A phase-cycled temperature-sensitive fast spin echo sequence with conductivity bias correction for monitoring of mild RF hyperthermia with PRFS

  • Mingming WuEmail author
  • Hendrik T. Mulder
  • Yuval Zur
  • Silke Lechner-Greite
  • Marion I. Menzel
  • Margarethus M. Paulides
  • Gerard C. van Rhoon
  • Axel Haase
Research Article



Mild hyperthermia (HT) treatments are generally monitored by phase-referenced proton resonance frequency shift calculations. A novel phase and thus temperature-sensitive fast spin echo (TFSE) sequence is introduced and compared to the double echo gradient echo (DEGRE) sequence.

Theory and methods

For a proton resonance frequency shift (PRFS)-sensitive TFSE sequence, a phase cycling method is applied to separate even from odd echoes. This method compensates for conductivity change-induced bias in temperature mapping as does the DEGRE sequence. Both sequences were alternately applied during a phantom heating experiment using the clinical setup for deep radio frequency HT (RF-HT). The B0 drift-corrected temperature values in a region of interest around temperature probes are compared to the temperature probe data and further evaluated in Bland–Altman plots. The stability of both methods was also tested within the thighs of three volunteers at a constant temperature using the subcutaneous fat layer for B0-drift correction.


During the phantom heating experiment, on average TFSE temperature maps achieved double temperature-to-noise ratio (TNR) efficiency in comparison with DEGRE temperature maps. In-vivo images of the thighs exhibit stable temperature readings of ± 1 °C over 25 min of scanning in three volunteers for both methods. On average, the TNR efficiency improved by around 25% for in vivo data.


A novel TFSE method has been adapted to monitor temperature during mild HT.


MR thermometry Hyperthermia Proton resonance frequency shift Fast spin echo Double echo gradient echo Intervention Conductivity 



This project was funded by the European Commission under Grant Agreement Number 605162. Research support was received from GE Global Research. The authors would like to thank Abdelali Ameziane for technical support and Fatih Süleyman Hafalir for helpful discussions.

Author’s contribution

Wu, Mulder, Zur and Menzel contributed to the design of the study. Conceptual work on the method was performed by Zur and Wu. Wu and Mulder performed the measurements and acquired the data. The analysis and interpretation of data was done by Wu and Zur. Wu drafted the manuscript. Mulder, Zur, Lechner-Greite, Menzel, Paulides, van Rhoon and Haase were involved in critical revision of the manuscript.

Compliance with ethical standards

Conflict of interest

Yual Zur, Silke Lechner-Greite, and Marion Menzel were employed with GE Healthcare during the generation of the presented work. The remaining authors have no conflict of interest to declare.

Ethical standards

For the in vivo feasibility study, three healthy subjects were scanned with approval by the Erasmus Medical Center Ethics Review Board (METC 2005-340).

Informed consent

Informed written consent was obtained from each volunteer prior to the study.


