Skip to main content

Advertisement

SpringerLink
Log in

Ferumoxytol-enhanced MR venography for mapping lower-extremity venous networks and evaluating varicose veins in patients with diabetes

  • Contrast Media
  • Published:
European Radiology Aims and scope Submit manuscript

Abstract

Objectives

Comprehensive evaluation of lower-extremity varicose veins (VVs) in patients with diabetes is crucial for treatment strategizing. The study aims to assess the feasibility of using ferumoxytol-enhanced MR venography (FE-MRV) for lower-extremity venous mapping and the detection of VVs in patients with diabetes.

Materials and methods

As part of a phase II clinical trial of a generic brand of ferumoxytol, documented patients with diabetes were enrolled and underwent FE-MRV on a 3-Τ MRI system. Two observers assessed FE-MRV images for image quality, signal intensity ratio (SIR), perforator (PV) diameter, and luminal signal uniformity in deep-to-superficial venous networks with the assessment of intra- and inter-rater reliability. FE-MRV was used to detect lower-extremity VVs.

Results

Eleven patients underwent FE-MRV without adverse events. The average image quality, as scored by the two observers who assessed 275 venous segments, was 3.4 ± 0.6. Two observers strongly agreed on image quality (κ = 0.90) and SIR measurements (interclass correlation coefficient [ICC]: 0.72) and had good agreement on PV diameter (ICC: 0.64). FE-MRV revealed uniform luminal signals in deep and saphenous venous networks (0.13 ± 0.05 vs 0.08 ± 0.03). Below-knee segments exhibited a significantly higher heterogeneity index than above-knee (p = 0.039) segments. Superficial VVs were observed in 55% (12/22) of legs in 64% (7/11) of patients. Calf muscle VVs were present in 64% (14/22) of legs in 9 patients.

Conclusion

FE-MRV safely and robustly mapped entire lower-extremity venous networks, enabling the detection and pre-treatment evaluation of both superficial, and deep VVs in patients with diabetes.

Clinical relevance statement

Ferumoxytol-enhanced magnetic resonance venography offers a “one-stop” imaging strategy for the detection and pre-operative evaluation of both superficial and deep VVs in diabetic patients.

Key Points

  • Diabetic patients with VVs are at a higher risk of ulcer-related complications.

  • FE-MRV allowed rapid and comprehensive visualization of the lower-limb venous networks and abdominopelvic veins in diabetic patients.

  • This technique allowed for the detection of superficial and deep VVs in diabetic patients before the development of severe peripheral artery disease.

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
Fig. 5
Fig. 6

Similar content being viewed by others

Abbreviations

CI:

Confidence interval

CKD:

Chronic kidney disease

CPR:

Curved multiplanar reconstruction

CTV:

CT venography

CVD:

Chronic venous diseases

DUS:

Duplex ultrasonography

DVT:

Deep venous thrombosis

FDA:

Food and Drug Administration

FE-MRV:

Ferumoxytol-enhanced MR venography

Gd-MRV:

Gadolinium-enhanced magnetic resonance venography

GSV:

Great saphenous vein

ICC:

Interclass correlation coefficient

IVC:

Inferior vena cava

MPR:

Multiplanar reconstruction

PAD:

Peripheral artery disease

PVs:

Perforating veins

ROI:

Region of interest

SD:

Standard deviation

SIR:

Signal intensity ratio

SSV:

Small saphenous vein

USPIO:

Ultrasmall superparamagnetic iron oxide

VVs:

Varicose veins

References

  1. Chang SL, Huang YL, Lee MC et al (2018) Association of varicose veins with incident venous thromboembolism and peripheral artery disease. JAMA 319:807–817

    Article  PubMed  PubMed Central  Google Scholar 

  2. Nyamekye IK (2022) European Society for Vascular Surgery (ESVS) 2022 clinical practice guidelines on the management of chronic venous disease of the lower limbs. J Med Vasc 47:53–55

    PubMed  Google Scholar 

  3. Gloviczki P, Lawrence PF, Wasan SM et al (2024) The 2023 Society for Vascular Surgery, American Venous Forum, and American Vein and Lymphatic Society clinical practice guidelines for the Management of varicose veins of the lower extremities. Part II. Endorsed by the Society of Interventional Radiology and the Society for Vascular Medicine. J Vasc Surg Venous Lymphat Disord 12:101670

  4. O’Donnell TF, Balk EM, Dermody M, Tangney E, Iafrati MD (2016) Recurrence of varicose veins after endovenous ablation of the great saphenous vein in randomized trials. J Vasc Surg Venous Lymphat Disord 4:97–105

