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

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

doi:10.1186/s13058-018-0982-2

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

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

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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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.

Original language	English
Article number	51
Pages (from-to)	1-9
Journal	Breast Cancer Research
Volume	20
Issue number	1
DOIs	https://doi.org/10.1186/s13058-018-0982-2
Publication status	Published - 14 Jun 2018

Keywords

7T MRI
APT CEST
Breast cancer
NAC treatment
Response prediction
Biomarkers, Tumor/chemistry
Protons
Amides/chemistry
Biomarkers, Pharmacological/chemistry
Humans
Middle Aged
Breast/chemistry
Magnetic Resonance Imaging
Statistics, Nonparametric
Adult
Female
Neoadjuvant Therapy
Contrast Media/administration & dosage
Neoplasm Staging
Breast Neoplasms/drug therapy
7 T MRI

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Krikken, E., Khlebnikov, V., Zaiss, M., Jibodh, R. A., van Diest, P. J., Luijten, P. R., Klomp, D. W. J., van Laarhoven, H. W. M., & Wijnen, J. P. (2018). Amide chemical exchange saturation transfer at 7T: A possible biomarker for detecting early response to neoadjuvant chemotherapy in breast cancer patients. Breast Cancer Research, 20(1), 1-9. Article 51. https://doi.org/10.1186/s13058-018-0982-2

@article{b05d3250251e40c49ad442690fb02454,

title = "Amide chemical exchange saturation transfer at 7T: A possible biomarker for detecting early response to neoadjuvant chemotherapy in breast cancer patients",

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.",

keywords = "7T MRI, APT CEST, Breast cancer, NAC treatment, Response prediction, Biomarkers, Tumor/chemistry, Protons, Amides/chemistry, Biomarkers, Pharmacological/chemistry, Humans, Middle Aged, Breast/chemistry, Magnetic Resonance Imaging, Statistics, Nonparametric, Adult, Female, Neoadjuvant Therapy, Contrast Media/administration \& dosage, Neoplasm Staging, Breast Neoplasms/drug therapy, 7 T MRI",

author = "Erwin Krikken and Vitaliy Khlebnikov and Moritz Zaiss and Jibodh, \{Rajni A.\} and \{van Diest\}, \{Paul J.\} and Luijten, \{Peter R.\} and Klomp, \{Dennis W.J.\} and \{van Laarhoven\}, \{Hanneke W.M.\} and Wijnen, \{Jannie P.\}",

note = "Funding Information: Dutch Cancer Society (Alpe d{\textquoteright}Huzes project nr: UU 2013–6302) and the NWO (VENI grant: J.P.Wijnen 016.148.002). Funding Information: We thank the Dutch Cancer Society (Alpe d{\textquoteright}Huzes project nr: UU 2013-6302) and the NWO (VENI grant: J.P.Wijnen 016.148.002) for financial support. Publisher Copyright: {\textcopyright} 2018 The Author(s).",

year = "2018",

month = jun,

day = "14",

doi = "10.1186/s13058-018-0982-2",

language = "English",

volume = "20",

pages = "1--9",

journal = "Breast Cancer Research",

issn = "1465-5411",

publisher = "BioMed Central Ltd.",

number = "1",

}

Krikken, E, Khlebnikov, V, Zaiss, M, Jibodh, RA, van Diest, PJ , Luijten, PR , Klomp, DWJ, van Laarhoven, HWM & Wijnen, JP 2018, 'Amide chemical exchange saturation transfer at 7T: A possible biomarker for detecting early response to neoadjuvant chemotherapy in breast cancer patients', Breast Cancer Research, vol. 20, no. 1, 51, pp. 1-9. https://doi.org/10.1186/s13058-018-0982-2

TY - JOUR

T1 - Amide chemical exchange saturation transfer at 7T

T2 - A possible biomarker for detecting early response to neoadjuvant chemotherapy in breast cancer patients

AU - Krikken, Erwin

AU - Khlebnikov, Vitaliy

AU - Zaiss, Moritz

AU - Jibodh, Rajni A.

AU - van Diest, Paul J.

AU - Luijten, Peter R.

AU - Klomp, Dennis W.J.

AU - van Laarhoven, Hanneke W.M.

AU - Wijnen, Jannie P.

N1 - Funding Information: Dutch Cancer Society (Alpe d’Huzes project nr: UU 2013–6302) and the NWO (VENI grant: J.P.Wijnen 016.148.002). Funding Information: We thank the Dutch Cancer Society (Alpe d’Huzes project nr: UU 2013-6302) and the NWO (VENI grant: J.P.Wijnen 016.148.002) for financial support. Publisher Copyright: © 2018 The Author(s).

PY - 2018/6/14

Y1 - 2018/6/14

N2 - 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.

AB - 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.

KW - 7T MRI

KW - APT CEST

KW - Breast cancer

KW - NAC treatment

KW - Response prediction

KW - Biomarkers, Tumor/chemistry

KW - Protons

KW - Amides/chemistry

KW - Biomarkers, Pharmacological/chemistry

KW - Humans

KW - Middle Aged

KW - Breast/chemistry

KW - Magnetic Resonance Imaging

KW - Statistics, Nonparametric

KW - Adult

KW - Female

KW - Neoadjuvant Therapy

KW - Contrast Media/administration & dosage

KW - Neoplasm Staging

KW - Breast Neoplasms/drug therapy

KW - 7 T MRI

UR - https://www.scopus.com/pages/publications/85048538700

U2 - 10.1186/s13058-018-0982-2

DO - 10.1186/s13058-018-0982-2

M3 - Article

C2 - 29898745

AN - SCOPUS:85048538700

SN - 1465-5411

VL - 20

SP - 1

EP - 9

JO - Breast Cancer Research

JF - Breast Cancer Research

IS - 1

M1 - 51

ER -

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

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