Quantitative magnetic resonance angiography as a potential predictor for cerebral hyperperfusion syndrome: a preliminary study

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Cerebral hyperperfusion syndrome (CHS) is a rare but devastating complication of carotid endarterectomy (CEA). This study sought to determine whether quantitative hemodynamic assessment using MR angiography can stratify CHS risk.


In this prospective trial, patients with internal carotid artery (ICA) stenosis were randomly selected for pre- and postoperative quantitative phase-contrast MR angiography (QMRA). Assessment was standardized according to a protocol and included Doppler/duplex sonography, MRI, and/or CT angiography and QMRA of the intra- and extracranial supplying arteries of the brain. Clinical and radiological data were analyzed to identify CHS risk factors.


Twenty-five of 153 patients who underwent CEA for ICA stenosis were randomly selected for pre- and postoperative QMRA. QMRA data showed a 2.2-fold postoperative increase in blood flow in the operated ICA (p < 0.001) and a 1.3-fold increase in the ipsilateral middle cerebral artery (MCA) (p = 0.01). Four patients had clinically manifested CHS. The mean flow increases in the patients with CHS were significantly higher than in the patients without CHS, both in the ICA and MCA (p < 0.001). Female sex and a low preoperative diastolic blood pressure were the clearest clinical risk factors for CHS, whereas the flow differences and absolute postoperative flow values in the ipsilateral ICA and MCA were identified as potential radiological predictors for CHS.


Cerebral blood flow in the ipsilateral ICA and MCA as assessed by QMRA significantly increased after CEA. Higher mean flow differences in ICA and MCA were associated with the development of CHS. QMRA might have the potential to become a noninvasive, operator-independent screening tool for identifying patients at risk for CHS.

ABBREVIATIONS ASA = acetylsalicylic acid; AUC = area under the receiver operating characteristic curve; CBF = cerebral blood flow; CEA = carotid endarterectomy; CHS = cerebral hyperperfusion syndrome; ICA = internal carotid artery; MCA = middle cerebral artery; mRS = modified Rankin Scale; NOVA = noninvasive optimal vessel analysis; QMRA = quantitative phase-contrast MR angiography; TCD = transcranial Doppler.

Article Information

Correspondence Michael Reinert, Department of Neurosurgery, Neurocenter Luga-no, Lugano 6930, Switzerland. email: michael.reinert@eoc.ch.

INCLUDE WHEN CITING Published online April 14, 2017; DOI: 10.3171/2016.11.JNS161033.

Disclosures Dr. Amin-Hanjani receives non–study-related research support from VasSol, Inc. Dr. Arnold is a consultant for and receives non–study-related research support from Bayer Schering, BMS, Pfizer, Boehringer, and Covidien.

© AANS, except where prohibited by US copyright law.



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    Blood flow values of the CEA patients as assessed by QMRA. Nonpatch CEA significantly increased blood flow in the operated ICA and ipsilateral MCA in all patients. A: A significant difference in blood flow was evident in the ipsilateral ICA in patients with or without CHS. Additionally, the postoperative flow values in the CHS patients were significantly higher than in non-CHS patients. B: MCA flow velocities were significantly higher in CHS patients than in non-CHS patients. C: Perioperative flow differences in CHS patients were significantly higher in both the ipsilateral ICA and MCA than in non-CHS patients. Data are given as the mean ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001. ns = not significant; post = postoperative; pre = preoperative.

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    Bland-Altman plots comparing sonography and QMRA. The narrower ± 1.96 (± SD) limits (dotted lines) indicate only moderate agreement for extracranial vessels (A and B) compared with intracranial vessels (C and D). There is a slight tendency toward better agreement between the 2 methods for smaller values. SD LOA = standard deviation with limits of agreement.

