Multi-dimensional MR spectroscopy: towards a better understanding of hepatic encephalopathy
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Hepatic encephalopathy (HE) is normally diagnosed by neuropsychological (NP) tests. The goals of this study were to quantify cerebral metabolites, separate glutamate (Glu) from glutamine (Gln) in patients with minimal hepatic encephalopathy (MHE) as well as healthy subjects using the prior-knowledge fitting (ProFit) algorithm on data acquired by two-dimensional (2D) localized correlated spectroscopy (L-COSY) on two different MR scanners, and to correlate the metabolite changes with neuropsychological (NP) tests. We studied 14 MHE patients and 18 healthy controls using a GE 1.5 T Signa MR scanner. Another group of 16 MHE patients and 18 healthy controls were studied using a Siemens 1.5 T Avanto MR scanner. The following parameters were used for L-COSY: TR/TE = 2 s/30 ms, 3 × 3 × 3 cm3 voxel size, 96 Δt1 increments with 8 averages per Δt1. Using the ProFit algorithm, we were able to differentiate Gln from Glu on the GE 1.5 T data in the medial frontal white/gray matter. The ratios of myo-inositol (mI), Glu, total choline, scyllo-inositol (sI), phosphoethanolamine (PE), and total N-acetyl aspartate (NAA) showed statistically significant decline in HE patients compared to healthy controls, while the ratio of Gln was significantly increased. Similar trend was seen in the ProFit quantified Siemens 1.5 T data in the frontal and occipito-parietal white/gray regions. Among the NP domain scores, motor function, cognitive speed, executive function and the global scores showed significant differences. Excellent correlations between various NP domains and metabolite ratios were also observed. ProFit based cerebral metabolite quantitation enhances the understanding and basis of the current hypothesis of MHE.
KeywordsMRS COSY Hepatic encephalopathy Glutamine Glutamate Neuropsychological tests
This research was supported by a National Institute of Mental Health (NIMH) RO1 grant (1R01MH06569501A1). Scientific support of Drs. Nader Binesh, Kenneth Yue, Shida Banakar, and Sherry Liu during the earlier phase of this project is gratefully acknowledged. Authors acknowledge the support of Dr. Rolf Schulte, Prof. Dr. Peter Boesiger and his group members at ETH-Zurich, Switzerland in sharing the earlier version of the ProFit algorithm for processing the localized 2D J-resolved spectrum.
Conflict of interest
The authors declare that they have no conflict of interest.
- Amodio P, Del Piccolo F, Marchetti P, Angeli P, Iemmolo R, Caregaro L, Merkel C, Gerunda G, Gatta A (1999) Clinical features and survivial of cirrhotic patients with subclinical cognitive alterations detected by the number connection test and computerized psychometric tests. Hepatology 29:1662–1667PubMedCrossRefGoogle Scholar
- Amodio P, Ridola L, Schiff S, Montagnese S, Pasquale C, Nardelli S, Pentassuglio I, Trezza M, Marzano C, Flaiban C, Angeli P, Cona G, Bisiacchi P, Gatta A, Riggio O (2010) Improving detection of minimal hepatic encephalopathy using the inhibitory control task. Gastroenterology 139:510–518PubMedCrossRefGoogle Scholar
- Bhujwalla ZM, Aboagye EO, Gillies RJ, Chacko VP, Mendola CE, Backer JM (1999) Nm23-transfected MDA-MB-435 human breast carcinoma cells form tumors with altered phospholipid metabolism and pH: a 31P nuclear magnetic resonance study in vivo and in vitro. Magn Reson Med 41:897–903PubMedCrossRefGoogle Scholar
- Bosman DK, Deutz NE, De Graaf AA, vd Hulst RW, Van Eijk HM, Bovée WM, Maas MA, Jörning GG, Chamuleau RA (1990) Changes in brain metabolism during hyperammonemia and acute liver failure: results of a comparative 1H-NMR spectroscopy and biochemical investigation. Hepatology 12:281–290Google Scholar
- Butterworth RF (1995) Hepatic encephalopathy. Neurologist 1:95–104Google Scholar
- Clarke DD, Sokoloff L (1999) Circulation and energy metabolism of the brain. In: Siegel GJ, Agranoff BW et al (eds) Basic neurochemistry. Lippincott-Raven, Philadelphia, pp 637–669Google Scholar
- Evanochko WT, Sakal TT, Ng TC, Krishnaa NR, Kimc HD, Zeidlerc RB, Ghantad VK, Brockmane RW, Schifferf LM, Braunschweigerf PG, Glicksona JD (1984) NMR study of in vivo RIF-1 tumors. Analysis of perchloric acid extracts and identification of 1H, 31P and 13C resonances. Biochim Biophys Acta 805:104–116PubMedCrossRefGoogle Scholar
- Ferenci P, Lockwood A, Mullen K, Tarter R, Weissenborn K, Blei AT (2002) Hepatic encephalopathy–definition, nomenclature, diagnosis, and quantification: final report of the working party at the 11th World Congresses of Gastroenterology, Vienna, 1998. Hepatology 35:716–721PubMedCrossRefGoogle Scholar
- Frias-Martinez E, Rajakumar N, Liu X, Singhal A, Banakar S, Lipnick S, Verma G, Ramadan S, Kumar A, Thomas MA (2008) ProFit-based Quantitation of Cerebral Metabolites using 2D L-COSY at 3 T Magnetic Resonance. Proc Intl Soc Mag Reson Med 16: 691, Toronto, CanadaGoogle Scholar
- Gitlin N (1996) Hepatic encephalopathy. In: Zorkin D, Boyer TD (eds) Hepatology. Saunders, Philadelphia, pp 605–617Google Scholar
- Heaton RK, Grant I, Matthews CG (1991) Comprehensive norms for an expanded Halstead-Reitan battery: demographic corrections, research findings, and clinical applications. Psychological Assessment Resources, OdessaGoogle Scholar
- Hilbe JM (2009) Logistic regression models. Chapman & Hall/CRC PressGoogle Scholar
- Hosmer DW, Lemeshow S (1995) Applied Logistic Regression. John Wiley and Sons, Inc Menard, ScottGoogle Scholar
- Lezak MD (1995) Neuropsychological assessment. Oxford University Press, New York, pp 333–685Google Scholar
- Pardridge WM, Cornford EM, Braun LD, Oldendorf WH (1979) Transport of choline and choline analogues through the blood-brain barrier. In: Barbeau A, Growdon JH, Wurtman RJ (eds) Nutrition and the Brain. Raven, New York, pp 25–33Google Scholar
- Weissenborn K, Ahl B, Fischer-Wasels D, van den Hoff J, Hecker H, Burchert W, Köstler H (2007) Correlations between magnetic resonance spectroscopy alterations and cerebral ammonia and glucose metabolism in cirrhotic patients with and without hepatic encephalopathy. Gut 56:1736–1742PubMedCrossRefGoogle Scholar