CardioVascular and Interventional Radiology

, Volume 36, Issue 2, pp 292–301 | Cite as

MR-Guided High-Intensity Focused Ultrasound Ablation of Breast Cancer with a Dedicated Breast Platform

  • Laura G. Merckel
  • Lambertus W. Bartels
  • Max O. Köhler
  • H. J. G. Desirée van den Bongard
  • Roel Deckers
  • Willem P. Th. M. Mali
  • Christoph A. Binkert
  • Chrit T. Moonen
  • Kenneth G. A. Gilhuijs
  • Maurice A. A. J. van den BoschEmail author


Optimizing the treatment of breast cancer remains a major topic of interest. In current clinical practice, breast-conserving therapy is the standard of care for patients with localized breast cancer. Technological developments have fueled interest in less invasive breast cancer treatment. Magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) is a completely noninvasive ablation technique. Focused beams of ultrasound are used for ablation of the target lesion without disrupting the skin and subcutaneous tissues in the beam path. MRI is an excellent imaging method for tumor targeting, treatment monitoring, and evaluation of treatment results. The combination of HIFU and MR imaging offers an opportunity for image-guided ablation of breast cancer. Previous studies of MR-HIFU in breast cancer patients reported a limited efficacy, which hampered the clinical translation of this technique. These prior studies were performed without an MR-HIFU system specifically developed for breast cancer treatment. In this article, a novel and dedicated MR-HIFU breast platform is presented. This system has been designed for safe and effective MR-HIFU ablation of breast cancer. Furthermore, both clinical and technical challenges are discussed, which have to be solved before MR-HIFU ablation of breast cancer can be implemented in routine clinical practice.


Breast Interventional oncology High-intensity focused ultrasound Cancer 



This research was supported by the Center for Translational Molecular Medicine (VOLTA, Work Package 3).

Conflict of interest

This research was performed in collaboration with Philips Healthcare. Max O. Köhler is currently employed in this company. The other authors declare that they have no conflict of interest.


