Skip to main content

Advertisement

SpringerLink
Log in

Resting-state functional magnetic resonance imaging in hepatic encephalopathy: current status and perspectives

  • Review Article
  • Published:
Metabolic Brain Disease Aims and scope Submit manuscript

Abstract

Hepatic encephalopathy (HE) is a neuropsychiatric syndrome which develops in patients with severe liver diseases and/or portal-systemic shunting. Minimal HE, the earliest manifestation of HE, has drawn increasing attention in the last decade. Minimal HE is associated with a series of brain functional changes, such as attention, working memory, and so on. Blood oxygen level dependent (BOLD) functional MRI (fMRI), especially resting-state fMRI has been used to explore the brain functional changes of HE, yielding important insights for understanding pathophysiological mechanisms and functional reorganization of HE. This paper briefly reviews the principles of BOLD fMRI, potential applications of resting-state fMRI with advanced post-processing algorithms such as regional homogeneity, amplitude of low frequency fluctuation, functional connectivity and future research perspective in this field.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

Abbreviations

BOLD:

Blood oxygen level dependent

fMRI:

Functional MRI

HE:

Hepatic encephalopathy

MHE:

Minimal hepatic encephalopathy

TIPS:

Transjugular intrahepatic portosystemic shunt

References

  • Amodio P, Montagnese S, Gatta A, Morgan MY (2004) Characteristics of minimal hepatic encephalopathy. Metab Brain Dis 19(3–4):253–267

    Article  PubMed  Google Scholar 

  • Bajaj JS, Wade JB, Sanyal AJ (2009) Spectrum of neurocognitive impairment in cirrhosis: implications for the assessment of hepatic encephalopathy. Hepatology 50(6):2014–2021

    Article  PubMed  Google Scholar 

  • Bajaj JS, Pinkerton SD, Sanyal AJ, Heuman DM (2012) Diagnosis and treatment of minimal hepatic encephalopathy to prevent motor vehicle accidents: a cost-effectiveness analysis. Hepatology 55(4):1164–1171

    Article  PubMed Central  PubMed  Google Scholar 

  • Boumezbeur F, Petersen KF, Cline GW, Mason GF, Behar KL, Shulman GI, Rothman DL (2010) The contribution of blood lactate to brain energy metabolism in humans measured by dynamic 13C nuclear magnetic resonance spectroscopy. J Neurosci 30(42):13983–13991

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Butterworth RF (2013) The liver-brain axis in liver failure: neuroinflammation and encephalopathy. Nat Rev Gastroenterol Hepatol 10(9):522–528

    Article  CAS  PubMed  Google Scholar 

  • Cagnin A, Taylor-Robinson SD, Forton DM, Banati RB (2006) In vivo imaging of cerebral “peripheral benzodiazepine binding sites” in patients with hepatic encephalopathy. Gut 55(4):547–553

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Chen HJ, Zhu XQ, Jiao Y, Li PC, Wang Y, Teng GJ (2012a) Abnormal baseline brain activity in low-grade hepatic encephalopathy: a resting-state fMRI study. J Neurol Sci 318(1–2):140–145

    Article  PubMed  Google Scholar 

  • Chen HJ, Zhu XQ, Shu H, Yang M, Zhang Y, Ding J, Wang Y, Teng GJ (2012b) Structural and functional cerebral impairments in cirrhotic patients with a history of overt hepatic encephalopathy. Eur J Radiol 81(10):2463–2469

    Article  PubMed  Google Scholar 

  • Chen HJ, Zhu XQ, Yang M, Liu B, Zhang Y, Wang Y, Teng GJ (2012c) Changes in the regional homogeneity of resting-state brain activity in minimal hepatic encephalopathy. Neurosci Lett 507(1):5–9

    Article  CAS  PubMed  Google Scholar 

  • Chen HJ, Jiao Y, Zhu XQ, Zhang HY, Liu JC, Wen S, Teng GJ (2013) Brain dysfunction primarily related to previous overt hepatic encephalopathy compared with minimal hepatic encephalopathy: resting-state functional MR imaging demonstration. Radiology 266(1):261–270

