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7/23/2019 Neuroimaging of Acute Ischemic Stroke
1/28
19/8/2015 Neuroimaging of acute ischemic stroke
http://www.uptodate.com.consultaremota.upb.edu.co/contents/neuroimaging-of-acute-ischemi c-stroke?topicKey=N EURO%2F1085&elapsedTim eMs= 0&sour
Offi cial reprint from UpToDatewww.uptodate.com 2015 UpToDate
AuthorJamary Oliveira Filho, MD,MS, PhD
Section EditorsScott E Kasner, MDEric D Schwartz, MD
Deputy EditorJohn F Dashe, MD, PhD
Neuroimaging of acute ischemic stroke
All topics are updated as new evidence becomes available and our peer review process is complete.Literature review current through: Jul 2015. | This topic last updated: Jul 29, 2015.
INTRODUCTION Imaging studies are used to exclude hemorrhage in the acute stroke patient, to assess the
degree of brain injury, and to identify the vascular lesion responsible for the ischemic deficit. Some advanced CT
and MRI technologies are able to distinguish between brain tissue that is irreversibly infarcted and that which is
potentially salvageable, thereby allowing better selection of patients likely to benefit from therapy. The use of this
technology is dependent upon availability, and its role in guiding treatment decisions is still under study.
Neuroimaging during the acute phase (first few hours) of an ischemic stroke will be reviewed here. Other aspects
of the acute evaluation of stroke, the clinical diagnosis of various types of stroke, and the subacute and long-term
assessment of patients who have had a stroke are discussed separately. (See "Initial assessment and
management of acute stroke" and "Clinical diagnosis of stroke subtypes" and "Overview of the evaluation ofstroke".)
COMPUTED TOMOGRAPHY The main advantages of CT are widespread access and speed of acquisition. In
the hyperacute phase, a noncontrast CT (NCCT) scan is usually ordered to exclude or confirm hemorrhage it is
highly sensitive for this indication. A NCCT scan should be obtained as soon as the patient is medically stable.
The presence of hemorrhage leads to very different management and concerns than a normal scan or one that
shows infarction. Immediate CT scanning of all patients with suspected stroke is also the most cost-effective
strategy when compared with alternate strategies such as scanning selected patients or delayed rather than
immediate imaging [1].
The utility of CT for acute stroke has been enhanced by the advent of additional CT techniques including CT
perfusion imaging (CTP) and CT angiography (CTA). Multimodal CT evaluation that employs the three techniques
(NCCT, CTA, and CTP) combined shows improved detection of acute infarction when compared with NCCT
evaluation alone [2-5]. In addition, multimodal evaluation that includes CTA and CTP may permit assessment of
the site of vascular occlusion, infarct core, salvageable brain tissue and degree of collateral circulation [ 6,7].
Early signs of infarction on noncontrast CT The sensitivity of standard noncontrast CT for brain ischemia
increases after 24 hours. However, in a systematic review involving 15 studies where CT scans were performed
within six hours of stroke onset, the prevalence of early CT signs of brain infarction was 61 percent (standard
deviation +/- 21 percent) [8].
Early signs of infarction include the following [8-12]:
The presence of early CT signs of infarction implies a worse prognosis. In the systematic review, the presence of
these signs was associated with an increased risk of poor functional outcome (odds ratio 3.11, 95% CI 2.77-3.49)
Hypoattenuationinvolving one-third or more of the middle cerebral artery (MCA) territory
Obscuration of the lentiform nucleus
Cortical sulcal effacement
Focal parenchymal hypoattenuation
Loss of the insular ribbon or obscuration of the Sylvian fissure
Hyperattenuation of large vessel (eg, "hyperdense MCA sign")
Loss of gray-white matter differentiation in the basal ganglia
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[8].
Hyperdensity of the MCA, indicating the presence of thrombus inside the artery lumen (bright artery sign), can be
visualized on noncontrast CT in 30 to 40 percent of patients with an MCA distribution stroke [11,13]. This finding
is highly specific for MCA occlusion, although it may be less useful for predicting outcome than the other early CT
signs.
While early CT signs of infarction are associated with a worse outcome, it remains unclear whether early infarction
signs should be considered when deciding whether to use intravenous (IV) thrombolytic treatment for acute
ischemic stroke [8]. An analysis from the NINDS trial found that early CT signs of infarction were notindependently associated with increased risk of adverse outcome after IV alteplase(tPA) treatment, and patients
treated with alteplase did better whether or not they had early CT signs [14]. (See "Reperfusion therapy for acute
ischemic stroke", section on 'Intravenous thrombolysis'.)
