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Imaging of AcuteIschemic StrokeCarlos Leiva-Salinas and Max Wintermark *

Stroke is the third leading cause of death in theUnited States, Canada, Europe, and Japan. The American Heart Association and the AmericanStroke Association estimate that approximately800,000 new strokes occur each year, resultingin more than 130,000 annual deaths in the UnitedStates alone. 1 Direct and indirect costs related tostroke are estimated to be $70 billion annually ,and will likely increase in the next decades. 2

Stroke is the l eading cause of adult disability inNorth America. 1

Ischemic stroke is caused by a reduction in theblood supply to the brain (usually a clot occludinga cerebral artery), which subsequently disrupts thesupply of oxygen and nutrients to brain tissue.

Ischemic strokes account for more than 80% of strokes 1 and can be further subdivided into cardio-genic, atherosclerotic, lacunar, hemodynamic, orcryptogenic sources. 3 Another 15% of strokesare related to the disruption of a cerebral artery, re-sulting in intracerebral hemorrhage (ICH). 1 Otherrare causes of stroke-like symptoms includesubarachnoid hemorrhage, cerebral venous sinusthrombosis, chronic subdural hematoma,neoplasms, inflammatory disease, migraine,reversible cerebral vasoconstriction syndrome,seizure, and hypoglycemia. Some of thesesubjects are discussed in other articles elsewherein this issue.

Imaging has revolutionized acute ischemicstroke diagnosis and management. Previously,structural imaging modalities, typically noncon-trast computed tomography (NCT), were used toassess the presence and extent of acute ischemic

stroke and exclude stroke mimics. With the devel-opment of functional imaging modalities such asperfusion CT (PCT) and perfusion magnetic reso-nance (MR) imaging, stroke has been redefinedfrom an all-or-none to a dynamic and evolvingprocess. In particular, the advent of effectivethrombolytic therapies, such as intravenous tissueplasminogen activator (tPA), 4 has motivated us tobetter define the so-called ischemic penumbraand improve patient selection for reperfusiontherapy. Studies have indicated favorable clinicaloutcomes with thrombolytic therapies adminis-tered to patients selected by imaging criteria inan extended time window. 5

In this article, the individual components of

multimodal CT and multimodal MR imaging arediscussed, the current status of neuroimaging forthe evaluation of the acute ischemic stroke is pre-sented, and the potential role of a combined multi-modal stroke protocol is addressed.

PHYSIOPATHOLOGY: THE CONCEPTOF PENUMBRA

When a cerebral artery is occluded, a core of braintissue dies rapidly. Surrounding this infarct core isan area of brain that is hypoperfused, but stillviable because of collateral blood flow. This areaof at-risk, but potentially salvageable, tissue iscalled the ischemic penumbra. 6 e 8

Studies in primates and positron emissiontomography studies in humans 9 e 12 have shownthat brain parenchyma can compensate for hypo-perfusion through an increase in oxygen extraction

The authors have nothing to disclose.

Division of Neuroradiology, Department of Radiology, University of Virginia, 1215 Lee Street-New Hospital,1st Floor, Room 1011, PO Box 800170, Charlottesville, VA 22908, USA* Corresponding author.E-mail address: [email protected]

KEYWORDSStroke MRI CT DW imagingPerfusion Thrombolysis

Neuroimag Clin N Am 20 (2010) 455468doi:10.1016/j.nic.2010.07.0021052-5149/10/$ e see front matter 2010 Elsevier Inc. All rights reserved. n

e u r o i m a g i n g . t h e c l i n i c s . c o m
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down to a cerebral blood flow (CBF) threshold of approximately 20 to 23 mL/100 g tissue/min. If the CBF decreases below this threshold, neuronalfunction is impaired. The affected neurons remainviable and recover without injury after normaliza-tion of the CBF as long as it remains more than

approximately 10 to 15 mL/100 g tissue/min. If the CBF decreases below this point, a shortageof metabolites occurs, causing an Na 1 /K1 channelfailure in the ischemic cells. This membranechannel failure results in an uncontrolled net shiftof extracellular water in the intracellular space.The consequence is cytotoxic edema and irrevers-ible damage to the neuronal cells. 6 The extent andseverity of the CBF reduction and the neuronalintegrity determine the size of the core and thepenumbra. 9 e 12

The rate of change in the size of the core andpenumbra is a dynamic process that dependsmainly on the reperfusion of the ischemic brain. If the occlusion is not removed, the infarct coremay grow and progressively replace thepenumbra. In early recanalization, either sponta-neously or resulting from thrombolysis, thepenumbra may be salvaged from infarction. 13

WHY IMAGE A PATIENT WITH ACUTESTROKE?

