Imaging in stroke and vasculardisease—part 1: ischaemic stroke

Shelley Renowden

Correspondence toDr Shelley Renowden,Department of Neuroradiology,Frenchay Hospital, NHS Trust,Bristol, UK; Shelley.Renowden@nbt.nhs.uk

▸ http://dx.doi.org/10.1136/practneurol-2013-000801

To cite: Renowden S. PractNeurol Published Online First:[please include Day MonthYear] doi:10.1136/practneurol-2013-000802

INTRODUCTIONStroke is the third leading cause of deathin Europe, the USA, Canada and Japanand is the primary cause of adult disabil-ity in these countries. Over 80% areischaemic (cardiogenic, atherosclerotic,lacunar, haemodynamic and cryptogenic).The remainder are haemorrhagic (largelyparenchymal and subarachnoid) and areconsidered in a separate article. Somepathologies may cause infarction andhaemorrhage, for example, hypertensivevascular disease, moyamoya, vasculitis,reversible vasoconstriction syndrome,arterial dissection and venous occlusivedisease.Cranial CT is the most useful initial

imaging modality to differentiatebetween ischaemia and haemorrhage andto exclude stroke mimics.

HYPERACUTE ISCHAEMIC STROKEFollowing arterial occlusion, a core ofbrain tissue dies. Surrounding this ishypoperfused, viable brain, survivingbecause of collaterals, at risk but poten-tially salvageable—the ischaemic penum-bra. Brain parenchyma compensates forhypoperfusion by increasing oxygenextraction when the cerebral blood flow(CBF) falls to 20–23 mL/100 g/min.Below this level, neuronal function isimpaired but remains viable, althoughcan recover unless CBF is below 10–15 mL/100/min. Membrane channelfailure then results in a net uncontrolledshift of extracellular water into the intra-cellular compartment. Cytotoxic oedemaand irreversible damage (infarct core)depend upon the extent and severity ofthe blood flow reduction. The rate ofchange in size of the core and penumbrais a dynamic process, depending onwhether or not cerebral reperfusionoccurs. Without revascularisation, theinfarct core enlarges and progressivelyreplaces the penumbra. If there is recana-lisation, the penumbra may be salvaged.

The volume of salvageable braindepends upon occlusion duration, collat-erals, site and extent of occlusion—theremay be viable parenchyma from betweenup to 3 h to more than 48 h, and 75–80% of hyperacute ischaemic stroke(HIS) patients have viable tissue after 6 h.The probability of a good outcome fallswith increasing time to recanalisation.Thus, time and collaterals are brain.The current standard of care in the

treatment of HIS is intravenous tissueplasminogen activator (tPA) within 4.5 h,and the only required neuroimagingmodality is non-contrast CT to excludehaemorrhage.

CT scanning in HISThis is the most practical way to evaluateHIS. CT is readily available, quick anduseful in those with moderate and severestrokes who cannot cooperate. CT maybe normal or may define subtle earlyischaemic change. However, within thefirst 2–3 h it has poor sensitivity andpoor inter-rater agreement in detectingearly ischaemic change. One should focuson the basal ganglia and insula. Theinsular cortex is particularly vulnerable toproximal middle cerebral artery (MCA)occlusion. Early ischaemic change is sug-gested by loss of definition of the grey-white interface—the ‘insular ribbonsign’—due to insular cortical/cytotoxicoedema (figure 1).The basal ganglia are also susceptible,

being supplied by end artery lenticulostri-ates. Loss of grey-white differentiationobscures the lentiform nucleus (figure 1).Using the Alberta Stroke Programme

Early CT Score (ASPECTS) can improvethe sensitivity for detecting early ischae-mic change in MCA stroke only (Barberet al, Lancet 2000). This divides theMCA territory into 10 regions. Onepoint is subtracted from 10 for eachregion containing early ischaemic change.Within the first 3 h of MCA stroke onset,

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Figure 1 Axial non-contrasted CT head scans (A–E) and a coronal CTA reconstruction (F) in a 60-year-old man with a hyperacuteischaemic stroke. Note, dense thrombus in the left terminal internal carotid and middle cerebral artery (MCA) and an MCA branch inthe Sylvian fissure. The hyperdense MCA is 100% specific, but only 5–50% sensitive for the diagnosis of MCA occlusion. There isloss of insular definition, obscuration of the lentiform nucleus and ill-defined low density in the left peri-Sylvian cortex reflecting earlyischaemic change. CTA confirms occlusion of the left terminal ICA, M1 and M2 branches with some distal MCA filling fromcollaterals.

Figure 2 Hyperdense basilar artery sign: Axial non-contrasted CT head scans (A–D) in a 66-year-old man who had experienced anepisode of dizziness and a few hours later became unconscious. Note, the dense thrombus within the occluded basilar artery;compare with non-contrasted CT obtained 2 weeks before (E and F). The hyperdense basilar artery sign is 71% sensitive and 98%specific for basilar artery thrombosis. CT detects fewer infarctions in the posterior fossa because of beam-hardening artefact inducedby the dense bony petrous ridges. Additionally, many brainstem infarctions are small, despite causing significant neurological deficit(see figure 15).

