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Erythropoietin therapy for acute stroke is both safe and beneficial.

BACKGROUND: Erythropoietin (EPO) and its receptor play a major role in embryonic brain, are weakly expressed in normal postnatal/adult brain and up-regulated upon metabolic stress. EPO protects neurons from hypoxic/ ischemic injury. The objective of this trial is to study the safety and efficacy of recombinant human EPO (rhEPO) for treatment of ischemic stroke in man. MATERIALS AND METHODS: The trial consisted of a safety part and an efficacy part. In the safety study, 13 patients received rhEPO intravenously (3.3 X 10(4) IU/50 ml/30 min) once daily for the first 3 days after stroke. In the double-blind randomized proof-of-concept trial, 40 patients received either rhEPO or saline. Inclusion criteria were age <80 years, ischemic stroke within the middle cerebral artery territory confirmed by diffusion-weighted MRI, symptom onset <8 hr before drug administration, and deficits on stroke scales. The study endpoints were functional outcome at day 30 (Barthel Index, modified Rankin scale), NIH and Scandinavian stroke scales, evolution of infarct size (sequential MRI evaluation using diffusion-weighted [DWI] and fluid-attenuated inversion recovery sequences [FLAIR]) and the damage marker S100ss. RESULTS: No safety concerns were identified. Cerebrospinal fluid EPO increased to 60-100 times that of nontreated patients, proving that intravenously administered rhEPO reaches the brain. In the efficacy trial, patients received rhEPO within 5 hr of onset of symptoms (median, range 2:40-7:55). Admission neurologic scores and serum S100beta concentrations were strong predictors ofoutcome. Analysis of covariance controlled for these two variables indicated that rhEPO treatment was associated with an improvement in follow-up and outcome scales. A strong trend for reduction in infarct size in rhEPO patients as compared to controls was observed by MRI. CONCLUSION: Intravenous high-dose rhEPO is well tolerated in acute ischemic stroke and associated with an improvement in clinical outcome at 1 month. A larger scale clinical trial is warranted.

Blood Platelets↗

Diffusion-perfusion MR evaluation of perihematomal injury in hyperacute intracerebral hemorrhage.

BACKGROUND: It has been suggested that a zone of perihematomal ischemia analogous to an ischemic penumbra exists in patients with primary intracerebral hemorrhage (ICH). Diffusion-perfusion MRI provides a novel means of assessing injury in perihematomal regions in patients with ICH. OBJECTIVE: To characterize diffusion-perfusion MRI changes in the perihematomal region in patients with hyperacute intracerebral hemorrhage. METHOD: Twelve patients presenting with hyperacute, primary ICH undergoing CT scanning and diffusion-perfusion MRI within 6 hours of symptom onset were reviewed. An automated thresholding technique was used to identify decreased apparent diffusion coefficient (ADC) values in the perihematomal regions. Perfusion maps were examined for regions of relative hypo- or hyperperfusion. RESULTS: Median baseline NIH Stroke Scale score was 17 (range, 6 to 28). Median hematoma volume was 13.3 mL (range, 3.0 to 74.8 mL). MRI detected the hematoma in all patients on echo-planar susceptibility-weighted imaging and in all seven patients imaged with gradient echo sequences. In six patients who underwent perfusion imaging, no focal defects were visualized on perfusion maps in tissues adjacent to the hematoma; however, five of six patients demonstrated diffuse ipsilateral hemispheric hypoperfusion. On diffusion imaging, perihematomal regions of decreased ADC values were identified in three of 12 patients. All three subsequently showed clinical and radiologic deterioration. CONCLUSIONS: A rim of perihematomal decreased ADC values was visualized in the hyperacute period in a subset of patients with ICH. The presence of a rim of decreased ADC outside the hematoma correlated with poor clinical outcome. Although perfusion maps did not demonstrate a focal zone of perihematomal decreased blood flow in any patient, most patients had ipsilateral hemispheric hypoperfusion.

Acute Disease↗

White matter tractography using diffusion tensor deflection.

Diffusion tensor MRI provides unique directional diffusion information that can be used to estimate the patterns of white matter connectivity in the human brain. In this study, the behavior of an algorithm for white matter tractography is examined. The algorithm, called TEND, uses the entire diffusion tensor to deflect the estimated fiber trajectory. Simulations and imaging experiments on in vivo human brains were performed to investigate the behavior of the tractography algorithm. The simulations show that the deflection term is less sensitive than the major eigenvector to image noise. In the human brain imaging experiments, estimated tracts were generated in corpus callosum, corticospinal tract, internal capsule, corona radiata, superior longitudinal fasciculus, inferior longitudinal fasciculus, fronto-occipital fasciculus, and uncinate fasciculus. This approach is promising for mapping the organizational patterns of white matter in the human brain as well as mapping the relationship between major fiber trajectories and the location and extent of brain lesions.

