RESUMEN
The feasibility of 4D flow MR imaging to visualize flow patterns and generate relative pressure maps in the dural venous sinus in healthy subjects (n = 60) and patients with dural arteriovenous fistulas (n = 7) was investigated. Dural venous drainage was classified based on torcular Herophili anatomy by using 4D flow MR imaging-derived angiograms and magnitude images. Subjects were scanned in a 3T clinical MR imaging system. 4D flow MR imaging enabled noninvasive characterization of dural sinus anatomy and mapping of relative pressure differences.
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Malformaciones Vasculares del Sistema Nervioso Central/diagnóstico por imagen , Senos Craneales/diagnóstico por imagen , Hemodinámica/fisiología , Imagen por Resonancia Magnética/métodos , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND AND PURPOSE: Stenosis of the carotid artery may be a cause of reduced cognitive performance that can be ameliorated with placement of a stent. The goal of this study was to measure cognitive performance and speed of psychomotor performance prospectively before and after carotid stent placement. MATERIALS AND METHODS: Patients referred for stent placement for a unilateral carotid artery stenosis were enrolled in the study. Neuropsychologic testing was performed with a Mini-Mental State Examination, an extended mental status examination, a subjective cognitive status measure, and a psychomotor performance test for speed. The severity of the stenosis was measured on angiograms performed before stent placement. Three months after stent placement, CT angiograms were performed and the neuropsychologic testing was repeated. Differences in neuropsychologic test scores before and after stent placement were calculated and tested for significance with a Student t test. RESULTS: Seventeen patients with a single unilateral carotid stenosis of more than 50% completed the study. Stenosis of the carotid artery averaged 80% before treatment and 18% after treatment. After stenting, the scores from the extended mental status examination improved significantly. The scores from the subjective cognitive status measure also improved. No significant change was noted in the scores from the Mini-Mental State Examination or in the speed of psychomotor performance. CONCLUSION: Carotid stent placement in patients with a unilateral stenosis of the carotid artery resulted in significant improvement in cognitive test scores in this highly selected patient group. Further studies are needed to confirm these preliminary observations.
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Prótesis Vascular , Estenosis Carotídea/complicaciones , Estenosis Carotídea/cirugía , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/prevención & control , Stents , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Resultado del TratamientoRESUMEN
HYPR TRICKS is an acquisition method that combines radial k-space trajectories, sampling k-space at different rates (TRICKS), and a new strategy for image reconstruction that uses highly constrained backprojection reconstruction (HYPR). This approach provides 3D time-resolved contrast-enhanced MR angiograms of the cerebral vessels with subsecond frame update times and submillimeter in-plane spatial resolution. Artifacts are suppressed, and signal-to-noise ratio is well maintained, by using HYPR reconstruction.
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Arterias Cerebrales/anatomía & histología , Procesamiento de Imagen Asistido por Computador/métodos , Imagenología Tridimensional , Angiografía por Resonancia Magnética/métodos , Arterias Cerebrales/patología , Circulación Cerebrovascular , Medios de Contraste , Gadolinio DTPA , Humanos , Aumento de la Imagen , Malformaciones Arteriovenosas Intracraneales/diagnósticoRESUMEN
BACKGROUND AND PURPOSE: Currently, more reliable parameters to predict the risk of aneurysmal rupture are needed. Intra-aneurysmal pressure gradients and flow maps could provide additional information regarding the risk of rupture. Our hypothesis was that phase contrast with vastly undersampled isotropic projection reconstruction (PC-VIPR), a novel 3D MR imaging sequence, could accurately assess intra-aneurysmal pressure gradients in a canine aneurysmal model when compared with invasive measurements. MATERIALS AND METHODS: A total of 13 surgically created aneurysms in 8 canines were included in this study. Pressure measurements were performed in the parent vessel, aneurysm neck, and 5 regions within the aneurysmal sac with a microcatheter. PC-VIPR sequence was used to obtain cardiac-gated velocity measurements in a region covering the entire aneurysm. The velocity and pressure gradient maps derived from the PC-VIPR data were then coregistered with the anatomic DSA images and compared with catheter measurements. RESULTS: In 7 of the bifurcation aneurysms, the velocity flow maps demonstrated a recirculation flow pattern with a small neck-to-dome pressure gradient (mean, +0.5 mm Hg). In 1 bifurcation aneurysm, a flow jet extending from the neck to the dome with significantly greater pressure gradient (+50.2 mm Hg) was observed. All sidewall aneurysms had low flow in the sac with intermediate pressure gradients (mean, +8.3 mm Hg). High statistical correlation existed between PC-VIPR aneurysmal pressures and microcatheter pressure measurements (R = 0.82, P < .01). CONCLUSION: PC-VIPR can provide anatomic as well as noninvasive quantitative and qualitative hemodynamic information in the canine aneurysm model. The PC-VIPR intra-aneurysmal pressure measurements correlated well with catheter measurements.