  1. 1.
    Kampinga HH (2006) Cell biological effects of hyperthermia alone or combined with radiation or drugs: a short introduction to newcomers in the field. Int J Hyperth 22(3):pp. 191–196CrossRefGoogle Scholar
  2. 2.
    Wust P, Gellermann J, Harder C, Tilly W, Rau B, Dinges S, Schlag P, Budach V, Felix R (1998) Rationale for using invasive thermometry for regional hyperthermia of pelvic tumors. Int J Radiat Oncol Biol Phys 41(5):pp. 1129–1137CrossRefGoogle Scholar
  3. 3.
    van der Zee J, Peer-Valstar JN, Rietveld PJ, de Graaf-Strukowska L, van Rhoon GC (1998) Practical limitations of interstitial thermometry during deep hyperthermia. Int J Radiat Oncol Biol Phys 40(5):pp. 1205–1212Google Scholar
  4. 4.
    Gellermann J, Wlodarczyk W, Ganter H, Nadobny J, Fähling H, Seebass M, Felix R, Wust P (2005) A practical approach to thermography in a hyperthermia/magnetic resonance hybrid system: validation in a heterogeneous phantom. Int J Radiat Oncol Biol Phys 61(1):pp. 267–277CrossRefGoogle Scholar
  5. 5.
    McDannold N (2005) Quantitative MRI-based temperature mapping based on the proton resonant frequency shift: review of validation studies. Int J Hyperth 21(6):pp. 533–546CrossRefGoogle Scholar
  6. 6.
    Ishihara Y, Calderon A, Watanabe H, Okamoto K, Suzuki Y, Kuroda K, Suzuki Y (1995) A precise and fast temperature mapping using water proton chemical shift. Magn Reson Med 34(6):pp. 814–823CrossRefGoogle Scholar
  7. 7.
    Gellermann J, Wlodarczyk W, Hildebrandt B, Ganter H, Nicolau A, Rau B, Tilly W, Fähling H, Nadobny J, Felix R, Wust P (2005) Noninvasive magnetic resonance thermography of recurrent rectal carcinoma in a 1.5 tesla hybrid system. Cancer Res 65(13):pp. 5872–5880CrossRefGoogle Scholar
  8. 8.
    Gellermann J, Hildebrandt B, Issels R, Ganter H, Wlodarczyk W, Budach V, Felix R, Tunn PU, Reichardt P, Wust P (2006) Noninvasive magnetic resonance thermography of soft tissue sarcomas during regional hyperthermia. Cancer 107(6):pp. 1373–1382CrossRefGoogle Scholar
  9. 9.
    Peters RD, Henkelman RM (2000) Proton-resonance frequency shift MR thermometry is affected by changes in the electrical conductivity of tissue. Magn Reson Med 43(1):pp. 62–71Google Scholar
  10. 10.
    Paulides MM, Curto S, Wu M, Winter L, van Rhoon GC, Yeo DTB (2017) Advances in magnetic resonance guided radiofrequency hyperthermia. In: 11th European Conference on Antennas and Propagation, Paris, pp. 3692–3696.
  11. 11.
    Vlaardingerbroek MT, Boer JA (2003) Magnetic resonance imaging. Springer, Berlin. Google Scholar
  12. 12.
    Edelstein WA, Glover GH, Hardy CJ, Redington RW (1986) The intrinsic signal-to-noise ratio in NMR imaging. Magn Reson Med 3(4):pp. 604–618CrossRefGoogle Scholar
  13. 13.
    Ronnau J, Haimov S, Gogineni S (1994) The effect of signal-to-noise ratio on phase measurements with polarimetric radars. Remote Sens Rev 9(1–2):pp. 27–37Google Scholar
  14. 14.
    Winter L, Oberacker E, Paul K, Ji Y, Oezerdem C, Ghadjar P, Thieme A, Budach V, Wust P, Niendorf T (2016) Magnetic resonance thermometry: methodology, pitfalls and practical solutions. Int J Hyperth 32(1):63–75CrossRefGoogle Scholar
  15. 15.
    Zur Y (2015) A new time shifted fast spin echo thermometry sequence. In: Proceedings of the 23rd scientific meeting, International Society for Magnetic Resonance in Medicine, Toronto, p 4054Google Scholar
  16. 16.
    Vogel MW, Pattynama PM, Lethimonnier FL, Le Roux P (2003) Use of fast spin echo for phase shift magnetic resonance thermometry. J Magn Reson Imaging 18(4):507–512CrossRefGoogle Scholar
  17. 17.
    Splice Schick F (1997) Sub-second diffusion-sensitive MR imaging using a modified fast spin-echo acquisition mode. Magn Reson Med 38(4):pp. 638–644Google Scholar
  18. 18.
    Paysen H, Paul K, Pham M, Winter L, Niendorf T (2017) Toward hybrid MR thermometry in aqueous and adipose tissue using simultaneous dual contrast weighting with double echo rare imaging. In: Proceedings of the 25th scientific meeting, International Society for Magnetic Resonance in Medicine, Honolulu, p 1181Google Scholar
  19. 19.
    Norris DG (2007) Selective parity rare imaging. Magn Reson Med 58(4):643–649CrossRefGoogle Scholar
  20. 20.
    Zur Y, Stokar S (1987) A phase-cycling technique for canceling spurious echoes in NMR imaging. J Magn Reson 71(2):212–228. Google Scholar
