Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Perfluorocarbons enhance a T2*-based MRI technique for identifying the penumbra in a rat model of acute ischemic stroke.

ABSTRACT: Accurate imaging of ischemic penumbra is crucial for improving the management of acute stroke patients. T2* magnetic resonance imaging (MRI) combined with a T2*oxygen challenge (T2*OC) is being developed to detect penumbra based on changes in blood deoxyhemoglobin. Using 100% O2, T2*OC-defined penumbra exhibits ongoing glucose metabolism and tissue recovery on reperfusion. However, potential limitations in translating this technique include a sinus artefact in human scans with delivery of 100% OC and relatively small signal changes. Here we investigate whether an oxygen-carrying perfluorocarbon (PFC) emulsion can enhance the sensitivity of the technique, enabling penumbra detection with lower levels of inspired oxygen. Stroke was induced in male Sprague-Dawley rats (n=17) with ischemic injury and perfusion deficit determined by diffusion and perfusion MRI, respectively. T2* signal change was measured in regions of interest (ROIs) located within ischemic core, T2*OC-defined penumbra and equivalent contralateral areas during 40% O2±prior PFC injection. Region of interest analyses between groups showed that PFC significantly enhanced the T2* response to 40% O2 in T2*-defined penumbra (mean increase of 10.6±2.3% compared to 5.6±1.5% with 40% O2, P<0.001). This enhancement was specific to the penumbra ROI. Perfluorocarbon emulsions therefore enhances the translational potential of the T2*OC technique for identifying penumbra in acute stroke patients.

SUBMITTER: Deuchar GA

PROVIDER: S-EPMC3764387 | biostudies-other | 2013 Sep

REPOSITORIES: biostudies-other

ACCESS DATA

Json Xml

Similar Datasets

CircRNA as Predictive Biomarker of Penumbra in Acute Ischemic Stroke

Project description:Acute ischemic stroke (AIS) is a leading cause of disability and mortality worldwide. By high-throughput sequencing of infarct and ischemic penumbra tissue from middle cerebral artery embolization (MCAO) mice, we identified the CircRNA expression was dramatically and selectively regulated in the penumbra tissues.

2022-11-01 | GSE186103 | GEO

The role of the cerebral capillaries in acute ischemic stroke: the extended penumbra model.

Project description:The pathophysiology of cerebral ischemia is traditionally understood in relation to reductions in cerebral blood flow (CBF). However, a recent reanalysis of the flow-diffusion equation shows that increased capillary transit time heterogeneity (CTTH) can reduce the oxygen extraction efficacy in brain tissue for a given CBF. Changes in capillary morphology are typical of conditions predisposing to stroke and of experimental ischemia. Changes in capillary flow patterns have been observed by direct microscopy in animal models of ischemia and by indirect methods in humans stroke, but their metabolic significance remain unclear. We modeled the effects of progressive increases in CTTH on the way in which brain tissue can secure sufficient oxygen to meet its metabolic needs. Our analysis predicts that as CTTH increases, CBF responses to functional activation and to vasodilators must be suppressed to maintain sufficient tissue oxygenation. Reductions in CBF, increases in CTTH, and combinations thereof can seemingly trigger a critical lack of oxygen in brain tissue, and the restoration of capillary perfusion patterns therefore appears to be crucial for the restoration of the tissue oxygenation after ischemic episodes. In this review, we discuss the possible implications of these findings for the prevention, diagnosis, and treatment of acute stroke.

| S-EPMC3652700 | biostudies-other

Early molecular oxidative stress biomarkers of ischemic penumbra in acute stroke.

