RESUMEN

We report the near-edge x-ray absorption spectroscopy (NEXAFS) at the Co/Mn L(3,2) edge and oxygen K edge of the well-characterized Bi-substituted Co(2)MnO(4) multiferroic samples. The evolution of peak features in NEXAFS spectra of the Co/Mn L(3,2) edge and O K edge show the Bi-induced redistribution of magnetic cations (Co/Mn). The variation in valence states of Co and Mn in all the substituted compositions is consistent with the observed ferrimagnetic behaviour of the samples. Magnetization data show the decrease in molecular field complementing the ferrimagnetism. The role of Bi in the enhancement of magnetic interactions as well as the appearance of ferroelectricity in Bi(x)Co(2-x)MnO(4) (0≤x≤0.3) is discussed.

RESUMEN

UNLABELLED: This study evaluated the test-retest reproducibility of D2 receptor quantification in the thalamus and temporal cortex using [123I]epidepride SPECT. METHODS: Ten healthy volunteers (4 men, 6 women; age range, 19-46 y) underwent 2 SPECT studies (interval, 2-26 d) using a bolus-plus-constant-infusion paradigm (bolus-to-infusion ratio = 6 h; infusion time = 9 h). Plasma clearance (in liters per hour) and free fraction (f1) of the parent tracer were measured. Radioactivity (in becquerels per gram) in the thalamus, temporal cortex, and cerebellum were normalized to the infusion rate (in becquerels per hour). Normalized striatal radioactivity was also measured to assess reproducibility in regions with a high density of receptors and better counting statistics. The outcome measures obtained were V3 (receptor density [Bmax]/equilibrium dissociation constant [KD]), V3' (f1 x Bmax/KD), and RT (specific-to-nondisplaceable tissue ratio). RESULTS: Test-retest variability and reliability (intraclass correlation coefficient) were 10.8% and 0.88, respectively, for plasma clearance and 15.3% and 0.77, respectively, for f1. The test-retest variability of brain-specific (target minus nondisplaceable) radioactivity was higher in the thalamus and temporal cortex than in the striatum, although reliability was comparable. Among the outcome measures, V3' showed better test-retest variability and reliability in the thalamus (13.3% and 0.75, respectively) and temporal cortex (13.4% and 0.86, respectively). CONCLUSION: Brain radioactivity was the main source of variability for quantification of extrastriatal D2 receptors with [123I]epidepride. The reproducibility of outcome measures in extrastriatal regions was good. However, because receptor density was lower in extrastriatal regions than in the striatum, the counting statistics in these regions were low and reproducibility was affected by the higher test-retest variability of brain-specific radioactivity. Compared with V3 and V3', RT showed less test-retest variability in the thalamus and temporal cortex but lower reliability. Moreover, measurement of RT may be affected by the presence of potential lipophilic metabolites entering the brain.

Asunto(s)

Benzamidas/farmacocinética , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Radioisótopos de Yodo/farmacocinética , Pirrolidinas/farmacocinética , Receptores de Dopamina D2/análisis , Tomografía Computarizada de Emisión de Fotón Único/métodos , Adulto , Cerebelo/diagnóstico por imagen , Cerebelo/metabolismo , Femenino , Humanos , Cinética , Masculino , Persona de Mediana Edad , Especificidad de Órganos , Reproducibilidad de los Resultados , Lóbulo Temporal/diagnóstico por imagen , Lóbulo Temporal/metabolismo , Tálamo/diagnóstico por imagen , Tálamo/metabolismo

