Kettunen Mikko I, Sierra Alejandra, Närväinen M Johanna, Valonen Piia K, Ylä-Herttuala Seppo, Kauppinen Risto A, Gröhn Olli H J
Department of Biotechnology and Molecular Medicine, A. I. Virtanen Institute for Molecular Sciences, University of Kuopio, Kuopio, Finland.
Radiology. 2007 Jun;243(3):796-803. doi: 10.1148/radiol.2433052077.
To prospectively assess the effectiveness of T1 relaxation in the rotating frame (T1 rho) dispersion and the low spin-lock radiofrequency field (B(1)) T1 rho magnetic resonance (MR) imaging relaxation time in noninvasive monitoring of gene therapy response in BT4C glioma in rats.
All animal studies were approved by the ethical committee of the National Laboratory Animal Center. Rats with BT4C gliomas (n=9) were treated with herpes simplex virus thymidine kinase gene therapy and were compared with untreated rats (n=5). Absolute T1 rho at a B(1) range of 2.0 x 10(-6) to 1.4 x 10(-4) T, T1, T2, and apparent diffusion constant were measured at 4.7 T during treatment. Statistical significance was tested by using repeated-measures analysis of variance.
A significant (P<.05) lengthening of T1 rho was observed beginning on the 4th day of treatment, and T1 rho values increased to be approximately 80% higher than values observed before treatment. These changes preceded T1 and T2 changes and resembled those of water diffusion. The T1 rho was associated with a treatment-induced decrease in cell density; this was the only measured MR imaging property that provided significant (P<.05) Pearson correlation with cell density in the tumor border. T1 rho relaxation dispersion, however, did not offer additional benefits over those offered in one B(1) experiment in the early phase of treatment.
T1 rho with low B(1) is an excellent MR imaging marker of early gene therapy response in gliomas. The low B(1) approach is not limited by specific absorption rate restrictions; this finding suggests that spin-lock methods could be applicable in clinical settings. (
前瞻性评估旋转坐标系下T1弛豫（T1ρ）弥散及低自旋锁定射频场（B1）T1ρ磁共振（MR）成像弛豫时间在大鼠BT4C胶质瘤基因治疗反应无创监测中的有效性。
所有动物研究均经国家实验动物中心伦理委员会批准。将患有BT4C胶质瘤的大鼠（n = 9）接受单纯疱疹病毒胸苷激酶基因治疗，并与未治疗的大鼠（n = 5）进行比较。在治疗期间于4.7T测量B1范围为2.0×10⁻⁶至1.4×10⁻⁴T时的绝对T1ρ、T1、T2及表观扩散常数。采用重复测量方差分析检验统计学显著性。
在治疗第4天开始观察到T1ρ显著（P <.05）延长，T1ρ值增加至比治疗前观察值高约80%。这些变化先于T1和T2变化，且与水扩散变化相似。T1ρ与治疗诱导的细胞密度降低相关；这是唯一在肿瘤边界与细胞密度具有显著（P <.05）Pearson相关性的测量MR成像特性。然而，在治疗早期，T1ρ弛豫弥散相比一个B1实验未提供额外优势。
低B1的T1ρ是胶质瘤早期基因治疗反应的优秀MR成像标志物。低B1方法不受比吸收率限制；这一发现表明自旋锁定方法可能适用于临床环境。