    Article  PubMed  Google Scholar 

  5. Expert Panels on Interventional Radiology and Vascular Imaging (2023) ACR appropriateness criteria® lower extremity chronic venous disease. J Am Coll Radiol 20:S481–S500

    Article  Google Scholar 

  6. Barnes JA, Eid MA, Creager MA, Goodney PP (2020) Epidemiology and risk of amputation in patients with diabetes mellitus and peripheral artery disease. Arterioscler Thromb Vasc Biol 40:1808–1817

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Necas M (2010) Duplex ultrasound in the assessment of lower extremity venous insufficiency. Australas J Ultrasound Med 13:37–45

    Article  PubMed  PubMed Central  Google Scholar 

  8. Zucker EJ, Ganguli S, Ghoshhajra BB, Gupta R, Prabhakar AM (2016) Imaging of venous compression syndromes. Cardiovasc Diagn Ther 6:519–532

    Article  PubMed  PubMed Central  Google Scholar 

  9. Min SK, Kim SY, Park YJ et al (2010) Role of three-dimensional computed tomography venography as a powerful navigator for varicose vein surgery. J Vasc Surg 51:893–899

    Article  PubMed  Google Scholar 

  10. Muller MA, Mayer D, Seifert B, Marincek B, Willmann JK (2008) Recurrent lower-limb varicose veins: effect of direct contrast-enhanced three-dimensional MR venographic findings on diagnostic thinking and therapeutic decisions. Radiology 247:887–895

    Article  PubMed  Google Scholar 

  11. Knobloch G, Colgan T, Wiens CN et al (2018) Relaxivity of ferumoxytol at 1.5 T and 3.0 T. Invest Radiol 53:257–263

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Finn JP, Nguyen KL, Hu P (2017) Ferumoxytol vs. gadolinium agents for contrast-enhanced MRI: thoughts on evolving indications, risks, and benefits. J Magn Reson Imaging 46:919–923

    Article  PubMed  PubMed Central  Google Scholar 

  13. Finn JP, Nguyen KL, Han F et al (2016) Cardiovascular MRI with ferumoxytol. Clin Radiol 71:796–806

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Chen B, Li Y, Zhang X, Liu F, Liu Y, Xiong F, Gu N (2016) An efficient synthesis of ferumoxytol induced by alternating-current magnetic field. Materials Letters 170:93–96

    Article  CAS  Google Scholar 

  15. De Maeseneer MG, Kakkos SK, Aherne T et al (2022) Editor’s Choice—European Society for Vascular Surgery (ESVS) 2022 clinical practice guidelines on the management of chronic venous disease of the lower limbs. Eur J Vasc Endovasc Surg 63:184–267

    Article  PubMed  Google Scholar 

  16. McHugh ML (2012) Interrater reliability: the kappa statistic. Biochem Med (Zagreb) 22:276–282

    Article  PubMed  Google Scholar 

  17. Koo TK, Li MY (2016) A guideline of selecting and reporting intraclass correlation coefficients for reliability research. J Chiropr Med 15:155–163

    Article  PubMed  PubMed Central  Google Scholar 

  18. Eid MA, Mehta K, Barnes JA et al (2023) The global burden of peripheral artery disease. J Vasc Surg 77:1119–1126 e1111

    Article  PubMed  Google Scholar 

  19. Zhong J, Chen J, Zhao ZG et al (2014) Diabetes mellitus is associated with early chronic venous disorder of the lower extremities in Chinese patients with cardiometabolic risk factors. Diabetes Metab Res Rev 30:505–512

    Article  CAS  PubMed  Google Scholar 

  20. Paneni F, Beckman JA, Creager MA, Cosentino F (2013) Diabetes and vascular disease: pathophysiology, clinical consequences, and medical therapy: part I. Eur Heart J 34:2436–2443

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Noor S, Zubair M, Ahmad J (2015) Diabetic foot ulcer-A review on pathophysiology, classification and microbial etiology. Diabetes Metab Syndr 9:192–199

    Article  PubMed  Google Scholar 

  22. Thomas MC, Brownlee M, Susztak K et al (2015) Diabetic kidney disease. Nat Rev Dis Primers 1:15018

    Article  PubMed  PubMed Central  Google Scholar 

  23. Spinowitz BS, Kausz AT, Baptista J et al (2008) Ferumoxytol for treating iron deficiency anemia in CKD. J Am Soc Nephrol 19:1599–1605

