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Objective: Accurate identification of the ischemic penumbra, the therapeutic target in acute clinical stroke, is of critical importance to identify patients who might benefit from reperfusion therapies beyond the established time windows. Therefore, we aimed to validate magnetic resonance imaging (MRI) mismatch–based penumbra detection against full quantitative positron emission tomography (15O‐PET), the gold standard for penumbra detection in acute ischemic stroke. Methods: Ten patients (group A) with acute and subacute ischemic stroke underwent perfusion‐weighted (PW)/diffusion‐weighted MRI and consecutive full quantitative 15O‐PET within 48 hours of stroke onset. Penumbra as defined by 15O‐PET cerebral blood flow (CBF), oxygen extraction fraction, and oxygen metabolism was used to validate a wide range of established PW measures (eg, time‐to‐maximum [Tmax]) to optimize penumbral tissue detection. Validation was carried out using a voxel‐based receiver‐operating‐characteristic curve analysis. The same validation based on penumbra as defined by quantitative 15O‐PET CBF was performed for comparative reasons in 23 patients measured within 48 hours of stroke onset (group B). Results: The PW map Tmax (area‐under‐the‐curve = 0.88) performed best in detecting penumbral tissue up to 48 hours after stroke onset. The optimal threshold to discriminate penumbra from oligemia was Tmax >5.6 seconds with a sensitivity and specificity of >80%. Interpretation: The performance of the best PW measure Tmax to detect the upper penumbral flow threshold in ischemic stroke is excellent. Tmax >5.6 seconds–based penumbra detection is reliable to guide treatment decisions up to 48 hours after stroke onset and might help to expand reperfusion treatment beyond the current time windows. ANN NEUROL 2019;85:875–886. [ABSTRACT FROM AUTHOR]

Background: In acute stroke, the magnetic resonance (MR) imaging-based mismatch concept is used to select patients with tissue at risk of infarction for reperfusion therapies. There is however a controversy if non-deconvolved or deconvolved perfusion weighted (PW) parameter maps perform better in tissue at risk prediction and which parameters and thresholds should be used to guide treatment decisions. Methods: In a group of 22 acute stroke patients with consecutive MR and quantitative positron emission tomography (PET) imaging, non-deconvolved parameters were validated with the gold standard for penumbral-flow (PF) detection 15O-water PET. Performance of PW parameters was assessed by a receiver operating characteristic curve analysis to identify the accuracy of each PWI map to detect the -upper PF threshold as defined by PET cerebral blood flow <20 mL/100 g/min. Results: Among normalized non-deconvolved parameters, PW-first moment without delay correction (FM without DC) > 3.6 s (area under the curve [AUC] = 0.89, interquartile range [IQR] 0.85–0.94), PW-maximum of the concentration curve (Cmax) < 0.66 (AUC = 0.92, IQR 0.84–0.96) and PW-time to peak (TTP) > 4.0 s (AUC = 0.92, IQR 0.87–0.94) perform significantly better than other non-deconvolved parameters to detect the PF threshold as defined by PET. Conclusions: Non-deconvolved parameters FM without DC, Cmax and TTP are an observer-independent alternative to established deconvolved parameters (e.g., Tmax) to guide treatment decisions in acute stroke. [ABSTRACT FROM AUTHOR]

