Vascular Phenotyping of Brain Tumors with MR Microscopy (μMRI)

INTRODUCTION: Brain tumors remain among the most refractory of human tumors and their “angiogenic” phenotype or vascular architecture is a critical determinant of their pathophysiology, efficacy of therapy and image contrast in MRI [1]. Traditionally the angiogenic phenotype has been characterized at “cellular” spatial resolutions in terms of blood volume, vessel diameter, fractal dimension, vessel branching and connectivity using optical imaging. However, a drawback of optical imaging is that it suffers from limited coverage, and information on 3D blood vessel geometry once destroyed by sectioning requires complex reconstruction. In contrast, in vivo MRI with its sub-millimeter resolution has proved useful for obtaining angiogenic biomarkers such as blood volume and vessel size index at the “systemic” spatial scale [2]. Noninvasive imaging techniques that enable characterization of the angiogenic phenotype at spatial resolutions intermediate to the “cellular” and “systemic” are scarce. Here we describe a new method for characterizing the angiogenic phenotype of a brain tumor model using magnetic resonance microscopy (μMRI), which is non-destructive and preserves the 3D tissue and blood vessel architecture. When combined with different kinds of MR contrast (e.g. diffusion-tensor imaging or DTI), μMRI can provide a wealth of information on the brain tumor microenvironment that is inaccessible by other imaging methods. As μMRI generates high-resolution 3D images of the vasculature, we were able to characterize morphological differences between the angio-architecture of the contralateral brain and that of the tumor using fractal analysis. METHODS: Five 9L brain tumor (12 days post-inoculation) bearing mouse brains