Martin; Huynh, Anh-Minh; Huysegoms, Marcel; Palomero-Gallagher, Nicola; Bjaalie, Jan G; Leergaard, Trygve B; Kirlangic, Mehmet E; Amunts, Katrin; Zilles, Karl

    2016-01-01

    High-resolution multiscale and multimodal 3D models of the brain are essential tools to understand its complex structural and functional organization. Neuroimaging techniques addressing different aspects of brain organization should be integrated in a reference space to enable topographically correct alignment and subsequent analysis of the various datasets and their modalities. The Waxholm Space (http://software.incf.org/software/waxholm-space) is a publicly available 3D coordinate-based standard reference space for the mapping and registration of neuroanatomical data in rodent brains. This paper provides a newly developed pipeline combining imaging and reconstruction steps with a novel registration strategy to integrate new neuroimaging modalities into the Waxholm Space atlas. As a proof of principle, we incorporated large scale high-resolution cyto-, muscarinic M2 receptor, and fiber architectonic images of rat brains into the 3D digital MRI based atlas of the Sprague Dawley rat in Waxholm Space. We describe the whole workflow, from image acquisition to reconstruction and registration of these three modalities into the Waxholm Space rat atlas. The registration of the brain sections into the atlas is performed by using both linear and non-linear transformations. The validity of the procedure is qualitatively demonstrated by visual inspection, and a quantitative evaluation is performed by measurement of the concordance between representative atlas-delineated regions and the same regions based on receptor or fiber architectonic data. This novel approach enables for the first time the generation of 3D reconstructed volumes of nerve fibers and fiber tracts, or of muscarinic M2 receptor density distributions, in an entire rat brain. Additionally, our pipeline facilitates the inclusion of further neuroimaging datasets, e.g., 3D reconstructed volumes of histochemical stainings or of the regional distributions of multiple other receptor types, into the Waxholm Space

  10. Imaging of sodium in the brain: a brief review.

    Science.gov (United States)

    Shah, N Jon; Worthoff, Wieland A; Langen, Karl-Josef

    2016-02-01

    Sodium-based MRI plays a vital role in the study of metabolism and can unveil valuable information about emerging and existing pathology--in particular in the human brain. Sodium is the second most abundant MR active nucleus in living tissue and, due to its quadrupolar nature, has magnetic properties not common to conventional proton MRI, which can reveal further insights, such as information on the compartmental distribution of intra- and extracellular sodium. Nevertheless, the use of sodium nuclei for imaging comes at the expense of a lower sensitivity and significantly reduced relaxation times, making in vivo sodium studies feasible only at high magnetic field strength and by the use of dedicated pulse sequences. Hybrid imaging combining sodium MRI and positron emission tomography (PET) simultaneously is a novel and promising approach to access information on dynamic metabolism with much increased, PET-derived specificity. Application of this new methodology is demonstrated herein using examples from tumour imaging.

  11. Structural similarity analysis for brain MR image quality assessment

    Science.gov (United States)

    Punga, Mirela Visan; Moldovanu, Simona; Moraru, Luminita

    2014-11-01

    Brain MR images are affected and distorted by various artifacts as noise, blur, blotching, down sampling or compression and as well by inhomogeneity. Usually, the performance of pre-processing operation is quantified by using the quality metrics as mean squared error and its related metrics such as peak signal to noise ratio, root mean squared error and signal to noise ratio. The main drawback of these metrics is that they fail to take the structural fidelity of the image into account. For this reason, we addressed to investigate the structural changes related to the luminance and contrast variation (as non-structural distortions) and to denoising process (as structural distortion)through an alternative metric based on structural changes in order to obtain the best image quality.

  12. The Multimodal Brain Tumor Image Segmentation Benchmark (BRATS)

    DEFF Research Database (Denmark)

    Menze, Bjoern H.; Jakab, Andras; Bauer, Stefan;

    2015-01-01

    In this paper we report the set-up and results of the Multimodal Brain Tumor Image Segmentation Benchmark (BRATS) organized in conjunction with the MICCAI 2012 and 2013 conferences. Twenty state-of-the-art tumor segmentation algorithms were applied to a set of 65 multi-contrast MR scans of low......- and high-grade glioma patients – manually annotated by up to four raters – and to 65 comparable scans generated using tumor image simulation software. Quantitative evaluations revealed considerable disagreement between the human raters in segmenting various tumor sub-regions (Dice scores in the range 74...... a hierarchical majority vote yielded segmentations that consistently ranked above all individual algorithms, indicating remaining opportunities for further methodological improvements. The BRATS image data and manual annotations continue to be publicly available through an online evaluation system as an ongoing...

  13. Aging-induced changes in brain regional serotonin receptor binding: Effect of Carnosine.

    Science.gov (United States)

    Banerjee, S; Poddar, M K

    2016-04-01

    Monoamine neurotransmitter, serotonin (5-HT) has its own specific receptors in both pre- and post-synapse. In the present study the role of carnosine on aging-induced changes of [(3)H]-5-HT receptor binding in different brain regions in a rat model was studied. The results showed that during aging (18 and 24 months) the [(3)H]-5-HT receptor binding was reduced in hippocampus, hypothalamus and pons-medulla with a decrease in their both Bmax and KD but in cerebral cortex the [(3)H]-5-HT binding was increased with the increase of its only Bmax. The aging-induced changes in [(3)H]-5-HT receptor binding with carnosine (2.0 μg/kg/day, intrathecally, for 21 consecutive days) attenuated in (a) 24-month-aged rats irrespective of the brain regions with the attenuation of its Bmax except hypothalamus where both Bmax and KD were significantly attenuated, (b) hippocampus and hypothalamus of 18-month-aged rats with the attenuation of its Bmax, and restored toward the [(3)H]-5-HT receptor binding that observed in 4-month-young rats. The decrease in pons-medullary [(3)H]-5-HT binding including its Bmax of 18-month-aged rats was promoted with carnosine without any significant change in its cerebral cortex. The [(3)H]-5-HT receptor binding with the same dosages of carnosine in 4-month-young rats (a) increased in the cerebral cortex and hippocampus with the increase in their only Bmax whereas (b) decreased in hypothalamus and pons-medulla with a decrease in their both Bmax and KD. These results suggest that carnosine treatment may (a) play a preventive role in aging-induced brain region-specific changes in serotonergic activity (b) not be worthy in 4-month-young rats in relation to the brain regional serotonergic activity. PMID:26808776

  14. Diffusion Tensor Imaging Of the Brain in Type 1 Diabetes

    Directory of Open Access Journals (Sweden)

    Jo Ann V. Antenor-Dorsey

    2014-10-01

    Full Text Available Individuals with Type 1 diabetes mellitus (T1DM are required to carefully manage their insulin dosing, dietary intake, and activity levels in order to maintain optimal blood sugar levels. Over time, exposure to hyperglycaemia is known to cause significant damage to the peripheral nervous system, but its impact on the central nervous system has been less well studied. Researchers have begun to explore the cumulative impact of commonly experienced blood glucose fluctuations on brain structure and function in patient populations. To date, these studies have typically used magnetic resonance imaging to measure regional grey and white matter volumes across the brain. However, newer methods, such as diffusion tensor imaging (DTI can measure the microstructural properties of white matter, which can be more sensitive to neurological effects than standard volumetric measures. Studies are beginning to use DTI to understand the impact of T1DM on white matter structure in the human brain. This work, its implications, future directions, and important caveats, are the focus of this review.

  15. Imaging study of brain damage from methanol intoxication of wine

    International Nuclear Information System (INIS)

    Objective: To investigate the imaging of CT and MRI in brain damage caused by methanol intoxication from false wine, and to study the relations between imaging manifestation and different degrees of the methanol intoxication. Method: Thirty nine cases with methanol intoxication from false wine were retrospectively reported, The latent period of these patients was 0-4 days, and the average latent period of these patients was 0.5 days, All cases were performed by serology examination, brain CT scan, and four cases performed by MRI scan after average 2.5 days (range, 1-6 days) the onset of methanol intoxication. Results: Six cases showed hyperintense signals in bilateral putamen, two cases also showed hyperintense signals in biolateral subcortex white substance regions. Four cases showed hyperintense signals in unilateral internal capsule. One case showed hyperintense changess in subcortex white substance regions. Our study showed the positive correlation between CT features and the amount of methanol and stage of clinic manifestation(χ2=4.232, P2=0.001, P>0.05). Conclusions: MRI was better than CT in finding early brain damage caused by methanol intoxication from false wine. The characteristic finding changes of the patients was showed mainly in in bilateral putamen, Prognosis for the patients combined with subcortex white substance lesion wasn't hopeful. (authors)

  16. Grid Computing Application for Brain Magnetic Resonance Image Processing

    International Nuclear Information System (INIS)

    This work emphasizes the use of grid computing and web technology for automatic post-processing of brain magnetic resonance images (MRI) in the context of neuropsychiatric (Alzheimer's disease) research. Post-acquisition image processing is achieved through the interconnection of several individual processes into pipelines. Each process has input and output data ports, options and execution parameters, and performs single tasks such as: a) extracting individual image attributes (e.g. dimensions, orientation, center of mass), b) performing image transformations (e.g. scaling, rotation, skewing, intensity standardization, linear and non-linear registration), c) performing image statistical analyses, and d) producing the necessary quality control images and/or files for user review. The pipelines are built to perform specific sequences of tasks on the alphanumeric data and MRIs contained in our database. The web application is coded in PHP and allows the creation of scripts to create, store and execute pipelines and their instances either on our local cluster or on high-performance computing platforms. To run an instance on an external cluster, the web application opens a communication tunnel through which it copies the necessary files, submits the execution commands and collects the results. We present result on system tests for the processing of a set of 821 brain MRIs from the Alzheimer's Disease Neuroimaging Initiative study via a nonlinear registration pipeline composed of 10 processes. Our results show successful execution on both local and external clusters, and a 4-fold increase in performance if using the external cluster. However, the latter's performance does not scale linearly as queue waiting times and execution overhead increase with the number of tasks to be executed.

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

    Science.gov (United States)

    Sidtis, John J.

    2007-01-01

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

  18. Effects of imipramine treatment on delta-opioid receptors of the rat brain cortex and striatum.

    Science.gov (United States)

    Varona, Adolfo; Gil, Javier; Saracibar, Gonzalo; Maza, Jose Luis; Echevarria, Enrique; Irazusta, Jon

    2003-01-01

    Imipramine (CAS 113-52-0) is being utilized widely for the treatment of major depression. In recent years, there has been evidence of the involvement of the endogenous opioid system in major depression and its treatment. There is some evidence indicating that opioid receptors could be involved in the antidepressant mechanism of action. Regarding this topic, mood-related behavior of endogenous enkephalins seems to be mediated by delta-opioid receptors. In this work, the effects of subacute (5 day) and chronic (15 day) treatments of imipramine on the density and the affinity of the delta-receptors in the striatum and in the parietal and frontal cortices of the rat brain are described. Studied parameters (Bmax and Kd) were calculated by a saturation binding assay with the delta-opioid agonists [3H]-DPDPE (tyrosyl-2,6-3H(N)-(2-D-penicillamine-5-D-penicillamine)-enkephalin) as specific ligand and DSLET ([D-serine2]-D-leucine-enkephalin-threonine) as non-radioactive competing ligand. It was found that 15 days treatment significantly decreased the delta-opioid receptor density,without changing the affinity, in the frontal cortex of the rat brain. That decrease was confirmed by delta-opioid receptor immunostaining. These results suggest that delta-opioid receptors could play a role in the chronic action mechanism of imipramine. PMID:12608010

  19. Adenosine A2A Receptors Modulate Acute Injury and Neuroinflammation in Brain Ischemia

    Directory of Open Access Journals (Sweden)

    Felicita Pedata

    2014-01-01

    Full Text Available The extracellular concentration of adenosine in the brain increases dramatically during ischemia. Adenosine A2A receptor is expressed in neurons and glial cells and in inflammatory cells (lymphocytes and granulocytes. Recently, adenosine A2A receptor emerged as a potential therapeutic attractive target in ischemia. Ischemia is a multifactorial pathology characterized by different events evolving in the time. After ischemia the early massive increase of extracellular glutamate is followed by activation of resident immune cells, that is, microglia, and production or activation of inflammation mediators. Proinflammatory cytokines, which upregulate cell adhesion molecules, exert an important role in promoting recruitment of leukocytes that in turn promote expansion of the inflammatory response in ischemic tissue. Protracted neuroinflammation is now recognized as the predominant mechanism of secondary brain injury progression. A2A receptors present on central cells and on blood cells account for important effects depending on the time-related evolution of the pathological condition. Evidence suggests that A2A receptor antagonists provide early protection via centrally mediated control of excessive excitotoxicity, while A2A receptor agonists provide protracted protection by controlling massive blood cell infiltration in the hours and days after ischemia. Focus on inflammatory responses provides for adenosine A2A receptor agonists a wide therapeutic time-window of hours and even days after stroke.

