Chemical exchange-sensitive spin-lock MRI of glucose analog 3-O-methyl-D-glucose in normal and ischemic brain

Glucose transport is important for understanding brain glucose metabolism. We studied glucose transport with a presumably non-toxic and non-metabolizable glucose analog, 3-O-methyl-D-glucose, using a chemical exchange-sensitive spin-lock MRI technique at 9.4 Tesla. 3-O-methyl-D-glucose showed comparable chemical exchange properties with D-glucose and 2-deoxy-D-glucose in phantoms, and higher and lower chemical exchange-sensitive spin-lock sensitivity than Glc and 2-deoxy-D-glucose in in vivo experiments, respectively. The changes of the spin-lattice relaxation rate in the rotating frame (Delta R-1 rho) in normal rat brain peaked at similar to 15 min after the intravenous injection of 1g/kg 3-O-methyl-D-glucose and almost maintained a plateau for >1 h. Doses up to 4 g/kg 3-O-methyl-D-glucose were linearly correlated with Delta R-1 rho. In rats with focal ischemic stroke, chemical exchange-sensitive spin-lock with 3-O-methyl-D-glucose injection at 1 h after stroke onset showed reduced Delta R-1 rho in the ischemic core but higher Delta R-1 rho in the peri-core region compared to normal tissue, which progressed into the ischemic core at 3 h after stroke onset. This suggests that the hyper-chemical exchange-sensitive spin-lock region observed at 1 h is the ischemic penumbra at-risk of infarct. In summary, 3-O-methyl-D-glucose-chemical exchange-sensitive spin-lock can be a sensitive MRI technique to probe the glucose transport in normal and ischemic brains.