Careful attention to the presence of these signs by experienced personnel is necessary mistakes have occurred
in up to 20 percent of cases in a controlled setting [ 15]. Studies that have examined the ability of neurologists,
neuroradiologists, and general practitioners have found that early infarction can be very difficult to recognize on CT
[16]. However, the importance of a truly normal head CT in acute stroke should not be underestimated it excludes
major ischemic damage with high specificity [17].
Standardized methods such as ASPECTS have been developed to aid recognition of early ischemia because of
the known difficulty in detecting such changes. In addition, accentuating the contrast between normal and
edematous (ischemic) brain tissue by variable window width and center level settings may improve detection of
early ischemic change on noncontrast CT [18].
ASPECTS method of assessing ischemic changes The Alberta stroke program early CT score (ASPECTS)
was developed to provide a simple and reliable method of assessing ischemic changes on head CT scan in order
to identify acute stroke patients unlikely to make an independent recovery despite thrombolytic treatment [ 19].
The ASPECTS value is calculated from two standard axial CT cuts one at the level of the thalamus and basal
ganglia, and one just rostral to the basal ganglia (figure 1 and figure 2) [19,20].
Therefore, a normal CT scan has an ASPECTS value of 10 points, while diffuse ischemic change throughout the
MCA territory gives a value of 0.
Utility of ASPECTS In the initial ASPECTS study, pretreatment noncontrast head CT scans from 156
patients with anterior circulation ischemia treated with intravenous alteplase (IV tPA) were prospectively scored
with ASPECTS [19]. The following observations were made for baseline values.
The score divides the MCA territory into 10 regions of interest.
Subcortical structures are allotted three points (one each for caudate, lentiform nucleus, and internal
capsule).
MCA cortex is allotted seven points. Four of these points come from the axial CT cut at the level of the
basal ganglia, with one point for insular cortex and one point each for M1, M2, and M3 regions (anterior,
lateral, and posterior MCA cortex).
Three points come from the CT cut just rostral to the basal ganglia, with one point each for M4, M5, and M6
regions (anterior, lateral, and posterior MCA cortex).
One point is subtracted for an area of early ischemic change, such as focal swelling or parenchymal
hypoattenuation, for each of the defined regions.
ASPECTS was inversely correlated with stroke severity.
The median ASPECTS value was 8 a value of 7 or less was associated with a sharp increase in
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In a prospective study of 100 patients with acute ischemic stroke, the ability to detect early ischemic changes by
ASPECTS was similar on noncontrast CT and diffusion-weighted imaging (DWI) [22].
ASPECTS has been retrospectively applied to baseline and 24-hour CT scans for patients with middle cerebral
artery occlusion who were randomized to intraarterial thrombolysis or placebo in the PROACT-II study [ 23].
Treated patients with a baseline ASPECTS >7 had a risk ratio (RR) of 3.2 (95% CI 1.2-9.1) for an independent
functional outcome, while patients with ASPECTS 7 had a RR of 1.0 (95% CI 0.6-1.9).
Despite its promise, the available data suggest that ASPECTS analysis of noncontrast CT does not identify
patients who may benefit from thrombolysis. The prospective CASES observational cohort study of 1135 patients
treated with IV tPA found that each one point decrement in the baseline ASPECTS scores was associated with a
lower probability of independent functional outcome (odds ratio 0.81, 95% CI 0.75-0.87) [ 24]. However, the
ASPECTS score was not a predictor of symptomatic intracranial hemorrhage in patients treated within the
standard three-hour time window.
Subsequent reports showed that the ASPECTS score of baseline noncontrast CT scans from the NINDS and
ECASS-II tPA stroke studies was not associated with a statistically significant modification of tPA treatment
effect [25,26]. This finding is in agreement with a report cited above from the NINDS cohort, which found that
signs of early ischemic change on CT were not independently associated with increased risk of adverse outcome
after IV tPA treatment [14]. (See 'Early signs of infarction on noncontrast CT' above.)
One problem with ASPECTS may be that the various types of parenchymal changes on noncontrast CT
considered to represent early ischemic change may actually have different pathophysiologic mechanisms. In
particular, there is evidence suggesting that hypoattenuation represents irreversible infarction, whereas focal
swelling may represent penumbral tissue [27,28]. ASPECTS may have greater accuracy for detection of ischemic
change and for identifying final infarct volume when used to analyze CTA-source images and the contrast CT
images obtained from CTP than when used to analyze noncontrast CT images [ 29,30]. (See 'Utility of CT contrast
dye' below and 'CT perfusion imaging' below.)
It is important to note that ASPECTS is not applicable to lacunar stroke, brainstem stroke, or any stroke outside of
the middle cerebral artery territory.
