Assessment of Blood Flow in Hepatocellular Carcinoma: Correlations of Computed Tomography Perfusion Imaging and Circulating Angiogenic Factors

Abstract

Hepatocellular carcinoma (HCC) is a highly vascular tumor through the process of angiogenesis. To evaluate more non-invasive techniques for assessment of blood flow (BF) in HCC, this study examined the relationships between BF of HCC measured by computer tomography (CT) perfusion imaging and four circulating angiogenic factors in HCC patients. Interleukin 6 (IL-6), interleukin 8 (IL-8), vascular endothelial growth factor (VEGF), and platelet derived growth factor (PDGF) in plasma were measured using Bio-Plex multiplex immunoassay in 21 HCC patients and eight healthy controls. Circulating IL-6, IL-8 and VEGF showed higher concentrations in HCC patients than in controls (p < 0.05), and predicted HCC occurrence better than chance (p < 0.01). Twenty-one patients with HCC received 21-phase liver imaging using a 64-slice CT. Total BF, arterial BF, portal BF, arterial fraction (arterial BF/total BF) of the HCC and surrounding liver parenchyma, and HCC-parenchyma ratio were measured using a dual-vessel model. After analyzing the correlations between BF in HCC and four circulating angiogenic factors, we found that the HCC-parenchyma ratio of arterial BF showed a significantly positive correlation with the level of circulating IL-8 (p < 0.05). This circulating biomarker, IL-8, provides a non-invasive tool for assessment of BF in HCC.

Preliminary qualification of a novel, hypoxic-based radiologic signature for trans-arterial chemoembolization in hepatocellular carcinoma

“…The prospect of predicting long-term outcomes following TACE based on pre-treatment radiologic features of the tumour is not a novel concept in HCC [ 13 ]. However this is the first study to comprehensively evaluate radiologic predictors relating to hypoxia and neo-angiogenesis on routine diagnostic CT scans without the need to extrapolate complex perfusion parameters [ 14 ].…”

“…Newly formed vasculature demonstrates increased permeability, tortuous course and wider luminal diameters compared to normal vessels, which can be easily detected on arterial CT sequences [ 14 ], often in form of aberrant AV shunting [ 18 ]. The emergence of ITN is an equally common finding in HCC and a surrogate marker of highly proliferating tumours that fail to maintain the required nutrient and oxygen supply [ 19 ].…”

Platelets and Hepatocellular Cancer: Bridging the Bench to the Clinics

“…Several in vitro and in vivo studies investigated the connection between PDGF and HCC (Table 1) [18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41]. In vitro studies showed a 7-fold increase in total PDGFR-alpha levels in HCC cells when compared to normal hepatocytes and a rise in chemosensitivity under normo- or hypoxic conditions when PDGF is repressed [18,19,20,21,22,24,25,26,28].…”

Comparison of vascularity observed using contrast-enhanced 3D ultrasonography and pathological changes in patients with hepatocellular carcinoma after sorafenib treatment

“…Chen et al evaluated blood flow in HCC using CT perfusion imaging 7 . Dynamic contrast-enhanced MRI 8 and diffusion MRI imaging 9 have also been used to evaluate blood flow in HCC.…”