Journal Article
. 2018 Oct;49(6).
doi: 10.1002/jmri.26539.

Test-retest repeatability and reproducibility of ADC measures by breast DWI: Results from the ACRIN 6698 trial

David C Newitt 1 Zheng Zhang 2 Jessica E Gibbs 1 Savannah C Partridge 3 Thomas L Chenevert 4 Mark A Rosen 5 Patrick J Bolan 6 Helga S Marques 7 Sheye Aliu 1 Wen Li 1 Lisa Cimino 8 Bonnie N Joe 1 Heidi Umphrey 9 Haydee Ojeda-Fournier 10 Basak Dogan 11 Karen Oh 12 Hiroyuki Abe 13 Jennifer Drukteinis 14 Laura J Esserman 15 Nola M Hylton 1 ACRIN Trial Team and I-SPY 2 TRIAL Investigators  
Affiliations
  • PMID: 30350329
  •     33 References
  •     15 citations

Abstract

Background: Quantitative diffusion-weighted imaging (DWI) MRI is a promising technique for cancer characterization and treatment monitoring. Knowledge of the reproducibility of DWI metrics in breast tumors is necessary to apply DWI as a clinical biomarker.

Purpose: To evaluate the repeatability and reproducibility of breast tumor apparent diffusion coefficient (ADC) in a multi-institution clinical trial setting, using standardized DWI protocols and quality assurance (QA) procedures.

Study Type: Prospective.

Subjects: In all, 89 women from nine institutions undergoing neoadjuvant chemotherapy for invasive breast cancer.

Field Strength/Sequence: DWI was acquired before and after patient repositioning using a four b-value, single-shot echo-planar sequence at 1.5T or 3.0T.

Assessment: A QA procedure by trained operators assessed artifacts, fat suppression, and signal-to-noise ratio, and determine study analyzability. Mean tumor ADC was measured via manual segmentation of the multislice tumor region referencing DWI and contrast-enhanced images. Twenty cases were evaluated multiple times to assess intra- and interoperator variability. Segmentation similarity was assessed via the Sørenson-Dice similarity coefficient.

Statistical Tests: Repeatability and reproducibility were evaluated using within-subject coefficient of variation (wCV), intraclass correlation coefficient (ICC), agreement index (AI), and repeatability coefficient (RC). Correlations were measured by Pearson's correlation coefficients.

Results: In all, 71 cases (80%) passed QA evaluation: 44 at 1.5T, 27 at 3.0T; 60 pretreatment, 11 after 3 weeks of taxane-based treatment. ADC repeatability was excellent: wCV = 4.8% (95% confidence interval [CI] 4.0, 5.7%), ICC = 0.97 (95% CI 0.95, 0.98), AI = 0.83 (95% CI 0.76, 0.87), and RC = 0.16 * 10-3 mm2 /sec (95% CI 0.13, 0.19). The results were similar across field strengths and timepoint subgroups. Reproducibility was excellent: interreader ICC = 0.92 (95% CI 0.80, 0.97) and intrareader ICC = 0.91 (95% CI 0.78, 0.96).

Data Conclusion: Breast tumor ADC can be measured with excellent repeatability and reproducibility in a multi-institution setting using a standardized protocol and QA procedure. Improvements to DWI image quality could reduce loss of data in clinical trials.

Level Of Evidence: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:1617-1628.

Keywords: breast MRI; breast cancer; diffusion; reproducibility; treatment response.

