Elsevier

The Lancet Neurology

Volume 1, Issue 7, November 2002, Pages 417-425
The Lancet Neurology

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

https://doi.org/10.1016/S1474-4422(02)00189-8Get rights and content

Summary

Advances in neuroimaging have been central to the expansion of knowledge in the neurosciences over the past 20 years. One of the most important roles of brain imaging is in the selection of patients for acute stroke therapy. Currently, computed tomography (CT) is commonly used to select patients who have had strokes for thrombolytic therapy on the basis of the absence of haemorrhage and, more controversially, the presence of early CT changes of ischaemia. Since patients with ischaemic penumbra are more likely than those without to respond to therapy, identification of patients with this feature will become increasingly important. Although several imaging modalities can identify the penumbra, the most practical is magnetic resonance imaging (MRI) showing perfusion-weighted and diffusion-weighted imaging mismatch. Although uncertainties in image interpretation remain, surrogate MRI outcome measures are becoming an important component of translational research. Future developments in imaging technologies may provide other opportunities for surrogate outcome studies.

Section snippets

CT

Without CT, the introduction of thrombolysis as the first successful form of acute stroke therapy would not have been possible. Indeed, one possible explanation for the unsuccessful outcome of the early trials of thrombolysis with streptokinase in the pre-CT era was the inability of the investigators to distinguish reliably between cerebral haemorrhage and infarction.9 CT can exclude cerebral haemorrhage with almost complete sensitivity and specificity.

More recently, CT has been used to detect

What is the ischaemic penumbra and how is it best imaged?

The ischaemic penumbra is functionally impaired but potentially viable tissue that (normally) surrounds an area of recent cerebral infarction.2, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49 Since the original definition proposed by Astrup and co-workers3 in a baboon model of cerebral ischaemia, in which blood flow was measured by the hydrogen electrode technique and tissue function by somatosensory evoked potentials, various ways of identifying the penumbra have been developed.39, 41, 42 Baron

Duration and temporal and spatial progression of the penumbra

The duration of the penumbra in human beingss is still uncertain. Heiss and colleagues80 suggested that beyond 6 h, 20% or less of penumbra remained. Hence, there is a need to focus most efforts at tissue salvage within the first 6 h after stroke onset. By contrast, Furlan and co-workers81 used PET with oxygen and water techniques and found that a mean of 30% of tissue was penumbral when scanned 7–17 h after stroke onset. Their findings were confirmed in a study by Read and colleagues51 with 18

Where to now?

Despite the advances in imaging technology over the past 20 years, we seem to be at the beginning of its effective use in translational stroke research.103 Various exciting developments have occurred including the introduction of magnetic resonance spectroscopy: for example, a neurochemical fingerprint of ischaemic tissue, which reflects its viability, can be obtained.104, 105 Work by our group has shown that spectroscopic changes in lesion concentrations of lactate and N-acetylaspartate

Search strategy and selection criteria

Data for this review were identified by searches of PubMed, and many articles were also identified through searches of the extensive files of the authors. The search terms “ischaemic penumbra”, “penumbra review”, and “neuroimaging” were used. Only papers published in English were reviewed.

References (112)

  • WD Heiss et al.

    Imaging in cerebrovascular disease.

    Curr Opin Neurol

    (2001)
  • J Astrup et al.

    Thresholds in cerebral ischemia: the ischemic penumbra.

    Stroke

    (1981)
  • Tissue plasminogen activator for acute ischemic stroke

    N Engl J Med

    (1995)
  • The International Stroke Trial (IST): a randomised trial of aspirin, subcutaneous heparin, both, or neither among 19 435 patients with acute ischaemic stroke

    Lancet

    (1997)
  • CAST: randomised placebo-controlled trial of early aspirin use in 20 000 patients with acute ischaemic stroke

    Lancet

    (1997)
  • G Donnan

    Lifesaving for stroke.

    Lancet

    (1993)
  • JS Meyer et al.

    Therapeutic thrombolysis in cerebral thromboembolism: randomized evaluation of intravenous streptokinase

  • G Del Zoppo et al.

    Ischemic damage of brain microvessels: inherent risks for thrombolytic treatment in stroke.

    J Neurol Neurosurg Psychiatry

    (1998)
  • R von Kummer et al.

    Acute stroke: usefulness of early CT findings before thrombolytic therapy.

    Radiology

    (1997)
  • von KummerR

    Effect of training in reading CT scans on patient selection for ECASS II.

    Neurology

    (1998)
  • R von Kummer et al.

    Interobserver agreement in assessing early CT signs of middle cerebral artery infarction.

