Multiparametric MRI characterization of the G144 GBM model

Trabajo presentado en el ESMRMB 38th Annual Scientific Meeting, celebrado en modalidad virtual del 07 al 09 de octubre de 2021.[Introduction]: Different orthotopic murine preclinical models have been developed to study the diagnosis, progression and therapy validation of glioblastoma multiforme (GBM)1, the most frequent and lethal malignant brain tumor2. Among them, the xenograft model established by stereotactic injection of the human G144 stem cells emerges as one of the best approaches to replicate the human GBM features in immunocompromised mice and to address GBM genetics and histopathology3,4,5. Magnetic resonance imaging (MRI) is a powerful tool to obtain structural, functional and molecular information on the physiopathology of intracranial tumors, but very few studies have been performed with this GBM model4. The aim of this work is to characterize the preclinical G144 glioma model by multiparametric (MP)-MRI approaches. [Methods]: The orthotopic GBM was developed in NOD-SCID mice (n=5) by injecting 105 G144 cells in the right caudate nucleus. MRI studies were carried out in a Bruker 7T system. Tumor growth was followed up by T2 weighted (T2W) images, and MP-MRI studies were performed when the tumor volume was ~70 mm3: T2 maps, magnetization transfer (MT) images, diffusion weighted images and dynamic contrast enhancement (DCE) using the intravenous injection of 0.25 mmol/Kg of Gadovist® (Bayer) as contrast agent (CA). Parametric maps were generated with a home-made software built in Matlab and relative contrast enhancement (RCE) maps were obtained using the software DCE@ourlab6. Regions of interest (ROIs) were manually selected to quantify the obtained parameters. [Results]: Tumors were visualized in T2W MRI 30-50 days post cell-injection (p.i.) and the volume to perform the MP-MRI studies was reached 53-104 days p.i. Hyperintensity spots were heterogeneously observed in the tumor in T2W and in contrast-enhance T1W (CE-tumor) images (Figure 1). DCE studies showed the progressive and faster accumulation of CA in the CE-tumor ROI than in the rest of the ROIs (Figure 2). CEtumor also showed higher T2 and Mean Diffusivity (MD) values, and lower MT and Fractional Anisotropy (FA) values (Figure 3). [Discussion]: To our knowledge, this is the first MP-MRI characterization of a GBM humanized mouse model established from G144 cells. The results point that necrosis, inflammatory processes and loss of structural integrity of the tissue are occurring in the CE-tumor area compared with the rest of the ROIs, similarly to MRI characteristics from human GBM patients7. In order to improve the knowledge of this GBM model utility, further experiments will be performed to evaluate different therapies effects in the MRI parameters