Utility of CT contrast dye Spiral (helical) CT and new generation multidetector CT scanners increase scan
speed and allow CTA of both extracranial and intracranial cerebral arteries. The speed of these CT units also
offers CTP capabilities. These scans can be performed immediately after conventional CT scanning, requiring only
5 to 10 minutes of additional time. In practice, one can perform both CTA and CTP during the same examination,
with separate contrast boluses [30].
Advantages of these fast CT scans include the ability to rapidly identify patients with occlusion of the major
vessels within the circle of Willis or extracranial cerebral arteries, as well as the ability to evaluate the perfusion
status of the brain parenchyma. Additional information about brain perfusion can be obtained by post imaging
analysis of the raw data (or source images) of CTA and CTP studies. (See 'CT angiography' below and 'CT
perfusion imaging' below.)
CT angiography CTA is performed by administering a rapid bolus of standard intravenous CT contrast through
a large bore intravenous line in the antecubital fossa. The helical CT scan is timed to capture the arrival of dye into
the brain. Dye can be seen in the great vessels on the raw CT images these serve as data for three dimensional
dependence and death at three months.
ASPECTS predicted functional outcome and symptomatic intracerebral hemorrhage, with good sensitivity
and specificity for functional outcome (0.78 and 0.96) and for intracerebral hemorrhage (ICH) (0.90 and 0.61).
The inter- and intraobserver reliability was good to excellent score reliability appears to be good when
performed in real time by treating physicians as compared with expert readers [ 21].
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computer reconstructions of the circle of Willis and extracranial cerebral arteries. Clot causes a filling defect in the
vessel on CTA, which often can be seen on the raw images (also called source images). (See "Principles of
computed tomography of the chest".)
For the detection of intracranial large vessel stenosis and occlusion, CTA in various studies had sensitivities of 92
to 100 percent and specificities of 82 to 100 percent when compared with conventional angiography [31]. The
accuracy of CTA for the diagnosis of extracranial carotid stenosis is discussed separately. (See "Evaluation of
carotid artery stenosis", section on 'CT angiography'.)
Recanalization rates for intravenous or intraarterial thrombolysis differ depending upon the site of arterial occlusion.CTA has become the standard of practice in our center to triage patients between intravenous thrombolysis,
mechanical thrombectomy, and intra-arterial thrombolysis. It is also helpful in diagnosing stroke mimics. As an
example, the patient with severe brainstem signs thought due to basilar thrombosis who has a normal basilar
artery on CTA demands an alternative diagnosis. (See "Differential diagnosis of transient ischemic attack and
stroke".)
The pial artery collateral vessels of the brain can be assessed using multiphase CTA, which acquires blood flow
information in three phases after contrast injection the first phase consists of conventional CTA with image
acquisition from the aortic arch to skull vertex during the peak arterial phase the second and third phases consist
of image acquisition from the skull base to vertex during the mid-venous and late-venous phases [ 32]. Compared
with perfusion CT, advantages of this method include whole brain coverage, reduced vulnerability to patientmotion, no need for additional contrast or postprocessing, and more rapid determination of collateral status. In the
ESCAPE trial, the presence of moderate-to-good pial collateral circulation, determined by multiphase CTA in a
majority of subjects, was one of the criteria used to select patients for mechanical thrombectomy in the setting of
acute ischemic stroke caused by a proximal intracranial artery occlusion in the anterior circulation [33]. (See
"Reperfusion therapy for acute ischemic stroke", section on 'Mechanical thrombectomy'.)
CTA source images CTA source images can provide an estimate of perfusion by taking advantage of the
contrast enhancement in the brain vasculature that occurs during a CTA [ 34], potentially obviating the need for a
separate CT perfusion study and a second contrast bolus. CTA source images typically cover the entire brain, in
contrast to CT perfusion source images that are limited to a few brain slices.
During a CTA, contrast dye fills the brain microvasculature in the normal perfused tissue that is accessible to the
blood pool and appears as increased signal intensity on the CTA source images. In distinction, contrast dye does
not fill the microvasculature in ischemic brain regions that are less accessible to the blood pool and have poor
collateral flow. These ischemic areas are easily seen as regions of hypoattenuation (low density or dark) on CTA
source images (image 1) [35,36].
CTA source images are more sensitive than noncontrast CT scans for the detection of early brain infarction
[31,37]. Hypoattenuation on CTA source images correlates with ischemic edema [ 36], and with the abnormality on
diffusion-weighted MRI [38]. In this sense, CTA source images (or raw images of CT perfusion studies) can be
considered as a surrogate for DWI. (See 'Diffusion-weighted imaging' below.)
