Evaluation of contrast agent dose and diffusion coefficient measurement on vessel size index estimation



The goal of this study is to examine the effect of contrast agent (CA) dose and diffusion coefficient on the estimation of vessel size index (VSI).

Materials and methods

Three groups of four participants were enrolled in this study and two different experiments were performed. Different dose of CA, namely 0.1 mmol/kg and 0.05 mmol/kg were assessed in two groups of normal subjects. Diffusion coefficient effect was assessed in the third group with high-grade glioma. Imaging included gradient echo and spin-echo DSC and DTI on a 3-T MR Scanner.


VSI estimation using half of standard dose of CA showed higher values compared to the application of standard, with a ratio of 2 for the WM and 1.5 for the GM. VSI estimates for tumor tissues (22 µm) were considerably higher compared to contra-lateral Normal-Appearing WM (NAWM, 4 µm, P < 0.01) and Normal-Appearing GM (NAGM, 8 µm, P < 0.04).


Application of standard dose for CA injection and also taking into account the effect of diffusion coefficient can lead to a better correlation of VSI with previous theoretically predicted values and improvement of individual diagnostics in tumor evaluations.

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  1. 1.

    Boxerman JL, Hamberg LM, Rosen BR, Weisskoff RM (1995) Mr contrast due to intravascular magnetic susceptibility perturbations. Magn Reson Med 34:555–566

    CAS  Article  Google Scholar 

  2. 2.

    Hsu Y-Y, Yang W-S, Lim K-E, Liu H-L (2009) Vessel size imaging using dual contrast agent injections. J Magn Reson Imaging 30:1078–1084

    Article  Google Scholar 

  3. 3.

    Tropres I, Grimault S, Vaeth A, Grillon E, Julien C, Payen J-F, Lamalle L, Decorps M (2001) Vessel size imaging. Magn Reson Med 45:397–408

    CAS  Article  Google Scholar 

  4. 4.

    Tropres I, Lamalle L, Farion R, Segebarth C, Remy C (2004) Vessel size imaging using low intravascular contrast agent concentrations. Magn Reson Mater Phy 17:313–316

    CAS  Article  Google Scholar 

  5. 5.

    Kang H-Y, Xiao H-L, Chen J-H, Tan Y, Chen X, Xie T, Fang J-Q, Wang S, Yang Y, Zhang W-G (2016) Comparison of the effect of vessel size imaging and cerebral blood volume derived from perfusion MR imaging on glioma grading. Am J Neuroradiol 37:51–57

    Article  Google Scholar 

  6. 6.

    Kiselev VG, Strecker R, Ziyeh S, Speck O, Hennig J (2005) Vessel size imaging in humans. Magn Reson Med 53:553–563

    CAS  Article  Google Scholar 

  7. 7.

    Kiselev VG (2005) Transverse relaxation effect of MRI contrast agents: a crucial issue for quantitative measurements of cerebral perfusion. J Magn Reson Imaging 22:693–696

    Article  Google Scholar 

  8. 8.

    Willats L, Calamante F (2013) The 39 steps: evading error and deciphering the secrets for accurate dynamic susceptibility contrast MRI: the 39 steps: towards accurate DSC-MRI. NMR Biomed 26:913–931

    Article  Google Scholar 

  9. 9.

    Schmainda KM, Rand SD, Joseph AM, Lund R, Ward BD, Pathak AP, Ulmer JL, Baddrudoja MA, Krouwer HG (2004) Characterization of a first-pass gradient-echo spin-echo method to predict brain tumor grade and angiogenesis. Am J Neuroradiol 25:1524–1532

    PubMed  Google Scholar 

  10. 10.

    Kennan RP, Zhong J, Gore JC (1994) Intravascular susceptibility contrast mechanisms in tissues. Magn Reson Med 31:9–21

    CAS  Article  Google Scholar 

  11. 11.

    Irène T, Pannetier N, Grand S, Lemasson B, Moisan A, Péoch M, Rémy C, Barbier EL (2015) Imaging the microvessel caliber and density: principles and applications of microvascular MRI. Magn Reson Med 73:325–341

    Article  Google Scholar 

  12. 12.

