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In vivo micro-CT imaging of untreated and irradiated orthotopic glioblastoma xenografts in mice: capabilities, limitations and a comparison with bioluminescence imaging

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 × 106...

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Main Authors: Kirschner, Stefanie (Author) , Hartmann, Linda (Author) , Bierbaum, Miriam (Author) , Maros, Máté E. (Author) , Kerl, Hans Ulrich (Author) , Wenz, Frederik (Author) , Glatting, Gerhard (Author) , Giordano, Frank Anton (Author)
Format: Article (Journal)
Language:English
Published: 22 January 2015
In: Journal of neuro-oncology
Year: 2015, Volume: 122, Issue: 2, Pages: 245-254
ISSN:1573-7373
DOI:10.1007/s11060-014-1708-7
Online Access:Verlag, Volltext: http://dx.doi.org/10.1007/s11060-014-1708-7
Verlag, Volltext: https://link-springer-com.ezproxy.medma.uni-heidelberg.de/article/10.1007/s11060-014-1708-7
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Author Notes:Stefanie Kirschner, Manuela C. Felix, Linda Hartmann, Miriam Bierbaum, Máté E. Maros, Hans U. Kerl, Frederik Wenz, Gerhard Glatting, Martin Kramer, Frank A. Giordano, Marc A. Brockmann
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Summary: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 × 106 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 mm3, 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.
Item Description:Gesehen am 15.11.2017
Physical Description:Online Resource
ISSN:1573-7373
DOI:10.1007/s11060-014-1708-7

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