Uptake of administered D-glucose (Glc) or 2-deoxy-D-glucose (2DG) has been indirectly mapped through the chemical exchange (CE) between glucose hydroxyl and water protons using CE-dependent saturation transfer (glucoCEST) magnetic resonance imaging (MRI). We propose an alternative technique—on-resonance CE-sensitive spin-lock (CESL) MRI—to enhance responses to glucose changes. Phantom data and simulations suggest higher sensitivity for this ‘glucoCESL' technique (versus glucoCEST) in the intermediate CE regime relevant to glucose. Simulations of CESL signals also show insensitivity to B0-fluctuations. Several findings are apparent from in vivo glucoCESL studies of rat brain at 9.4 Tesla with intravenous injections. First, dose-dependent responses are nearly linearly for 0.25-, 0.5-, and 1-g/kg Glc administration (obtained with 12-second temporal resolution), with changes robustly detected for all doses. Second, responses at a matched dose of 1 g/kg are much larger and persist for a longer duration for 2DG versus Glc administration, and are minimal for mannitol as an osmolality control. And third, with similar increases in steady-state blood glucose levels, glucoCESL responses are ∼2.2 times higher for 2DG versus Glc, consistent with their different metabolic properties. Overall, we show that glucoCESL MRI could be a highly sensitive and quantifiable tool for glucose transport and metabolism studies.

Our results demonstrate that glucoCESL MRI has both extracellular and intracellular contributions, and can be a useful tool for measurements of both vascular permeability and glucose uptake in tumors.

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 (Δ Rρ) in normal rat brain peaked at ∼15 min after the intravenous injection of 1 g/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 Δ Rρ. 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 Δ Rρ in the ischemic core but higher Δ Rρ 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.

Purpose To evaluate the performance of an independent recalculation and compare it against current measurement‐based patient specific intensity‐modulated radiation therapy (IMRT) quality assurance (QA) in predicting unacceptable phantom results as measured by the Imaging and Radiation Oncology Core (IROC). Methods When institutions irradiate the IROC head and neck IMRT phantom, they are also asked to submit their internal IMRT QA results. Separately from this, IROC has previously created reference beam models on the Mobius3D platform to independently recalculate phantom results based on the institution's DICOM plan data. The ability of the institutions’ IMRT QA to predict the IROC phantom result was compared against the independent recalculation for 339 phantom results collected since 2012. This was done to determine the ability of these systems to detect failing phantom results (i.e., large errors) as well as poor phantom results (i.e., modest errors). Sensitivity and specificity were evaluated using common clinical thresholds, and receiver operator characteristic (ROC) curves were used to compare across different thresholds. Results Overall, based on common clinical criteria, the independent recalculation was 12 times more sensitive at detecting unacceptable (failing) IROC phantom results than clinical measurement‐based IMRT QA. The recalculation was superior, in head‐to‐head comparison, to the EPID, ArcCheck, and MapCheck devices. The superiority of the recalculation vs these array‐based measurements persisted under ROC analysis as the recalculation curve had a greater area under it and was always above that for these measurement devices. For detecting modest errors (poor phantom results rather than failing phantom results), neither the recalculation nor measurement‐based IMRT QA performed well. Conclusions A simple recalculation outperformed current measurement‐based IMRT QA methods at detecting unacceptable plans. These findings highlight the value of an independent recalculation, and raise further questions about the current standard of measurement‐based IMRT QA.

Recent proof-of-principle studies have demonstrated the feasibility of measuring the uptake and metabolism of non-labelled 2-deoxy-D-glucose (2DG) by a chemical exchange-sensitive spin-lock (CESL) MRI approach. In order to gain better understanding of this new approach, we performed dynamic in vivo CESL MRI on healthy rat brains with an intravenous injection of 2DG under various conditions at 9.4 T. For three 2DG doses of 0.25, 0.5 and 1 g/kg, we found that 2DG-CESL signals increased linearly with injection dose at the initial (<20 min) but not the later period (>40 min) suggesting time-dependent differential weightings of 2DG transport and metabolism. Remaining 2DG-CESL studies were performed with 0.25 g/kg 2DG. Since a higher isoflurane level reduces glucose metabolism and increases blood flow, 2DG-CESL was measured under 0.5%, 1.5% and 2.2% isoflurane. The 2DG-CESL signal was reduced at higher isoflurane levels correlating well with the 2DG phosphorylation in the intracellular space. To detect regional heterogeneities of glucose metabolism, 2DG-CESL with 0.33×0.33×1.50 mm3 resolution was obtained, which indeed showed a higher response in the cortex compared to the corpus callosum. Lastly, unlike CESL MRI with the injection of non-transportable mannitol, the 2DG-CESL response decreased with an increased spin-lock pulse power confirming that 2DG-CESL is dominated by chemical exchange processes in the extravascular space. Taken together, our results showed that 2DG-CESL MRI signals mainly indicate glucose transport and metabolism and may be a useful biomarker for metabolic studies of normal and diseased brains.