Use of Ultrasmall Superparamagnetic Iron Oxide Enhanced Susceptibility Weighted Imaging and Mean Vessel Density Imaging to Monitor Antiangiogenic Effects of Sorafenib on Experimental Hepatocellular Carcinoma.

Shuohui Yang,Fang Lu,Zhihong Han,Hongchen Gu,Jiang Lin,Caixia Fu

doi:10.1155/2017/9265098

Abstract

We investigated effectiveness of ultrasmall superparamagnetic iron oxide enhanced susceptibility weighted imaging (USPIO-enhanced SWI) and mean vessel density imaging (Q) in monitoring antiangiogenic effects of Sorafenib on orthotopic hepatocellular carcinoma (HCC). Thirty-five HCC xenografts were established. USPIO-enhanced SWI and Q were performed on a 1.5 T MR scanner at baseline, 7, 14, and 21 days after Sorafenib treatment. Intratumoral susceptibility signal intensity (ITSS) and Q were serially measured and compared between the treated (n = 15) and control groups (n = 15). Both ITSS and Q were significantly lower in the treated group at each time point (P < 0.05). Measurements in the treated group showed that ITSS persisted at 7 days (P = 0.669) and increased at 14 and 21 days (P < 0.05), while Q significantly declined at 7 days (P = 0.028) and gradually increased at 14 and 21 days. In the treated group, significant correlation was found between Q and histologic microvessel density (MVD) (r = 0.753, P < 0.001), and ITSS correlated well with MVD (r = 0.742, P = 0.002) after excluding the data from baseline. This study demonstrated that USPIO-enhanced SWI and Q could provide novel biomarkers for evaluating antiangiogenic effects of Sorafenib on HCC.

Highlights

Hepatocellular carcinoma (HCC) is a highly vascular tumor
It is critical to identify some imaging biomarkers that may predict the efficacy of Sorafenib treatment at an early stage, because this helps in selecting responsive patients shortly after the start of treatment
By using combined USPIO-enhanced SWI and Q in this study, we demonstrated that intratumoral susceptibility signal (ITSS) scoring and Q quantification could be used with high intra- and interobserver agreement to reflect sequential effects of Sorafenib on both macro- and microtumor vasculature of HCC, and both ITSS and Q were correlated well with tumor volume and histologic microvessel density (MVD)

Summary

Introduction

Hepatocellular carcinoma (HCC) is a highly vascular tumor. The growth and metastasis of HCC require tumor angiogenesis, which has provided a strong rationale for using antiangiogenic therapy [1]. With inherent complexity and variable reproducibility, several noninvasive imaging modalities, such as dynamic contrast-enhanced (DCE) CT, MRI, ultrasound, and most recently intravoxel incoherent motion, have been used to assess the functional properties of tumor angiogenesis before and after antiangiogenic therapy [4,5,6,7]. These techniques do not demonstrate tumor macro- and microvessels themselves, nor do they allow quantification of tumor microvasculature which can be used as an imaging analogue to histological MVD.

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