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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The classic definition of the ischemic penumbra is a hypoperfused region in which metabolism is impaired, but still sufficient to maintain cellular polarization. Perfusion- and diffusion-weighted MRI (PWI, DWI) can identify regions of reduced perfusion and cellular depolarization, respectively, but it often remains unclear whether a PWI-DWI mismatch corresponds to benign oligemia or a true penumbra. We hypothesized that pH-weighted MRI (pHWI) can subdivide the PWI-DWI mismatch into these regions. Twenty-one rats underwent permanent middle cerebral artery occlusion and ischemic evolution over the first 3.5 h post-occlusion was studied using multiparametric MRI. End point was the stroke area defined by T(2)-hyperintensity at 24 h. In the acute phase, areas of reduced pH were always larger than or equal to DWI deficits and smaller than or equal to PWI deficits. Group analysis showed that pHWI deficits during this phase coincided with the resulting infarct area at endpoint. Final infarcts were smaller than PWI deficits (range 65% to 90%, depending on the severity of the occlusion) and much larger than acute DWI deficits. These data suggest that the outer boundary of the hypoperfused area showing a decrease in pH without DWI abnormality may correspond to the outer boundary of the ischemic penumbra, while the hypoperfused region at normal pH may correspond to benign oligemia. These first results show that pHWI can provide information complementary to PWI and DWI in the delineation of ischemic tissue.
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PMID:Detection of the ischemic penumbra using pH-weighted MRI. 1713 26

To evaluate impact of glucose burden on diffusion-weighted imaging (DWI)-lesion evolution according to ischemia duration in stroke. We studied 47 patients with transcranial Doppler (TCD)-documented artery occlusion treated with intravenous tissue plasminogen activator. Hyperglycemia (HG) was defined as glucose>140 mg/dL. A subcutaneous device continuously monitored glucose during 24 h. Magnetic resonance imaging was performed pretreatment (1) and at 24 to 36 h (2) in 30 patients. We measured initial PWI lesion (PW1) and DWI growth: DW2-DW1 (DWg). Serial TCD during 24 h determined occlusion time (OT). National Institutes of Health Stroke Scale (NIHSS) scores were obtained at baseline and 48 h. Poor short-term clinical course defined as <50% recovery of initial NIHSS. Baseline NIHSS was 18. On admission 10 patients (21.3%) were hyperglycemic and presented similar NIHSS, DW1, and PW1 lesion extension as those without HG. During monitoring 24 patients (51%) had HG, 21 (45%) of them during OT (median OT 12 h). Median 48 h-NIHSS was 10; 15 patients presented poor outcome. 48 h-NIHSS was higher in patients with HG during OT (15 versus 3; P<0.001). Patients with favorable outcome had shorter OT (8.4 versus 17.4 h; P<0.001). However, the only independent predictor of poor outcome was HG during OT (OR: 20.3; 95% CI: 3.77 to 108.8; P<0.001). At 24 h mean DWg was 52 cm(3). A receiver operating characteristic curve identified DWg>14 cm(3) best predictor of poor outcome (sensitivity, 85.7%; specificity, 75%). Total OT (P=0.007) and HG during OT (P=0.01) showed the strongest correlation with DWg. DWI lesion grew 2.7 times faster in patients with HG than without HG during OT (1.73 versus 4.63 cm(3)/h of occlusion; P=0.07). In a regression model the only independent predictor of DWg was HG during OT (OR: 10.83; 95% CI: 1.96 to 59.83; P=0.006). Hyperglycemia, especially during OT, has a powerful deleterious effect after stroke accelerating brain damage.
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PMID:Hyperglycemia during ischemia rapidly accelerates brain damage in stroke patients treated with tPA. 1729 52

