Neuroimaging of Acute Ischemic Stroke

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    19/8/2015 Neuroimaging of acute ischemic stroke

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    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.

    http://www.uptodate.com.consultaremota.upb.edu.co/contents/neuroimaging-of-acute-ischemic-stroke/abstract/116http://www.uptodate.com.consultaremota.upb.edu.co/contents/neuroimaging-of-acute-ischemic-stroke/abstract/112,113http://www.uptodate.com.consultaremota.upb.edu.co/contents/neuroimaging-of-acute-ischemic-stroke/abstract/114,115http://www.uptodate.com.consultaremota.upb.edu.co/contents/neuroimaging-of-acute-ischemic-stroke/abstract/108-113http://www.uptodate.com.consultaremota.upb.edu.co/contents/neuroimaging-of-acute-ischemic-stroke/abstract/31,117http://www.uptodate.com.consultaremota.upb.edu.co/contents/neuroimaging-of-acute-ischemic-stroke/abstract/31http://www.uptodate.com.consultaremota.upb.edu.co/contents/stroke-the-basics?source=see_link
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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.

    Use of UpToDate is subject to the Subscription and License Agreement.

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