    Kiselev VG, Posse S (1998) Analytical theory of susceptibility induced NMR signal dephasing in a cerebrovascular network. Phys Rev Lett 81:5696–5699

    CAS  Article  Google Scholar 

  13. 13.

    Kiselev VG, Posse S (1999) Analytical model of susceptibility-induced MR signal dephasing: effect of diffusion in a microvascular network. Magn Reson Med 41:499–509

    CAS  Article  Google Scholar 

  14. 14.

    Yablonskiy DA, Haacke EM (1994) Theory of NMR signal behavior in magnetically inhomogeneous tissues: the static dephasing regime. Magn Reson Med 32:749–763

    CAS  Article  Google Scholar 

  15. 15.

    Kiselev VG, Novikov DS (2002) Transverse NMR relaxation as a probe of mesoscopic structure. Phys Rev Lett. https://doi.org/10.1103/physrevlett.89.278101

    Article  PubMed  Google Scholar 

  16. 16.

    Kjølby BF, Østergaard L, Kiselev VG (2006) Theoretical model of intravascular paramagnetic tracers effect on tissue relaxation. Magn Reson Med 56:187–197

    Article  Google Scholar 

  17. 17.

    Fredrickson J, Serkova NJ, Wyatt SK, Carano RA, Pirzkall A, Rhee I, Rosen LS, Bessudo A, Weekes C, de Crespigny A (2017) Clinical translation of ferumoxytol-based vessel size imaging (VSI): feasibility in a phase I oncology clinical trial population. Magn Reson Med 77:814–825

    Article  Google Scholar 

  18. 18.

    Pannetier N, Lemasson B, Christen T, Tachrount M, Troprès I, Farion R, Segebarth C, Rémy C, Barbier EL (2012) Vessel size index measurements in a rat model of glioma: comparison of the dynamic (Gd) and steady-state (iron-oxide) susceptibility contrast MRI approaches: dynamic vs steady state VSI. NMR Biomed 25:218–226

    CAS  Article  Google Scholar 

  19. 19.

    Xu C, Kiselev VG, Möller HE, Fiebach JB (2013) Dynamic hysteresis between gradient echo and spin echo attenuations in dynamic susceptibility contrast imaging: dynamic hysteresis in double echo DSC imaging. Magn Reson Med 69:981–991

    Article  Google Scholar 

  20. 20.

    Essig M, Wenz F, Scholdei R, Brüning R, Berchtenbreiter C, Meurer M, Knopp MV (2002) Dynamic susceptibility contrast-enhanced echo-planar imaging of cerebral gliomas: effect of contrast medium extravasation. Acta Radiol 43:354–359

    CAS  Article  Google Scholar 

  21. 21.

    Shiroishi MS, Castellazzi G, Boxerman JL, D’Amore F, Essig M, Nguyen TB, Provenzale JM, Enterline DS, Anzalone N, Dörfler A, Rovira À, Wintermark M, Law M (2015) Principles of T2*-weighted dynamic susceptibility contrast MRI technique in brain tumor imaging: principles of T2*-weighted DSC-MRI. J Magn Reson Imaging 41:296–313

    Article  Google Scholar 

  22. 22.

    Carroll TJ, Horowitz S, Shin W, Mouannes J, Sawlani R, Ali S, Raizer J, Futterer S (2008) Quantification of cerebral perfusion using the “bookend technique”: an evaluation in CNS tumors. Magn Reson Imaging 26:1352–1359

    Article  Google Scholar 

  23. 23.

    Essig M, Shiroishi MS, Nguyen TB, Saake M, Provenzale JM, Enterline D, Anzalone N, Dörfler A, Rovira À, Wintermark M, Law M (2013) Perfusion MRI: the five most frequently asked technical questions. Am J Roentgenol 200:24–34

    Article  Google Scholar 

  24. 24.