CT perfusion imaging Using an intravenous bolus of CT dye, a whole brain "perfused blood volume map" canbe obtained by timing the scan to the passage of the contrast dye through the brain [ 39]. This can be obtained by
continuing to scan the brain during a CT angiogram or by using a new bolus of contrast following the CTA.
However, CTP requires repeatedly scanning the same portion of the brain parenchyma over the time required for
the bolus to pass through the vasculature.
Similar to CTA-SI, the source images of the CTP (CTP-SI) are available for analysis. As with CTA-SI, areas of
hypoattenuation on CTP-SI should correlate with ischemic brain regions. In addition, quantitative analysis of the
kinetics of a bolus of CT dye passing through the brain enable estimation of cerebral blood flow (CBF), cerebral
blood volume (CBV), and the mean transit time (MTT) that it takes blood to flow through the tissue. Thresholds of
CBF and CBV can be used to predict whether tissue will die or survive, but standardized, reliable, and validated
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thresholds have not been definitively established [40,41].
One study found that the ASPECTS method applied to CTP-SI or CBV maps was more accurate for identifying
irreversible ischemia and clinical outcome than ASPECTS applied to noncontrast CT or CTA-SI [30]. In addition,
ASPECTS applied to CBF maps or MTT appeared to identify the maximal extent of infarction in the absence of
major reperfusion, and the difference between CTP-SI (or CBV) and CBF (or MTT) on ASPECTS appeared to
identify ischemic tissue at risk for infarction. Thus, ASPECTS applied to CTP and its multiple parametric maps
(CBV, CBV, MTT) holds promise for improving patient selection for intravenous thrombolysis of acute ischemic
stroke, and for extending the time window beyond three hours [30,42]. However, this hypothesis should be
confirmed in randomized clinical trials.
MAGNETIC RESONANCE IMAGING Advanced MRI imaging techniques have the potential for further defining
stroke subgroup populations that may benefit from intravenous thrombolysis or interventional vascular treatments
[43]. In addition, MRI sequences using high susceptibility methods, such as gradient echo (GRE) pulse
sequences, are equivalent to CT for the detection of acute intracerebral hemorrhage (ICH) and better than CT for
the detection of chronic hemorrhage [44-46]. ICH can be diagnosed by MRI with up to 100 percent sensitivity and
accuracy by experienced readers [45]. (See "Spontaneous intracerebral hemorrhage: Pathogenesis, clinical
features, and diagnosis", section on 'Hemorrhage appearance'.)
Brain MRI protocols that combine conventional T1 and T2 sequences with diffusion-weighted imaging (DWI),
perfusion-weighted imaging (PWI), and GRE can reliably diagnose both acute ischemic stroke and acutehemorrhagic stroke in emergency settings. These MRI techniques may obviate the need for emergent CT in
centers where brain MRI is readily available. As an example, one specialized stroke center found that routine use
of these MRI sequences to screen patients prior to intravenous thrombolysis for suspected ischemic stroke was
practical and safe [47]. Furthermore, MRI screening did not cause excessive treatment delays or lead to worse
outcomes. On the other hand, MRI-specific selection criteria for acute thrombolysis of ischemic stroke have not
been validated, and no randomized studies have compared CT and MRI screening in this setting.
Newer ultrafast MRI imaging protocols can reduce acquisition times from the 15 to 20 minutes required by
conventional MRI to five minutes or less, but the utility of these newer methods is not yet established [48,49].
Diffusion-weighted imaging DWI is based upon the capacity of fast MRI to detect a signal related to the
movement of water molecules between two closely spaced radiofrequency pulses. This technique can detect
abnormalities due to ischemia within 3 to 30 minutes of onset, [ 50-52], when conventional MRI and CT images
would still appear normal.
In acute stroke, swelling of the ischemic brain parenchymal cells follows failure of the energy-dependent Na-K-
ATPase pumps and is believed to increase the ratio of intracellular to extracellular volume fractions [53].
DWI contains an additional component of T2 effect, and increased T2 signal due to vasogenic edema can "shine
through" on DWI images, making it difficult to distinguish vasogenic from cytotoxic edema on these images. This
problem can be overcome by use of the apparent diffusion coefficient (ADC). The ADC provides a quantitative
measure of the water diffusion. In acute ischemic stroke with cytotoxic edema, decreased water diffusion in
infarcted tissue causes increased (hyperintense) DWI signal and a decreased ADC, visualized as hypointensesignal on ADC maps of the brain. In contrast, vasogenic edema may cause increased DWI signal may occur due
to T2 shine through, but water diffusion is increased, and increased ADC is seen as hyperintense signal on ADC
maps.
