Valonen Piia K, Lehtimäki Kimmo K, Väisänen Tuula H, Kettunen Mikko I, Gröhn Olli H J, Ylä-Herttuala Seppo, Kauppinen Risto A
Department of Biomedical NMR and National Bio-NMR Facility, A.I. Virtanen Institute for Molecular Sciences, University of Kuopio, Kuopio, Finland.
J Magn Reson Imaging. 2004 Apr;19(4):389-96. doi: 10.1002/jmri.20026.
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.
The trace of the diffusion tensor (Dav = 1/3TraceD), T2, 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 (tD) at 4.7 T. Cell count and apoptotic cells were quantified by histological means.
Decline in cell count was strongly associated with increase in both Dav and T2. Spin density ratio between tumor and contralateral parietal cortex increased with a very similar time course as Dav and T2, 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 (D1), as acquired with tD > or = 47 msec, increased with kinetics similar to those of Dav (tD = 4.8 msec). The fractional size of D1 increased by 10% to 15% throughout the entire tD range. Apparent water residence time of the slow diffusion component, D2, shortened from a value of 38.3 +/- 1.7 msec on day 0 to 33.4 +/- 0.5 msec by day 8.
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.
研究在体内更昔洛韦（GCV）-胸苷激酶基因治疗诱导程序性细胞死亡（PCD）过程中，大鼠脑BT4C胶质瘤的扩散磁共振成像（MRI）对比特征。
在4.7T磁场下，使用大范围变化的b值和扩散时间（tD），通过MRI测定扩散张量的迹（Dav = 1/3TraceD）、T2和自旋密度，并通过扩散核磁共振（NMR）波谱法测定水的表观扩散系数（ADC）。通过组织学方法对细胞计数和凋亡细胞进行定量分析。
细胞计数的下降与Dav和T2的增加密切相关。肿瘤与对侧顶叶皮质之间的自旋密度比随时间变化的过程与Dav和T2非常相似，表明在正在被清除的肿瘤中有净水分增加。扩散波谱显示，在14 - 192毫秒的所有tD值下，信号衰减均为非单指数形式。在PCD过程中，当tD≥47毫秒时获得的具有快速扩散系数（D1）的成分的ADC增加，其动力学与Dav（tD = 4.8毫秒）相似。在整个tD范围内，D1的分数大小增加了10%至15%。慢扩散成分D2的表观水停留时间从第0天的38.3±1.7毫秒缩短至第8天的33.4±0.5毫秒。
目前的结果表明，由于PCD，在清除胶质瘤过程中，细胞密度降低和水分含量增加导致水微环境改变，这与水扩散系数增加相关。