  1. 1.
    Punglia RS, Morrow M, Winer EP et al (2007) Local therapy and survival in breast cancer. N Engl J Med 356(23):2399–2405PubMedCrossRefGoogle Scholar
  2. 2.
    Fisher B, Anderson S, Bryant J et al (2002) Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med 347(16):1233–1241PubMedCrossRefGoogle Scholar
  3. 3.
    Litiere S, Werutsky G, Fentiman IS et al (2012) Breast conserving therapy versus mastectomy for stage I-II breast cancer: 20-year follow-up of the EORTC 10801 phase 3 randomised trial. Lancet Oncol 13(4):412–419PubMedCrossRefGoogle Scholar
  4. 4.
    van Dongen JA, Bartelink H, Fentiman IS et al (1992) Factors influencing local relapse and survival and results of salvage treatment after breast-conserving therapy in operable breast cancer: EORTC trial 10801, breast conservation compared with mastectomy in TNM stage I and II breast cancer. Eur J Cancer 28A(4–5):801–805PubMedCrossRefGoogle Scholar
  5. 5.
    Veronesi U, Cascinelli N, Mariani L et al (2002) Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer. N Engl J Med 347(16):1227–1232PubMedCrossRefGoogle Scholar
  6. 6.
    Morin J, Traore A, Dionne G et al (2004) Magnetic resonance-guided percutaneous cryosurgery of breast carcinoma: technique and early clinical results. Can J Surg 47(5):347–351PubMedGoogle Scholar
  7. 7.
    Mumtaz H, Hall-Craggs MA, Wotherspoon A et al (1996) Laser therapy for breast cancer: MR imaging and histopathologic correlation. Radiology 200(3):651–658PubMedGoogle Scholar
  8. 8.
    van den Bosch MA, Daniel B, Rieke V et al (2008) MRI-guided radiofrequency ablation of breast cancer: preliminary clinical experience. J Magn Reson Imaging 27(1):204–208PubMedCrossRefGoogle Scholar
  9. 9.
    Kennedy JE (2005) High-intensity focused ultrasound in the treatment of solid tumours. Nat Rev Cancer 5(4):321–327PubMedCrossRefGoogle Scholar
  10. 10.
    Orsi F, Arnone P, Chen W et al (2010) High intensity focused ultrasound ablation: a new therapeutic option for solid tumors. J Cancer Res Ther 6(4):414–420PubMedCrossRefGoogle Scholar
  11. 11.
    Hynynen K (2010) MRI-guided focused ultrasound treatments. Ultrasonics 50(2):221–229PubMedCrossRefGoogle Scholar
  12. 12.
    LeBlang SD, Hoctor K, Steinberg FL (2010) Leiomyoma shrinkage after MRI-guided focused ultrasound treatment: report of 80 patients. AJR Am J Roentgenol 194(1):274–280PubMedCrossRefGoogle Scholar
  13. 13.
    Stewart EA, Gostout B, Rabinovici J et al (2007) Sustained relief of leiomyoma symptoms by using focused ultrasound surgery. Obstet Gynecol 110(2 Pt 1):279–287PubMedCrossRefGoogle Scholar
  14. 14.
    Gianfelice D, Gupta C, Kucharczyk W et al (2008) Palliative treatment of painful bone metastases with MR imaging–guided focused ultrasound. Radiology 249(1):355–363PubMedCrossRefGoogle Scholar
  15. 15.
    Liberman B, Gianfelice D, Inbar Y et al (2009) Pain palliation in patients with bone metastases using MR-guided focused ultrasound surgery: a multicenter study. Ann Surg Oncol 16(1):140–146PubMedCrossRefGoogle Scholar
  16. 16.
    Wijlemans JW, Bartels LW, Deckers R et al (2012) Magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) ablation of liver tumours. Cancer Imaging 12(2):387–394PubMedCrossRefGoogle Scholar
  17. 17.
    Anderson WF, Jatoi I, Devesa SS (2006) Assessing the impact of screening mammography: breast cancer incidence and mortality rates in Connecticut (1943–2002). Breast Cancer Res Treat 99(3):333–340PubMedCrossRefGoogle Scholar
  18. 18.
    Fracheboud J, Otto SJ, van Dijck JA et al (2004) Decreased rates of advanced breast cancer due to mammography screening in The Netherlands. Br J Cancer 91(5):861–867PubMedGoogle Scholar
  19. 19.
    Weigel S, Batzler WU, Decker T et al (2009) First epidemiological analysis of breast cancer incidence and tumor characteristics after implementation of population-based digital mammography screening. Rofo 181(12):1144–1150PubMedCrossRefGoogle Scholar
  20. 20.