The decrease in ADC in the region of the infarct is a necessary transition on the way to infarction. The decrease in
diffusion in the infarct is transient, lasting one to two weeks. It then actually reverses, passing through a phase of
pseudonormalization and later becoming elevated and bright on ADC maps [ 54]. DWI abnormalities last somewhat
longer due to the prominent T2 effect, but chronic infarction is not bright on DWI.
In a study comparing CT, DWI, and standard MRI, we found that abnormal DWI was a sensitive and specific
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indicator of ischemic stroke in patients presenting within six hours of symptom onset [ 55]. Others have confirmed
these results [56-60]. However, occasional patients with acute ischemic deficits have a normal DWI, but follow-up
MRI or CT confirms an infarct [61,62]. In some of these patients, the stroke was a small brainstem lacune in
others, ischemia was seen on perfusion MRI in regions that had not yet become abnormal on DWI [61].
MR and DWI utilizing higher magnetic field strengths of 3 Tesla (T) units are increasingly available in clinical
settings. However, there is only limited and conflicting evidence regarding whether DWI obtained using 3 T MRI
scanners is better for the detection of early (6 hours) and small infarcts compared with standard 1.5 T MRI
[63,64]. Although seemingly advantageous because of improved signal-to-noise ratios, higher magnetic field
strengths also introduce increased imaging artifacts and geometric distortions [ 65], and these artifacts may
obscure early ischemic changes, particularly in regions of brain near the skull base [ 64]. Thus, further refinement
of higher field strength DWI imaging is needed to determine if such imaging is useful in acute ischemic stroke.
Clinical utility of DWI A systematic review published in 2010 from the American Academy of Neurology
(AAN) concluded that DWI is superior to noncontrast CT for the diagnosis of acute ischemic stroke in patients
presenting within 12 hours of symptom onset [66]. Although based on weaker evidence, the AAN concluded that
DWI may be useful for predicting late clinical outcome as measured by the National Institutes of Health Stroke
Scale and the Barthel Index.
Even in patients with subacute ischemic stroke who delay seeking medical attention, DWI may add clinically
useful information to standard MRI. In a prospective observational study of 300 patients with suspected stroke ortransient ischemic attack (TIA) and a median delay of 17 days from symptom onset, DWI compared with T2
provided additional clinical information imaging for 108 patients (36 percent) such as clarification of diagnosis or
vascular territory this was considered likely to change management in 42 patients (14 percent) [ 67].
In the evaluation of acute ischemic stroke or TIA, the presence of multiple DWI lesions on the baseline MRI scan
is associated with an increased risk of early lesion recurrence [68-70]. Furthermore, the presence of multiple DWI
lesions of varying ages, as determined by the ADC value, is an independent predictor of future ischemic events
[71].
Perfusion-weighted imaging Diffusion-weighted imaging reveals evidence of ischemic injury, not ischemia
itself. In contrast, perfusion-weighted imaging (PWI) uses fast MRI techniques to quantify the amount of MR
contrast agent reaching the brain tissue after a fast intravenous bolus. Integration of the amount of gadolinium
entering the brain on first pass allows construction of maps of cerebral blood volume. Analysis that also includes
the time course of arrival and washout permits the construction of maps of relative cerebral blood flow and mean
transit time. The latter sensitively identifies the ischemic zone.
PWI can be performed with standard MRI and MR angiography, requiring a total imaging time of less than 15
minutes. Access to MRI is usually the limiting factor.
Another method of MRI perfusion imaging is continuous arterial spin labeling (CASL). Instead of using an
intravascular contrast agent, CASL magnetically labels the blood entering the brain. CASL imaging within 24 hours
of stroke symptom onset can depict perfusion defects and diffusion-perfusion mismatches [72]. In addition,
cerebral blood flow asymmetry on CASL appears to correlate with stroke severity and outcome.
Guidelines from the AAN published in 2010 concluded that the baseline lesion volume on PWI may predict
baseline stroke severity, but found that evidence was insufficient to support or refute the utility of PWI for use in
diagnosing acute ischemic stroke [66].
Identifying reversible ischemia Accurate identification of patients with reversible ischemic injury in the brain
is important for selecting those patients most likely to benefit and least likely to be harmed by reperfusion and
neuroprotective therapy. In patients with acute stroke, there are often areas that are ischemic but do not yet
appear abnormal by DWI or ADC maps on early scans. Regions with decreased cerebral blood volume are usually
involved in the final infarct, while regions with normal cerebral blood volume but low cerebral blood flow and
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increased mean transit time may or may not survive the ischemic insult.
