Department of Radiology, Northwestern University, 737 N Michigan Ave, Suite 1600, Chicago, IL 60611, USA.
Radiology. 2010 Jan;254(1):129-37. doi: 10.1148/radiol.09090410.
To investigate the relationship between gas-challenge blood oxygen level-dependent (BOLD) magnetic resonance (MR) imaging measurements and hepatic disease progression in a rat model of diethylnitrosamine (DEN)-induced liver fibrosis.
The institutional animal care and use committee approved all experiments. Liver fibrosis was induced in 27 male Wistar rats by means of weekly oral gavage with 5 mL of 1.5% DEN solution per kilogram of body weight for 3-11 weeks, which produced varying degrees of liver fibrosis. Eight rats developed nonsubstantial fibrosis; eight rats, substantial fibrosis; and 15 rats, cirrhosis. Four nontreated healthy rats served as controls. Multiple-gradient-echo MR images were acquired in the rats at steady-state normoxia and hyperoxia and then during dynamic gas challenges. The change in R2* (DeltaR2*) during the gas challenge and the ratio of number of activated voxels to total number of voxels in the liver were quantified. Masson trichrome staining of liver tissue was used to identify collagen tissue. Liver fibrosis was assessed by using a semiquantitative METAVIR scoring system and quantitative analysis of the percentage of liver fibrosis. Hepatic hemodynamic responses at BOLD MR imaging were compared across the fibrosis stages at independent-sample t test and linear regression analyses.
DeltaR2* was well correlated with gas-challenge interval. Mean DeltaR2* decreased during liver fibrosis progression, from 19.60 sec(-1) +/- 4.47 (standard deviation) in animals without substantial fibrosis to 14.02 sec(-1) +/- 2.88 and 6.26 sec(-1) +/- 7.40 in animals with substantial fibrosis and cirrhosis, respectively (P = .006 for rats without vs rats with substantial fibrosis, P = .001 for rats with substantial fibrosis vs rats with cirrhosis, P < .001 for rats without substantial fibrosis vs rats with cirrhosis). Mean DeltaR2* (r = -0.773) and liver activation (r = -0.691) were inversely correlated with liver fibrosis (P < .001).
Carbogen gas-challenge BOLD MR imaging can depict hepatic hemodynamic alterations during the progression of fibrosis and has the potential to serve as a noninvasive, nonenhanced imaging method for liver fibrosis diagnosis and staging.
在二乙基亚硝胺（DEN）诱导的肝纤维化大鼠模型中，研究气体激发血氧水平依赖（BOLD）磁共振（MR）成像测量与肝疾病进展之间的关系。
机构动物护理和使用委员会批准了所有实验。通过每周口服 5ml 1.5% DEN 溶液/kg 体重，对 27 只雄性 Wistar 大鼠进行肝纤维化诱导，共 3-11 周，产生不同程度的肝纤维化。8 只大鼠发生非实质性纤维化；8 只大鼠发生实质性纤维化；15 只大鼠发生肝硬化。4 只未治疗的健康大鼠作为对照。在稳定的常氧和高氧状态下以及在动态气体激发过程中，对大鼠进行多梯度回波 MR 成像。量化气体激发过程中的 R2*（DeltaR2*）变化以及肝脏中激活体素与总体素的比值。使用 Masson 三色染色法鉴定胶原组织。使用半定量 METAVIR 评分系统和肝纤维化百分比的定量分析评估肝纤维化。采用独立样本 t 检验和线性回归分析比较 BOLD MR 成像时的肝血流动力学反应在纤维化各阶段的差异。
DeltaR2与气体激发间隔有很好的相关性。随着肝纤维化的进展，平均 DeltaR2逐渐降低，从无实质性纤维化的大鼠的 19.60 sec(-1) +/- 4.47（标准差）降至实质性纤维化大鼠的 14.02 sec(-1) +/- 2.88 和肝硬化大鼠的 6.26 sec(-1) +/- 7.40（无实质性纤维化大鼠与实质性纤维化大鼠比较，P =.006；实质性纤维化大鼠与肝硬化大鼠比较，P =.001；无实质性纤维化大鼠与肝硬化大鼠比较，P <.001）。平均 DeltaR2*（r = -0.773）和肝激活（r = -0.691）与肝纤维化呈负相关（P <.001）。
碳化氢气体激发 BOLD MR 成像可以描绘纤维化进展过程中的肝血流动力学改变，有可能成为一种非侵入性、非增强的肝纤维化诊断和分期成像方法。