The central premise of acute stroke treatment is toresc ue the ischemic penumbra. The current guide-lines 14 neglect the fact that the portion of poten-tially salvageable ischemic tissue is not onlydependent on the time window, but also on theindividual patients collateral blood flow. The pres-ence and extent of the ischemic penumbra aretime-dependent , but are especially patient-dependent . From patient to patient, survival of the penumbra can vary from less than 3 hours towell beyond 48 hours. Of patients with supratento-

rial arterial occlusion, 90% to 100% showischemic penumbra in the first 3 hours of a stroke,but 75% to 80% of patients still have penumbraltissue at 6 hours after stroke onset. 13,15,16

The only drug treatment of acute strokeapproved by the US Food and Drug Administrationis intravenous thrombolysis with recombinant tPA.It is limited to the first 3 to 4.5 hours after symptomonset, and after intracranial hemorrhage has beenruled out by NCT or gradient echo MR imaging. 17

Only 3% to 8.5% of potentially eligible patientsare treated because few are medically evaluatedat an early enough stage, 18 and there is the wide-spread concern of hemorrhagic conversion result-ing from overly aggressive r eper fusion therapy.However, it hasbeen suggested 19,20 that intravenousthrombolytic therapy can be safely administered

beyond 3 to 4.5 hours in selected patients with asufficient amount of salvageable brain tissue, therebyaffording a safe treatment to a larger percentageof patients with stroke. This situation stronglyemphasizes the need for an improved delineationof the salvageable ischemic pe numbra by imaging

in patients with acute stroke. 21The negative results of thrombolysis trials

between 3 to 6 hours 16 may be because nomethod of penumbral imaging was used to selectpatients for therapy, despite penumbra being thetarget for treatment and despite the highpercentage of patients with penumbra within thistime window. Please see the article Acute Neuro-Interventional Therapies elsewhere in this issuefor additional information regarding neurointerven-tional therapy for acute ischemic infarction.

A tissue clock that determines the presenceand relative extent of both infarct and penumbrawould be an ideal guide to patient selectionfor thrombolysis, rather than a rigid time windowas is recommended by the current guidelines. 14

During the last decade, several models forischemic penumbra delineation using MRimaging, and increasingly, CT, have been devel-oped to predict the outcome of ischemic braintissue.

ACUTE STROKE MR IMAGINGMultimodal MR Imaging Stroke Protocol

A typical stroke MR imaging protocol consists of T2/fluid attenuated inversion recovery (FLAIR),T2*, diffusion-weighted (DW) and perfusion-weighted (PW) images ( Table 1 ) and MR angiog-raphy (MRA).22 This protocol can be performed inless than 30 minutes. It achieves reliable informa-tion about the site of vessel occlusion, the extentof potentially salvageable brain tissue, and theexclusion of differential diagnoses of ischemic

stroke.

The MR Imaging Protocol Sequenceby Sequence

T2 and FLAIR imagingOn T2-weighted and FLAIR images, ischemicinfarction appears as a hyperintense lesion usuallyseen within the first 3 to 8 hours after stroke onset( Fig. 1 ).23 e 25 In a recent study of patients withacute ischemic stroke studied by MR imagingwithin 6 hours of symptom onset, patients withouta visible hyperintense lesion on FLAIR images hadgreater than 90% probability of being imagedwithin the first 3 hours of symptom onset. Thus,a mismatch between positive DW imaging andnegative FLAIR images appears to be useful in

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the identification of patients who are likely tobenefit from thrombolysis. 24

