Rat Glioma Models for Preclinical Evaluation of Novel Therapeutic and Diagnostic Modalities

Kaur, Balveen; Barth, Rolf F.

doi:10.1007/978-1-60327-553-8_10

Cited by 1 publication

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“…Whereas the F98 glioma is highly vascular and it has a number of characteristics in common with glioblastoma multiforme,15,60,61 it is not as infiltrative of normal brain cortex as glioblastoma multiformes, nor is it as histologically pleomorphic. The incidence of hemorrhage identified within tumors imaged for this study was very low.…”

Section: Discussionmentioning

confidence: 99%

High Resolution Ultra High Field Magnetic Resonance Imaging of Glioma Microvascularity and Hypoxia Using Ultra-Small Particles of Iron Oxide

Christoforidis¹,

Yang²,

Kontzialis³

et al. 2009

Investigative Radiology

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Objectives-This study assessed whether ultra-small particles of iron oxide (USPIO) intravascular contrast agent could enhance visualization of tumor microvascularity in F98 glioma bearing rats by means of ultra high field (UHF) high-resolution gradient echo (GRE) magnetic resonance imaging (MRI). In an effort to explain differences in visualization of microvascularity before and after USPIO administration, hypoxia and vessel diameters were assessed on corresponding histopathologic sections.Materials and Methods-F98 glioma cells were implanted stereotactically into the brains of syngeneic Fischer rats. Based on clinical criteria, rats were imaged 1 to 2 days before their death with and without USPIO contrast on an 8 Tesla MRI. To identify hypoxic regions of the brain tumor by immunohistochemical, a subset of animals also received a nitroimidazole-based hypoxia marker, EF5, before euthanasia. These sections then were compared with noncontrast enhanced MR images. The relative caliber of tumor microvasculature, compared with that of normal brain, was analyzed in a third group of animals.Results-After USPIO administration, UHF high-resolution GRE MRI consistently predicted increased microvascular density relative to normal gray matter when correlated with histopathology. The in-plane visibility of glioma microvascularity in 22 rats increased by an average of 115% and signal intensity within the tumor decreased by 13% relative to normal brain. Tumor microvascularity identified on noncontrast MR images matched hypoxic regions identified by immunohistochemical staining with a sensitivity of 83% and specificity of 89%. UHF GRE MRI was able to resolve microvessels less than 20 μ in diameter, although differences in tumor vessel size did not consistently account for differences in visualization of microvascularity.Conclusions-USPIO administration significantly enhanced visualization of tumor microvascularity on gradient echo 8 T MRI and significantly improved visualization of tumor microvascularity. Microvascularity identified on pre-contrast images is suspected to be partly associated with hypoxia. Keywords NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptImproved signal-to-noise ratio with ultra high field (UHF) 8 T magnetic resonance imaging (MRI) allows acquisition of high-resolution (HR) images of the central nervous system. One major advantage of UHF MRI has been its ability to delineate cortical vascular anatomy. 1 MRI (8 T) can resolve microvessels with a diameter as small as 100 μm, using gradient echo (GRE) sequences with an in-plane resolution of 196 μm in normal human brain 2-4 and in glial tumors. 5,6 This 100-micron dimension is smaller than the voxel size used in acquisition, although the paramagnetic properties of deoxyhemoglobin, combined with increasing magnetic susceptibility effects at high field, allow microvessels to be resolved on T2*-weighted images. 3,7 Ultra-small superparamagnetic particles of iron oxide (USPIO) are intravascular magnetic resonance (MR) contrast a...

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Section: Discussionmentioning

confidence: 99%