Feasibility of 4D perfusion CT imaging for the assessment of liver treatment response following SBRT and sorafenib

OBJECTIVES: To evaluate the feasibility of 4-dimensional perfusion computed tomography (CT) as an imaging biomarker for patients with hepatocellular carcinoma and metastatic liver disease. METHODS AND MATERIALS: Patients underwent volumetric dynamic contrast-enhanced CT on a 320-slice scanner before and during stereotactic body radiation therapy and sorafenib, and at 1 and 3 months after treatment. Quiet free breathing was used in the CT acquisition and multiple techniques (rigid or deformable registration as well as outlier removal) were applied to account for residual liver motion. Kinetic modeling was performed on a voxel-by-voxel basis in the gross tumor volume and normal liver resulting in 3-dimensional parameter maps of blood perfusion, capillary permeability, blood volume, and mean transit time. Perfusion characteristics in the tumor and adjacent liver were correlated with radiation dose distributions to evaluate dose-response. Paired t tests assessed change in spatial and histogram parameters from baseline to different time points during and after treatment. Technique reproducibility as well as the impact of arterial and portal vein input functions was also investigated using intra- and inter-subject variance and Bland-Altman analysis. RESULTS: Quantitative perfusion parameters were reproducible (±5.7%; range, 2%-10%) depending on tumor/normal liver type and kinetic parameter. Statistically significant reductions in tumor perfusion were measurable over the course of treatment and as early as 1 week after sorafenib administration (P < .05). Marked liver parenchyma perfusion reduction was seen with a strong dose-response effect (R(2) = 0.95) that increased significantly over the course treatment. CONCLUSIONS: The proposed methodology demonstrated feasibility of evaluating spatiotemporal changes in liver tumor perfusion and normal liver function following antiangiogenic therapy and radiation treatment warranting further evaluation of biomarker prognostication.