J NeuroIntervent Surg 2013 González Neurintsurg 2013 010715
J NeuroIntervent Surg 2013 González Neurintsurg 2013 010715
J NeuroIntervent Surg 2013 González Neurintsurg 2013 010715
com
Ischemic stroke
SUPPLEMENT
ABSTRACT
The Massachusetts General Hospital Neuroradiology
Division employed an experience and evidence based
approach to develop a neuroimaging algorithm to best
select patients with severe ischemic strokes caused by
anterior circulation occlusions (ACOs) for intravenous
tissue plasminogen activator and endovascular
treatment. Methods found to be of value included
the National Institutes of Health Stroke Scale (NIHSS),
non-contrast CT, CT angiography (CTA) and diffusion
MRI. Perfusion imaging by CT and MRI were found to
be unnecessary for safe and effective triage of patients
with severe ACOs. An algorithm was adopted that
includes: non-contrast CT to identify hemorrhage and
large hypodensity followed by CTA to identify the ACO;
diffusion MRI to estimate the core infarct; and NIHSS
in conjunction with diffusion data to estimate the
clinical penumbra.
INTRODUCTION
The purpose was to use an experience and evidence
based approach to develop the neuroimaging algorithm that best improves outcomes in patients with
severe ischemic strokes caused by anterior circulation occlusions (ACOs). Patients with these strokes
account for the majority of individual, family, and
societal costs due to stroke, and they are treatable
with intravenous (IV) tissue plasminogen activator
(tPA) or/and intra-arterial therapy (IAT). Critically
evaluated was the capability of each specic method
to provide reliable information on three key components of stroke physiology: (1) site of arterial occlusion; (2) extent of irreversibly injured tissue (infarct
core); and (3) the size of the ischemic penumbra
(gure 1). Although varying denitions of the ischemic penumbra exist, the penumbra is dened herein
as severely hypoperfused brain tissue that may
eventually be recruited into the infarct core, if not
reperfused quickly enough.1
METHODOLOGY
To cite: Gonzlez RG,
Copen WA, Schaefer PW,
et al. J NeuroIntervent Surg
Published Online First:
[please include Day Month
Year] doi:10.1136/
neurintsurg-2013-010715
Intra-arterial therapy
The target of IAT is a proximal artery occlusion.
The focus here is on major ACOs which account
for approximately 90% of all such occlusions.3 In
patients with blockages of the intracranial internal
carotid artery (ICA) or middle cerebral artery stem
(M1 segment), two recent studies have demonstrated the critical role of infarct volume in determining long term functional outcome (gure 2).4 5
When patients have large nal infarcts, there is a
high likelihood of signicant disability or death. It
1
Ischemic stroke
Table 1 Massachusetts General Hospital experience and practice
based criteria
Level 1
Level 2
Level 3
ASSESSMENT OF METHODS
National Institutes of Health Stroke Scale
The NIHSS is a Level 1/Class I test in the assessment of the
acute stroke patient.2 It helps to quickly determine if the patient
is having a stroke and gives an indication of the severity of the
Non-contrast CT
NCCT is a Level 1/Class I test for excluding intracranial hemorrhage and mass lesions.2 Because of the low sensitivity, NCCT
was scored Level 2/Class IIa to detect the infarct core volume
during the rst few hours after stroke onset. The place of
NCCT in the workow and the order of imaging modalities were
also considered and it was agreed that NCCT should be the rst
test in the evaluation of acute stroke. There are exceptionsfor
example, MRI could be undertaken as the rst imaging study in
patients with poor renal function who cannot get CTA, young
patients presenting with acute stroke, or patients more likely
to have a non-ischemic etiology, such as a mass, seizure, or
migraines as the cause of their presenting symptoms.
CT angiography
CTA is a Level 1/Class I test for the rapid assessment of large
vessel occlusion.2 1315 It may also be effective for detection of
medium and small vessel occlusions, even though they can take
longer to nd. There was no concern regarding repeatability,
reliability, clinical efcacy, or overall utility of CTA. It was
agreed that CTA should be performed immediately after the
NCCT scan, when feasible.
Table 2
Class I
Class II
Class IIa
Class IIb
Class III
Ischemic stroke
CTA-SI was judged to be a Level 2/Class III examination in eliciting the core of an ischemic infarct.
