T2 relaxation time is related to liver fibrosis severity
T2 relaxation time is related to liver fibrosis severity
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DOI：
10.21037/qims.2016.03.02
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发表时间：
2016-04-01
影响因子：
2.8
通讯作者：
Caravan, Peter
中科院分区：
文献类型：
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作者：
Guimaraes, Alexander R.;Siqueira, Luiz;Caravan, Peter
背景：肝纤维化的分级依赖于肝活检。成像技术，包括弹性成像和松弛测量技术，在诊断中度纤维化方面取得了不同程度的成功。本研究的目的是确定是否有一个关系的T2弛豫时间的肝实质和肝纤维化的组织学分级的丙型肝炎患者接受常规，肝脏MRI和肝活检，并验证我们的方法与phanomaly和大鼠模型的肝纤维化。（I）1999年7月至2010年1月期间，在6个月内接受常规、临床肝脏MRI和活检的123名患者入选了一项回顾性研究。采用双回波快速自旋回波等效脉冲序列在1.5 T下进行MR成像。通过与组织病理学分级（Ishak 0-6）和常规血清肝脏炎症[天冬氨酸转氨酶（AST）和丙氨酸转氨酶（ALT）]相关的右叶内感兴趣区域（ROI）的单指数拟合计算患者肝实质的T2弛豫时间。使用普通逻辑和有序逻辑回归和ANOVA进行统计比较，比较T2与Ishak纤维化，而不使用AST和ALT作为协变量;（II）使用葡聚糖涂覆的磁性氧化铁纳米颗粒的系列稀释液制备体模。在1.5 T下，通过比较双回波快速自旋回波序列与Carr-Purcell-Meigboom-Gill（CPMG）多回波序列进行T2加权成像。使用配对t检验进行统计学比较;（III）每周腹膜内注射磷酸盐缓冲溶液（PBS）对照（n= 4只大鼠）;二乙基亚硝胺（DEN）5周（n= 5只大鼠）或8周（n= 4只大鼠）的雄性Wistar大鼠在具有自制鸟笼线圈的Bruker Pharmascan 4.7 T磁体上进行MR成像。通过对多切片多回波T2加权数据使用单指数拟合算法来量化T2。结果：（1）大鼠和人肝脏组织学检查均未发现脂肪变性和血色病，T2值随纤维化程度的增加而单调增加（对照组65.4 +/- 2.9 ms，n= 6例患者）;轻度（Ishak 1-2）66.7 +/- 1.9 ms（n= 30）;中度（Ishak 3-4）71.6 +/- 1.7 ms（n= 26）;重度（Ishak 5-6）72.4 +/- 1.4 ms（n= 61）;标准误相对较低（与2.9 ms相似）。基于T2和Ishak的逻辑回归，轻度（Ishak 4）之间存在统计学显著差异（P=0.03），当使用炎症标志物作为协变量时，差异变得不显著（P=0.07）。使用有序逻辑回归扩展该模型，比较T2与Ishak（P=0.01），在所有4个组中存在显著性，使用炎症作为协变量（P=0.03）具有显著性，并且通过ANOVA在所有组中接近统计学显著性（P=0.07）;（II）T2单调增加，并且具有统计学显著性（ANOVA P
Background: The grading of liver fibrosis relies on liver biopsy. Imaging techniques, including elastography and relaxometric, techniques have had varying success in diagnosing moderate fibrosis. The goal of this study was to determine if there is a relationship between the T2-relaxation time of hepatic parenchyma and the histologic grade of liver fibrosis in patients with hepatitis C undergoing both routine, liver MRI and liver biopsy, and to validate our methodology with phantoms and in a rat model of liver fibrosis.Methods: This study is composed of three parts: (I) 123 patients who underwent both routine, clinical liver MRI and biopsy within a 6-month period, between July 1999 and January 2010 were enrolled in a retrospective study. MR imaging was performed at 1.5 T using dual-echo turbo-spin echo equivalent pulse sequence. T2 relaxation time of liver parenchyma in patients was calculated by mono-exponential fit of a region of interest (ROI) within the right lobe correlating to histopathologic grading (Ishak 0-6) and routine serum liver inflammation [aspartate aminotransferase (AST) and alanine aminotransferase (ALT)]. Statistical comparison was performed using ordinary logistic and ordinal logistic regression and ANOVA comparing T2 to Ishak fibrosis without and using AST and ALT as covariates; (II) a phantom was prepared using serial dilutions of dextran coated magnetic iron oxide nanoparticles. T2 weighed imaging was performed by comparing a dual echo fast spin echo sequence to a Carr-Purcell-Meigboom-Gill (CPMG) multi-echo sequence at 1.5 T. Statistical comparison was performed using a paired t-test; (III) male Wistar rats receiving weekly intraperitoneal injections of phosphate buffer solution (PBS) control (n= 4 rats); diethylnitrosamine (DEN) for either 5 (n= 5 rats) or 8 weeks (n= 4 rats) were MR imaged on a Bruker Pharmascan 4.7 T magnet with a home-built bird-cage coil. T2 was quantified by using a mono-exponential fitting algorithm on multi-slice multi echo T2 weighted data. Statistical comparison was performed using ANOVA.Results: (I) Histopathologic evaluation of both rat and human livers demonstrated no evidence of steatosis or hemochromatosis There was a monotonic increase in mean T2 value with increasing degree of fibrosis (control 65.4 +/- 2.9 ms, n= 6 patients); mild (Ishak 1-2) 66.7 +/- 1.9 ms (n= 30); moderate (Ishak 3-4) 71.6 +/- 1.7 ms (n= 26); severe (Ishak 5-6) 72.4 +/- 1.4 ms (n= 61); with relatively low standard error (similar to 2.9 ms). There was a statistically significant difference between degrees of mild (Ishak 4) (P=0.03) based on logistic regression of T2 and Ishak, which became insignificant (P=0.07) when using inflammatory markers as covariates. Expanding on this model using ordinal logistic regression, there was significance amongst all 4 groups comparing T2 to Ishak (P=0.01), with significance using inflammation as a covariate (P=0.03) and approaching statistical significance amongst all groups by ANOVA (P=0.07); (II) there was a monotonic increase in T2 and statistical significance (ANOVA P