Evaluation of a reduced MR imaging sequencing protocol in adult patients with stroke.

PURPOSE: To compare a reduced (three-sequence) magnetic resonance (MR) imaging protocol with a full (eight- to 10-sequence) MR imaging protocol in adults suspected of having stroke. MATERIALS AND METHODS: Six neuroradiologists interpreted a consecutive sample of 265 MR images in patients suspected of having stroke. Each read reduced-protocol images in a discrete series of 40 patients (one read images in only 15) and corresponding full-protocol images 1 month later (reduced/full protocol). Five of the readers each read images in 10 additional cases, five each as full/full and reduced/reduced protocol controls. kappa values between full and reduced protocols, reader assessment of protocol adequacy, confidence level, and need for additional sequences or examinations were evaluated. RESULTS: In the reduced/full protocol, the kappa value for detecting ischemia was 0.797; and that for detecting any clinically important abnormality, 0.635. Statistically similar kappa values were found with the full/full control design (kappa = 0.802 and 0.715, respectively). The full protocol was judged more adequate than the reduced protocol (2.0 of 5.0 points vs 1.6, P <.001) and generated greater diagnostic confidence (8.6 of 10.0 points vs 8.9, P =.01), less need for additional sequences (2.7 of 6.0 points vs 1.5, P <.001), and more requests for additional examinations (28.4% vs 36.3%). CONCLUSION: Disagreement between interpretations of reduced- and full-protocol images might be attributable to baseline-level intraobserver inconsistency, as demonstrated in control designs. A greater number of sequences did not lead to greater consistency.

Differences between gray matter and white matter water diffusion in stroke: diffusion-tensor MR imaging in 12 patients.

PURPOSE: To investigate differences in water diffusion between white matter and gray matter in acute to early subacute stroke with diffusion-tensor magnetic resonance (MR) imaging. MATERIALS AND METHODS: Twelve patients with unilateral middle cerebral arterial infarcts were examined with diffusion tensor-encoded echo-planar MR imaging 17 hours to 5 days after stroke onset. Isotropic diffusion coefficient (D) and diffusion anisotropy (A(sigma)) images were computed. (D) values were measured in ischemic and contralateral gray matter and white matter by using A(sigma) images to differentiate white matter from gray matter. (D) images were compared with unidirectional and directionally averaged diffusion-weighted images. RESULTS: In all patients, (D) images showed two distinct levels of diffusion reduction in the infarct; more severe reduction occurred exclusively in white matter. (D) values were significantly less in infarcted white matter than in infarcted gray matter, whereas (D) values in the contralateral white matter and gray matter were not significantly different. Relative to the contralateral side, (D) values in the infarct were reduced by 46% in white matter and by 31% in gray matter (P <.001). Diffusion-weighted imaging caused underestimation of the magnitude and, in some cases, the spatial extent of the white matter diffusion abnormality. CONCLUSION: Isotropic diffusion is more reduced in white matter than in gray matter in acute to early subacute middle cerebral arterial stroke. Diffusion-tensor imaging may be more sensitive than diffusion-weighted imaging to white matter ischemia.

Comparison of scalar measures used in magnetic resonance diffusion tensor imaging.

The tensors derived from diffusion tensor imaging describe complex diffusion in tissues. However, it is difficult to compare tensors directly or to produce images that contain all of the information of the tensor. Therefore, it is convenient to produce scalar measures that extract desired aspects of the tensor. These measures map the three-dimensional eigenvalues of the diffusion tensor into scalar values. The measures impose an order on eigenvalue space. Many invariant scalar measures have been introduced in the literature. In the present manuscript, a general approach for producing invariant scalar measures is introduced. Because it is often difficult to determine in clinical practice which of the many measures is best to apply to a given situation, two formalisms are introduced for the presentation, definition, and comparison of measures applied to eigenvalues: (1) normalized eigenvalue space, and (2) parametric eigenvalue transformation plots. All of the anisotropy information contained in the three eigenvalues can be retained and displayed in a two-dimensional plot, the normalized eigenvalue plot. An example is given of how to determine the best measure to use for a given situation by superimposing isometric contour lines from various anisotropy measures on plots of actual measured eigenvalue data points. Parametric eigenvalue transformation plots allow comparison of how different measures impose order on normalized eigenvalue space to determine whether the measures are equivalent and how the measures differ. These formalisms facilitate the comparison of scalar invariant measures for diffusion tensor imaging. Normalized eigenvalue space allows presentation of eigenvalue anisotropy information.

