Phosphodiester content measured in human liver by in vivo 31 P MR spectroscopy at 7 tesla

Abstract

Purpose: Phosphorus (³¹ P) metabolites are emerging liver disease biomarkers. Of particular interest are phosphomonoester and phosphodiester (PDE) "peaks" that comprise multiple overlapping resonances in ³¹ P spectra. This study investigates the effect of improved spectral resolution at 7 Tesla (T) on quantifying hepatic metabolites in cirrhosis.

Methods: Five volunteers were scanned to determine metabolite T₁ s. Ten volunteers and 11 patients with liver cirrhosis were scanned at 7T. Liver spectra were acquired in 28 min using a 16-channel ³¹ P array and 3D chemical shift imaging. Concentrations were calculated using γ-adenosine-triphosphate (γ-ATP) = 2.65 mmol/L wet tissue.

Results: T₁ means ± standard deviations: phosphatidylcholine 1.05 ± 0.28 s, nicotinamide-adenine-dinucleotide (NAD⁺ ) 2.0 ± 1.0 s, uridine-diphosphoglucose (UDPG) 3.3 ± 1.4 s. Concentrations in healthy volunteers: α-ATP 2.74 ± 0.11 mmol/L wet tissue, inorganic phosphate 2.23 ± 0.20 mmol/L wet tissue, glycerophosphocholine 2.34 ± 0.46 mmol/L wet tissue, glycerophosphoethanolamine 1.50 ± 0.28 mmol/L wet tissue, phosphocholine 1.06 ± 0.16 mmol/L wet tissue, phosphoethanolamine 0.77 ± 0.14 mmol/L wet tissue, NAD⁺ 2.37 ± 0.14 mmol/L wet tissue, UDPG 2.00 ± 0.22 mmol/L wet tissue, phosphatidylcholine 1.38 ± 0.31 mmol/L wet tissue. Inorganic phosphate and phosphatidylcholine concentrations were significantly lower in patients; glycerophosphoethanolamine concentrations were significantly higher (P < 0.05).

Conclusion: We report human in vivo hepatic T₁ s for phosphatidylcholine, NAD⁺ , and UDPG for the first time at 7T. Our protocol allows high signal-to-noise, repeatable measurement of metabolite concentrations in human liver. The splitting of PDE into its constituent peaks at 7T may allow more insight into changes in metabolism. Magn Reson Med 78:2095-2105, 2017. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Keywords: 31P; 7 Tesla; cirrhosis; human; in vivo; liver; magnetic resonance spectroscopy; phosphorus.

Figure 1

Typical liver ³¹P‐MRS spectra acquired at 7T in the right lobe of the liver using our 3D UTE‐CSI protocol. a: The ¹H FLASH localizer. The red lines mark the CSI grid, the yellow band marks the outer volume BISTRO suppression. The spectrum for each colored voxel is given on the right side. The ellipses show the extent of the full width at half maximum of the point spread function for each voxel. b: A suppressed muscle spectrum taken from the blue voxel. c–e: Liver spectra from the red, green and pink voxels, respectively, showing the change as they are taken from deeper in the liver.

Figure 2

a: The decision tree of quality assurance (QA) tests for excluding voxels in the analysis of the CSI grid of the liver. The mean number of voxels remaining at each step are given. b: The number of voxels that pass each test. The black line shows the mean ± SD of the values. The stars show individual values, with each color representing a different subject. c: The locations of a single slice of CSI voxels overlaid on a ¹H localizer. Each color indicates a different exclusion parameter.

Figure 3

Illustration of ³¹P Look‐Locker CSI fitting for a typical set of liver data. a: Raw spectra from a single voxel of a single subject. Each line shows a different TI, with a gap to indicate the break for magnetization recovery in the pulse sequence. b: The model spectra that were fitted simultaneously to the experimental data. c: The residual error after fitting. a–c: Images are plotted with the same scaling. “^” marks the central frequency of the inversion pulse. d: The absolute intensity sampled at the fitted frequency of each metabolite. Each “x” marks an experimental TI, and the lines show the simulated data. These panels are drawn to help interpret the spectra in a–c, but were not used in the T₁ analysis.

Figure 4

Bland‐Altman plots of the concentrations of the two repeatability scans. Each blue cross marks a different subject. The blue dashed line is the mean difference and the red dashed line is 1.96 × SD, i.e., the 95% confidence interval.

Figure 5

A scatter plot of the concentrations of nine different peaks in normal volunteers and patients. Each red “+” marks a subject. The blue line shows the mean ± SD of each group. P_i and PtdC/PEP are significantly lower in cirrhosis than in normal volunteers, and GPE is significantly higher (P < 0.05).

Figure 6

Comparison of normal liver ³¹P metabolite concentrations from this study against the literature 21, 47, 51, 56, 59. SDs are shown by the error bars on each bar. Stars indicate level of significance of the difference from this study: *P < 0.05, **P < 0.01, ***P < 0.001.