Algorithms↗

Posterior encephalopathy subsequent to cyclosporin A presenting as irreversible abulia.

A case of cyclosporin A (Cys A)-induced posterior encephalopathy developed into persistent abulia despite rapid and marked improvement of abnormal T2- and FLAIR MRI hyperintense regions. Diffusion-weighted MRI signal intensity was also high at the onset. This change is atypical in Cys A-induced encephalopathy and was thought to predict poor recovery from the encephalopathy. Persistent abulia was probably due to marked hypoperfusion in the whole cortex including bilateral frontal lobes and basal ganglia as detected by SPECT. Apart from the breakdown of the blood-brain barrier, direct toxicity of Cys A to the brain may play a role in the pathogenesis of chronic, irreversible encephalopathy.

Akinetic Mutism↗

[Laboratory and imaging studies for the diagnosis of prion disease].

We evaluated the diagnostic sensitivity of periodic synchronous discharge (PSD) in EEG, brain specific proteins in CSF such as neuron specific enolase (NSE), 14-3-3 protein, and tau protein, and imaging studies performed by T2-weighted MRI (T2I) and diffusion-weighted MRI (DWI). 36 patients with a mean age of 68.6 years were enrolled. Their diagnostic levels were as follows: seven were definite, 28 were possible, and one was probable who had a disease-specific point mutation of V180I. The diagnostic sensitivities of PSD, NSE, 14-3-3 protein, tau protein, DWI, and T2I were 50% (N = 36), 70% (N = 30), 80.8% (N = 26), 87.5% (N = 16), 92.3% (N = 26), and 42.3% (N = 26), respectively. DWI could revealed the CJD-related lesions earlier than the appearance of PSD. DWI revealed the lesions even in the patients who did not show PSD. For the diagnosis of CJD, DWI and either 14-3-3 protein or tau protein are useful. Using western blot, we detected the protease-resistant PrP in the urine of 11 of 15 CJD patients. We also detected it in three of 25 disease control patients. Differing from previous reports, the detection of a protease-resistant PrP was not specific to CJD patients. However, the sensitivity was 73.3% and the specificity was 88.9%.

14-3-3 Proteins↗

Subcortical pathways serving cortical language sites: initial experience with diffusion tensor imaging fiber tracking combined with intraoperative language mapping.

The combination of mapping functional cortical neurons by intraoperative cortical stimulation and axonal architecture by diffusion tensor MRI fiber tracking can be used to delineate the pathways between functional regions. In this study the authors investigated the feasibility of combining these techniques to yield connectivity associated with motor speech and naming. Diffusion tensor MRI fiber tracking provides maps of axonal bundles and was combined with intraoperative mapping of eloquent cortex for a patient undergoing brain tumor surgery. Tracks from eight stimulated sites in the inferior frontal cortex including mouth motor, speech arrest, and anomia were generated from the diffusion tensor MRI data. The regions connected by the fiber tracking were compared to foci from previous functional imaging reports on language tasks. Connections were found between speech arrest, mouth motor, and anomia sites and the SMA proper and cerebral peduncle. The speech arrest and a mouth motor site were also seen to connect to the putamen via the external capsule. This is the first demonstration of delineation of subcortical pathways using diffusion tensor MRI fiber tracking with intraoperative cortical stimulation. The combined techniques may provide improved preservation of eloquent regions during neurological surgery, and may provide access to direct connectivity information between functional regions of the brain.

Adult↗

Quantitative diffusion characteristics of the human brain depend on MRI sequence parameters.

Quantitative diffusion-weighted MRI has been applied to the study of neurological diseases, including multiple sclerosis, where the molecular self-diffusion coefficient D has been measured in both lesions and normal-appearing white matter. Histograms of D have been used as a novel measure of the "lesion load", with potential applications that include the monitoring of efficacy in new treatment trials. However different ways of measuring D may affect its value, making comparison between different centres and research groups impossible. We aimed to assess the effect, if any, of using two different MRI sequences on the value of D. We studied 13 healthy volunteers, using two different quantitative diffusion sequences (including different b(max) values and gradient applications). Maps of D were analysed using both regions of interest (ROI) in white matter and "whole brain" histograms, and compared between the two sequences. In addition, we studied three standardised test liquids (with known values of D) using both sequences. Histograms from the two sequences had different distributions, with a greater spread and higher peak position from the sequence with lower b(max). This greater spread of D was also evident in the white matter and test liquid ROI. "Limits of agreement" analysis demonstrated that the differences could be clinically relevant, despite significant correlations between the sequences obtained using simple rank methods. We conclude that different quantitative diffusion sequences are unlikely to produce directly comparable values of D, particularly if different b(max) values are used. In addition, the use of inappropriate statistical tests may give false impressions of close agreement. Standardisation of methods for the measurement of D are required if these techniques are to become useful tools, for example in monitoring changes in the disease burden of multiple sclerosis.

