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Rüdiger von Kummer MD is
Professor of Diagnostic Radiology/
Neuroradiology and is Head of the
Department of Neuroradiology
at the University of Dresden,
Germany. Prior to taking up
these positions in 1996, Dr von
Kummer worked at the University
of Heidelberg School of Medicine
for 25 years. For 13 of these years,
he was Director of the Cerebral
Vascular Research Laboratory and
he also worked in the Departments
of Neurology and Neuroradiology.
Dr von Kummer’s research interests
include the pathophysiology of
cerebral circulation, together with
MRI and CT in acute ischemia.
He has published more than 170
original papers and has contributed
to over 50 books.
Imanuel Dzialowski MD is a
Stroke Fellow at the University
of Calgary, Department of
Neurosciences, Foothills Hospital.
Before taking up this appointment,
he participated in residencies in
Neurology and Neuroradiology
at the University of Dresden.
The subject of his MD thesis was
‘CT monitoring of experimental
ischaemic oedema during
ischaemia and reperfusion’. He
has published a number of papers
with Dr von Kummer on imaging
techniques in acute stroke. |
Role of diagnostic radiology in the management of acute stroke
Imanuel Dzialowski1,
Rüdiger von Kummer2
1 Department of Neurosciences, Stroke Program,
University of Calgary, Alberta, Canada;
2 Department of Neuroradiology, University of Dresden,
Germany
Address for correspondence:
Rüdiger von Kummer, MD
Professor of Neuroradiology
Head, Department of Neuroradiology
University Hospital, Fetscherstr. 74
D-01307 Dresden, Germany
Tel: +49-(351)-458-2660 Fax: +49-(351)-458-4370
Email: ruediger.vonkummer@uniklinikum-dresden.de
Abstract
This article discusses the clinical efficacy of diagnostic
imaging in acute stroke. It compares computed
tomography (CT) with magnetic resonance imaging
(MRI) according to six different levels of clinical efficacy.
The feasibility of MRI is limited. Both CT and MRI
have the technical capacity to exclude acute brain
haemorrhage. CT detects irreversibly injured brain
tissue with moderate reliability but high specificity. MRI
displays ischaemic tissue highly conspicuously and with
good sensitivity but cannot reliably distinguish between
reversible and irreversible brain damage within the first
hours following stroke onset. Both CT and MRI have
great therapeutic impact by differentiating haemorrhagic
from ischaemic stroke, thus allowing specific treatment
to take place. CT has been shown to improve patients’
outcome within the first 6 hours following stroke onset
and thereby reduce healthcare costs. The extent of early
ischaemic oedema that is apparent on CT may identify
patients who will not benefit from recanalisation
therapy. MRI assessment of acute stroke patients may
allow efficacious treatment beyond currently accepted
time-windows by applying the perfusion-diffusion
mismatch and assessment of arterial occlusion.
Introduction
It is well established that non-contrast computed
tomography (NCCT) identifies patients with acute
cerebral ischaemia among patients with a stroke
syndrome and thus enables effective thrombolytic
therapy.1 However, there is controversy regarding
whether the further information beyond the exclusion
of haemorrhage provided by computed tomography
(CT) or magnetic resonance imaging (MRI), CT- or MR-
angiography (CTA, MRA) or perfusion imaging with CT
(CTPI) or MRI (MRPI) can really improve patients’ clinical
outcome and reduce healthcare costs. In theory, CT
– like MRI – can be clinically effective in acute stroke
patients on six different levels:2
1. Brain imaging will reduce healthcare costs if it
prevents the disability and death of stroke victims
2. Brain imaging will improve the clinical outcome
of stroke patients if it can identify patients who
will benefit from an effective treatment - e.g.
thrombolysis
3. To identify patients who will benefit from a certain
treatment, brain imaging must provide information
relevant to the choice of treatment that is
unavailable from other sources
4. This might include imaging techniques that allow
the exclusion of brain haemorrhage and other
diseases that mimic ischaemic stroke and permit
the assessment of ischaemic oedema and perfusion
disturbance, mass effect, arterial wall pathology and
obstruction
5. The imaging modality should be sensitive and specific
for stroke pathology soon after symptom onset
6. In this way, the imaging modality should be
technically capable of reliably detecting the relevant
stroke pathology
Feasibility and technical capacity
 |
| Figure 1. CT in a 37-year-old woman obtained 0.5 h after the onset of
aphasia and right hemiparesis witnessed by her husband. The arrows
indicate an area with subtle hypo-attenuating brain tissue. |
CT is the standard of care in acute stroke imaging. It is
widely available, fast and practical, and therefore feasible
for routine clinical use. The feasibility of MRI in stroke
is limited. Even if 100% availability of MRI is assumed
for stroke centres in the near future, it appears that
20–30% of acute stroke patients either cannot tolerate
this examination or face specific risks during scanning.3-6
Consequently, CT should be the preferred modality in
patients with severe stroke, MRI contraindications or
claustrophobia.