Diffusion magnetic resonance imaging: an early surrogate marker of therapeutic efficacy in brain tumors.
T L Chenevert, L D Stegman, +4 authors, B D Ross.
J Natl Cancer Inst, 2000 Dec 21; 92(24). PMID: 11121466
Highly Cited.
Neoadjuvant chemotherapy in breast cancer: early response prediction with quantitative MR imaging and spectroscopy.
D J Manton, A Chaturvedi, +6 authors, L W Turnbull.
Br J Cancer, 2006 Feb 09; 94(3). PMID: 16465174    Free PMC article.
An overview on assessing agreement with continuous measurements.
Huiman X Barnhart, Michael J Haber, Lawrence I Lin.
J Biopharm Stat, 2007 Jul 07; 17(4). PMID: 17613641
Review.
Longitudinal study of the assessment by MRI and diffusion-weighted imaging of tumor response in patients with locally advanced breast cancer undergoing neoadjuvant chemotherapy.
Uma Sharma, Karikanni Kalathil A Danishad, Vurthaluru Seenu, Naranamangalam R Jagannathan.
NMR Biomed, 2008 Apr 04; 22(1). PMID: 18384182
Highly Cited.
I-SPY 2: an adaptive breast cancer trial design in the setting of neoadjuvant chemotherapy.
A D Barker, C C Sigman, +3 authors, L J Esserman.
Clin Pharmacol Ther, 2009 May 15; 86(1). PMID: 19440188
Highly Cited.
The role of mean diffusivity (MD) as a predictive index of the response to chemotherapy in locally advanced breast cancer: a preliminary study.
Chiara Iacconi, Marco Giannelli, +6 authors, Davide Caramella.
Eur Radiol, 2009 Sep 18; 20(2). PMID: 19760422
Applications of the repeatability of quantitative imaging biomarkers: a review of statistical analysis of repeat data sets.
Huiman X Barnhart, Daniel P Barboriak.
Transl Oncol, 2009 Dec 04; 2(4). PMID: 19956383    Free PMC article.
Diffusion tensor magnetic resonance imaging of the normal breast.
Savannah C Partridge, Revathi S Murthy, +3 authors, Constance D Lehman.
Magn Reson Imaging, 2010 Jan 12; 28(3). PMID: 20061111
Diffusion-weighted magnetic resonance imaging for pretreatment prediction and monitoring of treatment response of patients with locally advanced breast cancer undergoing neoadjuvant chemotherapy.
Line Nilsen, Anne Fangberget, +2 authors, Therese Seierstad.
Acta Oncol, 2010 Apr 20; 49(3). PMID: 20397769
Intraobserver and interobserver variability in the calculation of apparent diffusion coefficient (ADC) from diffusion-weighted magnetic resonance imaging (DW-MRI) of breast tumours.
G Petralia, L Bonello, +8 authors, M Bellomi.
Radiol Med, 2011 Jan 13; 116(3). PMID: 21225368
DW-MRI ADC values can predict treatment response in patients with locally advanced breast cancer undergoing neoadjuvant chemotherapy.
Xi-Ru Li, Liu-Quan Cheng, +7 authors, Lei Liu.
Med Oncol, 2011 Feb 03; 29(2). PMID: 21286861
Diffusion coefficient measurement using a temperature-controlled fluid for quality control in multicenter studies.
Thomas L Chenevert, Craig J Galbán, +7 authors, Brian D Ross.
J Magn Reson Imaging, 2011 Sep 20; 34(4). PMID: 21928310    Free PMC article.
Diffusion weighted imaging of the normal breast: reproducibility of apparent diffusion coefficient measurements and variation with menstrual cycle and menopausal status.
Elizabeth A M O'Flynn, Veronica A Morgan, Sharon L Giles, Nandita M deSouza.
Eur Radiol, 2012 Mar 01; 22(7). PMID: 22367471
Locally advanced breast cancer: MR imaging for prediction of response to neoadjuvant chemotherapy--results from ACRIN 6657/I-SPY TRIAL.
Nola M Hylton, Jeffrey D Blume, +11 authors, ACRIN 6657 Trial Team and I-SPY 1 TRIAL Investigators.
Radiology, 2012 May 25; 263(3). PMID: 22623692    Free PMC article.
Highly Cited.
Multi-system repeatability and reproducibility of apparent diffusion coefficient measurement using an ice-water phantom.
Dariya Malyarenko, Craig J Galbán, +5 authors, Thomas L Chenevert.
J Magn Reson Imaging, 2012 Oct 02; 37(5). PMID: 23023785    Free PMC article.
Diffusion-weighted MRI in pretreatment prediction of response to neoadjuvant chemotherapy in patients with breast cancer.
Raphael Richard, Isabelle Thomassin, +7 authors, Cedric de Bazelaire.
Eur Radiol, 2013 May 09; 23(9). PMID: 23652844