Adult↗

Combined MR measurements of magnetization transfer, tissue diffusion and proton spectroscopy. A feasibility study with neurological cases.

Magnetic resonance imaging (MRI) of diffusion and magnetization transfer was combined with 1H-spectroscopic imaging (CSI) to evaluate the clinical potential of in-vivo profiles of various brain pathologies. Ten patients (multiple sclerosis, cerebrovascular disease, leukodystrophy, Alzheimer dementia) and five healthy volunteers were investigated with diffusion-weighted MRI, magnetization transfer imaging, and CSI. Proton spectra were analyzed as ratios of NAA/Cr and Cho/Cr calculated from the peak areas of N-acetylaspartate (NAA), (phospho)-creatine (Cr) and choline (Cho). The apparent diffusion coefficient (ADC) and the magnetization transfer ratio (MTR) were determined in identical voxels to ensure identical partial volume effects compared to CSI. Compared to MTR and ADC assessments, the lower spatial resolution of CSI clearly indicates a hindrance at 1.5 T. In most demyelinating lesions, NAA/Cr reduction paralleled attenuated MTRs and elevated ADCs. By contrast, in acute stroke and some acute MS lesions the ADC was reduced, while MTR and NAA/Cr were also decreased. In Alzheimer's dementia, ADC was increased, MTR unchanged and Cho/Cr increased. In a case of leukodystrophy, ADC was pronouncedly increased, MTR and NAA/Cr both reduced, and Cho/Cr normal. Combined measurements of ADC, MTR and CSI are feasible and provide differential in-vivo information on various brain pathologies.

Adult↗

Comparison of water and lipid content measurements using diffuse optical spectroscopy and MRI in emulsion phantoms.

We present a quantitative comparison of lipid and water signals obtained from broadband Diffuse Optical Spectroscopy (DOS) and Magnetic Resonance Imaging (MRI). DOS and MRI measurements were performed on an identical set of emulsion phantoms that were composed of different water/soybean oil fractions. Absolute concentrations of water and lipid ranging from 35-94% and 63-6%, respectively were calculated from quantitative broadband near-infrared (NIR) absorption spectra (650-1000 nm). MR images of fat and water were separated using the three-point Dixon technique. DOS and MRI measured water and lipid were highly correlated (R(2) = 0.98 and R(2) = 0.99, respectively) suggesting that these techniques are complementary over a broad range of physiologically relevant water and lipid values. In addition, comparison of DOS derived concentrations to the MRI "gold standard" technique validates our quantitation approach and permits estimation of DOS accuracy and sensitivity in vivo.

Emulsions↗

Diffusion- and perfusion-weighted MRI response to thrombolysis in stroke.

Diffusion- and perfusion-weighted magnetic resonance imaging provides important pathophysiological information in acute brain ischemia. We performed a prospective study in 19 sub-6-hour stroke patients using serial diffusion- and perfusion-weighted imaging before intravenous thrombolysis, with repeat studies, both subacutely and at outcome. For comparison of ischemic lesion evolution and clinical outcome, we used a historical control group of 21 sub-6-hour ischemic stroke patients studied serially with diffusion- and perfusion-weighted imaging. The two groups were well matched for the baseline National Institutes of Health Stroke Scale and magnetic resonance parameters. Perfusion-weighted imaging-diffusion-weighted imaging mismatch was present in 16 of 19 patients treated with tissue plasminogen activator, and 16 of 21 controls. Perfusion-weighted imaging-diffusion-weighted imaging mismatch patients treated with tissue plaminogen activator had higher recanalization rates and enhanced reperfusion at day 3 (81% vs 47% in controls), and a greater proportion of severely hypoperfused acute mismatch tissue not progressing to infarction (82% vs -25% in controls). Despite similar baseline diffusion-weighted imaging lesions, infarct expansion was less in the recombinant tissue plaminogen activator group (14cm(3) vs 56cm(3) in controls). The positive effect of thrombolysis on lesion growth in mismatch patients translated into a greater improvement in baseline to outcome National Institutes of Health Stroke Scale in the group treated with recombinant tissue plaminogen activator, and a significantly larger proportion of patients treated with recombinant tissue plaminogen activator having a clinically meaningful improvement in National Institutes of Health Stroke Scale of > or = 7 points. The natural evolution of acute perfusion-weighted imaging-diffusion-weighted imaging mismatch tissue may be altered by thrombolysis, with improved stroke outcome. This has implications for the use of diffusion- and perfusion-weighted imaging in selecting and monitoring patients for thrombolytic therapy.

