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在小鼠肺移植模型中,磁化传递作为慢性气道纤维化的生物标志物

Magnetisation transfer as a biomarker for chronic airway fibrosis in a mouse lung transplantation model.

作者信息

Kenkel David, Yamada Yoshito, Weiger Markus, Wurnig Moritz C, Jungraithmayr Wolfgang, Boss Andreas

机构信息

1Department of Diagnostic and Interventional Radiology, University Hospital Zurich, Ramistrasse 100, 8091 Zurich, Switzerland.

2Division of Thoracic Surgery and Department, University Hospital Zurich, Zurich, Switzerland.

出版信息

Eur Radiol Exp. 2018;2(1):3. doi: 10.1186/s41747-017-0032-3. Epub 2018 Feb 12.

DOI:10.1186/s41747-017-0032-3
PMID:29708209
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5909363/
Abstract

BACKGROUND

Chronic airway fibrosis (CAF) is the most prevalent complication in human lung transplant recipients. The aim of the study is to evaluate magnetisation transfer (MT) as a biomarker of developing CAF of lung transplants in a mouse model.

METHODS

Lung transplantation was performed in 48 mice, applying major or minor histocompatibility mismatches between strains for the induction of CAF. MT measurements were performed in vivo with systematic variation of off-resonance frequencies and flip angle of the MT prepulse. MT ratios (MTRs) were compared for lungs showing CAF and without CAF.

RESULTS

Seven out of 24 animals (29%) showed a pattern of CAF at histology. All mice developing CAF also showed signs of acute rejection, whereas none of the lungs showed signs of other post-transplant complications. After lung transplantation, pulmonary infiltration was a frequent finding (14 out of 24) exhibiting a higher MTR (24.8% ± 4.5%) compared to well-ventilated lungs (12.3% ± 6.9%,  = 0.001) at 8000 Hz off-resonance frequency, 3000° flip angle. In infiltrated lung tissue exhibiting CAF, lower MTR values (21.8% ± 5.7%) were found compared to infiltrated lungs showing signs of acute rejection alone (26.5% ± 2.9%,  = 0.028), at 8000 Hz, 3000° flip angle. The highest MTR values were observed at 3000° flip angle, using a 1000 Hz off-resonance frequency.

CONCLUSION

MTR might serve as a tool for the detection of CAF in infiltrated lung tissue.

摘要

背景

慢性气道纤维化(CAF)是人类肺移植受者中最常见的并发症。本研究的目的是在小鼠模型中评估磁化传递(MT)作为肺移植中CAF发生的生物标志物。

方法

对48只小鼠进行肺移植,通过品系间主要或次要组织相容性不匹配来诱导CAF。采用MT预脉冲的失谐频率和翻转角的系统变化在体内进行MT测量。比较出现CAF和未出现CAF的肺的MT比率(MTR)。

结果

24只动物中有7只(29%)在组织学上表现出CAF模式。所有发生CAF的小鼠也表现出急性排斥反应的迹象,而没有肺显示出其他移植后并发症的迹象。肺移植后,肺部浸润是常见表现(24只中有14只),在失谐频率8000Hz、翻转角3000°时,其MTR(24.8%±4.5%)高于通气良好的肺(12.3%±6.9%,P=0.001)。在表现出CAF的浸润性肺组织中,在失谐频率8000Hz、翻转角3000°时,与仅表现出急性排斥反应迹象的浸润性肺(26.5%±2.9%,P=0.028)相比,MTR值较低(21.8%±5.7%)。使用1000Hz失谐频率时,在3000°翻转角观察到最高的MTR值。

结论

MTR可能作为检测浸润性肺组织中CAF的一种工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cae3/6091615/788d88a4a992/41747_2017_32_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cae3/6091615/1580feb128f3/41747_2017_32_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cae3/6091615/63afdb4032c2/41747_2017_32_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cae3/6091615/4a7ac499a6c6/41747_2017_32_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cae3/6091615/568d322ef2ee/41747_2017_32_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cae3/6091615/5482a2f9f5a0/41747_2017_32_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cae3/6091615/788d88a4a992/41747_2017_32_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cae3/6091615/1580feb128f3/41747_2017_32_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cae3/6091615/63afdb4032c2/41747_2017_32_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cae3/6091615/4a7ac499a6c6/41747_2017_32_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cae3/6091615/568d322ef2ee/41747_2017_32_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cae3/6091615/5482a2f9f5a0/41747_2017_32_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cae3/6091615/788d88a4a992/41747_2017_32_Fig6_HTML.jpg

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本文引用的文献

1
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J Magn Reson Imaging. 2016 Nov;44(5):1091-1098. doi: 10.1002/jmri.25266. Epub 2016 May 17.
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A radial sampling strategy for uniform k-space coverage with retrospective respiratory gating in 3D ultrashort-echo-time lung imaging.在3D超短回波时间肺部成像中采用径向采样策略并结合回顾性呼吸门控实现均匀的k空间覆盖
NMR Biomed. 2016 May;29(5):576-87. doi: 10.1002/nbm.3494. Epub 2016 Feb 18.
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In vivo magnetization transfer imaging of the lung using a zero echo time sequence at 4.7 Tesla in mice: Initial experience.
在4.7特斯拉场强下使用零回波时间序列对小鼠肺部进行的体内磁共振磁化传递成像:初步经验。
Magn Reson Med. 2016 Jul;76(1):156-62. doi: 10.1002/mrm.25882. Epub 2015 Aug 13.
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PLoS One. 2014 Jul 23;9(7):e101638. doi: 10.1371/journal.pone.0101638. eCollection 2014.
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Assessing lung transplantation ischemia-reperfusion injury by microcomputed tomography and ultrashort echo-time magnetic resonance imaging in a mouse model.利用微计算机断层扫描和超短回波时间磁共振成像评估小鼠肺移植缺血再灌注损伤。
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