    AJNR Am J Neuroradiol

    (1996)
  • von KummerR

    CT of acute cerebral ischemia.

    Radiology

    (2000)
  • MH Lev et al.

    Acute stroke: improved nonenhanced CT detection: benefits of soft-copy interpretation by using variable window width and center level settings.

    Radiology

    (1999)
  • DE Levy et al.

    Factors related to intracranial hematoma formation in patients receiving tissue-type plasminogen activator for acute ischemic stroke.

    Stroke

    (1994)
  • C Berger et al.

    Hemorrhagic transformation of ischemic brain tissue: asymptomatic or symptomatic?

    Stroke

    (2001)
  • W Hacke et al.

    Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke: the European Cooperative Acute Stroke Study (ECASS).

    JAMA

    (1995)
  • V Larrue et al.

    Risk factors for severe hemorrhagic transformation in ischemic stroke patients treated with recombinant tissue plasminogen activator: a secondary analysis of the European-Australasian Acute Stroke Study (ECASS II).

    Stroke

    (2001)
  • A Jaillard et al.

    Hemorrhagic transformation in acute ischemic stroke: the MAST-E study. MAST-E Group.

    Stroke

    (1999)
  • D Tanne et al.

    Markers of increased risk of intracerebral hemorrhage after intravenous recombinant tissue plasminogen activator therapy for acute ischemic stroke in clinical practice: the Multicenter rt-PA Stroke Survey.

    Circulation

    (2002)
  • JC Grotta et al.

    Agreement and variability in the interpretation of early CT changes in stroke patients qualifying for intravenous rtPA therapy.

    Stroke

    (1999)
  • SC Patel et al.

    Lack of clinical significance of early ischemic changes on computed tomography in acute stroke.

    JAMA

    (2001)
  • A Gilligan R Markus S Read et al Baseline blood pressure and not early CT changes predict major hemorrhage after...
  • C Cornu et al.

    Streptokinase in acute ischemic stroke: an individual patient data meta-analysis—the Thrombolysis in Acute Stroke Pooling Project.

    Stroke

    (2000)
  • P Barber et al.

    Identification of major ischemic change: diffusion-weighted imaging versus computed tomography.

    Stroke

    (1999)
  • PA Barber et al.

    Absent middle cerebral artery flow predicts the presence and evolution of the ischemic penumbra.

    Neurology

    (1999)
  • DG Darby et al.

    Pathophysiological topography of acute ischemia by combined diffusion-weighted and perfusion MRI.

    Stroke

    (1999)
  • JD Eastwood et al.

    CT perfusion scanning with deconvolution analysis: pilot study in patients with acute middle cerebral artery stroke.

    Radiology

    (2002)
  • PD Schellinger et al.

    A standardized MRI stroke protocol: comparison with CT in hyperacute intracerebral hemorrhage.

    Stroke

    (1999)
  • M Wiesmann et al.

    Detection of hyperacute parenchymal hemorrhage of the brain using echoplanar T2*-weighted and diffusion-weighted MRI.

    Eur Radiol

    (2001)
  • J Fiebach et al.

    Comparison of CT with diffusion-weighted MRI in patients with hyperacute stroke.

    Neuroradiology

    (2001)
  • PA Barber et al.

    Identification of major ischemic change: diffusion-weighted imaging versus computed tomography.

    Stroke

    (1999)
  • A Jaillard et al.

    Significance of early CT signs in acute stroke: a CT scan-diffusion MRI study.

    Cerebrovasc Dis

    (2002)
  • CS Kidwell et al.

    Predictors of hemorrhagic transformation in patients receiving intra-arterial thrombolysis.

    Stroke

    (2002)
  • WD Heiss et al.

    Which targets are relevant for therapy of acute ischemic stroke?

    Stroke

    (1999)
  • WD Heiss

    Ischemic penumbra: evidence from functional imaging in man.

    J Cereb Blood Flow Metab

    (2000)
  • WD Heiss et al.

    The ischemic penumbra.

    Curr Opin Neurol

    (1994)
  • J Baron et al.

    Use of PET methods for measurement of cerebral energy metabolism and hemodynamics in cerebrovascular disease.

    J Cereb Blood Flow Metab

    (1989)
  • J Baron

    Mapping the ischaemic penumbra with PET: implications for acute stroke treatment.

    Cerebrovasc Dis

    (1999)
  • M Fisher et al.

    Evolving stroke and the ischemic penumbra.

    Neurology

    (1996)
  • M Fisher et al.

    Applications of diffusion-perfusion magnetic resonance imaging in acute ischemic stroke.

    Neurology

    (1999)
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