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Published in: Breast Cancer Research 1/2018

Open Access 01-12-2018 | Research article

Amide chemical exchange saturation transfer at 7 T: a possible biomarker for detecting early response to neoadjuvant chemotherapy in breast cancer patients

Authors: Erwin Krikken, Vitaliy Khlebnikov, Moritz Zaiss, Rajni A. Jibodh, Paul J. van Diest, Peter R. Luijten, Dennis W. J. Klomp, Hanneke W. M. van Laarhoven, Jannie P. Wijnen

Published in: Breast Cancer Research | Issue 1/2018

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Abstract

Background

The purpose of this work was to investigate noninvasive early detection of treatment response of breast cancer patients to neoadjuvant chemotherapy (NAC) using chemical exchange saturation transfer (CEST) measurements sensitive to amide proton transfer (APT) at 7 T.

Methods

CEST images were acquired in 10 tumors of nine breast cancer patients treated with NAC. APT signals in the tumor, before and after the first cycle of NAC, were quantified using a three-pool Lorentzian fit of the z-spectra in the region of interest. The changes in APT were subsequently related to pathological response after surgery defined by the Miller-Payne system.

Results

Significant differences (P <  0.05, unpaired Mann-Whitney test) were found in the APT signal before and after the first cycle of NAC in six out of 10 lesions, of which two showed a pathological complete response. Of the remaining four lesions, one showed a pathological complete response. No significant difference in changes of APT signal were found between the different pathological responses to NAC treatment (P > 0.05, Kruskal-Wallis test).

Conclusions

This preliminary study shows the feasibility of using APT CEST magnetic resonance imaging as a noninvasive biomarker to assess the effect of NAC in an early stage of NAC treatment of breast cancer patients.