  • View in gallery

    Receiver operating characteristic curves for the discrimination of CHS and non-CHS patients assessed by QMRA. QMRA thresholds for discrimination between CHS and non-CHS patients were estimated to be approximately 3.49 for the mean flow value ratio in the ICA (AUC 0.8; sensitivity 75%; specificity 84%; likelihood ratio 4.75) (A) and 1.53 for the mean flow value ratio in the MCA (AUC 0.94; sensitivity 100%; specificity 90%; likelihood ratio 10) (B). The MCA ratio (p = 0.01) tended to be more efficient at predicting CHS than ICA ratio (p = 0.06). TCD thresholds for discrimination between CHS and non-CHS were estimated to be 0.26 for the mean flow value ratio in the ICA (AUC 0.89; sensitivity 100%; specificity 80%; likelihood ratio 5.0) (C) and 1.59 for the mean flow value ratio in the MCA (AUC 0.83; sensitivity 75%; specificity 80%; likelihood ratio 3.75) (D).


  • 1

    Alamowitch SEliasziw MAlgra AMeldrum HBarnett HJ: Risk, causes, and prevention of ischaemic stroke in elderly patients with symptomatic internal-carotid-artery stenosis. Lancet 357:115411602001

  • 2

    Ali SHModic MEMahmoud SYJones SE: Reducing clinical MRI motion degradation using a prescan patient information pamphlet. AJR Am J Roentgenol 200:6306342013

  • 3

    Amin-Hanjani SAlaraj ACalderon-Arnulphi MAletich VAThulborn KRCharbel FT: Detection of intracranial in-stent restenosis using quantitative magnetic resonance angiography. Stroke 41:253425382010

  • 4

    Amin-Hanjani SDu XPandey DKThulborn KRCharbel FT: Effect of age and vascular anatomy on blood flow in major cerebral vessels. J Cereb Blood Flow Metab 35:3123182015

  • 5

    Amin-Hanjani SDu XZhao MWalsh KMalisch TWCharbel FT: Use of quantitative magnetic resonance angiography to stratify stroke risk in symptomatic vertebrobasilar disease. Stroke 36:114011452005

  • 6

    Amin-Hanjani SPandey DKRose-Finnell LDu XRichardson DThulborn KR: Effect of hemodynamics on stroke risk in symptomatic atherosclerotic vertebrobasilar occlusive disease. JAMA Neurol 73:1781852016

  • 7

    Ascher EMarkevich NSchutzer RWKallakuri SJacob THingorani AP: Cerebral hyperperfusion syndrome after carotid endarterectomy: predictive factors and hemodynamic changes. J Vasc Surg 37:7697772003

  • 8

    Bauer AMAmin-Hanjani SAlaraj ACharbel FT: Quantitative magnetic resonance angiography in the evaluation of the subclavian steal syndrome: report of 5 patients. J Neuroimaging 19:2502522009

  • 9

    Buijs PCKrabbe-Hartkamp MJBakker CJde Lange EERamos LMBreteler MM: Effect of age on cerebral blood flow: measurement with ungated two-dimensional phase-contrast MR angiography in 250 adults. Radiology 209:6676741998

  • 10

    Calderon-Arnulphi MAmin-Hanjani SAlaraj AZhao MDu XRuland S: In vivo evaluation of quantitative MR angiography in a canine carotid artery stenosis model. AJNR Am J Neuroradiol 32:155215592011

  • 11

    Chang CHChang TYChang YJHuang KLChin SCRyu SJ: The role of perfusion computed tomography in the prediction of cerebral hyperperfusion syndrome. PLoS One 6:e198862011

  • 12

    Cohen DJStolker JMWang KMagnuson EAClark WMDemaerschalk BM: Health-related quality of life after carotid stenting versus carotid endarterectomy: results from CREST (Carotid Revascularization Endarterectomy Versus Stenting Trial). J Am Coll Cardiol 58:155715652011

  • 13

    Coutts SBHill MDHu WY: Hyperperfusion syndrome: toward a stricter definition. Neurosurgery 53:105310602003

  • 14

    Dalman JEBeenakkers ICMoll FLLeusink JAAckerstaff RG: Transcranial Doppler monitoring during carotid endarterectomy helps to identify patients at risk of postoperative hyperperfusion. Eur J Vasc Endovasc Surg 18:2222271999

  • 15

    Douglas AFChristopher SAmankulor NDin RPoullis MAmin-Hanjani S: Extracranial carotid plaque length and parent vessel diameter significantly affect baseline ipsilateral intracranial blood flow. Neurosurgery 69:7677732011

