Table 1.
Overview of scans acquired at several time points post-injection (PI).
Fig 1.
MR imaging and histological confirmation of brain metastasis development.
a-b. In vivo serial T2w MRI scans in the same rat (a) and mouse (b) showing metastasis development as soon as 3 weeks after intracardiac injection (metastases are indicated with an arrow). c-d. T2w MR image (c) and T1w MR image after Gd enhancement (d) both acquired in a rat brain 6 weeks after intracardiac injection (metastases are indicated with an arrow). e. Histological confirmation of metastasis by H&E staining on paraffin-embedded slices in the cerebellum of a rat.
Fig 2.
Correlation of brain metastasis and hypointensities.
a-b. Rat brain metastasis visible on a T2w image (a) could be correlated to a corresponding hypointense signal void on a T2*w image (b) as indicated with an arrow. c-d. Mouse brain metastases visible on a T2w image (c) could be correlated to corresponding signal voids on a T2*w image (d) as indicated with an arrow. e-h. Scatterplots describe the relation between ‘number of hypointensities’ and ‘number of brain metastases’ for rats (n = 13) injected with MPIO-labeled cancer cells 3 and 4 weeks PI (e and f, respectively) and mice (n = 5) injected with MPIO-cancer cells 3 and 4 weeks PI (g and h, respectively).
Fig 3.
a. Total volume of brain metastases (mm3) of rats injected with MPIO-labeled (n = 13) or unlabeled (n = 8) cancer cells; data acquired 3 and 4 weeks post-injection. b. Total number of brain metastases of rats injected with MPIO-labeled (n = 13) or unlabeled (n = 8) cancer cells; data acquired 3 and 4 weeks post-injection. c. Total volume of brain metastases (mm3) of mice (n = 5) injected with MPIO-cancer cells; data acquired 3 and 4 weeks post-injection. d. Total number of brain metastases of mice (n = 5) injected with MPIO-labeled cancer cells; data acquired 3 and 4 weeks post-injection. a-d. For all 3 groups, a significant difference was found between number of metastases measured 3 and 4 weeks PI and also between volume of metastases measured 3 and 4 weeks PI.
Fig 4.
a-d. High-resolution μCT images acquired on X-CUBE (recon: FDK—50 μm). Evaluation showed metastasis throughout the skeleton in 81% (17/21) of the rats. Examples of lytic bone lesions detected in vertebra (a), tibia (b), femur (c) and skull (d) are indicated with an arrow. e-f. Static full-body [18F]FDG PET image showing metastasis in the skeleton of rat (e) and no metastasis in the skeleton of mouse (f). g. Number of metastasis affected bones showing a significant difference between rats and mice. h. Kaplan Meier curves and log-rank test demonstrate a significant difference in clinical symptoms free survival times between rats and mice.
Fig 5.
[18F]FDG and [18F]NaF PET imaging in rats.
a. Static whole-body rat [18F]FDG PET image. b. Static whole-body rat [18F]NaF PET image. c. PET-CT image of rat vertebra; [18F]FDG PET image anatomically correlated with high resolution CT (recon: FDK—50 μm). This lytic lesion is clearly visible on the [18F]FDG PET images as a hypermetabolic lesion (‘hot spot’) d. PET-CT image of rat vertebra; [18F]NaF PET image anatomically correlated with high resolution CT (recon: FDK—50 μm). The bone lesions have a mixed appearance: both ‘hot spots’ and ‘cold spots’ are visualized in the lytic CT lesions, probably depending on the stage of destruction and reaction of the surrounding bone.