Journal of Neuro-Oncology

, Volume 135, Issue 1, pp 119–127 | Cite as

Temporal evolution of perfusion parameters in brain metastases treated with stereotactic radiosurgery: comparison of intravoxel incoherent motion and dynamic contrast enhanced MRI

  • Anish Kapadia
  • Hatef Mehrabian
  • John Conklin
  • Sean P. Symons
  • Pejman J. Maralani
  • Greg J. Stanisz
  • Arjun Sahgal
  • Hany Soliman
  • Chinthaka C. Heyn
Clinical Study


Intravoxel incoherent motion (IVIM) is a magnetic resonance imaging (MRI) technique that is seeing increasing use in neuro-oncology and offers an alternative to contrast-enhanced perfusion techniques for evaluation of tumor blood volume after stereotactic radiosurgery (SRS). To date, IVIM has not been validated against contrast enhanced techniques for brain metastases after SRS. In the present study, we measure blood volume for 20 brain metastases (15 patients) at baseline, 1 week and 1 month after SRS using IVIM and dynamic contrast enhanced (DCE)-MRI. Correlation between blood volume measurements made with IVIM and DCE-MRI show poor correlation at baseline, 1 week, and 1 month post SRS (r = 0.33, 0.14 and 0.30 respectively). At 1 week after treatment, no significant change in tumor blood volume was found using IVIM or DCE-MRI (p = 0.81 and 0.41 respectively). At 1 month, DCE-MRI showed a significant decrease in blood volume (p = 0.0002). IVIM, on the other hand, demonstrated the opposite effect and showed a significant increase in blood volume at 1 month (p = 0.03). The results of this study indicate that blood volume measured with IVIM and DCE-MRI are not equivalent. While this may relate to differences in the type of perfusion information each technique is providing, it could also reflect a limitation of tumor blood volume measurements made with IVIM after SRS. IVIM measurements of tumor blood volume in the month after SRS should therefore be interpreted with caution.


Stereotactic radiosurgery Brain metastases Perfusion magnetic resonance imaging Dynamic contrast enhanced Intravoxel incoherent motion Diffusion weighted magnetic resonance imaging 



The authors received no financial support for the research, authorship, and/or publication of this article.

Compliance with ethical standards

Conflict of interest

The authors report no conflict of interest related to this article.

Ethical approval

Informed consent was obtained and the study was conducted in accordance with the ethical standards of the institutional REB.


