Jost Sarah C, Hope Andrew, Kiehl Erich, Perry Arie, Travers Sarah, Garbow Joel R
Department of Neurosurgery, Washington University School of Medicine, St. Louis, MO 63110, USA.
Int J Radiat Oncol Biol Phys. 2009 Oct 1;75(2):527-33. doi: 10.1016/j.ijrobp.2009.06.007.
To develop a murine model of radiation necrosis using fractionated, subtotal cranial irradiation; and to investigate the imaging signature of radiation-induced tissue damage using advanced magnetic resonance imaging techniques.
Twenty-four mice each received 60 Gy of hemispheric (left) irradiation in 10 equal fractions. Magnetic resonance images at 4.7 T were subsequently collected using T1-, T2-, and diffusion sequences at selected time points after irradiation. After imaging, animals were killed and their brains fixed for correlative histologic analysis.
Contrast-enhanced T1- and T2-weighted magnetic resonance images at months 2, 3, and 4 showed changes consistent with progressive radiation necrosis. Quantitatively, mean diffusivity was significantly higher (mean = 0.86, 1.13, and 1.24 microm(2)/ms at 2, 3, and 4 months, respectively) in radiated brain, compared with contralateral untreated brain tissue (mean = 0.78, 0.82, and 0.83 microm(2)/ms) (p < 0.0001). Histology reflected changes typically seen in radiation necrosis.
This murine model of radiation necrosis will facilitate investigation of imaging biomarkers that distinguish between radiation necrosis and tumor recurrence. In addition, this preclinical study supports clinical data suggesting that diffusion-weighted imaging may be helpful in answering this diagnostic question in clinical settings.
利用分次全脑低剂量照射建立辐射性坏死的小鼠模型;并使用先进的磁共振成像技术研究辐射诱导组织损伤的成像特征。
24只小鼠每只接受10次均等剂量的60 Gy半球(左侧)照射。随后在照射后的选定时间点使用T1、T2和扩散序列在4.7 T下采集磁共振图像。成像后,处死动物并固定其大脑以进行相关组织学分析。
在第2、3和4个月时,对比增强T1加权和T2加权磁共振图像显示出与进行性辐射性坏死一致的变化。定量分析显示,与对侧未处理的脑组织(平均值分别为0.78、0.82和0.83μm²/ms)相比,辐射脑的平均扩散率显著更高(第2、3和4个月时分别为0.86、1.13和1.24μm²/ms)(p < 0.0001)。组织学反映了辐射性坏死中常见的变化。
这种辐射性坏死的小鼠模型将有助于研究区分辐射性坏死和肿瘤复发的成像生物标志物。此外,这项临床前研究支持临床数据,表明扩散加权成像可能有助于在临床环境中回答这个诊断问题。