RESUMEN
OBJECTIVES: We hypothesize that the combined use of MRI cortical thickness measurement and subcortical gray matter volumetry could provide an early and accurate in vivo assessment of the structural impact of cardiac arrest and therefore could be used for long-term neuroprognostication in this setting. DESIGN: Prospective cohort study. SETTING: Five Intensive Critical Care Units affiliated to the University in Toulouse (France), Paris (France), Clermont-Ferrand (France), Liège (Belgium), and Monza (Italy). PATIENTS: High-resolution anatomical T1-weighted images were acquired in 126 anoxic coma patients ("learning" sample) 16 ± 8 days after cardiac arrest and 70 matched controls. An additional sample of 18 anoxic coma patients, recruited in Toulouse, was used to test predictive model generalization ("test" sample). All patients were followed up 1 year after cardiac arrest. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Cortical thickness was computed on the whole cortical ribbon, and deep gray matter volumetry was performed after automatic segmentation. Brain morphometric data were employed to create multivariate predictive models using learning machine techniques. Patients displayed significantly extensive cortical and subcortical brain volumes atrophy compared with controls. The accuracy of a predictive classifier, encompassing cortical and subcortical components, has a significant discriminative power (learning area under the curve = 0.87; test area under the curve = 0.96). The anatomical regions which volume changes were significantly related to patient's outcome were frontal cortex, posterior cingulate cortex, thalamus, putamen, pallidum, caudate, hippocampus, and brain stem. CONCLUSIONS: These findings are consistent with the hypothesis of pathologic disruption of a striatopallidal-thalamo-cortical mesocircuit induced by cardiac arrest and pave the way for the use of combined brain quantitative morphometry in this setting.
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Encéfalo/diagnóstico por imagen , Encéfalo/patología , Paro Cardíaco/patología , Adulto , Corteza Cerebelosa/diagnóstico por imagen , Corteza Cerebelosa/patología , Coma/diagnóstico por imagen , Coma/patología , Femenino , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/patología , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Pronóstico , Estudios ProspectivosRESUMEN
We previously showed that the farnesyl transferase inihibitor, Tipifarnib induced vascularization normalization, oxygenation and radiosensitization in a pre-clinical glioblastoma (GBM) model. The aim of this study was to assess by dynamic-susceptibility-contrast MRI (DSC-MRI) the effect of radiotherapy (RT) and Tipifarnib combination on tumor perfusion in GBM patients. Eighteen patients with newly diagnosed GBM, enrolled in a phase I-II clinical trial associating RT with Tipifarnib, underwent anatomical MR imaging and DSC-MRI before (M0) and two months after treatment (M2). Anatomic volumes of interest (VOIs) were delineated according to contrast-enhanced and hyper-intense signal areas on T1-Gd and T2 images, respectively. Perfusion variations between M0 and M2 were assessed with median relative cerebral blood volume (rCBV) inside these VOIs. Another voxel by voxel analysis of CBV values classified 405,117 tumor voxels into High_, Normal_ and Low_CBVTUMOR according to the distribution of CBV in the contralateral normal tissue. These three categories of CBVTUMOR voxels were color-coded over anatomical MRI. Variations of median rCBV were significantly different for two groups of patients (P < 0.013): rCBV decreased when initial rCBV was ≥ 1.0 (Group_rCBV_M0 > 1) and rCBV increased when initial rCBV was < 1.0 (Group_rCBV_M0 < 1). Mapping of color-coded voxels provided additional spatial and quantitative information about tumor perfusion: Group_rCBV_M0 > 1 presented a significant decrease of High_CBVTUMOR volume (P = 0.015) simultaneously with a significant increase of Normal_CBVTUMOR volume (P = 0.009) after treatment. Group_rCBV_M0 < 1 presented a decrease of Low_CBVTUMOR volume with an increase of Normal_ and High_CBV TUMOR volume after treatment. Pre and post-treatment CBV measurements with DSC-MRI characterized tumor perfusion evolution in GBM patients treated with RT combined to Tipifarnib; showing variations in favour of tumor perfusion normalization in agreement with our pre-clinical results of vascular normalization.