  1. 1.
    Brown PD, Jaeckle K, Ballman KV, Farace E, Cerhan JH, Anderson SK, Carrero XW, Barker FG 2nd, Deming R, Burri SH, Menard C, Chung C, Stieber VW, Pollock BE, Galanis E, Buckner JC, Asher AL (2016) Effect of radiosurgery alone vs radiosurgery with whole brain radiation therapy on cognitive function in patients with 1 to 3 brain metastases: a randomized clinical trial. JAMA 316(4):401–409. doi: 10.1001/jama.2016.9839 CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Brurberg KG, Thuen M, Ruud EB, Rofstad EK (2006) Fluctuations in pO2 in irradiated human melanoma xenografts. Radiat Res 165(1):16–25CrossRefPubMedGoogle Scholar
  3. 3.
    Kioi M, Vogel H, Schultz G, Hoffman RM, Harsh GR, Brown JM (2010) Inhibition of vasculogenesis, but not angiogenesis, prevents the recurrence of glioblastoma after irradiation in mice. J Clin Invest 120(3):694–705. doi: 10.1172/JCI40283 CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Mantyla MJ, Toivanen JT, Pitkanen MA, Rekonen AH (1982) Radiation-induced changes in regional blood flow in human tumors. Int J Radiat Oncol Biol Phys 8(10):1711–1717CrossRefPubMedGoogle Scholar
  5. 5.
    Pirhonen JP, Grenman SA, Bredbacka AB, Bahado-Singh RO, Salmi TA (1995) Effects of external radiotherapy on uterine blood flow in patients with advanced cervical carcinoma assessed by color Doppler ultrasonography. Cancer 76(1):67–71CrossRefPubMedGoogle Scholar
  6. 6.
    Kocher M, Treuer H, Voges J, Hoevels M, Sturm V, Muller RP (2000) Computer simulation of cytotoxic and vascular effects of radiosurgery in solid and necrotic brain metastases. Radiother Oncol 54(2):149–156CrossRefPubMedGoogle Scholar
  7. 7.
    Kirkpatrick JP, Meyer JJ, Marks LB (2008) The linear-quadratic model is inappropriate to model high dose per fraction effects in radiosurgery. Semin Radiat Oncol 18(4):240–243. doi: 10.1016/j.semradonc.2008.04.005 CrossRefPubMedGoogle Scholar
  8. 8.
    Essig M, Waschkies M, Wenz F, Debus J, Hentrich HR, Knopp MV (2003) Assessment of brain metastases with dynamic susceptibility-weighted contrast-enhanced MR imaging: initial results. Radiology 228(1):193–199. doi: 10.1148/radiol.2281020298 CrossRefPubMedGoogle Scholar
  9. 9.
    Weber MA, Thilmann C, Lichy MP, Gunther M, Delorme S, Zuna I, Bongers A, Schad LR, Debus J, Kauczor HU, Essig M, Schlemmer HP (2004) Assessment of irradiated brain metastases by means of arterial spin-labeling and dynamic susceptibility-weighted contrast-enhanced perfusion MRI: initial results. Invest Radiol 39(5):277–287CrossRefPubMedGoogle Scholar
  10. 10.
    Huang J, Wang AM, Shetty A, Maitz AH, Yan D, Doyle D, Richey K, Park S, Pieper DR, Chen PY, Grills IS (2011) Differentiation between intra-axial metastatic tumor progression and radiation injury following fractionated radiation therapy or stereotactic radiosurgery using MR spectroscopy, perfusion MR imaging or volume progression modeling. Magn Reson Imaging 29(7):993–1001. doi: 10.1016/j.mri.2011.04.004 CrossRefPubMedGoogle Scholar
  11. 11.
    Lin Y, Li J, Zhang Z, Xu Q, Zhou Z, Zhang Z, Zhang Y, Zhang Z (2015) Comparison of intravoxel incoherent motion diffusion-weighted mr imaging and arterial spin labeling MR imaging in gliomas. Biomed Res Int 2015:234245. doi: 10.1155/2015/234245 PubMedPubMedCentralGoogle Scholar
  12. 12.
    Mazhar SM, Shiehmorteza M, Kohl CA, Middleton MS, Sirlin CB (2009) Nephrogenic systemic fibrosis in liver disease: a systematic review. J Magn Reson Imaging 30(6):1313–1322. doi: 10.1002/jmri.21983 CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Le Bihan D (1988) Intravoxel incoherent motion imaging using steady-state free precession. Magn Reson Med 7(3):346–351CrossRefPubMedGoogle Scholar
  14. 14.
    Le Bihan D, Turner R (1992) The capillary network: a link between IVIM and classical perfusion. Magn Reson Med 27(1):171–178CrossRefPubMedGoogle Scholar
  15. 15.
    Federau C, Meuli R, O’Brien K, Maeder P, Hagmann P (2014) Perfusion measurement in brain gliomas with intravoxel incoherent motion MRI. AJNR Am J Neuroradiol 35(2):256–262. doi: 10.3174/ajnr.A3686 CrossRefPubMedGoogle Scholar
  16. 16.
    Bisdas S, Koh TS, Roder C, Braun C, Schittenhelm J, Ernemann U, Klose U (2013) Intravoxel incoherent motion diffusion-weighted MR imaging of gliomas: feasibility of the method and initial results. Neuroradiology 55(10):1189–1196. doi: 10.1007/s00234-013-1229-7 CrossRefPubMedGoogle Scholar