    Article  PubMed  Google Scholar 

  • Córdoba J (2011) New assessment of hepatic encephalopathy. J Hepatol 54(5):1030–1040

    Article  PubMed  Google 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(3):716–721

    Article  PubMed  Google Scholar 

  • Fox MD, Snyder AZ, Vincent JL, Corbetta M, Van Essen DC, Raichle ME (2005) The human brain is intrinsically organized into dynamic, anticorrelated functional networks. Proc Natl Acad Sci U S A 102(27):9673–9678

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • García-Ayllón MS, Cauli O, Silveyra MX, Rodrigo R, Candela A, Compañ A, Jover R, Pérez-Mateo M, Martínez S, Felipo V, Sáez-Valero J (2008) Brain cholinergic impairment in liver failure. Brain 131(Pt 11):2946–2956

    Article  PubMed Central  PubMed  Google Scholar 

  • Glasser MF, Sotiropoulos SN, Wilson JA, Coalson TS, Fischl B, Andersson JL, Xu J, Jbabdi S, Webster M, Polimeni JR, Van Essen DC, Jenkinson M, WU-Minn HCP Consortium (2013) The minimal preprocessing pipelines for the Human Connectome Project. Neuroimage 80:105–124

    Article  PubMed  Google Scholar 

  • Glover GH (2011) Overview of functional magnetic resonance imaging. Neurosurg Clin N Am 22(2):133–139

    Article  PubMed Central  PubMed  Google Scholar 

  • Gore JC (2003) Principles and practice of functional MRI of the human brain. J Clin Invest 112(1):4–9

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Hassanein TI, Hilsabeck RC, Perry W (2008) Introduction to the Hepatic Encephalopathy Scoring Algorithm (HESA). Dig Dis Sci 53(2):529–538

    Article  PubMed  Google Scholar 

  • He Y, Dagher A, Chen Z, Charil A, Zijdenbos A, Worsley K, Evans A (2009) Impaired small-world efficiency in structural cortical networks in multiple sclerosis associated with white matter lesion load. Brain 132(Pt 12):3366–3379

    Article  PubMed Central  PubMed  Google Scholar 

  • Hsu TW, Wu CW, Cheng YF, Chen HL, Lu CH, Cho KH, Lin WC, Lin CP (2012) Impaired small-world network efficiency and dynamic functional distribution in patients with cirrhosis. PLoS One 7(5):e35266

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ivanov I, Liu X, Shulz K, Fan J, London E, Friston K, Halperin JM, Newcorn JH (2012) Parental substance abuse and function of the motivation and behavioral inhibition systems in drug-naïve youth. Psychiatry Res 201(2):128–135

    Article  PubMed Central  PubMed  Google Scholar 

  • 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(4):698–706

    Article  PubMed  Google Scholar 

  • Lee MH, Smyser CD, Shimony JS (2013) Resting-state fMRI: a review of methods and clinical applications. AJNR Am J Neuroradiol 34(10):1866–1872

    Article  CAS  PubMed  Google Scholar 

  • Liao LM, Zhou LX, Le HB, Yin JJ, Ma SH (2012) Spatial working memory dysfunction in minimal hepatic encephalopathy: an ethology and BOLD-fMRI study. Brain Res 1445:62–72

    CAS  PubMed  Google Scholar 

  • Lin WC, Hsu TW, Chen CL, Wu CW, Lu CH, Chen HL, Li SH, Yeh PY, Cheng YF, Lin CP (2012) Connectivity of default-mode network is associated with cerebral edema in hepatic encephalopathy. PLoS One 7(5):e36986

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Liu Y, Wang K, Yu C, He Y, Zhou Y, Liang M, Wang L, Jiang T (2008) Regional homogeneity, functional connectivity and imaging markers of Alzheimer’s disease: a review of resting-state fMRI studies. Neuropsychologia 46(6):1648–1656

    Article  PubMed  Google Scholar 

  • Logothetis NK (2008) What we can do and what we cannot do with fMRI. Nature 453(7197):869–878

