MR Imaging Features of High-Grade Gliomas in Murine Models: How They Compare with Human Disease, Reflect Tumor Biology, and Play a Role in Preclinical Trials

Flow chart for integrated MR imaging, histology, and genomic and proteomic approaches in models of HGG. A, Representative Swiss mouse. B, Gadolinium-enhanced axial T1-weighted image shows an implanted Gl261 HGG. C, Parametric T2*map of the tumor in B. D, Parametric histogram of T2* values of C. E, Isolated normal brain from a representative Swiss mouse. F, Representative hematoxylin-eosin–stained section across a formalin-fixed paraffin-embedded mouse brain carrying an implanted HGG. Reproduced from Lal et al¹⁷ with permission from the Journal of Neurosurgery Publishing Group. G, Microscopic view (×40) of a fixed and stained section across an HGG (small black bar on the lower right corner represents 50 μm) shows pseudopalisading necrosis characteristic of HGG. Reproduced from Collier et al¹⁸ with permission from the American Association for Cancer Research. H, Gene-expression profiling (RT qPCR results) from a representative Gl261 HGG. I, Representative VEGF-A protein expression as detected by Western blot analysis.

Serial axial T2-weighted (A) and contrast-enhanced T1-weighted (B) images of a Gl261 C57/Bl6 mouse model of HGG, showing tumor growth and increased enhancement over a period of 4 weeks. C, ROIs delineating the tumor (green limit) 1, 2, and 4 weeks after implantation; and nonlinear fitting (red) of signal intensity versus TE (blue) in representative pixel and parametric T2* maps depicting T2* values in the selected ROI. D, T2* histograms nicely depict the temporal variation of T2* values with tumor progression modified by small differences in oxygen blood saturation reflected by the paramagnetic effect of deoxyhemoglobin.

A, Multiple mouse parallel imaging. Coronal (left) and sagittal (right) sections from FSE multiple mouse MRI images of 4 mice (numbered 1–4). Each 3D image has a 100-μm isotropic resolution. Scan duration was 2 hours 50 minutes. Reproduced from Nieman et al¹⁶ with permission from John Wiley and Sons. B, Multiple mouse MRI of GEMMs of HGG T2-weighted (1), T1-weighted (2), and gadolinium-enhanced T1-weighted (3) images, obtained on a 1.5T Signa clinical scanner (GE Healthcare, Milwaukee, Wisconsin) by using a common receiver coil, clearly demonstrates which mice developed brain tumors (white arrows) and differentiates brain tumors from hydrocephalus. Reproduced from Koutcher et al with the authors' permission.²⁶

The visible mouse project (3D MR imaging of a whole fixed C57Bl/6J mouse). Images acquired with an isotropic array with a 256 × 256 × 1024 matrix and 110 × 110 × 110 μm in-plane resolution. Coronal (top) and representative axial T1-weighted sections from the brain (left), thorax (center), and abdomen (right). Reproduced from Johnson et al²¹ with permission from the Radiologic Society of North America.

Multiple mouse MRI loading system described by Dazai et al.²² Mice loading array equipped with anesthesia and a mouse hive, which holds up to 19 receiver coils. Reproduced from Dazai et al²² with permission from John Wiley and Sons.