RESUMEN

UNLABELLED: The purpose of this study was to extend the graphical analysis of reversible tracer binding to account for labeled lipophilic metabolites (metabolites) in quantifying [123I]epidepride binding to striatal and extrastriatal D2 receptors and, additionally, to evaluate the feasibility of simplified analysis to measure the specific volume of distribution (V3') using single-sample blood data because the tissue ratio (RT) may be a less reliable measure of D2 binding in the presence of metabolites. METHODS: Multilinear regression analysis (MLRA) and graphical analysis (GA) using plasma parent (P) plus metabolite (M) activities as input and time activities of receptor-free (RF, cerebellum) and receptor-containing regions (RR, striatum and temporal cortex) derived V3' = (alpha(RR)(P) - alpha(RF)(P)), V3' = (1 + delta) (alpha(RR) - alpha(RF)) and RT = V3'/(V2P' + deltaV2M'), where alpha is a regression coefficient, delta is the equilibrium area ratio of M and P, and (V2P'/V2M') are the corresponding nondisplaceable distribution volumes. V3' by simplified analysis (SA) was calculated from RT determined without blood data and (V2P' + deltaV2M') with single-blood sample data. The accuracy of these three V3' values was assessed relative to the metabolite-accounted kinetic analysis (KA) for [123I]epidepride SPECT studies of 11 healthy volunteers, in which each participant had 27 scans and 30 plasma samples drawn during the 14 h after injection. RESULTS: All three V3' values (mL/g) significantly correlated with those by KA (r > or = 0.90) (striatum/temporal cortex: MLRA, 77.8 +/- 36.6/2.35 +/- 1.16; GA, 98.8 +/- 34.2/4.61 +/- 1.77; SA, 83.9 +/- 24.8/4.26 +/- 1.74; KA, 107.6 +/- 34.4/5.61 +/- 1.84). However, the correlation between RT and V3' was only moderate (r < or = 0.65) because of significant intersubject variability (23%) in (V2P' + deltaV2M'). CONCLUSION: The graphical analysis can be extended to account for metabolites in measuring D2 binding with [123I]epidepride SPECT for both high and low D2 density regions. Additionally, simplified V3' measurements with single blood sampling are feasible and may be a practical alternative to the tissue ratio RT because RT suffers as a measure of D2 binding from significant intersubject variability in the metabolite-contributed distribution volume of the nondisplaceable compartment.

Asunto(s)

Benzamidas , Encéfalo/diagnóstico por imagen , Radioisótopos de Yodo , Pirrolidinas , Receptores de Dopamina D2/análisis , Tomografía Computarizada de Emisión de Fotón Único , Adulto , Encéfalo/metabolismo , Medios de Contraste , Cuerpo Estriado/diagnóstico por imagen , Cuerpo Estriado/metabolismo , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Receptores de Dopamina D2/metabolismo , Análisis de Regresión

RESUMEN

PURPOSE: To evaluate effects of vigabatrin (VGB) by using [123I]iomazenil single-photon emission computed tomography (SPECT) to estimate central gamma-aminobutyric acid (GABA(A))/benzodiazepine receptors (BZRs), and magnetic resonance spectroscopy (MRS) to assess tissue GABA levels. METHODS: Six patients with partial seizures had both SPECT and MRS before and 25-84 days after starting VGB (3 g p.o., q.d.). SPECT was acquired by using the constant-infusion method and, after nonuniform attenuation correction, coregistered with T1-weighted MR Imaging (MRI) A volume of interest (VOI) of 3 x 2 x 2 cc over the occipital cortex, used for MRS acquisition, was positioned on both MRI and coregistered SPECT. Occipital activity was divided by either total plasma activity or plasma [123I]iomazenil concentration to estimate BZR distribution volume (V(T)-p and V'(T), respectively). Wilcoxon's test was used for VOI differences in GABA levels, BZR V(T)-p or V'(T). SPM96 (either no global normalization or proportional scaling) was used to compare BZR V(T)-p changes in the patients with and without VGB with test-retest data in eight healthy age-matched controls. RESULTS: Occipital GABA levels were increased threefold (without VGB, 1.1+/-0.1 micromol/g; with VGB, 2.9+/-0.5 micromol/g; p = 0.027). BZR distribution volumes showed no change, when estimated by either V(T)-p (without VGB, 6.00+/-0.91 ml/g; with VGB, 5.86+/-0.44 ml/g; p = 0.92) or V(T) (without VGB, 41.1+/-11.2 ml/g; with VGB, 41.2+/-9.9 ml/g; p = 0.75). No significant changes were detected by SPM96. CONCLUSIONS: A clinically effective dose of VGB caused a threefold increase in tissue GABA levels but was not associated with a substantial BZR downregulation.