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Figure 3 Axial non-contrasted CT scans: 65-year-old woman with sudden onset left-sided weakness and left homonymoushemianopia showing dense thrombus in the right posterior cerebral artery (A, arrow). Compare (A) with (B, 36 h later). Theparenchyma appeared normal at this stage. There is subtle ischaemic change at 36 h (C and D) with low density in the cortex of theright occipital lobe and right anterior thalamus. The established infarct is clear at 5 days as a distinct, well-demarcated cortical lowdensity in the occipital lobe (E).

Figure 4 Axial cranial non-contrasted CT scans in an 81-year-old man, with hyperacute ischaemic stroke, 1.5 h post-ictus, NationalInstitutes of Health Stroke Scale (NIHSS) 26, in atrial fibrillation, and with type 2 diabetes mellitus. There is dense thrombus in theterminal left internal carotid artery, low density in the insula, obscuration of the lentiform nucleus, ill-defined low density involvingthe cortex of more than one-third of the middle cerebral artery territory and left cerebral hemisphere swelling with sulcal effacement.These imaging findings of extensive early ischaemic change with swelling would contraindicate lytic therapy or thrombus extractionbecause of the risk of haemorrhagic transformation and greater risk of iatrogenic damage.

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baseline ASPECT scores correlate inversely with theseverity of National Institutes of Health Stroke Scale(NIHSS) and with functional outcome. Scores belowseven indicate more extensive cerebral low density inthe MCA territory and correlate with both poor func-tional outcome and symptomatic intracerebral haem-orrhage. ASPECT scores of 8–10 suggest greaterbenefit from intravenous tPA.An acutely occluded artery may contain hyperdense

thrombus (figures 1–5). This sign is highly specific foracute thrombus but vascular calcification can causefalse positives.

More obvious low density in the occluded arterialterritory is highly specific for irreversible braindamage. Larger ischaemic areas can generate swelling,manifest by sulcal effacement (figure 4). Involvementof more than one-third of MCA territory is oftentaken as a contraindication for intravenous tPA within4.5 h of ictus because of the potential risk of haemor-rhagic transformation (figure 6).Intravenous tPA remains the standard of care but

intravenous therapy alone is less likely to help certainpatient groups: for example, patients with severestrokes with a large thrombus burden, terminal

Figure 5 Axial cranial CT scans: A 60-year-old man with a hyperacute ischaemic stroke (2 h post-ictus) with dense thrombus in hisright M1 (A, arrow). There is subtle cortical low-density early ischaemic change involving more than one-third of the middle cerebralartery (MCA) territory (B). He was treated with intravenous tissue plasminogen activator but without benefit (only 20–30% of M1occlusions respond and achieve a good outcome), and a scan 3 days later confirms established infarction of the right MCAterritory (C). The infarct is now easily seen—more hypodense and more defined with sharp margins and mild mass effect (the Sylvianfissure is effaced). Mass effect is usually most marked between days 3 and 5, and rarely is considerable, but on occasion, can beassociated with subfalcine herniation (see figure 7) and uncal herniation. Brain swelling begins to decrease after the first week andusually resolves by 12–21 days.

Figure 6 Axial non-contrasted CT scans show a large right middle cerebral artery infarction, 2 days after intravenous thrombolysis,complicated by haemorrhagic transformation. There is mass effect with sulcal effacement, effacement of the Sylvian fissure andventricular compression. Haemorrhagic transformation may follow reperfusion of severely ischaemic brain, often with embolicocclusions.

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internal carotid artery lesions, proximal MCA lesions(figure 5), tandem lesions and basilar artery occlu-sions. Initial experience suggests that in these,intra-arterial tPA or probably better, clot extraction,may be more effective although there are currently norandomised control studies to support this. Recentlyreported trials, largely using historical thrombectomydevices are flawed and many other trials are ongoing(figure 7).CTand MR are probably equivalent in triaging lytic/

clot extraction therapy. In practical terms, non-contrasted CT and CT angiography are the most useful—lyse/extract the thrombus without delay! CT perfu-sion or MR, is probably not worth the additional delay(except perhaps in ‘last seen well/wake up strokes’).

CT angiographyGood quality angiographic images from the aorticarch to the vertex can be obtained very quickly and

reformatted in three planes. The location and extentof arterial thrombus, pre-existing arterial disease andadequacy of the circle of Willis and other collaterals(with appropriate timing to allow delayed opacifica-tion) are readily defined to guide therapy (figure 8).CT angiography has 98% sensitivity, 98% specificityand 98% accuracy in showing major vessel occlusionin HIS, as compared with digital subtraction angiog-raphy (DSA).Parenchymal low density on CT angiogram source

images may define the infarct core.Single-session multidetector CT or CT angiogram of

the heart, aortic arch, extracranial and intracranial arter-ies is being evaluated in the ‘one stop’ work-up of HIS.

Perfusion CTThis technique (like MR perfusion, semiquantified)involves tracing the passage of a bolus of intravenouscontrast through the parenchyma. Tissue density

Figure 7 Axial non-contrasted CT in a 65-year-old man with left cervical internal carotid artery occlusion and a right hemiparesis.Initial scans (A–C) show hyperdensity in the left middle cerebral artery. The parenchyma was normal. Scans 24 h later (D–F) show thedefined infarction with mild swelling, and scans a further 24 h (G–I) later demonstrate massive infarct swelling with uncal herniation,risking secondary infarction in the posterior cerebral artery territory and subfalcine herniation which has resulted in anterior cerebralartery infarction. Decompressive craniectomy may help to avoid the effects of massive brain swelling (G–I) and secondary infarctions,but is controversial except in cerebellar hemisphere infarction.