  20. Purification of high affinity benzodiazepine receptor binding site fragments from rat brain

    International Nuclear Information System (INIS)

    In central nervous system benzodiazepine recognition sites occur on neuronal cell surfaces as one member of a multireceptor complex, including recognition sites for benzodiazepines, gamma aminobutyric acid (GABA), barbiturates and a chloride ionophore. During photoaffinity labelling, the benzodiazepine agonist, 3H-flunitrazepam, is irreversibly bound to central benzodiazepine high affinity recognition sites in the presence of ultraviolet light. In these studies a 3H-flunitrazepam radiolabel was used to track the isolation and purification of high affinity agonist binding site fragments from membrane-bound benzodiazepine receptor in rat brain. The authors present a method for limited proteolysis of 3H-flunitrazepam photoaffinity labeled rat brain membranes, generating photolabeled benzodiazepine receptor fragments containing the agonist binding site. Using trypsin chymotrypsin A4, or a combination of these two proteases, they have demonstrated the extent and time course for partial digestion of benzodiazepine receptor, yielding photolabeled receptor binding site fragments. These photolabeled receptor fragments have been further purified on the basis of size, using ultrafiltration, gel permeation chromatography, and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) as well as on the basis of hydrophobicity, using a high performance liquid chromatography (HPLC) precolumn, several HPLC elution schemes, and two different HPLC column types. Using these procedures, they have purified three photolabeled benzodiazepine receptor fragments containing the agonist binding site which appear to have a molecular weight of less than 2000 daltons each

  1. BDNF modulates GABAA receptors microtransplanted from the human epileptic brain to Xenopus oocytes

    Science.gov (United States)

    Palma, E.; Torchia, G.; Limatola, C.; Trettel, F.; Arcella, A.; Cantore, G.; Di Gennaro, G.; Manfredi, M.; Esposito, V.; Quarato, P. P.; Miledi, R.; Eusebi, F.

    2005-01-01

    Cell membranes isolated from brain tissues, obtained surgically from six patients afflicted with drug-resistant temporal lobe epilepsy and from one nonepileptic patient afflicted with a cerebral oligodendroglioma, were injected into frog oocytes. By using this approach, the oocytes acquire human GABAA receptors, and we have shown previously that the “epileptic receptors” (receptors transplanted from epileptic brains) display a marked run-down during repetitive applications of GABA. It was found that exposure to the neurotrophin BDNF increased the amplitude of the “GABA currents” (currents elicited by GABA) generated by the epileptic receptors and decreased their run-down; both events being blocked by K252A, a neurotrophin tyrosine kinase receptor B inhibitor. These effects of BDNF were not mimicked by nerve growth factor. In contrast, the GABAA receptors transplanted from the nonepileptic human hippocampal uncus (obtained during surgical resection as part of the nontumoral tissue from the oligodendroglioma margins) or receptors expressed by injecting rat recombinant α1β2γ2 GABAA receptor subunit cDNAs generated GABA currents whose time-course and run-down were not altered by BDNF. Loading the oocytes with the Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetate-acetoxymethyl ester (BAPTA-AM), or treating them with Rp-8-Br-cAMP, an inhibitor of the cAMP-dependent PKA, did not alter the GABA currents. However, staurosporine (a broad spectrum PK inhibitor), bisindolylmaleimide I (a PKC inhibitor), and U73122 (a phospholipase C inhibitor) blocked the BDNF-induced effects on the epileptic GABA currents. Our results indicate that BDNF potentiates the epileptic GABAA currents and antagonizes their use-dependent run-down, thus strengthening GABAergic inhibition, probably by means of activation of tyrosine kinase receptor B receptors and of both PLC and PKC. PMID:15665077

  2. The effect of ZMS on brain M receptor in aged rats

    International Nuclear Information System (INIS)

    Objective: The purpose of this work was to study the effect of ZMS, an active component of Yin tonic, Zhimu, on brain M2 receptor density of aged animals and its correlation with the effect on learning/memory ability. Methods: A dual-site competitive binding assay using 3H-quinuclidinyl benzilate (QNB) as non selective radioligand and unlabelled Methoctramine as selective competitive agent was established for measuring M2 receptor density in aged rats. Results: In addition to the change of total density of M receptors, the density of a subtype of M receptors, M2 receptor in brain was significantly decreased in aged rats [(231.8 +- 115.9) fmol·mg-1 (x-bar +- s) in young rats and (97.9 +- 46.3) fmol·mg-1 in aged rats]. When the aged rats were treated with ZMS for two months, in addition to the up-regulation of total M receptors, the M2 receptor was up-regulated significantly [being (213 +- 77) mg at a ZMS dose of 3.6 mg·kg-1·d-'1, and (212 +- 72) mg at a ZMS dose of 18 mg·kg-1·d-1]. When the correlation between M2 or total M receptor densities and the learning/memory ability measured by Y-maze performance was examined with linear regression, the correlation coefficient was remarkable (0.721 and 0.505, respectively). Conclusions: ZMS has the ability of up-regulating M2 receptor and this may be an important factor for the improvement of learning and memory by ZMS

  3. Laurate Biosensors Image Brain Neurotransmitters In Vivo: Can an Antihypertensive Medication Alter Psychostimulant Behavior?

    Directory of Open Access Journals (Sweden)

    Vivek Murthy

    2008-07-01

    Full Text Available Neuromolecular Imaging (NMI with novel biosensors enables the selective detection of neurotransmitters in vivo within seconds, on line and in real time. Biosensors remain in place for continuing studies over a period of months. This biotechnological advance is based on conventional electrochemistry; the biosensors detect neurotransmitters by electron transfer. Simply stated, biosensors adsorb electrons from each neurotransmitter at specific oxidation potentials; the current derived from electron transfer is proportional to neurotransmitter concentration. Selective electron transfer properties of these biosensors permit the imaging of neurotransmitters, metabolites and precursors. The novel BRODERICK PROBE® biosensors we have developed, differ in formulation and detection capabilities from biosensors/electrodes used in conventional electrochemistry/ voltammetry. In these studies, NMI, specifically, the BRODERICK PROBE® laurate biosensor images neurotransmitter signals within mesolimbic neuronal terminals, nucleus accumbens (NAc; dopamine (DA, serotonin (5-HT, homovanillic acid (HVA and Ltryptophan (L-TP are selectively imaged. Simultaneously, we use infrared photobeams to monitor open-field movement behaviors on line with NMI in the same animal subjects. The goals are to investigate integrated neurochemical and behavioral effects of cocaine and caffeine alone and co-administered and further, to use ketanserin to decipher receptor profiles for these psychostimulants, alone and co-administered. The rationale for selecting this medication is: ketanserin (a is an antihypertensive and cocaine and caffeine produce hypertension and (b acts at 5-HT2A/2C receptors, prevalent in NAc and implicated in hypertension and cocaine addiction. Key findings are: (a the moderate dose of caffeine simultaneously potentiates cocaine's neurochemical and behavioral responses. (b ketanserin simultaneously inhibits cocaine-increased DA and 5-HT release in

  4. Visualizing the blind brain: brain imaging of visual field defects from early recovery to rehabilitation techniques.

    Science.gov (United States)

    Urbanski, Marika; Coubard, Olivier A; Bourlon, Clémence

    2014-01-01

    Visual field defects (VFDs) are one of the most common consequences observed after brain injury, especially after a stroke in the posterior cerebral artery territory. Less frequently, tumors, traumatic brain injury, brain surgery or demyelination can also determine various visual disabilities, from a decrease in visual acuity to cerebral blindness. Visual field defects is a factor of bad functional prognosis as it compromises many daily life activities (e.g., obstacle avoidance, driving, and reading) and therefore the patient's quality of life. Spontaneous recovery seems to be limited and restricted to the first 6 months, with the best chance of improvement at 1 month. The possible mechanisms at work could be partly due to cortical reorganization in the visual areas (plasticity) and/or partly to the use of intact alternative visual routes, first identified in animal studies and possibly underlying the phenomenon of blindsight. Despite processes of early recovery, which is rarely complete, and learning of compensatory strategies, the patient's autonomy may still be compromised at more chronic stages. Therefore, various rehabilitation therapies based on neuroanatomical knowledge have been developed to improve VFDs. These use eye-movement training techniques (e.g., visual search, saccadic eye movements), reading training, visual field restitution (the Vision Restoration Therapy, VRT), or perceptual learning. In this review, we will focus on studies of human adults with acquired VFDs, which have used different imaging techniques (Positron Emission Tomography, PET; Diffusion Tensor Imaging, DTI; functional Magnetic Resonance Imaging, fMRI; Magneto Encephalography, MEG) or neurostimulation techniques (Transcranial Magnetic Stimulation, TMS; transcranial Direct Current Stimulation, tDCS) to show brain activations in the course of spontaneous recovery or after specific rehabilitation techniques.

  5. Visualizing the blind brain: brain imaging of visual field defects from early recovery to rehabilitation techniques

    Directory of Open Access Journals (Sweden)

    Marika eUrbanski

    2014-09-01

    Full Text Available Visual field defects (VFDs are one of the most common consequences observed after brain injury, especially after a stroke in the posterior cerebral artery territory. Less frequently, tumours, traumatic brain injury, brain surgery or demyelination can also determine various visual disabilities, from a decrease in visual acuity to cerebral blindness. VFD is a factor of bad functional prognosis as it compromises many daily life activities (e.g., obstacle avoidance, driving, and reading and therefore the patient’s quality of life. Spontaneous recovery seems to be limited and restricted to the first six months, with the best chance of improvement at one month. The possible mechanisms at work could be partly due to cortical reorganization in the visual areas (plasticity and/or partly to the use of intact alternative visual routes, first identified in animal studies and possibly underlying the phenomenon of blindsight. Despite processes of early recovery, which is rarely complete, and learning of compensatory strategies, the patient’s autonomy may still be compromised at more chronic stages. Therefore, various rehabilitation therapies based on neuroanatomical knowledge have been developed to improve VFDs. These use eye-movement training techniques (e.g., visual search, saccadic eye movements, reading training, visual field restitution (the Vision Restoration Therapy, VRT, or perceptual learning. In this review, we will focus on studies of human adults with acquired VFDs, which have used different imaging techniques (Positron Emission Tomography: PET, Diffusion Tensor Imaging: DTI, functional Magnetic Resonance Imaging: fMRI, MagnetoEncephalography: MEG or neurostimulation techniques (Transcranial Magnetic Stimulation: TMS; transcranial Direct Current Stimulation, tDCS to show brain activations in the course of spontaneous recovery or after specific rehabilitation techniques.

  6. Characterization of tyramine and octopamine receptors in the insect (Locusta migratoria migratorioides) brain.

    Science.gov (United States)

    Hiripi, L; Juhos, S; Downer, R G

    1994-01-01

    The kinetic and pharmacological properties of [3H]tyramine and [3H]octopamine binding to membrane preparations of locust (Locusta migratoria migratorioides) brain were studied to characterize the tyramine and octopamine receptors. [3H]Tyramine and [3H]octopamine bind specifically and reversibly to the locust brain membrane with equilibrium achieved after 20 min. The dissociation of [3H]tyramine is monophasic while that of the [3H]octopamine shows a biphasic tendency. Scatchard analysis of the saturation curves reveals a single high affinity binding site for each of tyramine and octopamine. The mean (+/- S.E.M.) values of Kd and Bmax are 6.11 +/- 0.71 nM and 21.45 +/- 3.0 fmol/mg tissue for tyramine and 5.65 +/- 0.91 nM and 15.0 +/- 2.4 fmol/mg tissue for octopamine, respectively. Pharmacological analysis of the binding suggests the presence of both tyramine and octopamine receptors in the locust brain. alpha-Adrenergic agonists and antagonists have a high affinity to the octopamine but not the tyramine receptor whereas dopaminergic drugs have a higher affinity to the tyramine receptor than the octopamine receptor. No highly effective inhibitors of tyramine binding were identified. The serotonergic blockers, mianserin, LSD, BOL are effective blockers for both tyramine and octopamine receptors, whereas the serotonergic antagonist gramine is more active against the octopamine than the serotonin receptor. The results suggest that a G-protein binding mechanism is involved in the expression of both the tyramine and octopamine effects. PMID:7907928

  7. Magnetic resonance imaging safety of deep brain stimulator devices.

    Science.gov (United States)