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Antineoplásicos/uso terapéutico , Neoplasias Encefálicas/terapia , Glioblastoma/terapia , Quinolonas/uso terapéutico , Radioterapia/métodos , Adulto , Anciano , Circulación Cerebrovascular , Medios de Contraste , Femenino , Estudios de Seguimiento , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: Structural gray matter characteristics of anxiety remain unclear. The aim of this study was to assess the influence of current depressive symptoms and history of depression on the gray matter characteristics of trait anxiety. METHODS: Structural magnetic resonance imaging (MRI) data from 393 individuals aged 65 years or older were used. Regions of interest (ROIs) included the amygdala, anterior cingulate cortex (ACC), insula, orbitofrontal cortex (OFC), and temporal cortex. Trait anxiety was measured by the State-Trait Anxiety Inventory (STAI). Depression and depressive symptoms were measured using DSM-IV criteria and the Center for Epidemiological Studies Depression Scale (CESD). RESULTS: After adjustments for sociodemographics and health-related variables, anxiety had a significant influence on the gray matter characteristics in all cortical ROIs. First, in participants without depression antecedents, higher trait anxiety was associated with a larger cortical thickness in all cortical ROIs. Second, in participants with a previous history of depression, higher trait anxiety was associated with a smaller cortical thickness in all cortical ROIs. CONCLUSIONS: These results suggest that anxiety is related to cortical thickness differently in healthy older adults and in older adults with psychiatric antecedents. Anxiety associated with thinner cortical areas could reflect symptoms of a specific type of depression or a vulnerability to develop depression.
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Ansiedad/patología , Encéfalo/patología , Depresión/patología , Anciano , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Neuroimagen , Escalas de Valoración PsiquiátricaRESUMEN
One the one hand, capillary permeability to water is a well-defined concept in microvascular physiology, and linearly relates the net convective or diffusive mass fluxes (by unit area) to the differences in pressure or concentration, respectively, that drive them through the vessel wall. On the other hand, the permeability coefficient is a central parameter introduced when modeling diffusible tracers transfer from blood vessels to tissue in the framework of compartmental models, in such a way that it is implicitly considered as being identical to the capillary permeability. Despite their simplifying assumptions, such models are at the basis of blood flow quantification by H2(15)O Positron Emission Tomgraphy. In the present paper, we use fluid dynamic modeling to compute the transfers of H2(15)O between the blood and brain parenchyma at capillary scale. The analysis of the so-obtained kinetic data by the Renkin-Crone model, the archetypal compartmental model, demonstrates that, in this framework, the permeability coefficient is highly dependent on both flow rate and capillary radius, contrarily to the central hypothesis of the model which states that it is a physiological constant. Thus, the permeability coefficient in Renkin-Crone׳s model is not conceptually identical to the physiologic permeability as implicitly stated in the model. If a permeability coefficient is nevertheless arbitrarily chosen in the computed range, the flow rate determined by the Renkin-Crone model can take highly inaccurate quantitative values. The reasons for this failure of compartmental approaches in the framework of brain blood flow quantification are discussed, highlighting the need for a novel approach enabling to fully exploit the wealth of information available from PET data.
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Capilares/diagnóstico por imagen , Capilares/fisiología , Permeabilidad Capilar/fisiología , Circulación Cerebrovascular/fisiología , Modelos Biológicos , Tomografía de Emisión de Positrones , Agua/metabolismo , Humanos , Cinética , Análisis Numérico Asistido por Computador , Radioisótopos de Oxígeno , Estándares de ReferenciaRESUMEN
One objective of modern neuroimaging is to identify markers that can aid in diagnosis, disease progression monitoring and long-term drug impact analysis. In this study, Parkinson-associated physiopathological modifications were characterized in six subcortical structures by simultaneously measuring quantitative magnetic resonance parameters sensitive to complementary tissue characteristics (i.e. volume atrophy, iron deposition and microstructural damage). Thirty patients with Parkinson's disease and 22 control subjects underwent 3-T magnetic resonance imaging with T2*-weighted, whole-brain T1-weighted and diffusion tensor imaging scans. The mean R2* value, mean diffusivity and fractional anisotropy in the pallidum, putamen, caudate nucleus, thalamus, substantia nigra and red nucleus were compared between patients with Parkinson's disease and control subjects. Comparisons were also performed using voxel-based analysis of R2*, mean diffusivity and fractional anisotropy maps to determine which subregion of the basal ganglia showed the greater difference for each parameter. Averages of each subregion were then used in a logistic regression analysis. Compared with control subjects, patients with Parkinson's disease displayed significantly higher R2* values in the substantia nigra, lower fractional anisotropy values in the substantia nigra and thalamus, and higher mean diffusivity values in the thalamus. Voxel-based analyses confirmed these results and, in addition, showed a significant difference in the mean diffusivity in the striatum. The combination of three markers was sufficient to obtain a 95% global accuracy (area under the receiver operating characteristic curve) for discriminating patients with Parkinson's disease from controls. The markers comprising discriminating combinations were R2* in the substantia nigra, fractional anisotropy in the substantia nigra and mean diffusivity in the putamen or caudate nucleus. Remarkably, the predictive markers involved the nigrostriatal structures that characterize Parkinson's physiopathology. Furthermore, highly discriminating combinations included markers from three different magnetic resonance parameters (R2*, mean diffusivity and fractional anisotropy). These findings demonstrate that multimodal magnetic resonance imaging of subcortical grey matter structures is useful for the evaluation of Parkinson's disease and, possibly, of other subcortical pathologies.
