Abstract
Hyperammonemia and inflammation are major contributing factors in the development of cerebral edema (CE) in acute liver failure (ALF). Aim of this study was to look for the relationship between proinflammatory cytokines with diffusion tensor imaging (DTI) derived metrics and 1H-MR spectroscopy (1H-MRS) derived Glutamate/Glutamine (Glx). Fourteen patients with ALF and 14 age/sex matched controls were included in this study. All subjects had undergone clinical, biochemical, MR imaging and 1H-MRS studies. Serum proinflammatory cytokines (IL-6 and TNF-α), blood ammonia level and Glx were computed for independent t-test and Pearson correlation. Serum proinflammatory cytokines, blood ammonia level and brain Glx were significantly increased in ALF patients as compared to controls. Blood ammonia level and Glx showed significant positive correlation with proinflammatory cytokines. Spectroscopy voxel derived spherical anisotropy (CS) showed positive correlation with Glx while mean diffusivity (MD) showed negative correlation. Proinflammatory cytokines showed positive correlation with CS and negative correlation with MD in various brain regions including spectroscopy voxel. Significant correlation of Glx, CS and MD with proinflammatory cytokines suggests that both DTI derived metrics and 1H-MRS measure the synergistic effect of hyperammonemia and proinflammatory cytokines and may be used as non-invasive tools for understanding the pathogenesis of CE in ALF.
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Abbreviations
- ALF:
-
acute liver failure
- CE:
-
cerebral edema
- HE:
-
hepatic encephalopathy
- Glx:
-
Glutamate/Glutamine
- IL-6:
-
interleukin-6
- TNF-α:
-
tumor necrosis factor-α
- 1H-MRS:
-
1H magnetic resonance spectroscopy
- DTI:
-
diffusion tensor imaging
- MD:
-
mean diffusivity
- CS:
-
spherical anisotropy
- MRI:
-
magnetic resonance imaging
- TR:
-
repetition time
- TE:
-
echo time
References
Atterbury CE, Maddrey WC, Conn HO (1978) Neomycin-sorbitol and lactulose in the treatment of acute portal-systemic encephalopathy. A controlled, double-blind clinical trial. Am J Dig Dis 23:398–406
Basser PJ (1995) Inferring microstructural features and the physiological state of tissues from diffusion-weighted images. NMR Biomed 8:333–344
Blei AT (2004) Infection, inflammation and hepatic encephalopathy, synergism redefined. J Hepatol 40:327–330
Brusilow SW, Traystman R (1986) Hepatic encephalopathy. N Engl J Med 20(314):786–787
Cauli O, Rodrigo R, Piedrafita B, Boix J, Felipo V (2007) Inflammation and hepatic encephalopathy: ibuprofen restores learning ability in rats with portacaval shunts. Hepatology 46:514–519
Chavarria L, Oria M, Romero-Gimenez J, Alonso J, Lope-Piedrafita S, Cordoba J (2010) Diffusion tensor imaging supports the cytotoxic origin of brain edema in a rat model of acute liver failure. Gastroenterology 138:1566–1573
Cordoba J, Gottstein J, Blei A (1996) Glutamine, myoinositol, and organic osmolytes after portacaval anastomosis in the rat: implications for ammonia-induced brain edema. Hepatology 27:919–923
Duchini A, Govindarajan S, Santucci M, Zampi G, Hofman FM (1996) Effects of tumor necrosis factor-alpha and interleukin-6 on fluid-phase permeability and ammonia diffusion in CNS-derived endothelial cells. J Investig Med 44:474–482
Hasan KM, Parker DL, Alexander AL (2001) Comparison of gradient encoding schemes for diffusion-tensor MRI. J Magn Reson Imaging 13:769–780
Jalan R, Olde Damink SW, Hayes PC, Deutz NE, Lee A (2004) Pathogenesis of intracranial hypertension in acute liver failure: inflammation, ammonia and cerebral blood flow. J Hepatol 41:613–620
Jayakumar AR, Norenberg MD (2010) The Na-K-Cl Co-transporter in astrocyte swelling. Metab Brain Dis 25:31–38