FLAIR images are also highly sensitive tosubarachnoid hemorrhage 26 as well as acute cere-bral venous sinus thrombosis. 27,28 In the setting of hyperacute stroke, T2-weighted images can beuseful to detect the loss of the arterial signal flowvoid in occluded vessels within minutesof thestrokeonset. 25 T2-weighted and FLAIR images are bothused to assess older cerebral infarctions and theextent of concomitant small vessel disease. 25

Diffusion-weighted imaging and apparent diffusion coefficient Diffusion MR imaging provides image contrast th atis dependent on the molecular motion of water. 29

Cerebral ischemia leads to energy metabolismdisruption with the failure of the Na 1 /K1 and otherionic pumps. This situation induces a loss of ionic

gradients and a net transfer of water from theextracellular to the intrac ellular compartmentcausing a cytotoxic edema. 6 Excessive intracel-lular water accumulation leads to a reduced extra-cellular volume, which usually facilitates watermobility, and therefore to a reduction of water

diffusion in the extracellular matrix. 29 Thisphenomenon is detected with DW imaging withinminutes of vessel occlusion 13,29 and can bemeasured quantitatively with the apparent diffu-sion coefficient (ADC).

DW imaging is the most sensitive method for thedepiction of ischemia in the hyperacute stage (seeFig. 1; Fig. 2 ).30,31 However, DW imaging lesionscan be at least partially reversible in the early phaseof ischemia, and the size of the DW imaging abnor-mality does not necessarily reflect irreversiblydamaged tissue.A recent seriesof 68acutepatientswith ischemic stroke 32 showed that 20% of thepatients had ADC normalization in greater than 5mL of brain tissue. The partial normalization waspredominantly seen in the basal ganglia and whitematter in patients with distally located vessel occlu-sions, and it was associated with a trend towarda better clinical outcome. This study suggests thatpatients with a perfusion/diffusion match within3 hoursofsymptomonset may stillhavesalvageabletissue at risk and might benefit from thrombolysis.

Noncontrast MR angiography The most commonly used noncontrast MRA tech-nique is time-of-flight (TOF) imaging. This sequencedepicts vascular flowby repeatedly applying a radio-frequency pulse to a volume of tissue, followed bydephasing and rephasing gradients. Stationarytissue in the volume becomes saturated by therepeated excitation pulses and has low signal.Conversely, inflowing blood protons are not satu-rated and therefore produce increased signal inten-sity. 25,33 The vessel contrast is proportional to the

blood velocity (ie, flow-related enhancement). Forselective imaging of arteries, saturation bands areapplied on the venous side of imaging sections tonull signal from the venous flow. 33

Three-dimensional (3D) TOF-MRAis thepreferredtechnique for the examination of intracranialvessels. MRA is particularly useful in the detectionof vascular occlusion and/or stenosis in patientswith ischemic stroke (see Fig. 2 ).25 Technicalimprovements such as parallel imaging and highermagnetic fields allow high spatial isotropic resol u-tion, fast acquisition times, and reduced artifacts. 25

Perfusion-weighted MR imagingPW imaging allows the measurement of capillaryperfusion to the brain. The bolus passage of a paramagnetic intravascular MR imaging contrast

Table 1Recommended acquisition protocol forperfusion-weighted MR imaging

SequenceSingle-shot Gradient EchoEchoplanar Imaging

Imageacquisitionparameters

TR 1500 msTE 5 35 to 45 ms at 1.5 TTE 5 25 to 30 ms at 3 TFlip angle 5 60 to 90 at 1.5 TFlip angle 5 60 at 3 T

Imageacquisitionduration

90 to 120 sImage acquisition started 10 s

before initiation of bolusinjection to achieve at least10 baseline images

Coverageand slicethickness

Field of view z 24 cmWhole brain coverage

using ! 12 slicesGap 0 to 1 mmSlice thickness 5 mmMatrix size 128 128

Sliceorientation

Parallel to hard palate

Contrastmaterial

Standard gadolinium-basedcontrast material

Contrastvolume

Single dose (for half molaragent z 20 mL for 100 kgperson) followed by 20 to40 mL saline flush

Injection rate 4 to 6 mL/s; same rate forsaline

IV access 18- to 20-gauge IV line; rightantecubital vein preferred

Abbreviations: IV, intravenous; TE, echo time; TR, repeti-tion time.

