In vivo imaging of the penumbra in mice using small animal 18F-FDG PET

Background and aims: Positron emission tomography (PET) is used to image the ischemic penumbra after stroke in humans. Until recently, however, the spatial resolution of these techniques was not high enough to properly image the brain and small rodents. The aim of the current study was therefore to investigate whether the ischemic penumbra can be identified and studied in a murine model of ischemic stroke using the latest generation of high resolution small animal PET scanners. Methods: Male C57/B16 mice (n=5) were investigated and subjected to laser Doppler-controlled left MCA occlusion (MCAo) by an intraluminal filament. As a measure of cerebral glucose metabolism 14 MBq 18F FDG were injected i.v. 20 min after induction of ischemia. A small animal PET scan was acquired (30-50 min p.i., microPET FOCUS F120 scanner (Siemens Medical Solutions, USA)), followed by a small animal whole body CT-scan (Siemens MicroCAT 2) for anatomic allocation. PET data were reconstructed with FBP (ramp filter with a cut-off at the Nyquist frequency). The image volume consisted of 128x128x95 voxels, with a size of 0.866 x 0.866 x 0.796 mm3 per voxel. Results: The acquired FDG PET images showed a significantly reduced cerebral metabolism (50% ± 11% of contralateral hemisphere) in the MCA territory, i.e. the area of cerebral ischemia (p<0,05, Fig 1, white arrow). Furthermore, we could demonstrate that the small animal PET can identify the increased glucose metabolism in the ischemic penumbra (114% ± 6% of contralateral hemisphere, Fig. 1, grey arrow). Conclusions: These results demonstrate the feasibility of PET imaging in murine models of ischemic stroke. The glucose metabolism of the infarct core as well as of the ischemic penumbra can be imaged with high resolution and accuracy. This method may therefore open new possibilities for the investigation of the brain metabolism in transgenic mice and for non invasive evaluation of neuroprotective substances.