Comparison of CT contrast blood pool agents for in-vivo 3D angiography using MicroCT

MicroCT small animal 3D angiography has various applications such as tumor growth evaluation or quantification of the pulmonary arterial tree morphometry. Due to longer acquisition times using preclinical systems, classical contrast agents are of little use in-vivo. Novel contrast agents such as gold nanoparticles and iodinated liposomes offer a possible solution to this difficulty by preventing rapid renal excretion. To evaluate different contrast agents, we filled pieces of polymer tubing (20 AWG) with solutions of 10 mg Au/ml and 30 mg Au/ml home-made gold nanoparticles, commercial gold nanoparticle (120 mg Au/ml), commercial iodinated liposomes, 30% barium sulfate solution, 6% iodine contrast solution and 100% saline (PBS), respectively. Each piece of tubing was imaged in our microCT together with the PBS filled tubing using identical imaging settings. Upon quantification and comparison of the phantom data, we imaged mice after injection of contrast agent. We also acquired data from excised lungs filled with contrast agent and gelatin solution. The barium sulfate solution had the highest measured radiodensity, which was 8 times higher than PBS. The solution with only 6% of iodine contrast gave us an increased radiodensity of 1.5x. Among the in-vivo compounds, the liposomal contrast agent had the highest radiodensity with 5 times than PBS, where the gold nanoparticles (10 mg/ml) were almost indistinguishable from PBS, but the higher concentrations show improvements in contrast. Our comparison shows that the traditional contrast agents have a higher radiodensity than novel compounds currently under development. Angiography using barium sulfate is a terminal experiment where the iodine contrast agent is cleared too quickly by the kidneys to be useful in-vivo. The small contrast improvement of the gold nanoparticles indicate that further development is still necessary for the particles to by useful in 3D angiography. In contrast, liposomal contrast agents appear to - - have reached a state where they can successfully highlight vessels in-vivo.