Quantitative measurement of redox state in human brain by P MRS at 7T with spectral simplification and inclusion of multiple nucleotide sugar components in data analysis.

PURPOSE

To develop a simplified method for quantitative measurement of NAD /NADH (nicotinamide adenine dinucleotides) levels in human brain by P MRS without interference from the α-ATP signal and with inclusion of multiple UDP-sugar components.

METHODS

Simple pulse-acquire P MR spectra were collected at 7T with and without a frequency-selective inversion pulse to remove the dominant α-ATP signal from the underlying NAD(H) signal. Careful inspection of the P signal at -9.8 ppm previously assigned to UDP-glucose revealed multiple UDP-sugar components that must also be considered when deconvoluting the NAD(H) signal to quantify NAD and NADH. Finally, the overlapping NAD(H) and UDP(G) resonances were deconvoluted into individual components using Voigt lineshape analysis and UDP(G) modeling.

RESULTS

The inversion-based spectral editing method enabled clean separation of the NAD(H) signal from the otherwise dominant α-ATP signal. In addition, the upfield signal near -9.8 ppm appears more "quartet-like" than a simple doublet consistent with contributions from other nucleotide sugars such as UDP-galactose, UDP-N-acetyl-galactosamine, and UDP-N-acetyl-glucosamine in addition to UDP-glucose. Deconvolution of the combined NAD(H) and UDP(G) signals showed that the measured NAD /NAD ratio was heavily influenced by UDP(G) modeling (7.5 ± 1.8 when the UDP(G) signal was fitted as multiple doublets versus 5.3 ± 0.6 when a simplified pseudo doublet model was used). In a test/re-test experiments separated by 2 weeks, consistent NAD /NADH ratios were measured in the brain of seven human subjects.

CONCLUSIONS

The NAD /NADH ratio in human brain can be measured using P MR spectra simplified by spectral editing and with inclusion of multiple UDP-sugar components in the data analysis.