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increases and then decreases in a linear fashion,reflecting perfusion status. Blood flow maps provideinformation regarding CBF, blood volume and meantransit time. In cerebral hypoperfusion, the meantransit time increases, reflecting supply by collateralcirculation. Autoregulation attempts to preserve CBFby vasodilating resistance vessels, thereby increasingcerebral blood volume. Areas with preserved autore-gulation are viable. If the ischaemic injury is severeand prolonged, autoregulation cannot maintain suffi-cient blood flow and neuronal death ensues. Cerebralblood volume is reduced. The area of reduced cerebralblood volume and CBF and elevated mean transittime reflects infarcted tissue. In the penumbra, meantransit time is prolonged and cerebral blood volumeelevated, due to vasodilatory compensation.Although cerebral blood volume most accurately

describes infarct core, we do not yet have a way todefine the penumbra clearly. CT perfusion cannotinform the rate of infarct progression. However, theabsolute values provided by CT perfusion (and perfu-sion MR) are poorly reproducible and should beviewed with caution. Differences in scanner equipmentand postprocessing methods affect precise values.In the author’s opinion, perfusion techniques (CT

or MR) may be most useful in ‘last seen well/wake upstrokes’ to define potentially salvageable brain.

MRI in HISCT is the most practically useful imaging technique inHIS, but some centres are resourced effectively (oursis not!) to achieve timely MRI—displaying infarctcore, ischaemic penumbra, site and extent of arterialocclusion. Patients with large strokes, however, maynot be able to comply.T2W gradient echo, or susceptibility-weighted tech-

niques, must be included to exclude haemorrhage.Infarcted tissue may become T2 hyperintense at 3–8 h(figure 9). If T2 and FLAIR images are normal, theictus occurred inside 3 h (>90% specificity and posi-tive predictive value)—this might help in ‘last seenwell/wake up strokes’. T2 images also detect arterialocclusion—lack of arterial flow void—since flowvoids occur because of high velocity, turbulence anddephasing. High T2 signal may develop in intracranialarteries distal to a tight stenosis or occlusion onFLAIR imaging (figure 9).Diffusion weighted MRI (DWI) is the most sensitive

way to detect acute ischaemia but is not 100%, DWIand reflects the molecular motion of water. Cytotoxicoedema results in restricted water mobility: diffusionis decreased (figure 10). Signal change can occurwithin minutes of occlusion but demonstration ofsignal change is dependent upon the extent of reduc-tion in CBF. Cerebral swelling and cytotoxic oedema

Figure 8 Hyperacute ischaemic stroke, 2 h post-ictus, National Institutes of Health Stroke Scale (NIHSS), 21 Axial non-contrasted CTscans (A and B) show dense thrombus in the left middle cerebral artery and terminal internal carotid artery (A), loss of grey-whitedefinition in basal ganglia with obscuration of the lentiform nucleus and loss of the insula. Coronal CTA reconstructions (C and D)confirm occlusion of the terminal ICA and M1 on the left, with distal branches filling via collaterals, but also a critical stenosisinvolving the left carotid bulb and cervical ICA origin (D, arrow). This tight stenosis required angioplasty after clot extraction from theintracranial terminal internal carotid artery and M1. It is extremely unlikely that he would have responded well to intravenous tissueplasminogen activator.

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may not result until CBF drops to around 20 mL/100 g/min.The hyperacute DWI lesions may be partially revers-

ible but a DWI lesion >100 mL suggests a badoutcome: even endovascular therapy is unlikely tohelp.

MR angiographyGadolinium-enhanced MR angiography (MRA) is thetechnique of choice for extracranial artery evaluation.The aortic arch to the circle of Willis can be imagedin 1–2 min (figure 10). Three-dimensional (3D)time-of-flight is preferred to assess intracranial vessels(see later). For major acute arterial occlusion, MRAhas a sensitivity of 84–87% and specificity of 85–98%compared with DSA.

Perfusion-weighted MRIThe passage of a bolus of gadolinium through thecerebral capillaries causes non-linear signal loss onT2* images. Perfusion-weighted imaging tracks thetissue signal change caused by the susceptibility effectof gadolinium and reflects tissue perfusion. A perfu-sion defect reflects the overall area of hypoperfusionand also includes benign oligaemic tissue that is not atrisk. Haemodynamic time-to-signal intensity curveand semiquantitative perfusion maps are generated,providing information about CBF, cerebral bloodvolume, time-to-peak and mean transit time.A diffusion-weighted/perfusion-weighted imaging

mismatch suggests that the ischaemic penumbra mightrespond well to endovascular therapy. Those withmatched defects are less likely to respond.

