Characterization of Tumor Vasculature in Mouse Brain by USPIO Contrast-Enhanced MRI

Abstract

Detailed characterization of the tumor vasculature provides a better understanding of the complex mechanisms associated with tumor development and is especially important to evaluate responses to current therapies which target the tumor vasculature. Magnetic resonance imaging (MRI) studies of tumors have been mostly performed using gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) contrast-enhanced imaging, which relies on Gd-DTPA leakage from hyperpermeable tumor vessels and subsequent accumulation in the tumor interstitium. In certain tumor types, especially diffuse glioma in the brain, incorporated tumor vessels are not necessarily leaky, complicating effective diagnosis via Gd-DTPA contrast-enhanced MRI. Another class of contrast agents, based on superparamagnetic ultrasmall iron oxide particles (USPIO), allows for non-invasive assessment of vascular volume within the tumor. Vascular volume can be obtained by calculating the change in water proton transverse relaxation rate (R 2 or R 2*) following USPIO administration. This allows for an objective comparison between vascular volumes of different tumors and also allows to perform longitudinal studies in order to assess, for example, treatment efficacy. Moreover, since the USPIO T 2 relaxivity is up to 20 times that of Gd-DTPA, USPIO provides a highly sensitive marker for alterations in vascular volume among tissues; this characteristic might be exploited for tumor detection. Thus, USPIO imaging may be a very attractive alternative to the most commonly used Gd-DTPA imaging and will at least have added value, especially for detection and delineation of diffuse infiltrative brain tumors.