Quantitative Assessment of Liver Function Using Gadoxetate-Enhanced Magnetic Resonance Imaging: Monitoring Transporter-Mediated Processes in Healthy Volunteers.
Quantitative Assessment of Liver Function Using Gadoxetate-Enhanced Magnetic Resonance Imaging: Monitoring Transporter-Mediated Processes in Healthy Volunteers.
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DOI：
10.1097/rli.0000000000000316
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发表时间：
2017-02
影响因子：
6.7
通讯作者：
Naish JH
中科院分区：
文献类型：
--
作者：
Georgiou L;Penny J;Nicholls G;Woodhouse N;Blé FX;Hubbard Cristinacce PL;Naish JH
本研究的目的是利用无创动态增强磁共振成像（MRI）技术，在体内研究肝胆造影剂加多西特在人体内的分布和消除，并利用一种新型示踪动力学模型，在一组健康志愿者中表征其进入肝细胞并随后外排到胆汁中的运输机制。通过广告招募10名健康志愿者（年龄18-29岁），无肾脏或肝脏损害史。参与者参加了2次MRI检查（间隔至少一周），加多赛特作为对比剂。动态增强MRI数据采集时间约为50分钟，轴向面三维梯度回波序列，时间分辨率为6.2秒。使用提出的2室摄取和外排模型分析来自肝脏感兴趣区域的数据，以估计肝细胞对加多赛特的摄取率及其进入胆汁的外排率。获得两次访问的再现性统计，以检验该技术的稳健性及其对采集时间的依赖性。8名参与者参加了两次研究，并被纳入分析。由此产生的图像能够同时监测gadoxetate在肝脏、脾脏和肾脏等多个器官的分布，以及其通过胆总管的消除、在胆囊的积聚和在十二指肠的排泄。在使用50分钟采集的2次访问中，肝细胞的平均摄取（ki）和排出（kef）率分别为0.22±0.05和0.017±0.006/min。肝脏提取分数估计为0.19±0.04/min。2次就诊之间在组水平（95%置信区间；ki：±0.02/min, kef：±0.004/min）的变异性低于个体变异性（可重复性；ki：±0.06/min, kef：±0.012/min）。数据截断表明，摄取率估计保留了其精度，以及他们的群体和个人可重复性下降到大约10分钟的采集。随着获取时间的减少，外溢率估计被低估了（与50分钟的获取相比），尽管这些影响在获取时间短于大约30分钟的情况下更为明显。这是第一个报道健康志愿者体内加多赛特的肝脏摄取和外排运输过程的研究。结果强调，动态对比增强MRI与gadoxetate可以提供新的定量洞察肝功能，因此可能在旨在监测肝脏病理的研究中被证明是有用的，以及作为研究肝脏药物-药物相互作用的替代方法。
The objective of this study was to use noninvasive dynamic contrast-enhanced magnetic resonance imaging (MRI) techniques to study, in vivo, the distribution and elimination of the hepatobiliary contrast agent gadoxetate in the human body and characterize the transport mechanisms involved in its uptake into hepatocytes and subsequent efflux into the bile using a novel tracer kinetic model in a group of healthy volunteers. Ten healthy volunteers (age range, 18–29 years), with no history of renal or hepatic impairment, were recruited via advertisement. Participants attended 2 MRI visits (at least a week apart) with gadoxetate as the contrast agent. Dynamic contrast-enhanced MRI data were acquired for approximately 50 minutes with a 3-dimensional gradient-echo sequence in the axial plane, at a temporal resolution of 6.2 seconds. Data from regions of interest drawn in the liver were analyzed using the proposed 2-compartment uptake and efflux model to provide estimates for the uptake rate of gadoxetate in hepatocytes and its efflux rate into the bile. Reproducibility statistics for the 2 visits were obtained to examine the robustness of the technique and its dependence in acquisition time. Eight participants attended the study twice and were included into the analysis. The resulting images provided the ability to simultaneously monitor the distribution of gadoxetate in multiple organs including the liver, spleen, and kidneys as well as its elimination through the common bile duct, accumulation in the gallbladder, and excretion in the duodenum. The mean uptake (ki) and efflux (kef) rates in hepatocytes, for the 2 visits using the 50-minute acquisition, were 0.22 ± 0.05 and 0.017 ± 0.006/min, respectively. The hepatic extraction fraction was estimated to be 0.19 ± 0.04/min. The variability between the 2 visits within the group level (95% confidence interval; ki: ±0.02/min, kef: ±0.004/min) was lower compared with the individual variability (repeatability; ki: ±0.06/min, kef: ±0.012/min). Data truncation demonstrated that the uptake rate estimates retained their precision as well as their group and individual reproducibility down to approximately 10 minutes of acquisition. Efflux rate estimates were underestimated (compared with the 50-minute acquisition) as the duration of the acquisition decreased, although these effects were more pronounced for acquisition times shorter than approximately 30 minutes. This is the first study that reports estimates for the hepatic uptake and efflux transport process of gadoxetate in healthy volunteers in vivo. The results highlight that dynamic contrast-enhanced MRI with gadoxetate can provide novel quantitative insights into liver function and may therefore prove useful in studies that aim to monitor liver pathology, as well as being an alternative approach for studying hepatic drug-drug interactions.