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Algoritmos , Velocidad del Flujo Sanguíneo , Interpretación de Imagen Asistida por Computador/métodos , Imagenología Tridimensional/métodos , Aneurisma Intracraneal/diagnóstico , Aneurisma Intracraneal/fisiopatología , Presión Intracraneal , Imagen por Resonancia Magnética/métodos , Animales , Anisotropía , Perros , Femenino , Aumento de la Imagen/métodos , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
The cerebral cortex reorganizes in response to central or peripheral lesions. Although basal ganglia and cerebellum are key components of the network dedicated to movement control, their role in motor reorganization remains elusive. We therefore tested if slowly progressive neurodegenerative motor disease alters the subcortical functional anatomy of the basal ganglia-thalamo-cerebellar circuitry. Ten patients with amyotrophic lateral sclerosis (ALS) and ten healthy controls underwent functional magnetic resonance imaging (fMRI), while executing a simple finger flexion task. Cued by an acoustic trigger, they squeezed a handgrip force transducer with their right hand at 10% of their maximum voluntary contraction force. Movement frequency, amplitude, and force were controlled. Statistical parametric mapping of task-related BOLD-response revealed increased activation in ALS patients as compared to healthy controls. The main activation increases were found in the supplementary motor area, basal ganglia, brainstem, and cerebellum. These findings suggest that degeneration of cortical and spinal motor neurons in ALS leads to a recruitment of subcortical motor structures. These subcortical activation patterns strongly resemble functional activation in motor learning and might therefore represent adaptations of cortico-subcortical motor loops as a - albeit finally ineffective - mechanism to compensate for the ongoing loss of motor neurons in ALS.
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Adaptación Fisiológica/fisiología , Esclerosis Amiotrófica Lateral/fisiopatología , Encéfalo/fisiología , Vías Nerviosas/fisiología , Plasticidad Neuronal/fisiología , Recuperación de la Función/fisiología , Estimulación Acústica , Adulto , Anciano , Ganglios Basales/anatomía & histología , Ganglios Basales/fisiología , Encéfalo/anatomía & histología , Mapeo Encefálico , Tronco Encefálico/anatomía & histología , Tronco Encefálico/fisiología , Cerebelo/anatomía & histología , Cerebelo/fisiología , Señales (Psicología) , Femenino , Lateralidad Funcional/fisiología , Fuerza de la Mano/fisiología , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Corteza Motora/anatomía & histología , Corteza Motora/fisiología , Vías Nerviosas/anatomía & histologíaRESUMEN
Functional imaging studies of the cerebellum have mostly investigated motor performance or have been limited to the anterior lobe and therefore the somatosensory representations in the human cerebellum have not been fully demonstrated. We used fMRI of the entire cerebellum during tactile stimulation of the hand and foot in six normal subjects. Our results demonstrate that the tactile projections to the cerebellum in humans are represented in both the anterior and posterior lobes. in agreement with previous functional imaging studies, our results show a large-scale, between-limb somatotopy comparable to that shown in early animal studies.