    Oluigbo, Chima O; Rezai, Ali R

    2013-01-01

    Magnetic resonance imaging (MRI) has become the standard of care for the evaluation of different neurological disorders of the brain and spinal cord due to its multiplanar capabilities and excellent soft tissue resolution. With the large and increasing population of patients with implanted deep brain stimulation (DBS) devices, a significant proportion of these patients with chronic neurological diseases require evaluation of their primary neurological disease processes by MRI. The presence of an implanted DBS device in a magnetic resonance environment presents potential hazards. These include the potential for induction of electrical currents or heating in DBS devices, which can result in neurological tissue injury, magnetic field-induced device migration, or disruption of the operational aspects of the devices. In this chapter, we review the basic physics of potential interactions of the MRI environment with implanted DBS devices, summarize results from phantom studies and clinical series, and discuss present recommendations for safe MRI in patients with implanted DBS devices. PMID:24112886

  8. CT and MRI imaging of the brain in MELAS syndrome

    International Nuclear Information System (INIS)

    MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis, stroke-like episodes) is a rare, multisystem disorder which belongs to a group of mitochondrial metabolic diseases. As other diseases in this group, it is inherited in the maternal line. In this report, we discussed a case of a 10-year-old girl with clinical and radiological picture of MELAS syndrome. We would like to describe characteristic radiological features of MELAS syndrome in CT, MRI and MR spectroscopy of the brain and differential diagnosis. The rarity of this disorder and the complexity of its clinical presentation make MELAS patients among the most difficult to diagnose. Brain imaging studies require a wide differential diagnosis, primarily to distinguish between MELAS and ischemic stroke. Particularly helpful are the MRI and MR spectroscopy techniques

  9. Magnetic resonance imaging safety of deep brain stimulator devices.

    Science.gov (United States)

    Oluigbo, Chima O; Rezai, Ali R

    2013-01-01

    Magnetic resonance imaging (MRI) has become the standard of care for the evaluation of different neurological disorders of the brain and spinal cord due to its multiplanar capabilities and excellent soft tissue resolution. With the large and increasing population of patients with implanted deep brain stimulation (DBS) devices, a significant proportion of these patients with chronic neurological diseases require evaluation of their primary neurological disease processes by MRI. The presence of an implanted DBS device in a magnetic resonance environment presents potential hazards. These include the potential for induction of electrical currents or heating in DBS devices, which can result in neurological tissue injury, magnetic field-induced device migration, or disruption of the operational aspects of the devices. In this chapter, we review the basic physics of potential interactions of the MRI environment with implanted DBS devices, summarize results from phantom studies and clinical series, and discuss present recommendations for safe MRI in patients with implanted DBS devices.

  10. Functional connectivity of the rodent brain using optical imaging

    Science.gov (United States)

    Guevara Codina, Edgar

    The aim of this thesis is to apply functional connectivity in a variety of animal models, using several optical imaging modalities. Even at rest, the brain shows high metabolic activity: the correlation in slow spontaneous fluctuations identifies remotely connected areas of the brain; hence the term "functional connectivity". Ongoing changes in spontaneous activity may provide insight into the neural processing that takes most of the brain metabolic activity, and so may provide a vast source of disease related changes. Brain hemodynamics may be modified during disease and affect resting-state activity. The thesis aims to better understand these changes in functional connectivity due to disease, using functional optical imaging. The optical imaging techniques explored in the first two contributions of this thesis are Optical Imaging of Intrinsic Signals and Laser Speckle Contrast Imaging, together they can estimate the metabolic rate of oxygen consumption, that closely parallels neural activity. They both have adequate spatial and temporal resolution and are well adapted to image the convexity of the mouse cortex. In the last article, a depth-sensitive modality called photoacoustic tomography was used in the newborn rat. Optical coherence tomography and laminar optical tomography were also part of the array of imaging techniques developed and applied in other collaborations. The first article of this work shows the changes in functional connectivity in an acute murine model of epileptiform activity. Homologous correlations are both increased and decreased with a small dependence on seizure duration. These changes suggest a potential decoupling between the hemodynamic parameters in resting-state networks, underlining the importance to investigate epileptic networks with several independent hemodynamic measures. The second study examines a novel murine model of arterial stiffness: the unilateral calcification of the right carotid. Seed-based connectivity analysis

  11. Selective vulnerabilities of N-methyl-D-aspartate (NMDA receptors during brain aging

    Directory of Open Access Journals (Sweden)

    Brenna L Brim

    2010-03-01

    Full Text Available N-methyl-D-aspartate (NMDA receptors are present in high density within the cerebral cortex and hippocampus and play an important role in learning and memory. NMDA receptors are negatively affected by aging, but these effects are not uniform in many different ways. This review discusses the selective age-related vulnerabilities of different binding sites of the NMDA receptor complex, different subunits that comprise the complex, and the expression and functions of the receptor within different brain regions. Spatial reference, passive avoidance, and working memory, as well as place field stability and expansion all involve NMDA receptors. Aged animals show deficiencies in these functions, as compared to young, and some studies have identified an association between age-associated changes in the expression of NMDA receptors and poor memory performance. A number of diet and drug interventions have shown potential for reversing or slowing the effects of aging on the NMDA receptor. On the other hand, there is mounting evidence that the NMDA receptors that remain within aged individuals are not always associated with good cognitive functioning. This may be due to a compensatory response of neurons to the decline in NMDA receptor expression or a change in the subunit composition of the remaining receptors. These studies suggest that developing treatments that are aimed at preventing or reversing the effects of aging on the NMDA receptor may aid in ameliorating the memory declines that are associated with aging. However, we need to be mindful of the possibility that there may also be negative consequences in aged individuals.

  12. Evidence for the presence of beta 3-adrenergic receptor mRNA in the human brain.

    Science.gov (United States)

    Rodriguez, M; Carillon, C; Coquerel, A; Le Fur, G; Ferrara, P; Caput, D; Shire, D

    1995-04-01

    The beta 3-adrenergic receptor (AR) is widely distributed in peripheral tissues, but up to now it has not been detected in the central nervous system. By using the polymerase chain reaction (PCR) technique, we found the beta 3-AR mRNA to be present in all the regions of the human brain we investigated. The quantities found were very low compared to those of the beta 1-AR and beta 2-AR mRNAs, being hardly detectable in adult brain. In contrast, the brain of very young infants contained about 100 times more beta 3-AR mRNA than the adult brain, whereas the amounts of beta 1-AR and beta 2-AR transcripts were essentially the same. In addition, using PCR we have cloned a central beta 3-AR coding region from a human frontal cortex cDNA library and have found it to be identical to the corresponding peripheral sequence. PMID:7609625

  13. Brain imaging and psychotherapy: methodological considerations and practical implications.

    Science.gov (United States)

    Linden, David E J

    2008-11-01

    The development of psychotherapy has been based on psychological theories and clinical effects. However, an investigation of the neurobiological mechanisms of psychological interventions is also needed in order to improve indication and prognosis, inform the choice of parallel pharmacotherapy, provide outcome measures and potentially even aid the development of new treatment protocols. This neurobiological investigation can be informed by animal models, for example of learning and conditioning, but will essentially need the non-invasive techniques of functional neuroimaging in order to assess psychotherapy effects on patients' brains, which will be reviewed here. Most research so far has been conducted in obsessive compulsive disorder (OCD), anxiety disorders and depression. Effects in OCD were particularly exciting in that both cognitive behavioural therapy and medication with a selective serotonin inhibitor led to a reduction in blood flow in the caudate nucleus. In phobia, brief courses of behavioural therapy produced marked reductions of paralimbic responses to offensive stimuli in line with the clinical improvement. Findings in depression are less consistent, with both increases and decreases in prefrontal metabolism being reported. However, they are important in pointing to different mechanisms for the clinical effects of pharmacotherapy (more "bottom up") and psychotherapy (more "top down"). For the future it would be desirable if the findings of psychotherapy changes to brain activation patterns were confirmed in larger groups with homogenous imaging protocols. Functional imaging has already made great contributions to the understanding of the neural correlates of psychopathology. For example, evidence converges to suggest that the subgenual cingulate is crucial for mood regulation. One current clinical application of these findings is deep brain stimulation in areas highlighted by such imaging studies. I will discuss their initial application in depression

  14. Study on measurement of free ligand concentration in blood and quantitative analysis of brain benzodiazepine receptor

    Energy Technology Data Exchange (ETDEWEB)

    Hashimoto, Kenji; Goromaru, Tsuyoshi; Inoue, Osamu; Itoh, Takashi; Yamasaki, Toshiro.

    1988-11-01

    We developed the method to determine rapidly the free ligand concentration in the blood as an input function for the purpose of quantitative analysis of binding potential (B/sub max//K/sub d/) of brain benzodiazepine receptor in vivo. It was found that the unmetabolized radioligand in the blood after intravenous administration of /sup 3/H-Ro 15 - 1788 could be extracted by chloroform, whereas the radioactive metabolites could not be extracted. And the plasma protein binding of /sup 3/H-Ro 15 - 1788 was determined using an ultrafiltration method. The biodistribution of /sup 3/H-Ro 15 - 1788 in the cerebral cortex, cerebellum and pons-medulla after intravenous administration of the radiotracer in the control and forced-swimmed mice was examined. And the time course of the free ligand concentration in the blood was determined as described above. Further, the binding potential of benzodiazepine receptor in the mouse brain was analyzed using a simple mathematical model. It was suggested that the binding potential of benzodiazepine receptor in the mouse brain was significantly decreased by forced-swimming. In conclusion, it was found that these methods would be useful for quantitative analysis of clinical data in the human brain using /sup 11/C-Ro 15 - 1788 and positron emission tomography (PET).

  15. Sexually dimorphic development and binding characteristics of NMDA receptors in the brain of the platyfish

    Science.gov (United States)

    Flynn, K. M.; Schreibman, M. P.; Yablonsky-Alter, E.; Banerjee, S. P.

    1999-01-01

    This study investigated age- and gender-specific variations in properties of the glutamate N-methyl-d-aspartate receptor (NMDAR) in a freshwater teleost, the platyfish (Xiphophorus maculatus). Prior localization of the immunoreactive (ir)-R1 subunit of the NMDAR protein (R1) in cells of the nucleus olfactoretinalis (NOR), a primary gonadotropin-releasing hormone (GnRH)-containing brain nucleus in the platyfish, suggests that NMDAR, as in mammals, is involved in modulation of the platyfish brain-pituitary-gonad (BPG) axis. The current study shows that the number of cells in the NOR displaying ir-R1 is significantly increased in pubescent and mature female platyfish when compared to immature and senescent animals. In males, there is no significant change in ir-R1 expression in the NOR at any time in their lifespan. The affinity of the noncompetitive antagonist ((3)H)MK-801 for the NMDAR is significantly increased in pubescent females while maximum binding of ((3)H)MK-801 to the receptor reaches a significant maximum in mature females. In males, both MK-801 affinity and maximum binding remain unchanged throughout development. This is the first report of gender differences in the association of NMDA receptors with neuroendocrine brain areas during development. It is also the first report to suggest NMDA receptor involvement in the development of the BPG axis in a nonmammalian vertebrate. Copyright 1999 Academic Press.

  16. Prebiotic feeding elevates central brain derived neurotrophic factor, N-methyl-d-aspartate receptor subunits and d-serine ☆

    OpenAIRE

    Savignac, Helene M.; Corona, Giulia; Mills, Henrietta; Chen, Li; Spencer, Jeremy P.E.; Tzortzis, George; Burnet, Philip W. J.

    2013-01-01

    The influence of the gut microbiota on brain chemistry has been convincingly demonstrated in rodents. In the absence of gut bacteria, the central expression of brain derived neurotropic factor, (BDNF), and N-methyl-d-aspartate receptor (NMDAR) subunits are reduced, whereas, oral probiotics increase brain BDNF, and impart significant anxiolytic effects. We tested whether prebiotic compounds, which increase intrinsic enteric microbiota, also affected brain BDNF and NMDARs. In addition, we exami...

  17. Anatomical Brain Magnetic Resonance Imaging of Typically Developing Children and Adolescents

    Science.gov (United States)

    Giedd, Jay N.; Lalonde, Francois M.; Celano, Mark J.; White, Samantha L.; Wallace, Gregory L.; Lee, Nancy R.; Lenroot, Rhoshel K.

    2009-01-01

    Methodological issues relevant to magnetic resonance imaging studies of brain anatomy are discussed along with the findings on the neuroanatomic changes during childhood and adolescence. The development of the brain is also discussed.

  18. Brain tumor imaging of rat fresh tissue using terahertz spectroscopy

    Science.gov (United States)

    Yamaguchi, Sayuri; Fukushi, Yasuko; Kubota, Oichi; Itsuji, Takeaki; Ouchi, Toshihiko; Yamamoto, Seiji

    2016-07-01

    Tumor imaging by terahertz spectroscopy of fresh tissue without dye is demonstrated using samples from a rat glioma model. The complex refractive index spectrum obtained by a reflection terahertz time-domain spectroscopy system can discriminate between normal and tumor tissues. Both the refractive index and absorption coefficient of tumor tissues are higher than those of normal tissues and can be attributed to the higher cell density and water content of the tumor region. The results of this study indicate that terahertz technology is useful for detecting brain tumor tissue.