Abnormal diffusion-weighted magnetic resonance images in Creutzfeldt-Jakob disease.

BACKGROUND: Traditional imaging methods, including computed tomography, routine magnetic resonance imaging (MRI), and magnetic resonance spectroscopy, have not been particularly useful in the diagnosis of Creutzfeldt-Jakob disease (CJD). Although abnormalities can be seen using these methods, the findings are evident only late in the disease or lack specificity or sensitivity. OBJECTIVE: To describe abnormalities on diffusion-weighted MRIs in 4 patients with proven CJD. METHODS: Diffusion-weighted MRIs were obtained on 4 patients with CJD as part of a routine MRI brain examination. RESULTS: In all 4 patients, diffusion-weighted MRIs of the brain demonstrated bilateral hyperintensity in the basal ganglia. In 1 patient, the most conspicuous abnormality seen in diffusion-weighted images was in the thalamus. Two patients also demonstrated hyperintensity in the cerebral cortex on diffusion-weighted images. Only 2 of 4 patients demonstrated clear abnormalities on routine (non-diffusion-weighted) MRIs. Diffusion abnormalities were visible in 1 patient within 1 month of symptom onset. The findings were most conspicuous and extensive in the patient with the longest duration of symptoms (7 months). CONCLUSIONS: Diffusion-weighted MRI might provide a noninvasive method of identifying patients with CJD. However, further investigations must be performed to determine the specificity of these findings for CJD.

A linear relationship exists among brain diffusion eigenvalues measured by diffusion tensor magnetic resonance imaging.

Diffusion in biological tissues can be measured by magnetic resonance diffusion tensor imaging The complex nature of anisotropic diffusion in the brain has been described by a diffusion tensor which contains information about the magnitude of diffusion in different directions. Each tensor contains a set of three eigenvalues which are related to the major, intermediate, and minor axes of a diffusion ellipsoid. This investigation demonstrates that the various sets of diffusion eigenvalues from different regions of the brain lie along a line in ordered eigenvalue space. Sets of ordered diffusion eigenvalues were considered points in ordered eigenvalue space. The line which best fit the data by minimizing the total squared deviations was determined. A new coordinate system was constructed through translation and rotation which spanned ordered eigenvalue space. Eigenvalues from both monkey brain and human brain were studied. It was found that the sets of eigenvalues from both species have significant linear trends. Moreover, the same line may describe the brain eigenvalues from both species. It is likely that this linear relationship of the eigenvalues observed in an ordered eigenvalue plot is related to a combination of (1) conservation of total isotropic diffusion and (2) the degree of orientational dispersion of the microfibers within each voxel.

Findings of retinitis on gadolinium-enhanced turbo fluid-attenuated inversion recovery images.