So far, reperfusion strategies have been shown to be
beneficial only in acute stroke,7-11 while neuroprotective
drugs have not shown an effect. Consequently, imaging
modalities that can reliably exclude brain haemorrhage
or assess arterial occlusion, cerebral perfusion deficit or ischaemic tissue damage may identify patients who
can benefit from thrombolysis. Kidwell et al have shown
that MRI can detect primary brain haemorrhage as
reliably as CT in acute stroke patients and is superior to
CT in detecting chronic haemorrhages within the brain
parenchyma.12
 |
| Figure 2. Same patient as in Figure 1. MRI was performed 3 h after CT. On
DWI (2a), an almost identical region to that demonstrated with CT shows
increased signal. On T2-weighted spin echo sequences (2b), the signal is
increased within the lentiform nucleus and the insular cortex. The tomeof-
flight MR angiography (2c) shows an occlusion of the distal MCA trunk
(arrow) resulting in a perfusion deficit on the time-to-peak-parameter map
(2d). Remarkably, the left lentiform nucleus (arrow) appears as already
hyper-perfused at this timepoint. |
Early after arterial occlusion occurs, it is difficult to
detect ischaemic damage, even under the microscope.
However, it has been shown that severely ischaemic
brain tissue, below the blood flow threshold for
structural integrity, takes up water immediately after
arterial occlusion.13,14 CT can detect and measure the
change in brain tissue water content and, in this way,
determine the volume of irreversibly injured brain
tissue.15,16 Because of the subtlety of the changes
(Figure 1), early ischaemic oedema is recognised with
only moderate inter-observer reliability within the first
hours following stroke onset.17-19 However, it has been
demonstrated that training in CT reading, altering the
window width and the use of a semi-quantitative score
considerably improves the sensitivity for detecting
ischaemic oedema.20-22
The signal of spin echo MRI sequences is relatively
insensitive for ischaemic brain oedema, and diffusionweighted
MR-imaging (DWI) does not directly show
the volume of irreversible brain injury (Figure 2). The
apparent diffusion coefficient (ADC) declines at cerebral
blood flow (CBF) values of 30 ml/100 g/min, exactly at
the CBF threshold where the extracellular fluid space
shrinks due to ischaemic cell swelling.13,23,24 That means
that brain tissue volume with increased signal on
DWI and associated decreased ADC may include both
irreversibly damaged brain tissue and tissue that can
recover if CBF is restored. The increase in DWI signal
can be detected with very good intra-and inter-observer
reliability.25
Diagnostic accuracy
Digital subtraction angiography is the accepted
gold standard for CTA and MRA in the assessment
of arterial obstructions, revealing high accuracy for
both modalities.26-28 However, for the assessment of
intracranial haemorrhage and ischaemic oedema, a reference standard is unavailable because surgery
or autopsy is, fortunately, not performed in most of
these patients.
In summary, NCCT seems to have a rather low
sensitivity for brain ischaemia that does not affect the
structural integrity of the tissue but a high specificity for
irreversible ischaemic injury, whereas diffusion-weighted
MRI has a high sensitivity for ischaemia but limited
specificity for irreversible tissue damage.
Diagnostic impact
The diagnostic impact of stroke imaging can be
measured by the percentage of patients in whom the
diagnosis made without it is changed when imaging
information is received.29 In acute haemorrhagic stroke,
MRI does not increase the frequency of this diagnosis,
if all patients were examined with CT, but MRI may
clarify the cause of brain haemorrhage if gradient echo
sequences are applied.
