Hedlund L W, Maronpot R R, Johnson G A, Cofer G P, Mills G I, Wheeler C T
Department of Radiology, Duke University Medical Center, Durham, North Carolina 27710.
Fundam Appl Toxicol. 1991 May;16(4):787-97. doi: 10.1016/0272-0590(91)90164-y.
The alkylhalide 2-bromoethylamine hydrobromide (BEA) produces renal injury in rats that mimics analgesic-related renal injury in humans. Our purpose was to examine this injury, in vivo in rats, with magnetic resonance (MR) microscopy and correlate MR findings with findings from light microscopy of hematoxylin-eosin-stained sections. Rats (n = 48) were injected intravenously with BEA (150 mg/kg) or saline and imaged with MR 6, 48, and 336 hr later. The spin-spin relaxation time, T2, was measured from the cortex to the papilla. In other rats, we measured regional water content of the kidney. Renal injury was present 48 and 336 hr after BEA dosing based on increased renal organ weights, decreased urine specific gravity, and significant renal lesions (H & E). T2 was elevated in the inner stripe of the outer medulla in injured kidneys at 48 hr. The differences in T2 between cortex and outer medulla were also elevated 48 hr after BEA. In the inner medulla, there were no changes in T2 after BEA treatment. However, in all groups there were significant regional differences in T2. The value of T2 increased from outer to inner medulla and this gradient was directly correlated with water content. Thus, MR microscopy detected damage in the outer medulla after BEA injury but not the damage in the inner medulla. T2 appeared to reflect the water content in the different regions of the medulla. The noninvasive in vivo capability of MR microscopy, with its high sensitivity to tissue water, allows the toxicologist to monitor the progression and regression of toxic insult in the same animal. At present the technology is complicated. The precise and accurate measure of MR-sensitive parameters in live animals at microscopic resolution is difficult. However, as the technology matures, there will be significant improvements providing the toxicologist a unique in vivo tool.
卤代烷2-溴乙胺氢溴酸盐(BEA)可在大鼠中引发肾损伤,这种损伤类似于人类与镇痛药相关的肾损伤。我们的目的是利用磁共振(MR)显微镜在大鼠体内研究这种损伤,并将MR结果与苏木精-伊红染色切片的光学显微镜结果相关联。将大鼠(n = 48)静脉注射BEA(150 mg/kg)或生理盐水,并在6、48和336小时后进行MR成像。测量从皮质到乳头的自旋-自旋弛豫时间T2。在其他大鼠中,我们测量了肾脏的局部含水量。基于肾脏器官重量增加、尿比重降低和明显的肾脏病变(苏木精-伊红染色),在BEA给药后48小时和336小时出现肾损伤。在48小时时,受损肾脏外髓质内带的T2升高。BEA给药48小时后,皮质和外髓质之间的T2差异也升高。在内髓质中,BEA处理后T2没有变化。然而,在所有组中,T2存在显著的局部差异。T2值从外髓质到内髓质增加,这种梯度与含水量直接相关。因此,MR显微镜检测到BEA损伤后外髓质的损伤,但未检测到内髓质的损伤。T2似乎反映了髓质不同区域的含水量。MR显微镜的非侵入性体内检测能力及其对组织水的高敏感性,使毒理学家能够在同一动物中监测毒性损伤的进展和消退。目前该技术很复杂。在微观分辨率下对活体动物的MR敏感参数进行精确准确的测量很困难。然而,随着技术的成熟,将会有显著的改进,为毒理学家提供一种独特的体内工具。