    Article  CAS  PubMed  Google Scholar 

  • Lv XF, Qiu YW, Tian JZ, Xie CM, Han LJ, Su HH, Liu ZY, Peng JP, Lin CL, Wu MS, Jiang GH, Zhang XL (2013a) Abnormal regional homogeneity of resting-state brain activity in patients with HBV-related cirrhosis without overt hepatic encephalopathy. Liver Int 33(3):375–383

    Article  CAS  PubMed  Google Scholar 

  • Lv XF, Ye M, Han LJ, Zhang XL, Cai PQ, Jiang GH, Qiu YW, Qiu SJ, Wu YP, Liu K, Liu ZY, Wu PH, Xie CM (2013b) Abnormal baseline brain activity in patients with HBV-related cirrhosis without overt hepatic encephalopathy revealed by resting-state functional MRI. Metab Brain Dis 28(3):485–492

    Article  PubMed  Google Scholar 

  • Madoff DC, Wallace MJ, Ahrar K, Saxon RR (2004) TIPS-related hepatic encephalopathy: management options with novel endovascular techniques. Radiographics 24(1):21–36

    Article  PubMed  Google Scholar 

  • McKiernan KA, D’Angelo BR, Kaufman JN, Binder JR (2006) Interrupting the “stream of consciousness”: an fMRI investigation. Neuroimage 29(4):1185–1191

    Article  PubMed Central  PubMed  Google Scholar 

  • McPhail MJ, Patel NR, Taylor-Robinson SD (2012) Brain imaging and hepatic encephalopathy. Clin Liver Dis 16(1):57–72

    Article  PubMed  Google Scholar 

  • McPhail MJ, Leech R, Grover VP, Fitzpatrick JA, Dhanjal NS, Crossey MM, Pflugrad H, Saxby BK, Wesnes K, Dresner MA, Waldman AD, Thomas HC, Taylor-Robinson SD (2013) Modulation of neural activation following treatment of hepatic encephalopathy. Neurology 80(11):1041–1047

    Article  PubMed Central  PubMed  Google Scholar 

  • Naismith SL, Norrie LM, Mowszowski L, Hickie IB (2012) The neurobiology of depression in later-life: clinical, neuropsychological, neuroimaging and pathophysiological features. Prog Neurobiol 98(1):99–143

    Article  PubMed  Google Scholar 

  • Ni L, Qi R, Zhang LJ, Zhong J, Zheng G, Zhang Z, Zhong Y, Xu Q, Liao W, Jiao Q, Wu X, Fan X, Lu GM (2012) Altered regional homogeneity in the development of minimal hepatic encephalopathy: a resting-state functional MRI study. PLoS One 7(7):e42016

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ortiz M, Cordoba J, Doval E, Jacas C, Pujadas F, Esteban R, Guardia J (2007) Development of a clinical hepatic encephalopathy staging scale. Aliment Pharmacol Ther 26(6):859–867

    Article  CAS  PubMed  Google Scholar 

  • Palomero-Gallagher N, Zilles K (2013) Neurotransmitter receptor alterations in hepatic encephalopathy: a review. Arch Biochem Biophys 536(2):109–121

    Article  CAS  PubMed  Google Scholar 

  • Pizoli CE, Shah MN, Snyder AZ, Shimony JS, Limbrick DD, Raichle ME, Schlaggar BL, Smyth MD (2011) Resting-state activity in development and maintenance of normal brain function. Proc Natl Acad Sci U S A 108(28):11638–11643

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Qi R, Xu Q, Zhang LJ, Zhong J, Zheng G, Wu S, Zhang Z, Liao W, Zhong Y, Ni L, Jiao Q, Zhang Z, Liu Y, Lu G (2012a) Structural and functional abnormalities of default mode network in minimal hepatic encephalopathy: a study combining DTI and fMRI. PLoS One 7(7):e41376