  19. Computed tomographical imaging of the brain in post hypoglycemic coma

    Energy Technology Data Exchange (ETDEWEB)

    Iwai, A.; Sakamoto, T.; Kinoshita, Y.; Yokota, J.I.; Yoshioka, T.; Sugimoto, T.

    1987-07-01

    A case of post severe hypoglycemic coma was studied by sequential Computed Tomographic Imaging (CT) of the brain. The CT 1) was normal in the early stage, 2) subsequently showed a low density area, which was enhanced by the contrast medium, in the cerebral cortex and the boundary zone between the major cerebral arteries, and 3) revealed marked enhancement in the entire cortical region and hypodensity in the periventricular region in the late stage. These CT findings, representing the course of neural cell damage by severe hypoglycemia, are discussed from the pathophysiological viewpoint.

  20. Functional magnetic resonance imaging of the brain: A quick review

    Directory of Open Access Journals (Sweden)

    Vaghela Viratsinh

    2010-01-01

    Full Text Available Ability to non-invasively map the hemodynamic changes occurring focally in areas of brain involved in various motor, sensory and cognitive functions by functional magnetic resonance imaging (fMRI has revolutionized research in neuroscience in the last two decades. This technique has already gained clinical use especially in pre-surgical evaluation of epilepsy and neurosurgical planning of resection of mass lesions adjacent to eloquent cortex. In this review we attempt to illustrate basic principles and techniques of fMRI, its applications, practical points to consider while performing and evaluating clinical fMRI and its limitations.

  1. Computed tomographical imaging of the brain in post hypoglycemic coma

    International Nuclear Information System (INIS)

    A case of post severe hypoglycemic coma was studied by sequential Computed Tomographic Imaging (CT) of the brain. The CT 1) was normal in the early stage, 2) subsequently showed a low density area, which was enhanced by the contrast medium, in the cerebral cortex and the boundary zone between the major cerebral arteries, and 3) revealed marked enhancement in the entire cortical region and hypodensity in the periventricular region in the late stage. These CT findings, representing the course of neural cell damage by severe hypoglycemia, are discussed from the pathophysiological viewpoint. (orig.)

  2. The recently identified P2Y-like receptor GPR17 is a sensor of brain damage and a new target for brain repair.

    Directory of Open Access Journals (Sweden)

    Davide Lecca

    Full Text Available Deciphering the mechanisms regulating the generation of new neurons and new oligodendrocytes, the myelinating cells of the central nervous system, is of paramount importance to address new strategies to replace endogenous damaged cells in the adult brain and foster repair in neurodegenerative diseases. Upon brain injury, the extracellular concentrations of nucleotides and cysteinyl-leukotrienes (cysLTs, two families of endogenous signaling molecules, are markedly increased at the site of damage, suggesting that they may act as "danger signals" to alert responses to tissue damage and start repair. Here we show that, in brain telencephalon, GPR17, a recently deorphanized receptor for both uracil nucleotides and cysLTs (e.g., UDP-glucose and LTD(4, is normally present on neurons and on a subset of parenchymal quiescent oligodendrocyte precursor cells. We also show that induction of brain injury using an established focal ischemia model in the rodent induces profound spatiotemporal-dependent changes of GPR17. In the lesioned area, we observed an early and transient up-regulation of GPR17 in neurons expressing the cellular stress marker heat shock protein 70. Magnetic Resonance Imaging in living mice showed that the in vivo pharmacological or biotechnological knock down of GPR17 markedly prevents brain infarct evolution, suggesting GPR17 as a mediator of neuronal death at this early ischemic stage. At later times after ischemia, GPR17 immuno-labeling appeared on microglia/macrophages infiltrating the lesioned area to indicate that GPR17 may also acts as a player in the remodeling of brain circuitries by microglia. At this later stage, parenchymal GPR17+ oligodendrocyte progenitors started proliferating in the peri-injured area, suggesting initiation of remyelination. To confirm a specific role for GPR17 in oligodendrocyte differentiation, the in vitro exposure of cortical pre-oligodendrocytes to the GPR17 endogenous ligands UDP-glucose and LTD(4

  3. Perfusion imaging with computed tomography: brain and beyond

    Energy Technology Data Exchange (ETDEWEB)

    Miles, K.A. [Div. of Clinical and Lab. Investigation, Brighton and Sussex Medical School, Univ. of Sussex, Falmer, Brighton (United Kingdom)

    2006-01-10

    The availability of rapid imaging with multidetector CT systems and commercial analysis software has made perfusion imaging with CT an everyday technique, not only for the brain but also for other body organs. Perfusion imaging is usually performed as an adjunct to a conventional CT examination and is therefore particularly appropriate when a conventional CT is part of routine clinical protocols. The derived values are reproducible and have been validated against a range of reference techniques. Within neuroradiology, perfusion CT has attracted interest in the assessment of acute stroke but can also be used to assess secondary injury in head trauma and as an adjunct to CT angiography to evaluate cerebral spasm in subarachnoid haemorrhage. Within oncology, perfusion CT provides an imaging correlate for tumour vascularity that can be used to discriminate benign and malignant lesions, as an indicator of tumour aggressiveness, to reveal occult tumour and improve the delineation of tumours during radiotherapy planning, and as a functional assessment of tumour response to therapy. By exploiting the ability of CT systems to quantify contrast enhancement. CT perfusion imaging uses contrast media to assess vascular physiology and so improve diagnosis, prognosis, treatment selection and therapy monitoring. (orig.)

  4. Three modality image registration of brain SPECT/CT and MR images for quantitative analysis of dopamine transporter imaging

    Science.gov (United States)

    Yamaguchi, Yuzuho; Takeda, Yuta; Hara, Takeshi; Zhou, Xiangrong; Matsusako, Masaki; Tanaka, Yuki; Hosoya, Kazuhiko; Nihei, Tsutomu; Katafuchi, Tetsuro; Fujita, Hiroshi

    2016-03-01

    Important features in Parkinson's disease (PD) are degenerations and losses of dopamine neurons in corpus striatum. 123I-FP-CIT can visualize activities of the dopamine neurons. The activity radio of background to corpus striatum is used for diagnosis of PD and Dementia with Lewy Bodies (DLB). The specific activity can be observed in the corpus striatum on SPECT images, but the location and the shape of the corpus striatum on SPECT images only are often lost because of the low uptake. In contrast, MR images can visualize the locations of the corpus striatum. The purpose of this study was to realize a quantitative image analysis for the SPECT images by using image registration technique with brain MR images that can determine the region of corpus striatum. In this study, the image fusion technique was used to fuse SPECT and MR images by intervening CT image taken by SPECT/CT. The mutual information (MI) for image registration between CT and MR images was used for the registration. Six SPECT/CT and four MR scans of phantom materials are taken by changing the direction. As the results of the image registrations, 16 of 24 combinations were registered within 1.3mm. By applying the approach to 32 clinical SPECT/CT and MR cases, all of the cases were registered within 0.86mm. In conclusions, our registration method has a potential in superimposing MR images on SPECT images.

  5. The Emergence of NMDA Receptor Metabotropic Function: Insights from Imaging

    Science.gov (United States)

    Dore, Kim; Aow, Jonathan; Malinow, Roberto

    2016-01-01

    The NMDA receptor (R) participates in many important physiological and pathological processes. For example, its activation is required for both long-term potentiation (LTP) and long-term depression (LTD) of synaptic transmission, cellular models of learning and memory. Furthermore, it may play a role in the actions of amyloid-beta on synapses as well as in the signaling leading to cell death following stroke. Until recently, these processes were thought to be mediated by ion-flux through the receptor. Using a combination of imaging and electrophysiological approaches, ion-flux independent functions of the NMDAR were recently examined. In this review, we will discuss the role of metabotropic NMDAR function in LTD and synaptic dysfunction. PMID:27516738

  6. Preparation and biological evaluation of (99m)Tc-ropinirole as a novel radiopharmaceutical for brain imaging.

    Science.gov (United States)

    Motaleb, M A; Ibrahem, I T; Ayoub, V R; Geneidi, A S

    2016-04-01

    Noninvasive brain imaging is a process that allows scientists and physicians to view and monitor the areas of the brain. The aim of this study was to formulate a novel radiopharmaceutical for the detection of brain disorders at early stages in susceptible patients. (99m) Tc-ropinirole was prepared by the direct complexation of ropinirole with technetium-99m. The results showed that the radiochemical yield (99m) Tc-ropinirole was 92 ± 2.87% and the radiochemical yield was evaluated by paper chromatography and HPLC. In vitro studies showed that the formed complex was stable for up to 6 h. In vivo uptake of (99m) Tc-ropinirole in the brain was 4.87 ± 0.15% injected dose/g organ at 30 min post-injection, which cleared from the brain with time till it reaches 2.3% at 2 h post-injection indicating that the brain uptake of (99m) Tc-ropinirole is higher than that of the commercially available (99m) Tc-HMPAO, which is 2.25% at 30 min. Pre-dosing mice with cold ropinirole reduced the brain uptake to 0.26 ± 0.01% injected dose/g organ, so this confirms the high specificity and selectivity of this radiotracer for the assessment of the dopamine receptors. PMID:26913705

  7. Autoradiographic visualization of insulin-like growth factor-II receptors in rat brain

    International Nuclear Information System (INIS)

    The documented presence of IGF-II in brain and CSF prompted us to investigate the distribution of receptors for IGF-II in rat brain slices. Human 125-I-IGF-II (10 pM) was incubated for 16 hrs at 40C with slide-mounted rat brain slices in the absence and presence of unlabeled human IGF-II (67 nM) or human insulin (86 nM). Slides were washed, dried, and exposed to X-ray film for 4-7 days. The results showed dense labeling in the granular layers of the olfactory bulbs, deep layers of the cerebral cortex, pineal gland, anterior pituitary, hippocampus (pyramidal cells CA1-CA2 and dentate gyrus), and the granule cell layers of the cerebellum. Unlabeled IGF-II eliminated most of the binding of these brain regions while insulin produced only a minimal reduction in the amount of 125I-IGF-II bound. These results indicate that a specific neural receptor for IGS-II is uniquely distributed in rat brain tissue and supports the notion that this peptide might play an important role in normal neuronal functioning

  8. TAM receptors affect adult brain neurogenesis by negative regulation of microglial cell activation.

    Science.gov (United States)

    Ji, Rui; Tian, Shifu; Lu, Helen J; Lu, Qingjun; Zheng, Yan; Wang, Xiaomin; Ding, Jixiang; Li, Qiutang; Lu, Qingxian

    2013-12-15

    TAM tyrosine kinases play multiple functional roles, including regulation of the target genes important in homeostatic regulation of cytokine receptors or TLR-mediated signal transduction pathways. In this study, we show that TAM receptors affect adult hippocampal neurogenesis and loss of TAM receptors impairs hippocampal neurogenesis, largely attributed to exaggerated inflammatory responses by microglia characterized by increased MAPK and NF-κB activation and elevated production of proinflammatory cytokines that are detrimental to neuron stem cell proliferation and neuronal differentiation. Injection of LPS causes even more severe inhibition of BrdU incorporation in the Tyro3(-/-)Axl(-/-)Mertk(-/-) triple-knockout (TKO) brains, consistent with the LPS-elicited enhanced expression of proinflammatory mediators, for example, IL-1β, IL-6, TNF-α, and inducible NO synthase, and this effect is antagonized by coinjection of the anti-inflammatory drug indomethacin in wild-type but not TKO brains. Conditioned medium from TKO microglia cultures inhibits neuron stem cell proliferation and neuronal differentiation. IL-6 knockout in Axl(-/-)Mertk(-/-) double-knockout mice overcomes the inflammatory inhibition of neurogenesis, suggesting that IL-6 is a major downstream neurotoxic mediator under homeostatic regulation by TAM receptors in microglia. Additionally, autonomous trophic function of the TAM receptors on the proliferating neuronal progenitors may also promote progenitor differentiation into immature neurons.

  9. Photoperiod and testosterone regulate androgen receptor immunostaining in the Siberian hamster brain.

    Science.gov (United States)

    Bittman, Eric L; Ehrlich, David A; Ogdahl, Justyne L; Jetton, Amy E

    2003-09-01

    Day length regulates the effects of gonadal steroids on gonadotropin secretion and behavior in seasonal breeders. To determine whether this influence of photoperiod results from changes in androgen receptor expression in Siberian hamster brain regions that regulate neuroendocrine function, androgen receptor immunostaining was examined in castrated animals given either no androgen replacement or one of three doses of testosterone (T) resulting in physiological serum concentrations. Half of the animals were housed under inhibitory photoperiod conditions, and immunostaining was quantified 11 days later. Measurement of serum gonadotropin and prolactin concentrations confirmed that androgen exerted graded effects on pituitary function but that the animals were killed before photoperiodic influences had fully developed. T significantly increased the numbers of androgen receptor-immunoreactive cells in every brain region examined. Photoperiod exerted no significant influence on androgen receptor-immunoreactive cell number in the arcuate nucleus, bed nucleus of the stria terminalis (BNST), medial preoptic nucleus, or in medial amygdala. An interaction between T and photoperiod was observed in the BNST and in the rostral and middle portions of the arcuate nucleus. Although increasing concentrations of T resulted in more intense cellular immunostaining in the BNST and arcuate, this effect was not influenced by day length. These results indicate that relatively short-duration (11 days) exposure to inhibitory photoperiod triggers localized and regionally specific changes in androgen receptor expression.