T2*-weighted images (T2 gradient echo)These are most important to exclude acute haemorrhage,but T2*-weighted images may also detect small haemosi-derin deposits not seen on routine MR sequences or CT(see later). These are tiny chronic microbleeds, indicatinga haemorrhage-prone vasculopathy, and suggest anincreased risk of intracranial haemorrhage. Their rela-tionship with post-thrombolysis-related intracranialhaemorrhage is unclear, but is probably small andunlikely to exceed the benefits of thrombolysis in HIS.

Imaging in transient ischaemic attack/minor strokeA transient ischaemic attack (TIA) is a transient episodeof neurological dysfunction caused by focal brain,spinal cord or retinal ischaemia, without acute infarc-tion. Fifteen per cent of stroke patients have a warningTIA. Up to 20% of TIA patients suffer a stroke within3 months, half of these within 48 h. The time windowfor secondary prevention is therefore limited. After aTIA, the 10-year risk of any first stroke, myocardialinfarction or vascular death is as high as 43%.It is important to identify TIA/minor stroke patients

at greatest risk. Motor or speech deficits, hyperten-sion, TIA duration >10 min, age >60 years and dia-betes mellitus are independent risk factors (ABCD2score) for stroke within 90 days. Patients with all fivehave a risk as high as 34%. The ABCD score obvi-ously does not define embolic source—cardiac versuscarotid/vertebrobasilar.Specialist assessment is crucial before imaging to

exclude TIA mimics (as high as 40% of referrals toregional neurovascular clinics). Patients with highABCD2 score (National Institute of Health and CareExcellence (NICE) guidelines state 4 or more) or

Figure 9 A 68-year-old man with pins and needles in his left arm who has a tight short-segment stenosis involving the right M1 (A,frontal oblique right carotid angiogram, arrow). FLAIR coronal MRI (B and C) confirm a small right temporal cortical infarction (B) andhyperintense signal in the middle cerebral artery branches distal to the stenosis (C, arrow).

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crescendo TIAs require specialist assessment within 24 h.With scores <4, patients should receive 300 mg aspirinimmediately, and review by a specialist, within 1 week.

DWI and gadolinium-enhanced MRA (figure 11)are the optimal imaging techniques, but oftenresources do not permit, and non-contrasted CT (to

Figure 10 Axial T2W MR (A–D) and a coronal FLAIR MRI (E) in a 30-year-old woman with sudden onset mild left hemiparesis anddysarthria, 10 h post-ictus. There is cortical T2 hyperintensity, due to embolic infarction in the right insular cortex and inferior frontalgyrus. Note, the absence of flow void from the right ICA, indicating occlusion (A, B and E arrows). Compare with the cranial CT scansperformed earlier ( J–N). The MR axial apparent diffusion coefficient maps (F and G) and diffusion image (H) confirm the decreaseddiffusion in the acute infarction. Diffusion remains decreased for approximately 5–7 days post-ictus. Contrast-enhanced MRangiography, coronal reconstruction (I) confirms occlusion of the right cervical ICA, probably due to dissection, with reconstitution ofintracranial flow via the anterior communicating artery. Note extensive recanalisation several months later on the CT angiographicreconstructions (O and P).

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exclude other diagnoses) and alternative vascularimaging (see below) often suffice.In TIA, DWI diagnostic yield falls rapidly with time.

Some studies report that as many as 68% of TIApatients have early DWI positivity—many othersreport much lower (20%). DWI positivity persists asevidence of infarction in half, and confers 5–10-foldgreater risk of further ischaemic events when com-pared with DWI-negative patients.Intracranial vessel occlusion is associated with an

increased risk of recurrent (risk ratio 7.9) and silentstroke on day 30 (risk ratio 3.3) compared with thosewithout occlusion. Patients with DWI positivity andintracranial occlusion are nearly nine times morelikely to have recurrent stroke at day 90 than those

with neither; both predict functional dependence at3 months.Combining clinical and imaging information therefore

enhances risk assessment (see Pavlovic et al, 2010).Perfusion-weighted imaging changes may occur in

one-third of TIA patients even after clinical resolution,and can occur in 6% of DWI-negative patients.

Vascular imaging in TIA/minor strokeVascular evaluation is important in all with ischaemicstroke/TIA. Carotid stenosis >50% is seen in 12–20%of all anterior circulation ischaemic strokes and carriesa stroke risk two to three times higher than less severeasymptomatic stenosis. The greater the stenosis, thegreater the risk of stroke.

Figure 10 Continued.

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Patients with acute non-disabling stroke or TIA whohave carotid stenosis of 50–99% according to theNASCET criteria, or 70–99% according to the ECSTcriteria, should be assessed and referred for carotidendarterectomy within 1 week of onset of symptomsand receive treatment within a maximum of 2 weeksof onset of symptoms, preferably within 72 h. Thereis minimal benefit after 12 weeks. With the benefits ofaggressive modern intensive medical therapy, it mightbe interesting to re-evaluate the relative benefits ofcarotid endarterectomy.Those with acute minor stroke/TIA who have symp-

tomatic carotid stenosis <50% (NASCET criteria) orless than 70% (ECST criteria) should receive bestmedical treatment.The Asymptomatic Carotid Atherosclerosis Study