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Cuerpo Estriado/patología , Imagen por Resonancia Magnética , Enfermedad de Parkinson/patología , Sustancia Negra/patología , Anciano , Biomarcadores , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/fisiopatologíaRESUMEN
Skin-brain signalling in itch reactions has been demonstrated with neuroimaging techniques showing specific brain activation. With positron emission tomography (PET), the itch model used must be adapted to technical and practical constraints. The technique of itch induction by histamine iontophoresis enables modulation of the sensation via the electrical charge applied. This itch model was validated on normal forearm skin of 56 subjects, with itch visual analogue scores peaking to approximately 1.0 cm after 3-4 min, falling to 0.2 cm at 15 min, with no influence of sex, zone, or order. Subsequently, the model was used in a PET study on 14 male volunteers, comparing histamine with physiological saline (control). The results show that the brain is able to discriminate these two conditions, with activated areas similar to those described previously, with, in addition, the anterior cingulate cortex and the insula being positively correlated with the intensity of the sensation.
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Mapeo Encefálico/métodos , Encéfalo/diagnóstico por imagen , Histamina/administración & dosificación , Iontoforesis , Prurito/inducido químicamente , Prurito/diagnóstico por imagen , Administración Cutánea , Adulto , Análisis de Varianza , Discriminación en Psicología , Femenino , Antebrazo , Francia , Humanos , Masculino , Tomografía de Emisión de Positrones , Valor Predictivo de las Pruebas , Prurito/psicología , Reproducibilidad de los Resultados , Índice de Severidad de la EnfermedadRESUMEN
Brain atrophy measured by magnetic resonance structural imaging has been proposed as a surrogate marker for the early diagnosis of Alzheimer's disease. Studies on large samples are still required to determine its practical interest at the individual level, especially with regards to the capacity of anatomical magnetic resonance imaging to disentangle the confounding role of the cognitive reserve in the early diagnosis of Alzheimer's disease. One hundred and thirty healthy controls, 122 subjects with mild cognitive impairment of the amnestic type and 130 Alzheimer's disease patients were included from the ADNI database and followed up for 24 months. After 24 months, 72 amnestic mild cognitive impairment had converted to Alzheimer's disease (referred to as progressive mild cognitive impairment, as opposed to stable mild cognitive impairment). For each subject, cortical thickness was measured on the baseline magnetic resonance imaging volume. The resulting cortical thickness map was parcellated into 22 regions and a normalized thickness index was computed using the subset of regions (right medial temporal, left lateral temporal, right posterior cingulate) that optimally distinguished stable mild cognitive impairment from progressive mild cognitive impairment. We tested the ability of baseline normalized thickness index to predict evolution from amnestic mild cognitive impairment to Alzheimer's disease and compared it to the predictive values of the main cognitive scores at baseline. In addition, we studied the relationship between the normalized thickness index, the education level and the timeline of conversion to Alzheimer's disease. Normalized thickness index at baseline differed significantly among all the four diagnosis groups (P < 0.001) and correctly distinguished Alzheimer's disease patients from healthy controls with an 85% cross-validated accuracy. Normalized thickness index also correctly predicted evolution to Alzheimer's disease for 76% of amnestic mild cognitive impairment subjects after cross-validation, thus showing an advantage over cognitive scores (range 63-72%). Moreover, progressive mild cognitive impairment subjects, who converted later than 1 year after baseline, showed a significantly higher education level than those who converted earlier than 1 year after baseline. Using a normalized thickness index-based criterion may help with early diagnosis of Alzheimer's disease at the individual level, especially for highly educated subjects, up to 24 months before clinical criteria for Alzheimer's disease diagnosis are met.