Project description:ObjectivesTo assess whether plasma biomarkers of oxidative stress predict diffusion-perfusion mismatch in patients with acute ischemic stroke (AIS).MethodsWe measured plasma levels of oxidative stress biomarkers such as F2-isoprostanes (F2-isoPs), total and perchloric acid Oxygen Radical Absorbance Capacity (ORACTOT and ORACPCA), urinary levels of 8-oxo-7,8-dihydro-2'-deoxyguoanosine, and inflammatory and tissue-damage biomarkers (high-sensitivity C-reactive protein, matrix metalloproteinase-2 and -9) in a prospective study of patients with AIS presenting within 9 hours of symptom onset. Diffusion-weighted (DWI) and perfusion-weighted (PWI) MRI sequences were analyzed with a semiautomated volumetric method. Mismatch was defined as baseline mean transit time volume minus DWI volume. A percent mismatch cutoff of >20% was considered clinically significant. A stricter definition of mismatch was also used. Mismatch salvage was the region free of overlap by final infarction.ResultsMismatch >20% was present in 153 of 216 (70.8%) patients (mean [±SD] age 69.2 ± 14.3 years, 41.2% women). Patients with mismatch >20% were more likely to have higher baseline plasma levels of ORACPCA (p = 0.020) and F2-isoPs (p = 0.145). Multivariate binary logistic regression demonstrated that lnF2-isoP (odds ratio [OR] 2.44, 95% confidence interval [CI] 1.19-4.98, p = 0.014) and lnORACPCA (OR 4.18, 95% CI 1.41-12.41, p = 0.010) were independent predictors of >20% PWI-DWI mismatch and the stricter mismatch definition, respectively. lnORACTOT significantly predicted mismatch salvage volume (>20% mismatch p = 0.010, stricter mismatch definition p = 0.003).ConclusionsElevated hyperacute plasma levels of F2-isoP and ORAC are associated with radiographic evidence of mismatch and mismatch salvage in patients with AIS. If validated, these findings may add to our understanding of the role of oxidative stress in cerebral tissue fate during acute ischemia.

| S-EPMC7011868 | biostudies-literature

Molecular signature of penumbra in acute ischemic stroke: a pilot transcriptomics study.

Project description:We aimed to characterize peripheral blood gene expression profile of penumbra defined as MRI perfusion-diffusion mismatch (PD MM) in peripheral blood of patients with acute ischemic stroke. We studied 23 patients. Perfusion-diffusion mismatch volume was observed to be associated and significantly correlated with the expression of 34 genes including those related to inflammation, SUMOylation, and coagulation; while lipopolysaccharide inhibition was identified to be a candidate upstream regulator of these processes (z-score -2.38, P = 0.04). Penumbral volume is correlated with a specific gene expression profile in the peripheral blood characterized by overlap of inflammatory and neuroprotective pathways that are regulated by lipopolysaccharide inhibition.

| S-EPMC6469246 | biostudies-literature

Development and validation of a penumbra-based predictive model for thrombolysis outcome in acute ischemic stroke patients.

Project description:The use of thrombolysis in acute ischemic stroke is restricted to a small proportion of patients because of the rigid 4·5-h window. With advanced imaging-based patient selection strategy, rescuing penumbra is critical to improving clinical outcomes. In this study, we included 155 acute ischemic stroke patients (84 patients in training dataset, age from 43 to 80, 59 males; 71 patients in validation dataset, age from 36 to 80, 45 males) who underwent MR scan within the first 9-h after onset, from 7 independent centers. Based on the mismatch concept, penumbra and core area were identified and quantitatively analyzed. Moreover, predictive models were developed and validated to provide an approach for identifying patients who may benefit from thrombolytic therapy. Predictive models were constructed, and corresponding areas under the curve (AUC) were calculated to explore their performances in predicting clinical outcomes. Additionally, the models were validated using an independent dataset both on Day-7 and Day-90. Significant correlations were detected between the mismatch ratio and clinical assessments in both the training and validation datasets. Treatment option, baseline systolic blood pressure, National Institutes of Health Stroke Scale score, mismatch ratio, and three regional radiological parameters were selected as biomarkers in the combined model to predict clinical outcomes of acute ischemic stroke patients. With the external validation, this predictive model reached AUCs of 0·863 as short-term validation and 0·778 as long-term validation. This model has the potential to provide quantitative biomarkers that aid patient selection for thrombolysis either within or beyond the current time window.

| S-EPMC6154778 | biostudies-literature

Clinical MRI of acute ischemic stroke.