PURPOSE: This study sought to determine the findings of retinal inflammation on gadolinium-enhanced turbo fluid-attenuated inversion recovery (tFLAIR) images. METHODS: Five patients with retinal abnormalities (acquired immunodeficiency syndrome complicated by cytomegalovirus retinitis, two patients; lymphoma complicated by Herpes zoster retinitis, one patient; and diabetic retinopathy, two patients) were identified on routine brain magnetic resonance imaging examinations performed with gadolinium-enhanced tFLAIR; five healthy subjects were retrospectively reviewed for comparison. Retinal signal features and thickness were evaluated comparing gadolinium-enhanced tFLAIR with turbo spin-echo T2-weighted and spin-echo T1-weighted images with and without gadolinium. RESULTS: Abnormal retinal thickening and hyperintensity were most conspicuous on gadolinium-enhanced tFLAIR images. Unenhanced T1-weighted images failed to demonstrate any abnormalities. In the enhanced tFLAIR and T1-weighted images, retinal thickness greater than 1.2 mm was abnormal. Abnormal retinal contour and signal was most apparent on the tFLAIR images. CONCLUSIONS: Of the sequences studied, gadolinium-enhanced tFLAIR images were found to be the best in identifying incidental retinitis and diabetic retinopathy discovered on routine brain magnetic resonance imaging examinations.

Dysembryoplastic neuroepithelial tumor and oligodendroglioma: the diagnostic value of magnetic resonance spectroscopy. Case report and review of the literature.

Preoperative differentiation between dysembryoplastic neuroepithelial tumor (DNT) and low-grade glioma is often not possible. Dysembryoplastic neuroepithelial tumor is a recently described entity of uncertain origin; however, the diagnosis has important clinical implications. Clinical and radiological findings of DNT and low-grade glioma, especially oligodendroglioma, may be similar. Treatment options and prognosis differ significantly between these two lesions; consequently, accurate diagnosis is imperative. The authors describe two individuals who presented simultaneously at their institution: one patient with an oligodendroglioma and a second patient with DNT. The natural history, neurodiagnostic, and pathological features of each are reviewed with special emphasis on the potential utility of magnetic resonance spectroscopy in differentiating these lesions.

Brain magnetic resonance diffusion abnormalities in Creutzfeldt-Jakob disease.

BACKGROUND: Magnetic resonance imaging of the brain has been of limited usefulness in the diagnosis of Creutzfeldt-Jakob disease. Abnormalities on T2-weighted images have been described, but these are neither highly sensitive nor specific. OBJECTIVE: To determine whether diffusion-weighted magnetic resonance images might be useful in the evaluation of Creutzfeldt-Jakob disease. CASE PRESENTATION: A 61-year-old woman with rapidly progressive dementia was referred for cranial magnetic resonance imaging. Diffusion-weighted images were obtained as part of the examination. Brain biopsy confirmed the diagnosis of Creutzfeldt-Jakob disease histologically. FINDINGS AND CONCLUSIONS: The diffusion-weighted magnetic resonance brain images demonstrated bilaterally symmetrical marked increase in signal intensity in the caudate nuclei, putamina, thalami, cingulate gyri, and right inferior frontal cortex. The apparent diffusion coefficient map showed abnormally low diffusion in these regions (as low as 40% of normal in the caudate head). This suggests that there is restricted diffusion in these regions. The T2-weighted images demonstrated slightly increased signal bilaterally in the caudate nuclei and putamina. These findings indicate that diffusion magnetic resonance imaging might be a sensitive means of imaging the abnormalities seen in Creutzfeldt-Jakob disease.

Localization of language cortices by functional MR imaging compared with intracarotid amobarbital hemispheric sedation.

OBJECTIVE: We undertook this study to investigate functional MR imaging as a new clinical method for determining hemispheric language dominance. Seven patients undergoing surgical evaluation for chronic intractable epilepsy were studied. Intracarotid amobarbital injection was also performed and the findings compared with the functional MR imaging results. CONCLUSION: Functional MR imaging studies enabled localization of the frontal and temporal lobe language cortices. The results of functional MR imaging and intracarotid amobarbital testing of hemispheric language dominance agreed in all seven patients, including two right-handed patients with right-hemisphere language dominance. These preliminary results show that functional MR imaging is an accurate noninvasive method of determining language dominance that may replace the amobarbital test for some purposes if confirmed by additional research.

Hippocampal pathology.

Medial temporal sclerosis of the hippocampus and other lesions in the adjacent temporal lobe that can cause epilepsy are discussed in this article. The technical factors to consider to optimally image the hippocampus and criteria to diagnose medial temporal sclerosis are emphasized.