(ACAS) and the Asymptomatic Carotid Surgery Trial(ACST) found carotid endarterectomy reduced strokerisk in those with asymptomatic carotid stenosis>60% although the stroke risk inherent in asymptom-atic patients is much less than symptomatic patients.Major improvements in medical therapy have signifi-cantly decreased the risk of stroke in asymptomaticstenoses. Stroke risk is greater in asymptomaticpatients with microemboli detected on Doppler ultra-sound, those with more than three plaque ulcers andecholucent plaque. Heterogeneous plaques with ulcer-ation, intraplaque haemorrhage, lipid and intraluminalthrombi all clearly relate to emboli and stroke.Routine plaque analysis however is currently notwidely available.Vascular screening may be effective before coronary

artery bypass surgery, in high-risk asymptomaticgroups with significant peripheral vascular disease and

those older than 65 years with atherosclerotic riskfactors.Screening of the general population is currently not

considered effective.The SAMMPRIS study concluded that in patients

with intracranial arterial stenosis, aggressive medicalmanagement was better than angioplasty using theWingspan stent system. The risk of early stroke afterangioplasty was higher, and the risk of stroke withaggressive medical therapy alone was lower thanexpected.

Imaging modalitiesMultiple modalities are often, but not universally,used to evaluate suspected cervical carotid stenoses.Two congruent tests are highly accurate and sufficientto replace DSA. Specific investigation will dependupon local resources.

MRAMRA is non-invasive and does not involve ionisingradiation or iodinated intravenous contrast. An unlim-ited number of projections can be obtained, as withCTA and DSA. Like CTA, MRA can also assess theintracranial circulation. The usual contraindications toMR apply. Calcification is not detected.3D-time-of-flight MRA and contrast-enhanced

MRA are the most frequently used techniques toevaluate the cervical and intracranial arteries inpatients with cerebrovascular disease. Contrast-enhanced MRA optimally assesses the cervical arteries(figure 11).Contrast-enhanced MRA, requiring injection of

gadolinium, using a power injector (taking care in

Figure 11 Axial apparent diffusion coefficient MRI (A) in a patient with a transient right hemiparesis demonstrates an area ofdecreased diffusion in the deep white matter adjacent to the left lateral ventricle. Contrast-enhanced MR angiography (coronal, B)and localised oblique sagittal reconstruction of the left ICA bifurcation (C) demonstrates that the source of the embolus was almostcertainly a severe, critically stenosed ulcerated plaque involving the carotid bulb (C arrow).

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those with renal impairment, with a risk of nephro-genic systemic fibrosis) is probably the most accuratetechnique overall. Like CTA, it has high spatial reso-lution. Delineation of the arteries is degradedhowever if overlying veins are filled with gadolinium,hence, timing of bolus injection is important to avoidvenous contamination.Contrast-enhanced MRA is independent of blood

flow artefacts from disordered or slow flow, so assess-ment of cervical carotid disease (atherosclerotic anddissection) is more accurate. Acquisition time is sig-nificantly faster than time-of-flight MRA, and a farlarger field of view can be covered. Contrast-enhancedMRA correlates well with DSA for vertebrobasilar andcarotid disease. There is a high degree of correlationfor high-grade stenosis and occlusion with specificityof up to 100% and sensitivity around 93%.Time-of-flight MRA does not require an injection of

contrast. Its spatial resolution is superior to contrast-enhanced MRA, but the area covered is limited and itis more suitable for assessment of intracranial vessels.Vascular signal depends upon flow direction and vel-ocity through the imaging plane, and time-of-flighttends to overestimate the degree and length of stenosisbecause of turbulent flow or slow or recirculating/reversed blood flow which results in signal loss,making it more difficult to differentiate moderatefrom severe stenosis. High-grade stenoses may resultin signal loss altogether.Time-of-flight MRA has an acceptable sensitivity for

depiction of cervical arterial stenosis/occlusion whencompared with DSA and CTA with a sensitivity andspecificity for diagnosis of 70–99% stenoses of 88%and 84%, respectively—similar to Doppler ultrasoundscanning.When using dedicated protocols (not currently rou-

tinely practiced), MRI can identify the lipid-rich nec-rotic core and fibrous capsule with high sensitivityand specificity, and can distinguish intact thick, thinor ruptured fibrous cap and thrombus within plaque.

Doppler ultrasoundThis is often the preferred initial diagnostic testbecause of low cost, accuracy, it is non-invasive, doesnot involve ionising radiation and is readily available.It reliably assesses the presence and severity of carotiddisease and identifies those who may have a surgicallytreatable stenosis. It can localise plaque, degree ofstenosis, length and composition of plaque. Althoughnot routine, it can also assess plaque morphology.Echo-poor plaques have high fat content, are softerand more susceptible to rupture and thromboemboli.Calcified plaque is echogenic and more stable.However, Doppler ultrasound scanning is veryoperator-dependent and must be performed in a reli-able laboratory.Atheromatous plaque involving the carotid bulb/

bifurcation not only causes vessel narrowing but also

turbulent blood flow; Doppler ultrasound scanningestimates the average flow velocity within thevessel using the Doppler effect, where the frequencyof a sound wave changes as it is reflected by themoving red blood cells. Doppler scanning has a sensi-tivity of 93% and specificity of 68% and overallaccuracy of 85% for detecting a 50–69% stenosis(asymptomatic patients may require additional alterna-tive imaging).The degree of stenosis is determined by the peak

