Jimin Ren1,2, Craig R Malloy1,2,3,4, A Dean Sherry1,3,5. 1. Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, USA. 2. Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA. 3. Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA. 4. VA North Texas Health Care System, Dallas, TX, USA. 5. Department of Chemistry & Biochemistry, University of Texas at Dallas, Richardson, TX, USA.
Abstract
PURPOSE: To develop a simplified method for quantitative measurement of NAD+ /NADH (nicotinamide adenine dinucleotides) levels in human brain by 31 P MRS without interference from the α-ATP signal and with inclusion of multiple UDP-sugar components. METHODS: Simple pulse-acquire 31 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 31 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 31 P MR spectra simplified by spectral editing and with inclusion of multiple UDP-sugar components in the data analysis.
PURPOSE: To develop a simplified method for quantitative measurement of NAD+ /NADH (nicotinamide adenine dinucleotides) levels in human brain by 31 P MRS without interference from the α-ATP signal and with inclusion of multiple UDP-sugar components. METHODS: Simple pulse-acquire 31 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 31 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 31 P MR spectra simplified by spectral editing and with inclusion of multiple UDP-sugar components in the data analysis.
Authors: Gaurav Sharma; Xiaodong Wen; Nesmine R Maptue; Thomas Hever; Craig R Malloy; A Dean Sherry; Chalermchai Khemtong Journal: ACS Sens Date: 2021-11-11 Impact factor: 7.711
Authors: Andreas Korzowski; Nina Weckesser; Vanessa L Franke; Johannes Breitling; Steffen Goerke; Heinz-Peter Schlemmer; Mark E Ladd; Peter Bachert; Daniel Paech Journal: Front Neurol Date: 2021-12-23 Impact factor: 4.003