Skip to main content
SpringerLink
Log in

The MRI enhancement ratio and plaque steepness may be more accurate for predicting recurrent ischemic cerebrovascular events in patients with intracranial atherosclerosis

  • Neuro
  • Published:
European Radiology Aims and scope Submit manuscript

Abstract

Objectives

To assess the complementary value of high-resolution multi-contrast MRI (hrMRI) in identifying symptomatic patients with intracranial atherosclerosis (ICAS) who are likely to experience recurrent ischemic cerebrovascular events.

Methods

In this retrospective cohort study, eighty patients with acute ischemic events attributed to ICAS who underwent hrMRI examination between January 2015 and January 2019 were included. Median follow-up for all patients was 30 months (range: 1 to 52 months) and recurrent ischemic cerebrovascular events were recorded. Cox regression analysis and time-dependent ROC were performed to quantify the association between the plaque characteristics and recurrent events.

Results

During the follow-up, 14 patients experienced recurrent ischemic cerebrovascular events. Young males and those with diabetes and poor medication persistence were more likely to experience recurrent events. ICAS in patients with recurrence had significantly higher enhancement ratio and steepness which is defined as the ratio between the plaque height and length than those without (p < 0.001 and p = 0.015, respectively). After adjustment of clinical factors, enhancement ratio (HR, 13.13 [95% CI, 3.58–48.20], p < 0.001) and plaque steepness (HR, 110.27 [95% CI, 4.75–2560.91], p = 0.003) were independent imaging biomarkers associated with recurrent events. Time-dependent ROC indicated that integrated high enhancement ratio and steepness into clinical risk factors improved discrimination power with the ROC increased from 0.79 to 0.94 (p = 0.008).

Conclusions

The enhancement ratio and plaque steepness improved the accuracy over traditional clinical risk factors in predicting recurrent ischemic cerebrovascular events for patients with ICAS.

Key Points

• High-resolution magnetic resonance imaging helps clinicians to evaluate high-risk Intracranial plaque.

• The higher enhancement ratio and plaque steepness (= height/length) were the primary biomarkers associated with future ischemic cerebrovascular events.

• High-resolution magnetic resonance imaging combined with clinical characteristics showed a higher accuracy for the prediction of recurrent events in patients with intracranial atherosclerosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

DWI:

Diffusion-weighted imaging

HR:

Hazard ratio

hrMRI:

High-resolution multi-contrast magnetic resonance imaging

ICAS:

Intracranial atherosclerosis

IPH:

Intraplaque hemorrhage

IQR:

Interquartile range

TOF:

Time-of-flight

VSS:

Vessel structural stress

References

  1. Wang Y, Zhao X, Liu L et al (2014) Prevalence and outcomes of symptomatic intracranial large artery stenoses and occlusions in China: the Chinese Intracranial Atherosclerosis (CICAS) Study. Stroke 45:663–669. https://doi.org/10.1161/strokeaha.113.003508

    Article  PubMed  Google Scholar 

  2. Ran Y, Wang Y, Zhu M et al (2020) Higher plaque burden of middle cerebral artery is associated with recurrent ischemic stroke: a quantitative magnetic resonance imaging study. Stroke 51:659–662. https://doi.org/10.1161/strokeaha.119.028405

    Article  PubMed  Google Scholar 

  3. Kern R, Steinke W, Daffertshofer M, Prager R, Hennerici M (2005) Stroke recurrences in patients with symptomatic vs asymptomatic middle cerebral artery disease. Neurology 65:859–864. https://doi.org/10.1212/01.wnl.0000175983.76110.59

    Article  CAS  PubMed  Google Scholar 

  4. Mazighi M, Tanasescu R, Ducrocq X et al (2006) Prospective study of symptomatic atherothrombotic intracranial stenoses: the GESICA study. Neurology 66:1187–1191. https://doi.org/10.1212/01.wnl.0000208404.94585.b2

    Article  CAS  PubMed  Google Scholar 

  5. Wabnitz AM, Derdeyn CP, Fiorella DJ et al (2018) Hemodynamic markers in the anterior circulation as predictors of recurrent stroke in patients with intracranial stenosis. Stroke. https://doi.org/10.1161/strokeaha.118.020840:Strokeaha118020840. 10.1161/strokeaha.118.020840

