Le Trung N T, Lim Heeseung, Hamilton Amanda M, Parkins Katie M, Chen Yuanxin, Scholl Timothy J, Ronald John A
Department of Medical Biophysics, Western University, London, ON, Canada.
Robarts Research Institute, Western University, London, ON, Canada.
Tomography. 2018 Jun;4(2):55-65. doi: 10.18383/j.tom.2018.00012.
Glioblastoma multiforme (GBM) is the most common primary brain tumor, with most patients dying within 15-18 months of diagnosis despite aggressive therapy. Preclinical GBM models are valuable for exploring GBM progression and for evaluating new therapeutics or imaging approaches. The rat C6 glioma model shares similarities with human GBM, and application of noninvasive imaging enables better study of disease progression. Here, multiparametric magnetic resonance imaging (mpMRI) and bioluminescence imaging (BLI) were applied to characterize longitudinal development of orthotopic luciferase-expressing C6 tumors. Across all rats ( 11), a large variability was seen for BLI signal, a relative measure of C6 cell viability, but in most individuals, BLI signal peaked at day 11 and decreased thereafter. T2 and contrast-enhanced T1 tumor volumes significantly increased over time ( < .05), and volume measures did not correlate with BLI signal. After day 11, tumor regions of noncontrast enhancement appeared in postcontrast T1-weighted magnetic resonance imaging, and had significantly higher apparent diffusion coefficient values compared with contrast-enhanced regions ( < .05). This suggests formation of ill-perfused, necrotic regions beyond day 11, which were apparent at end-point-matched tissue sections. Our study represents the first combined use of BLI and mpMRI to characterize the progression of disease in the orthotopic C6 rat model, and it highlights the variability in tumor growth, the complementary information from BLI and mpMRI, and the value of multimodality imaging to better characterize tumor development. Future application of these imaging tools will be useful for evaluation of treatment response, and should be pertinent for other preclinical models.
多形性胶质母细胞瘤（GBM）是最常见的原发性脑肿瘤，尽管进行了积极治疗，大多数患者在诊断后的15 - 18个月内死亡。临床前GBM模型对于探索GBM进展以及评估新的治疗方法或成像方法具有重要价值。大鼠C6胶质瘤模型与人类GBM有相似之处，非侵入性成像的应用能够更好地研究疾病进展。在此，应用多参数磁共振成像（mpMRI）和生物发光成像（BLI）来表征原位表达荧光素酶的C6肿瘤的纵向发展。在所有大鼠（n = 11）中，作为C6细胞活力相对指标的BLI信号存在很大差异，但在大多数个体中，BLI信号在第11天达到峰值，随后下降。T2和对比增强T1肿瘤体积随时间显著增加（P <.05），且体积测量值与BLI信号不相关。在第11天后，对比增强T1加权磁共振成像中出现了无对比增强的肿瘤区域，与对比增强区域相比，其表观扩散系数值显著更高（P <.05）。这表明在第11天后形成了灌注不良的坏死区域，在终点匹配的组织切片中很明显。我们的研究首次联合使用BLI和mpMRI来表征原位C6大鼠模型中的疾病进展，突出了肿瘤生长的变异性、BLI和mpMRI的互补信息以及多模态成像在更好地表征肿瘤发展方面的价值。这些成像工具的未来应用将有助于评估治疗反应，并且对其他临床前模型也应具有相关性。
