Sierra A, Michaeli S, Niskanen J-P, Valonen P K, Gröhn H I, Ylä-Herttuala S, Garwood M, Gröhn O H
Biomedical NMR Research Group, Department of Neurobiology and Biomedical Imaging Unit, A. I. Virtanen Institute for Molecular Sciences, University of Kuopio, and Kuopio University Hospital, Kuopio, Finland.
Magn Reson Med. 2008 Jun;59(6):1311-9. doi: 10.1002/mrm.21600.
Longitudinal and transverse relaxations in the rotating frame, with characteristic time constants T1rho and T2rho, respectively, have potential to provide unique MRI contrast in vivo. On-resonance spin-lock T1rho with different spin-lock field strengths and adiabatic T2rho with different radiofrequency-modulation functions were measured in BT4C gliomas treated with Herpes Simplex Virus thymidine kinase (HVS-tk) gene therapy causing apoptotic cell death. These NMR tools were able to discriminate different treatment responses in tumor tissue from day 4 onward. An equilibrium two-site exchange model was used to calculate intrinsic parameters describing changes in water dynamics. Observed changes included increased correlation time of water associated with macromolecules and a decreased fractional population of this pool. These results are consistent with destructive intracellular processes associated with cell death and the increase of extracellular space during the treatment. Furthermore, association between longer exchange correlation time and decreased pH during apoptosis is discussed. In this study, we demonstrated that T1rho and T2rho MR imaging are useful tools to quantify early changes in water dynamics reflecting treatment response during gene therapy.
旋转坐标系中的纵向和横向弛豫，其特征时间常数分别为T1rho和T2rho，有可能在体内提供独特的磁共振成像（MRI）对比度。在接受单纯疱疹病毒胸苷激酶（HVS-tk）基因治疗导致凋亡性细胞死亡的BT4C胶质瘤中，测量了不同自旋锁定场强下的共振自旋锁定T1rho和不同射频调制函数下的绝热T2rho。从第4天起，这些核磁共振工具能够区分肿瘤组织中的不同治疗反应。使用平衡两点交换模型来计算描述水动力学变化的内在参数。观察到的变化包括与大分子相关的水的相关时间增加以及该池的分数种群减少。这些结果与细胞死亡相关的破坏性细胞内过程以及治疗期间细胞外空间的增加一致。此外，还讨论了凋亡过程中较长的交换相关时间与pH值降低之间的关联。在本研究中，我们证明T1rho和T2rho磁共振成像（MRI）是量化反映基因治疗期间治疗反应的水动力学早期变化的有用工具。
