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定量磁化交换磁共振测量啮齿动物肝纤维化模型。

Quantitative Magnetization EXchange MRI Measurement of Liver Fibrosis Model in Rodents.

机构信息

Department of Biomedical Engineering, Faculty of Engineering, Tel Aviv University, Tel Aviv, Israel.

School of Chemistry, Faculty of Exact Sciences, Tel Aviv University, Tel Aviv, Israel.

出版信息

J Magn Reson Imaging. 2023 Jan;57(1):285-295. doi: 10.1002/jmri.28228. Epub 2022 May 6.

Abstract

BACKGROUND

Quantitative MRI can elucidate the complex microstructural changes in liver disease. The Magnetization EXchange (MEX) method estimates macromolecular fraction, such as collagen, and can potentially aid in this task.

HYPOTHESIS

MEX sequence, and its derived quantitative macromolecular fraction, should correlate with collagen deposition in rodents liver fibrosis model.

STUDY TYPE

Prospective.

ANIMAL MODEL

Sixteen adults Sprague-Dawley rats and 13 adults C57BL/6 strain mice given carbon tetrachloride (CCl ) twice weekly for 6 or 8 weeks.

FIELD STRENGTH/SEQUENCE: A 7 T scanner. MEX sequence (selective suppression and magnetization exchange), spin-echo and gradient-echo scans.

ASSESSMENT

Macromolecular fraction (F) and T were extracted for each voxel and for livers' regions of interest, additional to calculating the percentage of F > 0.1 pixels in F maps (high-F). Histology included staining with hematoxylin and eosin, picrosirius red and Masson trichrome, and inflammation scoring. Quantitative collagen percentage calculated using automatic spectral-segmentation of the staining.

STATISTICAL TESTS

Comparing CCl -treated groups and controls using Welch's t-test and paired t-test between different time points. Pearson's correlation used between ROI MEX parameters or high-F fraction, and quantitative histology. F or T , and inflammation scores were tested with one-sided t-test. P < 0.05 was deemed significant.

RESULTS

Rats: F values were significantly different after 6 weeks of treatment (0.10 ± 0.02) compared to controls (0.080 ± 0.003). After 8 weeks, F significantly increased (0.11 ± 0.02) in treated animals, while controls are not significant (0.0814 ± 0.0008, P = 0.079). F correlated with quantitative histology (R = 0.87), and T was significantly different between inflammation scores (1: 1332 ± 224 msec, 2: 2007 ± 464 msec). Mice: F was significantly higher (0.062 ± 0.006) in treatment group compared to controls (0.042 ± 0.006). F and high-F fraction correlated with quantitative histology (R = 0.88; R = 0.84). T was significantly different between inflammation scores (1:1366 ± 99 msec; 2:1648 ± 45 msec).

DATA CONCLUSION

MEX extracted parameters are sensitive to collagen deposition and inflammation and are correlated with histology results of mouse and rat liver fibrosis model.

EVIDENCE LEVEL

1 TECHNICAL EFFICACY: Stage 3.

摘要

背景

定量 MRI 可以阐明肝脏疾病中复杂的微观结构变化。磁化交换(MEX)方法可以估计大分子分数,如胶原蛋白,并且可以潜在地辅助该任务。

假设

MEX 序列及其衍生的定量大分子分数应与啮齿动物肝纤维化模型中的胶原蛋白沉积相关。

研究类型

前瞻性。

动物模型

给予十六只成年 Sprague-Dawley 大鼠和十三只成年 C57BL/6 品系小鼠每周两次四氯化碳(CCl )治疗 6 或 8 周。

磁场强度/序列:7T 扫描仪。MEX 序列(选择性抑制和磁化交换)、自旋回波和梯度回波扫描。

评估

每个体素以及肝脏感兴趣区域提取大分子分数(F)和 T,此外还计算 F 图中 F>0.1 像素的百分比(高 F)。组织学包括苏木精和伊红、苦味酸天狼星红和 Masson 三色染色以及炎症评分。使用染色的自动光谱分割计算定量胶原蛋白百分比。

统计检验

使用 Welch 检验比较 CCl 处理组和对照组,以及不同时间点之间的配对 t 检验。Pearson 相关用于 ROI MEX 参数或高 F 分数与定量组织学之间的相关性。F 或 T 和炎症评分使用单侧 t 检验进行检验。P<0.05 被认为具有统计学意义。

结果

大鼠:与对照组(0.080±0.003)相比,治疗 6 周后 F 值明显不同(0.10±0.02)。治疗 8 周后,F 值在处理组中显著增加(0.11±0.02),而对照组无显著变化(0.0814±0.0008,P=0.079)。F 与定量组织学相关(R=0.87),T 与炎症评分显著不同(1:1332±224msec;2:2007±464msec)。小鼠:与对照组(0.042±0.006)相比,治疗组的 F 值明显更高(0.062±0.006)。F 和高 F 分数与定量组织学相关(R=0.88;R=0.84)。T 与炎症评分显著不同(1:1366±99msec;2:1648±45msec)。

数据结论

MEX 提取的参数对胶原蛋白沉积和炎症敏感,并与小鼠和大鼠肝纤维化模型的组织学结果相关。

证据水平

1 技术功效:阶段 3。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3052/10084184/922bbdc91ce7/JMRI-57-285-g007.jpg

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