CT and MRI of stroke.

A review of the CT and MRI features of stroke imaging is presented. The pathophysiology of stroke is discussed as a basis for understanding the neuroimaging findings. Neuroimaging is divided according to the time interval between ictus and imaging: hyperacute, acute, subacute, and chronic. Newer MR stroke imaging techniques such as perfusion imaging and diffusion-weighted imaging are presented.

A single-step method for estimation of local cerebral blood volume from susceptibility contrast MRI images.

A new single-step method is described for estimation of local cerebral blood volume (CBV) from multiple rapidly acquired T2- or T2*-weighted MRI images after bolus administration of a susceptibility contrast agent. This method improves on existing methods in three ways. First, the method includes the baseline scan intensity value as a fitted parameter. Second, the model is fitted directly to the original scan intensity values instead of to transformed concentration curves, avoiding the propagation of errors that occurs in the transformation. Third, the equations are reparameterized with CBV fitted directly as a model parameter. Parameter estimation methods are compared by Monte Carlo simulation. The direct method described here yields more precise parameter estimates, with smaller mean absolute deviations from the true parameter values, than the existing method when compared using simulated data. Implementation is discussed and numerical evaluation of the Digamma or Psi function is described.

Dual-echo MRI segmentation using vector decomposition and probability techniques: a two-tissue model.

We combined a vector decomposition technique with Gaussian probability thresholding in feature space to segment normal brain tissues, tumors, or other abnormalities on dual-echo MR images. The vector decomposition technique assigns to each voxel a fractional volume for each of two tissues. A probability threshold, based on an assumed Gaussian probability density function describing random noise, isolates a region in feature space for fractional volume calculation that minimizes contamination from other tissues. The calculated fractional volumes are unbiased estimates of the true fractional volumes. The contrast-to-noise ratio (CNR) between tissues on the segmented images is the same as the Euclidean norm of CNRs in the original images. The method is capable of segmenting more than two tissues from a set of dual-echo images by sequentially analyzing different pairs of tissues. The model is analyzed mathematically and in experiments with a phantom. Two clinical examples are presented.

3-(2'-[18F]fluoroethyl)spiperone: in vivo biochemical and kinetic characterization in rodents, nonhuman primates, and humans.

3-(2'-[18F]fluoroethyl)spiperone (FESP), a recently developed dopamine D2-receptor binding radiopharmaceutical, was used for dynamic characterization of dopamine-receptor binding in Macaca nemestrina monkeys and humans with positron emission tomography (PET). FESP in vitro binding properties to the dopamine receptor (IC50 = 1.5 nM) are similar to those of spiperone. Serial PET scans in monkeys after intravenous bolus injection of FESP revealed specific radioactivity accumulation in striatum (rich in dopamine D2-receptors), whereas radioactivity concentration declined after 20 min in frontal cortex (serotonin receptors) and more rapidly in cerebellum (nonspecific binding). Specific dopamine D2-receptor binding was saturated with increasing concentrations of radioligand (specific activity range: 1-10,000 Ci/mmol), was stereospecifically blocked with (+)butaclamol (0.5 mg/kg), and showed only partial displacement with spiperone (200 micrograms/kg, i.v. administration 90 min after FESP injection). From PET experiments with FESP in humans, it is possible to visualize accumulation of radioactivity in striatum in a manner similar to that observed in monkeys and, ex vivo, in rodents (adult male Sprague-Dawley rats). Biochemical analyses in rat brain revealed that the activity (approximately 90%) in striatum was unmodified FESP up to 4 h after injection. On the other hand, FESP was metabolized peripherally (rat greater than monkey greater than human), with only 11% of plasma radioactivity remaining as intact FESP in rodents and 54% in humans after 2 h. Based on these interspecies scaling pharmacokinetic data, it is unequivocal that FESP peripheral metabolites do not significantly contribute to the accumulated radioactivity in striatal tissue. Therefore, it is concluded that FESP is suitable for the quantitative estimation of dopamine D2-receptor sites using PET.