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Enfermedad de Alzheimer/diagnóstico , Corteza Cerebral/patología , Trastornos del Conocimiento/etiología , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/patología , Enfermedad de Alzheimer/psicología , Mapeo Encefálico/métodos , Trastornos del Conocimiento/psicología , Estudios Transversales , Progresión de la Enfermedad , Diagnóstico Precoz , Escolaridad , Femenino , Estudios de Seguimiento , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Pruebas Neuropsicológicas , PronósticoRESUMEN
It is suggested that resting state networks reflecting correlated neural regional activities participate significantly in brain functioning. A fundamental issue is to understand how these networks interact and how their activities change during behavioral transitions. Our aim was to understand better with functional MRI connectivity how the brain switched from a "resting" to a movement-related state by exploring the transitory readiness state for an intended movement of the right hand. Our study does not address movement preparation occurring in a time scale of milliseconds before movement which has been widely studied but movement-readiness which can last longer. At rest, in the absence of overt goal-directed behavior, a "default-mode" network, whose main areas are the posterior cingulate cortex and precuneus (PCC/Pcu), shows high activity interpreted as day dreaming, free association, stream of consciousness, and inner rehearsal. We found that, during rest, the "default-mode" network and the sensorimotor network were not functionally correlated. During movement-readiness, the two networks were functionally correlated through an interaction between the PCC/Pcu and the medial superior parietal cortex in the upper precuneus. The complex PCC/Pcu has been shown to be involved in retrieval and/or setting up spatial attributes for motor imagery, and thus, would be a key region in the movement-readiness phase. It might functionally connect to the medial superior parietal cortex to initiate the movement programming through retrieval of suited movement parameters. The anterior cingulum, functionally correlated to the primary sensorimotor cortex during movement-readiness would have a motivational role or could generate predictions about the movement.
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Encéfalo/fisiología , Actividad Motora/fisiología , Descanso/fisiología , Adulto , Mapeo Encefálico , Femenino , Giro del Cíngulo/fisiología , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Modelos Neurológicos , Corteza Motora/fisiología , Lóbulo Parietal/fisiología , Corteza Somatosensorial/fisiología , Adulto JovenRESUMEN
Magnetic resonance imaging (MRI) studies have highlighted the possibility to investigate brain iron content in vivo. In this study, we combined T2* relaxometry and automatic segmentation of basal ganglia based on T1-weighted images in healthy subjects, with the aim of characterizing age related changes in volume and iron-related relaxivity values (R2*) of these structures. Thirty healthy subjects underwent MR imaging at 3 Tesla. Mean R2* values and volumes were calculated for the selected subcortical structures (pallidum, putamen, thalamus and caudate nucleus). Our results showed a correlation between R2* values and iron concentration as calculated from published post-mortem data. Furthermore, we observed a shrinkage/iron increase with a different pattern in the anatomical regions selected in this work, suggesting that the age-related changes on these MR parameters are specific to the subcortical structure considered. In particular, the putamen demonstrated a decrease of volume and an increase of iron level, with the posterior region of this structure appearing more disposed to iron deposition. Our work suggests that combining volumetry and iron estimation in MRI permits to investigate in vivo neurophysiological and neuropathological changes of basal ganglia.
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Ganglios Basales/anatomía & histología , Ganglios Basales/química , Hierro/análisis , Tálamo/anatomía & histología , Tálamo/química , Adulto , Envejecimiento , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Análisis Multivariante , Tamaño de los Órganos , Putamen/anatomía & histología , Putamen/química , Adulto JovenRESUMEN
Neuroimaging studies of reading converge to suggest that linguistically elementary stimuli are confined to the activation of bilateral posterior regions, whereas linguistically complex stimuli additionally recruit left hemispheric anterior regions, raising the hypotheses of a gradual bilateral-to-left and a posterior-to-anterior recruitment of reading related areas. Here, we tested these two hypotheses by contrasting a repertoire of eight categories of stimuli ranging from simple orthographic-like characters to words and pseudowords in a single experiment, and by measuring BOLD signal changes and connectivity while 16 fluent readers passively viewed the stimuli. Our results confirm the existence of a bilateral-to-left and posterior-to-anterior recruitment of reading related areas, straightforwardly resulting from the increase in stimuli's linguistic processing load, which reflects reading processes: visual analysis, orthographic encoding and phonological decoding. Connectivity analyses strengthened the validity of these observations and additionally revealed an enhancement of the left parieto-frontal information trafficking for higher linguistic processing. Our findings clearly establish the notion of a gradual spatio-functional recruitment of reading areas and demonstrate, to the best of our knowledge, the first evidence of a robust and staged link between the level of linguistic processing, the spatial distribution of brain activity and its information trafficking.