Imaging of Ischemic Stroke 457

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agent through the cerebral capillaries causesa nonlinear signal loss on T2* images. 34 Thisdynamic contrast-enhanced technique tracks thetissue signal changes caused by the susceptibilityeffect to creat e a hemodynamic time-to-signalintensity curve. 35

Gradient recalled echo (T2*) weighted imagingHyperacute stroke imaging demands the differen-tiation between ischemic stroke and hemorrhagic

stroke ( discussed in the article HemorrhagicStroke and Non-traumatic Intracranial Hemorrhageelsewhere in this issue ), which is impossible byclinical means only. Although CT is the standardmethod for the diagnosis of ICH, studies haveshown that hyperacute ICH can be identified onMR (mainly FLAIR and gradient-reca lled echo[GRE] imaging) with excellent accuracy. 36

Moreover, microbleeds (small hemosiderindeposits) not apparent on CT can be detected by

Fig. 1. 75-year-old man presenting with sudden onset of a left face-arm-leg hemisyndrome. Physical examinationrevealed a left hemianopsia, rightward gaze deviation, dysarthria, and left hemineglect. CT and MR examinationwere obtained 2 and 3 hours after admission, respectively. PCT (cerebral blood volume [CBV], mean transit time[MTT], CBF), and DW imaging trace images clearly depict an acute stroke extending to the superficial right middlecerebral artery territory. Note how the lesion is far more subtle on the corresponding T2-weighted image, andespecially on the NCT, where it features a cortical ribbon loss sign.

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Fig. 2. 71-year-old woman presenting with sudden onset of a right face-arm-leg hemisyndrome and nonfluentaphasia. Noncontrast cerebral CT/PCT and DW/PW MR imaging were performed 2 and 2.3 hours after symptom

onset, respectively. The NCT shows a left insular ribbon sign and subtle left parietal hypodensity. The cerebralinfarct and cerebral blood volume CBV abnormality on PCT (mL/100 g) show a similar size to the DW imaging-MR imaging abnormality. However, the size of the CBF/MTT abnormality on PCT ([mL/100 g/min]/[s]) and onthe MR MTT image involves the entire left MCA territory (ie, mismatched defect with penumbral tissue in theanterior MCA territory). The corresponding M1 occlusion is clearly identified on both the CTA and MRA. Thepatient underwent unsuccessful thrombolysis.


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T2*-weighted images. 37 These chronic lesions areassociated with an increased risk of spontaneousICH and may also be a r isk factor forthrombolysis-related hemorrhage. 38,39

In suspected acute stroke, T2*-weightedimages can detect an intraluminal thrombus as

a linear low signal region of magneticsusceptibility. 25

Alternative Sequences for Selected Conditions

Susceptibility-weighted imagingSusceptibility-weighted (SW) imaging is a high-resolution 3D gradient echo sequence that usesmagnitude and phase information to createa new source of contrast. It offers informationabout any tissue that has a different susceptibilitythan its surrounding structures, such as deoxy-

genated blood, hemosiderin, ferritin, andcalcium. 40

SW imaging is exquisitely sensitive in detectinghemorrhage. 40 Studies have shown that it ismore sensitive in detecting hemorrhagic conver-sion and old microbleeds than CT and conven-tional GRE sequences. 40,41

Fresh clots contain a high concentration of deoxyhemoglobin, and thus appear hypointenseon SW images. As a complementary sequence,SW imaging may be useful to depict distal branchthrombi that are not well visualized by MRA. 40

Because of a decrease in arterial flow, and subse-quent increase in the proportion of deoxyhemoglo-bin, acute thromboembolism may result inprominent hypointensity in the draining veinslocated in hypoperfused areas on SW imaging. In

suspected acute stroke, therefore, SW imagingcould also have a potential role by assessing ar ea sof hypoperfusion without the need of contrast. 40

Despite its many potential advantages, thistechnique is not available on all major MR manu-facturers systems and, despite the technical

advances, approximately 5 minutes are stillneeded to image the entire brain. 40

Fat-saturated T1-weighted imagingFat-saturated T1 (T1-FS)-weighted images shouldbe considered if cervical artery dissection is sus-pected. Vascular dissection is an important causeof acute infarction, causing up to 20% of cerebralinfarctions in young patients. It occurs when bloodextends into the wall of a vessel through an intimaltear. 42

