Soares Ana Francisca, Lei Hongxia
École Polytechnique Fédérale de Lausanne - Laboratory for Functional and Metabolic Imaging (LIFMET), Lausanne, Switzerland.
École Polytechnique Fédérale de Lausanne, Center for Biomedical Imaging (CIBM), Lausanne, Switzerland.
NMR Biomed. 2018 Feb;31(2). doi: 10.1002/nbm.3873. Epub 2017 Dec 20.
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 μm ) using a birdcage coil. Two-dimensional GRE MRI with high spatial resolution (in-plane resolution, 100 × 130 μm ; slices, 30 × 0.3 mm) was performed using a surface coil. Brain- (dorsal hippocampus) and liver-localized 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.
本研究证明了磁共振成像（MRI）和磁共振血管造影（MRA）适用于对小鼠先天性门体分流（PSS）进行成像，PSS是一种血管异常，其中肠系膜血液绕过肝脏，而是直接引流到体循环。与其他实验评估同时进行的非侵入性诊断能够进一步表征与PSS相关的肝脏、全身和脑代谢缺陷。在一台26厘米的水平孔径14.1-T磁体中进行磁共振测量。使用鸟笼线圈通过三维梯度回波序列（GRE；平面分辨率为234×250×234μm）获得MRA。使用表面线圈进行具有高空间分辨率的二维GRE MRI（平面分辨率为100×130μm；切片厚度为30×0.3mm）。还使用表面线圈进行脑（背侧海马体）和肝脏定位的氢磁共振波谱（MRS）。通过口服葡萄糖耐量试验（OGTT）评估全身代谢状态。MRA和解剖学MRI均能识别小鼠的肝血管并诊断PSS。PSS的发生率约为10%。PSS小鼠的肝脏脂质含量高于对照小鼠（5.1±2.8%对1.8±0.6%，p=0.02）。PSS小鼠的脑谷氨酰胺浓度高于对照小鼠（7.3±1.0μmol/g对2.7±0.6μmol/g，p<0.0001），相反，肌醇浓度较低（4.2±0.6μmol/g对6.0±0.4μmol/g，p<0.0001），牛磺酸（9.7±1.2μmol/g对11.0±0.4μmol/g，p<0.01）和总胆碱浓度（0.9±0.1μmol/g对1.2±0.1μmol/g，p<0.001）。PSS小鼠的空腹血糖和血浆胰岛素低于对照小鼠（分别为4.7±0.5mM对8.8±0.6mM，p<0.0001；以及0.04±0.03μg/L对0.3±0.2μg/L，p=0.02）。OGTT期间PSS小鼠的葡萄糖清除延迟且效率低于对照小鼠。因此，鉴于近交系小鼠中PSS的发生率不可忽视，未被诊断出的PSS的存在将重要地影响实验结果，特别是在涉及脑、肝脏或全身代谢的研究中。
