Liimatainen Timo, Hakumäki Juhana M, Kauppinen Risto A, Ala-Korpela Mika
University of Minnesota, Minneapolis, MN 55455, USA.
NMR Biomed. 2009 Apr;22(3):272-9. doi: 10.1002/nbm.1320.
The measurement of water diffusion by diffusion-weighted MRI (DWI) in vivo offers a non-invasive method for assessing tissue responses to anti-cancer therapies. The pathway of cell death after anti-cancer treatment is often apoptosis, which leads to accumulation of mobile lipids detectable by (1)H MRS in vivo. However, it is not known how these discrete MR markers of cell death relate to each other. In a rodent tumour model [i.e. ganciclovir-treated herpes simplex thymidine kinase (HSV-tk) gene-transfected BT4C gliomas], we studied the interrelationships between water diffusion (Trace{D}) and mobile lipids during apoptosis. Water diffusion and water-referenced concentrations of mobile lipids showed clearly increasing and interconnected trends during treatment. Of the accumulating (1)H MRS-visible lipids, the fatty acid --CH==CH-- groups and cholesterol compounds showed the strongest associations with water diffusion (r(2) = 0.30; P < 0.05 and r(2) = 0.48; P < 0.01, respectively). These results indicate that the tumour histopathology and apoptotic processes during tumour shrinkage can be interrelated in vivo by DWI of tissue water and (1)H MRS of mobile lipids, respectively. However, there is considerable individual variation in the associations, particularly at the end of the treatment period, and in the relative compositions of the accumulating NMR-visible lipids. The findings suggest that the assessment of individual treatment response in vivo may benefit from combining DWI and (1)H MRS. Absolute and relative changes in mobile lipids may indicate initiation of tumour shrinkage even when changes in tissue water diffusion are still small. Conversely, greatly increased water diffusion probably indicates that substantial cell decomposition has taken place in the tumour tissue when the (1)H MRS resonances of mobile lipids alone can no longer give a reliable estimate of tissue conditions.
通过体内扩散加权磁共振成像（DWI）测量水扩散，为评估组织对抗癌治疗的反应提供了一种非侵入性方法。抗癌治疗后细胞死亡的途径通常是凋亡，这会导致体内可通过氢质子磁共振波谱（1H MRS）检测到的流动脂质积累。然而，尚不清楚这些细胞死亡的离散磁共振标记物之间是如何相互关联的。在一个啮齿动物肿瘤模型中（即经更昔洛韦治疗的单纯疱疹病毒胸苷激酶（HSV-tk）基因转染的BT4C胶质瘤）研究了凋亡过程中水扩散（Trace{D}）与流动脂质之间的相互关系。在治疗过程中，水扩散和以水为参照的流动脂质浓度呈现出明显上升且相互关联的趋势。在积累的可通过1H MRS观察到的脂质中，脂肪酸的-CH==CH-基团和胆固醇化合物与水扩散的相关性最强（r2分别为0.30；P<0.05和r2为0.48；P<0.01）。这些结果表明，肿瘤缩小过程中的肿瘤组织病理学和凋亡过程，可分别通过组织水的DWI和流动脂质的1H MRS在体内相互关联。然而，这些关联存在相当大的个体差异，尤其是在治疗末期，以及在积累的可通过核磁共振观察到的脂质的相对组成方面。这些发现表明，将DWI和1H MRS结合起来可能有助于评估体内个体治疗反应。流动脂质的绝对和相对变化可能表明肿瘤缩小的开始，即使组织水扩散的变化仍然很小。相反，当单独的流动脂质的1H MRS共振不再能可靠地估计组织状况时，水扩散的大幅增加可能表明肿瘤组织中已经发生了大量细胞分解。
