Nonalcoholic fatty liver disease: detection of elevated nicotinamide adenine dinucleotide phosphate with in vivo 3.0-T 31P MR spectroscopy with proton decoupling.
OBJECTIVE
To determine if 3.0-T proton-decoupled phosphorus 31 ((31)P) magnetic resonance (MR) spectroscopy can be used to differentiate between stages of nonalcoholic fatty liver disease (NAFLD) by resolving the components of phosphomonoester (PME) and phosphodiester (PDE) and enabling detection of a greater number of other phosphorus-containing compounds.


METHODS
This study was approved by the ethics committee of Helsinki University Central Hospital, and written informed consent was obtained from all study subjects. A 3.0-T clinical imager was used to obtain proton-decoupled (31)P MR spectra in the liver of control subjects (n = 12), patients with biopsy-proved simple steatosis due to nonalcoholic causes (nonalcoholic fatty liver, n = 13; nonalcoholic steatohepatitis [NASH], n = 9), and patients with cirrhosis (n = 9) to determine PME, phosphoethanolamine (PE), phosphocholine, PDE, glycerophosphocholine (GPC), glycerophosphoryl ethanolamine, uridine diphosphoglucose, nicotinamide adenine dinucleotide phosphate (NADPH), inorganic phosphate, phosphoenolpyruvate, and alpha-, beta- and gamma-nucleotide triphosphate levels. Liver fat was determined with hydrogen 1 MR spectroscopy. Differences between the disease groups were analyzed with one-way analysis of variance.


RESULTS
The PME/(PME + PDE), PME/PDE, and PE/(PME + PDE) ratios were higher and the GPC/(PME + PDE) ratio was lower in patients with cirrhosis than in the other study groups (P < or = .001, one-way analysis of variance). The NADPH/(PME + PDE) ratio was higher in patients with NASH and those with cirrhosis than in control subjects (P < .05, post hoc analyses) and correlated with disease severity (P = .007).


CONCLUSIONS
NADPH, a marker of inflammation and fibrinogenic activity in the liver, is increased in patients with NASH and those with cirrhosis. Proton-decoupled (31)P 3.0-T MR spectroscopy shows promise in the differentiation of NAFLD stages.
Sevastianova
Ksenia
K
Department of Medicine, Division of Diabetes, University of Helsinki, PO Box 340, Helsinki 00029 HUCH, Finland.
Hakkarainen
Antti
A
Kotronen
Anna
A
Cornér
Anja
A
Arkkila
Perttu
P
Arola
Johanna
J
Westerbacka
Jukka
J
Bergholm
Robert
R
Lundbom
Jesper
J
Lundbom
Nina
N
Yki-Järvinen
Hannele
H
D000293:Adolescent; D000328:Adult; D000368:Aged; D000437:Alcoholism / Q000175:diagnosis / Q000378:metabolism; D015415:Biomarkers / Q000032:analysis; D003936:Diagnosis, Computer-Assisted / Q000379:methods*; D005234:Fatty Liver / Q000175:diagnosis / Q000378:metabolism*; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009249:NADP / Q000032:analysis*; D010759:Phosphorus Isotopes / Q000032:analysis; D017785:Photons; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D055815:Young Adult
D015415:Biomarkers; D010759:Phosphorus Isotopes; D009249:NADP