Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Santosh C

PROVIDER: S-EPMC3119432 | biostudies-literature | 2008 Oct

REPOSITORIES: biostudies-literature

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

Santosh Celestine C Brennan David D McCabe Christopher C Macrae I Mhairi IM Holmes William M WM Graham David I DI Gallagher Lindsay L Condon Barrie B Hadley Donald M DM Muir Keith W KW Gsell Willy W

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 20080611 10

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 se ...[more]

PMID: 18545262

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Project description: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.

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.

Dataset Information

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

Publications

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

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