  17. 17.
    Kim HS, Suh CH, Kim N, Choi CG, Kim SJ (2014) Histogram analysis of intravoxel incoherent motion for differentiating recurrent tumor from treatment effect in patients with glioblastoma: initial clinical experience. AJNR Am J Neuroradiol 35(3):490–497. doi: 10.3174/ajnr.A3719 CrossRefPubMedGoogle Scholar
  18. 18.
    Kim DY, Kim HS, Goh MJ, Choi CG, Kim SJ (2014) Utility of intravoxel incoherent motion MR imaging for distinguishing recurrent metastatic tumor from treatment effect following gamma knife radiosurgery: initial experience. AJNR Am J Neuroradiol 35(11):2082–2090. doi: 10.3174/ajnr.A3995 CrossRefPubMedGoogle Scholar
  19. 19.
    Joo I, Lee JM, Grimm R, Han JK, Choi BI (2016) Monitoring vascular disrupting therapy in a rabbit liver tumor model: relationship between tumor perfusion parameters at IVIM diffusion-weighted MR imaging and those at dynamic contrast-enhanced MR imaging. Radiology 278(1):104–113. doi: 10.1148/radiol.2015141974 CrossRefPubMedGoogle Scholar
  20. 20.
    Shaw E, Scott C, Souhami L, Dinapoli R, Kline R, Loeffler J, Farnan N (2000) Single dose radiosurgical treatment of recurrent previously irradiated primary brain tumors and brain metastases: final report of RTOG protocol 90-05. Int J Radiat Oncol Biol Phys 47(2):291–298CrossRefPubMedGoogle Scholar
  21. 21.
    Brenner DJ (2008) The linear-quadratic model is an appropriate methodology for determining isoeffective doses at large doses per fraction. Semin Radiat Oncol 18(4):234–239. doi: 10.1016/j.semradonc.2008.04.004 CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Turner R, Le Bihan D, Maier J, Vavrek R, Hedges LK, Pekar J (1990) Echo-planar imaging of intravoxel incoherent motion. Radiology 177(2):407–414. doi: 10.1148/radiology.177.2.2217777 CrossRefPubMedGoogle Scholar
  23. 23.
    Tofts PS, Brix G, Buckley DL, Evelhoch JL, Henderson E, Knopp MV, Larsson HB, Lee TY, Mayr NA, Parker GJ, Port RE, Taylor J, Weisskoff RM (1999) Estimating kinetic parameters from dynamic contrast-enhanced T(1)-weighted MRI of a diffusable tracer: standardized quantities and symbols. J Magn Reson Imaging 10(3):223–232CrossRefPubMedGoogle Scholar
  24. 24.
    Le Bihan D, Breton E, Lallemand D, Aubin ML, Vignaud J, Laval-Jeantet M (1988) Separation of diffusion and perfusion in intravoxel incoherent motion MR imaging. Radiology 168(2):497–505. doi: 10.1148/radiology.168.2.3393671 CrossRefPubMedGoogle Scholar
  25. 25.
    Le Bihan D, Turner R, MacFall JR (1989) Effects of intravoxel incoherent motions (IVIM) in steady-state free precession (SSFP) imaging: application to molecular diffusion imaging. Magn Reson Med 10(3):324–337CrossRefPubMedGoogle Scholar
  26. 26.
    Pekar J, Moonen CT, van Zijl PC (1992) On the precision of diffusion/perfusion imaging by gradient sensitization. Magn Reson Med 23(1):122–129CrossRefPubMedGoogle Scholar
  27. 27.
    Wirestam R, Borg M, Brockstedt S, Lindgren A, Holtas S, Stahlberg F (2001) Perfusion-related parameters in intravoxel incoherent motion MR imaging compared with CBV and CBF measured by dynamic susceptibility-contrast MR technique. Acta Radiol 42(2):123–128CrossRefPubMedGoogle Scholar
  28. 28.
    Conklin J, Heyn C, Roux M, Cerny M, Wintermark M, Federau C (2016) A simplified model for intravoxel incoherent motion perfusion imaging of the brain. AJNR Am J Neuroradiol. doi: 10.3174/ajnr.A4929 Google Scholar
  29. 29.
    Saad ZS, Glen DR, Chen G, Beauchamp MS, Desai R, Cox RW (2009) A new method for improving functional-to-structural MRI alignment using local Pearson correlation. Neuroimage 44(3):839–848. doi: 10.1016/j.neuroimage.2008.09.037 CrossRefPubMedGoogle Scholar
  30. 30.
    Follwell MJ, Khu KJ, Cheng L, Xu W, Mikulis DJ, Millar BA, Tsao MN, Laperriere NJ, Bernstein M, Sahgal A (2012) Volume specific response criteria for brain metastases following salvage stereotactic radiosurgery and associated predictors of response. Acta Oncol 51(5):629–635. doi: 10.3109/0284186X.2012.681066 CrossRefPubMedGoogle Scholar
  31. 31.
    Lee HJ, Rha SY, Chung YE, Shim HS, Kim YJ, Hur J, Hong YJ, Choi BW (2014) Tumor perfusion-related parameter of diffusion-weighted magnetic resonance imaging: correlation with histological microvessel density. Magn Reson Med 71(4):1554–1558. doi: 10.1002/mrm.24810 CrossRefPubMedGoogle Scholar
