Abstract WP350: Detecting Endogenous Neurogenesis After Ischemic Stroke: A F-18-fluorothymidine PET Study

Abstract

Background and Purpose: Adult neural stem cells (NSCs) can be activated after stroke, but currently noninvasive imaging technique to visualize cerebral neurogenesis is lacking. F-18-fluorothymidine (FLT) has been used as a PET tracer to image cell proliferation and could detect endogenous NSCs in vivo . In this study, we assessed the change in cerebral FLT uptake in a rat model of ischemic stroke. Methods: Cerebral FLT PET was performed in rats subjected to transient middle cerebral artery occlusion (MCAO). PET data were semiquantitatively analyzed and expressed as average mean standardized uptake value ratios (SUVRs) of regions of interest using cerebellar cortex as the reference region. Neurological function was assessed via modified Neurological Severity Score (mNSS) 1 day after MCAO, and infarct volume was analyzed by 2,3,5-Triphenyltetrazolium chloride staining method 7 days after MCAO. Results: Seven days after MCAO, rats exhibited a higher number of Ki67 immunoreactive cells at the subventricular zone, striatum, frontal and temporal cortices in the infarcted brain, indicating promotion of neurogenesis (Figure 1A). The FLT PET showed higher SUVR in the infarcted brain compared to the unaffected side (Figure 1B; Striatum: 1.03±0.36 vs 0.74±0.16, p=0.001; Frontal: 1.14±0.27 vs 0.96±0.13, p=0.004; Temporal: 1.16±0.26 vs 1.00±0.15, p=0.01). The cerebral FLT binding activity gradually declined from post MCAO day 7 to day 28 in the infarcted brain (Figure 1C and D). The FLT binding ratio (global SUVR in the infarcted brain divided by that in the contralateral side) was positively correlated to the severity of stroke, including mNSS (r=0.70, p<0.001) and infarct volume (r=0.90, p<0.001). Conclusion: In vivo FLT PET can detect NSCs in a rat model of ischemic stroke. The promising results of FLT PET suggest that it can be potentially applied in clinical studies as noninvasive longitudinal monitoring and quantification of endogenous NSC activation in the human brain.