Previously, we devised a novel strategy for in vivo 13C MRS using [2-13C]glucose infusion and low-power proton decoupling, and proposed that this strategy could be used to acquire 13C MR spectra from the frontal lobe of the human brain. Here, we demonstrate, for the first time, in vivo 13C MRS of human frontal lobe acquired at 3 T. Because the primary metabolites of [2-13C]glucose can be decoupled using very-low-radiofrequency power, we used a volume coil for proton decoupling in this study. The homogeneous B1 field of the volume coil was found to significantly enhance the decoupling efficiency of the stochastic decoupling sequence. Detailed specific absorption rates inside the human head were analyzed using the finite difference time domain method to ensure experimental safety. In vivo 13C spectra from the occipital and frontal lobes of the human brain were obtained. At a decoupling power of 30 W (time-averaged power, 2.45 W), the spectra from the occipital lobe showed well-resolved spectral resolution and excellent signal-to-noise ratio. Although frontal lobe 13C spectra were affected by local B0 field inhomogeneity, we demonstrated that the spectral quality could be improved using post-acquisition data processing. In particular, we showed that the frontal lobe glutamine C5 at 178.5 ppm and aspartate C4 at 178.3 ppm could be spectrally resolved with effective proton decoupling and B0 field correction. Because of its large spatial coverage, volume coil decoupling provides the potential to acquire 13C MRS from more than one brain region simultaneously.
Reliable detection of Glu, Gln, and GSH was achieved. Glu and Gln levels were significantly higher in frontal lobe GM than in frontal lobe WM. It is feasible to use the proposed proton MR spectroscopy method to measure the kinetics of (13) C incorporation into Glu and Gln during infusion of (13) C labeled glucose.
Nociceptin/orphanin FQ peptide (NOP) receptor is a new class of opioid receptor that may play a pathophysiologic role in anxiety and drug abuse and is a potential therapeutic target in these disorders. We previously developed a high-affinity PET ligand, 11C-NOP-1A, which yielded promising results in monkey brain. Here, we assessed the ability of 11C-NOP-1A to quantify NOP receptors in human brain and estimated its radiation safety profile. Methods After intravenous injection of 11C-NOP-1A, 7 healthy subjects underwent brain PET for 2 h and serial sampling of radial arterial blood to measure parent radioligand concentrations. Distribution volume (VT; a measure of receptor density) was determined by compartmental (1- and 2-tissue) and noncompartmental (Logan analysis and Ichise’s bilinear analysis [MA1]) methods. A separate group of 9 healthy subjects underwent whole-body PET to estimate whole-body radiation exposure (effective dose). Results After 11C-NOP-1A injection, the peak concentration of radioactivity in brain was high (~5–7 standardized uptake values), occurred early (~10 min), and then washed out quickly. The unconstrained 2-tissue-compartment model gave excellent VT identifiability (~1.1% SE) and fitted the data better than a 1-tissue-compartment model. Regional VT values (mL·cm−3) ranged from 10.1 in temporal cortex to 5.6 in cerebellum. VT was well identified in the initial 70 min of imaging and remained stable for the remaining 50 min, suggesting that brain radioactivity was most likely parent radioligand, as supported by the fact that all plasma radiometabolites of 11C-NOP-1A were less lipophilic than the parent radioligand. Voxel-based MA1 VT values correlated well with results from the 2-tissue-compartment model, showing that parametric methods can be used to compare populations. Whole-body scans showed radioactivity in brain and in peripheral organs expressing NOP receptors, such as heart, pancreas, and spleen. 11C-NOP-1A was significantly metabolized and excreted via the hepatobiliary route. Gallbladder had the highest radiation exposure (21 µSv/MBq), and the effective dose was 4.3 µSv/MBq. Conclusion 11C-NOP-1A is a promising radioligand that reliably quantifies NOP receptors in human brain. The effective dose in humans is low and similar to that of other 11C-labeled radioligands, allowing multiple scans in 1 subject.
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