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Qi R, Zhang L, Wu S, Zhong J, Zhang Z, Zhong Y, Ni L, Zhang Z, Li K, Jiao Q, Wu X, Fan X, Liu Y, Lu G (2012b) Altered resting-state brain activity at functional MR imaging during the progression of hepatic encephalopathy. Radiology 264(1):187–195

    Article  PubMed  Google Scholar 

  • Qi R, Zhang LJ, Xu Q, Zhong J, Wu S, Zhang Z, Liao W, Ni L, Zhang Z, Chen H, Zhong Y, Jiao Q, Wu X, Fan X, Liu Y (2012c) Lu G (2012c) Selective impairments of resting-state networks in minimal hepatic encephalopathy. PLoS One 7(5):e37400

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Qi R, Zhang LJ, Zhong J, Wu S, Zhang Z, Zhong Y, Ni L, Zheng G, Jiao Q, Wu X, Fan X, Liu Y, Lu G (2012d) Dynamic changes of intrinsic brain activity in cirrhotic patients after transjugular intrahepatic portosystemic shunt: a resting-state FMRI study. PLoS One 7(10):e46681

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Qi R, Zhang LJ, Zhong J, Zhang Z, Ni L, Jiao Q, Liao W, Zheng G, Lu G (2013a) Altered effective connectivity network of the basal ganglia in low-grade hepatic encephalopathy: a resting-state fMRI study with Granger causality analysis. PLoS One 8(1):e53677

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Qi R, Zhang LJ, Zhong J, Zhang Z, Ni L, Zheng G, Lu GM (2013b) Disrupted thalamic resting-state functional connectivity in patients with minimal hepatic encephalopathy. Eur J Radiol 82(5):850–856

    Article  PubMed  Google Scholar 

  • Raichle ME (2011) The restless brain. Brain Connectivity 1(1):3–12

    Article  PubMed Central  PubMed  Google Scholar 

  • Riordan SM, Williams R (2010) Gut flora and hepatic encephalopathy in patients with cirrhosis. N Engl J Med 362(12):1140–1142

    Article  PubMed  Google Scholar 

  • Rosazza C, Minati L (2011) Resting-state brain networks: literature review and clinical applications. Neurol Sci 32(5):773–785

    Article  PubMed  Google Scholar 

  • Sergeeva OA (2013) GABAergic transmission in hepatic encephalopathy. Arch Biochem Biophys 536(2):122–130

    Article  CAS  PubMed  Google Scholar 

  • Sheline YI, Raichle ME (2013) Resting state functional connectivity in preclinical Alzheimer’s disease. Biol Psychiatry 74(5):340–347

    Article  PubMed  Google Scholar 

  • Sporns O (2013) The human connectome: origins and challenges. NeuroImage 80:53–61

    Article  PubMed  Google Scholar 

  • Tanigami H, Rebel A, Martin LJ, Chen TY, Brusilow SW, Traystmana RJ, Koehler RC (2005) Effect of glutamine synthetase inhibition on astrocyte swelling and altered astroglial protein expression during hyper-ammonemia in rats. Neuroscience 131(2):437–449

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • van den Heuvel MP, Hulshoff Pol HE (2010) Exploring the brain network: a review on resting-state fMRI functional connectivity. Eur Neuropsychopharmacol 20(8):519–534

    Article  PubMed  Google Scholar 

  • Wehrl HF, Hossain M, Lankes K, Liu CC, Bezrukov I, Martirosian P, Schick F, Reischl G, Pichler BJ (2013) Simultaneous PET-MRI reveals brain function in activated and resting state on metabolic, hemodynamic and multiple temporal scales. Nat Med 19(9):1184–1189

    Article  CAS  PubMed  Google Scholar 

  • Xiang Y, Shen J (2011) Simultaneous detection of cerebral metabolism of different substrates by in vivo 13C isotopomer MRS. J Neurosci Methods 198(1):8–15

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Zafiris O, Kircheis G, Rood HA, Boers F, Häussinger D, Zilles K (2004) Neural mechanism underlying impaired visual judgement in the dysmetabolic brain: an fMRI study. Neuroimage 22(2):541–552