The expectation that PWI and DWI could reliably define the ischemic penumbra and infarct core in acute stroke is
still unrealized [73]. Although PWI can reveal the ischemic zone, the thresholds of PWI derived cerebral blood flow
and volume that might discriminate the ischemic penumbra from infarct core have not been definitively established
[74]. And while DWI can often reveal irreversibly infarcted tissue, it is now clear that some DWI lesions represent
injured but still viable tissue [75,76]. In addition, while some cases manifest with a "classic" mismatch pattern
where the ischemic core on DWI is embedded within a hypoperfused penumbral brain region on PWI ( image 2),
others show a "nonclassic" fragmented mismatch pattern in which part or all of the ischemic region on DWI is
dissociated from the hypoperfused region on PWI (image 3) [77-79].
Consensus guidelines from the American Heart Association published in 2003 concluded that no recommendation
could be given to employ PWI either to guide the use of thrombolysis or predict resulting complications such as
post-thrombolytic hemorrhage [80]. A subsequent review evaluated MRI methods for selecting patients for
thrombolysis and concluded that although DWI and PWI thresholds can delineate areas of brain with higher
probability of infarction or salvage, their precise role in acute stroke management is not yet settled [ 81].
Despite these limitations, DWI and PWI have clear utility.
The technique of cerebrospinal fluid-suppressed apparent diffusion coefficient (ADC) measurements can reduce
the false elevation of ADC that results from cerebrospinal fluid (CSF) artifact and allow for a more accurate
identification of ischemic tissue at risk for infarction [90]. This information may ultimately be most useful in
identifying risk groups of patients who would benefit from various therapies such as thrombolysis in the acute
setting.
MR angiography MR angiography (MRA) to detect vascular stenosis or occlusion is done at many centers as
part of a fast MRI protocol for acute ischemic stroke. Results from a case series showed that the combined use ofDWI with MRA within 24 hours of hospitalization substantially improved the early diagnostic accuracy of ischemic
stroke subtypes [91].
Contrast-enhanced MRA shows promise for improved imaging of intracranial large vessels compared with the
more established time-of-flight technique [92]. For the detection of intracranial large vessel stenosis and occlusion,
contrast-enhanced MRA in various studies had sensitivities of 86 to 97 percent and specificities of 62 to 91
percent when compared with conventional angiography [31]. The accuracy of MRA for the diagnosis of extracranial
carotid stenosis is discussed separately. (See "Evaluation of carotid artery stenosis", section on 'MR
angiography'.)
High susceptibility sequences Increasing evidence supports the utility of high susceptibility MRI sequences
Severe perfusion defects in areas with a diffusion-perfusion (DWI/PWI) mismatch may be a risk factor for
lesion enlargement [82,83].
Patients with an occluded artery are at a higher risk for lesion enlargement by growth of infarction into areas
of perfusion deficit, implying that early recanalization (either spontaneously or with thrombolytic agents) may
prevent lesion growth [84].
Abnormal volumes on DWI and PWI during an acute stroke correlate well with initial NIH stroke scale
scores, chronic scores, and final lesion volume, and also may predict early neurologic deterioration [ 85,86].
Significant correction of focal brain hypoperfusion on PWI after tPA can predict excellent outcome at three
months in ischemic stroke [87].
Patients with acute ischemic stroke may in theory be selected for thrombolytic therapy based on DWI/PWI
mismatch, thereby allowing extension of the conventional 3 hour window of opportunity for acute strokethrombolysis [88,89]. (See "Reperfusion therapy for acute ischemic stroke", section on 'Intravenous
thrombolysis'.)
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(ie, GRE or T2* weighted images) for the early detection of acute thrombosis and occlusion involving the middle
cerebral artery (MCA) or internal carotid artery (ICA) [93,94]. Acute thrombotic occlusion may appear on high
susceptibility MRI as a hypointense (dark) signal within the MCA or ICA, often in a curvilinear shape the diameter
of the hypointense signal is larger than that of the contralateral unaffected vessel. This finding is called the
susceptibility sign, and it is analogous to the hyperdense MCA sign described for CT imaging. (See 'Computed
tomography'above.)
In a retrospective report of 42 patients with stroke in the MCA territory who had MR imaging 95 to 360 minutes
from stroke onset, a positive susceptibility sign corresponding to MCA or ICA occlusion was found in 30 (71
percent) [94]. The specificity of the sign was 100 percent. The overall sensitivity was 83 percent compared with
MR angiography but varied widely depending on location, from 38 percent for occlusions distal to the MCA
bifurcation to 97 percent for occlusions proximal to the MCA trunk. Patients who had positive susceptibility signs
had significantly higher NIHSS scores (table 1) compared with patients who did not have the sign, but no
significant differences were found for infarct volume.