Combining CT or MRI tissue assessment with vascular
imaging might allow for estimating tissue at risk for
infarction30 and thereby improve patient selection for
thrombolytic therapy. The diagnostic impact of perfusion
imaging still needs to be elucidated.31,32
The detection of areas with a high signal on DWI may
allow assessment of the pattern of affected brain
territories and the cause of stroke early on, and signals
an increased risk for stroke in patients with transient
ischaemic attacks.33
Therapeutic impact
The therapeutic impact of stroke imaging is measured
by the percentage of patients in whom the results
of imaging changes the treatment originally planned
without it. Both CT and MRI have enormous therapeutic
impact in distinguishing between haemorrhagic and
ischaemic stroke, thus permitting tailored treatment.
In acute cerebral ischaemia, the only effective treatment
is intravenous thrombolysis with rt-PA applied within
3 hours of symptom onset or, in patients with middle
cerebral artery (MCA) occlusion, intra-arterial infusion
of pro-urokinase administered within 6 hours of
symptom onset.7,10 Whereas the National Institute
of Neurological Disorders and Stroke (NINDS) rt-PA
Study Group used CT only to exclude patients with
intracranial haemorrhage, the Prolyse in Acute Cerebral
Thromboembolism (PROACT) investigators excluded
from the study patients with a hypo-attenuating area
on CT exceeding one-third of the MCA territory. The
European Cooperative Acute Stroke Studies (ECASS I
and II) and prospective data on the use of the Alberta
Stroke Program Early CT Score (ASPECTS) support the
hypothesis that patients with such a large area
of ischaemic oedema do not benefit from rt-PA
treatment and have an increased risk for brain
haematoma.8,9,22,34,35
The therapeutic impact of CTA and CTPI still needs
to be proven. However, the finding, using MRI, of an
extended brain perfusion deficit but relatively small
tissue volume with impaired water diffusion (perfusiondiffusion
mismatch) may allow treatment beyond
currently accepted time windows. Parsons et al. showed
a beneficial outcome after thrombolysis in patients with
perfusion-diffusion mismatch within 6 hours of stroke
onset but did not compare the effect of rt-PA with
placebo treatment.36
Impact on patients’ clinical outcome
The combined analysis of prospective and randomised
stroke thrombolysis trials that included 2,775 patients
showed that thrombolysis improves outcome in patients
with acute ischaemic stroke as demonstrated by NCCT
in a highly time-dependent fashion.1 The odds for
favourable outcome were 2.8 if treated within
90 minutes and were approaching 1 after 270 minutes
of stroke onset.
The Desmoteplase in Acute Ischaemic Stroke Trial
(DIAS) was based on MRI and included patients with
perfusion-diffusion mismatch up to 9 hours after
symptom onset.11 This study showed a beneficial
effect of desmoteplase on reperfusion and clinical
outcome. Using weight-adjusted doses, the frequency of
symptomatic secondary haemorrhage was low. Patients
without perfusion-diffusion mismatch were not studied.
Consequently, the impact of MRI findings on patients’
clinical outcome remains unclear. However, the study
shows that a beneficial treatment effect can be achieved
based on MRI imaging only.
Impact on healthcare costs
Each disabling stroke that is prevented saves estimated
lifetime costs of around US$90,000.37 It has been shown that a strategy of CT examination immediately after
stroke onset improves patients’ clinical outcome and
lowers healthcare costs compared with a strategy
of scanning no-one. The gain is 78.2 quality adjusted
life years and £560,324 per 1,000 acute stroke
patients.38
Conclusion
CT is the current standard of care in acute stroke
patients presenting within 3 hrs of symptom onset or
with a severe stroke syndrome. MRI allows extending
the time window for thrombolysis in selected patients
and can help triaging patients with transient ischemic
attacks. Current experience with imaging supports the
view that a rigid time window for stroke interventions
can be replaced by the imaging of stroke pathology and
functional impairment.
Key Learning
• CT is the standard of care in acute stroke imaging since it is widely available, fast and practical. The feasibility
of acute MRI is limited
• CT only has moderate sensitivity for brain ischaemia but high specificity for irreversible tissue injury
• Diffusion-weighted imaging on MRI has a high sensitivity for ischaemia but limited specificity for irreversible
tissue damage
• Both CT and MRI have enormous therapeutic impact by distinguishing between ischaemic and haemorrhagic
stroke thus enabling thrombolytic therapy within 3 hours from onset
• Patients with acute ischaemic stroke and extensive area of hypo-attenuation on CT are at higher risk for
thrombolysis-related intracerebral haemorrhage if treated beyond 3 hours from onset
• A ‘perfusion-diffusion mismatch’ on MRI might identify patients suitable for thrombolysis beyond currently
accepted time-windows |
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