Normobaric hyperoxia (NBO) has been shown to extend the reperfusion window after focal cerebral ischemia. Employing diffusion (DWI)- and perfusion (PWI)-weighted magnetic resonance imaging (MRI), the effect of NBO (100% started at 30 mins after middle cerebral artery occlusion (MCAO)) on the spatiotemporal evolution of ischemia during and after permanent (pMCAO) and transient suture middle cerebral artery occlusion (tMCAO) was investigated (experiment 3). In two additional experiments, time window (experiment 1) and cell death pathways (experiment 2) were investigated in the pMCAO model. In experiment 1, NBO treatment reduced infarct volume at 24 h after pMCAO by 10% when administered for 3 h (P>0.05) and by 44% when administered for 6 h (P<0.05). In experiment 2, NBO acutely (390 mins, P<0.05) reduced in situ end labeling (ISEL) positivity in the ipsilesional penumbra but increased contralesional necrotic as well as caspase-3-mediated apoptotic cell death. In experiment 3, CBF characteristics and CBF-derived lesion volumes did not differ between treated and untreated animals, whereas the apparent diffusion coefficient (ADC)-derived lesion volume essentially stopped progressing during NBO treatment, resulting in a persistent PWI/DWI mismatch that could be salvaged by delayed (3 h) reperfusion. In conclusion, NBO (1) acutely preserved the perfusion/diffusion mismatch without altering CBF, (2) significantly extended the time window for reperfusion, (3) induced lasting neuroprotection in permanent ischemia, and (4) although capable of reducing cell death in hypoperfused tissue it also induced cell death in otherwise unaffected areas. Our data suggest that NBO may represent a promising strategy for acute stroke treatment.
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PMID:Normobaric hyperoxia delays perfusion/diffusion mismatch evolution, reduces infarct volume, and differentially affects neuronal cell death pathways after suture middle cerebral artery occlusion in rats. 1731 Oct 78

Ultrasound harmonic imaging of perfusion after ultrasound contrast agent (UCA) bolus injection (BHI) can detect cerebral perfusion deficits. In a pilot study, we evaluated the ability of time-intensity curve (TIC) measurements to differentiate between normal and hypoperfused brain areas in acute ischemic stroke. Ten patients with symptoms of acute middle cerebral artery infarction were investigated (SONOS 5500, Harmonic Imaging 1.6/3.8 MHz, diencephalic plane, 10 cm investigation depth, SonoVue 2.4 mL bolus). Peak signal increase (PSI), time-to-peak intensity (TPI) and area under the curve (AUC) were calculated for 60 regions-of-interest (ROIs) in each patient. Reference methods: Perfusion- and diffusion-weighted MRI (PWI/DWI) within 4 h before/after BHI (PWI threshold: 4 s). Receiver operating characteristics (ROC) analysis defined cut-off values for each TIC variable to distinguish between normal and affected brain areas as defined by PWI/DWI. In five patients, PWI showed a perfusion delay >4 s; seven patients had a DWI lesion. In three patients, both PWI and DWI findings showed pathology; one patient had a normal MRI of the insonation plane. Cut-off values for PWI delay: PSI: 5.53% (sensitivity .98, specificity .89); TPI: 4.04 s (sensitivity .74, specificity .69) and AUC: .63 (sensitivity .94, specificity .58). Referred to the mean value in unaffected brain areas the relative thresholds were 17.6%, 109.5% and 16.1%, respectively. Regarding DWI, only for PSI, a significant cut-off value was defined: 10.86%, sensitivity .84, specificity .60 (34.6% of mean). In conclusion, these thresholds distinguish between normal and affected brain areas in acute ischemic stroke.
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PMID:Ultrasound perfusion imaging: determination of thresholds for the identification of critically disturbed perfusion in acute ischemic stroke--a pilot study. 1744 70

Echo-planar imaging (EPI) is the standard technique for dynamic susceptibility-contrast (DSC) perfusion MRI. However, EPI suffers from well-known geometric distortions, which can be reduced by increasing the k-space phase velocity. Moreover, the long echo times (TEs) used in DSC lead to signal saturation of the arterial input signal, and hence to severe quantitation errors in the hemodynamic information. Here, through the use of interleaved shot acquisition and parallel imaging (PI), rapid volumetric EPI is performed using pseudo-single-shot (ss)EPI with the effective T(*)(2) blur and susceptibility distortions of a multishot EPI sequence. The reduced readout lengths permit multiple echoes to be acquired with temporal resolution and spatial coverage similar to those obtained with a single-echo method. Multiecho readouts allow for unbiased R(*)(2) mapping to avoid incorrect estimation of tracer concentration due to signal saturation or T(1) shortening effects. Multiecho perfusion measurement also mitigates the signal-to-noise ratio (SNR) reduction that results from utilizing PI. Results from both volunteers and clinical stroke patients are presented. This acquisition scheme can aid most rapid time-series acquisitions. The use of this method for DSC addresses the problem of signal saturation and T(1) contamination while it improves image quality, and is a logical step toward better quantitative MR PWI.
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PMID:Perfusion mapping with multiecho multishot parallel imaging EPI. 1765 30

