title: Diffusion-weighted MRI of breast lesions: a prospective clinical investigation of the quantitative imaging biomarker characteristics of reproducibility, repeatability, and diagnostic accuracy.
abstract: Diffusion-weighted MRI (DWI) provides insights into tissue microstructure by visualization and quantification of water diffusivity. Quantitative evaluation of the apparent diffusion coefficient (ADC) obtained from DWI has been proven helpful for differentiating between malignant and benign breast lesions, for cancer subtyping in breast cancer patients, and for prediction of response to neoadjuvant chemotherapy. However, to further establish DWI of breast lesions it is important to evaluate the quantitative imaging biomarker (QIB) characteristics of reproducibility, repeatability, and diagnostic accuracy. In this intra-individual prospective clinical study 40 consecutive patients with suspicious findings, scheduled for biopsy, underwent an identical 3T breast MRI protocol of the breast on two consecutive days (>24 h). Mean ADC of target lesions was assessed (two independent readers) in four separate sessions. Reproducibility, repeatability, and diagnostic accuracy between examinations (E1, E2), readers (R1, R2), and measurements (M1, M2) were assessed with intraclass correlation coefficients (ICCs), coefficients of variation (CVs), Bland-Altman plots, and receiver operating characteristic (ROC) analysis with calculation of the area under the ROC curve (AUC). The standard of reference was either histopathology (n = 38) or imaging follow-up of up to 24 months (n = 2). Eighty breast MRI examinations (median E1-E2, 2 ± 1.7 days, 95% confidence interval (CI) 1-2 days, range 1-11 days) in 40 patients (mean age 56, standard deviation (SD) ±14) were evaluated. In 55 target lesions (mean size 25.2 ± 20.8 (SD) mm, range 6-106 mm), mean ADC values were significantly (P < 0.0001) higher in benign (1.38, 95% CI 1.27-1.49 × 10(-3)  mm(2) /s) compared with malignant (0.86, 95% CI 0.81-0.91 × 10(-) (3)  mm(2) /s) lesions. Reproducibility and repeatability showed high agreement for repeated examinations, readers, and measurements (all ICCs >0.9, CVs 3.2-8%), indicating little variation. Bland-Altman plots demonstrated no systematic differences, and diagnostic accuracy was not significantly different in the two repeated examinations (all ROC curves >0.91, P > 0.05). High reproducibility, repeatability, and diagnostic accuracy of DWI provide reliable characteristics for its use as a potential QIB, to further improve breast lesion detection, characterization, and treatment monitoring of breast lesions.
authors.affiliation: Department of Biomedical Imaging and Image-Guided Therapy, Division of Molecular and Gender Imaging, Medical University of Vienna, Waehringer-Guertel 18-20, A-1090, Vienna, Austria.
authors.forename: Claudio
authors.initials: C
authors.lastname: Spick
authors.affiliation: Department of Biomedical Imaging and Image-Guided Therapy, Division of Molecular and Gender Imaging, Medical University of Vienna, Waehringer-Guertel 18-20, A-1090, Vienna, Austria.
authors.forename: Hubert
authors.initials: H
authors.lastname: Bickel
authors.affiliation: Department of Biomedical Imaging and Image-Guided Therapy, Division of Molecular and Gender Imaging, Medical University of Vienna, Waehringer-Guertel 18-20, A-1090, Vienna, Austria.
authors.forename: Katja
authors.initials: K
authors.lastname: Pinker
authors.affiliation: Department of Biomedical Imaging and Image-Guided Therapy, Division of Molecular and Gender Imaging, Medical University of Vienna, Waehringer-Guertel 18-20, A-1090, Vienna, Austria.
authors.forename: Maria
authors.initials: M
authors.lastname: Bernathova
authors.affiliation: Department of Biomedical Imaging and Image-Guided Therapy, Division of Molecular and Gender Imaging, Medical University of Vienna, Waehringer-Guertel 18-20, A-1090, Vienna, Austria.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Kapetas
authors.affiliation: Department of Biomedical Imaging and Image-Guided Therapy, Division of Molecular and Gender Imaging, Medical University of Vienna, Waehringer-Guertel 18-20, A-1090, Vienna, Austria.
authors.forename: Ramona
authors.initials: R
authors.lastname: Woitek
authors.affiliation: Department of Biomedical Imaging and Image-Guided Therapy, Division of Molecular and Gender Imaging, Medical University of Vienna, Waehringer-Guertel 18-20, A-1090, Vienna, Austria.
authors.forename: Paola
authors.initials: P
authors.lastname: Clauser
authors.affiliation: Department of Biomedical Imaging and Image-Guided Therapy, Division of Molecular and Gender Imaging, Medical University of Vienna, Waehringer-Guertel 18-20, A-1090, Vienna, Austria.
authors.forename: Stephan H
authors.initials: SH
authors.lastname: Polanec
authors.affiliation: Clinical Institute of Pathology, Medical University of Vienna, Waehringer-Guertel 18-20, A-1090, Vienna, Austria.
authors.forename: Margaretha
authors.initials: M
authors.lastname: Rudas
authors.affiliation: Department of Internal Medicine, Division of Oncology, Medical University of Vienna, Waehringer-Guertel 18-20, A-1090, Vienna, Austria.
authors.forename: Rupert
authors.initials: R
authors.lastname: Bartsch
authors.affiliation: Department of Biomedical Imaging and Image-Guided Therapy, Division of Molecular and Gender Imaging, Medical University of Vienna, Waehringer-Guertel 18-20, A-1090, Vienna, Austria.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Helbich
authors.affiliation: Department of Biomedical Imaging and Image-Guided Therapy, Division of Molecular and Gender Imaging, Medical University of Vienna, Waehringer-Guertel 18-20, A-1090, Vienna, Austria. pascal.baltzer@meduniwien.ac.at.
authors.forename: Pascal A
authors.initials: PA
authors.lastname: Baltzer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology*; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D005260:Female; D006801:Humans; D007089:Image Enhancement / Q000379:methods; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D008875:Middle Aged; D015588:Observer Variation; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D055815:Young Adult
chemical_list: D015415:Biomarkers
keywords: DWI; breast cancer; diagnostic accuracy; diffusion-weighted imaging; quantitative imaging biomarker; repeatability; reproducibility