systolic velocity and end-diastole velocity. Peak systolicvelocity of 125+ cm/s predicts a >50% carotid sten-osis and >230 cm/s predicts a >70% stenosis.Peak systolic velocity >230 cm/s for 70+% stenosis

has a sensitivity of 99%, specificity of 86% andoverall accuracy of 95%. ICA peak systolic velocity issignificantly more accurate than end diastole velocityor internal carotid/common carotid artery ratio indetecting ≥70% and ≥50% stenosis.Velocities tend to be generally higher in women and

in the presence of contralateral carotid arterialocclusion.The accuracy of Doppler ultrasound falls with the

presence of a high carotid bifurcation, severe arterialtortuosity, vascular calcification and obesity. It mayalso fail to differentiate between subtotal and totalcarotid occlusion, although power Doppler and con-trast Doppler ultrasound scanning may be more usefulin this respect. Additionally, the intracranial circula-tion cannot be assessed.

CTACTA involves a single bolus of intravenous contrast,fast scanning obtaining thin axial slices with highsubmillimetre spatial resolution and producing axial,coronal and sagittal reconstructions of the aortic arch,neck and intracranial vessels (figures 8, 10, 12and 13).It has a sensitivity of 85% compared with DSA, and

a specificity of 93% in detecting 70–99% carotid sten-oses (and sensitivity and specificity of 97% and 99%,respectively, for occlusion). It is not reliable for asses-sing plaque morphology. Other disadvantages are theuse of intravenous iodinated contrast, ionising radi-ation, and that a large calcium burden can limit theability to distinguish contrast in the lumen from calci-fication during postprocessing (figure 13).As with MRA, it is also useful for diagnosing arter-

ial dissection (see below).

Contrast DSAThis achieves high-quality, accurate, gold-standardimages from the arch to circle of Willis, which areobjective and relatively easy to interpret, but riskscausing stroke. DSA is now almost never done forTIA/stroke, and is reserved, and as part of therapeuticstenting.

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Arterial dissectionDissection causes about 20% strokes in the young(70% occur aged 35–50 years), with a peak incidencein the 40 s. It is also a possible cause of stroke in theelderly. Completed stroke usually occurs within 7 daysbut can occur up to 1 month.Arterial dissection results from intimal injury, lacer-

ation of the arterial wall or spontaneous haemorrhageof the vasa vasorum causing subintimal or intramuralhaematoma. Most are caused by an intimal tear,

which allows blood to dissect the vessel wall. Masseffect from the haematoma can narrow (causing tur-bulent flow or impaired flow) or occlude the artery.Anterograde flow through the false lumen may createa double lumen. Intramural haematoma expandinginto the subadventitia can cause a dissecting aneur-ysm; these pseudoaneurysms may develop acutely oras the dissection heals.Most dissections occur spontaneously. Some are

associated with major trauma or happen after minor

Figure 12 CTA reconstructions (A, oblique coronal, B, sagittal, C, oblique sagittal) including the aortic arch, cervical and intracranialarteries in a 65-year-old man who has suffered a left hemisphere transient ischaemic attack. Note, the critical irregular stenosis of theleft carotid bulb and ICA origin.

Figure 13 CTA reconstructions (A, oblique sagittal; B, oblique coronal) of the left common carotid artery in a patient with leftcarotid artery territory transient ischaemic attacks show tandem lesions. There is a densely calcified plaque creating a critical stenosisat the origin of the left ICA, and a second severe stenosis at the origin of the left common carotid artery (arrow). This secondimportant lesion would not have been detected by Doppler ultrasound scanning. Such dense irregular plaque calcification at the ICAbifurcation can make it difficult to measure the precise luminal dimension.

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episodes (coughing, vomiting, sneezing), after generalanaesthesia or chiropractic manipulation—minor ormajor inciting events involving neck hyperextensionor rotation when the artery contacts a bony structure.Hypertension, connective tissue disorders, fibromus-cular dysplasia and other arteriopathies predispose todissection. Sixty-eight per cent involve the internalcarotid and 27% the vertebral artery; occasionally,multiple vessels are involved. Most are extracranialbecause of the greater arterial mobility in the neck.Sixty per cent of spontaneous internal carotid arterydissections are purely extracranial and are typicallylocated 2–3 cm above the carotid bifurcation, extendto the middle or distal internal carotid artery, but withfurther cranial migration usually limited by the bonyconfines of the carotid canal of the skull base(figure 14). Twenty per cent are both intracranial andextracranial, and 20% are primarily intracranial.Although often asymptomatic, the classic presentingtriad is of ipsilateral headache or neck pain, Horner’ssyndrome and cerebral ischaemic events. Pulsatile tin-nitus and lower cranial nerve palsies may also occur.Seventy-five per cent are visible on regular MR scansat or near the skull base with haematoma in theexpanded blood vessel wall, as a circumferential or

crescenteric usually hyperintense signal peripheral tothe flow void (figure 14) of an irregularly narrowedinternal carotid artery or vertebral artery. The signalof the wall haematoma depends upon age. It isimportant not to confuse periarterial fat (also high T1signal) with intramural thrombus, and some advocatefat saturation techniques to avoid this problem.Intimal flaps are not often seen.Vertebral artery dissections are associated with pos-

