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Defining the ischemic penumbra using magnetic resonance oxygen metabolic index.

ABSTRACT: Penumbral biomarkers promise to individualize treatment windows in acute ischemic stroke. We used a novel magnetic resonance imaging approach that measures oxygen metabolic index (OMI), a parameter closely related to positron emission tomography-derived cerebral metabolic rate of oxygen utilization (CMRO2), to derive a pair of ischemic thresholds: (1) an irreversible-injury threshold that differentiates ischemic core from penumbra and (2) a reversible-injury threshold that differentiates penumbra from tissue not-at-risk for infarction.Forty patients with acute ischemic stroke underwent magnetic resonance imaging at 3 time points after stroke onset: <4.5 hours (for OMI threshold derivation), 6 hours (to determine reperfusion status), and 1 month (for infarct probability determination). A dynamic susceptibility contrast method measured cerebral blood flow, and an asymmetrical spin echo sequence measured oxygen extraction fraction, to derive OMI (OMI=cerebral blood flow×oxygen extraction fraction). Putative ischemic threshold pairs were iteratively tested using a computation-intensive method to derive infarct probabilities in 3 tissue groups defined by the thresholds (core, penumbra, and not-at-risk tissue). An optimal threshold pair was chosen based on its ability to predict infarction in the core, reperfusion-dependent survival in the penumbra, and survival in not-at-risk tissue. The predictive abilities of the thresholds were then tested within the same cohort using a 10-fold cross-validation method.The optimal OMI ischemic thresholds were found to be 0.28 and 0.42 of normal values in the contralateral hemisphere. Using the 10-fold cross-validation method, median infarct probabilities were 90.6% for core, 89.7% for nonreperfused penumbra, 9.95% for reperfused penumbra, and 6.28% for not-at-risk tissue.OMI thresholds, derived using voxel-based, reperfusion-dependent infarct probabilities, delineated the ischemic penumbra with high predictive ability. These thresholds will require confirmation in an independent patient sample.

SUBMITTER: An H

PROVIDER: S-EPMC4533116 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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Defining the ischemic penumbra using magnetic resonance oxygen metabolic index.

An Hongyu H Ford Andria L AL Chen Yasheng Y Zhu Hongtu H Ponisio Rosana R Kumar Gyanendra G Shanechi Amirali Modir AM Khoury Naim N Vo Katie D KD Williams Jennifer J Derdeyn Colin P CP Diringer Michael N MN Panagos Peter P Powers William J WJ Lee Jin-Moo JM Lin Weili W

Stroke 20150226 4

<h4>Background and purpose</h4>Penumbral biomarkers promise to individualize treatment windows in acute ischemic stroke. We used a novel magnetic resonance imaging approach that measures oxygen metabolic index (OMI), a parameter closely related to positron emission tomography-derived cerebral metabolic rate of oxygen utilization (CMRO2), to derive a pair of ischemic thresholds: (1) an irreversible-injury threshold that differentiates ischemic core from penumbra and (2) a reversible-injury thresh ...[more]

PMID: 25721017

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Project description:The ability to identify metabolically active and potentially salvageable ischaemic penumbra is crucial for improving treatment decisions in acute stroke patients. Our solution involves two complementary novel MRI techniques (Glasgow Oxygen Level Dependant (GOLD) Metabolic Imaging), which when combined with a perfluorocarbon (PFC) based oxygen carrier and hyperoxia can identify penumbra due to dynamic changes related to continued metabolism within this tissue compartment. Our aims were (i) to investigate whether PFC offers similar enhancement of the second technique (Lactate Change) as previously demonstrated for the T2*OC technique (ii) to demonstrate both GOLD metabolic imaging techniques working concurrently to identify penumbra, following administration of Oxycyte® (O-PFC) with hyperoxia. Methods: An established rat stroke model was utilised. Part-1: Following either saline or PFC, magnetic resonance spectroscopy was applied to investigate the effect of hyperoxia on lactate change in presumed penumbra. Part-2; rats received O-PFC prior to T2*OC (technique 1) and MR spectroscopic imaging, which was used to identify regions of tissue lactate change (technique 2) in response to hyperoxia. In order to validate the techniques, imaging was followed by [14C]2-deoxyglucose autoradiography to correlate tissue metabolic status to areas identified as penumbra. Results: Part-1: PFC+hyperoxia resulted in an enhanced reduction of lactate in the penumbra when compared to saline+hyperoxia. Part-2: Regions of brain tissue identified as potential penumbra by both GOLD metabolic imaging techniques utilising O-PFC, demonstrated maintained glucose metabolism as compared to adjacent core tissue. Conclusion: For the first time in vivo, enhancement of both GOLD metabolic imaging techniques has been demonstrated following intravenous O-PFC+hyperoxia to identify ischaemic penumbra. We have also presented preliminary evidence of the potential therapeutic benefit offered by O-PFC. These unique theranostic applications would enable treatment based on metabolic status of the brain tissue, independent of time from stroke onset, leading to increased uptake and safer use of currently available treatment options.

Project description:BackgroundIt has been hypothesized that an absolute quantitative dynamic susceptibility contrast (DSC) cerebral perfusion-weighted imaging (PWI) technique based on self-calibrated echo-planar imaging (EPI) could be a reliable measurement of quantitative cerebral blood flow (qCBF) and quantitative cerebral blood volume (qCBV). This study aimed to investigate the clinical value of this technique in offering a unique insight into ischemic stroke (IS) pathophysiology and improving the sensitivity of IS diagnosis.MethodsA total of 14 patients with IS who underwent routine magnetic resonance imaging (MRI) and Self-CALibrated EPI Perfusion-Weighted Imaging (SCALE-PWI) scanning were prospectively recruited as a consecutive convenience sample. qCBF and qCBV maps were processed immediately online after the scan. Then, 2 radiologists independently drew the region of interest (ROI) of the infarct core, ischemic penumbra, and the contralateral normal tissues on each map for the statistical analyses. The paired-samples t-test, Wilcoxon signed-rank test, independent-samples t-test, and receiver operating characteristic (ROC) curve were performed. A value of P<0.05 was considered statistically significant with 95% confidence intervals (CI).ResultsAll the values of qCBF and qCBV in the lesions were lower than those in the contralateral normal tissues (all P<0.05). The values of qCBF and qCBV in the infarct core were lower than those in the ischemic penumbra (mean values: 16.42 vs. 21.54 mL/100 g/min, P=0.013; 1.23 vs. 1.47 mL/100 g, P=0.049, respectively). The qCBF threshold of the infarct core was 18.18 mL/100 g/min (sensitivity, 71.40%; specificity, 64.30%) and the qCBF threshold of the ischemic penumbra was 28.09 mL/100 g/min (sensitivity, 78.60%; specificity, 85.70%).ConclusionsDifferent from the previous semi-quantitative measurement, the SCALE-PWI technique has the potential to provide absolute quantitative hemodynamic information which may be used to detect the infarct core and ischemic penumbra in a relatively short scan time.

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Defining the ischemic penumbra using magnetic resonance oxygen metabolic index.

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Defining the ischemic penumbra using magnetic resonance oxygen metabolic index.

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