  10. Imaging diagnosis--magnetic resonance imaging findings in a dog with sequential brain infarction.

    Science.gov (United States)

    Major, Alison C; Caine, Abby; Rodriguez, Sue B; Cherubini, Giunio B

    2012-01-01

    An adult greyhound was evaluated on three occasions for acute, intracranial neurologic signs. Based on magnetic resonance (MR) imaging, there were T2-hyperintense and T1-hypointense, noncontrast enhancing lesions in the cerebellum, and brain stem. Using diffusion-weighted imaging (DWI), the lesions were characterized initially by restricted water diffusion. The presumptive diagnosis on each occasion was acute ischemic cerebrovascular accident leading to infarction. This allowed us to characterize the changes in appearance of infarcted neural tissue on the standard MR sequences over time, and to confirm that the DWI could be successfully used in low-field imaging. © 2012 Veterinary Radiology & Ultrasound. PMID:22731883

  11. [Studying specific effects of nootropic drugs on glutamate receptors in the rat brain].

    Science.gov (United States)

    Firstova, Iu Iu; Vasil'eva, E V; Kovalev, G I

    2011-01-01

    The influence of nootropic drugs of different groups (piracetam, phenotropil, nooglutil, noopept, semax, meclofenoxate, pantocalcine, and dimebon) on the binding of the corresponding ligands to AMPA, NMDA, and mGlu receptors of rat brain has been studied by the method of radio-ligand binding in vitro. It is established that nooglutil exhibits pharmacologically significant competition with a selective agonist of AMPA receptors ([G-3H]Ro 48-8587) for the receptor binding sites (with IC50 = 6.4 +/- 0.2 microM), while the competition of noopept for these receptor binding sites was lower by an order of magnitude (IC50 = 80 +/- 5.6 microM). The heptapeptide drug semax was moderately competitive with [G-3H]LY 354740 for mGlu receptor sites (IC50 = 33 +/- 2.4 microM). Dimebon moderately influenced the specific binding of the ligand of NMDA receptor channel ([G-3H]MK-801) at IC50 = 59 +/- 3.6 microM. Nootropic drugs of the pyrrolidone group (piracetam, phenotropil) as well as meclofenoxate, pantocalcine (pantogam) in a broad rage of concentrations (10(-4)-10(-10) M) did not affect the binding of the corresponding ligands to glutamate receptors (IC50 100 pM). Thus, the direct neurochemical investigation was used for the first time to qualitatively characterize the specific binding sites for nooglutil and (to a lower extent) noopept on AMPA receptors, for semax on metabotropic glutamate receptors, and for dimebon on the channel region of NMDA receptors. The results are indicative of a selective action of some nootropes on the glutamate family. PMID:21476267

  12. Serotonin transporter and dopamine transporter imaging in the canine brain

    Energy Technology Data Exchange (ETDEWEB)

    Peremans, Kathelijne [Department of Medical Imaging, Faculty of Veterinary Sciences, Ghent University, B-9000 Ghent (Belgium); Goethals, Ingeborg [Division of Nuclear Medicine, University Hospital Ghent, B-9000 Ghent (Belgium); De Vos, Filip [Laboratory of Radiopharmacy, Pharmaceutical Sciences, Ghent University, B-9000 Ghent (Belgium); Dobbeleir, A. [Department of Medical Imaging, Faculty of Veterinary Sciences, Ghent University, B-9000 Ghent (Belgium); Ham, Hamphrey [Division of Nuclear Medicine, University Hospital Ghent, B-9000 Ghent (Belgium); Van Bree, Henri [Department of Medical Imaging, Faculty of Veterinary Sciences, Ghent University, B-9000 Ghent (Belgium); Heeringen, Cees van [Department of Psychiatry and Medical Psychology, Faculty of Medical and Health Sciences, Ghent University, B-9000, Ghent (Belgium); Audenaert, Kurt [Division of Nuclear Medicine, University Hospital Ghent, B-9000 Ghent (Belgium) and Department of Psychiatry and Medical Psychology, Faculty of Medical and Health Sciences, Ghent University, B-9000, Ghent (Belgium)]. E-mail: kurt.audenaert@ugent.be

    2006-10-15

    The serotonergic and dopaminergic systems are involved in a wide range of emotional and behavioral aspects of animals and humans and are involved in many neuropsychiatric disorders. Selective serotonin (5-HT) reuptake inhibitors (SSRIs) are designed to block the 5-HT transporter (SERT), thereby increasing the available 5-HT in the brain. Functional imaging with specific SERT and dopamine transporter (DAT) ligands contributes to the study of the SSRI-transporter interaction. First, we evaluated the feasibility of a canine model in the study of the SERT and DAT with the radioligands [{sup 123}I]-{beta}-CIT and [{sup 123}I]-FP-CIT as well as single-photon emission computed tomography imaging. Second, we studied the effect of SSRIs (sertraline, citalopram and escitalopram) on the SERT and DAT in two dogs. The position of the canine model in the study of the SERT and DAT is discussed and compared with other animal models.

  13. Self-illuminating nanoprobe for in vivo imaging of cancers over-expressing the folate receptor

    Science.gov (United States)

    Miller, Steven C.; Beviglia, Lucia; Yeung, Pete; Bhattacharyya, Sukanta; Sobek, Daniel

    2012-03-01

    New in vivo imaging reagents with increased sensitivity and penetration depth are needed to advance our understanding of metastases and accelerate the development of therapeutics. The folate receptor (FR) is a promising imaging target that is up-regulated in many human carcinomas, including cancers of the ovary, breast, pancreas, endometrium, lungs, kidneys, colon, brain, and myeloid cells. Zymera has developed a self-illuminating Bioluminescence Resonance Energy Transfer Quantum Dot (BRET-Qdot) nanoprobe conjugated with folate (BQ-Folate) for in vivo imaging of cancers overexpressing FR. BQ-Folate is a novel nanoprobe formed by co-conjugating Renilla reniformis luciferase enzyme and folate to near-infrared (NIR) emitting quantum dots. The luciferase substrate, coelenterazine, activates the BQ-Folate nanoprobe generating luminescence emission in the near-infrared (NIR) region (655 nm) for increased sensitivity and penetration depth. Because BQ-Folate requires no external light source for light emission, it has significant advantages for challenging in vivo preclinical optical imaging applications, such as the detection of early stage metastases. Zymera and OncoMed Pharmaceuticals have demonstrated that in vivo imaging with the BQ-Folate nanoprobe detected the primary tumor and early stage metastases in an orthotopic NOD/SCID mouse model of human pancreatic cancer.

  14. Changes in sensitivity of brain dopamine and serotonin receptors during long-term treatment with carbidine

    Energy Technology Data Exchange (ETDEWEB)

    Zharkovskii, A.M.; Allikmets, L.K.; Chereshka, K.S.; Zharkovskaya, T.A.

    1986-04-01

    The authors study the state of the dopamine and serotonin receptors of the brain during chronic administration of carbidine to animals. Parts of the brain from two rats were pooled and binding of tritium-spiperone and tritium-LSD was determined. Statistical analysis of the data for apomorphine sterotypy was carried out and the Student's test was used for analysis of the remaining data. It is shown that after discontinuation of carbidine binding of tritium-spiperone and tritium-LSD in the cortex was reduced.

  15. Characterization of 5-HT1D receptor binding sites in post-mortem human brain cortex.

    OpenAIRE

    Martial, J; de Montigny, C; Cecyre, D; Quirion, R

    1991-01-01

    The present study provides further evidence for the presence of serotonin1D (5-HT1D) receptors in post-mortem human brain. Receptor binding parameters in temporal cortex homogenates were assessed using [3H]5-HT in the presence of 100 nM 8-OH-DPAT, 1 microM propranolol and 1 microM mesulergine to prevent labelling of the 5-HT1A, 5-HT1B and 5-HT1C sites, respectively. Under these conditions, [3H]5-HT apparently bound to a class of high affinity (Kd = 5.0 +/- 1.0 nM) low capacity (Bmax = 96 +/- ...

  16. Optimising rigid motion compensation for small animal brain PET imaging

    Science.gov (United States)

    Spangler-Bickell, Matthew G.; Zhou, Lin; Kyme, Andre Z.; De Laat, Bart; Fulton, Roger R.; Nuyts, Johan

    2016-10-01

    Motion compensation (MC) in PET brain imaging of awake small animals is attracting increased attention in preclinical studies since it avoids the confounding effects of anaesthesia and enables behavioural tests during the scan. A popular MC technique is to use multiple external cameras to track the motion of the animal’s head, which is assumed to be represented by the motion of a marker attached to its forehead. In this study we have explored several methods to improve the experimental setup and the reconstruction procedures of this method: optimising the camera-marker separation; improving the temporal synchronisation between the motion tracker measurements and the list-mode stream; post-acquisition smoothing and interpolation of the motion data; and list-mode reconstruction with appropriately selected subsets. These techniques have been tested and verified on measurements of a moving resolution phantom and brain scans of an awake rat. The proposed techniques improved the reconstructed spatial resolution of the phantom by 27% and of the rat brain by 14%. We suggest a set of optimal parameter values to use for awake animal PET studies and discuss the relative significance of each parameter choice.

  17. Tomographic brain imaging with nucleolar detail and automatic cell counting

    Science.gov (United States)

    Hieber, Simone E.; Bikis, Christos; Khimchenko, Anna; Schweighauser, Gabriel; Hench, Jürgen; Chicherova, Natalia; Schulz, Georg; Müller, Bert

    2016-09-01

    Brain tissue evaluation is essential for gaining in-depth insight into its diseases and disorders. Imaging the human brain in three dimensions has always been a challenge on the cell level. In vivo methods lack spatial resolution, and optical microscopy has a limited penetration depth. Herein, we show that hard X-ray phase tomography can visualise a volume of up to 43 mm3 of human post mortem or biopsy brain samples, by demonstrating the method on the cerebellum. We automatically identified 5,000 Purkinje cells with an error of less than 5% at their layer and determined the local surface density to 165 cells per mm2 on average. Moreover, we highlight that three-dimensional data allows for the segmentation of sub-cellular structures, including dendritic tree and Purkinje cell nucleoli, without dedicated staining. The method suggests that automatic cell feature quantification of human tissues is feasible in phase tomograms obtained with isotropic resolution in a label-free manner.

  18. Tomographic brain imaging with nucleolar detail and automatic cell counting.

    Science.gov (United States)

    Hieber, Simone E; Bikis, Christos; Khimchenko, Anna; Schweighauser, Gabriel; Hench, Jürgen; Chicherova, Natalia; Schulz, Georg; Müller, Bert

    2016-01-01

    Brain tissue evaluation is essential for gaining in-depth insight into its diseases and disorders. Imaging the human brain in three dimensions has always been a challenge on the cell level. In vivo methods lack spatial resolution, and optical microscopy has a limited penetration depth. Herein, we show that hard X-ray phase tomography can visualise a volume of up to 43 mm(3) of human post mortem or biopsy brain samples, by demonstrating the method on the cerebellum. We automatically identified 5,000 Purkinje cells with an error of less than 5% at their layer and determined the local surface density to 165 cells per mm(2) on average. Moreover, we highlight that three-dimensional data allows for the segmentation of sub-cellular structures, including dendritic tree and Purkinje cell nucleoli, without dedicated staining. The method suggests that automatic cell feature quantification of human tissues is feasible in phase tomograms obtained with isotropic resolution in a label-free manner. PMID:27581254

  19. Comparative mouse brain tractography of diffusion magnetic resonance imaging

    Science.gov (United States)

    Moldrich, Randal X.; Pannek, Kerstin; Hoch, Renee; Rubenstein, John L.; Kurniawan, Nyoman D.; Richards, Linda J.