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Mapeo Encefálico , Encéfalo/fisiología , Lateralidad Funcional/fisiología , Lectura , Adulto , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Reconocimiento Visual de Modelos/fisiologíaRESUMEN
The T1 head template model used in Statistical Parametric Mapping Version 2000 (SPM2), was segmented into five layers (scalp, skull, CSF, grey and white matter) and implemented in 2 mm voxels. We designed a resistor mesh model (RMM), based on the finite volume method (FVM) to simulate the electrical properties of this head model along the three axes for each voxel. Then, we introduced four dipoles of high eccentricity (about 0.8) in this RMM, separately and simultaneously, to compute the potentials for two sets of conductivities. We used the direct cortical imaging technique (CIT) to recover the simulated dipoles, using 60 or 107 electrodes and with or without addition of Gaussian white noise (GWN). The use of realistic conductivities gave better CIT results than standard conductivities, lowering the blurring effect on scalp potentials and displaying more accurate position areas when CIT was applied to single dipoles. Simultaneous dipoles were less accurately localized, but good qualitative and stable quantitative results were obtained up to 5% noise level for 107 electrodes and up to 10% noise level for 60 electrodes, showing that a compromise must be found to optimize both the number of electrodes and the noise level. With the RMM defined in 2 mm voxels, the standard 128-electrode cap and 5% noise appears to be the upper limit providing reliable source positions when direct CIT is used. The admittance matrix defining the RMM is easy to modify so as to adapt to different conductivities. The next step will be the adaptation of individual real head T2 images to the RMM template and the introduction of anisotropy using diffusion imaging (DI).
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Algoritmos , Mapeo Encefálico/métodos , Corteza Cerebral/fisiología , Cráneo/fisiología , Encéfalo/anatomía & histología , Encéfalo/fisiología , Diagnóstico por Imagen/métodos , Impedancia Eléctrica , Electroencefalografía/métodos , Electrofisiología/métodos , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Modelos Anatómicos , Modelos Neurológicos , Modelos Estadísticos , Reproducibilidad de los Resultados , Cuero Cabelludo/anatomía & histología , Cuero Cabelludo/fisiología , Cráneo/anatomía & histologíaRESUMEN
Whereas many studies have considered the role of attention in prospective timing, fewer have established relations between movement complexity and prospective timing. The present study aims at assessing to what extent motion complexity interferes with prospective timing and at delineating a neuropsychophysical plausible model. We have thus designed a visual paradigm presenting stimuli in sequential pairs (reference comparison interval). Stimuli are motionless or moving according to different complexities, and stimulus complexities are intermixed within each pair. To prevent a possible attention-sharing effect, no concurrent task was required. Our study suggests that movement complexity is a key component of duration perception, and that the relative judgement of durations depends on spatio-temporal features of stimuli. In particular, it shows that movement complexity can bias subjects' perception and performance, and that subjects detect that comparison intervals are longer than reference before their end. In the discussion, we advocate that the classical internal clock model cannot easily account for our results. Consequently, we propose a model for time perception, based on a parallel processing between comparison interval perception and the reconstruction of the reference duration.
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Percepción de Movimiento , Estimulación Luminosa , Percepción del Tiempo/fisiología , Adolescente , Adulto , Anciano , Discriminación en Psicología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos Psicológicos , Análisis Multivariante , Psicofísica , Tiempo de Reacción/fisiologíaRESUMEN
Functional magnetic resonance imaging (fMRI) using paced auditory serial addition test (PASAT) as paradigm was used to study the functional connectivity in 18 patients at the very early stage of multiple sclerosis (MS) compared with 18 controls, to determine the existence of circuitry disturbance inside the working memory network and its relationship with white matter abnormalities assessed by conventional MRI and magnetization transfer ratio (MTR) imaging. The left BA 45/46 was selected as the seed region to compute correlation maps with other brain regions. After obtaining the correlation map for each subject, between-group comparisons were performed using random effect procedure. Compared with controls, patients did not show any greater functional connectivity between left BA 45/46 and other regions during PASAT. In contrast, decrease in functional connectivity was observed in patients between left BA 45/46 and left BA 9, right BA 3, and the anterior cingulate cortex (BA 24). In patients, no correlations were found between altered functional connectivity and clinical data. However, functional connectivity observed between left BA 45/46 and BA 24 in patients was correlated with the MTR of normal appearing white matter, and with brain T(2) lesion load. Altered functional connectivity is present inside the working memory network of patients at the very early stage of MS and is related to the extent of diffuse white matter changes.
