Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea.
Department of Radiology, Seoul National University College of Medicine, Seoul, Republic of Korea.
PLoS One. 2021 Jul 9;16(7):e0254448. doi: 10.1371/journal.pone.0254448. eCollection 2021.
To assess glioblastoma multiforme (GBM) formation with similar imaging characteristics to human GBM using multiparametric magnetic resonance imaging (MRI) in an orthotopic xenograft canine GBM model.
The canine GBM cell line J3T1 was subcutaneously injected into 6-week-old female BALB/c nude mice to obtain tumour fragments. Tumour fragments were implanted into adult male mongrel dog brains through surgery. Multiparametric MRI was performed with conventional MRI, diffusion-weighted imaging, and dynamic susceptibility contrast-enhanced perfusion-weighted imaging at one week and two weeks after surgery in a total of 15 surgical success cases. The presence of tumour cells, the necrotic area fraction, and the microvessel density (MVD) of the tumour on the histologic specimen were assessed. Tumour volume, diffusion, and perfusion parameters were compared at each time point using Wilcoxon signed-rank tests, and the differences between tumour and normal parenchyma were compared using unpaired t-tests. Spearman correlation analysis was performed between the imaging and histologic parameters.
All animals showed a peripheral enhancing lesion on MRI and confirmed the presence of a tumour through histologic analysis (92.3%). The normalized perfusion values did not show significant decreases through at least 2 weeks after the surgery (P > 0.05). There was greater cerebral blood volume and flow in the GBM than in the normal-appearing white matter (1.46 ± 0.25 vs. 1.13 ± 0.16 and 1.30 ± 0.22 vs. 1.02 ± 0.14; P < 0.001 and P < 0.001, respectively). The MVD in the histologic specimens was correlated with the cerebral blood volume in the GBM tissue (r = 0.850, P = 0.004).
Our results suggest that the canine GBM model showed perfusion imaging characteristics similar to those of humans, and it might have potential as a model to assess novel technical developments for GBM treatment.
利用磁共振多参数成像(MRI)在犬脑原位异种移植胶质母细胞瘤(GBM)模型中评估与人类 GBM 具有相似影像学特征的 GBM。
将犬 GBM 细胞系 J3T1 皮下注射到 6 周龄雌性 BALB/c 裸鼠中以获得肿瘤碎片。肿瘤碎片通过手术植入成年雄性杂种犬脑中。在总共 15 例手术成功的病例中,于手术后 1 周和 2 周进行常规 MRI、弥散加权成像和动态对比增强灌注加权成像的多参数 MRI。评估组织学标本中的肿瘤细胞存在、坏死区域分数和肿瘤微血管密度(MVD)。使用 Wilcoxon 符号秩检验比较每个时间点的肿瘤体积、弥散和灌注参数,并使用独立样本 t 检验比较肿瘤与正常脑实质之间的差异。进行成像和组织学参数之间的 Spearman 相关性分析。
所有动物的 MRI 均显示出周边增强病变,并通过组织学分析证实存在肿瘤(92.3%)。至少在手术后 2 周内,归一化灌注值没有明显下降(P > 0.05)。GBM 中的脑血容量和血流均大于正常外观的白质(1.46 ± 0.25 比 1.13 ± 0.16 和 1.30 ± 0.22 比 1.02 ± 0.14;P < 0.001 和 P < 0.001,分别)。组织学标本中的 MVD 与 GBM 组织中的脑血容量呈正相关(r = 0.850,P = 0.004)。
我们的结果表明,犬 GBM 模型显示出与人类相似的灌注成像特征,并且可能有潜力成为评估 GBM 治疗新技术发展的模型。