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


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.


CONCLUSIONS
Clinical CT scanners may reliably be used for in vivo imaging and volumetric analysis of brain tumor growth in mice.
Department of Neuroradiology, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, 68167, Mannheim, Germany.
Stefanie
S
Kirschner
Department of Neuroradiology, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, 68167, Mannheim, Germany.
Bettina
B
Mürle
Medical Radiation Physics/Radiation Protection, Department of Radiation Oncology, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, 68167, Mannheim, Germany.
Manuela
M
Felix
Department of Radiation Oncology, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, 68167, Mannheim, Germany.
Anna
A
Arns
Department of Neuroradiology, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, 68167, Mannheim, Germany.
Christoph
C
Groden
Department of Radiation Oncology, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, 68167, Mannheim, Germany.
Frederik
F
Wenz
Spinal Cord Injury Center, University Hospital Heidelberg, Schlierbacher Landstr. 200a, 69118, Heidelberg, Germany.
Andreas
A
Hug
Medical Radiation Physics/Radiation Protection, Department of Radiation Oncology, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, 68167, Mannheim, Germany.
Gerhard
G
Glatting
Department of Veterinary Clinical Sciences, Small Animal Clinic, Justus-Liebig-University, 35392, Giessen, Germany.
Martin
M
Kramer
Department of Radiation Oncology, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, 68167, Mannheim, Germany.
Frank A
FA
Giordano
Department of Neuroradiology, University Medical Center of the Johannes Gutenberg University Mainz, 55131, Mainz, Germany.
Marc A
MA
Brockmann
D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000473:pathology; D001932:Brain Neoplasms / Q000000981:diagnostic imaging*; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000008:administration & dosage; D005260:Female; D005909:Glioblastoma / Q000000981:diagnostic imaging*; D006801:Humans; D053631:Interleukin Receptor Common gamma Subunit / Q000172:deficiency / Q000235:genetics; D007479:Iopamidol / Q000008:administration & dosage / Q000031:analogs & derivatives; D008297:Male; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D015203:Reproducibility of Results; D059629:Signal-To-Noise Ratio; D014183:Transplantation, Heterologous; D055114:X-Ray Microtomography / Q000379:methods*
D003287:Contrast Media; C507942:Il2rg protein, mouse; D053631:Interleukin Receptor Common gamma Subunit; C057937:iomeprol; D007479:Iopamidol