title: High-resolution MRI analysis of breast cancer xenograft on the chick chorioallantoic membrane.
abstract: The chick chorioallantoic membrane (CAM) model has been successfully used to study angiogenesis, cancer progression and its pharmacological treatment, tumor pharmacokinetics, and properties of novel nanomaterials. MRI is an attractive technique for non-invasive and longitudinal monitoring of physiological processes and tumor growth. This study proposes an age-adapted cooling regime for immobilization of the chick embryo, enabling high-resolution MRI of the embryo and the CAM tumor xenograft. 64 chick embryos were enrolled in this study. The novel immobilization and imaging protocol was optimized in 29 embryos. From d7 to d18 immobilization of the embryo up to 90 min was achieved by cooling at 4 °C pre-imaging, with cooling times adapted to age. Its application to tumor growth monitoring was evaluated in 15 embryos after xenotransplantation of human MDA-MB-231 breast cancer cells on CAM. Tumor volumes were monitored from d4 to d9 after grafting (d11 to d16 after incubation) applying a T2 -weighted multislice RARE sequence. At d9 after grafting, the tumors were collected and compared with the MRI-derived data by histology and weight measurements. Additional imaging methods comprising DWI, T2 mapping, and the bio-distribution of contrast agents were tested at d9 after grafting in 20 further embryos. With the adaptive cooling regime, motion artifacts could be completely avoided for up to 90 min scan time, enabling high-resolution in ovo imaging. Excellent anatomical details could be obtained in the embryo and tumors. Tumor volumes could be quantified over time. The results prove the feasibility of high-resolution MRI for longitudinal tumor and organ growth monitoring. The suggested method is promising for future applications such as testing tailored and/or targeted treatment strategies, longitudinal monitoring of tumor development, analysis of therapeutic efficacies of drugs, or assessment of tumor pharmacokinetics. The method provides an alternative to animal experimentation.
authors.affiliation: Department of Cardiology, Zhongda Hospital, Medical School of Southeast University, Nanjing, China; Department of Internal Medicine II, University Hospital Ulm, Ulm, Germany; Core Facility Small Animal MRI, Medical Faculty, Ulm University, Ulm, Germany.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Zuo
authors.forename: Tatiana
authors.initials: T
authors.lastname: Syrovets
authors.forename: Felicitas
authors.initials: F
authors.lastname: Genze
authors.forename: Alireza
authors.initials: A
authors.lastname: Abaei
authors.forename: Genshan
authors.initials: G
authors.lastname: Ma
authors.forename: Thomas
authors.initials: T
authors.lastname: Simmet
authors.forename: Volker
authors.initials: V
authors.lastname: Rasche
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D002642:Chick Embryo; D049033:Chorioallantoic Membrane; D003287:Contrast Media; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods; D004529:Egg White; D004530:Egg Yolk; D005240:Feasibility Studies; D005260:Female; D005682:Gadolinium; D064593:Heterografts; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009942:Organometallic Compounds; D015203:Reproducibility of Results; D013696:Temperature; D047368:Tumor Burden
chemical_list: D003287:Contrast Media; D009942:Organometallic Compounds; D005682:Gadolinium; C109932:gadofosveset trisodium
keywords: CAM; breast cancer xenograft; chick chorioallantoic membrane; high resolution; in ovo; magnetic resonance imaging; tumor