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Evaluation of Renal Hypoxia in Diabetic Mice by BOLD MRI

机译:BOLD MRI对糖尿病小鼠肾脏缺氧的评估

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Objective: Renal hypoxia has been proposed to be a pathophysiologic feature of diabetic kidney disease but it has been difficult to demonstrate in vivo, particularly in mouse models of diabetes. The objective of this work was to examine the sensitivity of blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) to assess renal oxygenation in vivo in a mouse model of diabetic kidney disease, the db/db mice. Research Design and Methods: Kidney BOLD MRI studies were performed on a 3.0 T scanner using multiple gradient echo sequence with a custom-designed surface coil to acquire T_2*-weighted images. Studies were performed in 10-week-old db/db mice (n = 7) and db/m controls (n = 6). Results: R2~* is a measure of the tissue deoxyhemoglobin concentration and higher values of R2~* are associated with hypoxia. The db/db mice had higher medullary (43.1 +- 5.1 s~-1 vs. 32.3 +- 3.7 s~-1 P = 0.001) and cortical R2~* (31.7 +- 3.1 s~-1 vs. 27.1 +- 4.1 s~-1 P = 0.04) values. Using pimonidazole staining as a marker of kidney hypoxia, in kidney sections from 10-week-old db/db mice neither cortex nor medulla had significant differences as compared with 10-week-old db/m mice (cortex: db/db 2.14 +- 0.05 vs. db/m 2.02 +- 0.28, medulla: db/db 2.81 +- 0.08 vs. db/m 2.6 +- 0.08). The db/db mice demonstrated further increased cortical and medullary hypoxia when scanned again at 15 weeks of age.Conclusions: The report shows that renal BOLD MRI is a sensitive method for the in vivo evaluation of renal hypoxia in a mouse model of diabetic kidney disease where progressive renal hypoxia can be documented over time. BOLD MRI may be useful to monitor therapeutic interventions that may improve tissue hypoxia in the diabetic kidney.
机译:目的:肾脏缺氧被认为是糖尿病肾病的病理生理特征,但很难在体内证明,特别是在糖尿病小鼠模型中。这项工作的目的是检查血氧水平依赖性(BOLD)磁共振成像(MRI)的敏感性,以评估糖尿病性肾脏疾病小鼠模型db / db小鼠体内的肾脏氧合作用。研究设计和方法:肾脏BOLD MRI研究是在3.0 T扫描仪上进行的,其中使用具有定制设计的表面线圈的多个梯度回波序列来获取T_2 *加权图像。在10周大的db / db小鼠(n = 7)和db / m对照(n = 6)中进行研究。结果:R2〜*是组织脱氧血红蛋白浓度的量度,R2〜*的较高值与缺氧有关。 db / db小鼠的髓质较高(43.1 +-5.1 s〜-1对32.3 +-3.7 s〜-1 P = 0.001)和皮质R2〜*(31.7 +-3.1 s〜-1对27.1 +- 4.1 s〜-1 P = 0.04)值。使用pimonidazole染色作为肾脏缺氧的标志物,与10周龄db / m小鼠相比,在10周龄db / db小鼠的肾脏切片中皮质和髓质均无显着差异(皮质:db / db 2.14 + -0.05 vs. db / m 2.02 +-0.28,延髓:db / db 2.81 +-0.08 vs. db / m 2.6 +-0.08)。 db / db小鼠在15周龄再次扫描时表现出进一步的皮质和髓质缺氧增加。结论:该报告显示,肾脏BOLD MRI是一种在糖尿病性肾病小鼠模型中体内评估肾脏缺氧的灵敏方法。随着时间的推移,可以记录到进行性肾脏缺氧。 BOLD MRI可能对监测可改善糖尿病肾组织缺氧的治疗干预很有用。

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