Characterization of the tumor invasion area in the rat intracerebral glioma.

Tumor cell invasion surrounding intracerebrally implanted tumors in rats was studied by comparing the results of cerebral microangiography, fluorescence imaging of blood-brain barrier (BBB) disruption and histopathology. Each comparison was on subsequent sections taken from an initial 1 mm coronal slice of brain taken through the cell injection site containing tumor using the RT-2 glioma model. Tumor extension was assessed at 3, 5, 7 and 9 days after tumor implantation. Analysis of the brain adjacent to tumor shows that the actual tumor cell invasion area is greater than the area of BBB disruption at later stages of tumor growth and the extent of tumor vascularization lies well within the area defined by the extent of tumor cell invasion. Furthermore, this study found that the size of the area of tumor cell invasion remains relatively stable in proportion to the solid tumor mass at various stages of growth such that the area of tumor invaded brain was approximately 2.5 times greater than the area outlined by solid tumor mass. We conclude that measurement of the solid tumor mass, tumor vascular area and region of blood-brain barrier disruption due to tumor, grossly underestimate the total tumor volume. Therapies aimed at controlling glial tumor growth must, therefore, include normal appearing regions of brain peripheral to the abnormal region defined as tumor and tumor invaded brain as defined by radiographic and imaging studies.