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Mapeo Encefálico , Cerebelo/fisiología , Tacto/fisiología , Adulto , Mano , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Estimulación Física , Corteza Somatosensorial/fisiologíaRESUMEN
BACKGROUND AND PURPOSE: In subjects performing no specific cognitive task ("resting state"), time courses of voxels within functionally connected regions of the brain have high cross-correlation coefficients ("functional connectivity"). The purpose of this study was to measure the contributions of low frequencies and physiological noise to cross-correlation maps. METHODS: In four healthy volunteers, task-activation functional MR imaging and resting-state data were acquired. We obtained four contiguous slice locations in the "resting state" with a high sampling rate. Regions of interest consisting of four contiguous voxels were selected. The correlation coefficient for the averaged time course and every other voxel in the four slices was calculated and separated into its component frequency contributions. We calculated the relative amounts of the spectrum that were in the low-frequency (0 to 0.1 Hz), the respiratory-frequency (0.1 to 0.5 Hz), and cardiac-frequency range (0.6 to 1.2 Hz). RESULTS: For each volunteer, resting-state maps that resembled task-activation maps were obtained. For the auditory and visual cortices, the correlation coefficient depended almost exclusively on low frequencies (<0.1 Hz). For all cortical regions studied, low-frequency fluctuations contributed more than 90% of the correlation coefficient. Physiological (respiratory and cardiac) noise sources contributed less than 10% to any functional connectivity MR imaging map. In blood vessels and cerebrospinal fluid, physiological noise contributed more to the correlation coefficient. CONCLUSION: Functional connectivity in the auditory, visual, and sensorimotor cortices is characterized predominantly by frequencies slower than those in the cardiac and respiratory cycles. In functionally connected regions, these low frequencies are characterized by a high degree of temporal coherence.
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Nivel de Alerta/fisiología , Corteza Cerebral/fisiología , Imagen por Resonancia Magnética , Red Nerviosa/fisiología , Adulto , Artefactos , Mapeo Encefálico , Dominancia Cerebral/fisiología , Femenino , Humanos , Masculino , Valores de Referencia , DescansoRESUMEN
The time-resolved contrast-enhanced magnetic resonance (MR) angiographic technique TRICKS (time-resolved imaging of contrast kinetics) reconstructs a temporal series of three-dimensional (3D) images. The temporal resolution is increased by using a short TR (<8 ms) and TE (<2 ms), zero filling, partial echo sampling, view sharing, and temporally sampling k-space at variable rates. TRICKS allows reconstruction of multiple sequential 3D volumes following bolus injection of a gadolinium chelate (0.2 mmol/kg body weight up to 40 ml, injection rate -2 ml/s). The resulting temporally defined datasets are conceptually similar to a catheter-based intra-arterial digital subtraction angiographic series, except that they are 3D volumes and not projection images. Similar to other contrast-enhanced MR angiographic methods, TRICKS improves delineation of carotid artery stenosis by minimizing saturation effects. TRICKS and other contrast-enhanced MR angiographic techniques use short echo times and small voxels, thus reducing intravoxel dephasing. Surface morphology of atherosclerotic plaque and slow flow in nearly occluded vessels ("string sign") are well delineated. The major advantage of the TRICKS technique is that the timing of the acquisition in relation to the passage of the contrast bolus occurs automatically, allowing for consistent capture of the arterial phase. and eliminating the need for sophisticated synchronization methods.
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Arterias Carótidas/anatomía & histología , Angiografía por Resonancia Magnética/métodos , Medios de Contraste , Humanos , Aumento de la Imagen , Cinética , Factores de TiempoRESUMEN
A magnetic resonance (MR) angiographic protocol was evaluated in the carotid bifurcation with use of a pulse sequence for time-resolved three-dimensional imaging of contrast material kinetics. The enhancement ratio, a quantitative measure of contrast enhancement, indicated that all studies included an image obtained near the peak of the intraarterial concentration of contrast agent (enhancement ratio, 90% +/- 9 [standard deviation]). Studies acquired at a higher frame rate (4.1-4.9 seconds) exhibited less venous enhancement (enhancement ratio, 25% +/- 16) than studies acquired with slower (6.0-9.6-second) frame rates (enhancement ratio, 46% +/- 25).
