Non-invasive diagnosis and metabolic consequences of congenital portosystemic shunts in C57BL/6 J mice

This study demonstrates the suitability of magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) for the imaging of congenital portosystemic shunts (PSS) in mice, a vascular abnormality in which mesenteric blood bypasses the liver and is instead drained directly to the systemic circulation. The non-invasive diagnosis performed in tandem with other experimental assessments permits further characterization of liver, whole-body and brain metabolic defects associated with PSS. Magnetic resonance measurements were performed in a 26-cm, horizontal-bore, 14.1-T magnet. MRA was obtained with a three-dimensional gradient echo sequence (GRE; in-plane resolution, 234 × 250 × 234 μm3 ) using a birdcage coil. Two-dimensional GRE MRI with high spatial resolution (in-plane resolution, 100 × 130 μm2 ; slices, 30 × 0.3 mm) was performed using a surface coil. Brain- (dorsal hippocampus) and liver-localized 1 H magnetic resonance spectroscopy (MRS) was also performed with the surface coil. Whole-body metabolic status was evaluated with an oral glucose tolerance test (OGTT). Both MRA and anatomical MRI allowed the identification of hepatic vessels and the diagnosis of PSS in mice. The incidence of PSS was about 10%. Hepatic lipid content was higher in PSS than in control mice (5.1 ± 2.8% versus 1.8 ± 0.6%, p = 0.02). PSS mice had higher brain glutamine concentration than controls (7.3 ± 1.0 μmol/g versus 2.7 ± 0.6 μmol/g, p < 0.0001) and, conversely, lower myo-inositol (4.2 ± 0.6 μmol/g versus 6.0 ± 0.4 μmol/g, p < 0.0001), taurine (9.7 ± 1.2 μmol/g versus 11.0 ± 0.4 μmol/g, p < 0.01) and total choline (0.9 ± 0.1 μmol/g versus 1.2 ± 0.1 μmol/g, p < 0.001) concentrations. Fasting blood glucose and plasma insulin were lower in PSS than in control mice (4.7 ± 0.5mM versus 8.8 ± 0.6mM, p < 0.0001; and 0.04 ± 0.03 μg/L versus 0.3 ± 0.2 μg/L, p = 0.02, respectively). Glucose clearance during OGTT was delayed and less efficient in PSS mice than in controls. Thus, given the non-negligible incidence of PSS in inbred mice, the undiagnosed presence of PSS will, importantly, have an impact on experimental outcomes, notably in studies addressing brain, liver or whole-body metabolism.