    2010-01-01

    Diffusion magnetic resonance imaging (dMRI) tractography can be employed to simultaneously analyse three-dimensional white matter tracts in the brain. Numerous methods have been proposed to model diffusion-weighted magnetic resonance data for tractography, and we have explored the functionality of some of these for studying white and grey matter pathways in ex vivo mouse brain. Using various deterministic and probabilistic algorithms across a range of regions of interest we found that probabilistic tractography provides a more robust means of visualizing both white and grey matter pathways than deterministic tractography. Importantly, we demonstrate the sensitivity of probabilistic tractography profiles to streamline number, step size, curvature, fiber orientation distribution, and whole-brain versus region of interest seeding. Using anatomically well-defined cortico-thalamic pathways, we show how density maps can permit the topographical assessment of probabilistic tractography. Finally, we show how different tractography approaches can impact on dMRI assessment of tract changes in a mouse deficient for the frontal cortex morphogen, fibroblast growth factor 17. In conclusion, probabilistic tractography can elucidate the phenotypes of mice with neurodegenerative or neurodevelopmental disorders in a quantitative manner. PMID:20303410

  20. Segmentation of Tumor Region in MRI Images of Brain using Mathematical Morphology

    OpenAIRE

    Ashwini Gade; Rekha Vig; Vaishali Kulkarni

    2014-01-01

    This paper introduces an efficient detection of brain tumor from cerebral MRI images. The methodology consists of two steps: enhancement and segmentation. To improve the quality of images and limit the risk of distinct regions fusion in the segmentation phase an enhancement process is applied. We applied mathematical morphology to increase the contrast in MRI images and to segment MRI images. Some of experimental results on brain images show the feasibility and the performance of the proposed...

  1. Segmentation of Tumor Region in MRI Images of Brain using Mathematical Morphology

    Directory of Open Access Journals (Sweden)

    Ashwini Gade

    2014-06-01

    Full Text Available This paper introduces an efficient detection of brain tumor from cerebral MRI images. The methodology consists of two steps: enhancement and segmentation. To improve the quality of images and limit the risk of distinct regions fusion in the segmentation phase an enhancement process is applied. We applied mathematical morphology to increase the contrast in MRI images and to segment MRI images. Some of experimental results on brain images show the feasibility and the performance of the proposed approach.

  2. Assessment of α7 nicotinic acetylcholine receptor availability in juvenile pig brain with [18F]NS10743

    International Nuclear Information System (INIS)

    To conduct a quantitative PET assessment of the specific binding sites in the brain of juvenile pigs for [18F]NS10743, a novel diazabicyclononane derivative targeting α7 nicotinic acetylcholine receptors (α7 nAChRs). Dynamic PET recordings were made in isoflurane-anaesthetized juvenile pigs during 120 min after administration of [18F]NS10743 under baseline conditions (n = 3) and after blocking of the α7 nAChR with NS6740 (3 mg.kg-1 bolus + 1 mg.kg-1.h-1 continuous infusion; n = 3). Arterial plasma samples were collected for determining the input function of the unmetabolized tracer. Kinetic analysis of regional brain time-radioactivity curves was performed, and parametric maps were calculated relative to arterial input. Plasma [18F]NS10743 passed readily into the brain, with peak uptake occurring in α7 nAChR-expressing brain regions such as the colliculi, thalamus, temporal lobe and hippocampus. The highest SUVmax was approximately 2.3, whereas the lowest uptake was in the olfactory bulb (SUVmax 1.53 ± 0.32). Administration of NS6740 significantly decreased [18F]NS10743 binding late in the emission recording throughout the brain, except in the olfactory bulb, which was therefore chosen as reference region for calculation of BPND. The baseline BPND ranged from 0.39 ± 0.08 in the cerebellum to 0.76 ± 0.07 in the temporal lobe. Pretreatment and constant infusion with NS6740 significantly reduced the BPND in regions with high [18F]NS10743 binding (temporal lobe -29%, p = 0.01; midbrain: -35%, p = 0.02), without significantly altering the BPND in low binding regions (cerebellum: -16%, p = 0.2). This study confirms the potential of [18F]NS10743 as a target-specific radiotracer for the molecular imaging of central α7 nAChRs by PET. (orig.)

  3. Development of novel mixed ligand technetium complexes for imaging 5-HT1A neural system receptors

    International Nuclear Information System (INIS)

    The development of 99mTc complexes for imaging 5-HT1A neural system receptors using the 3 + 1 mixed ligand approach is described. Six novel complexes (I-VI) were designed using two different strategies. In complexes I-IV the pharmacophore 1-(2-methoxyphenyl)piperazine was attached to a monodentate thiol used as co-ligand and combined with tridentate dianionic aminothiols (SNS and NNS). On the other hand, complexes V and VI were obtained using thiophenol and 4-methoxy-thiophenol as co-ligand and a tridentate ligand (SNS) with the pharmacophore bound to the nitrogen through an alkyl chain. All complexes were prepared at tracer level using 99mTc-glucoheptonate as precursor. Ligand and co-ligand concentration, reaction time and temperature were optimized to achieve high substitution yield and radiochemical purity. Structure was studied at carrier level through the corresponding rhenium complexes. Complexes I and II presented the expected ReOLK structure and a distorted trigonal bipyramidal geometry. The structure of the other four complexes has not been completely elucidated yet. Biodistribution studies of all the complexes demonstrated selective brain uptake and retention. Uptake of complex I in receptor-rich hippocampus was significantly higher than that of the cerebellum (P = 0.05) 1 h post-injection. Oxorhenium complexes I and II showed affinity for the 5-HT1A receptor binding sites, with IC50 values in the nanomolar range. The results demonstrate the potential of the mixed ligand approach for the design of 99mTc complexes with the ability to bind neuroreceptors. However, the goal of imaging 5-HT1A receptors with technetium requires further development of complexes with improved biological profiles. (author)

  4. DPABI: Data Processing & Analysis for (Resting-State) Brain Imaging.

    Science.gov (United States)

    Yan, Chao-Gan; Wang, Xin-Di; Zuo, Xi-Nian; Zang, Yu-Feng

    2016-07-01

    Brain imaging efforts are being increasingly devoted to decode the functioning of the human brain. Among neuroimaging techniques, resting-state fMRI (R-fMRI) is currently expanding exponentially. Beyond the general neuroimaging analysis packages (e.g., SPM, AFNI and FSL), REST and DPARSF were developed to meet the increasing need of user-friendly toolboxes for R-fMRI data processing. To address recently identified methodological challenges of R-fMRI, we introduce the newly developed toolbox, DPABI, which was evolved from REST and DPARSF. DPABI incorporates recent research advances on head motion control and measurement standardization, thus allowing users to evaluate results using stringent control strategies. DPABI also emphasizes test-retest reliability and quality control of data processing. Furthermore, DPABI provides a user-friendly pipeline analysis toolkit for rat/monkey R-fMRI data analysis to reflect the rapid advances in animal imaging. In addition, DPABI includes preprocessing modules for task-based fMRI, voxel-based morphometry analysis, statistical analysis and results viewing. DPABI is designed to make data analysis require fewer manual operations, be less time-consuming, have a lower skill requirement, a smaller risk of inadvertent mistakes, and be more comparable across studies. We anticipate this open-source toolbox will assist novices and expert users alike and continue to support advancing R-fMRI methodology and its application to clinical translational studies.

  5. Statistical shape model-based segmentation of brain MRI images.

    Science.gov (United States)

    Bailleul, Jonathan; Ruan, Su; Constans, Jean-Marc

    2007-01-01

    We propose a segmentation method that automatically delineates structures contours from 3D brain MRI images using a statistical shape model. We automatically build this 3D Point Distribution Model (PDM) in applying a Minimum Description Length (MDL) annotation to a training set of shapes, obtained by registration of a 3D anatomical atlas over a set of patients brain MRIs. Delineation of any structure from a new MRI image is first initialized by such registration. Then, delineation is achieved in iterating two consecutive steps until the 3D contour reaches idempotence. The first step consists in applying an intensity model to the latest shape position so as to formulate a closer guess: our model requires far less priors than standard model in aiming at direct interpretation rather than compliance to learned contexts. The second step consists in enforcing shape constraints onto previous guess so as to remove all bias induced by artifacts or low contrast on current MRI. For this, we infer the closest shape instance from the PDM shape space using a new estimation method which accuracy is significantly improved by a huge increase in the model resolution and by a depth-search in the parameter space. The delineation results we obtained are very encouraging and show the interest of the proposed framework. PMID:18003193

  6. [Imaging the brain, from the cell to the organ].

    Science.gov (United States)

    Cabanis, Emmanuel Alain; Iba-Zizen, Marie-Thérèse; Habas, Christophe; Istoc, Adrian; Stievenart, Jean-Louis; Yoshida, Masaki; Nguyen, Thien Huong; Goepel, Roland

    2009-04-01

    Brain imaging has progressed over the centuries, from prehistory (surgical and sculptural empiricism), through the Middle Ages (dissection and drawings), the Renaissance (printing) and the 18th century (Spallanzani and ultrasounds), to the 19th century and the discovery of piezoelectricity by the Curie brothers and X-rays by Röntgen in 1895. The head had finally become transparent! The microscope was used by Ramon Y Cajal for histological and neuropathological brain studies. Marie Curie's discovery of radioisotopes paved the way for advances in in vivo neurophysiology. In the 20th century, technical progress accelerated with the advent of computed tomography. Injected contrast products were initially negative (air for ventriculography and pneumo-encephalography), and subsequently positive (intraventricular then intraarterial iodine, cerebral arteriography, increasingly hyperselective). Neurology and neurosurgery were followed by neuroradiology, stereotaxy, and interventional neuroradiology. G.N. Hounsfield's EMI CT scanner replaced silver salts crystals with computed pixels and voxels. Magnetic resonance imaging (MRI, 1981), which dispenses with the need for X-rays, is evolving at the same pace as computer science itself (Moore's Law) in the form of nanometric biophotonics for example. Diffusion MRI is providing precious information on neuroanatomy (axonal organization of the white matter and neuro-tractography, vascular anatomy), neurochemistry (MRS) and neurophysiology. Functional MRI of sensory activation and resting connectivity, the substrate of thought, is giving fascinating results. Functional stereotactic neurosurgery (for epilepsy, abnormal movements, etc.), stereotactic radiosurgery and endovascular interventional neuroradiology are among the latest approaches. PMID:20120272

  7. Diffusion-weighted imaging in normal fetal brain maturation

    Energy Technology Data Exchange (ETDEWEB)

    Schneider, J.F. [University Children' s Hospital UKBB, Department of Pediatric Radiology, Basel (Switzerland); Confort-Gouny, S.; Le Fur, Y.; Viout, P.; Cozzone, P. [UMR-CNRS 6612, Faculte de Medecine, Universite de la Mediterranee, Centre de Resonance Magnetique Biologique et Medicale, Marseille (France); Bennathan, M.; Chapon, F.; Fogliarini, C.; Girard, N. [Universite de la Mediterranee, Department of Neuroradiology AP-HM Timone, Marseille (France)

    2007-09-15

    Diffusion-weighted imaging (DWI) provides information about tissue maturation not seen on conventional magnetic resonance imaging. The aim of this study is to analyze the evolution over time of the apparent diffusion coefficient (ADC) of normal fetal brain in utero. DWI was performed on 78 fetuses, ranging from 23 to 37 gestational weeks (GW). All children showed at follow-up a normal neurological evaluation. ADC values were obtained in the deep white matter (DWM) of the centrum semiovale, the frontal, parietal, occipital and temporal lobe, in the cerebellar hemisphere, the brainstem, the basal ganglia (BG) and the thalamus. Mean ADC values in supratentorial DWM areas (1.68 {+-} 0.05 mm{sup 2}/s) were higher compared with the cerebellar hemisphere (1.25 {+-} 0.06 mm{sup 2}/s) and lowest in the pons (1.11 {+-} 0.05 mm{sup 2}/s). Thalamus and BG showed intermediate values (1.25 {+-} 0.04 mm{sup 2}/s). Brainstem, cerebellar hemisphere and thalamus showed a linear negative correlation with gestational age. Supratentorial areas revealed an increase in ADC values, followed by a decrease after the 30th GW. This study provides a normative data set that allows insights in the normal fetal brain maturation in utero, which has not yet been observed in previous studies on premature babies. (orig.)

  8. Noninvasive, in vivo imaging of the mouse brain using photoacoustic microscopy

    OpenAIRE

    Stein, Erich W.; Maslov, Konstantin; Wang, Lihong V.

    2009-01-01

    Noninvasive, high resolution imaging of mouse brain activity is poised to provide clinically translatable insights into human neurological disease progression. Toward noninvasive imaging of brain activity through the hemodynamic response, the dark-field photoacoustic microscopy (PAM) technique was enhanced to image the cortex vasculature of the mouse brain in vivo using endogenous hemoglobin contrast. Specifically, the PAM system was redesigned to efficiently collect photoacoustic waves origi...

  9. Brain aromatase (Cyp19A2) and estrogen receptors, in larvae and adult pejerrey fish Odontesthes bonariensis: Neuroanatomical and functional relations

    Science.gov (United States)

    Strobl-Mazzulla, P. H.; Lethimonier, C.; Gueguen, M.M.; Karube, M.; Fernandino, J.I.; Yoshizaki, G.; Patino, R.; Strussmann, C.A.; Kah, O.; Somoza, G.M.