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Encéfalo/fisiopatología , Memoria/fisiología , Esclerosis Múltiple/fisiopatología , Fibras Nerviosas Mielínicas/patología , Red Nerviosa/fisiopatología , Estimulación Acústica , Adulto , Encéfalo/patología , Mapeo Encefálico , Estudios de Casos y Controles , Humanos , Imagen por Resonancia Magnética , Esclerosis Múltiple/patologíaRESUMEN
We hypothesized that selective serotonin reuptake inhibitors (SSRIs) could modulate motor activity in healthy subjects in a dose-dependent manner. The effects of a single dose of paroxetine were tested in a double-blind, placebo-controlled study. Six randomized and counterbalanced subjects performed behavioral tests in three sessions 1 week apart (E1, E2 and E3) at peak plasma concentration (5 h after drug intake). Each subject was given 20 mg or 60 mg of the drug, or a placebo. Tasks were the Nine Peg Hole test (three trials), Moede dexteritymeter (two trials), and compatible and incompatible reaction time tasks. The results show that at the first trials, performance did not differ after placebo or paroxetine intake. However, 20 and 60 mg of paroxetine improved performance significantly at the third trial of the Nine Peg Hole test and subjects receiving the drug performed 7% faster than those under placebo. An amount of 20 mg, but not 60 mg, of paroxetine improved dexterity significantly at the second trial of the Moede test and subjects performed 30% faster. Conversely, the drug did not affect reaction time for the compatible task and subjects were 11% slower under 20 mg with the incompatible task. Thus, paroxetine decreased the ability to inhibit automatism. Thus, it was concluded that a single dose of paroxetine improved motor performance through practice. But negative effects occurred on tasks including the inhibition of an automatism. Paroxetine enhanced brain motor output (motor activity in S1M1) [NeuroImage, 15 (2002) 26]. This S1M1 hyperactivation is likely to be responsible for the better performance. The brain effect and motor improvement were dose dependent. For both, 20 mg was the optimal dose.
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Destreza Motora/efectos de los fármacos , Paroxetina/farmacología , Inhibidores Selectivos de la Recaptación de Serotonina/farmacología , Anciano , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Paroxetina/administración & dosificación , Placebos , Tiempo de Reacción , Inhibidores Selectivos de la Recaptación de Serotonina/administración & dosificación , Análisis y Desempeño de TareasRESUMEN
Most of the neuroimaging studies that have shown visual category-specific activations or categorization effects have been based on a subtractive approach. In the present study, we investigated, by means of EEG, not only the net result of the categorization but also the dynamics of the process. Subjects had to perform a target detection task throughout an image set of distractors belonging to six categories: letters, geometrical figures, faces, tools, structured textures and Asiatic characters. Multivariate analyses were performed on the responses to the non-target stimuli according to their category. Categorical neural responses were only obtained on P2 latencies and N2 amplitudes. This result suggests that there are no differences in the first stage of the implicit categorization of the distractors (visual analysis and proximal stimulus representation elaboration from 100 to 220 ms) and that differences appear between 220 and 280 ms (matching to structural representations). Over-learned stimuli (e.g. letters) elicited the shortest P2 latency, contrasting with unknown categories (e.g. Asiatic characters) that revealed the longest P2 latencies and flattened N2 waves. Categorical differences indicate that the more a subject knows about an object, the less cognitive resources are used. In conclusion, our results suggest that a reduction in neural activity could reflect an improved accuracy in cognitive and cortical processing.
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Potenciales Evocados Visuales/fisiología , Reconocimiento Visual de Modelos/clasificación , Reconocimiento Visual de Modelos/fisiología , Estimulación Luminosa/métodos , Tiempo de Reacción/fisiología , Adulto , Análisis de Varianza , Femenino , Humanos , Masculino , Análisis Multivariante , Red Nerviosa/fisiologíaRESUMEN
The understanding and the prediction of the clinical outcomes of focal or degenerative cerebral lesions, as well as the assessment of rehabilitation procedures, necessitate knowing the cerebral substratum of cognitive or sensorimotor functions. This is achieved by activation studies, where subjects are asked to perform a specific task while data of their brain functioning are obtained through functional neuroimaging techniques. Such studies, as well as animal experiments, have shown that sensorimotor or cognitive functions are the offspring of the activity of large-scale networks of anatomically connected cerebral regions. However, no one-to-one correspondence between activated networks adn functions can be found. Our research aims at understanding how the activation of large-scale networks derives from cerebral information processing mechanisms, which can only explain apparently conflicting activation data. Our work falls at the crossroads of neuroimaging interpretation techniques and computational neuroscience. Since knowledge in cognitive neuroscience is permanently evolving, our research aims more precisely at defining a new modeling formalism and at building a flexible simulator, allowing a quick implementation of the models, for a better interpretation of cerebral functional images. It also aims at providing plausible models, at eht level of large-scale networks, of cerebral information processing mechanisms in humans. In this paper, we propose a formalism, based on dynamic Bayesian networks (DBNs), that respects the following constraints: an oriented, networks architecture, whose nodes (the cerebral structures) can all be different, the implementation of causality--the activation of the structure is caused by upstream nodes' activation--the explicit representation of different time scales (from 1 ms for the cerebral activity to many seconds for a PET scan image acquisition), the representation of cerebral information at the integrated level of neuronal populations, the imprecision of functional neuroimaging data, the nonlinearity and the uncertainty in cerebral mechanisms, and brain's plasticity (learning, reorganization, modulation). One of the main problems, nonlinearity, has been tackled thanks to new extensions of the Kalman filter. The capabilities of the formalism's current version are illustrated by the modeling of a phoneme categorization process, explaining the different cerebral activations in normal and dyslexic subjects.