Asunto(s)

Anticonvulsivantes/farmacología , Flumazenil/análogos & derivados , Espectroscopía de Resonancia Magnética , Lóbulo Occipital/química , Receptores de GABA/análisis , Receptores de GABA/efectos de los fármacos , Tomografía Computarizada de Emisión de Fotón Único/estadística & datos numéricos , Vigabatrin/farmacología , Adulto , Femenino , Humanos , Radioisótopos de Yodo , Masculino , Persona de Mediana Edad , Lóbulo Occipital/efectos de los fármacos , Lóbulo Occipital/metabolismo

RESUMEN

Quantitative SPECT measures of dopamine D(2) like receptors with [(123)I]epidepride is complicated by its high affinity and lipophilic metabolites. The purpose of this study was to use both parent (P) and lipophilic metabolites (M) as input functions in a kinetic paradigm and in comparison to the results of equilibrium studies. Kinetic studies on eleven healthy human subjects, ages 32+/- 10 were performed following i.v. injection of approximately 370 MBq of [(123)I]epidepride. Images were acquired for 13.5+/-1.0 hours. Equilibrium studies were done on seven of eleven subjects with a bolus injection of approximately 140 MBq, bolus/infusion ratio of 10 hours, and infusion for 30-32 hours. High (striatum) and low (temporal cortex) density regions were studied. Two (P and M) and one (P) input function models were applied in the kinetic studies. In receptor-rich regions, the distribution volumes in nondisplaceable compartments were fixed to those in cerebellum. In addition, in the two input function model, K(1)(P)/K(1)(M) was fixed to the values in the cerebellum. The one input function model provided V'(3) values (=f(1)*B'(max)/K(D)) which were consistent with those obtained in equilibrium studies in both receptor-rich regions, while the two input function model provided consistent values only in striatum. Poor identifiability of the rate constants of metabolites seemed to be the source of errors in the two input function model. These results suggest that correct V'(3) values can be obtained with the one input function model both in high- and low-density regions.

Asunto(s)

Benzamidas/metabolismo , Neostriado/metabolismo , Pirrolidinas/metabolismo , Receptores de Dopamina D2/metabolismo , Lóbulo Temporal/metabolismo , Adulto , Benzamidas/administración & dosificación , Benzamidas/sangre , Benzamidas/farmacocinética , Cerebelo/metabolismo , Femenino , Humanos , Cinética , Masculino , Matemática , Modelos Biológicos , Pirrolidinas/administración & dosificación , Pirrolidinas/sangre , Pirrolidinas/farmacocinética , Termodinámica , Factores de Tiempo

RESUMEN

Changes of central type GABA(A)/benzodiazepine receptors during 24-day per-oral administration of alprazolam (2 mg/day) were measured with single photon emission computed tomography (SPECT) in nine healthy human subjects. Receptor densities were measured on days -4 (baseline), 3, 10, 17 and 24. Comparison of baseline and day 3 SPECT images was used to assess receptor occupancy; comparisons of the four scans on medication were used to assess alterations in receptor levels. Clinical effects were evaluated by subjective ratings of mood and the Hopkins verbal learning test. Alprazolam induced sedation associated with a 16% receptor occupancy. Unoccupied receptor levels decreased 10% from day 3 to day 10 but then normalized to baseline values by day 17. Clinical effects showed corresponding changes 1-2 weeks after the changes in the receptor. Thus, the decrease of benzodiazepine receptor densities may be one of the major mechanisms for tolerance development in humans.