    2008-01-01

    Although estrogens exert many functions on vertebrate brains, there is little information on the relationship between brain aromatase and estrogen receptors. Here, we report the cloning and characterization of two estrogen receptors, ?? and ??, in pejerrey. Both receptors' mRNAs largely overlap and were predominantly expressed in the brain, pituitary, liver, and gonads. Also brain aromatase and estrogen receptors were up-regulated in the brain of estradiol-treated males. In situ hybridization was performed to study in more detail, the distribution of the two receptors in comparison with brain aromatase mRNA in the brain of adult pejerrey. The estrogen receptors' mRNAs exhibited distinct but partially overlapping patterns of expression in the preoptic area and the mediobasal hypothalamus, as well as in the pituitary gland. Moreover, the estrogen receptor ??, but not ??, were found to be expressed in cells lining the preoptic recess, similarly as observed for brain aromatase. Finally, it was shown that the onset expression of brain aromatase and both estrogen receptors in the head of larvae preceded the morphological differentiation of the gonads. Because pejerrey sex differentiation is strongly influenced by temperature, brain aromatase expression was measured during the temperature-sensitive window and was found to be significantly higher at male-promoting temperature. Taken together these results suggest close neuroanatomical and functional relationships between brain aromatase and estrogen receptors, probably involved in the sexual differentiation of the brain and raising interesting questions on the origin (central or peripheral) of the brain aromatase substrate. ?? 2008 Elsevier Inc.

  10. Opposite modulation of brain stimulation reward by NMDA and AMPA receptors in the ventral tegmental area.

    Directory of Open Access Journals (Sweden)

    Charles eDucrot

    2013-10-01

    Full Text Available Previous studies have shown that blockade of ventral midbrain (VM glutamate N-Methyl-D-Aspartate (NMDA receptors induces reward, stimulates forward locomotion and enhances brain stimulation reward. Glutamate induces two types of excitatory response on VM neurons, a fast and short lasting depolarisation mediated by a-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA receptors and a longer lasting depolarization mediated by NMDA receptors. A role for the two glutamate receptors in modulation of VM neuronal activity is evidenced by the functional change in AMPA and NMDA synaptic responses that result from repeated exposure to reward. Since both receptors contribute to the action of glutamate on VM neuronal activity, we studied the effects of VM AMPA and NMDA receptor blockade on reward induced by electrical brain stimulation. Experiments were performed on rats trained to self-administer electrical pulses in the medial posterior mesencephalon. Reward thresholds were measured with the curve-shift paradigm before and for two hours after bilateral VM microinjections of the AMPA antagonist, NBQX (2,3,-Dioxo-6-nitro-1,2,3,4-tetrahydrobenzo(fquinoxaline-7-sulfonamide, 0, 80, and 800 pmol/0.5ul/side and of a single dose (0.825 nmol/0.5ul/side of the NMDA antagonist, PPPA (2R,4S-4-(3-Phosphonopropyl-2-piperidinecarboxylic acid. NBQX produced a dose-dependent increase in reward threshold with no significant change in maximum rate of responding. Whereas PPPA injected at the same VM sites produced a significant time dependent decrease in reward threshold and increase in maximum rate of responding. We found a negative correlation between the magnitude of the attenuation effect of NBQX and the enhancement effect of PPPA; moreover, NBQX and PPPA were most effective when injected respectively into the anterior and posterior VM. These results suggest that glutamate acts on different receptor sub-types, most likely located on different VM neurons, to modulate

  11. Physiology and physiopathology of central type Benzodiazepine receptors: Study in the monkey and in human brain using positron emission tomography

    International Nuclear Information System (INIS)

    A new non-invasive technique that allows to study in a living subject central type benzodiazepine receptors is developed. A combined approach is applied using a specific positron-emitting radiotracer for the in vivo labelling of the receptors and positron emission tomography allowing, by external detection, a quantitative determination of tissue radioactivity. The radioligand used for the in vivo labelling of benzodiazepine receptors is the antagonist RO 15-1788 labelled with carbon 11. The various stages of the study are described: in vivo characterization in the monkey of central type benzodiazepine receptors; characterization of central type benzodiazepine receptors in human brain using selective molecules for the BZ1 benzodiazepine subclass; demonstration of the heterogeneity of central type benzodiazepine receptors in the brain; study of pathological alteration of benzodiazepine receptors in experimental epilepsy

  12. Optimizing brain tumor resection. Midfield interventional MR imaging.

    Science.gov (United States)

    Alexander, E

    2001-11-01

    The development of the intraoperative MR imager represents an important example of creative vision and interdisciplinary teamwork. The result is a remarkable tool for neurosurgical applications. MRT allows surgical manipulation under direct visualization of the intracranial contents through the eye of the surgeon and through the volumetric images of the MR imaging system. This technology can be applied to cranial and spinal cases, and forseeably can encompass application to the entire gamut of neurosurgical efforts. The author's experience has been that this device is easy and comfortable for the surgeon to use. Image acquisition, giving views in the plane of choice, lasts no more than 2 to 60 seconds (depending on the imaging method), and does not increase the duration of a given procedure substantially. The author believes that the information received through intraoperative MR imaging scanning ultimately will contribute to decreasing the duration of surgery. Future possibilities include combining the intraoperative MR imager with other technologies, such as the endoscope, focused ultrasound, robotics, and the evaluation of brain function intraoperatively. The development of the intraoperative MR imager marks a significant advance in neurosurgery, an advance that will revolutionize intraoperative visualization as fully as the operating microscope. The combination of intraoperative visualization and precise surgical navigation is unparalleled, and its enhancement of surgical applications will be widespread. Considering the remarkable potential of the intraoperative MR imager for neurosurgical applications, optimal magnet design, image quality, and navigational methods are necessary to capitalize on the advantages of this revolutionary tool. The intraoperative MR imaging system that the author's team has developed and used has combined these features, and allows the performance of open surgical procedures without the need of patient or magnet repositioning. By

  13. Brain MR imaging finding in patients with central vertigo

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Chun Keun; Kim, Sang Joon; Kim, You Me; Cha, Min Jung; Lee, Young Seok; Kim, Jae Il; Lee, Geun Ho; Rhee, Chung Koo; Park, Hyun Min [Dankook Univ. College of Medicine, Chonan (Korea, Republic of)

    1998-11-01

    To investigate brain lesions and their locations in patients with central vertigo, as seen on MR imaging. We retrospectively reviewed MR images of 85 patients with central type vertigo diagnosed on the basis of clinical symptoms and vestibular function test(VFT), and analyzed lesions fand their locations. Those located along the known central vestibular pathway were included in our study. In 29 of 85 patients(34%), lesions considered to be associated with central vertigo were detected on MR imaging. These included infarction(18 patients), hemorrhage(5), tumor(2), cavernous angioma(1), cerebellopontine angle cyst(1), tuberous sclerosis(1) and olivopontocerebellar atrophy (1);they were located in the parietal lobe(6 patients), the lateral medulla(5), the pons(5), the middle cerebellar peduncle(4), the corona radiata(3), and the cerebellar vermis(3). Thirty-eight cases showed high signal intensity lesions in deep cerebral matter, the basal ganglia, and pons but these were considered to be unrelated to central vertigo. MR imaging could be a useful tool for the evaluation of patients with central vertigo.=20.

  14. Nicotinic receptor imaging with F-18 A85380 PET in Alzheimer's disease and normal ageing

    International Nuclear Information System (INIS)

    Full text: Central nicotinic acetylcholine receptors (nAChR) mediate excitatory neurotransmission and contribute to a variety of brain functions including learning and memory. Post mortem studies in patients with Alzheimer's disease have revealed losses of nAChR from the neocortex and hippocampal formation with ligand binding studies showing a reduction of over 50% compared to normal elderly brains in the temporal cortex and hippocampus (Sabbagh 1998). This is consistent with the loss of cholinergic neurones that has been well documented in this condition. Nicotinic AChR are predominantly located presynaptically on the cholinergic neurones. Consequently the ability to image and quantify these receptors may provide a measure of cholinergic loss and therefore a test for the early diagnosis of Alzheimer's disease and for monitoring therapy designed' to preserve cholinergic neurones. Aging is known to effect nAChR (Hellstrom-Lindahl 2000) so this variable must be quantified and incorporated into analysis of the scans. Nicotinic receptors also have important modulatory effects on glutamate, dopamine, serotonin and noradrenaline release and profound receptor loss has been documented in Parkinson's disease and Diffuse Lewy Body disease in addition to AD. Abnormalities in the alpha 7 subtype have been reported in schizophrenia. Imaging studies of nAChR have been hampered by the lack of a suitable tracer for in-vivo imaging. Nicotine itself labelled with carbon-11 for PET imaging has been used but has been shown to reflect regional cerebral blood flow not nAChR due to high nonspecific binding (Nyback et al, 1994). Potent nAChR ligands such as Epibatidine have been very useful for in-vitro studies but are too toxic for routine human use due to strong activation of nAChR including those in the sympathetic ganglia (A3B4 subtype). Recently, the Abbott Laboratories developed A85380 (3-[2(S)-2- azetidinylmethoxyl]pyridine) an azetidine derivative of the 3-pyridyl ethers that has

  15. Fetal magnetic resonance imaging of the brain: technical considerations and normal brain development

    Energy Technology Data Exchange (ETDEWEB)

    Huisman, Thierry A.G.M.; Kubik-Huch, Rahel; Marincek, Borut [Institute of Diagnostic Radiology, University Hospital Zurich, 8091 Zurich (Switzerland); Martin, Ernst [Department of Neuroradiology and Magnetic Resonance, University Children' s Hospital, 8091 Zurich (Switzerland)

    2002-08-01

    Fetal MRI examines non-invasively the unborn fetus. Ultrafast MRI sequences effectively suppress fetal motion. Multiple case reports and studies have shown that fetal MRI is particularly helpful in the evaluation of the central nervous system. The high contrast-to-noise ratio, the high spatial resolution, the multiplanar capabilities, the large field of view and the simultaneous visualisation of fetal and maternal structures have proven to be advantageous. Fetal MRI is particularly helpful in the evaluation of the normal and pathological development of the brain. Despite the fact that no side effects have been reported or are to be expected, the use of MRI during pregnancy is still limited to the second and third trimester of pregnancy. Magnetic resonance imaging contrast media are not to be used as it passes the placenta. Ultrasound remains the primary screening modality for fetal pathology; fetal MRI can serve as an adjunct or second-line imaging modality. (orig.)

  16. Ultrastructural localization of cholinergic muscarinic receptors in rat brain cortical capillaries

    OpenAIRE

    Luiten, PGM; DEJONG, GI; VANDERZEE, EA; vanDijken, H; van Dijken, H.

    1996-01-01

    Cholinergic innervation of the cerebrovasculature is known to regulate vascular tone, perfusion rate and permeability of the microvascular wall. Notably the cholinergic innervation of cerebral capillaries is of interest since these capillaries form the blood-brain barrier. Although there is a general consensus as to the presence of nicotinic and muscarinic receptors in the domain of the capillary wall, their precise anatomical position is unknown. The subcellular localization of muscarinic re...

  17. A quantitative MRI method for imaging blood-brain barrier leakage in experimental traumatic brain injury.

    Directory of Open Access Journals (Sweden)

    Wei Li

    Full Text Available Blood-brain barrier (BBB disruption is common following traumatic brain injury (TBI. Dynamic contrast enhanced (DCE MRI can longitudinally measure the transport coefficient Ktrans which reflects BBB permeability. Ktrans measurements however are not widely used in TBI research because it is generally considered to be noisy and possesses low spatial resolution. We improved spatiotemporal resolution and signal sensitivity of Ktrans MRI in rats by using a high-sensitivity surface transceiver coil. To overcome the signal drop off profile of the surface coil, a pre-scan module was used to map the flip angle (B1 field and magnetization (M0 distributions. A series of T1-weighted gradient echo images were acquired and fitted to the extended Kety model with reversible or irreversible leakage, and the best model was selected using F-statistics. We applied this method to study the rat brain one hour following controlled cortical impact (mild to moderate TBI, and observed clear depiction of the BBB damage around the impact regions, which matched that outlined by Evans Blue extravasation. Unlike the relatively uniform T2 contrast showing cerebral edema, Ktrans shows a pronounced heterogeneous spatial profile in and around the impact regions, displaying a nonlinear relationship with T2. This improved Ktrans MRI method is also compatible with the use of high-sensitivity surface coil and the high-contrast two-coil arterial spin-labeling method for cerebral blood flow measurement, enabling more comprehensive investigation of the pathophysiology in TBI.

