Quantification of NAD ⁺ T ₁ and T ₂ relaxation times using downfield ¹ H MRS at 7 T in human brain in vivo

Abstract

Introduction

The purpose of this study was to use a single-slice spectrally-selective sequence to measure T ₁ and T ₂ relaxation times of NAD ⁺ proton resonances in the downfield ¹ H MRS spectrum in human brain at 7 T in vivo and assess the propagation of relaxation time uncertainty in NAD ⁺ quantification.

Methods

Downfield spectra from 7 healthy volunteers were acquired at multiple echo times in all subjects to measure T ₂ relaxation, and saturation recovery data were to measure T ₁ relaxation. 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. For the multiple echo experiment, spectra were collected with echo times ranging from 13 to 33 ms. For the saturation recovery experiment, saturation was performed prior to excitation using the same spectrally-selective sinc pulse as was used for excitation. Saturation delay times (TS) ranged from 100 to 600 ms. Uncertainty propagation analysis was performed analytically and with Monte Carlo simulation.

Results

The mean ± standard deviation of T ₁ relaxation times of the H2, H6, and H4 protons were 152.7 ± 16.6, 163.6 ± 22.3, and 169.9 ± 11.2 ms, respectively. The mean ± standard deviation of T ₂ relaxation times of the H2, H6, and H4 protons were 32.5 ± 7.0, 27.4 ± 5.2, and 38.1 ± 11.7 ms, respectively. The mean R ² of the H2 and H6 T ₁ fits were 0.98. The mean R ² of the H4 proton T ₁ fit was 0.96. The mean R ² of the T ₂ fits of the H2 and H4 proton resonances were 0.98, while the mean R ² of the T ₂ fits of the H4 proton was 0.93. The relative uncertainty in NAD ⁺ concentration due to relaxation time uncertainty was 8.5%-11%.

Conclusion

Using downfield spectrally-selective spectroscopy with single-slice localization, we found NAD ⁺ T ₁ and T ₂ relaxation times to be approximately 162 ms and 32 ms respectively in the human brain in vivo at 7 T.

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