Asunto(s)

Alprazolam/farmacología , Ansiolíticos/farmacología , Receptores de GABA-A/metabolismo , Administración Oral , Adulto , Alprazolam/sangre , Alprazolam/farmacocinética , Ansiolíticos/farmacocinética , Femenino , Flumazenil/análogos & derivados , Flumazenil/farmacocinética , Humanos , Radioisótopos de Yodo , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Receptores de GABA-A/efectos de los fármacos , Reproducibilidad de los Resultados , Tomografía Computarizada de Emisión de Fotón Único , Resultado del Tratamiento , Aprendizaje Verbal/efectos de los fármacos

RESUMEN

Deficient inhibitory neurotransmission of gamma-aminobutyric acid (GABA) has been implicated in the pathophysiology of schizophrenia based on postmortem studies. However, in vivo studies have shown predominantly negative or conflicting results. The goal of this study was to better characterize possible changes of the regional GABA(A)-benzodiazepine receptor distribution volume (BZR V3-p) in schizophrenia in vivo, using a larger sample size than previous studies. Single photon emission computed tomography (SPECT) with [123I]iomazenil was used with a constant infusion paradigm to measure the BZR V3-p under sustained radiotracer equilibrium conditions. Twenty-five patients with schizophrenia and 24 matched healthy control subjects were studied. Positive and Negative Syndrome Scale (PANSS) ratings were done in all subjects. Statistical parametric mapping (SPM) 96 was used to compare patients and control subjects as well as to study the relationship between SPECT results and composite PANSS scores based on two factorial models: the pentagonal model (positive, negative, dysphoric mood, activation, and autistic preoccupation factors) and the taxometric model (disorganized dimension). On the basis of 'absolute' values of V3-p with no normalization for total brain uptake, the schizophrenic patients showed no significant differences in BZR levels compared to the healthy control subjects. With a global normalization procedure, which is more sensitive to relative regional differences in activity, BZR V3-p was significantly decreased in the patients in the left precentral gyrus (BA 6). The relative BZR V3-p showed a significant positive correlation with duration of illness in the superior occipital gyri (BA 19). No significant correlations were observed between either absolute or relative BZR V3-p and either age or any of the composite PANSS scores based on any of the two factorial models in either patients or control subjects. No significant differences were observed between cigarette smoking vs. non-smoking patients, nor between the patients on atypical antipsychotics vs. on typical antipsychotics vs. not on any antipsychotics. In general, no significant differences in BZR V3-p were observed between patients and control subjects, except for a decrease in relative BZR V3-p in the left precentral gyrus. Grey matter atrophy is unlikely to be the cause for this decrease. However, we could not exclude that possibility. The positive correlation with duration of illness might reflect the relative preservation of neurons expressing BZR in the superior occipital gyri as compared to other cortical brain regions in schizophrenia.

Asunto(s)

Encéfalo/diagnóstico por imagen , Flumazenil/análogos & derivados , Receptores de GABA-A/fisiología , Esquizofrenia/diagnóstico por imagen , Tomografía Computarizada de Emisión de Fotón Único , Adulto , Encéfalo/fisiopatología , Mapeo Encefálico , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/fisiopatología , Dominancia Cerebral/fisiología , Femenino , Lóbulo Frontal/diagnóstico por imagen , Lóbulo Frontal/fisiopatología , Humanos , Radioisótopos de Yodo , Masculino , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica , Esquizofrenia/fisiopatología

RESUMEN

BACKGROUND: Prior research has suggested reductions in the density of serotonin transporter (SERT) binding sites in blood platelets and post-mortem brain tissue of depressed patients. We sought to determine whether patients with unipolar major depression have diminished SERT availability as assessed by both brainstem [123I] beta-CIT SPECT and platelet [3H]paroxetine binding. METHODS: Drug-free depressed and healthy subjects were injected with 211 +/- 22 MBq [123I] beta-CIT and imaged 24 +/- 2 h later under equilibrium conditions. A ratio of specific to nonspecific brain uptake (V3" = (brainstem-occipital)/occipital), a measure proportional to the binding potential (Bmax/Kd), was used for all comparisons. RESULTS: Results showed a statistically significant reduction in brainstem V3" values in depressed as compared to healthy subjects (3.1 +/- .9 vs. 3.8 +/- .8, p = .02). Platelet [3H]paroxetine binding was not altered (Bmax = 2389 +/- 484 vs. 2415 +/- 538 fmol/mg protein, p = .91) and was not significantly correlated with brainstem [123I] beta-CIT binding (r = -0.14, p = .48). CONCLUSIONS: These data are the first to suggest reductions in the density of brain SERT binding sites in living depressed patients. These findings provide further support for a preeminent role for alterations in serotonergic neurons in the pathophysiology of depression.

