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

Martyna Dziadosz, Maike Hoefemann, André Döring, Malgorzata Marjańska, Edward John Auerbach, Roland Kreis

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Purpose: The detection of nicotinamide-adenine-dinucleotide (NAD+) is challenging using standard 1H 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 1H 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.

Original languageEnglish (US)
Pages (from-to)1027-1038
Number of pages12
JournalMagnetic resonance in medicine
Issue number3
StatePublished - Sep 2022

Bibliographical note

Funding Information:
This work is supported by the Swiss National Science Foundation (SNSF #320030‐175984, 202962). M.M. and E.J.A. acknowledge support from the following National Institutes of Health grants: BTRC P41 EB027061 and P30 NS076408.

Publisher Copyright:
© 2022 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.


  • MR spectroscopy
  • NAD
  • brain
  • detectability
  • fitting
  • magnetization exchange
  • modeling
  • precision
  • quantification
  • saturation transfer

Center for Magnetic Resonance Research (CMRR) tags

  • SMCT
  • P41

PubMed: MeSH publication types

  • Comparative Study
  • Journal Article
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural


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