Kale RA, Gupta RK, Saraswat VA, Hasan KM, Trivedi R, Mishra AM, Ranjan P, Pandey CM, Narayana PA (2006) Demonstration of interstitial cerebral edema with diffusion tensor MR imaging in type C hepatic encephalopathy. Hepatology 43:698–706
Martinez-Hernandez A, Bell KP, Norenberger MD (1977) Glutamine synthetase: glial localization in brain. Science 195:1356–1385
Norenberg MD (1987) The role of astrocytes in hepatic encephalopathy. Neurochem Pathol 6:13–33
O’Beirne JP, Chouhan M, Hughes RD (2006) The role of infection and inflammation in the pathogenesis of hepatic encephalopathy and cerebral edema in acute liver failure. Nat Clin Pract Gastroenterol Hepatol 3:118–119
Odeh M, Sabo E, Srugo I, Oliven A (2005) Relationship between tumor necrosis factor-alpha and ammonia in patients with hepatic encephalopathy due to chronic liver failure. Ann Med 37:603–612
Provencher SW (2001) Automatic quantitation of localized in vivo 1H spectra with LC Model. NMR Biomed 14:260–264
Rai V, Nath K, Saraswat VA, Purwar A, Rathore RKS, Gupta RK (2008) Measurement of cytotoxic and interstitial components of cerebral edema in acute hepatic failure by diffusion tensor imaging. J Magn Reson Imaging 28:334–341
Rolando N, Wade JIM, Davalos M, Wendon J, Philpott-Howard J, Williams R (2000) The systemic inflammatory response syndrome in acute liver failure. Hepatology 32:734–739
Saksena S, Rai V, Saraswat VA, Rathore RKS, Purwar A, Kumar M, Thomas MA, Gupta RK (2008) Cerebral diffusion tensor imaging and in vivo proton magnetic resonance spectroscopy in patients with fulminant hepatic failure. J Gastroenterol Hepatol 23:e111–e119
Shawcross DL, Wright G, Olde Damink SWM, Jalan R (2007) Role of ammonia and inflammation in minimal hepatic encephalopathy. Metab Brain Dis 22:125–138
Tandon BN, Bernauau J, O’Grady J, Gupta SD, Krisch RE, Liaw YF, Okuda K, Acharya SK (1999) Recommendations of the International Association for the Study of the Liver Subcommittee on nomenclature of acute and subacute liver failure. J Gastroenterol Hepatol 14:403–404
Vaquero J, Fontana RJ, Larson AM, Bass NM, Davern TJ, Shakil AO, Han S, Harrison ME, Stravitz TR, Munoz S, Brown R, Lee WM, Blei AT (2005) Complications and use of intracranial pressure monitoring in patients with acute liver failure and severe encephalopathy. Liver Transplant 11:1581–1589
Verma A, Saraswat VA, Krishna RY, Nath K, Thomas MA, Gupta RK (2008) Role of 1H-MR spectroscopy in the differentiation of acute on chronic liver failure from acute liver failure. Liver Int 28:1095–1103
Ware AJ, D’Agostino AN, Combes B (1971) Cerebral edema: a major complication of massive hepatic necrosis. Gastroenterology 61:877–884
Westin CF, Maier SE, Mamata H, Nabavi A, Jolesz FA, Kikinis R (2002) Processing and visualization for diffusion tensor MRI. Med Image Anal 6:93–108
Wright G, Davies NA, Shawcross DL, Hodges SJ, Zwingmann C, Brooks HF, Mani AR, Harry D, Stadlbauer V, Zou Z, Williams R, Davies C, Moore KP, Jalan R (2007) Endotoxemia produces coma and brain swelling in bile duct ligated rats. Hepatology 45:1517–1526
Acknowledgments
This study was supported by Indian Council of Medical Research (grant No.5/9/62/2008-RHN), New Delhi, India. Santosh Kumar Yadav gratefully acknowledge the financial assistance from the Indian Council of Medical Research, New Delhi, India.
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Gupta, R.K., Yadav, S.K., Rangan, M. et al. Serum proinflammatory cytokines correlate with diffusion tensor imaging derived metrics and 1H-MR spectroscopy in patients with acute liver failure. Metab Brain Dis 25, 355–361 (2010). https://doi.org/10.1007/s11011-010-9206-x
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DOI: https://doi.org/10.1007/s11011-010-9206-x