Assessing breast cancer angiogenesis in vivo: which susceptibility contrast MRI biomarkers are relevant?

Abstract

There is an impending need for noninvasive biomarkers of breast cancer angiogenesis to evaluate the efficacy of new anti-angiogenic therapies in vivo. The purpose of this study was to systematically evaluate the sensitivity of in vivo steady-state susceptibility contrast-MRI biomarkers of angiogenesis in a human breast cancer model. Orthotopic MDA-MB-231 human breast cancer xenografts were imaged by steady-state susceptibility contrast-MRI at post-inoculation week 3 and post-inoculation week 5, followed by ex vivo whole tumor 3D micro-CT angiography. "Absolute" (i.e., measures of vascular morphology in appropriate units) and "relative" (i.e., proportional to measures of vascular morphology) MRI biomarkers of tumor blood volume, vessel size, and vessel density were computed and their ability to predict the corresponding micro-CT analogs assessed using cross-validation analysis. All MRI biomarkers significantly correlated with their micro-CT analogs and were sensitive to the micro-CT-measured decreases in tumor blood volume and vessel density from post-inoculation week 3 to post-inoculation week 5. However, cross-validation analysis revealed there was no significant difference between the predictive accuracy of "absolute" and "relative" biomarkers. As "relative" biomarkers are more easily computed from steady-state susceptibility contrast-MRI (i.e., without additional MRI measurements) than "absolute" biomarkers, it makes them promising candidates for assessing breast cancer angiogenesis in vivo.