  • 16

    Faivre JMFreysz MCoulon CJaboeuf RDavid M: Post carotid endarterectomy hypertension: clonidine therapy. Anaesth Intensive Care 9:1791801981

  • 17

    Ghogawala ZAmin-Hanjani SCurran JCiarleglio MBerenstein AStabile L: The effect of carotid endarterectomy on cerebral blood flow and cognitive function. J Stroke Cerebrovasc Dis 22:102910372013

  • 18

    Hendrikse Jvan Raamt AFvan der Graaf YMali WPvan der Grond J: Distribution of cerebral blood flow in the circle of Willis. Radiology 235:1841892005

  • 19

    Hines GLOleske AFeuerman M: Post-carotid endarterectomy hyperperfusion syndrome-is it predictable by lack of cerebral reserve?. Ann Vasc Surg 25:5025072011

  • 20

    Hirooka ROgasawara KInoue TFujiwara SSasaki MChida K: Simple assessment of cerebral hemodynamics using single-slab 3D time-of-flight MR angiography in patients with cervical internal carotid artery steno-occlusive diseases: comparison with quantitative perfusion single-photon emission CT. AJNR Am J Neuroradiol 30:5595632009

  • 21

    Iwata TMori TMiyazaki YTanno YKasakura SAoyagi Y: Global oxygen extraction fraction by blood sampling to anticipate cerebral hyperperfusion phenomenon after carotid artery stenting. Neurosurgery 75:5465512014

  • 22

    Iwata TMori TTajiri HNakazaki M: Predictors of hyperperfusion syndrome before and immediately after carotid artery stenting in single-photon emission computed tomography and transcranial color-coded real-time sonography studies. Neurosurgery 68:6496562011

  • 23

    Kaku YYoshimura SKokuzawa J: Factors predictive of cerebral hyperperfusion after carotid angioplasty and stent placement. AJNR Am J Neuroradiol 25:140314082004

  • 24

    Karapanayiotides TMeuli RDevuyst GPiechowski-Jozwiak BDewarrat ARuchat P: Postcarotid endarterectomy hyperperfusion or reperfusion syndrome. Stroke 36:21262005

  • 25

    Kawamata TOkada YKawashima AYoneyama TYamaguchi KOno Y: Postcarotid endarterectomy cerebral hyperperfusion can be prevented by minimizing intraoperative cerebral ischemia and strict postoperative blood pressure control under continuous sedation. Neurosurgery 64:4474542009

  • 26

    Lal BKBeach KWRoubin GSLutsep HLMoore WSMalas MB: Restenosis after carotid artery stenting and endarterectomy: a secondary analysis of CREST, a randomised controlled trial. Lancet Neurol 11:7557632012

  • 27

    Langer DJLefton DROstergren LBrockington CDSong JNiimi Y: Hemispheric revascularization in the setting of carotid occlusion and subclavian steal: a diagnostic and management role for quantitative magnetic resonance angiography?. Neurosurgery 58:5285332006

  • 28

    Lin CJChang FCTsai FYGuo WYHung SCChen DY: Stenotic transverse sinus predisposes to poststenting hyperperfusion syndrome as evidenced by quantitative analysis of peritherapeutic cerebral circulation time. AJNR Am J Neuroradiol 35:113211362014

  • 29

    Maas MBKwolek CJHirsch JAJaff MRRordorf GA: Clinical risk predictors for cerebral hyperperfusion syndrome after carotid endarterectomy. J Neurol Neurosurg Psychiatry 84:5695722013

  • 30

    Matsubara SMoroi JSuzuki ASasaki MNagata KKanno I: Analysis of cerebral perfusion and metabolism assessed with positron emission tomography before and after carotid artery stenting. Clinical article. J Neurosurg 111:28362009

  • 31

    Moulakakis KGMylonas SNSfyroeras GSAndrikopoulos V: Hyperperfusion syndrome after carotid revascularization. J Vasc Surg 49:106010682009

  • 32

    Muzzi DABlack SLosasso TJCucchiara RF: Labetalol and esmolol in the control of hypertension after intracranial surgery. Anesth Analg 70:68711990

