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

for the ACRIN Trial Team and I-SPY 2 TRIAL Investigators

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63 Scopus citations


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 mm 2 /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.

Original languageEnglish (US)
Pages (from-to)1617-1628
Number of pages12
JournalJournal of Magnetic Resonance Imaging
Issue number6
StatePublished - Jun 2019


  • breast MRI
  • breast cancer
  • diffusion
  • reproducibility
  • treatment response

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging


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