Using an autoradiography technique, Mori et al. found that BMSC transplantation significantly improves glucose metabolism in the thalamus and barrel cortex in response to whisker stimulation after neocortical freezing injury [12]. The study by Dr. Wang et al. demonstrated functional recovery in a rat stroke model treated by intraventricularly administered ESCs and iPSCs along with increased ¹⁸F-FDG uptake in stroke lesions depicted by small-animal PET and autoradiography. Immunohistochemistry examination at 4 weeks after cell transplantation also indicated the presence of neuronal differentiation among injected cells [44, 45]. Du et al. reported that the BMSCs delivered via the intra-arterial route promoted angiogenesis and improved functional recovery in a rat transient MCA occlusion model, using ^99mTc-ECD SPECT and ¹⁸F-FDG PET [46]. We also serially assessed local glucose metabolism in the rats subjected to permanent MCA occlusion and found that BMSC transplantation significantly enhances the recovery in the peri-infarct area, using small-animal ¹⁸F-FDG PET/CT system. As shown in Fig. 9.2, glucose utilization was markedly decreased in the ipsilateral neocortex at 6 days after ischemia. In the vehicle-treated animals, glucose utilization improved to some extent in the peri-infarct neocortex at 35 days after ischemia, that is, 28 days after transplantation. However, BMSC transplantation significantly enhanced the recovery in the peri-infarct neocortex at the same time point [5]. Considering together with ¹²³I-IMZ study, the BMSCs may enhance the recovery of local glucose metabolism by improving neuronal integrity in the peri-infarct area, when directly transplanted into the infarct brain, because oxidative glucose metabolism is quite high in the neurons. Therefore, BMSC transplantation may possibly contribute to accelerate functional recovery by improving neuronal integrity and local metabolism in the peri-infarct brain. However, some alternative possibilities are not completely excluded. The increase in ¹⁸F-FDG uptake might indicate not only neural but also glial proliferation by cell therapy, neovascular growth facilitated by treatment, or a simple reflection of macrophage migration and microglial activation after ischemia. Although the mechanisms of ¹⁸F-FDG uptake in the stem cell-treated lesions are still not clear, the uptake and functional recovery measured by behavioral testing appear to correlate in some studies [45].

It would be essential to establish functional bio-imaging technique serially and noninvasively validating the effects of cell therapy on the host CNS in order to achieve clinical application of cell therapy for cerebral stroke. Although there are few studies that indicate the utility of imaging techniques to monitor the response of the host CNS after cell therapy and further investigation is needed, ¹²³I-IMZ SPECT and ¹⁸F-FDG PET may be promising modalities to assess the therapeutic benefits of cell therapy for ischemic stroke without subjective bias in clinical situation.