Time dependent changes in tumor growth of NDEA-treated c-Myc transgenic mice.

<p>(A) The organ and tumor volume was assessed by CT and by histopathology. Depicted is the percentage tumor volume at different stages measured either by histopathology (light gray) or by contrast enhanced CT imaging (dark gray). The mean diameter of lesions (B) and the total number of lesions (C) are shown. *p<0.05. **p<0.01.</p

Mean tumor volume for NDEA treated c-Myc transgenic mice separated by gender.

<p>Data were obtained by CT and histopathology and are defined as mean percentage tumor volume and standard error of the mean for NDEA treated animals. Data are broken down by gender. At the age of 5.5 months the tumor incidence was 100% for male and female animals. No gender specific difference in tumor volume was observed except for histopathology findings at the age of 7 months;</p><p>*P<0.05.</p

Histopathology of the liver of c-Myc treated transgenic animals.

<p>(A) Diffuse liver cell dysplasia of physiological saline ( = vehicle) treated transgenic mice at (A1) 50- and (A2) 200-fold magnification. (B) Large cell dysplasia of various degrees in BHT treated animals at (B1) 50- and (B2) 200-fold magnification. (C) Hepatocellular carcinoma of a transgenic mouse treated with the genotoxic carcinogen NDEA at (C1) 50 and (C2) 200-fold magnification.</p

Contrast-enhanced CT, ¹⁸F-FDG-PET and fused images of c-Myc transgenic mice treated with NDEA at the age of 5.5 and 7 months.

<p>(A) CT image demonstrates a single tumor lesion (A1) in a 5.5 months old mouse without increased ¹⁸F-FDG uptake (A2). The fused CT and PET image is depicted in A3. (B) At the age of 7 months expansive tumor growth (B1) as well as an increased tracer uptake in hepatocellular carcinoma (B2) is observed. The fused CT and PET image is depicted in B3. G = gallbladder, K = kidney, L = liver, S = spine, St = stomach, T = tumor.</p

CT and histopathology of the lung of NDEA treated c-Myc transgenic mice.

<p>(A) Normal lung parenchyma of a vehicle treated control animal as shown by CT (A1) and by histopathology (A2). CT of NDEA treated animals at the age of 8.5 months. Depicted are lung nodules of different size (red arrows). Histopathology evidenced those lung nodules as metastasis of a poorly differentiated HCC (B2) and as well adenocarcinoma of the lung (C2).</p

Study groups and imaging protocol.

<p>Histopathology was carried out for all groups and for all time points (4, 5.5, 7, 8.5 months).</p><p>*<b>No CT/PET imaging was done,</b></p><p>**<b>CT/PET was acquired at the age of 8.5 months only. m, months; w, weeks.</b></p

Fused μPET/μCT images of the liver of c-Myc transgenic mice treated with physiological saline, BHT or NDEA.

<p>Depicted are the liver morphology as determined by CT (A1, B1,C1), the glucose metabolism (A2, B2, C2) and fused PET and CT scans (A3, B3, C3) of transgenic animals treated with either physiological saline (A), with BHT (B) or with NDEA (C) at the age of 8.5 months. Note, after treatment with NDEA expansive tumor growth with large increase of liver weight and compression and displacement of adjacent organs was observed. Here, the lesions showed an increased 18F-FDG uptake. In contrast, in corresponding control animals treated with physiological saline no liver lesions were observed. After treatment with BHT small hypodens lesions are noticed, but PET did not show an increased 18F-FDG uptake. K = kidney, L = liver, S = spine, Sp = spleen, St = stomach, T = tumor.</p

Results of TLD-measurements at different positions (mean doses with standard deviation).

<p>Designations of positions according to <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0044427#pone-0044427-t002" target="_blank">table 2</a>. White columns: measured dose of the TLD, black columns: calculated dose for the mice according to <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0044427#pone.0044427.e005" target="_blank">equation 5</a>.</p

Segmentation of aerated lung volume as a surrogate to assess the multifocal tumor spread in SPC-raf transgenic animals.

<p>Micro-CT showing the diffuse bilateral tumour growth (A). Seed points are placed manually in the aerated lung (B). Segmentation of the aerated lung is performed applying a region growing algorithm (C).</p

Placement of TLD on anaesthetized mouse.

<p>A: Cranial view showing TLD positions 1–7 (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0044427#pone-0044427-t002" target="_blank">table 2</a>). B: Lateral view showing TLD positions 8 and 9 (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0044427#pone-0044427-t002" target="_blank">Table 2</a>).</p