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Abstract
PurposeTo 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.Materials and methodsThe 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.ResultsAll 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).ConclusionOur 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.
Highlights
Glioblastoma multiforme (GBM) is the most common malignant primary brain tumour and carries a poor prognosis [1]
Multiparametric magnetic resonance imaging of canine glioblastoma funded by the Ministry of Science, ICT & Future Planning (NRF-2020R1A2C2008949 and NRF2020R1A4A1018714), by the Creative-Pioneering Researchers Program through Seoul National University (SNU), and by the Institute for Basic Science (IBS-R006-A1))
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
Summary
Glioblastoma multiforme (GBM) is the most common malignant primary brain tumour and carries a poor prognosis [1]. It is essential to obtain evidence for applying new diagnostic and treatment methods in preclinical GBM models similar to human GBM. The small animal GBM models’ limitation is that they are too small to evaluate newly applied diagnostic or treatment devices [3,4,5,6]. The preclinical testing of novel devices for effective treatment requires easier access to diagnostic and therapeutic manipulations in animal models similar in size to humans. A multiparametric magnetic resonance imaging (MRI) approach for physiologic imaging and treatment response assessment in GBM can be used for both primary brain tumours in dogs and humans, which could further facilitate the application of new methods in human patients
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