MRI 测量小鼠肝纤维化

MRI Measures of Murine Liver Fibrosis.

机构信息

Imaging Research Center, Department of Radiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.

Department of Radiology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.

出版信息

J Magn Reson Imaging. 2021 Sep;54(3):739-749. doi: 10.1002/jmri.27601. Epub 2021 Mar 18.

DOI:10.1002/jmri.27601

PMID:33738856

Abstract

BACKGROUND

An imaging method that allows quantitative fibrosis estimates is needed to facilitate the diagnosis of chronic liver disease. Amide proton transfer (APT) and tissue sodium concentration (TSC) estimates could meet this need.

HYPOTHESIS

APT and TSC estimates correlate with fibrosis in a mouse model of chronic liver disease.

STUDY TYPE

Prospective.

PHANTOMS/ANIMAL MODEL: Male C57Bl/6 mice given CCl or vehicle (N = 8 each) twice weekly for 16 weeks.

FIELD STRENGTH/SEQUENCE: Liver T (Look-Locker gradient recalled echo [GRE] sequence), T (multiecho spin echo sequence), T (fast spin echo sequence with 500 Hz spin locking pulse), and APT (GRE sequence with off-resonance pulses) data were acquired at 7 T at 12 and 16 weeks. Liver sodium data (multiple echo GRE sequence) were acquired at 12 weeks at 9.4 T.

ASSESSMENT

Liver proton T , T , T , APT, sodium T *, and TSC were calculated. Histological measures included Sirius Red, hematoxylin and eosin, liver hydroxyproline content, and serum alanine transaminase (ALT).

STATISTICAL TESTS

Welch's two-sided t-test was used to test for differences between control and CCl -treated groups for serum ALT, hydroxyproline, Sirius Red staining, T , T , T , APT, TSC, and sodium T *. Pearson's correlations between liver T , APT, TSC, or sodium T * with Sirius Red staining and hydroxyproline levels were calculated.

RESULTS

APT was significantly different (P < 0.05) between groups in the left liver lobe at 16 weeks (CCl : 8.0% ± 1.2%, controls: 6.2% ± 1.0%), as were average liver TSC at 12 weeks (CCl : 38 mM ± 5 mM, controls: 27 mM ± 2 mM), and average sodium liver T * at 12 weeks (CCl : 10 msec ± 1.0 msec, controls: 12 msec ± 1.9 msec). APT, TSC, and sodium T * correlated significantly (P < 0.05) with Sirius Red staining and hydroxyproline levels.

DATA CONCLUSION

Liver TSC and APT significantly correlated with histopathologic markers of fibrosis in this mouse model.

EVIDENCE LEVEL

1 TECHNICAL EFFICACY: Stage 3.

摘要

背景

需要一种能够定量纤维化估计的成像方法，以促进慢性肝病的诊断。酰胺质子转移（APT）和组织钠浓度（TSC）估计可以满足这一需求。

假设

APT 和 TSC 估计与慢性肝病小鼠模型中的纤维化相关。

研究类型

前瞻性。

体模/动物模型：雄性 C57Bl/6 小鼠每周两次给予 CCl 或载体（每组 8 只），共 16 周。

磁场强度/序列：在 7T 时，在 12 周和 16 周时采集肝脏 T（Look-Locker 梯度回波[GRE]序列）、T（多回波自旋回波序列）、T（带有 500Hz 自旋锁定脉冲的快速自旋回波序列）和 APT（带有失谐脉冲的 GRE 序列）数据。在 9.4T 时，在 12 周时采集肝脏钠数据（多回波 GRE 序列）。

评估

计算肝脏质子 T、T、T、APT、钠 T*和 TSC。组织学测量包括天狼星红、苏木精和伊红、肝羟脯氨酸含量和血清丙氨酸转氨酶（ALT）。

统计检验

使用 Welch 双侧 t 检验检验对照组和 CCl 处理组之间血清 ALT、羟脯氨酸、天狼星红染色、T、T、T、APT、TSC 和钠 T的差异。计算肝 T、APT、TSC 或钠 T与天狼星红染色和羟脯氨酸水平之间的 Pearson 相关关系。

结果

在 16 周时，左肝叶的 APT 在两组之间存在显著差异（P<0.05）（CCl：8.0%±1.2%，对照组：6.2%±1.0%），12 周时的平均肝 TSC 也存在显著差异（CCl：38mM±5mM，对照组：27mM±2mM），12 周时的平均钠肝 T也存在显著差异（CCl：10msec±1.0msec，对照组：12msec±1.9msec）。APT、TSC 和钠 T与天狼星红染色和羟脯氨酸水平显著相关（P<0.05）。