  6. Teng Z, Sadat U, Brown AJ, Gillard JH (2014) Plaque hemorrhage in carotid artery disease: pathogenesis, clinical and biomechanical considerations. J Biomech 47:847–858. https://doi.org/10.1016/j.jbiomech.2014.01.013

    Article  PubMed  PubMed Central  Google Scholar 

  7. Underhill HR, Hatsukami TS, Fayad ZA, Fuster V, Yuan C (2010) MRI of carotid atherosclerosis: clinical implications and future directions. Nat Rev Cardiol 7:165–173. https://doi.org/10.1038/nrcardio.2009.246

    Article  PubMed  Google Scholar 

  8. Sun J, Underhill HR, Hippe DS, Xue Y, Yuan C, Hatsukami TS (2012) Sustained acceleration in carotid atherosclerotic plaque progression with intraplaque hemorrhage: a long-term time course study. JACC Cardiovasc Imaging 5:798–804. https://doi.org/10.1016/j.jcmg.2012.03.014

    Article  PubMed  PubMed Central  Google Scholar 

  9. Teng Z, Peng W, Zhan Q et al (2016) An assessment on the incremental value of high-resolution magnetic resonance imaging to identify culprit plaques in atherosclerotic disease of the middle cerebral artery. Eur Radiol 26:2206–2214. https://doi.org/10.1007/s00330-015-4008-5

    Article  PubMed  Google Scholar 

  10. Kim JM, Jung KH, Sohn CH et al (2016) Intracranial plaque enhancement from high resolution vessel wall magnetic resonance imaging predicts stroke recurrence. Int J Stroke 11:171–179. https://doi.org/10.1177/1747493015609775

    Article  PubMed  Google Scholar 

  11. Song X, Zhao X, Liebeskind DS et al (2020) Incremental value of plaque enhancement in predicting stroke recurrence in symptomatic intracranial atherosclerosis. Neuroradiology 62:1123–1131. https://doi.org/10.1007/s00234-020-02418-8

    Article  PubMed  Google Scholar 

  12. Lyu J, Ma N, Tian C et al (2019) Perfusion and plaque evaluation to predict recurrent stroke in symptomatic middle cerebral artery stenosis. Stroke Vasc Neurol 4:129–134. https://doi.org/10.1136/svn-2018-000228

    Article  PubMed  PubMed Central  Google Scholar 

  13. Liu X, Xu G, Wu W, Zhang R, Yin Q, Zhu W (2006) Subtypes and one-year survival of first-ever stroke in Chinese patients: the Nanjing Stroke Registry. Cerebrovasc Dis 22:130–136

    Article  Google Scholar 

  14. Cappola AR, Fried LP, Arnold AM et al (2006) Thyroid status, cardiovascular risk, and mortality in older adults. JAMA 295:1033–1041. https://doi.org/10.1001/jama.295.9.1033

  15. Kim YH, Her AY, Jeong MH et al (2021) Effects of stent generation on clinical outcomes after acute myocardial infarction compared between prediabetes and diabetes patients. Sci Rep 11:9364. https://doi.org/10.1038/s41598-021-88593-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) (2002) Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation 106(25):3143–3421.

  17. Tao L, Li XQ, Hou XW et al (2021) Intracranial atherosclerotic plaque as a potential cause of embolic stroke of undetermined source. J Am Coll Cardiol 77:680–691. https://doi.org/10.1016/j.jacc.2020.12.015

    Article  PubMed  Google Scholar 

  18. Yang WJ, Chen XY, Zhao HL et al (2016) In vitro assessment of histology verified intracranial atherosclerotic disease by 1.5T magnetic resonance imaging: concentric or eccentric? Stroke 47:527–530. https://doi.org/10.1161/strokeaha.115.011086

    Article  PubMed  Google Scholar 

  19. Yang WJ, Abrigo J, Soo YO et al (2020) Regression of plaque enhancement within symptomatic middle cerebral artery atherosclerosis: a high-resolution MRI study. Front Neurol 11:755. https://doi.org/10.3389/fneur.2020.00755