    Article  PubMed  Google Scholar 

  • Zang Y, Jiang T, Lu Y, He Y, Tian L (2004) Regional homogeneity approach to fMRI data analysis. Neuroimage 22(1):394–400

    Article  PubMed  Google Scholar 

  • Zang YF, He Y, Zhu CZ, Cao QJ, SuiMQ LM, Tian LX, Jiang TZ, Wang YF (2007) Altered baseline brain activity in children with ADHD revealed by resting-state functional MRI. Brain Dev 29(1):83–91

    PubMed  Google Scholar 

  • Zhang LJ, Yang G, Yin J, Liu Y, Qi J (2007a) Neural mechanism of cognitive control impairment in patients with hepatic cirrhosis: a functional magnetic resonance imaging study. Acta Radiol 48(5):577–587

    Article  CAS  PubMed  Google Scholar 

  • Zhang LJ, Yang G, Yin J, Liu Y, Qi J (2007b) Abnormal default-mode network activation in cirrhotic patients: a functional magnetic resonance imaging study. Acta Radiol 48(7):781–787

    Article  PubMed  Google Scholar 

  • Zhang L, Qi R, Wu S, Zhong J, Zhong Y, Zhang Z, Zhang Z, Lu G (2012a) Brain default-mode network abnormalities in hepatic encephalopathy: a resting-state functional MRI study. Hum Brain Mapp 33(6):1384–1392

    Article  PubMed  Google Scholar 

  • Zhang LJ, Zheng G, Zhang L, Zhong J, Wu S, Qi R, Li Q, Wang L, Lu G (2012b) Altered brain functional connectivity in patients with cirrhosis and minimal hepatic encephalopathy: a functional MR imaging study. Radiology 265(2):528–536

    Article  PubMed  Google Scholar 

  • Zhang LJ, Qi R, Zhong J, Ni L, Zheng G, Xu J, Lu GM (2013a) Disrupted functional connectivity of the anterior cingulate cortex in cirrhotic patients without overt hepatic encephalopathy: a resting state fMRI study. PLoS One 8(1):e53206

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Zhang LJ, Zhong J, Lu GM (2013b) Multimodality MR imaging findings of low-grade brain edema in hepatic encephalopathy. AJNR Am J Neuroradiol 34(4):707–715

    Article  CAS  PubMed  Google Scholar 

  • Zhu XQ, Chen HJ, Wang Y, Cui Y, Teng GJ (2012) Aberrant resting-state corticostriatal functional connectivity in cirrhotic patients with hyperintense globus pallidus on T1-weighted MR imaging. PLoS One 7(11):e48886

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgment

We express our thanks for the grants from Natural Scientific Foundation of China (30700194, 81171313, 81322020, 81230032 to L.J.Z.) and Program for New Century Excellent Talents in University (NCET-12-0260 to L.J.Z.).

Author information

Authors and Affiliations

  1. Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, 305 Zhongshan East Road, Xuanwu District, Nangjing, Jiangsu Province, China, 210002

    Long Jiang Zhang & Guang Ming Lu

  2. MGH-Martinos Center, Harvard Medical School, Bldg 149, 13th Street, Charlestown, MA, 02129, USA

    Shengyong Wu & Jiaqian Ren

  3. Medical Imaging Institute of Tianjin, Tianjin, 300192, China

    Shengyong Wu

  4. Department of Medical Imaging, Jinling Hospital, Clinical School of Medical College, Nanjing University, 305 Zhongshan East Road, Xuanwu District, Nanjing, Jiangsu Province, China, 210002

    Long Jiang Zhang

Authors
  1. Long Jiang Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shengyong Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jiaqian Ren
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Guang Ming Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Long Jiang Zhang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhang, L.J., Wu, S., Ren, J. et al. Resting-state functional magnetic resonance imaging in hepatic encephalopathy: current status and perspectives. Metab Brain Dis 29, 569–582 (2014). https://doi.org/10.1007/s11011-014-9504-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11011-014-9504-9

Keywords

Search

Navigation