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Arterias Carótidas/diagnóstico por imagen , Angiografía por Resonancia Magnética/métodos , Adulto , Anciano , Anciano de 80 o más Años , Medios de Contraste , Femenino , Humanos , Imagenología Tridimensional , Masculino , Persona de Mediana Edad , Fantasmas de Imagen , RadiografíaRESUMEN
Functional magnetic resonance imaging favors the use of multi-slice gradient-recalled echo-planar imaging due to its short image acquisition times, whole brain coverage and sensitivity to BOLD contrast. However, despite its advantages, gradient-recalled echo-planar imaging also is sensitive to static magnetic field gradients arising primarily from air-tissue interfaces. This can lead to image artifacts such as voxel shifts and complete signal loss. A method to recover signal loss by adjusting the refocusing gradient amplitude in the slice-select direction, preferably axially, is proposed. This method is implemented as an automated computer algorithm that partitions echo-planar images into regions of recoverable signal intensities using a histogram analysis and determines each region's proper refocusing gradient amplitude. As an example, different refocusing gradient amplitudes are interleaved in a fMRI acquisition to maximize the signal to noise ratio and obtain functional activation in normal and dropout regions. The effectiveness of this method is demonstrated by recovering signal voids in the orbitofrontal cortex, parahippocampal/amygdala region, and inferior visual association cortex near the cerebellum.
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Encefalopatías/fisiopatología , Encéfalo/fisiología , Imagen Eco-Planar/métodos , Algoritmos , Artefactos , Encéfalo/irrigación sanguínea , Encefalopatías/patología , Humanos , Procesamiento de Imagen Asistido por Computador , Magnetismo , Procesamiento de Señales Asistido por ComputadorRESUMEN
BACKGROUND AND PURPOSE: In subjects who are performing no prescribed cognitive task, functional connectivity mapped with MR imaging (fcMRI) shows regions with synchronous fluctuations of cerebral blood flow. When specific tasks are performed, functional MR imaging (fMRI) can map locations in which regional cerebral blood flow increases synchronously with the performance of the task. We tested the hypothesis that fcMRI maps, based on the synchrony of low-frequency blood flow fluctuations, identify brain regions that show activation on fMRI maps of sensorimotor, visual, language, and auditory tasks. METHODS: In four volunteers, task-activation fMRI and functional connectivity (resting-state) fcMRI data were acquired. A small region of interest (in an area that showed maximal task activation) was chosen, and the correlation coefficient of the corresponding resting-state signal with the signal of all other voxels in the resting data set was calculated. The correlation coefficient was decomposed into frequency components and its distribution determined for each fcMRI map. The fcMRI maps were compared with the fMRI maps. RESULTS: For each task, fcMRI maps based on one to four seed voxel(s) produced clusters of voxels in regions of eloquent cortex. For each fMRI map a closely corresponding fcMRI map was obtained. The frequencies that predominated in the cross-correlation coefficients for the functionally related regions were below 0.1 Hz. CONCLUSION: Functionally related brain regions can be identified by means of their synchronous slow fluctuations in signal intensity. Such blood flow synchrony can be detected in sensorimotor areas, expressive and receptive language regions, and the visual cortex by fcMRI. Regions identified by the slow synchronous fluctuations are similar to those activated by motor, language, or visual tasks.
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Mapeo Encefálico , Circulación Cerebrovascular , Imagen por Resonancia Magnética , Adulto , Encéfalo/fisiología , Cognición , Humanos , Procesamiento de Imagen Asistido por Computador , Procesos Mentales , Desempeño PsicomotorRESUMEN
Test-retest reliability of resting regional cerebral metabolic rate of glucose (rCMR) was examined in selected subcortical structures: the amygdala, hippocampus, thalamus, and anterior caudate nucleus. Findings from previous studies examining reliability of rCMR suggest that rCMR in small subcortical structures may be more variable than in larger cortical regions. We chose to study these subcortical regions because of their particular interest to our laboratory in its investigations of the neurocircuitry of emotion and depression. Twelve normal subjects (seven female, mean age = 32.42 years, range 21-48 years) underwent two FDG-PET scans separated by approximately 6 months (mean = 25 weeks, range 17-35 weeks). A region-of-interest approach with PET-MRI coregistration was used for analysis of rCMR reliability. Good test-retest reliability was found in the left amygdala, right and left hippocampus, right and left thalamus, and right and left anterior caudate nucleus. However, rCMR in the right amygdala did not show good test-retest reliability. The implications of these data and their import for studies that include a repeat-test design are considered.
