Imaging of Orthotopic Glioblastoma Xenografts in Mice Using a Clinical CT Scanner: Comparison with Micro-CT and Histology

PLoS One. 2016 Nov 9;11(11):e0165994. doi: 10.1371/journal.pone.0165994. eCollection 2016.

Abstract

Purpose: There is an increasing need for small animal in vivo imaging in murine orthotopic glioma models. Because dedicated small animal scanners are not available ubiquitously, the applicability of a clinical CT scanner for visualization and measurement of intracerebrally growing glioma xenografts in living mice was validated.

Materials and methods: 2.5x106 U87MG cells were orthotopically implanted in NOD/SCID/ᵞc-/- mice (n = 9). Mice underwent contrast-enhanced (300 μl Iomeprol i.v.) imaging using a micro-CT (80 kV, 75 μAs, 360° rotation, 1,000 projections, scan time 33 s, resolution 40 x 40 x 53 μm) and a clinical CT scanner (4-row multislice detector; 120 kV, 150 mAs, slice thickness 0.5 mm, feed rotation 0.5 mm, resolution 98 x 98 x 500 μm). Mice were sacrificed and the brain was worked up histologically. In all modalities tumor volume was measured by two independent readers. Contrast-to-noise ratio (CNR) and Signal-to-noise ratio (SNR) were measured from reconstructed CT-scans (0.5 mm slice thickness; n = 18).

Results: Tumor volumes (mean±SD mm3) were similar between both CT-modalities (micro-CT: 19.8±19.0, clinical CT: 19.8±18.8; Wilcoxon signed-rank test p = 0.813). Moreover, between reader analyses for each modality showed excellent agreement as demonstrated by correlation analysis (Spearman-Rho >0.9; p<0.01 for all correlations). Histologically measured tumor volumes (11.0±11.2) were significantly smaller due to shrinkage artifacts (p<0.05). CNR and SNR were 2.1±1.0 and 1.1±0.04 for micro-CT and 23.1±24.0 and 1.9±0.7 for the clinical CTscanner, respectively.

Conclusion: Clinical CT scanners may reliably be used for in vivo imaging and volumetric analysis of brain tumor growth in mice.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Brain / diagnostic imaging*
  • Brain / pathology
  • Brain Neoplasms / diagnostic imaging*
  • Cell Line, Tumor
  • Contrast Media / administration & dosage
  • Female
  • Glioblastoma / diagnostic imaging*
  • Humans
  • Interleukin Receptor Common gamma Subunit / deficiency
  • Interleukin Receptor Common gamma Subunit / genetics
  • Iopamidol / administration & dosage
  • Iopamidol / analogs & derivatives
  • Male
  • Mice, Inbred NOD
  • Mice, Knockout
  • Mice, SCID
  • Reproducibility of Results
  • Signal-To-Noise Ratio
  • Transplantation, Heterologous
  • X-Ray Microtomography / methods*

Substances

  • Contrast Media
  • Il2rg protein, mouse
  • Interleukin Receptor Common gamma Subunit
  • iomeprol
  • Iopamidol

Grants and funding

None of the authors of the above manuscript have declared any conflict of interest. The acquisition of the micro-CT (Yxlon Y. Fox) was funded by the Federal Ministry of Education and Research and the Land Baden-Württemberg (HBFG grant #125-648). This work was funded by the Deutsche Forschungsgemeinschaft (grants FL 880/1-1, GI 771/1-1, GL 236/9-1 and WE 2063/9-1), the Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research, grant BMBF 01EZ1130), the Klaus Tschira Stiftung (grant 00.211.2012) and the Bundesamt für Strahlenschutz (Federal Office for Radiation Protection, grant BfS 3608S04001) for establishment of the endowed professorship Medizinische Strahlenphysik/Strahlenschutz (Medical Radiation Physics/Radiation Protection).