terior neck or occipital pain and result in posterior cir-culation ischaemic events in 80–90%. Ten per cent aresolely intracranial, and 10% originate from the extra-cranial portion and extend intracranially, forming dis-secting aneurysms, which can rupture resulting insubarachnoid haemorrhage. Less commonly, vertebralartery dissection can produce cervical radiculopathyfrom direct compression of spinal nerve roots andspinal cord ischaemia from emboli to the anterior andposterior spinal arteries or radiculomedullary arteries.The most common site for vertebral artery dissectionis the segment that runs lateral to the lateral masses ofC1 and C2 after the artery has exited the foramentransversarium (figure 15), and before it has enteredthe foramen magnum, and also at point of entry intothe transverse foramen at C6/7.

Figure 14 T2W (A) and T1W (B) axial MRI at the level of the foramen magnum demonstrate the typical findings of a left ICAdissection with hyperintense haematoma in the arterial wall (arrows). The patient presented with left-sided neck pain and a Horner’ssyndrome. Contrast-enhanced MR angiography (C) confirmed the full extent of the dissection, ICA narrowing, commencing justabove the carotid bulb and finishing at the skull base. The bony confines of the carotid canal usually prevents the vessel wallhaematoma from progressing intracranially.

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Doppler ultrasound is of only limited use in diag-nosis of arterial dissection. DSA is the gold standardand is especially indicated with subarachnoid

haemorrhage. Its limitation is that it only visualisesthe lumen, not the wall. It is also invasive and risksstroke.

Figure 16 Coronal (A) and sagittal (B) CTA reconstructions in a 77-year-old woman presenting with subarachnoid haemorrhagesecondary to rupture of a 3 mm basilar top aneurysm (C arrow). The CTA shows typical features of medial fibromuscular dysplasiaaffecting the cervical ICA bilaterally (no ICA digital subtraction angiogram performed). Note, the typical ruffled, string of beads orbaggy stockings appearance so characteristic of this condition—areas of concentric narrowing and outpouchings. The vertebral arterydigital subtraction angiogram (performed at the time of aneurysm coiling) lateral projection also confirms involvement of the distalcervical left vertebral artery.

Figure 15 Axial T2W MRIs (A–C) in a patient presenting with right-sided neck pain, dysarthria and swallowing difficulties,demonstrate a small right lateral medullary infarction, and a small right-sided cerebellar infarction due to right vertebral arterydissection. Note, the stenosis (arrows) at C1/2, the commonest site for a vertebral artery dissection on the contrast-enhanced MRangiography images (D and E).

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The most common angiographic sign is the stringsign—a smooth tapered narrowing, seen in 65%(figures 14 and 15). Arterial occlusion (figure 10),irregular stenoses, intimal flap and double lumen aresometimes seen. Abrupt flame-shaped (or ‘rat’s tail’)occlusion strongly suggests the diagnosis and the‘string of pearls’ sign refers to long segments of arter-ial narrowing with one or more areas of arterialdilatation.Dissecting aneurysms, especially in vertebral artery

dissections, occur in 25–35% and are often oval orfusiform in shape.

These angiographic signs can be seen using MRAand CTA—the non-invasive modalities of choice fordiagnosis.CTA is highly sensitive (92–100%) in diagnosing

extracranial dissections when compared with DSA,visualising both lumen and thickened wall. Dissectinganeurysms are well demonstrated, but intimal flaps ordouble lumen, are rarely seen. CTA is reported to bemore accurate (98–100% sensitive compared withDSA) in diagnosing vertebral artery dissections thancontrast-enhanced MRA (60% sensitive) and equiva-lent to contrast-enhanced MRA for carotid dissection.

Figure 17 T2W axial MRIs (A–D) in a 22-year-old man presenting with transient left-sided weakness. Note, the ischaemic deepwhite matter changes in a watershed distribution, more extensive on the right. Wallerian degeneration is present in the right cerebralpeduncle. Note the diminished abnormal flow voids of the terminal ICAs, and proximal anterior and middle cerebral arteries. Digitalsubtraction angiogram (lateral projections of a right ICA angiogram, E and F) confirms distal ICA, proximal anterior and middlecerebral artery narrowing and hypertrophy of the lenticulostriates (the ‘puff of smoke’). Note also the collateral circulation from theposterior cerebral artery supplying distal anterior and middle cerebral artery territory. These changes were similar on the left (notshown).

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Reduced sensitivity of contrast-enhanced MRA for ver-tebral dissections relates to small vessel size and diffi-culty in distinguishing the methaemoglobin crescentfrom flow-related enhancement of the paravertebralvenous plexus. MRI and contrast-enhanced MRA are87–100% sensitive in diagnosing extracranial internalcarotid artery dissection, compared with DSA.Contrast-enhanced MRA is better than time-of-flighttechniques. It has higher spatial resolution, eliminatesin-plane saturation effects (which especially occur inthe vertebral artery at C1/2), flow-related artefacts dueto dephasing and turbulent flow, which can simulatestenosis and intimal flaps.Up to 85% of extracranial dissections heal spontan-

eously. Two per cent of dissections recur within4–6 weeks and 1% annually thereafter. Dissectinganeurysms have a more variable course and mostpersist—only 36% heal. Those involving extracranialvessels are benign and may not require treatment orfollow-up. Intracranial dissecting aneurysms are veryfragile, and those presenting with subarachnoid haem-orrhage are prone to early rehaemorrhage and carry abad prognosis. Early definitive treatment in these isrecommended.More than two-thirds of occluded arteries eventu-

ally recanalise (figure 10), but an occlusion stillpresent at 3 months is likely to persist.There is no evidence for routine follow-up for dis-

section. Follow-up imaging is recommended if thereare new symptoms, when a previously chosen treat-ment needs to be reconsidered, in patients with mul-tiple dissections, recurrent dissections, and those whohave undergone stenting.