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Encéfalo/metabolismo , Glucosa/metabolismo , Adulto , Amígdala del Cerebelo/anatomía & histología , Amígdala del Cerebelo/diagnóstico por imagen , Amígdala del Cerebelo/metabolismo , Encéfalo/anatomía & histología , Encéfalo/diagnóstico por imagen , Mapeo Encefálico , Núcleo Caudado/anatomía & histología , Núcleo Caudado/diagnóstico por imagen , Núcleo Caudado/metabolismo , Femenino , Hipocampo/anatomía & histología , Hipocampo/diagnóstico por imagen , Hipocampo/metabolismo , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Tálamo/anatomía & histología , Tálamo/diagnóstico por imagen , Tálamo/metabolismo , Factores de Tiempo , Tomografía Computarizada de EmisiónRESUMEN
With contrast-enhanced MR angiographic techniques, a T1-shortening contrast agent is injected into the blood stream. Imaging during the first pass of the contrast agent permits acquisition of a high-contrast MR angiogram. Scan parameters such as flip angle, repetition time, echo time, and scan duration, and injection parameters, such as dose and rate, must be carefully chosen to achieve maximum contrast between blood vessels and stationary tissues. A critical parameter affecting image quality is the timing of the acquisition relative to the injection. If the collection of the center of k-space does not coincide with peak arterial concentration, artifacts, reduced SNR, and venous enhancement may result. Several techniques have been developed to address the timing issue. Post-processing techniques such as subtracting a pre-contrast image from a post-contrast angiogram can be used to improve image quality. Intravascular contrast agents that may also lead to improved image quality are currently being developed.
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Arterias Carótidas/anatomía & histología , Arterias Carótidas/patología , Medios de Contraste , Gadolinio , Angiografía por Resonancia Magnética/métodos , Angiografía de Substracción Digital , Arteriosclerosis/diagnóstico , Estenosis Carotídea/diagnóstico , Humanos , Procesamiento de Imagen Asistido por Computador , Intensificación de Imagen Radiográfica/métodosRESUMEN
Magnetic resonance angiography is an essential component of the acute stroke MR imaging work-up. Defining the location and extent of vascular compromise greatly aids in the selection of the appropriate therapy. In this article, the most common MR angiography manifestations of acute stroke are illustrated to emphasize the role of MR angiography in the evaluation of patients presenting with symptoms of acute cerebral ischemia.
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Angiografía por Resonancia Magnética , Accidente Cerebrovascular/diagnóstico , Enfermedad Aguda , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/etiología , Isquemia Encefálica/terapia , Humanos , Sensibilidad y Especificidad , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/terapiaRESUMEN
Fast-spin-echo magnetic resonance (MR) images are routine components of a standard MR brain examination. On these images, blood vessels are visible as black flow void. We report that by applying an enhancement filter to a stack of routine fast-spin-echo MR images, projected angiographic images can be generated. The vascular detail in the projected image is similar to that observed in a phase-contrast image. In addition to its advantage in obtaining vessel information from routine images, the proposed post-processing technique is fast, easy to implement and completely automatic. These images provide additional vessel information that is useful when MR angiography is unavailable or as an aid in planning dedicated MR angiographic studies.
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Encéfalo/irrigación sanguínea , Procesamiento de Imagen Asistido por Computador , Angiografía por Resonancia Magnética/métodos , HumanosRESUMEN
Functional MR imaging, similar to positron-emission tomography, shows the regions in which cerebral blood flow changes as neurons are active in the performance of cognitive tasks. Blood flow increases (activation) exceed that needed to supply oxygen for the increased metabolic needs for the increased neuronal activity. Therefore, in regions with activation, the deoxyhemoglobin concentration in the capillary blood decreases below levels found in the brain where neurons are not active.