Trial registration

Registration number, NL49333.041.14/NTR4980. Registered on 16 October 2014.
Literature
1.
go back to reference Loibl S, Von Minckwitz G, Blohmer J, et al. Surgical procedures after neoadjuvant chemotherapy in operable breast cancer: results of the GEPARDUO trial. Ann Surg Oncol. 2006;13(11):1434–42.CrossRefPubMed Loibl S, Von Minckwitz G, Blohmer J, et al. Surgical procedures after neoadjuvant chemotherapy in operable breast cancer: results of the GEPARDUO trial. Ann Surg Oncol. 2006;13(11):1434–42.CrossRefPubMed
2.
go back to reference Kaufmann M, Hortobagyi GN, Goldhirsch A, et al. Recommendations from an international expert panel on the use of neoadjuvant (primary) systemic treatment of operable breast cancer: an update. J Clin Oncol. 2006;24(12):1940–9.CrossRefPubMed Kaufmann M, Hortobagyi GN, Goldhirsch A, et al. Recommendations from an international expert panel on the use of neoadjuvant (primary) systemic treatment of operable breast cancer: an update. J Clin Oncol. 2006;24(12):1940–9.CrossRefPubMed
3.
go back to reference Kaufmann M, Von Minckwitz G, Bear HD, et al. Recommendations from an international expert panel on the use of neoadjuvant (primary) systemic treatment of operable breast cancer: new perspectives 2006. Ann Oncol. 2007;18(11):1927–34.CrossRefPubMed Kaufmann M, Von Minckwitz G, Bear HD, et al. Recommendations from an international expert panel on the use of neoadjuvant (primary) systemic treatment of operable breast cancer: new perspectives 2006. Ann Oncol. 2007;18(11):1927–34.CrossRefPubMed
4.
go back to reference Kaufmann M, Von Minckwitz G, Mamounas EP, et al. Recommendations from an international consensus conference on the current status and future of neoadjuvant systemic therapy in primary breast cancer. Ann Surg Oncol. 2011;19:1508–16.CrossRefPubMed Kaufmann M, Von Minckwitz G, Mamounas EP, et al. Recommendations from an international consensus conference on the current status and future of neoadjuvant systemic therapy in primary breast cancer. Ann Surg Oncol. 2011;19:1508–16.CrossRefPubMed
5.
go back to reference Fisher B, Brown A, Mamounas E, et al. Effect of preoperative chemotherapy on local-regional disease in women with operable breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-18. J Clin Oncol. 1997;15(7):2483–93.CrossRefPubMed Fisher B, Brown A, Mamounas E, et al. Effect of preoperative chemotherapy on local-regional disease in women with operable breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-18. J Clin Oncol. 1997;15(7):2483–93.CrossRefPubMed
6.
go back to reference Bonadonna G, Valagussa P, Zucali R, Salvadori B. Primary chemotherapy in surgically resectable breast cancer. CA Cancer J Clin. 1995;45(4):227–43.CrossRefPubMed Bonadonna G, Valagussa P, Zucali R, Salvadori B. Primary chemotherapy in surgically resectable breast cancer. CA Cancer J Clin. 1995;45(4):227–43.CrossRefPubMed
7.
go back to reference Tudorica A, Oh KY, Chui SYC, et al. Early prediction and evaluation of breast cancer response to neoadjuvant chemotherapy using quantitative DCE-MRI. Transl Oncol. 2016;9(1):8–17.CrossRefPubMedPubMedCentral Tudorica A, Oh KY, Chui SYC, et al. Early prediction and evaluation of breast cancer response to neoadjuvant chemotherapy using quantitative DCE-MRI. Transl Oncol. 2016;9(1):8–17.CrossRefPubMedPubMedCentral
8.
go back to reference Harry VN, Semple SI, Parkin DE, Gilbert FJ. Use of new imaging techniques to predict tumour response to therapy. Lancet Oncol. 2010;11(1):92–102.CrossRefPubMed Harry VN, Semple SI, Parkin DE, Gilbert FJ. Use of new imaging techniques to predict tumour response to therapy. Lancet Oncol. 2010;11(1):92–102.CrossRefPubMed
9.
go back to reference Padhani AR, Miles KA. Multiparametric imaging of tumor response to therapy. Radiology. 2010;256(2):348–64.CrossRefPubMed Padhani AR, Miles KA. Multiparametric imaging of tumor response to therapy. Radiology. 2010;256(2):348–64.CrossRefPubMed
10.
go back to reference Wolff SD, Balaban RS. NMR imaging of labile proton exchange. J Magn Reson. 1990;86(1):164–9. Wolff SD, Balaban RS. NMR imaging of labile proton exchange. J Magn Reson. 1990;86(1):164–9.
11.