  32. 32.
    Hu YC, Yan LF, Wu L, Du P, Chen BY, Wang L, Wang SM, Han Y, Tian Q, Yu Y, Xu TY, Wang W, Cui GB (2014) Intravoxel incoherent motion diffusion-weighted MR imaging of gliomas: efficacy in preoperative grading. Sci Rep 4:7208. doi: 10.1038/srep07208 CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Togao O, Hiwatashi A, Yamashita K, Kikuchi K, Mizoguchi M, Yoshimoto K, Suzuki SO, Iwaki T, Obara M, Van Cauteren M, Honda H (2016) Differentiation of high-grade and low-grade diffuse gliomas by intravoxel incoherent motion MR imaging. Neuro Oncol 18(1):132–141. doi: 10.1093/neuonc/nov147 CrossRefPubMedGoogle Scholar
  34. 34.
    Federau C, Cerny M, Roux M, Mosimann PJ, Maeder P, Meuli R, Wintermark M (2016) IVIM perfusion fraction is prognostic for survival in brain glioma. Clin Neuroradiol. doi: 10.1007/s00062-016-0510-7 PubMedGoogle Scholar
  35. 35.
    Suh CH, Kim HS, Lee SS, Kim N, Yoon HM, Choi CG, Kim SJ (2014) Atypical imaging features of primary central nervous system lymphoma that mimics glioblastoma: utility of intravoxel incoherent motion MR imaging. Radiology 272(2):504–513. doi: 10.1148/radiol.14131895 CrossRefPubMedGoogle Scholar
  36. 36.
    Shim WH, Kim HS, Choi CG, Kim SJ (2015) Comparison of apparent diffusion coefficient and intravoxel incoherent motion for differentiating among glioblastoma, metastasis, and lymphoma focusing on diffusion-related parameter. PLoS ONE 10(7):e0134761. doi: 10.1371/journal.pone.0134761 CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Sourbron SP, Buckley DL (2012) Tracer kinetic modelling in MRI: estimating perfusion and capillary permeability. Phys Med Biol 57(2):R1–R33. doi: 10.1088/0031-9155/57/2/R1 CrossRefPubMedGoogle Scholar
  38. 38.
    Iima M, Reynaud O, Tsurugizawa T, Ciobanu L, Li JR, Geffroy F, Djemai B, Umehana M, Le Bihan D (2014) Characterization of glioma microcirculation and tissue features using intravoxel incoherent motion magnetic resonance imaging in a rat brain model. Invest Radiol 49(7):485–490. doi: 10.1097/RLI.0000000000000040 CrossRefPubMedGoogle Scholar
  39. 39.
    Henkelman RM, Neil JJ, Xiang QS (1994) A quantitative interpretation of IVIM measurements of vascular perfusion in the rat brain. Magn Reson Med 32(4):464–469CrossRefPubMedGoogle Scholar
  40. 40.
    Mardor Y, Pfeffer R, Spiegelmann R, Roth Y, Maier SE, Nissim O, Berger R, Glicksman A, Baram J, Orenstein A, Cohen JS, Tichler T (2003) Early detection of response to radiation therapy in patients with brain malignancies using conventional and high b-value diffusion-weighted magnetic resonance imaging. J Clin Oncol 21(6):1094–1100CrossRefPubMedGoogle Scholar
  41. 41.
    Nougaret S, Vargas HA, Lakhman Y, Sudre R, Do RK, Bibeau F, Azria D, Assenat E, Molinari N, Pierredon MA, Rouanet P, Guiu B (2016) Intravoxel incoherent motion-derived histogram metrics for assessment of response after combined chemotherapy and radiation therapy in rectal cancer: initial experience and comparison between single-section and volumetric analyses. Radiology 280(2):446–454. doi: 10.1148/radiol.2016150702 CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Fujima N, Yoshida D, Sakashita T, Homma A, Tsukahara A, Tha KK, Kudo K, Shirato H (2014) Intravoxel incoherent motion diffusion-weighted imaging in head and neck squamous cell carcinoma: assessment of perfusion-related parameters compared to dynamic contrast-enhanced MRI. Magn Reson Imaging 32(10):1206–1213. doi: 10.1016/j.mri.2014.08.009 CrossRefPubMedGoogle Scholar
  43. 43.
    Bisdas S, Braun C, Skardelly M, Schittenhelm J, Teo TH, Thng CH, Klose U, Koh TS (2014) Correlative assessment of tumor microcirculation using contrast-enhanced perfusion MRI and intravoxel incoherent motion diffusion-weighted MRI: is there a link between them? NMR Biomed 27(10):1184–1191. doi: 10.1002/nbm.3172 CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  1. 1.Department of Medical ImagingSunnybrook Health Sciences Centre and University of TorontoTorontoCanada
  2. 2.Physical SciencesSunnybrook Research InstituteTorontoCanada
  3. 3.Department of Radiation Oncology, Sunnybrook Odette Cancer CenterUniversity of TorontoTorontoCanada

Personalised recommendations