Asunto(s)

Antidepresivos/farmacocinética , Encéfalo/diagnóstico por imagen , Encéfalo/fisiopatología , Proteínas Portadoras/fisiología , Cocaína/análogos & derivados , Trastorno Depresivo/diagnóstico , Trastorno Depresivo/fisiopatología , Glicoproteínas de Membrana/fisiología , Proteínas de Transporte de Membrana , Proteínas del Tejido Nervioso , Serotonina/fisiología , Tomografía Computarizada de Emisión de Fotón Único , Adulto , Antidepresivos/uso terapéutico , Tronco Encefálico/fisiopatología , Cocaína/farmacocinética , Cocaína/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Paroxetina/sangre , Escalas de Valoración Psiquiátrica , Proteínas de Transporte de Serotonina en la Membrana Plasmática

RESUMEN

OBJECTIVE: Alterations in cortical benzodiazepine receptor density have been described in postmortem and in vivo studies of alcoholic subjects. The authors attempted to replicate these findings using single photon emission computed tomography and the benzodiazepine receptor radiotracer [123I]iomazenil. METHOD: They measured the distribution volume of benzodiazepine receptors in 11 recently detoxified patients with type II alcoholism and 11 healthy comparison subjects. The tracer was given as a bolus followed by a continuous infusion to achieve sustained binding equilibrium at the benzodiazepine receptors. Data were analyzed by using a region of interest method (regions of interest were identified on coregistered magnetic resonance imaging scans) and by a pixel-by-pixel method (distribution volume maps were analyzed with statistical parametric mapping for between-group differences). RESULTS: The region of interest analysis revealed that alcoholic patients had significantly lower benzodiazepine distribution volume than comparison subjects in the frontal, anterior cingulate, and cerebellar cortices. Statistical parametric mapping revealed two large excursions in which the distribution volume in alcoholic patients was significantly lower than in comparison subjects: the anterior cingulate, extending into the right middle frontal gyrus, and the left occipital cortex. CONCLUSIONS: Benzodiazepine receptor distribution volume is significantly lower in several cortical regions and the cerebellum in alcoholic subjects than in healthy comparison subjects. These results are consistent with previous reports and might indicate either a toxic effect of alcoholism on benzodiazepine receptors or a vulnerability factor for developing alcoholism.

Asunto(s)

Alcoholismo/diagnóstico por imagen , Alcoholismo/metabolismo , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Flumazenil/análogos & derivados , Receptores de GABA-A/metabolismo , Tomografía Computarizada de Emisión de Fotón Único , Adulto , Alcoholismo/patología , Encéfalo/patología , Cerebelo/diagnóstico por imagen , Cerebelo/metabolismo , Cerebelo/patología , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/metabolismo , Corteza Cerebral/patología , Lóbulo Frontal/diagnóstico por imagen , Lóbulo Frontal/metabolismo , Lóbulo Frontal/patología , Giro del Cíngulo/diagnóstico por imagen , Giro del Cíngulo/metabolismo , Giro del Cíngulo/patología , Humanos , Procesamiento de Imagen Asistido por Computador , Radioisótopos de Yodo , Imagen por Resonancia Magnética , Masculino , Receptores de GABA-A/genética , Receptores de GABA-A/fisiología , Factores de Riesgo

