title: Collagen fibers mediate MRI-detected water diffusion and anisotropy in breast cancers.
abstract: Collagen 1 (Col1) fibers play an important role in tumor interstitial macromolecular transport and cancer cell dissemination. Our goal was to understand the influence of Col1 fibers on water diffusion, and to examine the potential of using noninvasive diffusion tensor imaging (DTI) to indirectly detect Col1 fibers in breast lesions. We previously observed, in human MDA-MB-231 breast cancer xenografts engineered to fluoresce under hypoxia, relatively low amounts of Col1 fibers in fluorescent hypoxic regions. These xenograft tumors together with human breast cancer samples were used here to investigate the relationship between Col1 fibers, water diffusion and anisotropy, and hypoxia. Hypoxic low Col1 fiber containing regions showed decreased apparent diffusion coefficient (ADC) and fractional anisotropy (FA) compared to normoxic high Col1 fiber containing regions. Necrotic high Col1 fiber containing regions showed increased ADC with decreased FA values compared to normoxic viable high Col1 fiber regions that had increased ADC with increased FA values. A good agreement of ADC and FA patterns was observed between in vivo and ex vivo images. In human breast cancer specimens, ADC and FA decreased in low Col1 containing regions. Our data suggest that a decrease in ADC and FA values observed within a lesion could predict hypoxia, and a pattern of high ADC with low FA values could predict necrosis. Collectively the data identify the role of Col1 fibers in directed water movement and support expanding the evaluation of DTI parameters as surrogates for Col1 fiber patterns associated with specific tumor microenvironments as companion diagnostics and for staging.
authors.affiliation: JHU ICMIC Program, Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science; Department of Chemistry and Biology, University of Bremen, Bremen, Germany.
authors.forename: Samata
authors.initials: S
authors.lastname: Kakkad
authors.affiliation: JHU ICMIC Program, Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science.
authors.forename: Jiangyang
authors.initials: J
authors.lastname: Zhang
authors.affiliation: JHU ICMIC Program, Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science.
authors.forename: Alireza
authors.initials: A
authors.lastname: Akhbardeh
authors.affiliation: JHU ICMIC Program, Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science.
authors.forename: Desmond
authors.initials: D
authors.lastname: Jacob
authors.affiliation: JHU ICMIC Program, Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science.
authors.forename: Balaji
authors.initials: B
authors.lastname: Krishnamachary
authors.affiliation: JHU ICMIC Program, Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science.
authors.forename: Meiyappan
authors.initials: M
authors.lastname: Solaiyappan
authors.affiliation: JHU ICMIC Program, Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science; Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Jacobs
authors.affiliation: JHU ICMIC Program, Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science; Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Venu
authors.initials: V
authors.lastname: Raman
authors.affiliation: Department of Chemistry and Biology, University of Bremen, Bremen, Germany.
authors.forename: Dieter
authors.initials: D
authors.lastname: Leibfritz
authors.affiliation: JHU ICMIC Program, Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science; Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Kristine
authors.initials: K
authors.lastname: Glunde
authors.affiliation: JHU ICMIC Program, Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science; Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: zaver@mri.jhu.edu.
authors.forename: Zaver M
authors.initials: ZM
authors.lastname: Bhujwalla
mesh_terms: D000818:Animals; D016880:Anisotropy; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism*; D045744:Cell Line, Tumor; D024042:Collagen Type I / Q000378:metabolism*; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods; D004195:Disease Models, Animal; D005260:Female; D005347:Fibroblasts; D064593:Heterografts; D006801:Humans; D051379:Mice
chemical_list: D024042:Collagen Type I