    Article  PubMed  PubMed Central  Google Scholar 

  20. Zhang X, Chen L, Li S et al (2021) enhancement characteristics of middle cerebral arterial atherosclerotic plaques over time and their correlation with stroke recurrence. J Magn Reson Imaging 53:953–962. https://doi.org/10.1002/jmri.27351

    Article  PubMed  Google Scholar 

  21. Teng Z, Brown AJ, Gillard JH (2017) Carotid intraplaque hemorrhage: a biomarker for subsequent ischemic cerebrovascular event? Cerebrovasc Dis 43:257–258. https://doi.org/10.1159/000462994

    Article  PubMed  Google Scholar 

  22. Truijman MT, Kwee RM, van Hoof RH et al (2013) Combined 18F-FDG PET-CT and DCE-MRI to assess inflammation and microvascularization in atherosclerotic plaques. Stroke 44:3568–3570. https://doi.org/10.1161/strokeaha.113.003140

    Article  CAS  PubMed  Google Scholar 

  23. Millon A, Boussel L, Brevet M et al (2012) Clinical and histological significance of gadolinium enhancement in carotid atherosclerotic plaque. Stroke 43:3023–3028. https://doi.org/10.1161/strokeaha.112.662692

    Article  PubMed  Google Scholar 

  24. Cai J, Hatsukami TS, Ferguson MS et al (2005) In vivo quantitative measurement of intact fibrous cap and lipid-rich necrotic core size in atherosclerotic carotid plaque: comparison of high-resolution, contrast-enhanced magnetic resonance imaging and histology. Circulation 112:3437–3444. https://doi.org/10.1161/circulationaha.104.528174

    Article  PubMed  Google Scholar 

  25. Shi Z, Tian X, Tian B et al (2021) Identification of high risk clinical and imaging features for intracranial artery dissection using high-resolution cardiovascular magnetic resonance. J Cardiovasc Magn Reson 23:74. https://doi.org/10.1186/s12968-021-00766-9

    Article  PubMed  PubMed Central  Google Scholar 

  26. Qiao Y, Etesami M, Astor BC, Zeiler SR, Trout HH 3rd, Wasserman BA (2012) Carotid plaque neovascularization and hemorrhage detected by MR imaging are associated with recent cerebrovascular ischemic events. AJNR Am J Neuroradiol 33:755–760. https://doi.org/10.3174/ajnr.A2863

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Teng Z, Sadat U, Ji G et al (2011) Lumen irregularity dominates the relationship between mechanical stress condition, fibrous-cap thickness, and lumen curvature in carotid atherosclerotic plaque. J Biomech Eng 133:034501. https://doi.org/10.1115/1.4003439

    Article  PubMed  Google Scholar 

  28. Brown AJ, Teng Z, Calvert PA et al (2016) Plaque structural stress estimations improve prediction of future major adverse cardiovascular events after intracoronary imaging. Circ Cardiovasc Imaging 910.1161/circimaging.115.004172

  29. Sadat U, Teng Z, Young VE et al (2010) Association between biomechanical structural stresses of atherosclerotic carotid plaques and subsequent ischaemic cerebrovascular events--a longitudinal in vivo magnetic resonance imaging-based finite element study. Eur J Vasc Endovasc Surg 40:485–491. https://doi.org/10.1016/j.ejvs.2010.07.015

    Article  CAS  PubMed  Google Scholar 

  30. Leung TW, Wang L, Zou X et al (2020) Plaque morphology in acute symptomatic intracranial atherosclerotic disease. J Neurol Neurosurg Psychiatry 92:370–376. https://doi.org/10.1136/jnnp-2020-325027

    Article  Google Scholar 

  31. Leng X, Lan L, Ip HL et al (2019) Hemodynamics and stroke risk in intracranial atherosclerotic disease. Ann Neurol 85:752–764. https://doi.org/10.1002/ana.25456

