title: In vivo MRI for effective non-invasive detection and follow-up of an orthotopic mouse model of lung cancer.
abstract: One of the main reasons for the dismal prognosis of lung cancer is related to the late diagnosis of this pathology. In this study, we evaluated the potential of optimized lung MRI techniques as a completely non-invasive approach for non-small-cell lung cancer (NSCLC) MRI in vivo detection and follow-up in a mouse model of lung adenocarcinoma expressing the luciferase gene. Bioluminescent lung tumour cells were orthotopically implanted in immuno-deficient mice. Ultra-short echo-time (UTE) MRI free-breathing acquisitions were compared with standard gradient-echo lung MRI (FLASH) using both respiratory-gated and free-breathing protocols. The MRI findings were validated against bioluminescence imaging (BLI) and gold-standard histopathology analysis. Adenocarcinoma-like pathological tissue was successfully identified in all the mice with gated-FLASH and non-gated UTE MRI, and good tumour co-localization was found between MRI, BLI and histological analyses. An excellent or good correlation was found between the measured bioluminescent signal and the total tumour volumes quantified with UTE MRI or gated-FLASH MRI, respectively. No significant correlation was found when the tumours were segmented on non-gated MR FLASH images. MRI was shown to be a powerful imaging tool able to detect, quantify and longitudinally monitor the development of sub-millimetric NSCLCs. To our knowledge, this is the first study which proves the feasibility of a completely non-invasive MRI quantitative detection of lung adenocarcinoma in freely breathing mice. The absence of ionizing radiation and the high-resolution of MRI, along with the complete non-invasiveness and good reproducibility of the proposed non-gated protocol, make this imaging tool ideal for direct translational applications.
authors.affiliation: Centre de Résonance Magnétique des Systèmes Biologiques, CNRS UMR 5536, Université Bordeaux Segalen, 146, rue Léo Saignat, Bordeaux, France.
authors.forename: Andrea
authors.initials: A
authors.lastname: Bianchi
authors.forename: Sandrine
authors.initials: S
authors.lastname: Dufort
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Fortin
authors.forename: François
authors.initials: F
authors.lastname: Lux
authors.forename: Gérard
authors.initials: G
authors.lastname: Raffard
authors.forename: Nawal
authors.initials: N
authors.lastname: Tassali
authors.forename: Olivier
authors.initials: O
authors.lastname: Tillement
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Coll
authors.forename: Yannick
authors.initials: Y
authors.lastname: Crémillieux
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008163:Luminescent Measurements; D008175:Lung Neoplasms / Q000175:diagnosis*; D008279:Magnetic Resonance Imaging; D008819:Mice, Nude; D059629:Signal-To-Noise Ratio; D013997:Time Factors; D023041:Xenograft Model Antitumor Assays
keywords: MRI; bioluminescence imaging; lung MRI; lung cancer; orthotopic adenocarcinoma model