    Landheer ML, Klinkenbijl JH, Pasker-de Jong PC et al (2004) Residual disease after excision of non-palpable breast tumours: analysis of tumour characteristics. Eur J Surg Oncol 30(8):824–828PubMedGoogle Scholar
  21. 21.
    Faverly DR, Hendriks JH, Holland R (2001) Breast carcinomas of limited extent: frequency, radiologic-pathologic characteristics, and surgical margin requirements. Cancer 91(4):647–659PubMedCrossRefGoogle Scholar
  22. 22.
    Rieke V, Butts PK (2008) MR thermometry. J Magn Reson Imaging 27(2):376–390PubMedCrossRefGoogle Scholar
  23. 23.
    Peters NH, Borel RI, Zuithoff NP et al (2008) Meta-analysis of MR imaging in the diagnosis of breast lesions. Radiology 246(1):116–124PubMedCrossRefGoogle Scholar
  24. 24.
    Berg WA, Gutierrez L, NessAiver MS et al (2004) Diagnostic accuracy of mammography, clinical examination, US, and MR imaging in preoperative assessment of breast cancer. Radiology 233(3):830–849PubMedCrossRefGoogle Scholar
  25. 25.
    Boetes C, Mus RD, Holland R et al (1995) Breast tumors: comparative accuracy of MR imaging relative to mammography and US for demonstrating extent. Radiology 197(3):743–747PubMedGoogle Scholar
  26. 26.
    Deurloo EE, Klein Zeggelink WF, Teertstra HJ et al (2006) Contrast-enhanced MRI in breast cancer patients eligible for breast-conserving therapy: complementary value for subgroups of patients. Eur Radiol 16(3):692–701PubMedCrossRefGoogle Scholar
  27. 27.
    Uematsu T, Yuen S, Kasami M et al (2008) Comparison of magnetic resonance imaging, multidetector row computed tomography, ultrasonography, and mammography for tumor extension of breast cancer. Breast Cancer Res Treat 112(3):461–474PubMedCrossRefGoogle Scholar
  28. 28.
    van Goethem M, Schelfout K, Dijckmans L et al (2004) MR mammography in the pre-operative staging of breast cancer in patients with dense breast tissue: comparison with mammography and ultrasound. Eur Radiol 14(5):809–816PubMedCrossRefGoogle Scholar
  29. 29.
    Denis de Senneville B, Quesson B, Moonen CT (2005) Magnetic resonance temperature imaging. Int J Hyperthermia 21(6):515–531PubMedCrossRefGoogle Scholar
  30. 30.
    Quesson B, de Zwart JA, Moonen CT (2000) Magnetic resonance temperature imaging for guidance of thermotherapy. J Magn Reson Imaging 12(4):525–533PubMedCrossRefGoogle Scholar
  31. 31.
    Holland R, Veling SH, Mravunac M et al (1985) Histologic multifocality of Tis, T1–2 breast carcinomas. Implications for clinical trials of breast-conserving surgery. Cancer 56(5):979–990PubMedCrossRefGoogle Scholar
  32. 32.
    Schmitz AC, van den Bosch MA, Loo CE et al (2010) Precise correlation between MRI and histopathology: exploring treatment margins for MRI-guided localized breast cancer therapy. Radiother Oncol 97(2):225–232PubMedCrossRefGoogle Scholar
  33. 33.
    Jolesz FA (2009) MRI-guided focused ultrasound surgery. Annu Rev Med 60:417–430PubMedCrossRefGoogle Scholar
  34. 34.
    Lynn JG, Zwemer RL, Chick AJ et al (1942) A new method for the generation and use of focused ultrasound in experimental biology. J Gen Physiol 26(2):179–193PubMedCrossRefGoogle Scholar
  35. 35.
    Fan X, Hynynen K (1995) Control of the necrosed tissue volume during noninvasive ultrasound surgery using a 16-element phased array. Med Phys 22(3):297–306PubMedCrossRefGoogle Scholar
  36. 36.
    Salomir R, Palussiere J, Vimeux FC et al (2000) Local hyperthermia with MR-guided focused ultrasound: spiral trajectory of the focal point optimized for temperature uniformity in the target region. J Magn Reson Imaging 12(4):571–583PubMedCrossRefGoogle Scholar
  37. 37.
    Köhler MO, Mougenot C, Quesson B et al (2009) Volumetric HIFU ablation under 3D guidance of rapid MRI thermometry. Med Phys 36(8):3521–3535PubMedCrossRefGoogle Scholar
  38. 38.
    Voogt MJ, Trillaud H, Kim YS et al (2012) Volumetric feedback ablation of uterine fibroids using magnetic resonance-guided high intensity focused ultrasound therapy. Eur Radiol 22(2):411–417PubMedCrossRefGoogle Scholar
  39. 39.
    Hynynen K, Darkazanli A, Unger E et al (1993) MRI-guided noninvasive ultrasound surgery. Med Phys 20(1):107–115PubMedCrossRefGoogle Scholar
