title: Non invasive blood flow measurement in cerebellum detects minimal hepatic encephalopathy earlier than psychometric tests.
abstract: OBJECTIVE
  To assess whether non invasive blood flow measurement by arterial spin labeling in several brain regions detects minimal hepatic encephalopathy.
  
  
  METHODS
  Blood flow (BF) was analyzed by arterial spin labeling (ASL) in different brain areas of 14 controls, 24 cirrhotic patients without and 16 cirrhotic patients with minimal hepatic encephalopathy (MHE). Images were collected using a 3 Tesla MR scanner (Achieva 3T-TX, Philips, Netherlands). Pulsed ASL was performed. Patients showing MHE were detected using the battery Psychometric Hepatic Encephalopathy Score (PHES) consisting of five tests. Different cognitive and motor functions were also assessed: alterations in selective attention were evaluated using the Stroop test. Patients and controls also performed visuo-motor and bimanual coordination tests. Several biochemical parameters were measured: serum pro-inflammatory interleukins (IL-6 and IL-18), 3-nitrotyrosine, cGMP and nitrates+nitrites in plasma, and blood ammonia. Bivariate correlations were evaluated.
  
  
  RESULTS
  In patients with MHE, BF was increased in cerebellar hemisphere (P = 0.03) and vermis (P = 0.012) and reduced in occipital lobe (P = 0.017). BF in cerebellar hemisphere was also increased in patients without MHE (P = 0.02). Bimanual coordination was impaired in patients without MHE (P = 0.05) and much more in patients with MHE (P < 0.0001). Visuo-motor coordination was impaired only in patients with MHE (P < 0.0001). Attention was slightly affected in patients without MHE and more strongly in patients with MHE (P < 0.0001). BF in cerebellar hemisphere and vermis correlated with performance in most tests of PHES [(number connection tests A (NCT-A), B (NCT-B)and line tracing test] and in the congruent task of Stroop test. BF in frontal lobe correlated with NCT-A. Performance in bimanual and visuomotor coordination tests correlated only with BF in cerebellar hemisphere. BF in occipital lobe correlates with performance in the PHES battery and with CFF. BF in cerebellar hemisphere correlates with plasma cGMP and nitric oxide (NO) metabolites. BF in vermis cerebellar also correlates with NO metabolites and with 3-nitrotyrosine. IL-18 in plasma correlates with BF in thalamus and occipital lobe.
  
  
  CONCLUSIONS
  Non invasive BF determination in cerebellum using ASL may detect MHE earlier than the PHES. Altered NO-cGMP pathway seems to be associated to altered BF in cerebellum.
authors.affiliation: Vicente Felipo, Carla Giménez-Garzó, Omar Cauli, Laboratory of Neurobiology, Centro Investigación Príncipe Felipe, 46012 Valencia, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Felipo
authors.affiliation: Vicente Felipo, Carla Giménez-Garzó, Omar Cauli, Laboratory of Neurobiology, Centro Investigación Príncipe Felipe, 46012 Valencia, Spain.
authors.forename: Amparo
authors.initials: A
authors.lastname: Urios
authors.affiliation: Vicente Felipo, Carla Giménez-Garzó, Omar Cauli, Laboratory of Neurobiology, Centro Investigación Príncipe Felipe, 46012 Valencia, Spain.
authors.forename: Carla
authors.initials: C
authors.lastname: Giménez-Garzó
authors.affiliation: Vicente Felipo, Carla Giménez-Garzó, Omar Cauli, Laboratory of Neurobiology, Centro Investigación Príncipe Felipe, 46012 Valencia, Spain.
authors.forename: Omar
authors.initials: O
authors.lastname: Cauli
authors.affiliation: Vicente Felipo, Carla Giménez-Garzó, Omar Cauli, Laboratory of Neurobiology, Centro Investigación Príncipe Felipe, 46012 Valencia, Spain.
authors.forename: Maria-Jesús
authors.initials: MJ
authors.lastname: Andrés-Costa
authors.affiliation: Vicente Felipo, Carla Giménez-Garzó, Omar Cauli, Laboratory of Neurobiology, Centro Investigación Príncipe Felipe, 46012 Valencia, Spain.
authors.forename: Olga
authors.initials: O
authors.lastname: González
authors.affiliation: Vicente Felipo, Carla Giménez-Garzó, Omar Cauli, Laboratory of Neurobiology, Centro Investigación Príncipe Felipe, 46012 Valencia, Spain.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Serra
authors.affiliation: Vicente Felipo, Carla Giménez-Garzó, Omar Cauli, Laboratory of Neurobiology, Centro Investigación Príncipe Felipe, 46012 Valencia, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Sánchez-González
authors.affiliation: Vicente Felipo, Carla Giménez-Garzó, Omar Cauli, Laboratory of Neurobiology, Centro Investigación Príncipe Felipe, 46012 Valencia, Spain.
authors.forename: Roberto
authors.initials: R
authors.lastname: Aliaga
authors.affiliation: Vicente Felipo, Carla Giménez-Garzó, Omar Cauli, Laboratory of Neurobiology, Centro Investigación Príncipe Felipe, 46012 Valencia, Spain.
authors.forename: Remedios
authors.initials: R
authors.lastname: Giner-Durán
authors.affiliation: Vicente Felipo, Carla Giménez-Garzó, Omar Cauli, Laboratory of Neurobiology, Centro Investigación Príncipe Felipe, 46012 Valencia, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Belloch
authors.affiliation: Vicente Felipo, Carla Giménez-Garzó, Omar Cauli, Laboratory of Neurobiology, Centro Investigación Príncipe Felipe, 46012 Valencia, Spain.
authors.forename: Carmina
authors.initials: C
authors.lastname: Montoliu
mesh_terms: D000368:Aged; D000641:Ammonia / Q000097:blood; D001288:Attention; D015415:Biomarkers / Q000097:blood; D001783:Blood Flow Velocity; D002531:Cerebellum / Q000098:blood supply*; D002560:Cerebrovascular Circulation; D003071:Cognition; D006152:Cyclic GMP / Q000097:blood; D042241:Early Diagnosis; D005260:Female; D006501:Hepatic Encephalopathy / Q000097:blood / Q000175:diagnosis* / Q000209:etiology / Q000503:physiopathology / Q000523:psychology; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D008103:Liver Cirrhosis / Q000150:complications; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009043:Motor Activity; D009569:Nitric Oxide / Q000097:blood; D055420:Perfusion Imaging / Q000379:methods*; D011237:Predictive Value of Tests; D011594:Psychometrics; D012039:Regional Blood Flow; D012189:Retrospective Studies; D057190:Stroop Test
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators; D009569:Nitric Oxide; D000641:Ammonia; D006152:Cyclic GMP
keywords: Arterial spin labelling; Blood flow; Cerebellum; Minimal hepatic encephalopathy; Neurological impairment