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E D I T O R I A L C O M M E N T

Stroke: Cause and Effect—Seek and Ye Shall Find*

Alan Moody, FRCR, FRCP

Toronto, Ontario, Canada

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There is increasing evidence that carotid plaquemorphology plays a significant role in the genera-tion of cerebral ischemic symptoms in additionto—and potentially independent from—carotid ar-tery stenosis. Imaging techniques that have theability to characterize atheromatous plaque nonin-vasively may therefore be used to identify vessel walldisease that is associated with clinical events. Mag-netic resonance imaging (MRI) is emerging as onesuch noninvasive imaging tool that is able to dis-tinguish different plaque constituents.

See pages 388 and 397

When vessel wall MRI is coupled with theproven benefit of brain MRI to identify acuteischemic brain lesions, this technique provides asingle imaging modality for comprehensive carotico-cerebral imaging not provided by computed tomog-raphy (CT) or ultrasound, which are both com-monly used imaging techniques for the carotidartery and brain. The feasibility of imaging thecausative carotid artery lesion and end-organ braininjury in patients with acute stroke has been furtherenhanced by the application of high-field (3-T)MRI scanners. 3-T MRIs for brain and carotidassessment exploit the increased signal-to-noiseratio generated at this field strength, which can betranslated into improved spatial or temporal reso-lution. Previous work by Kerwin et al. (1) hasshown the feasibility of applying similar proven

*Editorials published in JACC: Cardiovascular Imaging reflect the views ofthe authors and do not necessarily represent the views of JACC: Cardio-vascular Imaging or the American College of Cardiology.

From the Department of Medical Imaging, Sunnybrook Health Sciences

aCentre, Toronto, Ontario, Canada. Dr. Moody has reported that he hasno relationships relevant to the contents of this paper to disclose.

echniques used at the lower field strength of 1.5-Tt this higher level, and 3-T imaging of the carotidrteries is becoming the method of choice forigh-resolution vessel wall imaging.Similarly, MRI has a distinct advantage over

lternative techniques for imaging the brain inyperacute stroke because it allows identification ofcute cerebral infarction using diffusion-weightedmaging within a very short time (minutes) of theerebral insult. It is therefore possible to use an

RI to definitively diagnose acute cerebral infarc-ion overcoming the known limitation of relying onlinical diagnosis of stroke (2).

Two papers in this issue of iJACC have applied-T MRI carotid and brain imaging to diagnoseerebral infarction and to better understand thenderlying cause. Freilinger et al. (3) used 3-Tmaging to assess patients with imaging evidence ofcute cerebral infarction but with no obvious un-erlying cause (e.g., cryptogenic stroke). Patientsnderwent extensive investigation to exclude a car-iogenic source of thromboemboli or emboli arisingrom the proximal thoracic aorta; patients also hado significant carotid stenosis, at least not greaterhan 50% according to NASCET (North Americanymptomatic Carotid Endarterectomy Trial) crite-ia. Lindsay et al. (4) undertook a similar combinedpproach of brain and carotid imaging at 3-T in thecute phase of MRI-proven cerebral infarction. Al-hough not restricted to a specific level of carotidtenosis, the majority of cases were found to be �70%.

Freilinger et al. (3) assessed carotid plaque for theresence of American Heart Association (AHA) typeI plaque defined according to intraplaque hemor-

hage (IPH), surface thrombus, or cap rupture, allhought to play a significant role in the generation ofeurological symptoms by artery-to-artery emboliza-ion. Lindsay et al. (4) studied these individual char-

cteristics in more depth and compared the prevalence

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of IPH, cap rupture, and surface thrombus with anage- and sex-matched asymptomatic control groupwho were also matched for degree of carotid stenosis.Both studies demonstrated that AHA type VI plaquewas significantly more common ipsilateral to the indexcerebral infarct compared with either a controlasymptomatic group or the patients’ contralateralasymptomatic carotid artery.

In addition to the use of combined carotid/brainimaging and the use of 3-T MRI, used in both thesestudies, each report offers new information regardingthe acute phase of stroke and its underlying etiology.As noted by Freilinger et al. (3), cryptogenic stroke,defined according to current methods, comprises asignificant proportion of strokes, which has the poten-tial to leave patients underdiagnosed. This limitedinformation, arising from the lack of diagnosis of anunderlying cause for their stroke, will result insuboptimal secondary prevention. Even in patientswith �50% stenosis, the prevalence of type VI

laque was found to be 37.5%, providing evidencef an otherwise hidden but potentially treatableource of future ischemic cerebral events.