  40. 40.
    Cline HE, Hynynen K, Watkins RD et al (1995) Focused US system for MR imaging-guided tumor ablation. Radiology 194(3):731–737PubMedGoogle Scholar
  41. 41.
    Vimeux FC, de Zwart JA, Palussiere J et al (1999) Real-time control of focused ultrasound heating based on rapid MR thermometry. Invest Radiol 34(3):190–193PubMedCrossRefGoogle Scholar
  42. 42.
    Diederich CJ, Hynynen K (1999) Ultrasound technology for hyperthermia. Ultrasound Med Biol 25(6):871–887PubMedCrossRefGoogle Scholar
  43. 43.
    Diederich CJ (2005) Thermal ablation and high-temperature thermal therapy: overview of technology and clinical implementation. Int J Hyperthermia 21(8):745–753PubMedCrossRefGoogle Scholar
  44. 44.
    Hynynen K, Pomeroy O, Smith DN et al (2001) MR imaging-guided focused ultrasound surgery of fibroadenomas in the breast: a feasibility study. Radiology 219(1):176–185PubMedGoogle Scholar
  45. 45.
    Huber PE, Jenne JW, Rastert R et al (2001) A new noninvasive approach in breast cancer therapy using magnetic resonance imaging-guided focused ultrasound surgery. Cancer Res 61(23):8441–8447PubMedGoogle Scholar
  46. 46.
    Gianfelice D, Khiat A, Amara M et al (2003) MR imaging-guided focused US ablation of breast cancer: histopathologic assessment of effectiveness—initial experience. Radiology 227(3):849–855PubMedCrossRefGoogle Scholar
  47. 47.
    Furusawa H, Namba K, Thomsen S et al (2006) Magnetic resonance-guided focused ultrasound surgery of breast cancer: reliability and effectiveness. J Am Coll Surg 203(1):54–63PubMedCrossRefGoogle Scholar
  48. 48.
    Furusawa H, Namba K, Nakahara H et al (2007) The evolving non-surgical ablation of breast cancer: MR guided focused ultrasound (MRgFUS). Breast Cancer 14(1):55–58PubMedCrossRefGoogle Scholar
  49. 49.
    Gianfelice D, Khiat A, Amara M et al (2003) MR imaging-guided focused ultrasound surgery of breast cancer: correlation of dynamic contrast-enhanced MRI with histopathologic findings. Breast Cancer Res Treat 82(2):93–101PubMedCrossRefGoogle Scholar
  50. 50.
    Gianfelice D, Khiat A, Boulanger Y et al (2003) Feasibility of magnetic resonance imaging-guided focused ultrasound surgery as an adjunct to tamoxifen therapy in high-risk surgical patients with breast carcinoma. J Vasc Interv Radiol 14(10):1275–1282PubMedCrossRefGoogle Scholar
  51. 51.
    Khiat A, Gianfelice D, Amara M et al (2006) Influence of post-treatment delay on the evaluation of the response to focused ultrasound surgery of breast cancer by dynamic contrast enhanced MRI. Br J Radiol 79(940):308–314PubMedCrossRefGoogle Scholar
  52. 52.
    Zippel DB, Papa MZ (2005) The use of MR imaging guided focused ultrasound in breast cancer patients; a preliminary phase one study and review. Breast Cancer 12(1):32–38PubMedCrossRefGoogle Scholar
  53. 53.
    Moonen CT, Mougenot C (2006) MRI-guided focused ultrasound, apparatus for novel treatment of breast cancer, vol 6. Springer, Philips Research Book Series, New York, pp 183–200Google Scholar
  54. 54.
    Payne A, Merrill R, Minalga E et al (2012) Design and characterization of a laterally mounted phased-array transducer breast-specific MRgHIFU device with integrated 11-channel receiver array. Med Phys 39(3):1552–1560PubMedCrossRefGoogle Scholar
  55. 55.
    Mougenot C, Köhler M, Tillander M, Moonen C, Bartels W, Ehnholm GJ (2011) Large aperture transducer designed for MR-HIFU treatment of breast tumors. Paper presented at the ISMRM 2011 in the session Interventional MRI: MR-Guided Focused UltrasoundGoogle Scholar
  56. 56.
    Mougenot C, Tillander M, Koskela J et al (2012) High intensity focused ultrasound with large aperture transducers: a MRI based focal point correction for tissue heterogeneity. Med Phys 39(4):1936–1945PubMedCrossRefGoogle Scholar
  57. 57.
    Sprinkhuizen SM, Konings MK, van der Bom MJ et al (2010) Temperature-induced tissue susceptibility changes lead to significant temperature errors in PRFS-based MR thermometry during thermal interventions. Magn Reson Med 64(5):1360–1372PubMedCrossRefGoogle Scholar
