Bannas Peter, Kramer Harald, Hernando Diego, Agni Rashmi, Cunningham Ashley M, Mandal Rakesh, Motosugi Utaroh, Sharma Samir D, Munoz del Rio Alejandro, Fernandez Luis, Reeder Scott B
Department of Radiology, University of Wisconsin-Madison, Madison, WI.
Department of Radiology, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
Hepatology. 2015 Nov;62(5):1444-55. doi: 10.1002/hep.28012. Epub 2015 Sep 28.
Emerging magnetic resonance imaging (MRI) biomarkers of hepatic steatosis have demonstrated tremendous promise for accurate quantification of hepatic triglyceride concentration. These methods quantify the proton density fat-fraction (PDFF), which reflects the concentration of triglycerides in tissue. Previous in vivo studies have compared MRI-PDFF with histologic steatosis grading for assessment of hepatic steatosis. However, the correlation of MRI-PDFF with the underlying hepatic triglyceride content remained unknown. The aim of this ex vivo study was to validate the accuracy of MRI-PDFF as an imaging biomarker of hepatic steatosis. Using ex vivo human livers, we compared MRI-PDFF with magnetic resonance spectroscopy-PDFF (MRS-PDFF), biochemical triglyceride extraction, and histology as three independent reference standards. A secondary aim was to compare the precision of MRI-PDFF relative to biopsy for the quantification of hepatic steatosis. MRI-PDFF was prospectively performed at 1.5 Tesla in 13 explanted human livers. We performed colocalized paired evaluation of liver fat content in all nine Couinaud segments using single-voxel MRS-PDFF (n=117) and tissue wedges for biochemical triglyceride extraction (n=117), and five core biopsies performed in each segment for histologic grading (n=585). Accuracy of MRI-PDFF was assessed through linear regression with MRS-PDFF, triglyceride extraction, and histology. Intraobserver agreement, interobserver agreement, and repeatability of MRI-PDFF and histologic grading were assessed through Bland-Altman analyses. MRI-PDFF showed an excellent correlation with MRS-PDFF (r=0.984, confidence interval 0.978-0.989) and strong correlation with histology (r=0.850, confidence interval 0.791-0.894) and triglyceride extraction (r=0.871, confidence interval 0.818-0.909). Intraobserver agreement, interobserver agreement, and repeatability showed a significantly smaller variance for MRI-PDFF than for histologic steatosis grading (all P<0.001).
MRI-PDFF is an accurate, precise, and reader-independent noninvasive imaging biomarker of liver triglyceride content, capable of steatosis quantification over the entire liver.
新兴的肝脏脂肪变性磁共振成像(MRI)生物标志物已显示出在准确量化肝脏甘油三酯浓度方面的巨大前景。这些方法可量化质子密度脂肪分数(PDFF),它反映了组织中甘油三酯的浓度。先前的体内研究已将MRI-PDFF与组织学脂肪变性分级进行比较,以评估肝脏脂肪变性。然而,MRI-PDFF与潜在肝脏甘油三酯含量之间的相关性仍不清楚。这项离体研究的目的是验证MRI-PDFF作为肝脏脂肪变性成像生物标志物的准确性。我们使用离体人类肝脏,将MRI-PDFF与磁共振波谱-PDFF(MRS-PDFF)、生化甘油三酯提取和组织学作为三种独立的参考标准进行比较。第二个目的是比较MRI-PDFF相对于活检在量化肝脏脂肪变性方面的精度。在1.5特斯拉下对13个离体人类肝脏前瞻性地进行了MRI-PDFF检查。我们使用单体素MRS-PDFF(n = 117)和用于生化甘油三酯提取的组织楔块(n = 117)对所有九个Couinaud肝段的肝脏脂肪含量进行了共定位配对评估,并在每个肝段进行了五次核心活检以进行组织学分级(n = 585)。通过与MRS-PDFF进行线性回归以及与甘油三酯提取和组织学进行比较来评估MRI-PDFF的准确性。通过Bland-Altman分析评估MRI-PDFF和组织学分级的观察者内一致性、观察者间一致性和可重复性。MRI-PDFF与MRS-PDFF显示出极好的相关性(r = 0.984,置信区间0.978 - 0.989),与组织学(r = 0.850,置信区间0.791 - 0.894)和甘油三酯提取(r = 0.871,置信区间0.818 - 0.909)显示出强相关性。观察者内一致性、观察者间一致性和可重复性表明,MRI-PDFF的方差明显小于组织学脂肪变性分级(所有P < 0.001)。
MRI-PDFF是一种准确、精确且与阅片者无关的肝脏甘油三酯含量无创成像生物标志物,能够对整个肝脏的脂肪变性进行量化。