Acute Disease↗

Multishot diffusion-weighted FSE using PROPELLER MRI.

A method for obtaining diffusion-weighted images that are free from the artifacts associated with echo-planar acquisitions, such as signal pile-up and geometric warping, is introduced. It uses an ungated, multishot fast spin-echo (FSE) acquisition that is self-navigated. The phase of the refocusing pulses is alternated to minimize non-Carr-Purcell-Meiboom-Gill (CPMG) artifacts. Several reconstruction methods are combined to make this method robust against motion artifacts. Examples are shown of clinical diffusion-weighted imaging and high-resolution diffusion tensor imaging.

Algorithms↗

Serial investigation of perfusion disturbances and vasogenic oedema in hypertensive encephalopathy by diffusion and perfusion weighted imaging.

Serial MRI including diffusion and perfusion imaging was performed in a patient with hypertensive encephalopathy. At admission, the patient was disorientated and presented with seizures and cortical blindness. Perfusion imaging showed a marked reduction in blood volume and flow, with corresponding vasogenic oedema in the occipital, posterior temporal, and, to a lesser extent, frontal lobes. The clinical symptoms disappeared rapidly following treatment, whereas the disturbed circulation pattern and vasogenic oedema resolved more slowly. A complete normalisation was seen after 1 year.

Brain↗

Cerebral ischemia and white matter edema in experimental hydrocephalus: a combined in vivo MRI and MRS study.

T2 and diffusion weighted MRI, as well as 31P and 1H MRS were performed in kaolin-induced hydrocephalic rats. Extracellular white matter edema was detected in the early stages of progressive hydrocephalus. Phosphocreatine (PCr)/inorganic phosphate (Pi) ratios in hydrocephalic animals were decreased compared to controls, and lactate was detected during the acute and chronic stages of hydrocephalus. These MR spectroscopic results are indicative of a compromised energy metabolism and suggest the occurrence of cerebral ischemia in experimental hydrocephalus.

Animals↗

Fluid-attenuated inversion recovery and diffusion- and perfusion-weighted MRI abnormalities in 117 consecutive patients with stroke symptoms.

BACKGROUND AND PURPOSE: Diffusion-weighted MRI (DWI) is highly sensitive to early cerebral ischemia, but its dependence on lesion location, acuity, and etiology remains unknown. Furthermore, although a marked perfusion-weighted MRI (PWI)-DWI mismatch may exist in a subset of acute strokes, the frequency and distribution of these mismatches have never been methodically characterized in an unselected population. To address these 2 issues, we evaluated echo-planar imaging in 117 consecutive patients with signs and symptoms of acute stroke. METHODS: Clinical diagnoses were determined by chart review. Fluid-attenuated inversion recovery (FLAIR), DWI, and PWI sequences were scored for lesion acuity, neuroanatomy, and vascular territory. Lesion and PWI-DWI mismatch volumes were determined by image analysis. RESULTS: DWI was more sensitive than was FLAIR for the detection of stroke for all subtypes in all anatomic distributions and at all tested time intervals. Although DWI exhibited its greatest benefit over FLAIR during the first 6 hours, it was still superior to FLAIR even after 24 hours. PWI abnormalities were detected in 49% of patients with DWI abnormalities. In the majority of these cases, the PWI-DWI mismatch was substantially larger than the DWI lesion itself. Both the largest DWI lesion volumes and the largest mismatch volumes occurred in patients with carotid disease. CONCLUSIONS: DWI nearly doubles the likelihood of detecting acute ischemic stroke lesions compared with FLAIR for all etiologies and in all anatomic locations. In the hyperacute period (0 to 6 hours), DWI more than triples the likelihood of acute-stroke detection over FLAIR. PWI reveals a measurable mismatch compared with DWI nearly 50% of the time; and in more than half of these patients, the ratio of the volume of the PWI lesion to the DWI lesion is several times larger than the core ischemic lesion itself. In the final analysis, approximately one fourth of all stroke patients present with a large volume of potentially salvageable tissue at risk for infarction.