Dissection occurs most frequently in the distalextracranial portion of the internal carotid arteryand vertebral artery. It causes ischemic strokeprimarily through embolization rather than throughhemodynamic flow limitation. 25 The intramuralblood appears hyperintense on T1-FS-weightedimages when met-hemoglobin develops, typicallywithin 2 to 3 days after dissection ( Fig. 3 ).42

Contrast-enhanced MRA of the cervical arteriesContrast-enhanced MRA (CE-MRA) is the tech-nique of choice for extracranial artery imaging. 29

It relies on injection of a paramagnetic agentsuch as gadolinium to reduce the T1 relaxationtime of tissue and to generate contrast betwe enthe intravascular lumen and surrounding tissues. 43

Unlike TOF-MRA, vascular contrast is thereforerelatively independent of flow dynamics, and

Fig. 3. 40-year-old man presenting with left-sided neck pain and right-sided weakness. ( A ) Axial T1 fat-saturated(T1-FS)-weighted MR image shows a large crescent of hyperintense signal (representing intramural met-hemoglobin) within the cervical portion of the left ICA, consistent with a carotid dissection. ( B) Coronalcontrast-enhanced MRA maximum intensity projection image shows narrowing of the left ICA at the site ofdissection ( arrows ).


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artifacts associated with saturation effects aresubstantially reduced. Vessels from the aorticarch to the circle of Willis can be obtained in lessthan 1 minute. This sequence enables potent ialassessment of stenosis or vessel occlusion. 43

CE-MRA is also used to show luminal narrowing

in acute dissection (see Fig. 3 ).44

MR Imaging for the Differentiation of Infarct Core and Penumbra

It has been hypothesized that DW imaging reflectsthe irreversibly damaged infarct, whereas PWimag ing reflects the overall area of hypoperfu-sion. 45 The volume difference between these tech-niques, termed the PW/DW imaging mismatch ,represents the MR imaging correlate of theischemic penumbra (see Figs. 1 and 2 ).

Conversely, if there is no difference in PW andDW imaging volumes, or even a negative differ-ence (PW < DW imaging), this is termed a PW/ DW imaging match . This matched defect is seenin the patient who does not have penumbral tissueeither because of normalization of previous hypo-perfusion or because of completion of the infarc-tion and the total loss of penumbra. 45 e 47 It maybe argued that this model does not take intoaccount that the PW imaging lesion also assessesareas of oligemia that are not in danger and thatDW imaging abnormalities do not necessarilyturn into infarction. 32,48 It is not yet clear whichparameter gives the best approximation to criticalhypoperfusion and allows differentiation of infarctfrom penumbra. However, most investigatorsagree that in current clinical practice, T max andmean transit time (MTT) seem to give the bestresults.

Stroke MR Imaging in Clinical Trials

Stroke MR imaging has been investigated in the

clinical setting to evaluate its role for thrombolysisin an extended time window. The DIAS (Desmote-plase in Acute Ischemic Stroke) and DEDAS (DoseEscalation of Desmoteplase for Acute IschemicStroke) trials 19,20 used a new fibrinolytic drug, des-moteplase, in patients with acute ischemic strokewithin a 3- to 9-hour time window after symptomonset. Patient screening was based on clinicalexamination and medical history and guided bystroke MR imaging. Only patients showing a clearDW/PW imaging mismatch were randomized. Thepatients who received a placebo or an ineffectivedosage showed a lower recanalization rate andan unfavorable outcome. Patients who achievedearly vessel recanalization and reperfusion of penumbral tissue showed a significant clinicalbenefit, and 60% of the patients from the most

effective dose tier had an excellent clinicaloutcome. 19

In the DIAS 2 study, 49 patients were enrolledbased on a mismatch diagnosed either by MRimaging or by PCT. The intention-to-treat analysisfound no significant difference between the

groups in clinical response rates, contrastingwith their previous findings with desmoteplase inthe DIAS and DEDAS trials. Clinical responserate was 46.0% in the placebo group, 47.4% inthe group who received 90 mg/kg, and 36.4% inthe group who received 125 mg/kg.