    Article  CAS  PubMed  Google Scholar 

  32. Samady H, Eshtehardi P, McDaniel MC et al (2011) Coronary artery wall shear stress is associated with progression and transformation of atherosclerotic plaque and arterial remodeling in patients with coronary artery disease. Circulation 124:779–788. https://doi.org/10.1161/circulationaha.111.021824

    Article  CAS  PubMed  Google Scholar 

  33. Zhang L, Shi J, Pan Y et al (2021) Secondary prevention medication persistence and prognosis of acute ischaemic stroke or transient ischaemic attack. Stroke Vasc Neurol. https://doi.org/10.1136/svn-2020-000471

  34. Ekker MS, Boot EM, Singhal AB et al (2018) Epidemiology, aetiology, and management of ischaemic stroke in young adults. Lancet Neurol 17:790–801. https://doi.org/10.1016/s1474-4422(18)30233-3

    Article  PubMed  Google Scholar 

  35. Boot E, Ekker MS, Putaala J, Kittner S, De Leeuw FE, Tuladhar AM (2020) Ischaemic stroke in young adults: a global perspective. J Neurol Neurosurg Psychiatry 91:411–417. https://doi.org/10.1136/jnnp-2019-322424

    Article  PubMed  Google Scholar 

  36. Maaijwee NA, Rutten-Jacobs LC, Schaapsmeerders P, van Dijk EJ, de Leeuw FE (2014) Ischaemic stroke in young adults: risk factors and long-term consequences. Nat Rev Neurol 10:315–325. https://doi.org/10.1038/nrneurol.2014.72

    Article  PubMed  Google Scholar 

  37. Shi Z, Zhao M, Li J et al (2021) Association of hypertension with both occurrence and outcome of symptomatic patients with mild intracranial atherosclerotic stenosis: a prospective higher resolution magnetic resonance imaging study. J Magn Reson Imaging 54:76–88. https://doi.org/10.1002/jmri.27516

    Article  PubMed  PubMed Central  Google Scholar 

  38. Zhang T, Tang R, Liu S et al (2021) Plaque characteristics of middle cerebral artery assessed using strategically acquired gradient echo (STAGE) and vessel wall MR contribute to misery downstream perfusion in patients with intracranial atherosclerosis. Eur Radiol 31:65–75. https://doi.org/10.1007/s00330-020-07055-6

    Article  CAS  PubMed  Google Scholar 

  39. Kasner SE, Chimowitz MI, Lynn MJ et al (2006) Predictors of ischemic stroke in the territory of a symptomatic intracranial arterial stenosis. Circulation 113:555–563. https://doi.org/10.1161/circulationaha.105.578229

    Article  PubMed  Google Scholar 

  40. Chimowitz MI, Lynn MJ, Derdeyn CP et al (2011) Stenting versus aggressive medical therapy for intracranial arterial stenosis. N Engl J Med 365:993–1003. https://doi.org/10.1056/NEJMoa1105335

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Zhao DL, Deng G, Xie B et al (2015) High-resolution MRI of the vessel wall in patients with symptomatic atherosclerotic stenosis of the middle cerebral artery. J Clin Neurosci 22:700–704. https://doi.org/10.1016/j.jocn.2014.10.018

    Article  PubMed  Google Scholar 

  42. Little WC, Constantinescu M, Applegate RJ et al (1988) Can coronary angiography predict the site of a subsequent myocardial infarction in patients with mild-to-moderate coronary artery disease? Circulation 78:1157–1166. https://doi.org/10.1161/01.cir.78.5.1157

    Article  CAS  PubMed  Google Scholar 

  43. Bos D, Arshi B, van den Bouwhuijsen QJA et al (2021) Atherosclerotic carotid plaque composition and incident stroke and coronary events. J Am Coll Cardiol 77:1426–1435. https://doi.org/10.1016/j.jacc.2021.01.038

    Article  PubMed  Google Scholar 

  44. Schindler A, Schinner R, Altaf N et al (2020) Prediction of stroke risk by detection of hemorrhage in carotid plaques: meta-analysis of individual patient data. JACC Cardiovasc Imaging 13:395–406. https://doi.org/10.1016/j.jcmg.2019.03.028