go back to reference Van Zijl PCM, Zhou J, Mori N, Payen JF, Wilson D, Mori S. Mechanism of magnetization transfer during on-resonance water saturation. A new approach to detect mobile proteins, peptides, and lipids. Magn Reson Med. 2003;49(3):440–9.CrossRefPubMed Van Zijl PCM, Zhou J, Mori N, Payen JF, Wilson D, Mori S. Mechanism of magnetization transfer during on-resonance water saturation. A new approach to detect mobile proteins, peptides, and lipids. Magn Reson Med. 2003;49(3):440–9.CrossRefPubMed
12.
go back to reference Zhou JY, Lal B, Wilson DA, Laterra J, van Zijl PCM. Amide proton transfer (APT) contrast for imaging of brain tumors. Magn Reson Med. 2003;50(6):1120–6.CrossRefPubMed Zhou JY, Lal B, Wilson DA, Laterra J, van Zijl PCM. Amide proton transfer (APT) contrast for imaging of brain tumors. Magn Reson Med. 2003;50(6):1120–6.CrossRefPubMed
13.
go back to reference Dula AN, Arlinghaus LR, Dortch RD, et al. Amide proton transfer imaging of the breast at 3 T: establishing reproducibility and possible feasibility assessing chemotherapy response. Magn Reson Med. 2013;70:216–24.CrossRefPubMed Dula AN, Arlinghaus LR, Dortch RD, et al. Amide proton transfer imaging of the breast at 3 T: establishing reproducibility and possible feasibility assessing chemotherapy response. Magn Reson Med. 2013;70:216–24.CrossRefPubMed
14.
go back to reference Klomp DWJ, Dula AN, Arlinghaus LR, et al. Amide proton transfer imaging of the human breast at 7T: development and reproducibility. NMR Biomed. 2013;26(10):1271–7.CrossRefPubMedPubMedCentral Klomp DWJ, Dula AN, Arlinghaus LR, et al. Amide proton transfer imaging of the human breast at 7T: development and reproducibility. NMR Biomed. 2013;26(10):1271–7.CrossRefPubMedPubMedCentral
15.
go back to reference Zaiss M, Windschuh J, Paech D, et al. Relaxation-compensated CEST-MRI of the human brain at 7T: unbiased insight into NOE and amide signal changes in human glioblastoma. Neuroimage. 2015;112:180–8.CrossRefPubMed Zaiss M, Windschuh J, Paech D, et al. Relaxation-compensated CEST-MRI of the human brain at 7T: unbiased insight into NOE and amide signal changes in human glioblastoma. Neuroimage. 2015;112:180–8.CrossRefPubMed
16.
go back to reference Zaiss M, Xu J, Goerke S, et al. Inverse Z-spectrum analysis for spillover-, MT-, and T1-corrected steady-state pulsed CEST-MRI—application to pH-weighted MRI of acute stroke. NMR Biomed. 2014;27(3):240–52.CrossRefPubMedPubMedCentral Zaiss M, Xu J, Goerke S, et al. Inverse Z-spectrum analysis for spillover-, MT-, and T1-corrected steady-state pulsed CEST-MRI—application to pH-weighted MRI of acute stroke. NMR Biomed. 2014;27(3):240–52.CrossRefPubMedPubMedCentral
17.
go back to reference Khlebnikov V, Polders D, Hendrikse J, et al. Amide proton transfer (APT) imaging of brain tumors at 7 T : the role of tissue water T1-relaxation properties. Magn Reson Imaging. 2017;77:1525–32. Khlebnikov V, Polders D, Hendrikse J, et al. Amide proton transfer (APT) imaging of brain tumors at 7 T : the role of tissue water T1-relaxation properties. Magn Reson Imaging. 2017;77:1525–32.
18.
go back to reference Khlebnikov V, Siero JCW, Wijnen J, et al. Is there any difference in amide and NOE CEST effects between white and gray matter at 7 T? J Magn Reson. 2016;272:82–6.CrossRefPubMed Khlebnikov V, Siero JCW, Wijnen J, et al. Is there any difference in amide and NOE CEST effects between white and gray matter at 7 T? J Magn Reson. 2016;272:82–6.CrossRefPubMed
19.
go back to reference Dula AN, Dewey BE, Arlinghaus LR, et al. Optimization of 7-T chemical exchange saturation transfer parameters for validation of glycosaminoglycan and amide proton transfer of fibroglandular breast tissue. Radiology. 2014;275(1):255–61.CrossRefPubMedPubMedCentral Dula AN, Dewey BE, Arlinghaus LR, et al. Optimization of 7-T chemical exchange saturation transfer parameters for validation of glycosaminoglycan and amide proton transfer of fibroglandular breast tissue. Radiology. 2014;275(1):255–61.CrossRefPubMedPubMedCentral
20.
go back to reference Van Der Velden TA, Italiaander M, Der Kemp WJM V, et al. Radiofrequency configuration to facilitate bilateral breast 31P MR spectroscopic imaging and high-resolution MRI at 7 Tesla. Magn Reson Med. 2015;74(6):1803–10.CrossRefPubMed Van Der Velden TA, Italiaander M, Der Kemp WJM V, et al. Radiofrequency configuration to facilitate bilateral breast 31P MR spectroscopic imaging and high-resolution MRI at 7 Tesla. Magn Reson Med. 2015;74(6):1803–10.CrossRefPubMed