The DEFUSE trial5 was designed to determinewhether a mismatch between perfusion and diffu-sion could be used to predict clinical outcome inpatients with early reperfusion after treatmentwith recombinant tPA during the 3- to 6-hourtime window after symptom onset. Patients witha baseline mismatch between PW and DWimaging of at least 20% and a reduction in perfu-sion abnormality volume of at least 10 mL hada better clinical outcome. The trial thus showedthat baseline MR imaging findings can be usedto identify groups of patients who are more likelyto benefit from thrombolytic therapy and, poten-tially, other forms of reperfusion therapy. Datafrom this study suggested that a larger difference,a mismatch ratio (PW imaging volume-DWimaging volume/DW imaging volume) of 2.6,

provided the highest sensitivity and specificity foridentifying patients in whom reperfusion was asso-ciated with a favorable response. However, evenin the presence of a large PW/DW imagingmismatch, no benefit could be expected if earlyrecanalization of the occluded vessel failed. 50

Other trials have studied the role of early MRimaging changes for the prediction of thrombolysisoutcome. Large ischemic lesions on DW imagingare predictive of poor outcome regardless of whether thrombolysis is performed. 51 A prospec-

tive study in patients with anterior circulationischemic stroke treated with tPA within 3 hoursof stroke onset compared the baseline DWimaging findings using the Alberta Stroke ProgramEarly CT Score (ASPECTS) with patient clinicaloutcome at 7 days. 51 Clinical worsening andpoor outcome were noted more frequently inpatients with ASPECTS 5 or less. The investigatorssuggested that these patients should be excludedfrom studies of thrombolysis beyond the 3-hourtime window.

ACUTE STROKE CTMultimodal CT Stroke Protocol

Modern CT imaging, including NCT, PCT( Table 2 ), and CT angiography (CTA), fulfills all


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the re qu irements for hyperacute strokeimaging. 52 NCT can exclude hemorrhage; PCTcan differentiate between pe numbra and irrevers-ibly damaged brain tissue 52 ; and CTA identifiesintracranial thrombus and vascular narrowing.Multimodal CT offers rapid data acquisition andcan be performed with conventional CTequipment.

The CT Protocol Sequence by Sequence

Noncontrast CT

With its widespread availability, short scan time,noninvasiveness and safety, NCT has been thetraditional first-line imaging modality for the evalu-ation of acute ischemic stroke. In this setting, NCTis typically used to rule out intracranial hemorrhage

and other stroke mimics. Occasionally, NCT canprovide information that supp orts the diagnosisof hyperacute infarction. 53 e 55 Early CT signs of brain ischemia include

1) Insular ribbon sign. The insular cortex is partic-

ularly vulnerable to a proximal middle cerebralartery (MCA) occlusion because it is the regionmost distal from the potential anterior andposterior collateral circulation, and therefore itis a watershed arterial zone. When ischemic,the insular region shows loss of definition of the gray-white interface, o r loss of the insularribbon (see Figs. 1 and 2 ).53

2) Obscuration of the lentiform nucleus. Becauseof their blood supply via end arteries, the basalganglia ar e also particularly vulnerable to earlyinfarction. 54 When ischemic, an obscuredoutline or partial disappearance of the lentiformnucleus can be seen on NCT ( Fig. 4 ).

3) Hyperdense artery sign. The presence of anacute thrombus in the MCA creates a linear hy-perattenuation on NCT, the so-called hyper-dense artery sign (see Fig. 4; Fig. 5 ).55

Contrary to the other early CT signs, this onerepresents not an infarction but a thromboticevent. 55 Although it is highly specific forischemia, its sensitivity is poor, 56 and false-positive results such as high hematocrit level

or atherosclerotic calcification should beexcluded. However, in those cases the hyperat-tenuation is usually bilateral. 57

Although these early signs can be helpful instroke detection, they are subtle, difficult to detect,and exhibit limited sensitivity in the hyperacutestage of ischemic stroke (approximately 25%during the first 3 hours) when compared with DWMR imaging. 58 Moreover, the relationship betweenearly ischemic changes on CT and adverseoutcomes after tPA treatment is notstraightforward. 59,60

