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Virtual measurements of paracellular permeability and chronic inflammation via color coded pixel-wise T1 mapping.
American Journal of Physiology-Renal Physiology ( IF 3.7 ) Pub Date : 2020-07-27 , DOI: 10.1152/ajprenal.00025.2020
Nishant Singh 1 , Irina Zabbarova 2 , Youko Ikeda 2 , Jodi Maranchie 1 , Christopher Chermansky 1 , Lesley Foley 3 , T Kevin Hitchens 3 , Naoki Yoshimura 1 , Anthony Kanai 2 , Jonathan Kaufman 4 , Pradeep Tyagi 1
Affiliation  

To assess whether quantitative T1 relaxometry can measure permeability, assess chronic inflammation and mural thickening of mouse bladder wall. Adult female C57BL6 mice unexposed to radiation (controls) or 40 weeks post-irradiation10Gy were scanned at 9.4T before and after instillation (0.1mL) of aqueous, novel contrast mixture containing 4mM Gadobutrol and 5mM Ferumoxytol. Rapid Acquisition with Refocused Echo (RARE) sequence with variable Repetition Times (TR) generated pixel wise map of T1 relaxation times for segmented bladder wall layers from voxel-wise, nonlinear least square data fitting of TR dependent signal intensity acquired with TR array of 0.4-10s followed by the histology of harvested bladder. Significant differences between pre-contrast and post contrast T1 (DT1) noted in urothelium and lamina propria of both groups but only in detrusor of irradiated group (p<0.001; Two-way ANOVA). Nearly two-fold higher Gadobutrol permeability (550 ± 73μM vs 294 ± 160μM; p<0.01) derived as per 1/DT1 = r1. [C] in urothelium of irradiated group (0.75± 0.04mm vs 0.44± 0.08mm; p<0.001). Inflammation and bladder wall thickening predicted by MRI was subsequently confirmed by histology and altered expression of CD45 and zonula occludens-1 (ZO-1) relative to controls. Novel contrast mixture enhanced MRI relies on the retention of large molecular weight Ferumoxytol in lumen for negative contrast, while permeation of the non-ionic, small molecular weight Gadobutrol through ZO-1 generates positive contrast in bladder wall for virtual measurement of paracellular permeability and assessment of chronic inflammation in thin and distensible bladder wall, which is also defined by its variable shape and location within pelvis.

中文翻译:

通过颜色编码的像素级 T1 映射虚拟测量细胞旁通透性和慢性炎症。

为了评估定量 T 1弛豫测量是否可以测量渗透性,评估慢性炎症和小鼠膀胱壁的壁增厚。未暴露于辐射(对照)或辐射后 40 周 10Gy 的成年雌性 C57BL6 小鼠在滴注(0.1mL)含有 4mM Gadobutrol 和 5mM Ferumoxytol 的水性新型对比混合物之前和之后以 9.4T 扫描。具有可变重复时间 (TR) 的重聚焦回波 (RARE) 序列的快速采集为分段的膀胱壁层生成 T 1弛豫时间的像素方式图,该图来自用 TR 阵列采集的 TR 相关信号强度的体素方式、非线性最小二乘数据拟合0.4-10 秒,然后是收获膀胱的组织学。对比前和对比后 T 1之间的显着差异(DT 1 ) 在两组的尿路上皮和固有层中发现,但仅在照射组的逼尿肌中发现 (p<0.001;双向 ANOVA)。根据 1/DT 1得出的钆布醇渗透率几乎高出两倍(550 ± 73μM 对比 294 ± 160μM;p<0.01)= r1。[C] 照射组尿路上皮(0.75±0.04mm vs 0.44±0.08mm;p<0.001)。MRI 预测的炎症和膀胱壁增厚随后通过组织学和 CD45 和 zonula occludens-1 (ZO-1) 相对于对照组的表达改变得到证实。新型造影剂混合物增强 MRI 依赖于将大分子量 Ferumoxytol 保留在腔内以获得负造影,而非离子、小分子量钆布醇通过 ZO-1 的渗透在膀胱壁中产生正造影,用于虚拟测量细胞旁渗透性和评估膀胱壁薄而可扩张的慢性炎症,这也由其在骨盆内的可变形状和位置定义。
更新日期:2020-08-20
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