High susceptibility MRI sequences are also useful for the detection of acute intraparenchymal hemorrhage,
especially if this is a concern after intra-arterial therapy, a situation where retained contrast is not easily
distinguished from blood on CT [95]. (See "Spontaneous intracerebral hemorrhage: Pathogenesis, clinical features,
and diagnosis", section on 'Hemorrhage appearance'.)
CT VERSUS MRI TECHNIQUES IN HYPERACUTE STROKE The goals of very early neuroimaging are toexclude hemorrhage or stroke mimics, detect signs of early infarction, depict the infarct core and extent of
perfusion deficit, reveal the status of large cervical and intracranial arteries, and guide treatment decisions [96]. As
already noted, diffusion-weighted MRI (DWI) is more sensitive than CT for the early detection of acute ischemia,
and high susceptibility MRI sequences such as gradient echo (GRE) are now known to be as good as CT for the
detection of acute hemorrhage. (See 'Magnetic resonance imaging'above.)
These points are illustrated by a prospective single-center study that evaluated 356 patients referred because of
suspicion for acute stroke irrespective of time from symptom onset [ 57]. Of these, 217 had a final clinical
diagnosis of acute stroke. All 356 patients had both brain MRI (employing DWI and GRE) and head CT, with
median times from symptom onset to scanning of 6.1 and 6.5 hours, respectively. Assessment of all brain images
was blinded to clinical information.
The following observations were reported [57]:
These results suggest that MRI can be used as the only imaging method for patients with suspected acute
ischemic or hemorrhagic stroke who have no MRI contraindications. In addition, a few reports have demonstrated
that it is possible to use MRI routinely as the sole neuroimaging screening method prior to intravenous
thrombolytic therapy [97,98]. In one such study of 135 patients screened with MRI and treated with intravenous
tPA, quality improvement processes led to reduced door-to-needle times of 60 minutes [97].
Limited evidence suggests that the utility of head CT, when performed with CT perfusion imaging (CTP), may be
equal to that of MRI in hyperacute stroke evaluation, as found in a study of 22 patients who were evaluated using
both CT and MRI techniques within six hours of stroke onset (average time interval of 2.33 hours for CT and 3.0
Acute ischemic stroke was detected in more patients by MRI than by CT (46 versus 10 percent), a
difference that was statistically significant
Acute intracranial hemorrhage detection was similar with MRI and CT (6 versus 7 percent)
The sensitivity for the detection of any acute stroke was much greater for MRI than for CT (83 versus 26
percent), while specificity was similar (98 versus 97 percent)
Contraindications to MRI (eg, electronic implants, patient intolerance, or medical instability) led to the
exclusion of about 11 percent of the 450 patients screened for this study
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hours for MRI) [99]. The following results were noted:
Other studies have shown that the CTP derived map of cerebral blood volume (CBV) correlates with the MRI DWIlesion size [38] and is predictive of infarcted brain tissue that is not salvageable despite reperfusion [ 35].
Many more patients considered for the study were eligible for contrast-enhanced CT than for MRI (93 versus 58
percent) [99]. This reflects the well-known problem that MRI in practice is more limited by patient contraindications
or intolerance than CT. In addition, MRI is less widely available than CT outside of major stroke centers.
ULTRASOUND METHODS Carotid Duplex ultrasound (CDUS) and transcranial Doppler (TCD) ultrasound are
noninvasive methods for neurovascular evaluation of the extracranial and intracranial large vessels. Carotid and
vertebral Duplex and TCD have traditionally been used independently in an elective fashion to evaluate patients
with transient ischemic attack (TIA) and ischemic stroke of possible large artery origin.
Although both methods may help to establish the source of an embolic stroke, they have rarely been used acutely
for this purpose. However, accumulating evidence suggests that both Duplex and TCD can be used urgently at
the bedside to select patients for interventional thrombolytic or endovascular treatment [100-103]. (See 'Combined
duplex and TCD' below.)
Carotid and vertebral duplex Color flow guided duplex ultrasound is well established as a noninvasive
examination to evaluate extracranial atherosclerotic disease. This topic is discussed separately. (See "Evaluation
of carotid artery stenosis".)
Transcranial Doppler TCD ultrasound uses low frequency (2 MHz) pulsed sound to penetrate bony windows
and visualize intracranial vessels of the circle of Willis. Its use has gained wide acceptance in stroke and
neurologic intensive care units as a noninvasive means of assessing the patency of intracranial vessels.
In patients with acute stroke, TCD is able to detect intracranial stenosis, identify collateral pathways, detect
emboli on a real-time basis, and monitor reperfusion after thrombolysis [104-106]. Major drawbacks include
examiner-dependence, poor patient windows (unable to insonate a flow signal in 15 percent of cases), and low
sensitivity in the vertebrobasilar system.