In contrast to these early ischemic changes,obvious hypoattenuation is highly specific forirreversible tissue damage, 61 and its extent ispredictive of the risk of hemorrhagic transforma-tion. 62 In the European Cooperative Acute StrokeStudy trials (ECASS I and II), involvement of morethan one-third of the MCA territory on NCT wasused as a criterion for patient exclusion fromreperfusion therapy because of the potent ialincreased risk for hemorrhagic transformation. 63

Despite its many advantages, NCT providessolely anatomic (and not physiologic) informationand it cannot reliably differentiate between irre-versibly damaged brain tissue and penumbraltissue.

Table 2Recommended acquisition protocol for PCT

Imageacquisitionrate

Image acquisition 6 e 7 s afterstart of injection of thecontrast bolus

2 phases:First phase: 1 image per s,duration 30 to 45 s

Second phase: 1 image per 2or 3 s, duration 30 to 45 s

Total duration at least 70 sImage

acquisitionparameters

80 kVp, 100 mAs

Coverageand slicethickness

Field of view z 24 cmMaximal coverage possible

based on CT scanner

configuration (minimalcoverage of 20 mm slab perbolus injection preferable.Two boluses injection ispossible to double coveragein scanners with less than40 mm detector lengthunder precluded by contrastdose considerations)

Sliceorientation

Parallel to hard palate

Contrast

material

High concentration

(350e

370 mg/mL) low/isoosmolar contrast preferredContrast

volume35 to 50 mL, followed by 20

to 40 mL saline flushInjection rate 4 to 6 mL/s; same rate for

salineIV access 18- to 20-gauge IV line. Right

antecubital vein preferred


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Perfusion CT PCT imaging, using standard nonionic iodinatedcontrast, relies on the speed of modern helicalCT scanners, which can sequentially trace theentry and washout of a bolus of contrast inject edinto an arm vein through an intravenous line. 64

The relationship between contrast concentrationand signal intensity of CT data is linear. Thereby,analysis of the signal density first increasing thendecreasing during the passage of the contrast

provides information about brain perfusion.65

More specifically, the PCT evaluation of brainperfusion consists of 3 types of parametricmaps: cerebral blood volume (CBV), MTT, andCBF. CBV reflects the blood volume per unit of

brain (4e 6 mL/100g in gray matter). MTT desig-nates the average time required by a bolus of blood to cross the capillary network (4 secondsin gray matter). CBF relates to the volume of bloodflowing per brain mass during a time interval of 1minute (50 e 60 mL/100 g/min in gray matter). 64,65

The relationship between CBV, MTT and CB F isexpressed by the equation CBF 5 CBV/MTT.64,65

Recently, CBF values from PCT imaging havebeen shown to be highly accurate in humans

when compared with the gold standard (PET).66

CT angiography Advances in multidetector row CT technologyhave made CTA a valid alternative to conventional

Fig. 4. Acute MCA infarction with hyperdense MCA. Noncontrast brain CT in a 62-year-old man obtained 4 hoursafter the onset of symptoms shows a hyperdense right MCA ( arrow ), obscuration of the right lentiform nucleus,and subtle loss of gray-white differentiation within the right orbitofrontal lobe.

Fig. 5. 86-year-old woman admitted to the emergency department after sudden onset of right face-arm-leg hem-isyndrome. ( A ) NCT of the brain shows a hyperdense left MCA ( arrow ). (B) Concurrent CTA shows nonfilling of theleft MCA, consistent with intraluminal thrombus. Note how the margins of the infarct are more conspicuous onthe CTA source image.


