Quantification of NAD+ in human brain with 1 H MR spectroscopy at 3 T: Comparison of three localization techniques with different handling of water magnetization.

ABSTRACT

PURPOSE: The detection of nicotinamide-adenine-dinucleotide (NAD+ ) is challenging using standard 1 H MR spectroscopy, because it is of low concentration and affected by polarization-exchange with water. Therefore, this study compares three techniques to access NAD+ quantification at 3 T-one with and two without water presaturation. METHODS: A large brain volume in 10 healthy subjects was investigated with three techniques semi-LASER with water-saturation (WS) (TE = 35 ms), semi-LASER with metabolite-cycling (MC) (TE = 35 ms), and the non-water-excitation (nWE) technique 2D ISIS-localization with chemical-shift-selective excitation (2D I-CSE) (TE = 10.2 ms). Spectra were quantified with optimized modeling in FiTAID. RESULTS: NAD+ could be well quantified in cohort-average spectra with all techniques. Obtained apparent NAD+ tissue contents are all lower than expected from literature confirming restricted visibility by 1 H MRS. The estimated value from WS-MRS (58 µM) was considerably lower than those obtained with non-WS techniques (146 µM for MC-semi-LASER and 125 µM for 2D I-CSE). The nWE technique with shortest TE gave largest NAD+ signals but suffered from overlap with large amide signals. MC-semi-LASER yielded best estimation precision as reflected in relative Cramer-Rao bounds (14%, 21 µM/146 µM) and also best robustness as judged by the coefficient-of-variance over the cohort (11%, 10 µM/146 µM). The MR-visibility turned out as 16% with WS and 41% with MC. CONCLUSION: Three methods to assess NAD+ in human brain at 3 T have been compared. NAD+ could be detected with a visibility of ∼41% for the MC method. This may open a new window for the observation of pathological changes in the clinical research setting.