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Corwin MT, Fananapazir G, Chaudhari AJ (2016) MR angiography of renal transplant vasculature with ferumoxytol:: comparison of high-resolution steady-state and first-pass acquisitions. Acad Radiol 23:368–373

    Article  PubMed  Google Scholar 

  25. Li W, Salanitri J, Tutton S et al (2007) Lower extremity deep venous thrombosis: evaluation with ferumoxytol-enhanced MR imaging and dual-contrast mechanism-preliminary experience. Radiology 242:873–881

    Article  PubMed  Google Scholar 

  26. Bashir MR, Mody R, Neville A et al (2014) Retrospective assessment of the utility of an iron-based agent for contrast-enhanced magnetic resonance venography in patients with endstage renal diseases. J Magn Reson Imaging 40:113–118

    Article  PubMed  Google Scholar 

  27. Bellmunt-Montoya S, Escribano JM, Pantoja Bustillos PE, Tello-Diaz C, Martinez-Zapata MJ (2021) CHIVA method for the treatment of chronic venous insufficiency. Cochrane Database Syst Rev 9:CD009648

    PubMed  Google Scholar 

  28. Aschauer M, Deutschmann HA, Stollberger R et al (2003) Value of a blood pool contrast agent in MR venography of the lower extremities and pelvis: preliminary results in 12 patients. Magn Reson Med 50:993–1002

    Article  PubMed  Google Scholar 

  29. Stoumpos S, Hall Barrientos P, Black DH et al (2020) Ferumoxytol MR angiography: a novel technique for assessing iliac vasculature in potential kidney transplant recipients. JACC Cardiovasc Imaging 13:1847–1848

    Article  PubMed  Google Scholar 

  30. Hope MD, Hope TA, Zhu C et al (2015) Vascular imaging with ferumoxytol as a contrast agent. AJR Am J Roentgenol 205:W366–W373

    Article  Google Scholar 

  31. Lehrman ED, Plotnik AN, Hope T, Saloner D (2019) Ferumoxytol-enhanced MRI in the peripheral vasculature. Clin Radiol 74:37–50

    Article  CAS  PubMed  Google Scholar 

  32. Ghodrati V, Rivenson Y, Prosper A et al (2022) Automatic segmentation of peripheral arteries and veins in ferumoxytol-enhanced MR angiography. Magn Reson Med 87:984–998

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank Zhenyue Gao and Jinling Xue of Chia Tai Tianqing Pharmaceutical Group Co., Ltd. for their assistance. Chia Tai Tianqing Pharmaceutical Group Co., Ltd. supplied ferumoxytol free of charge.

Funding

This work was supported by the National Nature Science Foundation of China (No. 2021YFC2501100 and 92249301), the Beijing Research Ward Demonstration Construction Project (No. BCRW202110), and the Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding (No. ZLRK202306).

Author information

Author notes

  1. These authors contributed equally: Yuehong Liu, Bin Cao.

Authors and Affiliations

  1. Department of Radiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China

    Yuehong Liu, Xinyu Wang & Qi Yang

  2. Department of Endocrinology, Beijing Luhe Hospital, Capital Medical University, Beijing, China

    Bin Cao & Dong Zhao

  3. Department of Radiology, Beijing Luhe Hospital, Capital Medical University, Beijing, China

    Jiali Zhong & Ruchen Peng

  4. Department of Radiology, Central Hospital Affiliated to Xinxiang Medical University, Xinxiang, China

    Zhenyu Li

  5. Medical School of Nanjing University, Nanjing, China

    Ning Gu

  6. Laboratory for Clinical Medicine, Capital Medical University, Beijing, China

    Qi Yang

Authors
  1. Yuehong Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bin Cao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xinyu Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jiali Zhong
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Zhenyu Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ruchen Peng
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Dong Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ning Gu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Qi Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Dong Zhao, Ning Gu or Qi Yang.

Ethics declarations

Guarantor

The scientific guarantor of this publication is Qi Yang.

Conflict of interest

The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article.

Statistics and biometry

No complex statistical methods were necessary for this paper.

Informed consent

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

Ethical approval

This study was approved by the institutional review board (REC reference: 2021-LHKY-104-02).

Study subjects or cohorts overlap

None study subjects or cohorts have been previously reported.

Methodology

  • Observational

  • Single-center study

Additional information

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

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, Y., Cao, B., Wang, X. et al. Ferumoxytol-enhanced MR venography for mapping lower-extremity venous networks and evaluating varicose veins in patients with diabetes. Eur Radiol (2024). https://doi.org/10.1007/s00330-024-10772-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00330-024-10772-x

Keywords

Search

Navigation