Diffusion MRI
Diffusion MRI is a Level 1/Class I test for the early detection of
infarct core. Diffusion weighted imaging (DWI) is nearly 100%
sensitive and specic in diagnosing acute stroke1825 although it
is not perfect in identifying the infarct core. Positron emission
tomography (PET) studies have shown that some non-viable
tissue occasionally may not demonstrate restricted diffusion26 27
Also, DWI abnormalities are sometimes reversible.2833
However, reversal of a DWI abnormality is unusual.34 7 When
DWI reversal does occur, it usually involves only a small part of
the lesion.35 Also, most of the time, the apparent DWI reversal
is actually a pseudo-reversal, in that the tissue involved proceeds
to infarction anyway.7 31 33
Perfusion imaging
Brain perfusion imaging provides information on cerebral hemodynamics imbedded in parameters such as cerebral blood ow
(CBF), cerebral blood volume (CBV), and mean transit time
(MTT). Perfusion imaging may provide many types of important information in the care of acute stroke patients.36 37
Additionally, much research has been devoted to demonstrating
that perfusion imaging can identify the core and penumbra, and
that perfusion imaging is useful for identifying patients with
major ACOs that are suitable for interventional therapy.2 38 39
However, evidence based reviews have questioned this.2 40 41
CT perfusion
Several issues and concerns about CTP were raised in addition
to radiation exposure. These concernswhich are related to the
workow, process of obtaining CTP maps, and the utility of the
information derived from a CTP studyare summarized below.
Ischemic stroke
between DWI and CTP derived core volumes in individual
patients (see online supplementary appendix figure A3).
The above considerations led to the following guidelines on
the use of CTP.
CTP is a Level 3/Class IIb method for early estimation of
the infarct core in acute stroke patients. Because CTP is
unable to adequately estimate the core, it necessarily
follows that it is a Level 3/Class IIb method for estimation
of the penumbra.
CTP has no proven role in selecting ACO patients for IV
thrombolysis or endovascular therapy. Its roles should be
limited to:
Research patients
Patients who cannot get a diffusion weighted MRI
Perfusion data could be used for other purposes such as
hypertensive therapy. However, there are scant data on
this application.
MR perfusion
MRP was deemed preferable to CTP because there is no radiation exposure and it has a generally superior workow.
However, the repeatability, reliability, and clinical efcacy of
MRP raise similar concerns to those of CTP, including:
Quantication using MR perfusion maps is not validated.
There is high inter-vendor variability.
The variability of MRP maps with respect to physiologic
variables (eg, heart rate, blood pressure, ejection fraction)
and scan parameters (eg, rate of infusion, osmolality of IV
contrast, rotation time, etc) is unknown.
Carroll and colleagues46 performed a BlandAltman analysis
of eight smokers who were imaged with MRP and H2 15O PET
and concluded that Until reproducibility is improved, MR is not
suitable for reliable quantitative perfusion measurements. Other
research assessing the reliability of MRP was also reviewed. For
example, Takasawa and colleagues47 studied perfusion MR
(deconvolution method) and PET in ve patients, back to back,
at a mean time interval of 16 h after stroke onset. The authors
concluded that MRP appears sufciently reliable for clinical
purposes. However, most participants deliberating on the value
of the methods thought that reliability does not override the concerns regarding high variability and low repeatability.
Overall, MRP was judged to be a Level 3/Class IIb technique in
the management of acute stroke. There was broad agreement that:
MRP has no proven role in selecting ACO patients for
endovascular therapy. There is preliminary evidence that it
may improve patient selection for intravenous thrombolysis but this evidence is currently insufcient to justify
MRPs clinical use in this role.
Clinical indications for MRP may include:
Research patients
If perfusion data are deemed essential for evaluating the
full clinical picture
When perfusion data can be used for other purposes
such as hypertensive therapy, although there are few
data on this.
Ischemic stroke
are not met, the patient cannot be scanned by MRI, or is not
otherwise eligible for IAT and there is relevant clinical information that may be provided by the perfusion data.
After the algorithm was adopted, there was a signicant
decline in the number of perfusion CT examinations performed,
as shown in the online supplementary appendix figure A4.
From 4050 CTP examinations per month in stroke patients
performed during the peak years of 20052008, it fell to
approximately 10 per month. There has been no discernible
effect on patient outcomes.
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References
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