Schmidbauer Martina, Rong Song, Gutberlet Marcel, Chen Rongjun, Bräsen Jan Hinrich, Hartung Dagmar, Meier Martin, Wacker Frank, Haller Hermann, Gueler Faikah, Greite Robert, Derlin Katja
Institute for Diagnostic and Interventional Radiology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany.
Clinic for Nephrology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany.
J Clin Med. 2021 Sep 23;10(19):4318. doi: 10.3390/jcm10194318.
We hypothesized that multiparametric MRI is able to non-invasively assess, characterize and monitor renal allograft pathology in a translational mouse model of chronic allograft rejection. Chronic rejection was induced by allogenic kidney transplantation (ktx) of BALB/c-kidneys into C57BL/6-mice ( = 23). Animals after isogenic ktx ( = 18) and non-transplanted healthy animals ( = 22) served as controls. MRI sequences (7T) were acquired 3 and 6 weeks after ktx and quantitative T1, T2 and apparent diffusion coefficient (ADC) maps were calculated. In addition, in a subset of animals, histological changes after ktx were evaluated. Chronic rejection was associated with a significant prolongation of T1 time compared to isogenic ktx 3 (1965 ± 53 vs. 1457 ± 52 ms, < 0.001) and 6 weeks after surgery (1899 ± 79 vs. 1393 ± 51 ms, < 0.001). While mean T2 times and ADC were not significantly different between allogenic and isogenic kidney grafts, histogram-based analysis of ADC revealed significantly increased tissue heterogeneity in allografts at both time points (standard derivation/entropy/interquartile range, < 0.05). Correspondingly, histological analysis showed severe inflammation, graft fibrosis and tissue heterogeneity in allogenic but not in isogenic kidney grafts. In conclusion, renal diffusion weighted imaging and mapping of T2 and T1 relaxation times enable detection of chronic renal allograft rejection in mice. The combined quantitative assessment of mean values and histograms provides non-invasive information of chronic changes in renal grafts and allows longitudinal monitoring.
我们假设,在慢性移植肾排斥反应的转化小鼠模型中,多参数磁共振成像(MRI)能够对移植肾病理进行无创评估、特征描述和监测。通过将BALB/c小鼠的肾脏同种异体移植到C57BL/6小鼠体内(n = 23)诱导慢性排斥反应。同基因肾移植(n = 18)的动物和未移植的健康动物(n = 22)作为对照。在肾移植后3周和6周采集MRI序列(7T),并计算定量T1、T2和表观扩散系数(ADC)图。此外,在一部分动物中,评估肾移植后的组织学变化。与同基因肾移植相比,慢性排斥反应与T1时间显著延长有关,术后3周(1965±53 vs. 1457±52 ms,P < 0.001)和6周(1899±79 vs. 1393±51 ms,P < 0.001)均如此。虽然同种异体和同基因肾移植之间的平均T2时间和ADC无显著差异,但基于直方图的ADC分析显示,在两个时间点同种异体移植中的组织异质性均显著增加(标准差/熵/四分位数间距,P < 0.05)。相应地,组织学分析显示同种异体肾移植中有严重炎症、移植纤维化和组织异质性,而同基因肾移植中则没有。总之,肾脏扩散加权成像以及T2和T1弛豫时间成像能够检测小鼠慢性移植肾排斥反应。平均值和直方图的联合定量评估提供了移植肾慢性变化的无创信息,并允许进行纵向监测。