  • 33

    Newman JEAli MSharpe RBown MJSayers RDNaylor AR: Changes in middle cerebral artery velocity after carotid endarterectomy do not identify patients at high-risk of suffering intracranial haemorrhage or stroke due to hyperperfusion syndrome. Eur J Vasc Endovasc Surg 45:5625712013

  • 34

    Niibo TOhta HYonenaga KIkushima IMiyata STakeshima H: Arterial spin-labeled perfusion imaging to predict mismatch in acute ischemic stroke. Stroke 44:260126032013

  • 35

    Ogasawara KMikami CInoue TOgawa A: Delayed cerebral hyperperfusion syndrome caused by prolonged impairment of cerebrovascular autoregulation after carotid endarterectomy: case report. Neurosurgery 54:125812622004

  • 36

    Ogasawara KSakai NKuroiwa THosoda KIihara KToyoda K: Intracranial hemorrhage associated with cerebral hyperperfusion syndrome following carotid endarterectomy and carotid artery stenting: retrospective review of 4494 patients. J Neurosurg 107:113011362007

  • 37

    Ogasawara KYukawa HKobayashi MMikami CKonno HTerasaki K: Prediction and monitoring of cerebral hyperperfusion after carotid endarterectomy by using single-photon emission computerized tomography scanning. J Neurosurg 99:5045102003

  • 38

    Olivot JMMlynash MZaharchuk GStraka MBammer RSchwartz N: Perfusion MRI (Tmax and MTT) correlation with xenon CT cerebral blood flow in stroke patients. Neurology 72:114011452009

  • 39

    Pennekamp CWImmink RVden Ruijter HMKappelle LJFerrier CMBots ML: Near-infrared spectroscopy can predict the onset of cerebral hyperperfusion syndrome after carotid endarterectomy. Cerebrovasc Dis 34:3143212012

  • 40

    Prabhakaran SWarrior LWells KRJhaveri MDChen MLopes DK: The utility of quantitative magnetic resonance angiography in the assessment of intracranial instent stenosis. Stroke 40:9919932009

  • 41

    Reinert MMono MLKuhlen DMariani LBarth ABeck J: Restenosis after microsurgical non-patch carotid endarterectomy in 586 patients. Acta Neurochir (Wien) 154:4234312012

  • 42

    Schültke ENanko NPinsker MKatzev MSebastian AFeige B: Improving MRT image quality in patients with movement disorders. Acta Neurochir Suppl 117:13172013

  • 43

    Seeger AKlose UPoli SKramer UErnemann UHauser TK: Acute stroke imaging: feasibility and value of MR angiography with high spatial and temporal resolution for vessel assessment and perfusion analysis in patients with wake-up stroke. Acad Radiol 22:4134222015

  • 44

    Suga YOgasawara KSaito HKomoribayashi NKobayashi MInoue T: Preoperative cerebral hemodynamic impairment and reactive oxygen species produced during carotid endarterectomy correlate with development of postoperative cerebral hyperperfusion. Stroke 38:271227172007

  • 45

    Tietjen CSHurn PDUlatowski JAKirsch JR: Treatment modalities for hypertensive patients with intracranial pathology: options and risks. Crit Care Med 24:3113221996

  • 46

    Vagal ASLeach JLFernandez-Ulloa MZuccarello M: The acetazolamide challenge: techniques and applications in the evaluation of chronic cerebral ischemia. AJNR Am J Neuroradiol 30:8768842009

  • 47

    van Mook WNRennenberg RJSchurink GWvan Oostenbrugge RJMess WHHofman PA: Cerebral hyperperfusion syndrome. Lancet Neurol 4:8778882005

  • 48

    Voeks JHHoward GRoubin GSMalas MBCohen DJSternbergh WC III: Age and outcomes after carotid stenting and endarterectomy: the carotid revascularization endarterectomy versus stenting trial. Stroke 42:348434902011

  • 49

    Yao Jvan Sambeek MRDall'Agata Avan Dijk LCKozakova MKoudstaal PJ: Three-dimensional ultrasound study of carotid arteries before and after endarterectomy; analysis of stenotic lesions and surgical impact on the vessel. Stroke 29:202620311998




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