RESUMEN

UNLABELLED: The purposes of this study were to develop a method for nonuniform attenuation correction of 123I emission brain images based on transmission imaging with a longer-lived isotope (i.e., 57Co) and to evaluate the relative improvement in quantitative SPECT images achieved with nonuniform attenuation correction. METHODS: Emission and transmission SPECT scans were acquired on three different sets of studies: a heterogeneous brain phantom filled with 1231 to simulate the distribution of dopamine transporters labeled with 2beta-carbomethoxy-3beta-(4-123I-iodophenyl)tropane (123I-beta-CIT); nine healthy human control subjects who underwent transmission scanning using two separate line sources (57Co and 123I); and a set of eight patients with Parkinson's disease and five healthy control subjects who received both emission and transmission scans after injection of 123I-beta-CIT. Attenuation maps were reconstructed using a Bayesian transmission reconstruction algorithm, and attenuation correction was performed using Chang's postprocessing method. The spatial distribution of errors within the brain was obtained from attenuation correction factors computed from uniform and nonuniform attenuation maps and was visualized on a pixel-by-pixel basis as an error image. RESULTS: For the heterogeneous brain phantom, the uniform attenuation correction had errors of 2%-6.5% for regions corresponding to striatum and background, whereas nonuniform attenuation correction was within 1%. Analysis of 123I transmission images of the nine healthy human control subjects showed differences between uniform and nonuniform attenuation correction to be in the range of 6.4%-16.0% for brain regions of interest (ROIs). The human control subjects who received transmission scans only were used to generate a curvilinear function to convert 57Co attenuation values into those for 123I, based on a pixel-by-pixel comparison of two coregistered transmission images for each subject. These values were applied to the group of patients and healthy control subjects who received transmission 57Co scans and emission 123I scans after injection of 123I-beta-CIT. In comparison to nonuniform attenuation correction as the gold standard, uniform attenuation with the ellipse drawn around the transmission image caused an approximately 5% error, whereas placement of the ellipse around the emission image caused a 15% error. CONCLUSION: Nonuniform attenuation correction allowed a moderate improvement in the measurement of absolute activity in individual brain ROIs. When images were analyzed as target-to-background activity ratios, as is commonly performed with 123I-beta-CIT, these outcome measures showed only small differences when Parkinson's disease patients and healthy control subjects were compared using nonuniform, uniform or even no attenuation correction.

Asunto(s)

Encéfalo/diagnóstico por imagen , Enfermedad de Parkinson/diagnóstico por imagen , Tomografía Computarizada de Emisión de Fotón Único/métodos , Adulto , Estudios de Casos y Controles , Radioisótopos de Cobalto , Cocaína/análogos & derivados , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Inmovilización , Radioisótopos de Yodo , Masculino , Persona de Mediana Edad , Fantasmas de Imagen

Asunto(s)

Antiinflamatorios/uso terapéutico , Glucocorticoides/uso terapéutico , Granuloma de Células Gigantes/tratamiento farmacológico , Enfermedades Mandibulares/tratamiento farmacológico , Triamcinolona Acetonida/uso terapéutico , Adolescente , Antiinflamatorios/administración & dosificación , Regeneración Ósea/efectos de los fármacos , Femenino , Estudios de Seguimiento , Glucocorticoides/administración & dosificación , Humanos , Inyecciones Intralesiones , Diente Molar , Triamcinolona Acetonida/administración & dosificación

RESUMEN

A new class of fast maximum-likelihood estimation (MLE) algorithms for emission computed tomography (ECT) is developed. In these cyclic iterative algorithms, vector extrapolation techniques are integrated with the iterations in gradient-based MLE algorithms, with the objective of accelerating the convergence of the base iterations. This results in a substantial reduction in the effective number of base iterations required for obtaining an emission density estimate of specified quality. The mathematical theory behind the minimal polynomial and reduced rank vector extrapolation techniques, in the context of emission tomography, is presented. These extrapolation techniques are implemented in a positron emission tomography system. The new algorithms are evaluated using computer experiments, with measurements taken from simulated phantoms. It is shown that, with minimal additional computations, the proposed approach results in substantial improvement in reconstruction.