Combined duplex and TCD The combination of urgent duplex and TCD appears to have high utility when
performed by skilled ultrasonographers, although the available data come mainly from small studies. As an
example, a study of 150 patients found that the detection of arterial lesions amenable to interventional treatment
(LAITs) by combined duplex and TCD (n=150) at mean time of 128 minutes after stroke or TIA onset was 100
percent sensitive and specific compared with digital subtraction angiography (DSA, n=30) [107]. The combination
of duplex and TCD detected LAITs in 96 percent of patients eligible for thrombolysis. Accuracy of the individual
components was lower but still good duplex ultrasound had a sensitivity and specificity of 96 and 90 percent
compared with DSA, while that of TCD was 96 and 75 percent. About 10 percent of patients had incomplete TCD
studies because of inadequate temporal windows.
A major limitation of this approach is that most centers are unable to perform examinations acutely because they
lack sufficient numbers of experienced ultrasonographers.
CONVENTIONAL ANGIOGRAPHY Digital subtraction angiography, the most widely used method of
conventional catheter-based angiography, remains the gold standard for evaluating the cerebral vessels with regard
to determining the degree of arterial stenosis and the presence of dissection, vasculopathy, vasculitis, or occult
Perfusion lesion volumes derived by CTP did not differ from those derived by perfusion-weighted imaging
(PWI) for both time to peak maps and cerebral blood volume maps.
CTA-SI ischemic lesion volumes did not differ from DWI ischemic lesion volumes.
Lesion volumes on CTP cerebral blood flow maps significantly correlated with lesion volumes on follow-up
non-contrast CT.
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lesions such as vascular malformations [31]. In addition, it provides information about collateral flow and perfusion
status.
Nevertheless, diagnostic conventional angiography is rarely performed in the acute setting for two main reasons.
One is the availability of the noninvasive techniques, such as CT angiography, MR angiography, duplex
ultrasonography, and transcranial Doppler ultrasound, to rapidly visualize intracranial and extracranial arterial
disease. The other is the risk of stroke, albeit low, associated with conventional angiography.
The major exception is suspected large vessel occlusion angiography is more sensitive than noninvasive methods
in these cases and offers the potential for "in-situ" treatment. In addition, angiography shows promise whencombined with neurointerventional techniques for acute intraarterial thrombolysis and angioplasty.
The main drawback to conventional cerebral angiography is the risk of stroke (0.14 to 1 percent) and transient
ischemia (0.4 to 3 percent) [108-113]. The risk of neurologic complications appears to be higher in patients 55
years of age, in patients with atherosclerotic cerebrovascular disease or cardiovascular disease, and with
fluoroscopic time 10 minutes [112,113]. Clinically silent embolism as detected by diffusion-weighted magnetic
resonance imaging (DWI) may occur in up to 25 percent of cerebral angiographic procedures [114,115]. The rate of
clinically silent embolism may be reduced by use of air filters and heparin [116], but it is unclear if such methods
reduce the more important clinical parameter of ischemic stroke.
INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and
"Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5 to 6 grade
reading level, and they answer the four or five key questions a patient might have about a given condition. These
articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond
the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written
at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable
with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these
topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on
"patient info" and the keyword(s) of interest.)
SUMMARY AND RECOMMENDATIONS Our recommendations are based upon the available literature,
consensus guidelines [31,117], and clinical experience.
Brain imaging plays a vital role in acute stroke by:
Head CT is the preferred imaging study at most centers because of widespread availability, rapid scan times, and
ease of detecting intracranial hemorrhage. MRI has an advantage in the very early detection of ischemia with DWIimaging, and it reliably detects hyperacute hemorrhage with proper sequences including high susceptibility images.
Advances in the use of CT angiography (CTA) source images and CT perfusion imaging (CTP) suggest that CT
techniques are increasingly able to provide crucial information regarding early ischemia and perfusion lesions in
hyperacute stroke assessment. CT remains indispensable in the frequent circumstance where there are
contraindications to MRI such as pacemakers and patient intolerance due to anxiety or motion.
th th
th th
Basics topics (see "Patient information: Stroke (The Basics)")
Delineating ischemia from hemorrhage
Estimating tissue at risk for infarction
Excluding some stroke mimics, such as tumor
Brain imaging and a comprehensive neurovascular evaluation should be obtained for most patients suspected
of having acute ischemic stroke or transient ischemic attack. Neurovascular imaging is important in acute
stroke to determine the potential sources of embolism or low flow in ischemic stroke and to detect possible
aneurysms or vessel malformations in hemorrhagic stroke.
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ACKNOWLEDGMENT The editorial staff at UpToDate would like to acknowledge Walter Koroshetz, MD, who
contributed to an earlier version of this topic review.
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