21.
go back to reference Klomp DWJ, van der Kemp WJM, Korteweg M, Wijnen JP, Van De Bosch M, Luijten PR. P MRS at 7T can be more sensitive and specific than 1 H MRS in monitoring breast cancer treatment. Proc Intl Soc Mag Reson Med. 2011;19:343. Klomp DWJ, van der Kemp WJM, Korteweg M, Wijnen JP, Van De Bosch M, Luijten PR. P MRS at 7T can be more sensitive and specific than 1 H MRS in monitoring breast cancer treatment. Proc Intl Soc Mag Reson Med. 2011;19:343.
22.
go back to reference Hancu I, Govenkar A, Lenkinski RE, Lee SK. On shimming approaches in 3T breast MRI. Magn Reson Med. 2013;69(3):862–7.CrossRefPubMed Hancu I, Govenkar A, Lenkinski RE, Lee SK. On shimming approaches in 3T breast MRI. Magn Reson Med. 2013;69(3):862–7.CrossRefPubMed
23.
go back to reference Khlebnikov V, Geades N, Klomp DWJ, Hoogduin H, Gowland P, Mougin O. Comparison of pulsed three-dimensional CEST acquisition schemes at 7 Tesla: steady state versus pseudosteady state. Magn Reson Med. 2017;77:2280–7.CrossRefPubMed Khlebnikov V, Geades N, Klomp DWJ, Hoogduin H, Gowland P, Mougin O. Comparison of pulsed three-dimensional CEST acquisition schemes at 7 Tesla: steady state versus pseudosteady state. Magn Reson Med. 2017;77:2280–7.CrossRefPubMed
24.
go back to reference Kim M, Gillen J, Landman BA, Zhou J, Van Zijl PCM. Water saturation shift referencing (WASSR) for chemical exchange saturation transfer (CEST) experiments. Magn Reson Med. 2009;61(6):1441–50.CrossRefPubMedPubMedCentral Kim M, Gillen J, Landman BA, Zhou J, Van Zijl PCM. Water saturation shift referencing (WASSR) for chemical exchange saturation transfer (CEST) experiments. Magn Reson Med. 2009;61(6):1441–50.CrossRefPubMedPubMedCentral
25.
go back to reference Windschuh J, Zaiss M, Meissner J, et al. Correction of B1-inhomogeneities for relaxation-compensated CEST imaging at 7T. NMR Biomed. 2015;28:529–37.CrossRefPubMed Windschuh J, Zaiss M, Meissner J, et al. Correction of B1-inhomogeneities for relaxation-compensated CEST imaging at 7T. NMR Biomed. 2015;28:529–37.CrossRefPubMed
26.
go back to reference Ogston KN, Miller ID, Payne S, et al. A new histological grading system to assess response of breast cancers to primary chemotherapy: prognostic significance and survival. Breast. 2003;12:320–7.CrossRefPubMed Ogston KN, Miller ID, Payne S, et al. A new histological grading system to assess response of breast cancers to primary chemotherapy: prognostic significance and survival. Breast. 2003;12:320–7.CrossRefPubMed
27.
go back to reference Salhotra A, Lal B, Laterra J, Sun PZ, van Zijl PCM, Zhou J. Amide proton transfer imaging of 9L gliosarcoma and human glioblastoma xenografts. NMR Biomed. 2008;21:489–97.CrossRefPubMedPubMedCentral Salhotra A, Lal B, Laterra J, Sun PZ, van Zijl PCM, Zhou J. Amide proton transfer imaging of 9L gliosarcoma and human glioblastoma xenografts. NMR Biomed. 2008;21:489–97.CrossRefPubMedPubMedCentral
28.
29.
go back to reference Zhou J, Blakeley JO, Hua J, et al. Practical data acquisition method for human brain tumor amide proton transfer (APT) imaging. Magn Reson Med. 2008;60(4):842–9.CrossRefPubMedPubMedCentral Zhou J, Blakeley JO, Hua J, et al. Practical data acquisition method for human brain tumor amide proton transfer (APT) imaging. Magn Reson Med. 2008;60(4):842–9.CrossRefPubMedPubMedCentral
30.
go back to reference Zhou J, Tryggestad E, Wen Z, et al. Differentiation between glioma and radiation necrosis using molecular magnetic resonance imaging of endogenous proteins and peptides. Nat Med Nature. 2011;17(1):130–4.CrossRef Zhou J, Tryggestad E, Wen Z, et al. Differentiation between glioma and radiation necrosis using molecular magnetic resonance imaging of endogenous proteins and peptides. Nat Med Nature. 2011;17(1):130–4.CrossRef
31.
go back to reference Jones CK, Schlosser MJ, Van Zijl PCM, Pomper MG, Golay X, Zhou J. Amide proton transfer imaging of human brain tumors at 3T. Magn Reson Med. 2006;56(3):585–92.CrossRefPubMed Jones CK, Schlosser MJ, Van Zijl PCM, Pomper MG, Golay X, Zhou J. Amide proton transfer imaging of human brain tumors at 3T. Magn Reson Med. 2006;56(3):585–92.CrossRefPubMed
32.