An AUC-like index for agreement assessment.
Zheng Zhang, Youdan Wang, Fenghai Duan.
J Biopharm Stat, 2014 Apr 05; 24(4). PMID: 24697741
Real-Time Measurement of Functional Tumor Volume by MRI to Assess Treatment Response in Breast Cancer Neoadjuvant Clinical Trials: Validation of the Aegis SER Software Platform.
David C Newitt, Sheye O Aliu, +4 authors, Nola M Hylton.
Transl Oncol, 2014 Apr 29; 7(1). PMID: 24772212    Free PMC article.
Repeatability of quantitative MRI measurements in normal breast tissue.
Sheye O Aliu, Ella F Jones, +9 authors, Nola M Hylton.
Transl Oncol, 2014 Apr 29; 7(1). PMID: 24772216    Free PMC article.
Diffusion-weighted imaging in assessing pathological response of tumor in breast cancer subtype to neoadjuvant chemotherapy.
Shangang Liu, Ruimei Ren, +4 authors, Pinliang Zhang.
J Magn Reson Imaging, 2015 Jan 13; 42(3). PMID: 25580585
Multi-site clinical evaluation of DW-MRI as a treatment response metric for breast cancer patients undergoing neoadjuvant chemotherapy.
Craig J Galbán, Bing Ma, +12 authors, Brian D Ross.
PLoS One, 2015 Mar 31; 10(3). PMID: 25816249    Free PMC article.
Role of the Apparent Diffusion Coefficient in the Prediction of Response to Neoadjuvant Chemotherapy in Patients With Locally Advanced Breast Cancer.
Enida Bufi, Paolo Belli, +8 authors, Lorenzo Bonomo.
Clin Breast Cancer, 2015 Apr 22; 15(5). PMID: 25891905
Assessment and quantification of sources of variability in breast apparent diffusion coefficient (ADC) measurements at diffusion weighted imaging.
E Giannotti, S Waugh, +3 authors, S Vinnicombe.
Eur J Radiol, 2015 Jun 17; 84(9). PMID: 26078100
Is there a systematic bias of apparent diffusion coefficient (ADC) measurements of the breast if measured on different workstations? An inter- and intra-reader agreement study.
Paola Clauser, Magda Marcon, +3 authors, Pascal A T Baltzer.
Eur Radiol, 2015 Oct 08; 26(7). PMID: 26443604
Reproducibility of Apparent Diffusion Coefficient Measurements in Malignant Breast Masses.
Mijung Jang, Sun Mi Kim, +4 authors, Sung-Won Kim.
J Korean Med Sci, 2015 Nov 06; 30(11). PMID: 26539016    Free PMC article.
Neoadjuvant Chemotherapy for Breast Cancer: Functional Tumor Volume by MR Imaging Predicts Recurrence-free Survival-Results from the ACRIN 6657/CALGB 150007 I-SPY 1 TRIAL.
Nola M Hylton, Constantine A Gatsonis, +13 authors, ACRIN 6657 Trial Team and I-SPY 1 TRIAL Investigators.
Radiology, 2015 Dec 02; 279(1). PMID: 26624971    Free PMC article.
Highly Cited.
Diffusion-weighted MRI of breast lesions: a prospective clinical investigation of the quantitative imaging biomarker characteristics of reproducibility, repeatability, and diagnostic accuracy.
Claudio Spick, Hubert Bickel, +9 authors, Pascal A Baltzer.
NMR Biomed, 2016 Aug 25; 29(10). PMID: 27553252
Diffusion-weighted imaging of breast lesions: Region-of-interest placement and different ADC parameters influence apparent diffusion coefficient values.
Hubert Bickel, Katja Pinker, +7 authors, Pascal Baltzer.
Eur Radiol, 2016 Sep 01; 27(5). PMID: 27578047
Diffusion-weighted breast MRI: Clinical applications and emerging techniques.
Savannah C Partridge, Noam Nissan, +2 authors, Eric E Sigmund.
J Magn Reson Imaging, 2016 Oct 01; 45(2). PMID: 27690173    Free PMC article.
Highly Cited. Review.
Apparent diffusion coefficient in estrogen receptor-positive and lymph node-negative invasive breast cancers at 3.0T DW-MRI: A potential predictor for an oncotype Dx test recurrence score.
Sunitha B Thakur, Manuela Durando, +5 authors, Elizabeth A Morris.
J Magn Reson Imaging, 2017 Jun 24; 47(2). PMID: 28640531    Free PMC article.
Repeatability, reproducibility, and accuracy of quantitative mri of the breast in the community radiology setting.
Anna G Sorace, Chengyue Wu, +9 authors, John Virostko.
J Magn Reson Imaging, 2018 Mar 24;. PMID: 29570895    Free PMC article.
Diffusion-weighted MRI Findings Predict Pathologic Response in Neoadjuvant Treatment of Breast Cancer: The ACRIN 6698 Multicenter Trial.