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catheter-based cerebral angiography. 67,68 Withcurrent CT scanners, the region from the aorticarch up to the circle of Willis can be covered ina single data acquisition with excellent, isotropicspatial resolution, in less than 5 seconds. Multi-planar reformatted images, maximum-intensity

projection images, and 3D reconstructions of source images provide images comparable withthose obtained with conventional angiography. 69,70

CTA allows a detailed evaluation of the intra-and extracranial vasculature. 70,71 Its usefulnessin acute stroke lies not only in its ability to detectlarge vessel thrombi within intracranial vessels(see Fig. 2 ), and to evaluate the carotid and verte-bral arteries in the neck 71 but also in its potentialfor guiding therapy. In particular, the exact locationand the extent of vascular occlusion have beenshown to have prognostic value in the responseto thrombolytics and the determination of collat-eral circulation and possible risk of subsequentrecanalization. 72 For example, patients witha top-of-carotid occlusion, proximal MCA branchocclusion, or significant thrombus burden mightbe poor candidates for intravenous thrombolytics,and may be better candidates for intra-arterial ormechanical thrombolysis. 73

CT in Differentiation of Infarct Coreand Penumbra

PCT distinction of the infarct core from thepenumbra is based on the concept of cerebralvascular autoregulation. 65,74,75 In hypoperfusedareas of brain parenchyma, there are typicallyhigh MTT values as a result of supply via collateralcirculation. Autoregulation attempts to preserveCBF values by inducing vasodilatation, whichresults in an increased CBV. Brain regions charac-terized by such PCT values are considered areasof ischemic penumbra that could benefit from re-

perfusion. Conversely, when ischemic injury ismore severe and prolonged, autoregulation isunable to maintain the CBV above the thresholdfor neuronal death, and the tissue experiencesirreversible hypoxic damage with a subsequentdecrease in CBV; this area represents the infarctcore, where tissue no longer viable does notbenefit from reperfusion and is at risk for hemor-rhage (see Figs. 1 and 2 ).65,74

Large prospective studies on patients with acuteischemic infarction have proved the validity of thistheory and have provided evidence about theoptimal ap proach to defining the infarct core andpenumbra. 76 The PCT parameter that most accu-rately describes the tissue at risk of infarction isthe relative MTT, with an optimal threshold of 145%. The parameter that most accurately

describes theinfarctcore on admission is theabso-lute CBV, with anoptimal threshold of 2.0 mL/100g.The mismatch between these 2 parameters affordsthe most accurate delineation of the tissue at riskof infarction in the absence of recanalization.

Therefore, by combining MTT and CBV results,

PCT has the ability to reliably identify the reversibleischemic penumbra and the irreversible infarctcore in patients with acute stroke immediatelyafter admission. 76 In the infarct core, MTT is prolonged and CBV values are lowered, whereas inthe penumbra, cerebral vascular autoregulation attempts to compensate for a reduced CBF by a local vasodilatation, resulting in increased CBV values. 65,74

The penumbra, as described by PCT, has beenshown to be accurate when compared with acuteand delayed DW/PW imaging (see Fig. 2 ).75,77

CT or MR: Which One to Choose?

CT and MR imaging provide similar information.The infarct core and the ischemic penumbra, asshown by DW/PW imaging and by PCT, arecomparable. 74,77 In addition to the similarity of their results, both CT and MR imaging techniqueshave respective advantages and drawbacks to beconsidered in the special setting of acute stroke.

Stroke MR imaging is still available only in

a limited number of hospitals. Depending oneach individual setting, it is difficult to conductstroke MR imaging without losing too much timebefore treatment onset. The main advantages of MR imaging are the direct visualization of the fullextent of infarction that is seen on DW imagingand the whole brain coverage that allows thedetection of small but clinically relevant hypoper-fusion areas. Visualization of the circle of Willis canbe performed in w 3 minutes with a TOF-MRA.No additional radiograph dosage or iodinated

contrast agent is needed and hence no nephrotox-icity or relevant allergic reactions are expected.However, the control of vital signs and the accessto the patient during the MR imaging study arelimited by the magnet. In addition, it takes someeffort to train technicians to conduct a stroke MRimaging in a short period to establish an adequatework flow during the hyperacute phase of anischemic stroke.

CT is often criticized for its use of radiation andiodinated contrast material. Nevertheless, whenusing such parameters, the effective radiationdose associated with a single-slab PCT study isapproximately equal to tha t of an unenhancedhead CT, roughly 2 to 3 mSv, 78 and no renal failurehas yet been reported following a PCT examina-tion. 79 However, because of limited spatial


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