Neuroimaging, the ischaemic penumbra, and selection of patients for acute stroke therapy

Donnan, Geoffrey A.; Davis, Stephen M.

doi:10.1016/s1474-4422(02)00189-8

Cited by 123 publications

(77 citation statements)

References 98 publications

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“…Using this technique, the CBF penumbra threshold has been found to stand B20 mL/100 g per min in humans, consistent with early reports using various perfusion techniques (Baron, 2001b;Donnan and Davis, 2002;Heiss, 2000), and accordingly, this flow threshold is widely used as a gold standard (Olivot et al, 2009;Sobesky et al, 2004;Takasawa et al, 2008;ZaroWeber et al, 2009ZaroWeber et al, , 2010a. However, using absolute CBF to define the penumbra in acute stroke does have two main limitations.…”

Section: Introductionsupporting

confidence: 80%

The Vascular Mean Transit Time: A Surrogate for the Penumbra Flow Threshold?

Carrera

Jones

Iglesias

et al. 2010

J Cereb Blood Flow Metab

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Depicting the salvageable tissue is increasingly used in the clinical setting following stroke. As absolute cerebral blood flow (CBF) is difficult to measure using perfusion magnetic resonance or computed tomography and has limitations as a penumbral marker, time-based variables, particularly the mean transit time (MTT), are routinely used as surrogates. However, a direct validation of MTT as a predictor of the penumbra threshold using gold-standard positron emission tomography (PET) is lacking. Using 15 O-PET data sets obtained from two independent acute stroke samples (N = 7 and N = 30, respectively), we derived areas under the curve (AUCs), optimal thresholds (OTs), and 90%-specificity thresholds (90%-Ts) from receiver operating characteristic curves for absolute MTT, MTT delay, and MTT ratio to predict three penumbra thresholds ('classic': CBF < 20 mL/100 g per min; 'normalized': CBF ratio < 0.5; and 'stringent': both CBF < 20 mL/100 g per min and oxygen extraction fraction > 0.55). In sample 1, AUCs ranged from 0.79 to 0.92, indicating good validity; OTs ranged from 7.8 to 8.3 seconds, 2.8 to 4.7 seconds, and 151% to 267% for absolute MTT, MTT delay, and MTT ratio, respectively, while as expected, 90%-Ts were longer. There was no significant difference between sample 1 and sample 2 for any of the above measurements, save for a single MTT parameter with a single penumbra threshold. These consistent findings from gold-standard PET obtained in two independent cohorts document that MTT is a very good surrogate to CBF for depicting the penumbra threshold.

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Section: Introductionsupporting

confidence: 80%

The Vascular Mean Transit Time: A Surrogate for the Penumbra Flow Threshold?

Carrera

Jones

Iglesias

et al. 2010

J Cereb Blood Flow Metab

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“…Finally, it was shown that the rescue of penumbral tissue correlates with clinical recovery (Alawneh et al, 2011;Furlan et al, 1996;Heiss et al, 1998;Marchal et al, 1999;Muir et al, 2006). Although this concept seems straightforward, the equation mismatch = penumbra has to be considered carefully as several methodological issues remain unresolved (Alawneh et al, 2011;Donnan and Davis, 2002;Kidwell et al, 2003;Sobesky et al, 2005) and as clinical studies of acute stroke therapy that used the mismatch concept for patient stratification produced inconclusive results (Mishra et al, 2010). Thus, the current mismatch concept has to be evaluated with respect to the following questions: (1) Can DW identify the infarct core?…”

Section: The Magnetic Resonance Imagingbased Concept Of Mismatchmentioning

confidence: 99%

Refining the Mismatch Concept in Acute Stroke: Lessons Learned from PET and MRI

Sobesky

2012

J Cereb Blood Flow Metab

110

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In ischemic stroke, positron-emission tomography (PET) established the imaging-based concept of penumbra. It defines hypoperfused, but functionally impaired, tissue with preserved viability that can be rescued by timely reperfusion. Diffusion-weighted and perfusion-weighted (PW) magnetic resonance imaging (MRI) translated the concept of penumbra to the concept of mismatch. However, the use of mismatch-based patient stratification for reperfusion therapy remains a matter of debate. The equivalence of mismatch and penumbra, as well as the validity of the classical mismatch concept is questioned for several reasons. First, methodological differences between PET and MRI lead to different definitions of the tissue at risk. Second, the mismatch concept is still poorly standardized among imaging facilities causing relevant variability in stroke research. Third, relevant conceptual issues (e.g., the choice of the adequate perfusion measure, the best quantitative approach to perfusion maps, and the required size of the mismatch) need further refinement. Fourth, the use of single thresholds does not account for the physiological heterogeneity of the penumbra and probabilistic approaches may be more promising. The implementation of this current knowledge into an optimized state-of-the-art mismatch model and its validation in clinical stroke studies remains a major challenge for future stroke research.

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“…In animal models, changes in ADC signal correspond very well to cellular swelling measured using electron microscopy (EM) in perfusion-fixed brain sections [48]. The final volume of the brain damage in stroke strongly correlates with changes in the ADC [49][50][51]. Therefore cellular edema is closely associated with ischemic brain damage.…”

Section: Volume-regulated Anion Channels and The Reversed Mode Of Glumentioning

confidence: 99%

Disruption of ionic and cell volume homeostasis in cerebral ischemia: The perfect storm

Mongin

2007

Pathophysiology

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The mechanisms of brain tissue damage in stroke are strongly linked to the phenomenon of excitotoxicity, which is defined as damage or death of neural cells due to excessive activation of receptors for the excitatory neurotransmitters glutamate and aspartate. Under physiological conditions, ionotropic glutamate receptors mediate the processes of excitatory neurotransmission and synaptic plasticity. In ischemia, sustained pathological release of glutamate from neurons and glial cells causes prolonged activation of these receptors, resulting in massive depolarization and cytoplasmic Ca 2+ overload. The NMDA subtype of glutamate receptors is particularly important as it represents the main initial route for the Ca 2+ influx. High cytoplasmic levels of Ca 2+ activate many degradative processes that, depending on the metabolic status, cause immediate or delayed death of neural cells. This traditional view has been expanded by a number of observations that implicate Cl − channels and several types of non-channel transporter proteins, such as the Na + ,K + ,2Cl − cotransporter, Na + /H + exchanger, and Na + /Ca 2+ exchanger, in the development of glutamate toxicity. Some of these ion transporters increase tissue damage by promoting pathological cell swelling and necrotic cell death, while others contribute to a long term accumulation of cytoplasmic Ca 2+ . This brief review is aimed at illustrating how the dysregulation of various ion transport processes combine in a 'perfect storm' that disrupts neural ionic homeostasis and culminates in the irreversible damage and death of neural cells. The clinical relevance of individual transporters as targets for therapeutic intervention in stroke is also briefly discussed.

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Neuroimaging, the ischaemic penumbra, and selection of patients for acute stroke therapy

Cited by 123 publications

References 98 publications

The Vascular Mean Transit Time: A Surrogate for the Penumbra Flow Threshold?

The Vascular Mean Transit Time: A Surrogate for the Penumbra Flow Threshold?

Refining the Mismatch Concept in Acute Stroke: Lessons Learned from PET and MRI

Disruption of ionic and cell volume homeostasis in cerebral ischemia: The perfect storm

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