title: Evaluation of breast cancer using intravoxel incoherent motion (IVIM) histogram analysis: comparison with malignant status, histological subtype, and molecular prognostic factors.
abstract: OBJECTIVE
  To examine heterogeneous breast cancer through intravoxel incoherent motion (IVIM) histogram analysis.
  
  
  METHODS
  This HIPAA-compliant, IRB-approved retrospective study included 62 patients (age 48.44 ± 11.14 years, 50 malignant lesions and 12 benign) who underwent contrast-enhanced 3 T breast MRI and diffusion-weighted imaging. Apparent diffusion coefficient (ADC) and IVIM biomarkers of tissue diffusivity (Dt), perfusion fraction (fp), and pseudo-diffusivity (Dp) were calculated using voxel-based analysis for the whole lesion volume. Histogram analysis was performed to quantify tumour heterogeneity. Comparisons were made using Mann-Whitney tests between benign/malignant status, histological subtype, and molecular prognostic factor status while Spearman's rank correlation was used to characterize the association between imaging biomarkers and prognostic factor expression.
  
  
  RESULTS
  The average values of the ADC and IVIM biomarkers, Dt and fp, showed significant differences between benign and malignant lesions. Additional significant differences were found in the histogram parameters among tumour subtypes and molecular prognostic factor status. IVIM histogram metrics, particularly fp and Dp, showed significant correlation with hormonal factor expression.
  
  
  CONCLUSIONS
  Advanced diffusion imaging biomarkers show relationships with molecular prognostic factors and breast cancer malignancy. This analysis reveals novel diagnostic metrics that may explain some of the observed variability in treatment response among breast cancer patients.
  
  
  CONCLUSIONS
  • Novel IVIM biomarkers characterize heterogeneous breast cancer. • Histogram analysis enables quantification of tumour heterogeneity. • IVIM biomarkers show relationships with breast cancer malignancy and molecular prognostic factors.
authors.affiliation: Center for Advanced Imaging Innovation and Research (CAI2R), New York University School of Medicine, 660 First Ave. 4th Floor, New York City, NY, 10016, USA. gyc219@nyumc.org.|Bernard and Irene Schwartz Center for Biomedical Imaging, Department of Radiology, New York University School of Medicine, New York, NY, 10016, USA. gyc219@nyumc.org.
authors.forename: Gene Young
authors.identifier: http://orcid.org/0000-0003-3422-673X
authors.initials: GY
authors.lastname: Cho
authors.affiliation: Center for Advanced Imaging Innovation and Research (CAI2R), New York University School of Medicine, 660 First Ave. 4th Floor, New York City, NY, 10016, USA.|Bernard and Irene Schwartz Center for Biomedical Imaging, Department of Radiology, New York University School of Medicine, New York, NY, 10016, USA.
authors.forename: Linda
authors.initials: L
authors.lastname: Moy
authors.affiliation: Center for Advanced Imaging Innovation and Research (CAI2R), New York University School of Medicine, 660 First Ave. 4th Floor, New York City, NY, 10016, USA.|Bernard and Irene Schwartz Center for Biomedical Imaging, Department of Radiology, New York University School of Medicine, New York, NY, 10016, USA.
authors.forename: Sungheon G
authors.initials: SG
authors.lastname: Kim
authors.affiliation: Center for Advanced Imaging Innovation and Research (CAI2R), New York University School of Medicine, 660 First Ave. 4th Floor, New York City, NY, 10016, USA.|Bernard and Irene Schwartz Center for Biomedical Imaging, Department of Radiology, New York University School of Medicine, New York, NY, 10016, USA.
authors.forename: Steven H
authors.initials: SH
authors.lastname: Baete
authors.affiliation: New York University Langone Medical Center - Cancer Institute, New York, NY, 10016, USA.
authors.forename: Melanie
authors.initials: M
authors.lastname: Moccaldi
authors.affiliation: Center for Advanced Imaging Innovation and Research (CAI2R), New York University School of Medicine, 660 First Ave. 4th Floor, New York City, NY, 10016, USA.|Bernard and Irene Schwartz Center for Biomedical Imaging, Department of Radiology, New York University School of Medicine, New York, NY, 10016, USA.
authors.forename: James S
authors.initials: JS
authors.lastname: Babb
authors.affiliation: Center for Advanced Imaging Innovation and Research (CAI2R), New York University School of Medicine, 660 First Ave. 4th Floor, New York City, NY, 10016, USA.|Bernard and Irene Schwartz Center for Biomedical Imaging, Department of Radiology, New York University School of Medicine, New York, NY, 10016, USA.
authors.forename: Daniel K
authors.initials: DK
authors.lastname: Sodickson
authors.affiliation: Center for Advanced Imaging Innovation and Research (CAI2R), New York University School of Medicine, 660 First Ave. 4th Floor, New York City, NY, 10016, USA.|Bernard and Irene Schwartz Center for Biomedical Imaging, Department of Radiology, New York University School of Medicine, New York, NY, 10016, USA.
authors.forename: Eric E
authors.initials: EE
authors.lastname: Sigmund
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D001940:Breast / Q000000981:diagnostic imaging*; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D005260:Female; D006801:Humans; D008875:Middle Aged; D011379:Prognosis; D015203:Reproducibility of Results; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor
keywords: Breast MR; Breast cancer; Diffusion-weighted MRI; Intravoxel incoherent motion; Tumour heterogeneity