Quantitative contrast enhanced CT for the assessment of hepatic extracellular volume: optimisation and application in liver-directed cancer therapy

Abstract

Background: Equilibrium CT (EQ-CT) is a quantitative contrast enhanced CT technique that is used to measure extracellular volume (ECV). ECV measurements have been shown to correlate with fibrotic burden in a range of chronic liver conditions, however evidence in liver cancer is lacking. ECV has the potential to be related to the aggressiveness and metastatic potential of tumours and could be used to monitor response to treatment. However, in order to be a useful diagnostic and prognostic tool, the accuracy, precision and repeatability of the technique must be understood. This has not been addressed in the literature. Aims: The main research aims of this study are to establish the optimal acquisition and reconstruction parameters for EQ-CT in the liver; to determine the accuracy and clinical reproducibility of the technique; to measure ECV in liver cancers and to establish the feasibility of ECV measurement after the administration of novel radiopaque transarterial chemoembolisation (TACE) beads to monitor response to treatment. Materials and methods: A literature search was carried out, followed by a phantom study to investigate the effect of kVp, CTDIvol and slice width on simulated ECV measurements in both conventional and dual energy CT modes. Accuracy of the technique was established and precision was related to a novel imaging metric for EQ-CT: 'enhancement to noise ratio' (ENR). A clinical study of ECV measurements made in patients with liver cancer being treated with TACE followed. ECV was measured in unaffected liver and tumour lesions at successive visits, prior to and after therapy, using conventional and dual energy CT. All imaging was performed using a wide beam (16 cm) CT system. Results: The literature search revealed there was little technical detail attributed to existing EQ-CT protocols, which were predominantly clinically focussed. The phantom study demonstrated a mean error of 0.1% (interquartile range 9.1%) associated with simulated ECV measurements. Accuracy was robust to changes in acquisition parameters and precision was maximised at low kVp values and increased with ENR. Images from 6 patients indicated dual energy iodine density mode was unsuitable for clinical ECV measurements. Accuracy at clinically obtained ENR values was approximately +/-17%. Results were reproducible across two patient visits separated by up to seven days. It was not possible to establish a definitive difference between ECV measured in tumour lesions and uninvolved tissue due to low patient numbers and lack of histopathological analysis. ECV measurement was possible with TACE beads present. Image registration was highlighted as problematic. Conclusions: EQ-CT to measure ECV in the liver is accurate and clinically reproducible. Precision is related to acquisition and reconstruction settings and dual energy iodine density mode offers no advantages over conventional CT. The technique is a potentially useful tool for the diagnosis and monitoring of patients with liver cancer.

Date of Award	1 Aug 2022
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Julia-Claire Handley (Supervisor) & Joseph Bastin (Supervisor)