Evaluation of neovascularization with spectral computed tomography in a rabbit VX2 liver model: a comparison with real-time contrast-enhanced ultrasound and molecular biological findings

Abstract

Objective: To validate the feasibility of using the parameters of spectral CT and CT perfusion and the dynamic features of real-time contrast-enhanced ultrasound (CEUS) to evaluate the vascularization of VX2 hepatic tumours. Methods: Spectral CT imaging, CT perfusion and CEUS analysis were performed on rabbits implanted with VX2 hepatic tumours, 7 and 14 days after implantation. The perfusion parameters of CT, normalized iodine concentration (NIC) and dynamic features of CEUS were measured in the rim of the tumour (TR) and the normal liver region. The expression of vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF2) was also determined. Results: Increased perfusion parameters of CT were found in the TR. In addition, the NIC was elevated in TR during the arterial phase, and the peak intensity of the CEUS of the TR was reached significantly earlier than that on normal liver region. At 14 days, the perfusion parameters of CT (blood volume, permeability surface and hepatic arterial fraction) offered higher accuracy and stability in differentiating the TR from the normal liver region. Furthermore, CEUS was more accurate in diagnosing tumours ,1.0 cm in diameter. In addition, VEGF and FGF2 expression was higher in the TR and were positively correlated with CT and CEUS parameters, except mean transit time, rise time, washout time and peak time. Conclusion: Use of spectral CT with perfusion techniques, iodine-based material-decomposition analysis and dynamic CEUS changes may reflect the angiogenesis and haemodynamic information of hepatic tumours. Advances in knowledge: It is feasible to assess vascularization in hepatic cancer using CT or CEUS. INTRODUCTIONPrimary hepatic carcinoma is one of the most common malignant tumours, with a steadily increasing mortality rate over the past few years. 1 The newly emerging techniques of spectral CT imaging and CT perfusion reveal the haemodynamic features in the tumour tissues and play an important role in the detection and differential diagnosis of a solid mass in the liver.2,3 Dual-energy CT performed during two consecutive scans or with a dual X-ray source or dual-detector assembly has existed for a number of years. It was demonstrated that the additional information was provided by using dual-energy material separation technique, which had potential clinical applications.4,5 By revealing the blood supply and the haemodynamic features of the tumours, the real-time contrast-enhanced ultrasound (CEUS) provides high accuracy and specificity for diagnosing small hepatic tumours and enables the detection of early malignant diseases.

High-Performance Poly(lactic-co-glycolic acid)-Magnetic Microspheres Prepared by Rotating Membrane Emulsification for Transcatheter Arterial Embolization and Magnetic Ablation in VX2 Liver Tumors

“…To acquire more concrete proof that TAEMA is an effective and feasible strategy, the real-time relative-quantitative polymerase chain reaction (Q-PCR) was used to investigate the expressive changes of important genes related to the HCC, including tumor protein p53 (p53), 51 aldehyde dehydrogenase 1 family (ALDH1A1, also known as retinaldehyde dehydrogenase 1), 52 and vascular endothelial growth factor (VEGF), respectively. 53 In fact, p53 possesses sophisticated mechanisms of anticancer function and plays a role in apoptosis, genomic stability, and inhibition of angiogenesis. Meanwhile, the enzymatic activity of ALDH1A1 has been identified as one of the markers of cancer stem cells, and the high expression is associated with prognosis in a variety of solid tumors.…”

Spectral computed tomography in advanced gastric cancer: Can iodine concentration non-invasively assess angiogenesis?

“…VEGF, one of the most prominent biomarkers of angiogenesis studied to date, has been shown to correlate well with CT perfusion in peripheral pulmonary nodules[ 28 ]. Moreover, the study of Zhou et al[ 13 ] in a rabbit VX2 liver model suggested that nIC and contrast-enhanced ultrasound parameters positively correlated with VEGF and FGF2 expression, while several reports failed to show such a correlation, for example, the GC study performed by Yao et al[ 6 ] and the colorectal cancer research by Goh et al[ 24 ]. The relationship between VEGF expression and imaging of tumor vascularity is complex.…”