Fibromuscular dysplasiaThis is a heterogeneous idiopathic segmental non-inflammatory, non-atherosclerotic vascular disease ofsmall to medium-sized arteries, often mild, most com-monly affecting the renal and carotid arteries althoughreported in just about every arterial bed in the body.The cause is unknown but is probably inherited. Itoccurs more frequently in women and the young. Itsprevalence is difficult to assess because it is asymp-tomatic or minimally symptomatic (it may cause pulsa-tile tinnitus). When cerebral angiography was moreroutine—rather than CTA and MRA—the prevalenceranged from 0.3% to 3.2% in that highly selectedpopulation. Fibromuscular dysplasia is reported in0.02% of autopsies and usually affects the internalcarotid artery in its middle and distal cervical seg-ments and vertebral artery at C1/2 (figure 16).Ninety-five per cent involve the internal carotid arteryand it is often bilateral (60–85%).It results from various degrees of collagen hyperpla-

sia, internal elastic lamina rupture and disorganisationof the media producing alternating areas of thickeningand thinning of the arterial wall with mural aneur-ysms. Sometimes the disease is focal.

Although considered benign, it can be associatedwith severe ischaemic (thromboembolic or haemo-dynamic) or haemorrhagic stroke. The risk ofstroke is reported as 0–5% per year. Intracranialaneurysms occur in 7–10% (figure 16). Up to 15%of patients with cervical artery dissection havefibromuscular dysplasia. Carotid cavernous fistulasmay also occur.▸ Intimal fibromuscular dysplasia (<10%) involves a cir-

cumferential eccentric deposition of collagen in theintima. The internal elastic lamina may be fragmented orduplicated.

▸ Medial fibromuscular dysplasia (80%) features alternat-ing areas of thinned media and thickened fibromuscularridges containing collagen with multiple stenoses andaneurysmal outpouchings (figure 16). The mostcommon appearance on angiography is the ‘string ofbeads’ appearance, though some have long concentricstenoses and short isolated stenoses. There are two sub-types: perimedial fibromuscular dysplasia (10%) involv-ing extensive collagen deposition in the outer media,and medial hyperplasia involving smooth muscle hyper-plasia without fibrosis (seen as a concentric smooth sten-osis on angiography).

▸ Adventitial fibromuscular dysplasia is very rare; the fibroustissue of the adventitia is replaced by dense collagen.Intracranial fibromuscular dysplasia is very rare.

Knowledge of the natural history is poor and, hence,management is uncertain. Antithrombotic medicationmay help, and there are reports of angioplasty andstenting where necessary.

Extra reading

Leiva-Salinas C, Wintermark M. Imaging of acute ische-mic stroke. Neuroimaging Clin N Am 2010;20:455–68.De Lucas EM, Sanchez E, Gutierrez A, et al. CT protocolfor acute stroke: tips and tricks for general radiologists.Radiographics 2008;28:1673–87.Barber PA, Demchuk AM, Zhang J, et al. Validity and reliabil-ity of a quantitative computed tomography score in predict-ing outcome of hyperacute stroke before thrombolytictherapy. ASPECTS Study Group. Alberta Stroke ProgrammeEarly CT Score. Lancet 2000;355:1670.Pavlovic AM, Barras CD, Hand PJ, et al. Brain Imaging intransient ischaemic attack- redefining TIA. J Clin Neurosci2010;17:1105–10.Rodallec MH, Marteau V, Gerber S, et al. Craniocervicalarterial dissection: spectrum of imaging findings and dif-ferential diagnosis. Radiographics 2008;28:1711–28.Touze E, Oppenheim C, Trystram D, et al. Fibromusculardysplasia of cervical and intracranial arteries. Int J Stroke2010;5:296–305.

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MoyamoyaThis is a slowly progressive arteriopathy of unknowncause producing progressive bilateral stenosis of thecarotid T, proximal M1 and A1 segments (figure 17)and subsequently, of the basilar artery. Patientspresent with ischaemic stroke but, also, 20% develophaemorrhage. Intracerebral haemorrhage (basalganglia, intraventricular, subarachnoid) results fromfragile collateral vessels or from flow aneurysms in

the posterior circulation. MRI/A shows the ischaemiclesions—often basal ganglia or watershed—as well asarterial occlusive changes and hypertrophy of the len-ticulostriates. DSA is required if surgery is planned.

Competing interests None.

Provenance and peer review Commissioned; externally peerreviewed. This paper was reviewed by Joanna Wardlaw,Edinburgh, UK.

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