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.
Bibliographical noteFunding Information:
This research was supported by the National Cancer Institute (NCI) through the grants U01 CA151235, R01 CA132870, U01 CA166104, R01 CA151326, P41 EB015894. ACRIN receives funding from the NCI through the grants U01 CA079778, U01 CA080098, U24 CA180803.
This research was supported by the National Cancer Institute (NCI) through the grants U01 CA151235, R01 CA132870, U01 CA166104, R01 CA151326, P41 EB015894. ACRIN receives funding from the NCI through the grants U01 CA079778, U01 CA080098, U24 CA180803. The authors thank the individuals who contributed substantially to the work reported in the article, including the ACRIN 6698 and I-SPY 2 Trial Teams, the patients who participated in the study, and the staff members who contributed to the conduct of the study at the University of California, San Francisco; University of Minnesota; University of Pennsylvania; University of Washington; University of Alabama, Birmingham; University of California, San Diego; University of Texas MD Anderson Cancer Center; Oregon Health Sciences University; University of Chicago; and H. Lee Moffitt Cancer Center and Research Institute.
© 2018 International Society for Magnetic Resonance in Medicine
- breast MRI
- breast cancer
- treatment response