Functional Parameters Derived from Magnetic Resonance Imaging Reflect Vascular Morphology in Preclinical Tumors and in Human Liver Metastases.

Abstract

<b>Purpose:</b> Tumor vessels influence the growth and response of tumors to therapy. Imaging vascular changes <i>in vivo</i> using dynamic contrast-enhanced MRI (DCE-MRI) has shown potential to guide clinical decision making for treatment. However, quantitative MR imaging biomarkers of vascular function have not been widely adopted, partly because their relationship to structural changes in vessels remains unclear. We aimed to elucidate the relationships between vessel function and morphology <i>in vivo</i> <b>Experimental Design:</b> Untreated preclinical tumors with different levels of vascularization were imaged sequentially using DCE-MRI and CT. Relationships between functional parameters from MR (<i>i</i>AUC, <i>K</i> ^trans, and BAT_frac) and structural parameters from CT (vessel volume, radius, and tortuosity) were assessed using linear models. Tumors treated with anti-VEGFR2 antibody were then imaged to determine whether antiangiogenic therapy altered these relationships. Finally, functional-structural relationships were measured in 10 patients with liver metastases from colorectal cancer.<b>Results:</b> Functional parameters <i>i</i>AUC and <i>K</i> ^trans primarily reflected vessel volume in untreated preclinical tumors. The relationships varied spatially and with tumor vascularity, and were altered by antiangiogenic treatment. In human liver metastases, all three structural parameters were linearly correlated with <i>i</i>AUC and <i>K</i> ^trans For <i>i</i>AUC, structural parameters also modified each other's effect.<b>Conclusions:</b> Our findings suggest that MR imaging biomarkers of vascular function are linked to structural changes in tumor vessels and that antiangiogenic therapy can affect this link. Our work also demonstrates the feasibility of three-dimensional functional-structural validation of MR biomarkers <i>in vivo</i> to improve their biological interpretation and clinical utility. <i>Clin Cancer Res; 24(19); 4694-704. ©2018 AACR</i>.