MRI of mouse models for gliomas shows similarities to humans and can be used to identify mice for preclinical trials

Abstract

Magnetic resonance imaging (MRI) has been utilized for screening and detecting brain tumors in mice based upon their imaging characteristics appearance and their pattern of enhancement. Imaging of these tumors reveals many similarities to those observed in humans with identical pathology. Specifically, high-grade murine gliomas have histologic characteristics of glioblastoma multiforme (GBM) with contrast enhancement after intravenous administration of gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA), implying disruption of the blood-brain barrier in these tumors. In contrast, low-grade murine oligodendrogliomas do not reveal contrast enhancement, similar to human tumors. MRI can be used to identify mice with brain neoplasms as inclusion criteria in preclinical trials.

Figure 1

T2- and T1-weighted (pre- and postcontrast) images from a mouse with hydrocephalus. The hyperintense signal in the T2-weighted images reflect the dilated lateral ventricles. Areas of hydrocephalus have high signal intensity on T2- and low signal intensity on T1-weighted image, reflecting the higher T1 and T2 values of fluid. Note the lack of enhancement postcontrast.

Figure 2

Images and histopathologic sections of brain tumor obtained by infecting Ntv-a mice with combined RCAS-Ras and RCAS-Akt vectors. Images obtained with single mouse coil. (A) Intracranial tumor exhibits hyperintense signal on T2-weighted images and on postcontrast T1-weighted images. (B) Whole mount section corresponding to the images obtained by MRI. (C) Microscopic images of the GBM show histologic similarities to GBMs in humans.

Figure 3

Images and histopathologic sections of a brain tumor obtained by infecting Ntv-a mice with RCAS-PDGF. (A) Pre- and postcontrast MRI with lack of enhancement in the tumor region. (B) Corresponding whole mount brain section. (C) Microscopic histology of this tumor consistent with an oligodendroglioma.

Figure 4

Images and histopathologic sections of brain tumor obtained by infecting Ntv-a INK4a-ARF-/- mice with RCAS-PDGF. (A) Pre- and postcontrast MRI demonstrating lesion enhancement post Gd-DTPA (arrow). (B,C) Whole mount of the section shown in (A) revealing that the enhancing region has higher cellular density and necrosis.

Figure 5

Histologic analysis of the vasculature of the enhancing and nonenhancing regions of the tumor from Figure 4. (A) Nonenhancing regions of tumor have “chicken wire” vasculature (arrow) seen in human low-grade oligodendrogliomas. (B) Regions of tumor that enhanced with gadolinium showed glomeruloid microvascular proliferation similar to that seen in high grade oligodendrogliomas.

Figure 6

Images obtained on Ntv-a mice that had been infected with the combination of RCAS-Akt and RCAS-Ras. Plates (A), (B), and (C) are T2. T1 (precontrast) and T1 (postcontrast) from a single slice of multiple mice. Arrows indicate tumor as seen best on post Gd-DTPA images. Areas of hyperintense signal in the T2-weighted images correspond to areas of hydrocephalus, which are noted to not enhance with Gd-DTPA. Acquisition parameters included TR= 5500 ms, TE= 102 ms, NEX=4, 512x512, 8x8 cm², slice thickness= 1.5 mm, gap =0.5 mm.