Analysis of plaque morphology by Lindsay et al.4) demonstrated that characteristics (e.g., plaqueupture) within AHA type VI plaque may havereater down-stream end-organ effects as evidencedy greater acute cerebral infarct volume. This vol-me will depend on a number of factors, includingmbolic load from the causative carotid lesion andow proximal the emboli impact within the cerebralirculation. Large areas of plaque ulceration mighte expected to deliver larger thromboemboli com-ared with minor plaque surface disruption orndothelial activation. The demonstration of feweresions and decreased infarct volume with IPHuggests this might act as a useful harbinger ofuture events before significant brain damage.

The demonstration of complicated AHA type VIlaque in symptomatic but not severely stenotic ca-

1523. 2012;5:388–396.

of a higher prevalence of complicated plaque associ-ated with cerebral symptoms (6). Parmar et al. (7)recently demonstrated the association of AHA typeVI plaque with transient ischemic stroke and stroke inthe acute setting. Lindsay et al. (4), however, have alsoshown the specific role of carotid plaque rupture inbrain infarct generation. The demonstration of onlypartial healing of this plaque feature on follow-upimaging also suggests this represents an ongoingsource for thromboemboli and a potential therapeutictarget for secondary prevention. These unhealed le-sions are presumably similar to those identified byTakaya et al. (8), who found these lesions to be at riskof causing events over a 2-year follow-up period in anasymptomatic population.

The demonstration of complicated carotid ath-eroma in nonstenosing (�50%) vessel wall diseaseas shown by Freilinger et al. (3) is supported by anumber of recent studies (9,10). It is becoming clearthat minimal carotid disease (as little as 2 mm inthickness) may contain areas of advanced athero-sclerosis, which, despite its size, is presumably stillprone to causing thromboembolism. The realiza-tion that even apparently “minor” atherosclerosismay harbor high-risk disease should change ourperception of what constitutes risk for a patient.

The imaging tools (multimodal MRI) are nowavailable to identify arteries, and thus patients, atincreased risk. This patient population (i.e., strokepatients) is self-selecting and is already likely under-going brain, and potentially carotid, MRI. Vessel wallcharacterization is therefore a practical addition toroutine imaging assessment of these patients. How-ever, while seeking and finding is the first step,knowing what to do with the information is a wholeother question.

Reprint requests and correspondence: Dr. Alan Moody,epartment of Medical Imaging, Sunnybrook Health

ciences Centre, 2075 Bayview Avenue, Toronto M4N

otid disease is not new (5), nor is the demonstration 3M5, Ontario, Canada. E-mail: Alan.moody@sunnybrook.ca.

R E F E R E N C E S

1. Kerwin WS, Liu F, Yarnykh V, et al.Signal features of the atheroscleroticplaque at 3.0 Tesla versus 1.5 Tesla:impact on automatic classification.J Magn Reson Imaging 2008;28:987–95.

2. Allder SJ, Moody AR, Martel AL,et al. Limitations of clinical diagno-sis in acute stroke. Lancet 1999;354:

3. Freilinger TM, Schindler A, SchmidtC, et al. Prevalence of nonstenosing,complicated atherosclerotic plaques incryptogenic stroke. J Am Coll CardiolImg 2012;5:397–405.

4. Lindsay AC, Biasiolli L, Lee JMS, etal. Plaque features associated with in-creased cerebral infarction after minorstroke and TIA: a prospective, case-control, 3-T carotid artery MR imag-ing study. J Am Coll Cardiol Img

5. Moody AR, Allder S, Lennox G,Gladman J, Fentem P. Direct mag-netic resonance imaging of carotidartery thrombus in acute stroke. Lan-cet 1999;353:122–3.

6. Murphy RE, Moody AR, Morgan PS, etal. Prevalence of complicated carotid ath-eroma as detected by magnetic resonancedirect thrombus imaging in patients withsuspected carotid artery stenosis and pre-vious acute cerebral ischemia. Circulation

2003;107:3053–8.

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7. Parmar J, Rogers WJ, Mugler JP 3rd,et al. MRI of carotid atheroscleroticplaque in clinically suspected acutetransient ischemic attack and acuteischemic stroke. Circulation 2010;122:2031–8.

8. Takaya N, Yuan C, Chu B, et al.Association between carotid plaquecharacteristics and subsequent isch-emic cerebrovascular events: a pro-

spective assessment with MRI—

initial results. Stroke 2006;37:818 –23.

9. Cheung HM, Moody AR, Singh N,Bitar R, Zhan J, Leung G. Latestage complicated atheroma in low-grade stenotic carotid disease: MRimaging depiction—prevalence andrisk factors. Radiology 2011;260:841–7.

0. van den Bouwhuijsen QJ, Vernooij

MW, Hofman A, Krestin GP, van

der Lugt A, Witteman JC. Determi-nants of magnetic resonance imag-ing detected carotid plaque compo-nents: the Rotterdam Study. EurHeart J 2011 Aug 6 [E-pub ahead ofprint].

Key Words: brain y carotid y

MRI y stroke.