The Infarct Core is Well Represented by the Acute Diffusion Lesion: Sustained Reversal is Infrequent

Campbell, Bruce C.V.; Purushotham, Archana; Christensen, Søren; Desmond, Patricia; Nagakane, Yoshinari; Parsons, Mark; Lansberg, Maarten G.; Mlynash, Michael; Straka, Matús; Silva, Deidre Anne De; Olivot, Jean‐Marc; Bammer, Roland; Albers, Gregory W.; Donnan, Geoffrey A.; Davis, Stephen M.

doi:10.1038/jcbfm.2011.102

Cited by 181 publications

(174 citation statements)

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“…Patients were excluded because more than 50% of the DWI lesion had normal perfusion at the time of CTP (n ¼ 18), there was insufficient quality of the baseline CTP data (n ¼ 4) and coregistration failures due to image distortions (n ¼ 3). The mean age of the included population was 68 years (SD 14), median baseline National Institutes of Health Stroke Scale (NIHSS) score was [16][17][18][19], median time from stroke onset to CT was 185 min (IQR 180-238) and the median time between completion of CT and start of MR was 36 min (IQR 25-79, range 15-181 min). Twenty-nine patients received intravenous thrombolysis only, 16 underwent endovascular therapy only, 14 had both therapies and the remaining 44 had no revascularization therapy.…”

Section: Resultsmentioning

confidence: 99%

“…We, however, found no association between time from CT-to-MRI and the optimal rCBF threshold, suggesting that the dataset is sufficiently uniform in terms of the patients' CT-to-MRI intervals. Additional factors that make DWI an imperfect gold standard include the effects of edema, partial reversal of the DWI after reperfusion, 19,20 and the inherently subjective nature of lesion outlines. 21 Consequently, MRI can over-or underestimate the ischemic core in individual patients, which makes it unrealistic to expect perfect concordance between ischemic core measurements on CT and MRI.…”

Section: Discussionmentioning

confidence: 99%

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A benchmarking tool to evaluate computer tomography perfusion infarct core predictions against a DWI standard

Cereda

Christensen

Campbell

et al. 2016

J Cereb Blood Flow Metab

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Differences in research methodology have hampered the optimization of Computer Tomography Perfusion (CTP) for identification of the ischemic core. We aim to optimize CTP core identification using a novel benchmarking tool. The benchmarking tool consists of an imaging library and a statistical analysis algorithm to evaluate the performance of CTP. The tool was used to optimize and evaluate an in-house developed CTP-software algorithm. Imaging data of 103 acute stroke patients were included in the benchmarking tool. Median time from stroke onset to CT was 185 min (IQR 180-238), and the median time between completion of CT and start of MRI was 36 min (IQR 25-79). Volumetric accuracy of the CTP-ROIs was optimal at an rCBF threshold of <38%; at this threshold, the mean difference was 0.3 ml (SD 19.8 ml), the mean absolute difference was 14.3 (SD 13.7) ml, and CTP was 67% sensitive and 87% specific for identification of DWI positive tissue voxels. The benchmarking tool can play an important role in optimizing CTP software as it provides investigators with a novel method to directly compare the performance of alternative CTP software packages.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A benchmarking tool to evaluate computer tomography perfusion infarct core predictions against a DWI standard

Cereda

Christensen

Campbell

et al. 2016

J Cereb Blood Flow Metab

Self Cite

161

160

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“…The initial diffusion lesion does not consist of only irreversibly infarcted tissue; diffusion lesions may be reversed if blood flow is restored at an early time point. However, the reversal of acute diffusion lesions beyond 3-4.5 h is infrequent (19). Critically hypoperfused tissue (i.e., the penumbra) cannot be clearly differentiated from tissue experiencing oligemia without the application of well-defined perfusion maps and thresholds (20); the PWI abnormality often overestimates the amount of tissue at risk of infarction.…”

Section: Mri Mismatch As Surrogate For Penumbramentioning

confidence: 99%

Validation of MRI Determination of the Penumbra by PET Measurements in Ischemic Stroke

Heiss

Weber

2016

J Nucl Med

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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 diffusionweighted 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. ENERGY REQUIREMENTS OF BRAIN TISSUEBecause the energy demand of nervous tissue is very high, sufficient blood supply to the brain must be maintained consistently. The oxygen consumption of the brain is involved almost entirely in the oxidative metabolism of glucose which, in normal physiologic conditions, is the almost exclusive substrate for the energy metabolism of the brain (1). The glucose metabolized in neuronal cell bodies is used mainly to support cellular vegetative and hou...

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“…Davis et al [19] provide appealing arguments in support of the PWI/DWI mismatch as a potential means for identifying a sub-group of patients who may benefit from tPA beyond 4.5 h or other reperfusion therapies. Specifically, although DWI signal reversal has been observed, pooled Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET) and Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution Study (DEFUSE) data suggest that DWI reversal is rare particularly for reperfusion beyond 3 h [20,21]. In addition, without reperfusion, DWI lesions are typically expanded into the PWI-defined abnormal areas [22,23].…”

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confidence: 99%

Editorial

Lin

2012

Transl. Stroke Res.

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The Infarct Core is Well Represented by the Acute Diffusion Lesion: Sustained Reversal is Infrequent

Cited by 181 publications

References 34 publications

A benchmarking tool to evaluate computer tomography perfusion infarct core predictions against a DWI standard

A benchmarking tool to evaluate computer tomography perfusion infarct core predictions against a DWI standard

Validation of MRI Determination of the Penumbra by PET Measurements in Ischemic Stroke

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