MRI versus histological methods for time course monitoring of steatosis amount in a murine model of NAFLD.

PURPOSE: Hepatic steatosis is an increasingly frequent disease with potentially severe complications. A simple quantification method is required for pretherapeutic studies to allow steatosis monitoring. This study aimed at evaluating steatosis quantification via a standard 1.5T MRI machine in a murine model. MATERIALS AND METHODS: Eleven groups of two rats received a choline methionine deficient diet. MRI was performed at days 0, 2, 4, 5, 6, 7 and 8, and weeks 2, 3, 4 and 5. A phased array surface coil system was used to acquire a GE T1 in- and out-of-phase multi-echo sequence, with neither cardiac nor respiratory synchronization. Steatosis was calculated with the 3-echoes method. Histological quantifications were performed both by optical analysis (percentage of fatty hepatocytes) and by automated measurement of the area of steatosis (AOS). The reference was total intrahepatic triglycerides (TIT). Protocol was approved by the ethic committee. RESULTS: Steatosis without inflammation, increasing with diet duration, was obtained. MRI provided better agreement (intraclass correlation coefficient) with TIT (0.889, p<0.001) than did AOS (0.629, p=0.001) or optical analysis (0.280, p=0.098). MRI permitted closer monitoring of TIT over time than did AOS or optical analysis. By multivariate analysis, MRI was an independent predictor of TIT on first step and ALT on second step. A model combining these 2 variables provided excellent agreement with TIT (0.953, p<0.001) and permitted excellent monitoring of steatosis over time. CONCLUSION: MRI is reliable, easy, fast and superior to histological techniques for the assessment of hepatic steatosis in a murine model.

Effect of head-upright tilt on the dynamic of cerebral autoregulation.

The effect of head-upright tilting on the rate of cerebral autoregulation was studied in 12 healthy volunteers (nine men and three women; age range 20-36 years). The dynamics of cerebral autoregulation was determined from the rate of change in cerebral resistance (RoR) during a drop in arterial blood pressure induced by rapid deflation of a 3-min ischaemic thigh cuff and from the ratio of changes in cerebral blood flow and arterial blood pressure (CAI) during the recovery period after the drop in arterial blood pressure. The test was performed supine and with 40 degrees head-up tilt (40 degrees HUT). Middle cerebral artery mean blood flow velocity was measured by transcranial Doppler simultaneously with peripheral arterial blood pressure using Finapres. The thigh cuff deflation induced a larger drop in arterial pressure during 40 degrees HUT [median -28% (25 percentile -36, 75 percentile -19)] than in the supine position [-16% (-23, -15)] (P < 0.01) and in cerebral resistance [supine: -12% (-15, -6); 40 degrees HUT: -15% (-20, -12); P < 0.05]. There was no significant change in RoR [15% s-1 (12, 15)] and CAI [1.9 (1.5, 3.1)] measured supine and during 40 degrees HUT [RoR: 13% s-1 (12, 15); CAI: 1.3 (0.99, 1.9)]. During the drop in arterial pressure, the relationship between arterial blood pressure and systolic peak-to-peak interval exhibited an hysteresis loop, indicating a cardiopulmonary and/or baroreflex activation that was not observed with cerebral resistance. The rate of autoregulation is an intrinsic property of the cerebral vascular bed and is not affected by the vasodilator state in the range of arterial blood pressure changes induced by the tight cuff method.