Diffusion-weighted and perfusion-weighted magnetic resonance imaging (DWI, PWI) are useful in detecting early cerebral ischemic lesions. Intra-arterial thrombolysis is an effective treatment for some patients with acute thromboembolic occlusion. We evaluated the efficacy of acute thrombolytic therapy by using DWI and PWI in 3 patients who presented with internal carotid artery or middle cerebral artery occlusion. On the initial magnetic resonance imaging scans, the abnormal areas shown by PWI were bigger than those shown by DWI. All patients received thrombolytic therapy within 6 hours after stroke onset. In 1 patient, the hyperintensity area detected by initial DWI scanning diminished after thrombolysis. DWI and PWI may be useful to monitor the effectiveness of intra-arterial thrombolysis.
J Stroke Cerebrovasc Dis
PMID:Diffusion-weighted and perfusion-weighted magnetic resonance imaging to monitor acute intra-arterial thrombolysis. 1789 7

During the acute phase shortly after the onset of an ischemic stroke, tissue in the penumbra surrounding an infarct receives sufficient blood flow to survive, but not enough to function. As time passes, neurons in this penumbra die. Imaging techniques have given valuable information about the length of time that brain cells can survive under these ischemic conditions. 15O positron-emission tomography (PET) scanning gives information about perfusion of tissue, its oxygen consumption, and its oxygen extraction fraction. Tissue in the penumbra has a reduced blood flow, near normal oxygen consumption, but markedly raised oxygen extraction fraction. With the use of a set of rigorous criteria, PET scanning has provided evidence that, in a fraction of the patients, a penumbra of viable, potentially salvageable neurons exists for at least 7 hours, and possibly for as long as 16 hours, after the onset of ischemic stroke, whereas in others the infarct reaches its maximal extent only a few hours after clinical onset. Recent developments in magnetic resonance imaging (MRI) technology, especially diffusion-weighted and perfusion-weighted imaging (DWI and PWI), also have enabled potentially salvageable penumbral tissue to be identified in patients who have suffered ischemic strokes. The typical signature of salvageable tissue is that it has a PWI-DWI mismatch. This type of MRI evidence shows that there may be salvageable tissue as late as 24 hours after the onset of symptoms.
J Stroke Cerebrovasc Dis 2000 Nov
PMID:For how long is brain tissue salvageable? Imaging-based evidence. 1789 15

Preventing death and limiting handicap from ischaemic stroke are major goals that can be achieved only if the pathophysiology of infarct expansion is properly understood. Primate studies showed that following occlusion of the middle cerebral artery (MCA)--the most frequent and prototypical stroke, local tissue fate depends on the severity of hypoperfusion and duration of occlusion, with a fraction of the MCA territory being initially in a 'penumbral' state. Physiological quantitative PET imaging has translated this knowledge in man and revealed the presence of considerable pathophysiological heterogeneity from patient to patient, largely unpredictable from elapsed time since onset or clinical deficit. While these observations underpinned key trials of thrombolysis, they also indicate that only patients who are likely to benefit should be exposed to its risks. Accordingly, imaging-based diagnosis is rapidly becoming an essential component of stroke assessment, replacing the clock by individually customized management. Diffusion- and perfusion-weighted MR (DWI-PWI) and CT-based perfusion imaging are increasingly being used to implement this, and are undergoing formal validation against PET. Beyond thrombolysis per se, knowledge of the individual pathophysiology also guides management of variables like blood pressure, blood glucose and oxygen saturation, which can otherwise precipitate the penumbra into the core, and the oligaemic tissue into the penumbra. We propose that future therapeutic trials use physiological imaging to select the patient category that best matches the drug's presumed mode of action, rather than lumping together patients with entirely different pathophysiological patterns in so-called 'large trials', which have all failed so far.
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PMID:Pathophysiology of ischaemic stroke: insights from imaging, and implications for therapy and drug discovery. 1803 22