Models for in vivo kinetic interactions of dopamine D2-neuroreceptors and 3-(2'-[18F]fluoroethyl)spiperone examined with positron emission tomography.

The in vivo tracer kinetics of 3-(2'-[18F]fluoroethyl)spiperone (FESP) in the caudate/striatum and cerebellar regions of the human and monkey brain were studied with positron emission tomography (PET). The minimal model configuration that can describe the kinetics was determined statistically. Three two-compartment model configurations were found to be suitable for describing the kinetics in caudate/striatum and cerebellum: (1) a nonlinear model (five parameters) applicable to studies using nontracer (partially saturating) quantities of FESP in monkey striatum, (2) a linear four-parameter model applicable to the caudate/striatal and cerebellar kinetics in human and monkey studies with tracer quantities of FESP, and (3) a linear three-parameter model derived from the four-parameter model by assuming irreversible binding applicable to tracer studies of the human caudate. In the human studies, when the caudate kinetics (n = 4) were fit by model 2 (with four parameters), the value of the in vivo ligand dissociation constant kd was found to be 0.0015 +/- 0.0032/min. The three-parameter model (model 3) was found to fit the data equally well: this model is equivalent to model 2 with kd set to zero. In the monkey studies, it was found that for short (90 min) studies using tracer quantities of FESP, model 2 fit the striatal kinetics better than model 3. The parameters estimated using model 2 (four parameters) were in better agreement with those estimated by the nonlinear model (model 1) than those estimated using model 3 (three parameters). The use of a graphical approach gives estimates of the plasma-tissue fractional transport rate constant K1 and the net uptake constant K3 comparable to estimates using model 3 for both human and monkey studies.

A double-injection technique for in vivo measurement of dopamine D2-receptor density in monkeys with 3-(2'-[18F]fluoroethyl)spiperone and dynamic positron emission tomography.

Dopamine D2-receptor density in striatum of monkey was measured with 3-(2'-[18F]fluoroethyl)spiperone (FESP) and dynamic positron emission tomography (PET), using a double-injection technique. A first bolus of high specific activity (SA) FESP (5 mCi; approximately equal to 1 Ci/mumol) was injected i.v.; 90 min later, a second bolus of lower SA FESP (5 mCi; approximately equal to 0.04 Ci/mumol) was injected. A dynamic PET study was performed to measure the kinetics of FESP in striatum over 180 min, and the metabolite-corrected concentration of FESP in plasma as a function of time was obtained from arterial blood samples. A nonlinear compartmental model that took into account the saturability of the receptor binding was used to describe the kinetics of FESP in striatum. Model parameters were estimated by regression with a constraint based on information about the equilibrium dissociation constant of the ligand-receptor binding. Dopamine D2-receptor density in striatum was estimated to be 25.9 +/- 12.7 pmol/g in seven Macaca nemestrina monkeys. The method does not require the use of cerebellum as a reference tissue region and an estimate of dopamine D2-receptor density can be obtained from a single study.

A minimax approach to the single-point method of drug dosing.

The single-point dose prediction method is based on the observation that for drugs obeying single compartment elimination kinetics there is a nearly constant reciprocal relation between the plasma level at a fixed time following a single loading dose and the dose that is required to maintain the desired steady state plasma level of the drug. This paper describes an improved method for choosing a plasma sampling time and a proportionality constant. It applies to either drugs administered intravenously or to drugs whose rates of absorption from the site of administration are very rapid compared to their rates of elimination from the body. The sampling time and proportionality constant chosen are those that minimize the maximum relative deviation of the maintenance dose estimated by the single-point method from the dose that would be estimated if the individual's true elimination rate constant were known. The paper also supplies a method to determine the maximum error that may be introduced into the estimation of the maintenance dose by using the single-point method.