Objective: Accurate identification of the ischemic penumbra, the therapeutic target in acute clinical stroke, is of critical importance to identify patients who might benefit from reperfusion therapies beyond the established time windows. Therefore, we aimed to validate magnetic resonance imaging (MRI) mismatch-based penumbra detection against full quantitative positron emission tomography (15 O-PET), the gold standard for penumbra detection in acute ischemic stroke.Methods: Ten patients (group A) with acute and subacute ischemic stroke underwent perfusion-weighted (PW)/diffusion-weighted MRI and consecutive full quantitative 15 O-PET within 48 hours of stroke onset. Penumbra as defined by 15 O-PET cerebral blood flow (CBF), oxygen extraction fraction, and oxygen metabolism was used to validate a wide range of established PW measures (eg, time-to-maximum [Tmax]) to optimize penumbral tissue detection. Validation was carried out using a voxel-based receiver-operating-characteristic curve analysis. The same validation based on penumbra as defined by quantitative 15 O-PET CBF was performed for comparative reasons in 23 patients measured within 48 hours of stroke onset (group B).Results: The PW map Tmax (area-under-the-curve = 0.88) performed best in detecting penumbral tissue up to 48 hours after stroke onset. The optimal threshold to discriminate penumbra from oligemia was Tmax >5.6 seconds with a sensitivity and specificity of >80%.Interpretation: The performance of the best PW measure Tmax to detect the upper penumbral flow threshold in ischemic stroke is excellent. Tmax >5.6 seconds-based penumbra detection is reliable to guide treatment decisions up to 48 hours after stroke onset and might help to expand reperfusion treatment beyond the current time windows. ANN NEUROL 2019;85:875-886. [ABSTRACT FROM AUTHOR]

The concept of the ischemic penumbra was formulated on the basis of animal experiments showing functional impairment and electrophysiologic disturbances with decreasing flow to the brain below defined values (the threshold for function) and irreversible tissue damage with blood supply further decreased (the threshold for infarction). The perfusion range between these thresholds was termed the "penumbra," and restitution of flow above the functional threshold was able to reverse the deficits without permanent damage. In further experiments, the dependency of the development of irreversible lesions on the interaction of the severity and the duration of critically reduced blood flow was established, proving that the lower the flow, the shorter the time for efficient reperfusion. As a consequence, infarction develops from the core of ischemia to the areas of less severe hypoperfusion. The translation of this experimental concept as the basis for the efficient treatment of stroke requires noninvasive methods with which regional flow and energy metabolism can be repeatedly investigated to demonstrate penumbra tissue, which can benefit from therapeutic interventions. PET allows the quantification of regional cerebral blood flow, the regional oxygen extraction fraction, and the regional metabolic rate for oxygen. With these variables, clear definitions of irreversible tissue damage and of critically hypoperfused but potentially salvageable tissue (i.e., the penumbra) in stroke patients can be achieved. However, PET is a research tool, and its complex logistics limit clinical routine applications. Perfusion-weighted or diffusion-weighted MRI is a widely applicable clinical tool, and the "mismatch" between perfusion-weighted and diffusion-weighted abnormalities serves as an indicator of the penumbra. However, comparative studies of perfusion-weighted or diffusion-weighted MRI and PET have indicated overestimation of the core of irreversible infarction as well as of the penumbra by the MRI modalities. Some of these discrepancies can be explained by the nonselective application of relative perfusion thresholds, which might be improved by more complex analytic procedures. The heterogeneity of the MRI signatures used for the definition of the mismatch are also responsible for disappointing results in the application of perfusion-weighted or diffusion-weighted MRI to the selection of patients for clinical trials. As long as validation of the mismatch selection paradigm is lacking, the use of this paradigm as a surrogate marker of outcome is limited., (© 2017 by the Society of Nuclear Medicine and Molecular Imaging.)

Background: Brain tissue hypoattenuation on early computed tomography is frequently included in decision making in acute stroke management. However, its pathophysiological counterpart needs further evaluation., Methods: By comparative imaging with diffusion-weighted imaging and 15O-water positron emission tomography we aimed to interpret early (<6 h) hypoattenuation., Results: In 11 patients, the hypoattenuation corresponded to a decreased proton diffusion (median 115.9% relative DWI value) measured by magnetic resonance imaging and to a severe hypoperfusion (below 12 ml/100 g/ min) assessed by positron emission tomography. The volume of parenchymal hypoattenuation correlated to the tissue with disturbed diffusion (Spearman's rho=0.73), but largely underestimated the hypoperfusion below 20 ml/100 g/min., Conclusions: Early hypoattenuation reflects the coupling of the severity of ischemia and resulting diffusion changes. It allows an estimate of the infarct core but underestimates the penumbral hypoperfusion., (Copyright (c) 2006 S. Karger AG, Basel.)