Although the perfusion-weighted imaging/diffusion-weighted imaging (PWI/DWI) mismatch model has been proposed to identify acute stroke patients who benefit from reperfusion therapy, the optimal definition of a mismatch is uncertain. We evaluated the odds ratio for a favorable clinical response in mismatch patients with reperfusion compared with no reperfusion for various mismatch ratio thresholds in patients enrolled in the diffusion and perfusion imaging evaluation for understanding stroke evolution (DEFUSE) study. A mismatch ratio of 2.6 provided the highest sensitivity (90%) and specificity (83%) for identifying patients in whom reperfusion was associated with a favorable response. Defining mismatch with a larger PWI/DWI ratio may provide greater power for detecting beneficial effects of reperfusion.
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PMID:Optimal definition for PWI/DWI mismatch in acute ischemic stroke patients. 1818 31

Mismatches between tissue perfusion-weighted imaging (PWI; an index of blood flow deficit) and cellular diffusion-weighted imaging (DWI; an index of tissue injury) provide information on potentially salvageable penumbra tissue in focal stroke and can identify "treatable" stroke patients. The present pre-clinical studies were conducted to: a.) Determine PWI (using perfusion delay) and DWI measurements in two experimental stroke models, b.) Utilize these measurements to characterize selective ET(A) receptor antagonism (i.e., determine efficacy, time-to-treatment and susceptibility to treatment in the different stroke models), and c.) Determine if increasing the reduced blood flow following a stroke is a mechanism of protection. Permanent middle cerebral artery occlusion (MCAO) or sham surgeries were produced in Sprague Dawley rats (SD; proximal MCAO; hypothesized to be a model of slowly evolving brain injury with a significant penumbra) and in spontaneously hypertensive rats (SHR; distal MCAO; hypothesized to be a model of rapidly evolving brain injury with little penumbra). Infusions of vehicle or SB 234551 (3, 10, or 30 microg/kg/min) were initiated at 0, 75, and/or 180 min post-surgery and maintained for the remainder of 24 h post-surgery. Hyper-intense areas of perfusion delay (PWI) in the forebrain were measured using Gadolinium (Gd) bolus contrast. DWI hyper-intense areas were also measured, and the degree of forebrain DWI-PWI mismatch was determined. Region specific analyses (ROI) were also conducted in the core ischemic and low perfusion/penumbra areas to provide indices of perfusion and changes in the degree of tissue perfusion due to SB 234551 treatment. At 24 h post-surgery, final infarct volume was measured by DWI and by staining forebrain slices. Following SD proximal MCAO, there was a significant mismatch in the ischemic forebrain PWI compared to DWI (PWI>DWI) at 60 min which was maintained up to 150 min (all p<0.05). By 24 h post-stroke, infarct volume was identical to the area of early perfusion deficit/PWI, suggesting a slow progression of infarct development that expanded into the significant, earlier cortical penumbra (i.e., model with salvageable tissue with potential for intervention). When SB 234551 was administered within the period of peak mismatch (i.e., at 75 min post-stroke), SB 234551 provided significant dose-related reductions in cortical (penumbral) progression to infarction (p<0.05). Cortical protection was related to an increased/normalization of the stroke-induced decrease in tissue perfusion in cortical penumbra areas (p<0.05). No SB 234551-induced changes in reduced tissue perfusion were observed in the striatum core ischemic area. Also, when SB-234551 was administered beyond the time of mismatch, no effect on cortical penumbra progression to infarct was observed. In comparison and strikingly different, following SHR distal MCAO there was no mismatch between PWI and DWI (PWI=DWI) as early as 60 min post-stroke, with this early change in SHR DWI being identical to the final infarct volume at 24 h, suggesting a rapidly occurring brain injury with little cortical penumbra (i.e., model with little salvageable tissue or potential for intervention). In distal MCAO, SB 234551 administered immediately at the time of stroke did not have any effect on infarct volume in SHR. These data demonstrate that selective blockade of ET(A) receptors is protective following proximal MCAO in SD (i.e. a model similar to "treatable" clinical patients). The protective mechanism appears to be due to enhanced collateral blood flow and salvage of penumbra. Therefore, the use of PWI-DWI mismatch signatures can identify treatable stroke models characterized by a salvageable penumbra and can define appropriate time to treatment protocols. In addition, tissue perfusion information obtained under these conditions might clarify mechanism of protection in the evaluation of protective compounds for focal stroke.
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PMID:SB 234551 selective ET(A) receptor antagonism: perfusion/diffusion MRI used to define treatable stroke model, time to treatment and mechanism of protection. 1846 20


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