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Encefalopatías/rehabilitación , Lesiones Encefálicas/rehabilitación , Corteza Cerebral/fisiología , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/rehabilitación , Teorema de Bayes , Encefalopatías/patología , Lesiones Encefálicas/patología , Dislexia , Humanos , Pronóstico , Tomografía Computarizada de EmisiónRESUMEN
We have synthesized gadolinium oxysulfide nanoparticles (NPs) doped with other lanthanides (Eu(3+), Er(3+), Yb(3+)) via a hydroxycarbonate precursor precipitation route followed by a sulfuration process under a H2S-Ar atmosphere at 750 °C in order to propose new multimodal nanoplatforms for Magnetic Resonance (MR), X-ray and photoluminescence imaging. Gd2O2S:Eu(3+) NPs strongly absorb near UV (≈ 300-400 nm) and re-emit strong red light (624 nm). They can be easily internalized by cancer cells, and imaged by epifluorescence microscopy under excitation in the NUV (365 nm). They are not cytotoxic for living cells up to 100 µg mL(-1). Consequently, they are well adapted for in vitro imaging on cell cultures. Gd2O2S:Eu(3+) NPs also show strong transverse relaxivity and strong X-ray absorption allowing their use as contrast agents for T2-weighted MRI and X-ray tomography. Our study shows that Gd2O2S:Eu(3+) NPs are considerably better than commercial Ferumoxtran-10 NPs as negative contrast agents for MRI. Upconversion emission of Gd2O2S:Er; Yb (1; 8%) NPs under infrared excitation (λ(ex) = 980 nm) shows mainly red emission (≈ 650-680 nm). Consequently, they are more specifically designed for in vivo deep fluorescence imaging, because both excitation and emission are located inside the "transparency window" of biological tissues (650-1200 nm). Magnetic relaxivity and X-ray absorption behaviors of Gd2O2S:Er; Yb NPs are almost similar to Gd2O2S:Eu(3+) NPs.
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Medios de Contraste/química , Gadolinio/química , Nanopartículas del Metal/química , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Medios de Contraste/toxicidad , Dextranos/química , Europio/química , Humanos , Imagen por Resonancia Magnética , Magnetismo , Nanopartículas de Magnetita/química , Nanopartículas del Metal/toxicidad , Tomografía por Rayos XRESUMEN
PURPOSE: Because lactate accumulation is considered a surrogate for hypoxia and tumor radiation resistance, we studied the spatial distribution of the lactate-to-N-acetyl-aspartate ratio (LNR) before radiation therapy (RT) with 3D proton magnetic resonance spectroscopic imaging (3D-(1)H-MRSI) and assessed its impact on local tumor control in glioblastoma (GBM). METHODS AND MATERIALS: Fourteen patients with newly diagnosed GBM included in a phase 2 chemoradiation therapy trial constituted our database. Magnetic resonance imaging (MRI) and MRSI data before RT were evaluated and correlated to MRI data at relapse. The optimal threshold for tumor-associated LNR was determined with receiver-operating-characteristic (ROC) curve analysis of the pre-RT LNR values and MRI characteristics of the tumor. This threshold was used to segment pre-RT normalized LNR maps. Two spatial analyses were performed: (1) a pre-RT volumetric comparison of abnormal LNR areas with regions of MRI-defined lesions and a choline (Cho)-to- N-acetyl-aspartate (NAA) ratio ≥ 2 (CNR2); and (2) a voxel-by-voxel spatial analysis of 4,186,185 voxels with the intention of evaluating whether pre-RT abnormal LNR areas were predictive of the site of local recurrence. RESULTS: A LNR of ≥ 0.4 (LNR-0.4) discriminated between tumor-associated and normal LNR values with 88.8% sensitivity and 97.6% specificity. LNR-0.4 voxels were spatially different from those of MRI-defined lesions, representing 44% of contrast enhancement, 64% of central necrosis, and 26% of fluid-attenuated inversion recovery (FLAIR) abnormality volumes before RT. They extended beyond the overlap with CNR2 for most patients (median: 20 cm(3); range: 6-49 cm(3)). LNR-0.4 voxels were significantly predictive of local recurrence, regarded as contrast enhancement at relapse: 71% of voxels with a LNR-0.4 before RT were contrast enhanced at relapse versus 10% of voxels with a normal LNR (P<.01). CONCLUSIONS: Pre-RT LNR-0.4 in GBM indicates tumor areas that are likely to relapse. Further investigations are needed to confirm lactate imaging as a tool to define additional biological target volumes for dose painting.