  21. 21.
    Carr HY, Purcell EM (1954) Effects of diffusion on free precession in nuclear magnetic resonance experiments. Phys Rev 94(3):630–638CrossRefGoogle Scholar
  22. 22.
    Meiboom S, Gill D (1958) Modified spin-echo method for measuring nuclear relaxation times. Rev Sci Instrum 29(8):688–691CrossRefGoogle Scholar
  23. 23.
    Norris DG, Bornert P (1993) Coherence and interference in ultrafast RARE experiments. J Magn Reson A 105(2):123–127CrossRefGoogle Scholar
  24. 24.
    Zur Y, Chen W (2014) A technique to eliminate artifacts in 3D fast spin echo imaging. In: Proceedings of the 22nd scientific meeting, International Society for Magnetic Resonance in Medicine, Milan, p 1648Google Scholar
  25. 25.
    Zur Y (2017) Analysis of the multi-echo spin-echo pulse sequence. Concepts Magn Reson A 46A:e21402. CrossRefGoogle Scholar
  26. 26.
    Zur Y (2016) Improved thermometry based on a fast spin echo sequence. In: Proceedings of the 24th scientific meeting, International Society for Magnetic Resonance in Medicine, Singapore, p 3598Google Scholar
  27. 27.
    El-Sharkawy AM, Schär M, Bottomley PA, Atalar E (2006) Monitoring and correcting spatio-temporal variations of the MR scanner’s static magnetic field. Magn Reson Mater Phy 19(5):223–236CrossRefGoogle Scholar
  28. 28.
    Bing C, Staruch RM, Tillander M, Köhler MO, Mougenot C, Ylihautala M, Laetsch TW, Chopra R (2016) Drift correction for accurate PRF-shift MR thermometry during mild hyperthermia treatments with MR-HIFU. Int J Hyperth 32(6):pp. 673–687CrossRefGoogle Scholar
  29. 29.
    Hofstetter LW, Yeo DT, Dixon WT, Kempf JG, Davis CE, Foo TK (2012) Fat-referenced MR thermometry in the breast and prostate using IDEAL. J Magn Reson Imaging 36(3):722–732CrossRefGoogle Scholar
  30. 30.
    Bowman RR (1976) A probe for measuring temperature in radio-frequency-heated material. IEEE Trans Microw Theory Tech 24(1):43–45CrossRefGoogle Scholar
  31. 31.
    Busse RF, Brau AC, Vu A, Michelich CR, Bayram E, Kijowski R, Reeder SB, Rowley HA (2008) Effects of refocusing flip angle modulation and view ordering in 3D fast spin echo. Magn Reson Med 60(3):640–649CrossRefGoogle Scholar
  32. 32.
    Craciunescu OI, Stauffer PR, Soher BJ, Wyatt CR, Arabe O, Maccarini R, Das SK, Cheng KS, Wong TZ, Jones EL, Dewhirst MW, Vujaskovic Z, MacFall JR (2009) Accuracy of real time noninvasive temperature measurements using magnetic resonance thermal imaging in patients treated for high grade extremity soft tissue sarcomas. Med Phys 36(11):4848–4858CrossRefGoogle Scholar
  33. 33.
    Simonis FFJ, Petersen ET, Lagendijk JJW, van den Berg CAT (2016) Feasibility of measuring thermoregulation during RF heating of the human calf muscle using MR based methods. Magn Reson Med 75:1743–1751CrossRefGoogle Scholar
  34. 34.
    Simonis FFJ, Raajimakers AJE, Lagendijk JJW, van den Berg CAT (2017) Validating subject-specific RF and thermal simulations in the calf muscle using MR-based temperature measurements. Magn Reson Med 77:1691–1700CrossRefGoogle Scholar
  35. 35.
    Dadakova T, Gellermann J, Voigt O, Korvink JG, Pavlina JM, Hennig J, Bock M (2015) Fast PRF-based MR thermometry using double-echo EPI: in vivo comparison in a clinical hyperthermia setting. Magn Reson Mater Phy 28:305–314CrossRefGoogle Scholar
  36. 36.
    Marx M, Butts Pauly K (2016) Improved MRI thermometry with multiple-echo spirals. Magn Reson Med 76:747–756. CrossRefGoogle Scholar
  37. 37.
    Yuan J, Mei CS, Panych LP, McDannold NJ, Madore B (2012) Towards fast and accurate temperature mapping with proton resonance frequency-based MR thermometry. Quant Imaging Med Surg 2(1):21Google Scholar
  38. 38.
    Gellermann J, Faehling H, Mielec M, Cho CH, Budach V, Wust P (2008) Image artifacts during MRT hybrid hyperthermia—causes and elimination. Int J Hyperthermia 24(4):327–335CrossRefGoogle Scholar

Copyright information

© European Society for Magnetic Resonance in Medicine and Biology (ESMRMB) 2018

Authors and Affiliations

  1. 1.Munich School of BioengineeringTechnical University of MunichGarching bei MünchenGermany
  2. 2.Erasmus MC Cancer InstituteRotterdamThe Netherlands
  3. 3.GE HealthcareHaifaIsrael
  4. 4.GE HealthcareMunichGermany

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