Single‐Voxel ¹H MR spectroscopy of cerebral nicotinamide adenine dinucleotide (NAD⁺) in humans at 7T using a 32‐channel volume coil

Abstract

Purpose: Reliable monitoring of tissue nicotinamide adenine dinucleotide (NAD + ) concentration may provide insights on its roles in normal and pathological aging.In the present study, we report a 1 H MRS pulse sequence for the in vivo, localized 1 H MRS detection of NAD + from the human brain.Methods: Studies were carried out on a 7T Siemens MRI scanner using a 32-channel product volume coil. The pulse sequence consisted of a spectrally selective low bandwidth E-BURP-1 90° pulse. PRESS localization was achieved using optimized Shinnar-Le Roux 180° pulses and overlapping gradients were used to minimize the TE. The reproducibility of NAD + quantification was measured in 11 healthy volunteers. The association of cerebral NAD + with age was assessed in 16 healthy subjects 26-78 years old. Results: Spectra acquired from a voxel placed in subjects' occipital lobe consisted of downfield peaks from the H 2 , H 4 , and H 6 protons of the nicotinamide moiety of NAD + between 8.9-9.35 ppm. The mean ± SD within-session and between-session coefficients of variation were found to be 6.14 ± 2.03% and 6.09 ± 3.20%, respectively. In healthy volunteers, an age-dependent decline of the NAD + levels in the brain was also observed (β = −1.24 μM/y, SE = 0.21, P < 0.001). Conclusion:We demonstrated the feasibility and robustness of a newly developed 1 H MRS technique to measure localized cerebral NAD + at 7T MRI using a | 807 BAGGA et Al.

Non‐water‐excitation MR spectroscopy techniques to explore exchanging protons in human brain at 3 T

“…24 A similar TE was achieved for 7 T with a 3D-localizing triple-echo sequence with optimized Shinnar-Le Roux refocusing pulses. 25 The nWE method with the shortest reported TE so far was suggested by Gonçalves et al 28 for use in rat brain at 9.4T. It was similar to our 3D I-CSE method, first reported at about the same time in Ref.…”

“…Instead, to obtain a short TE of 18 ms at 7 T, 1D‐LASER was used to localize a whole slice 24 . A similar TE was achieved for 7 T with a 3D‐localizing triple‐echo sequence with optimized Shinnar‐Le Roux refocusing pulses 25 . The nWE method with the shortest reported TE so far was suggested by Gonçalves et al 28 for use in rat brain at 9.4T.…”

“…5 It consisted of combining either PRESS 21 or Image-selected in vivo spectroscopy (ISIS) 22 localization with frequency-selective excitation, although only PRESSbased nWE was recommended. Later, LASER-based 23 double-echo, 23,24 and triple-echo 25 methods have been optimized for the detection of nicotinamide-adenine dinucleotide (NAD + ). Furthermore, the transfer of longitudinal magnetization in the recovery period after excitation was exploited at UHF up to 21 T to obtain longitudinal relaxation enhancement (LRE) in animal experiments, based on LASER localization 13,26,27 or a spin-echo.…”

Brain NAD Is Associated With ATP Energy Production and Membrane Phospholipid Turnover in Humans

“…The first 31 P-MRS study to report NAD in the aging human brain found that tNAD, NAD + , and the NAD + /NADH redox ratio decreased with age in the occipital region (Zhu et al, 2015). Similar findings were found for NAD + measured by 1 H-MRS (Bagga et al, 2020), but this was not replicated in a recent 31 P-MRS study in which NAD was not affected by age (Elhassan et al, 2019). When NAD was measured in the frontal lobe of healthy participants (Kim et al, 2017), an age-dependent increase in NADH and decrease in the NAD + /NADH redox ratio was observed, but no change in NAD + was detected.…”

Age-Dependent Decline of NAD+ - Universal Truth or Confounded Consensus?

“…This is, in part, caused by the measuring of combined NAD + and NAD, but NADH levels do not account for the multiple orders of magnitude difference observed here. Despite these caveats, the relative change in CSF NAD(H) with age is consistent with later reports on brain NAD + levels [89,90].…”