  18. Effects of visual deprivation during brain development on expression of AMPA receptor subunits in rat’s hippocampus

    Directory of Open Access Journals (Sweden)

    Sayyed Alireza Talaei

    2015-06-01

    Conclusion: Dark rearing of rats during critical period of brain development changes the relative expression and also arrangement of both AMPA receptor subunits, GluR1 and GluR2 in the hippocampus, age dependently.

  19. Notch receptor expression in neurogenic regions of the adult zebrafish brain.

    Directory of Open Access Journals (Sweden)

    Vanessa de Oliveira-Carlos

    Full Text Available The adult zebrash brain has a remarkable constitutive neurogenic capacity. The regulation and maintenance of its adult neurogenic niches are poorly understood. In mammals, Notch signaling is involved in stem cell maintenance both in embryonic and adult CNS. To better understand how Notch signaling is involved in stem cell maintenance during adult neurogenesis in zebrafish we analysed Notch receptor expression in five neurogenic zones of the adult zebrafish brain. Combining proliferation and glial markers we identified several subsets of Notch receptor expressing cells. We found that 90 [Formula: see text] of proliferating radial glia express notch1a, notch1b and notch3. In contrast, the proliferating non-glial populations of the dorsal telencephalon and hypothalamus rarely express notch3 and about half express notch1a/1b. In the non-proliferating radial glia notch3 is the predominant receptor throughout the brain. In the ventral telencephalon and in the mitotic area of the optic tectum, where cells have neuroepithelial properties, notch1a/1b/3 are expressed in most proliferating cells. However, in the cerebellar niche, although progenitors also have neuroepithelial properties, only notch1a/1b are expressed in a high number of PCNA [Formula: see text] cells. In this region notch3 expression is mostly in Bergmann glia and at low levels in few PCNA [Formula: see text] cells. Additionally, we found that in the proliferation zone of the ventral telencephalon, Notch receptors display an apical high to basal low gradient of expression. Notch receptors are also expressed in subpopulations of oligodendrocytes, neurons and endothelial cells. We suggest that the partial regional heterogeneity observed for Notch expression in progenitor cells might be related to the cellular diversity present in each of these neurogenic niches.

  20. Localization of receptors for bombesin-like peptides in the rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Moody, T.W.; Getz, R.; O' Donohue, T.L.; Rosenstein, J.M.

    1988-01-01

    BN-like peptides and receptors are present in discrete areas of the mammalian brain. By radioimmunoassay, endogenous BN/GRP, neuromedin B, and ranatensin-like peptides are present in the rat brain. High-to-moderate concentrations of BN/GRP are present in the rat hypothalamus and thalamus, whereas moderate-to-high densities of neuromedin B and ranatensin-like peptides are present in the olfactory bulb and hippocampus, as well as in the hypothalamus and thalamus. While the distribution of neuromedin B and ranatensin-like peptides appears similar, it is distinct from that of BN/GRP. When released from CNS neurons, these peptides may interact with receptors for BN-like peptides. BN, GRP, ranatensin, and neuromedin B inhibit specific (/sup 125/I-Tyr4)BN binding with high affinity. By use of in vitro autoradiographic techniques to detect binding of (/sup 125/I-Tyr4)BN to receptors for BN-like peptides, high grain densities were found in the olfactory bulb and tubercle, the nucleus accumbens, the suprachiasmatic and paraventricular nucleus of the hypothalamus, the central medial and paraventricular thalamic nuclei, the hippocampus, the dentate gyrus, and the amygdala of the rat brain. Some of these receptors may be biologically active and mediate the biological effects of BN-like peptides. For example, when BN is directly injected into the nucleus accumbens, pronounced grooming results and the effects caused by BN are reversed by spantide and (D-Phe12)BN. Thus, the putative BN receptor antagonists may serve as useful agents to investigate the biological significance of BN-like peptides in the CNS.

  1. The serotonin receptor 7 and the structural plasticity of brain circuits

    Science.gov (United States)

    Volpicelli, Floriana; Speranza, Luisa; di Porzio, Umberto; Crispino, Marianna; Perrone-Capano, Carla

    2014-01-01

    Serotonin (5-hydroxytryptamine, 5-HT) modulates numerous physiological processes in the nervous system. Together with its function as neurotransmitter, 5-HT regulates neurite outgrowth, dendritic spine shape and density, growth cone motility and synapse formation during development. In the mammalian brain 5-HT innervation is virtually ubiquitous and the diversity and specificity of its signaling and function arise from at least 20 different receptors, grouped in 7 classes. Here we will focus on the role 5-HT7 receptor (5-HT7R) in the correct establishment of neuronal cytoarchitecture during development, as also suggested by its involvement in several neurodevelopmental disorders. The emerging picture shows that this receptor is a key player contributing not only to shape brain networks during development but also to remodel neuronal wiring in the mature brain, thus controlling cognitive and emotional responses. The activation of 5-HT7R might be one of the mechanisms underlying the ability of the CNS to respond to different stimuli by modulation of its circuit configuration. PMID:25309369

  2. The serotonin receptor 7 and the structural plasticity of brain circuits

    Directory of Open Access Journals (Sweden)

    Floriana eVolpicelli

    2014-09-01

    Full Text Available Serotonin (5-hydroxytryptamine, 5-HT modulates numerous physiological processes in the nervous system. Together with its function as neurotrasmitter, 5-HT regulates neurite outgrowth, dendritic spine shape and density, growth cone motility and synapse formation during development. In the mammalian brain 5-HT innervation is virtually ubiquitous and the diversity and specificity of its signaling and function arise from at least 20 different receptors, grouped in 7 classes. Here we will focus on the role 5-HT7 receptor (5-HT7R in the correct establishment of neuronal cytoarchitecture during development, as also suggested by its involvement in several neurodevelopmental disorders. The emerging picture shows that this receptor is a key player contributing not only to shape brain networks during development but also to remodel neuronal wiring in the mature brain, thus controlling cognitive and emotional responses. The activation of 5-HT7R might be one of the mechanisms underlying the ability of the CNS to respond to different stimuli by modulation of its circuit configuration.

  3. Estradiol decreases cortical reactive astrogliosis after brain injury by a mechanism involving cannabinoid receptors.

    Science.gov (United States)

    López Rodríguez, Ana Belén; Mateos Vicente, Beatriz; Romero-Zerbo, Silvana Y; Rodriguez-Rodriguez, Noé; Bellini, María José; Rodriguez de Fonseca, Fernando; Bermudez-Silva, Francisco Javier; Azcoitia, Iñigo; Garcia-Segura, Luis M; Viveros, María-Paz

    2011-09-01

    The neuroactive steroid estradiol reduces reactive astroglia after brain injury by mechanisms similar to those involved in the regulation of reactive gliosis by endocannabinoids. In this study, we have explored whether cannabinoid receptors are involved in the effects of estradiol on reactive astroglia. To test this hypothesis, the effects of estradiol, the cannabinoid CB1 antagonist/inverse agonist AM251, and the cannabinoid CB2 antagonist/inverse agonist AM630 were assessed in the cerebral cortex of male rats after a stab wound brain injury. Estradiol reduced the number of vimentin immunoreactive astrocytes and the number of glial fibrillary acidic protein immunoreactive astrocytes in the proximity of the wound. The effect of estradiol was significantly inhibited by the administration of either CB1 or CB2 receptor antagonists. The effect of estradiol may be in part mediated by alterations in endocannabinoid signaling because the hormone increased in the injured cerebral cortex the messenger RNA levels of CB2 receptors and of some of the enzymes involved in the synthesis and metabolism of endocannabinoids. These findings suggest that estradiol may decrease reactive astroglia in the injured brain by regulating the activity of the endocannabinoid system.

  4. Phosphatase inhibitors remove the run-down of γ-aminobutyric acid type A receptors in the human epileptic brain

    Science.gov (United States)

    Palma, E.; Ragozzino, D. A.; Di Angelantonio, S.; Spinelli, G.; Trettel, F.; Martinez-Torres, A.; Torchia, G.; Arcella, A.; Di Gennaro, G.; Quarato, P. P.; Esposito, V.; Cantore, G.; Miledi, R.; Eusebi, F.

    2004-01-01

    The properties of γ-aminobutyric acid (GABA) type A receptors (GABAA receptors) microtransplanted from the human epileptic brain to the plasma membrane of Xenopus oocytes were compared with those recorded directly from neurons, or glial cells, in human brains slices. Cell membranes isolated from brain specimens, surgically obtained from six patients afflicted with drug-resistant temporal lobe epilepsy (TLE) were injected into frog oocytes. Within a few hours, these oocytes acquired GABAA receptors that generated GABA currents with an unusual run-down, which was inhibited by orthovanadate and okadaic acid. In contrast, receptors derived from membranes of a nonepileptic hippocampal uncus, membranes from mouse brain, or recombinant rat α1β2γ2-GABA receptors exhibited a much less pronounced GABA-current run-down. Moreover, the GABAA receptors of pyramidal neurons in temporal neocortex slices from the same six epileptic patients exhibited a stronger run-down than the receptors of rat pyramidal neurons. Interestingly, the GABAA receptors of neighboring glial cells remained substantially stable after repetitive activation. Therefore, the excessive GABA-current run-down observed in the membrane-injected oocytes recapitulates essentially what occurs in neurons, rather than in glial cells. Quantitative RT-PCR analyses from the same TLE neocortex specimens revealed that GABAA-receptor β1, β2, β3, and γ2 subunit mRNAs were significantly overexpressed (8- to 33-fold) compared with control autopsy tissues. Our results suggest that an abnormal GABA-receptor subunit transcription in the TLE brain leads to the expression of run-down-enhanced GABAA receptors. Blockage of phosphatases stabilizes the TLE GABAA receptors and strengthens GABAergic inhibition. It may be that this process can be targeted to develop new treatments for intractable epilepsy. PMID:15218107

  5. Simplified PET measurement for evaluating histamine H{sub 1} receptors in human brains using [{sup 11}C]doxepin

    Energy Technology Data Exchange (ETDEWEB)

    Mochizuki, Hideki [Department of Pharmacology, Tohoku University School of Medicine, Sendai, 980-8575 (Japan); Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Itabashi, Tokyo, 173-0022 (Japan); Kimura, Yuichi [Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Itabashi, Tokyo, 173-0022 (Japan)]. E-mail: ukimura@ieee.org; Ishii, Kenji [Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Itabashi, Tokyo, 173-0022 (Japan); Oda, Keiichi [Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Itabashi, Tokyo, 173-0022 (Japan); Sasaki, Toru [Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Itabashi, Tokyo, 173-0022 (Japan); Tashiro, Manabu [Department of Pharmacology, Tohoku University School of Medicine, Sendai, 980-8575 (Japan); Yanai, Kazuhiko [Department of Pharmacology, Tohoku University School of Medicine, Sendai, 980-8575 (Japan); Ishiwata, Kiichi [Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Itabashi, Tokyo, 173-0022 (Japan)

    2004-11-01

    The aim of this study was to develop simplified positron emission tomography measurement using [{sup 11}C]doxepin ([{sup 11}C]DOX) to evaluate histamine H{sub 1} receptors (H1Rs) in human brains. We evaluated the correlation between the distribution volume (DV) of [{sup 11}C]DOX, estimated quantitatively with a two-compartment model, and the [{sup 11}C]DOX uptake obtained at various time intervals and normalized using the metabolite-corrected plasma radioactivity. We found that the static 70- to 90-min images normalized using the plasma radioactivity at 10 min postinjection reflected the DV of [{sup 11}C]DOX-H1R binding.

  6. A D-peptide ligand of nicotine acetylcholine receptors for brain-targeted drug delivery.

    Science.gov (United States)

    Wei, Xiaoli; Zhan, Changyou; Shen, Qing; Fu, Wei; Xie, Cao; Gao, Jie; Peng, Chunmei; Zheng, Ping; Lu, Weiyue

    2015-03-01

    Lysosomes of brain capillary endothelial cells are implicated in nicotine acetylcholine receptor (nAChR)-mediated transcytosis and act as an enzymatic barrier for the transport of peptide ligands to the brain. A D-peptide ligand of nAChRs (termed (D)CDX), which binds to nAChRs with an IC50 value of 84.5 nM, was developed by retro-inverso isomerization. (D)CDX displayed exceptional stability in lysosomal homogenate and serum, and demonstrated significantly higher transcytosis efficiency in an in vitro blood-brain barrier monolayer compared with the parent L-peptide. When modified on liposomal surface, (D)CDX facilitated significant brain-targeted delivery of liposomes. As a result, brain-targeted delivery of (D)CDX modified liposomes enhanced therapeutic efficiency of encapsulated doxorubicin for glioblastoma. This study illustrates the importance of ligand stability in nAChRs-mediated transcytosis, and paves the way for developing stable brain-targeted entities.

  7. Blockage of transient receptor potential vanilloid 4 inhibits