Initial evaluation of hepatic T1 relaxation time as an imaging marker of liver disease associated with autosomal recessive polycystic kidney disease (ARPKD)
Initial evaluation of hepatic T1 relaxation time as an imaging marker of liver disease associated with autosomal recessive polycystic kidney disease (ARPKD)
复制标题
DOI：
10.1002/nbm.3442
复制
发表时间：
2016-01-01
影响因子：
2.9
通讯作者：
Flask, Chris A.
中科院分区：
文献类型：
--
作者：
Gao, Ying;Erokwu, Bernadette O.;Flask, Chris A.
常染色体隐性遗传性多囊肾病（ARPKD）是一种影响肾脏和肝脏的潜在致死性多器官疾病。不幸的是，目前还没有非侵入性方法来监测ARPKD患者的肝脏疾病进展，限制了潜在治疗干预措施的研究。在此，我们对T-1弛豫时间作为一种潜在的成像生物标志物进行了初步研究，以定量评估ARPKD肝脏疾病的两个主要病理标志：ARPKD PCK大鼠模型中的胆管扩张和门静脉周围纤维化。在Bruker BioSpec 7.0T MRI扫描仪上，使用Look-tap采集获得5只3月龄PCK大鼠的T-1弛豫时间结果。6只3月龄Sprague-Dawley（SD）大鼠也被扫描作为对照。所有动物在三个月扫描后被安乐死，以进行胆管扩张和肝纤维化的组织学和生化评估以进行比较。与年龄匹配的SD对照大鼠（847 +/-26 ms，p=0.01）相比，PCK大鼠的肝脏T-1值（平均值+/-标准差=935 +/-39 ms）显著增加。一只PCK大鼠表现出严重的胆管炎（平均T-1= 1413 ms），这在ARPKD患者中周期性发生。观察到的体内肝脏T-1弛豫时间的增加与胆管扩张和纤维化的三个组织学和生化指标显著相关：胆管面积百分比（R=0.85，p=0.002），门静脉周围纤维化面积百分比（R=0.82，p=0.004）和羟脯氨酸含量（R=0.76，p=0.01）。这些结果表明，肝脏T-1弛豫时间可能提供一个敏感的和非侵入性的成像生物标志物，以监测ARPKD肝病。版权所有（c）2015约翰威利父子有限公司
Autosomal recessive polycystic kidney disease (ARPKD) is a potentially lethal multi-organ disease affecting both the kidneys and the liver. Unfortunately, there are currently no non-invasive methods to monitor liver disease progression in ARPKD patients, limiting the study of potential therapeutic interventions. Herein, we perform an initial investigation of T-1 relaxation time as a potential imaging biomarker to quantitatively assess the two primary pathologic hallmarks of ARPKD liver disease: biliary dilatation and periportal fibrosis in the PCK rat model of ARPKD. T-1 relaxation time results were obtained for five PCK rats at 3months of age using a Look-Locker acquisition on a Bruker BioSpec 7.0T MRI scanner. Six three-month-old Sprague-Dawley (SD) rats were also scanned as controls. All animals were euthanized after the three-month scans for histological and biochemical assessments of bile duct dilatation and hepatic fibrosis for comparison. PCK rats exhibited significantly increased liver T-1 values (mean +/- standard deviation=935 +/- 39ms) compared with age-matched SD control rats (847 +/- 26ms, p=0.01). One PCK rat exhibited severe cholangitis (mean T-1=1413ms), which occurs periodically in ARPKD patients. The observed increase in the in vivo liver T-1 relaxation time correlated significantly with three histological and biochemical indicators of biliary dilatation and fibrosis: bile duct area percent (R=0.85, p=0.002), periportal fibrosis area percent (R=0.82, p=0.004), and hydroxyproline content (R=0.76, p=0.01). These results suggest that hepatic T-1 relaxation time may provide a sensitive and non-invasive imaging biomarker to monitor ARPKD liver disease. Copyright (c) 2015 John Wiley & Sons, Ltd.