Acute Disease↗

A comparative study of acquisition schemes for diffusion tensor imaging using MRI.

This study has investigated the effects of the selection of the diffusion-weighted (DW) gradient directions on the precision of a diffusion tensor imaging (DTI) experiment. The theoretical analysis provided a quantitative framework in which the noise performance of DTI schemes could be assessed objectively and for the development of novel DTI schemes, which employ multiple DW gradient directions. This generic framework was first applied to the examination of two commonly used DTI schemes, which employed 6 DW gradient directions and hitherto were used indiscriminately under the sole condition of noncollinearity. It was then used to design and assess a novel 12-DW-gradient-direction DTI protocol, which employed the same total number of DW acquisitions as the two conventional schemes (12). This theoretical investigation was then corroborated using rigorous simulation and DTI experiments on both an isotropic phantom and a healthy human brain. Both the theoretical and the experimental analysis demonstrated that the two conventional schemes showed a significantly different noise performance and that use of the new multiple-DW-gradient-direction scheme clearly improved the precision of the DTI measurements.

Anisotropy↗

Relevance of diffusion and perfusion weighted mri for endovascular treatment of vasospasm in subarachnoid hemorrhage.

The endovascular treatment of vasospasm is effective when implemented rapidly. However its indication often proves difficult on account of the lack of diagnostic arguments or the difficulties in obtaining them in daily practice. We report a case that highlights the relevance of MRI in the decision-making process. A 37-year-old patient presented with symptomatic vasospasm of the middle cerebral artery and was subjected to morphological, diffusion- and perfusion-weighted MRI. These investigations confirmed the presence of significant oligemia in the MCA territory and revealed onsetting diffusion disorders. Angioplasty was immediately performed, resulting in normal diffusion and hemodynamic parameters and complete regression of clinical signs. This case highlights the relevance of MRI when assessing vasospasm before treatment. Coupled with transcranial Doppler, it should help teams quickly select patients most likely to benefit from angioplasty.

Adult↗

[Diffusion and perfusion MR imaging in stroke].

Magnetic resonance imaging (MRI) in stroke makes it possible to visualize the initial infarct in cases of acute cerebral ischemia. Perfusion MRI serves to determine which tissues are additionally at risk of infarction due to persistent hypoperfusion. MRI also allows those examiners with limited experience to reliably confirm an infarct. The most important differential diagnosis of cerebral ischemia, intracerebral hemorrhage, can likewise be recognized with certainty using MRI. Although diffusion and perfusion MRI only demonstrate the pathophysiology of cerebral ischemia approximately, the method is suited for identifying those patients who would profit from reperfusion therapy. Whether MRI is also appropriate as an aid to reaching a prognosis on the risk of secondary hemorrhage has not yet been resolved.

Brain↗

Clinicotopographical correlation of corticospinal tract stroke: a color-coded diffusion tensor imaging study.

UNLABELLED: Background- Small capsular strokes are difficult to assess with regard to the precise location and the extent of pyramidal tract damage with conventional brain imaging. Color-coded diffusion tensor imaging (CDTI) provides a means to visualize the course of the corticospinal tract within the white matter. In addition to T2-weighted MRI, diffusion-weighted MRI and CDTI were used to analyze the topographical patterns of small lacunar corticospinal tract strokes. METHODS: We examined 15 patients with pyramidal tract strokes in the subacute phase (days 3 to 7). Lesions were identified on diffusion-weighted MRI and superimposed on CDTI images. The anatomic location and pattern of the lesion were visualized on CDTI with regard to the corticospinal tract and subsequently compared with the clinical presentation. In addition, infarct areas were evaluated with quantitative parameters: mean diffusivity and lattice anisotropy index of lesions were determined. RESULTS: We identified 5 different patterns of corticospinal tract stroke falling into 2 clinical subgroups: (1) those with marked deficits and minor improvement (6/15) and (2) those with good recovery (9/15). Group 1 had long lesions centered in the pyramidal tract, involving the basal ganglia (anterior choroidal artery); group 2 lesions were very small and/or located anteriorly and medially (periventricular anterior choroidal artery territory; thalamogeniculate, tuberothalamic, and lateral striate branches). Lesions showed a significant increase of mean diffusivity and decrease of lattice anisotropy. CONCLUSIONS: CDTI allows in vivo differentiation of distinct subcortical stroke subtypes. Improved anatomic definition of lesion localization using CDTI may help in better establishing the prognosis for patients after subcortical stroke.

Aged↗