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Encéfalo/fisiología , Imagen por Resonancia Magnética/métodos , Corteza Auditiva/fisiología , Encéfalo/metabolismo , Encefalopatías/prevención & control , Capilares , Circulación Cerebrovascular , Cognición/fisiología , Lóbulo Frontal/fisiología , Hemoglobinas/análisis , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Lenguaje , Neuronas/metabolismo , Neuronas/fisiología , Oxígeno/sangre , Consumo de Oxígeno/fisiología , Complicaciones Posoperatorias/prevención & control , Tomografía Computarizada de EmisiónRESUMEN
The role of the amygdala in major depression was investigated. Resting regional cerebral metabolic rate (rCMRglu) was measured with [18F]fluorodeoxyglucose positron emission tomography (PET) in two samples of subjects using two different PET cameras. The samples consisted of 10 and 17 medication-free depressives and 11 and 13 controls, respectively. Using coregistration of PET and magnetic resonance images, regions were individually delineated for the amygdala and thalamus, the latter of which was used as a control region. Within the depressed groups, right amygdalar rCMRglu was positively correlated with negative affect. Thalamic rCMRglu was not related to negative affect, and amygdalar rCMRglu accounted for a significant portion of variance in depressives' negative affect scores over and above the contribution of thalamic rCMRglu.
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Amígdala del Cerebelo/metabolismo , Amígdala del Cerebelo/fisiopatología , Depresión/fisiopatología , Depresión/diagnóstico por imagen , Emociones/fisiología , Femenino , Glucosa/metabolismo , Humanos , Imagen por Resonancia Magnética , Masculino , Tálamo/metabolismo , Tomografía Computarizada de EmisiónRESUMEN
Four U.S. sites formed a consortium to conduct a multisite study of fMRI methods. The primary purpose of this consortium was to examine the reliability and reproducibility of fMRI results. FMRI data were collected on healthy adults during performance of a spatial working memory task at four different institutions. Two sets of data from each institution were made available. First, data from two subjects were made available from each site and were processed and analyzed as a pooled data set. Second, statistical maps from five to eight subjects per site were made available. These images were aligned in stereotactic space and common regions of activation were examined to address the reproducibility of fMRI results when both image acquisition and analysis vary as a function of site. Our grouped and individual data analyses showed reliable patterns of activation in dorsolateral prefrontal cortex and posterior parietal cortex during performance of the working memory task across all four sites. This multisite study, the first of its kind using fMRI data, demonstrates highly consistent findings across sites.
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Lóbulo Frontal/fisiología , Imagen por Resonancia Magnética/métodos , Memoria/fisiología , Lóbulo Parietal/fisiología , Percepción Espacial/fisiología , Adulto , Mapeo Encefálico/métodos , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Reproducibilidad de los ResultadosRESUMEN
PURPOSE: To compare the delineation of stenosis at the carotid artery bifurcation on three-dimensional (3D) magnetic resonance (MR) digital subtraction angiographic (DSA) images with that on two-dimensional (2D) and 3D time-of-flight (TOF) MR angiographic images. MATERIALS AND METHODS: Twenty-six patients with 29 carotid artery bifurcations and symptoms of cerebral ischemia underwent 3D MR DSA. A time-resolved series was generated with 3D MR DSA after the bolus injection of gadodiamide. The resolution for a carotid artery examination was 0.4 x 0.4 x 1.0 mm, with volumes reconstructed at 4.5-second intervals. The 3D MR DSA images were compared with contemporaneously acquired unenhanced 2D and 3D TOF images. Two observers ranked the 2D and 3D TOF MR angiographic and 3D MR DSA images according to the following: (a) stenosis delineation, (b) internal carotid artery delineation, (c) intravascular signal intensity, and (d) diagnostic confidence. RESULTS: The mean ranking for diagnostic confidence was 1.10 (1 = best technique, 3 = worst technique) for 3D MR DSA. Compared with the pooled 2D TOF and 3D TOF ranks, the 3D MR DSA rank was significantly better (P < .01). Similar levels of statistical significance were found for the other criteria. CONCLUSION: Three-dimensional MR DSA improves the delineation of carotid arterial stenosis by virtually eliminating saturation effects and reducing intravoxel dephasing. Surface morphology and nearly occluded vessels ("string sign") were easily identified. Confidence in identifying carotid arterial occlusions was also very high with this technique.