go back to reference Wen Z, Hu S, Huang F, et al. Neuroimage MR imaging of high-grade brain tumors using endogenous protein and peptide-based contrast. Neuroimage. 2010;51(2):616–22.CrossRefPubMedPubMedCentral Wen Z, Hu S, Huang F, et al. Neuroimage MR imaging of high-grade brain tumors using endogenous protein and peptide-based contrast. Neuroimage. 2010;51(2):616–22.CrossRefPubMedPubMedCentral
33.
go back to reference Zhou J, Payen JF, Wilson DA, Traystman RJ, Van Zijl PCM. Using the amide proton signals of intracellular proteins and peptides to detect pH effects in MRI. Nat Med. 2003;9(8):1085–90.CrossRefPubMed Zhou J, Payen JF, Wilson DA, Traystman RJ, Van Zijl PCM. Using the amide proton signals of intracellular proteins and peptides to detect pH effects in MRI. Nat Med. 2003;9(8):1085–90.CrossRefPubMed
34.
go back to reference Foulkes WD, Smith IE, Reis-Filho JS. Triple-negative breast cancer. N Engl J Med. 2010;363:1938–48.CrossRefPubMed Foulkes WD, Smith IE, Reis-Filho JS. Triple-negative breast cancer. N Engl J Med. 2010;363:1938–48.CrossRefPubMed
35.
go back to reference Yu T, Di G. Role of tumor microenvironment in triple-negative breast cancer and its prognostic significance. Chinese J Cancer Res. 2017;29(3):237–52.CrossRef Yu T, Di G. Role of tumor microenvironment in triple-negative breast cancer and its prognostic significance. Chinese J Cancer Res. 2017;29(3):237–52.CrossRef
36.
go back to reference Delille J, Slanetz PJ, Yeh ED, Kopans DB, Garrido L. Physiologic changes in breast magnetic resonance imaging during the menstrual cycle: perfusion imaging, signal enhancement, and influence of the T1 relaxation time of breast tissue. Breast J. 2005;11(4):236–41.CrossRefPubMed Delille J, Slanetz PJ, Yeh ED, Kopans DB, Garrido L. Physiologic changes in breast magnetic resonance imaging during the menstrual cycle: perfusion imaging, signal enhancement, and influence of the T1 relaxation time of breast tissue. Breast J. 2005;11(4):236–41.CrossRefPubMed
37.
go back to reference Zhang S, Keupp J, Wang X, et al. Z-spectrum appearance and interpretation in the presence of fat: influence of acquisition parameters. Magn Reson Med. 2017;0:1–7. Zhang S, Keupp J, Wang X, et al. Z-spectrum appearance and interpretation in the presence of fat: influence of acquisition parameters. Magn Reson Med. 2017;0:1–7.
38.
go back to reference Zu Z, Li K, Janve VA, Does MD, Gochberg DF. Optimizing pulsed-chemical exchange saturation transfer imaging sequences. Magn Reson Med. 2011;66(4):1100–8.CrossRefPubMedPubMedCentral Zu Z, Li K, Janve VA, Does MD, Gochberg DF. Optimizing pulsed-chemical exchange saturation transfer imaging sequences. Magn Reson Med. 2011;66(4):1100–8.CrossRefPubMedPubMedCentral
39.
go back to reference Singh A, Cai K, Haris M, Hariharan H. On B1 inhomogeneity correction of in vivo human brain glutamate chemical exchange saturation transfer contrast at 7T. Magn Reson Imaging. 2013;69:818–24. Singh A, Cai K, Haris M, Hariharan H. On B1 inhomogeneity correction of in vivo human brain glutamate chemical exchange saturation transfer contrast at 7T. Magn Reson Imaging. 2013;69:818–24.
40.
go back to reference Khlebnikov V, Windschuh J, Siero JCW, et al. On the transmit field inhomogeneity correction of relaxation-compensated amide and NOE CEST effects at 7 T. NMR Biomed. 2017;30:e3687.CrossRefPubMedCentral Khlebnikov V, Windschuh J, Siero JCW, et al. On the transmit field inhomogeneity correction of relaxation-compensated amide and NOE CEST effects at 7 T. NMR Biomed. 2017;30:e3687.CrossRefPubMedCentral
41.
go back to reference Raaijmakers AJE, Italiaander M, Voogt IJ, et al. The fractionated dipole antenna: a new antenna for body imaging at 7 Tesla. Magn Reson Med. 2016;75(3):1366–74.CrossRefPubMed Raaijmakers AJE, Italiaander M, Voogt IJ, et al. The fractionated dipole antenna: a new antenna for body imaging at 7 Tesla. Magn Reson Med. 2016;75(3):1366–74.CrossRefPubMed
42.
Metadata
Title
Amide chemical exchange saturation transfer at 7 T: a possible biomarker for detecting early response to neoadjuvant chemotherapy in breast cancer patients
Authors
Erwin Krikken
Vitaliy Khlebnikov
Moritz Zaiss
Rajni A. Jibodh
Paul J. van Diest
Peter R. Luijten
Dennis W. J. Klomp
Hanneke W. M. van Laarhoven
Jannie P. Wijnen
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 1/2018
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/s13058-018-0982-2

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