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.
Stefanie Kirschner  1 ,  Bettina Mürle  1 ,  Manuela Felix  2 ,  Anna Arns  3 ,  Christoph Groden  1 ,  Frederik Wenz  3 ,  Andreas Hug  4 ,  Gerhard Glatting  2 ,  Martin Kramer  5 ,  Frank A Giordano  3 ,  Marc A Brockmann  6
Affiliations
  • 1. Department of Neuroradiology, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, 68167, Mannheim, Germany.
  • 2. Medical Radiation Physics/Radiation Protection, Department of Radiation Oncology, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, 68167, Mannheim, Germany.
  • 3. Department of Radiation Oncology, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, 68167, Mannheim, Germany.
  • 4. Spinal Cord Injury Center, University Hospital Heidelberg, Schlierbacher Landstr. 200a, 69118, Heidelberg, Germany.
  • 5. Department of Veterinary Clinical Sciences, Small Animal Clinic, Justus-Liebig-University, 35392, Giessen, Germany.
  • 6. Department of Neuroradiology, University Medical Center of the Johannes Gutenberg University Mainz, 55131, Mainz, Germany.
PMID: 27829015 DOI: 10.1371/journal.pone.0165994
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.