    Leu K, Boxerman JL, Ellingson BM (2017) Effects of MRI protocol parameters, preload injection dose, fractionation strategies, and leakage correction algorithms on the fidelity of dynamic-susceptibility contrast MRI estimates of relative cerebral blood volume in gliomas. Am J Neuroradiol 38:478–484

    CAS  Article  Google Scholar 

  25. 25.

    Kim YS, Choi SH, Yoo R-E, Kang KM, Yun TJ, Kim J, Sohn C-H, Park S-H, Won J-K, Kim TM, Park C-K, Kim IH (2018) Leakage correction improves prognosis prediction of dynamic susceptibility contrast perfusion MRI in primary central nervous system lymphoma. Sci Rep. https://doi.org/10.1038/s41598-017-18901-x

    Article  PubMed  PubMed Central  Google Scholar 

  26. 26.

    Xu C, Schmidt WU, Villringer K, Brunecker P, Kiselev V, Gall P, Fiebach JB (2011) Vessel size imaging reveals pathological changes of microvessel density and size in acute ischemia. J Cereb Blood Flow Metab 31:1687–1695

    Article  Google Scholar 

  27. 27.

    Marusyk A, Polyak K (2010) Tumor heterogeneity: causes and consequences. Biochim Biophys Acta (BBA) Rev Cancer 1805:105–117

    CAS  Article  Google Scholar 

  28. 28.

    Perkiö J, Aronen HJ, Kangasmäki A, Liu Y, Karonen J, Savolainen S, Østergaard L (2002) Evaluation of four postprocessing methods for determination of cerebral blood volume and mean transit time by dynamic susceptibility contrast imaging: determination of CBV and MTT by DSC-MRI. Magn Reson Med 47:973–981

    Article  Google Scholar 

  29. 29.

    Jensen JH, Lu H, Inglese M (2006) Microvessel density estimation in the human brain by means of dynamic contrast-enhanced echo-planar imaging. Magn Reson Med 56:1145–1150

    Article  Google Scholar 

  30. 30.

    Kellner E, Breyer T, Gall P, Müller K, Trippel M, Staszewski O, Stein F, Saborowski O, Dyakova O, Urbach H, Kiselev VG, Mader I (2015) MR evaluation of vessel size imaging of human gliomas: validation by histopathology: vessel size imaging of human gliomas. J Magn Reson Imaging 42:1117–1125

    Article  Google Scholar 

  31. 31.

    Heiland DH, Demerath T, Kellner E, Kiselev VG, Pfeifer D, Schnell O, Staszewski O, Urbach H, Weyerbrock A, Mader I (2017) Molecular differences between cerebral blood volume and vessel size in glioblastoma multiforme. Oncotarget 8(7)

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The authors must thank the research affair of Medicine faculty of Tehran University of Medical Sciences, Medical Imaging Center of Imam Khomeini Hospital (Tehran), and all participants in this study.


This research has been supported by Tehran University of Medical Sciences, Grant number 96-03-30-36318.

Author information




BVA: acquisition of data, analysis and interpretation of data, drafting of manuscript, study conception and design; SM: analysis and interpretation of data, and drafting of manuscript; MAO: study conception and design; SRG: study conception and design; MRNZ: critical revision; EE: critical revision; MF: critical revision; MG: acquisition of data; HH: study conception and design, critical revision.

Corresponding author

Correspondence to Hasan Hashemi.

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Conflict of interest

There is not any conflict of interest to disclose.

Ethical approval

The study was approved by the local committee for medical research ethics (IR.TUMS.MEDICINE.REC.1396.4153).

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Written Informed consent was obtained from all participants before proceeding with the study.

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Vejdani Afkham, B., Masjoodi, S., Oghabian, M.A. et al. Evaluation of contrast agent dose and diffusion coefficient measurement on vessel size index estimation. Magn Reson Mater Phy 32, 529–537 (2019). https://doi.org/10.1007/s10334-019-00760-4

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  • Contrast agent
  • Dynamic susceptibility contrast
  • Vessel size index
  • Diffusion tensor imaging