title: In vivo micro-CT imaging of untreated and irradiated orthotopic glioblastoma xenografts in mice: capabilities, limitations and a comparison with bioluminescence imaging.
abstract: Small animal imaging is of increasing relevance in biomedical research. Studies systematically assessing the diagnostic accuracy of contrast-enhanced in vivo micro-CT of orthotopic glioma xenografts in mice do not exist. NOD/SCID/γc(-/-) mice (n = 27) underwent intracerebral implantation of 2.5 × 10(6) GFP-Luciferase-transduced U87MG cells. Mice underwent bioluminescence imaging (BLI) to detect tumor growth and afterwards repeated contrast-enhanced (300 µl Iomeprol i.v.) micro-CT imaging (80 kV, 75 µAs, 360° rotation, 1,000 projections, 33 s scan time, resolution 40 × 40 × 53 µm, 0.5 Gy/scan). Presence of tumors, tumor diameter and tumor volume in micro-CT were rated by two independent readers. Results were compared with histological analyses. Six mice with tumors confirmed by micro-CT received fractionated irradiation (3 × 5 Gy every other day) using the micro-CT (5 mm pencil beam geometry). Repeated micro-CT scans were tolerated well. Tumor engraftment rate was 74 % (n = 20). In micro-CT, mean tumor volume was 30 ± 33 mm(3), and the smallest detectable tumor measured 360 × 620 µm. The inter-rater agreement (n = 51 micro-CT scans) for the item tumor yes/no was excellent (Spearman-Rho = 0.862, p < 0.001). Sensitivity and specificity of micro-CT were 0.95 and 0.71, respectively (PPV = 0.91, NPV = 0.83). BLI on day 21 after tumor implantation had a sensitivity and specificity of 0.90 and 1.0, respectively (PPV = 1.0, NPV = 0.5). Maximum tumor diameter and volume in micro-CT and histology correlated excellently (tumor diameter: 0.929, p < 0.001; tumor volume: 0.969, p < 0.001, n = 17). Irradiated animals showed a large central tumor necrosis. Longitudinal contrast enhanced micro-CT imaging of brain tumor growth in live mice is feasible at high sensitivity levels and with excellent inter-rater agreement and allows visualization of radiation effects.
authors.affiliation: Department of Neuroradiology, Medical Faculty Mannheim, University, Medical Center Mannheim, Heidelberg University, 68167, Mannheim, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Kirschner
authors.forename: Manuela C
authors.initials: MC
authors.lastname: Felix
authors.forename: Linda
authors.initials: L
authors.lastname: Hartmann
authors.forename: Miriam
authors.initials: M
authors.lastname: Bierbaum
authors.forename: Máté E
authors.initials: ME
authors.lastname: Maros
authors.forename: Hans U
authors.initials: HU
authors.lastname: Kerl
authors.forename: Frederik
authors.initials: F
authors.lastname: Wenz
authors.forename: Gerhard
authors.initials: G
authors.lastname: Glatting
authors.forename: Martin
authors.initials: M
authors.lastname: Kramer
authors.forename: Frank A
authors.initials: FA
authors.lastname: Giordano
authors.forename: Marc A
authors.initials: MA
authors.lastname: Brockmann
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000528:radiation effects; D001932:Brain Neoplasms / Q000000981:diagnostic imaging* / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D003287:Contrast Media; D019583:Dose Fractionation, Radiation; D005240:Feasibility Studies; D005260:Female; D005909:Glioblastoma / Q000000981:diagnostic imaging* / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D012680:Sensitivity and Specificity; D047368:Tumor Burden; D055114:X-Ray Microtomography / Q000379:methods*
chemical_list: D003287:Contrast Media