Quantification of NAD⁺<i>T</i>₁ and <i>T</i>₂ Relaxation Times Using Downfield ¹H MRS at 7 T in Human Brain In Vivo

The purpose of this study was to measure T₁ and T₂ relaxation times of NAD⁺ proton resonances in the downfield ¹H MRS spectrum in human brain at 7 T in vivo and to assess the propagation of relaxation time uncertainty in NAD⁺ quantification. Downfield spectra from eight healthy volunteers were acquired at multiple echo times to measure T₂ relaxation times, and saturation recovery data were acquired to measure T₁ relaxation times. The downfield acquisition used a spectrally selective 90° sinc pulse for excitation centered at 9.1 ppm with a bandwidth of 2 ppm, followed by a 180° spatially selective Shinnar-Le Roux refocusing pulse for localization. Uncertainty propagation analysis on metabolite quantification was performed analytically and with Monte Carlo simulation. [NAD⁺] was quantified in five participants. The mean ± standard deviation of T₁ relaxation times of the H2, H6, and H4 NAD⁺ protons were 205.6 ± 25.7, 211.6 ± 33.5, and 237.3 ± 42.4 ms, respectively. The mean ± standard deviation of T₂ relaxation times of the H2, H6, and H4 protons were 33.6 ± 7.4, 29.1 ± 4.7, and 42.3 ± 11.6 ms, respectively. The relative uncertainty in NAD⁺ concentration due to relaxation time uncertainty was 8.4%-11.4%, and measured brain [NAD⁺] (N = 5) was 0.324 ± 0.050 mM. Using downfield spectrally selective spectroscopy with single-slice localization, we found T₁ and T₂ relaxation times averaged across all NAD⁺ resonances to be approximately 218 and 35 ms, respectively, in the human brain in vivo at 7 T.