Project description:The most important service that imaging provides to patients with ischemic stroke is to rapidly identify those patients who are most likely to benefit from immediate treatment. This group includes patients who have severe neurological symptoms due to an occlusion of a major artery, and who are candidates for recanalization using intravenous thrombolysis or intra-arterial intervention to remove the occlusion. Outcomes for these patients are determined by symptom severity, the artery that is occluded, the size of the infarct at the time of presentation, and the effect of treatment. MRI provides key physiological information through MR angiography and diffusion MRI that has been proven to be of high clinical value in identify patients who are in need of immediate treatment. Perfusion MRI provides information about the ischemic penumbra, but its clinical value is unproven. In current clinical practice, the time since stroke onset is dominant over physiologic information provided by MRI in treatment decisions. This will change only when clinical trials prove that stroke physiology as revealed by MRI is superior to time from stroke onset in promoting good clinical outcomes.

| S-EPMC3400122 | biostudies-literature

Potential use of oxygen as a metabolic biosensor in combination with T2*-weighted MRI to define the ischemic penumbra.

Project description:We describe a novel magnetic resonance imaging technique for detecting metabolism indirectly through changes in oxyhemoglobin:deoxyhemoglobin ratios and T2(*) signal change during 'oxygen challenge' (OC, 5 mins 100% O(2)). During OC, T2(*) increase reflects O(2) binding to deoxyhemoglobin, which is formed when metabolizing tissues take up oxygen. Here OC has been applied to identify tissue metabolism within the ischemic brain. Permanent middle cerebral artery occlusion was induced in rats. In series 1 scanning (n=5), diffusion-weighted imaging (DWI) was performed, followed by echo-planar T2(*) acquired during OC and perfusion-weighted imaging (PWI, arterial spin labeling). Oxygen challenge induced a T2(*) signal increase of 1.8%, 3.7%, and 0.24% in the contralateral cortex, ipsilateral cortex within the PWI/DWI mismatch zone, and ischemic core, respectively. T2(*) and apparent diffusion coefficient (ADC) map coregistration revealed that the T2(*) signal increase extended into the ADC lesion (3.4%). In series 2 (n=5), FLASH T2(*) and ADC maps coregistered with histology revealed a T2(*) signal increase of 4.9% in the histologically defined border zone (55% normal neuronal morphology, located within the ADC lesion boundary) compared with a 0.7% increase in the cortical ischemic core (92% neuronal ischemic cell change, core ADC lesion). Oxygen challenge has potential clinical utility and, by distinguishing metabolically active and inactive tissues within hypoperfused regions, could provide a more precise assessment of penumbra.

| S-EPMC3119432 | biostudies-literature

Does Clot Burden Score on Baseline T2*-MRI Impact Clinical Outcome in Acute Ischemic Stroke Treated with Mechanical Thrombectomy?

Project description:BACKGROUND AND PURPOSE:A long clot, defined by a low (0-6) clot burden score (CBS) assessed by T2*-MR sequence, is associated with worse clinical outcome after intravenous thrombolysis (IVT) for acute ischemic stroke than is a small clot (CBS, 7-10). The added benefit of mechanical thrombectomy (MT) might be higher in patients with long clot. The aim of this pre-specified post hoc analysis of the THRombectomie des Artères CErebrales (THRACE) trial was to assess the association between T2*-CBS, successful recanalization and clinical outcome. METHODS:Of 414 patients randomized in the THRACE trial, 281 patients were included in this analysis. Associations between T2*-CBS and clinical outcome on the modified Rankin Scale (mRS) at 3 months were tested. RESULTS:High T2*-CBS, i.e., small clot, was associated with a shift toward better outcome on the mRS; proportional odds ratio (POR) per point CBS was 1.19 (95% confidence interval [CI], 1.05 to 1.34) in the whole population, 1.34 (95% CI, 1.13 to 1.59) in IVT group, and 1.04 (95% CI, 0.87 to 1.23) in IVTMT group. After adjustment for baseline prognostic variables, the effect of the full scale T2*-CBS was not statistically significant in the whole population and for the IVTMT group but remains significant for the IVT group (POR, 1.32; 95% CI, 1.11 to 1.58). CONCLUSION:s A small clot, as assessed using T2*-CBS, is associated with improved outcome and may be used as a prognostic marker. Despite the worst outcome with long clot, the relative benefit of MT over IVT seemed to increase with low T2*-CBS and longer clot.

| S-EPMC6372898 | biostudies-literature

Predicting Penumbra Salvage and Infarct Growth in Acute Ischemic Stroke: A Multifactor Survival Game.