  58. 58.
    Sprinkhuizen SM, Bakker CJ, Ippel JH et al (2011) Temperature dependence of the magnetic volume susceptibility of human breast fat tissue: an NMR study. MAGMA 25(1):33–39PubMedCrossRefGoogle Scholar
  59. 59.
    Peters NH, Bartels LW, Sprinkhuizen SM et al (2009) Do respiration and cardiac motion induce magnetic field fluctuations in the breast and are there implications for MR thermometry? J Magn Reson Imaging 29(3):731–735PubMedCrossRefGoogle Scholar
  60. 60.
    Hey S, Maclair G, de Senneville BD et al (2009) Online correction of respiratory-induced field disturbances for continuous MR-thermometry in the breast. Magn Reson Med 61(6):1494–1499PubMedCrossRefGoogle Scholar
  61. 61.
    Arnedos M, Nerurkar A, Osin P et al (2009) Discordance between core needle biopsy (CNB) and excisional biopsy (EB) for estrogen receptor (ER), progesterone receptor (PgR) and HER2 status in early breast cancer (EBC). Ann Oncol 20(12):1948–1952PubMedCrossRefGoogle Scholar
  62. 62.
    Tamaki K, Sasano H, Ishida T et al (2010) Comparison of core needle biopsy (CNB) and surgical specimens for accurate preoperative evaluation of ER, PgR and HER2 status of breast cancer patients. Cancer Sci 101(9):2074–2079PubMedCrossRefGoogle Scholar
  63. 63.
    Darby S, McGale P, Correa C et al (2011) Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10,801 women in 17 randomised trials. Lancet 378(9804):1707–1716PubMedCrossRefGoogle Scholar
  64. 64.
    Hurkmans CW, Borger JH, Pieters BR et al (2001) Variability in target volume delineation on CT scans of the breast. Int J Radiat Oncol Biol Phys 50(5):1366–1372PubMedCrossRefGoogle Scholar
  65. 65.
    Landis DM, Luo W, Song J et al (2007) Variability among breast radiation oncologists in delineation of the postsurgical lumpectomy cavity. Int J Radiat Oncol Biol Phys 67(5):1299–1308PubMedCrossRefGoogle Scholar
  66. 66.
    Struikmans H, Warlam-Rodenhuis C, Stam T et al (2005) Interobserver variability of clinical target volume delineation of glandular breast tissue and of boost volume in tangential breast irradiation. Radiother Oncol 76(3):293–299PubMedCrossRefGoogle Scholar
  67. 67.
    van Mourik AM, Elkhuizen PH, Minkema D et al (2010) Multi-institutional study on target volume delineation variation in breast radiotherapy in the presence of guidelines. Radiother Oncol 94(3):286–291PubMedCrossRefGoogle Scholar
  68. 68.
    Borger JH, Kemperman H, Smitt HS et al (1994) Dose and volume effects on fibrosis after breast conservation therapy. Int J Radiat Oncol Biol Phys 30(5):1073–1081PubMedCrossRefGoogle Scholar
  69. 69.
    den Hartogh MD, van AB, Monninkhof EM (2011) Excised and irradiated volumes in relation to the tumor size in breast-conserving therapy. Breast Cancer Res Treat 129(3):857–865PubMedCrossRefGoogle Scholar
  70. 70.
    Lagendijk JJ, Raaymakers BW, Raaijmakers AJ et al (2008) MRI/linac integration. Radiother Oncol 86(1):25–29PubMedCrossRefGoogle Scholar
  71. 71.
    Raaymakers BW, Lagendijk JJ, Overweg J et al (2009) Integrating a 1.5 T MRI scanner with a 6 MV accelerator: proof of concept. Phys Med Biol 54(12):N229–N237PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) 2012

Authors and Affiliations

  • Laura G. Merckel
    • 1
  • Lambertus W. Bartels
    • 2
  • Max O. Köhler
    • 3
  • H. J. G. Desirée van den Bongard
    • 4
  • Roel Deckers
    • 2
  • Willem P. Th. M. Mali
    • 1
  • Christoph A. Binkert
    • 5
  • Chrit T. Moonen
    • 2
  • Kenneth G. A. Gilhuijs
    • 1
    • 2
  • Maurice A. A. J. van den Bosch
    • 1
    Email author
  1. 1.Department of RadiologyUniversity Medical Center UtrechtCX UtrechtThe Netherlands
  2. 2.Image Sciences InstituteUniversity Medical Center UtrechtUtrechtThe Netherlands
  3. 3.Philips HealthcareVantaaFinland
  4. 4.Department of RadiotherapyUniversity Medical Center UtrechtUtrechtThe Netherlands
  5. 5.Department of RadiologyCantonal Hospital WinterthurWinterthurSwitzerland

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