Absolute quantification of human liver metabolite concentrations by localized in vivo 31P NMR spectroscopy in diffuse liver disease

Abstract

Phosphorus-31 NMR spectroscopy using slice selection (DRESS) was used to investigate the absolute concentrations of metabolites in the human liver. Absolute concentrations provide more specific biochemical information compared to spectrum integral ratios. Nine patients with histopathologically proven diffuse liver disease and 12 healthy individuals were examined in a 1.5-T MR scanner (GE Signa LX Echospeed plus). The metabolite concentration quantification procedures included: (1) determination of optimal depth for the in vivo measurements, (2) mapping the detection coil characteristics, (3) calculation of selected slice and liver volume ratios using simple segmentation procedures and (4) spectral analysis in the time domain. The patients had significantly lower concentrations of phosphodiesters (PDE), 6.3+/-3.9 mM, and ATP-beta, 3.6+/-1.1 mM, (P<0.05) compared with the control group (10.0+/-4.2 mM and 4.2+/-0.3 mM, respectively). The concentrations of phosphomonoesters (PME) were higher in the patient group, although this was not significant. Constructing an anabolic charge (AC) based on absolute concentrations, [PME]/([PME] + [PDE]), the patients had a significantly larger AC than the control subjects, 0.29 vs. 0.16 (P<0.005). Absolute concentration measurements of phosphorus metabolites in the liver are feasible using a slice selective sequence, and the technique demonstrates significant differences between patients and healthy subjects.

Can imaging modalities diagnose and stage hepatic fibrosis and cirrhosis accurately?

“…Several studies have investigated the use of 31 P-MRS in the diagnosis of hepatic fibrosis and diffuse liver disease. A significant correlation between phosphodiester concentration and stage of fibrosis and a correlation between ''anabolic charge" (phosphomonoester/[phosphomonoester + phosphodiester]) and stage of fibrosis were found in a study comparing a group of patients with steatosis and no to moderate inflammation to a group of patients with severe fibrosis or cirrhosis [128,129]. Phosphomonoester to phosphodiester ratio and phosphomonoester to inorganic phosphate ratios were shown to be an index of cell membrane turnover and correlated closely with disease severity, assessed by histology in HCV [122,[130][131][132].…”

In-vivo 31P-MRS of skeletal muscle and liver: A way for non-invasive assessment of their metabolism

“…31 P MRS provides information about human liver metabolism in a non-invasive manner [17], [57], [190], [191], [192], [193], [194], [195], [196], [197], [198], [199], [200], [201], [202], [203], [204], [205]. As mentioned in the paragraph about the information content of the 31 P-MR spectrum, the main feature of the healthy liver 31 P spectrum is the lack of PCr signal, due to the fact that, under normal conditions, hepatocytes do not express creatine kinase.…”

“…Therefore, it is very common to use techniques to select a volume in this organ [52], [53], [54], [55], [56], [57], [58], [59], [60], including the suppression of signal from abdominal muscle. Investigations on MR systems at 1.5 T reported highly discrepant hepatic metabolite concentrations, which was later investigated and attributed to T 1 dependent saturation losses, as well as to differences in post-processing and quantification methods [59].…”

Nonalcoholic Fatty Liver Disease: Detection of Elevated Nicotinamide Adenine Dinucleotide Phosphate with in Vivo 3.0-T31P MR Spectroscopy with Proton Decoupling

“…Another limitation was the fact that we did not perform absolute quantitation of MR spectroscopy ( 37 ). Efforts toward absolute quantitation include correction of the measured data, which introduces additional error sources and is complex to perform in the clinical setting.…”