Savannah C Partridge, Zheng Zhang, +17 authors, ACRIN 6698 Trial Team and I-SPY 2 Trial Investigators.
Radiology, 2018 Sep 05; 289(3). PMID: 30179110    Free PMC article.
Highly Cited.
Assessing reproducibility by the within-subject coefficient of variation with random effects models.
H Quan, W J Shih.
Biometrics, 1996 Dec 01; 52(4). PMID: 8962450
Additive value of diffusion-weighted MRI in the I-SPY 2 TRIAL.
Wen Li, David C Newitt, +10 authors, Nola M Hylton.
J Magn Reson Imaging, 2019 Apr 27; 50(6). PMID: 31026118    Free PMC article.
Limited role of DWI with apparent diffusion coefficient mapping in breast lesions presenting as non-mass enhancement on dynamic contrast-enhanced MRI.
Daly Avendano, Maria Adele Marino, +10 authors, Katja Pinker.
Breast Cancer Res, 2019 Dec 06; 21(1). PMID: 31801635    Free PMC article.
Consensus-based technical recommendations for clinical translation of renal diffusion-weighted MRI.
Alexandra Ljimani, Anna Caroli, +23 authors, Eric E Sigmund.
MAGMA, 2019 Nov 05; 33(1). PMID: 31676990    Free PMC article.
Systematic Review.
Diffusion-weighted imaging of the breast-a consensus and mission statement from the EUSOBI International Breast Diffusion-Weighted Imaging working group.
Pascal Baltzer, Ritse M Mann, +11 authors, EUSOBI international Breast Diffusion-Weighted Imaging working group.
Eur Radiol, 2019 Dec 02; 30(3). PMID: 31786616    Free PMC article.
Diffusion tensor imaging for characterizing tumor microstructure and improving diagnostic performance on breast MRI: a prospective observational study.
Jing Luo, Daniel S Hippe, +3 authors, Savannah C Partridge.
Breast Cancer Res, 2019 Sep 06; 21(1). PMID: 31484577    Free PMC article.
Repeatability and reproducibility of 3D MR fingerprinting relaxometry measurements in normal breast tissue.
Ananya Panda, Yong Chen, +7 authors, Vikas Gulani.
J Magn Reson Imaging, 2019 Mar 21; 50(4). PMID: 30892807    Free PMC article.
Current and Emerging Magnetic Resonance-Based Techniques for Breast Cancer.
Apekshya Chhetri, Xin Li, Joseph V Rispoli.
Front Med (Lausanne), 2020 Jun 02; 7. PMID: 32478083    Free PMC article.
Review.
Retrospective Correction of ADC for Gradient Nonlinearity Errors in Multicenter Breast DWI Trials: ACRIN6698 Multiplatform Feasibility Study.
Dariya I Malyarenko, David C Newitt, +10 authors, Thomas L Chenevert.
Tomography, 2020 Jun 18; 6(2). PMID: 32548284    Free PMC article.
Repeatability and Reproducibility of ADC Histogram Metrics from the ACRIN 6698 Breast Cancer Therapy Response Trial.
David C Newitt, Ghoncheh Amouzandeh, +6 authors, Dariya I Malyarenko.
Tomography, 2020 Jun 18; 6(2). PMID: 32548294    Free PMC article.
Evaluation of the Efficacy of Neoadjuvant Chemotherapy for Breast Cancer.
Huan Wang, Xiaoyun Mao.
Drug Des Devel Ther, 2020 Jul 02; 14. PMID: 32606609    Free PMC article.
Review.
Predictors of Neoadjuvant Chemotherapy Response in Breast Cancer: A Review.
Weilin Xu, Xiu Chen, +3 authors, Jinhai Tang.
Onco Targets Ther, 2020 Jul 02; 13. PMID: 32606799    Free PMC article.
Review.
Variability and Standardization of Quantitative Imaging: Monoparametric to Multiparametric Quantification, Radiomics, and Artificial Intelligence.
Akifumi Hagiwara, Shohei Fujita, Yoshiharu Ohno, Shigeki Aoki.
Invest Radiol, 2020 Mar 27; 55(9). PMID: 32209816    Free PMC article.
Review.
Co-Clinical Imaging Resource Program (CIRP): Bridging the Translational Divide to Advance Precision Medicine.
Kooresh I Shoghi, Cristian T Badea, +13 authors, Rong Zhou.
Tomography, 2020 Sep 04; 6(3). PMID: 32879897    Free PMC article.
[Diffusion-weighted imaging-diagnostic supplement or alternative to contrast agents in early detection of malignancies?]
S Bickelhaupt, C Dreher, +4 authors, T A Kuder.
Radiologe, 2019 May 09; 59(6). PMID: 31065738
Review.
Predicting breast cancer response to neoadjuvant treatment using multi-feature MRI: results from the I-SPY 2 TRIAL.
Wen Li, David C Newitt, +59 authors, Nola M Hylton.
NPJ Breast Cancer, 2020 Dec 11; 6(1). PMID: 33298938    Free PMC article.