    Article  PubMed  Google Scholar 

  45. Xu WH, Li ML, Gao S et al (2012) Middle cerebral artery intraplaque hemorrhage: prevalence and clinical relevance. Ann Neurol 71:195–198. https://doi.org/10.1002/ana.22626

    Article  PubMed  Google Scholar 

  46. Turan TN, Rumboldt Z, Granholm AC et al (2014) Intracranial atherosclerosis: correlation between in-vivo 3T high resolution MRI and pathology. Atherosclerosis 237:460–463. https://doi.org/10.1016/j.atherosclerosis.2014.10.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Jiang Y, Zhu C, Peng W et al (2016) Ex-vivo imaging and plaque type classification of intracranial atherosclerotic plaque using high resolution MRI. Atherosclerosis 249:10–16. https://doi.org/10.1016/j.atherosclerosis.2016.03.033

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Teng Z, Degnan AJ, Sadat U et al (2011) Characterization of healing following atherosclerotic carotid plaque rupture in acutely symptomatic patients: an exploratory study using in vivo cardiovascular magnetic resonance. J Cardiovasc Magn Reson 13:64. https://doi.org/10.1186/1532-429x-13-64

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This study is supported in part by DRAGON, the European Research Council and Innovative Medicines Initiative, and the National Institute of Health Research Cambridge Biomedical Research Centre.

Funding

This study has received funding from the Fundamental Research Funds for the Central Universities (WK9110000056) and the National Natural Science Foundation of China (U20A20357, 81870946).

Author information

Author notes

  1. Dahong Yang and Jia Liu contributed equally to the manuscript as first author.

  2. Xinfeng Liu and Juan Du are corresponding authors.

Authors and Affiliations

  1. Department of Neurology, Jinling Hospital, The First School of Clinical Medicine, Southern Medical University, No. 305 E Zhongshan Rd, Nanjing, 210002, Jiangsu Province, China

    Dahong Yang & Xinfeng Liu

  2. Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, Nanjing, China

    Jia Liu, Changsheng Zhou, Jun Bi, Xiaoqing Cheng, Jun Zhang, Longjiang Zhang & Jun Cai

  3. Department of Neurology, Affiliated Jinling Hospital, Medical School of Nanjing University, No. 305 E Zhongshan Rd, Nanjing, 210002, Jiangsu Province, China

    Weihe Yao, Kangmo Huang, Minmin Ma, Wusheng Zhu, Juan Du & Xinfeng Liu

  4. Department of Radiology, University of Cambridge, Cambridge, UK

    Zhongzhao Teng

  5. Stroke Center & Department of Neurology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China

    Xinfeng Liu

Authors
  1. Dahong Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jia Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Weihe Yao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kangmo Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Changsheng Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jun Bi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Xiaoqing Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Minmin Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Wusheng Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Jun Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Longjiang Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Jun Cai
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Zhongzhao Teng
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Juan Du
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Xinfeng Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Juan Du or Xinfeng Liu.

Ethics declarations

Guarantor

The scientific guarantor of this publication is Xinfeng Liu, MD, PhD, Department of Neurology, Jinling Hospital, The First School of Clinical Medicine, Southern Medical University, Email: xfliu2@vip.163.com.

Conflict of interest

Dr. Zhongzhao Teng is the chief scientist of Tenoke Ltd., Cambridge, UK, and Nanjing Jingsan Medical Science and Technology, Ltd., Nanjing, China. Other authors declare no relationships with any companies, whose products or services may be related to the subject matter of the article.

Statistics and biometry

One of the authors has significant statistical expertise.

Informed consent

Written informed consent was obtained from all subjects (patients) in this study.

Ethical approval

Institutional Review Board approval was obtained.

Methodology

• Retrospective cohort

• observational

• performed at one institution

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

ESM 1

(DOCX 36 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yang, D., Liu, J., Yao, W. et al. The MRI enhancement ratio and plaque steepness may be more accurate for predicting recurrent ischemic cerebrovascular events in patients with intracranial atherosclerosis. Eur Radiol 32, 7004–7013 (2022). https://doi.org/10.1007/s00330-022-08893-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00330-022-08893-2

Keywords

Search

Navigation