Water diffusion in a rat glioma during ganciclovir-thymidine kinase gene therapy-induced programmed cell death in vivo:: Correlation with cell density
Water diffusion in a rat glioma during ganciclovir-thymidine kinase gene therapy-induced programmed cell death in vivo:: Correlation with cell density
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DOI：
10.1002/jmri.20026
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发表时间：
2004-04-01
影响因子：
4.4
通讯作者：
Kauppinen, RA
中科院分区：
文献类型：
--
作者：
Valonen, PK;Lehtimäki, KK;Kauppinen, RA
目的：研究更昔洛韦(GCV)-胸苷激酶基因治疗诱导的程序性细胞死亡(PCD)过程中大鼠脑BT4C胶质瘤的磁共振弥散成像(MRI)增强特征。结果：细胞计数的下降与水的表观扩散系数(ADC)密切相关。肿瘤与对侧顶叶皮质之间的自旋密度比增加的时间进程与D-av和T-2非常相似，表明肿瘤的净水分增加到了根除肿瘤中。扩散谱显示信号在Td值为14-192毫秒的范围内呈非单指数衰减。在PCD过程中，当t(D)大于或等于47毫秒时，产生快速扩散系数(D-1)的分量的ADC以类似于D-av(t(D)=4.8毫秒)的动力学增加。在整个t(D)范围内，D-1的分数尺寸增加了10%到15%。慢扩散组分的表观水滞留时间D-2从0天的38.3±-1.7毫秒缩短到8天的33.4+/-0.5毫秒。结论：细胞密度降低和水含量增加，导致水微环境改变，与PCD所致的水扩散系数增加有关。
Purpose: To study the characteristics of diffusion magnetic resonance imaging (MRI) contrast in a rat brain BT4C glioma during progression of ganciclovir (GCV)-thymidine kinase gene therapy-induced programmed cell death (PCD) in vivo.Materials and Methods: The trace of the diffusion tensor (D-av = 1/3TraceD), T-2, and spin density were determined by MRI and the apparent diffusion coefficient (ADC) of water by diffusion nuclear MR (NMR) spectroscopy using largely varying b values and diffusion times (t(D)) at 4.7 T. Cell count and apoptotic cells were quantified by histological means.Results: Decline in cell count was strongly associated with increase in both D, and T-2. Spin density ratio between tumor and contralateral parietal cortex increased with a very similar time course as D-av and T-2, indicating net water gain into the eradicating tumor. Diffusion spectroscopy showed a nonmonoexponential signal decay at all tD values ranging from 14-192 msec. During PCD, the ADC of the component yielding fast diffusion coefficient (D-1), as acquired with t(D) greater than or equal to 47 msec, increased with kinetics similar to those of D-av (t(D) = 4.8 msec). The fractional size of D-1 increased by 10% to 15% throughout the entire t(D) range. Apparent water residence time of the slow diffusion component, D-2, shortened from a value of 38.3 +/- 1.7 msec on day 0 to 33.4 +/- 0.5 msec by day 8.Conclusion: The present results show that reduced cell density and increased water content, leading to altered water microenvironment, are associated with increased water diffusion coefficient in eradicating gliomas as a result of PCD.