Asunto(s)
Ácido Aspártico/análogos & derivados , Biomarcadores de Tumor/metabolismo , Neoplasias Encefálicas/metabolismo , Glioblastoma/metabolismo , Ácido Láctico/metabolismo , Espectroscopía de Resonancia Magnética/métodos , Recurrencia Local de Neoplasia , Adulto , Anciano , Antineoplásicos/uso terapéutico , Ácido Aspártico/metabolismo , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/radioterapia , Colina/metabolismo , Creatina/metabolismo , Femenino , Glioblastoma/mortalidad , Glioblastoma/radioterapia , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Quinolonas/uso terapéutico , Radioterapia Conformacional , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: To integrate 3D MR spectroscopy imaging (MRSI) in the treatment planning system (TPS) for glioblastoma dose painting to guide simultaneous integrated boost (SIB) in intensity-modulated radiation therapy (IMRT). METHODS: For sixteen glioblastoma patients, we have simulated three types of dosimetry plans, one conventional plan of 60-Gy in 3D conformational radiotherapy (3D-CRT), one 60-Gy plan in IMRT and one 72-Gy plan in SIB-IMRT. All sixteen MRSI metabolic maps were integrated into TPS, using normalization with color-space conversion and threshold-based segmentation. The fusion between the metabolic maps and the planning CT scans were assessed. Dosimetry comparisons were performed between the different plans of 60-Gy 3D-CRT, 60-Gy IMRT and 72-Gy SIB-IMRT, the last plan was targeted on MRSI abnormalities and contrast enhancement (CE). RESULTS: Fusion assessment was performed for 160 transformations. It resulted in maximum differences <1.00 mm for translation parameters and ≤1.15° for rotation. Dosimetry plans of 72-Gy SIB-IMRT and 60-Gy IMRT showed a significantly decreased maximum dose to the brainstem (44.00 and 44.30 vs. 57.01 Gy) and decreased high dose-volumes to normal brain (19 and 20 vs. 23% and 7 and 7 vs. 12%) compared to 60-Gy 3D-CRT (p < 0.05). CONCLUSIONS: Delivering standard doses to conventional target and higher doses to new target volumes characterized by MRSI and CE is now possible and does not increase dose to organs at risk. MRSI and CE abnormalities are now integrated for glioblastoma SIB-IMRT, concomitant with temozolomide, in an ongoing multi-institutional phase-III clinical trial. Our method of MR spectroscopy maps integration to TPS is robust and reliable; integration to neuronavigation systems with this method could also improve glioblastoma resection or guide biopsies.
Asunto(s)
Neoplasias Encefálicas/patología , Neoplasias Encefálicas/radioterapia , Glioblastoma/patología , Glioblastoma/radioterapia , Procesamiento de Imagen Asistido por Computador/métodos , Espectroscopía de Resonancia Magnética/métodos , Radioterapia de Intensidad Modulada/métodos , Medios de Contraste/farmacología , Dacarbazina/análogos & derivados , Dacarbazina/uso terapéutico , Humanos , Imagenología Tridimensional/métodos , Persona de Mediana Edad , Radiometría/métodos , Planificación de la Radioterapia Asistida por Computador/métodos , Radioterapia Conformacional/métodos , Recurrencia , Temozolomida , Tomografía Computarizada por Rayos X/métodosRESUMEN
The Prader-Willi syndrome (PWS), a rare multisystem genetic disease, leads to severe disabilities, such as morbid obesity, endocrine dysfunctions, psychiatric disorders, and social disturbances. We explored the whole brain of patients with PWS to detect abnormalities that might explain the behavioral and social disturbances, as well as the psychiatric disorders of these patients. Nine patients with PWS (six males, three females; mean age 16.4 years) underwent a positron emission tomography (PET) scan with H(2)(15)O as a tracer to measure regional cerebral blood flow (rCBF). The images were compared with those acquired from nine controls (six males, three females; mean age 21.2 years). A morphologic magnetic resonance imaging (MRI) was also performed in PWS patients, and their cognitive and behavioral skills were assessed with Wechsler Intelligence Scale for Children III and the Child Behavior Check List (CBCL). The MRI images showed no evident anatomic abnormalities, whereas PET scans revealed hypoperfused brain regions in PWS patients compared with controls, particularly in the anterior cingulum and superior temporal regions. We observed a significant relationship (P<0.05) between rCBF in the hypoperfused regions and CBCL scores. The functional consequences of these perfusion abnormalities in specific brain regions might explain the behavioral and social problems observed in these individuals.