Robin A de Graaf1,2, Henk M De Feyter1, Peter B Brown1, Terence W Nixon1, Douglas L Rothman1,2, Kevin L Behar3. 1. Department of Radiology and Biomedical Imaging, Magnetic Resonance Research Center, Yale University School of Medicine, New Haven, Connecticut, USA. 2. Department of Biomedical Engineering, Magnetic Resonance Research Center, Yale University School of Medicine, New Haven, Connecticut, USA. 3. Department of Psychiatry, Magnetic Resonance Research Center, Yale University School of Medicine, New Haven, Connecticut, USA.
Abstract
PURPOSE: To develop 1 H-based MR detection of nicotinamide adenine dinucleotide (NAD+ ) in the human brain at 7T and validate the 1 H results with NAD+ detection based on 31 P-MRS. METHODS: 1 H-MR detection of NAD+ was achieved with a one-dimensional double-spin-echo method on a slice parallel to the surface coil transceiver. Perturbation of the water resonance was avoided through the use of frequency-selective excitation. 31 P-MR detection of NAD+ was performed with an unlocalized pulse-acquire sequence. RESULTS: Both 1 H- and 31 P-MRS allowed the detection of NAD+ signals on every subject in 16 min. Spectral fitting provided an NAD+ concentration of 107 ± 28 μM for 1 H-MRS and 367 ± 78 μM and 312 ± 65 μM for 31 P-MRS when uridine diphosphate glucose (UDPG) was excluded and included, respectively, as an overlapping signal. CONCLUSIONS: NAD+ detection by 1 H-MRS is a simple method that comes at the price of reduced NMR visibility. NAD+ detection by 31 P-MRS has near-complete NMR visibility, but it is complicated by spectral overlap with NADH and UDPG. Overall, the 1 H- and 31 P-MR methods both provide exciting opportunities to study NAD+ metabolism on human brain in vivo.
PURPOSE: To develop 1 H-based MR detection of nicotinamide adenine dinucleotide (NAD+ ) in the human brain at 7T and validate the 1 H results with NAD+ detection based on 31 P-MRS. METHODS: 1 H-MR detection of NAD+ was achieved with a one-dimensional double-spin-echo method on a slice parallel to the surface coil transceiver. Perturbation of the water resonance was avoided through the use of frequency-selective excitation. 31 P-MR detection of NAD+ was performed with an unlocalized pulse-acquire sequence. RESULTS: Both 1 H- and 31 P-MRS allowed the detection of NAD+ signals on every subject in 16 min. Spectral fitting provided an NAD+ concentration of 107 ± 28 μM for 1 H-MRS and 367 ± 78 μM and 312 ± 65 μM for 31 P-MRS when uridine diphosphate glucose (UDPG) was excluded and included, respectively, as an overlapping signal. CONCLUSIONS:NAD+ detection by 1 H-MRS is a simple method that comes at the price of reduced NMR visibility. NAD+ detection by 31 P-MRS has near-complete NMR visibility, but it is complicated by spectral overlap with NADH and UDPG. Overall, the 1 H- and 31 P-MR methods both provide exciting opportunities to study NAD+ metabolism on human brain in vivo.
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