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

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.