Project description:BackgroundEffective treatment of acute ischemic stroke requires reperfusion of salvageable tissue. We investigated the predictors of penumbra salvage (PS) and infarct growth (IG) in a large cohort of stroke patients.MethodsIn the ASTRAL registry from 2003 to 2016, we selected middle cerebral artery strokes <24 h with a high-quality CT angiography and CT perfusion. PS and IG were correlated in multivariate analyses with clinical, biochemical and radiological variables, and with clinical outcomes.ResultsAmong 4090 patients, 551 were included in the study, 50.8% male, mean age (±SD) 66.3 ± 14.7 years, mean admission NIHSS (±SD 13.3 ± 7.1) and median onset-to-imaging-time (IQR) 170 (102 to 385) minutes. Increased PS was associated with the following: higher BMI and lower WBC; neglect; larger penumbra; absence of early ischemic changes, leukoaraiosis and other territory involvement; and higher clot burden score. Reduced IG was associated with the following: non-smokers; lower glycemia; larger infarct core; absence of early ischemic changes, chronic vascular brain lesions, other territory involvement, extracranial arterial pathology and hyperdense middle cerebral artery sign; and higher clot burden score. When adding subacute variables, recanalization was associated with increased PS and reduced IG, and the absence of haemorrhage with reduced IG. Collateral status was not significantly associated with IG nor with PS. Increased PS and reduced IG correlated with better 3- and 12-month outcomes.ConclusionIn our comprehensive analysis, multiple factors were found to be responsible for PS or IG, the strongest being radiological features. These findings may help to better select patients, particularly for more aggressive or late acute stroke treatment.

| S-EPMC10380847 | biostudies-literature

Stroke penumbra defined by an MRI-based oxygen challenge technique: 1. Validation using [14C]2-deoxyglucose autoradiography.

Project description:Accurate identification of ischemic penumbra will improve stroke patient selection for reperfusion therapies and clinical trials. Current magnetic resonance imaging (MRI) techniques have limitations and lack validation. Oxygen challenge T(2)(*) MRI (T(2)(*) OC) uses oxygen as a biotracer to detect tissue metabolism, with penumbra displaying the greatest T(2)(*) signal change during OC. [(14)C]2-deoxyglucose (2-DG) autoradiography was combined with T(2)(*) OC to determine metabolic status of T(2)(*)-defined penumbra. Permanent middle cerebral artery occlusion was induced in anesthetized male Sprague-Dawley rats (n=6). Ischemic injury and perfusion deficit were determined by diffusion- and perfusion-weighted imaging, respectively. At 147 ± 32 minutes after stroke, T(2)(*) signal change was measured during a 5-minute 100% OC, immediately followed by 125 μCi/kg 2-DG, intravenously. Magnetic resonance images were coregistered with the corresponding autoradiograms. Regions of interest were located within ischemic core, T(2)(*)-defined penumbra, equivalent contralateral structures, and a region of hyperglycolysis. A T(2)(*) signal increase of 9.22% ± 3.9% (mean ± s.d.) was recorded in presumed penumbra, which displayed local cerebral glucose utilization values equivalent to contralateral cortex. T(2)(*) signal change was negligible in ischemic core, 3.2% ± 0.78% in contralateral regions, and 1.41% ± 0.62% in hyperglycolytic tissue, located outside OC-defined penumbra and within the diffusion abnormality. The results support the utility of OC-MRI to detect viable penumbral tissue following stroke.

| S-EPMC3154682 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data