Imaging of pulmonary embolism and t-PA therapy effects using MDCT and liposomal iohexol blood pool agent: preliminary results in a rabbit model

Abstract

Rationale and objectives: Polyethylene glycol-coated liposomal blood pool contrast agents maintain contrast enhancement over several hours. This study aimed to evaluate (long-term) imaging of pulmonary arteries, comparing conventional iodinated contrast with a liposomal blood pool contrast agent. Also, visualization of the (real-time) therapeutic effects of tissue plasminogen activator (t-PA) on pulmonary embolism (PE) was attempted.

Materials and methods: Six rabbits (weight approximately 4 kg) had autologous blood clots injected through the superior vena cava. Imaging was performed using conventional contrast (iohexol, 350 mg I/ml; GE HealthCare, Princeton, NJ) at a dose of 1400 mg I per animal, and after wash-out, animals were imaged using an iodinated liposomal blood pool agent (88 mg I/mL, dose 900 mg I/animal). Subsequently, five animals were injected with 2 mg of t-PA and imaging continued for up to 4(1/2) hours.

Results: Both contrast agents identified PE in the pulmonary trunk and main pulmonary arteries in all rabbits. Liposomal blood pool agent yielded uniform enhancement, which remained relatively constant throughout the experiments. Conventional agents exhibited nonuniform opacification and rapid clearance postinjection. Three of six rabbits had mistimed bolus injections, requiring repeat injections. Following t-PA, pulmonary embolus volume (central to segmental) decreased in four of five treated rabbits (range 10-57%, mean 42%). One animal showed no response to t-PA.

Conclusions: Liposomal blood pool agents effectively identified acute PE without need for reinjection. PE resolution following t-PA was quantifiable over several hours. Blood pool agents offer the potential for repeated imaging procedures without need for repeated (nephrotoxic) contrast injections.

Figure 1

This graph depicts a typical time-attenuation curve in the pulmonary artery and aorta over time with stable attenuation above 100 HU for four hours.

Figure 2

These images demonstrate side-by-side comparison of the images in the same rabbit using conventional versus liposomal iohexol contrast agent. A central pulmonary embolus at the bifurcation is present (bold arrow) and the key structures are idenfied. Notice that the liposomal agent gives almost homogeneous contrast in both the right and left sided heart, whereas the conventional contrast necessitates bolus timing for right sided enhancement.

Figure 3

Side-by-side comparison of images in a rabbit following central PE injection, demonstrating the clot in the left main/lower lobe branch using both conventional and liposomal iohexol contrast agents (bold arrows). There is a slight difference in slice position, but otherwise there is excellent correlation both in axial and reconstructed coronal planes.

Figure 4

This graph demonstrates the clot size measurements (% volume from baseline) over time following injection of t-PA. Rabbit 2 shows no significant response, but the other 4 treated rabbits show a clot volume decrease in the range of 40–60%.

Figure 5

These image series demonstrate clot resolution of a central embolus (bold arrow) in response to t-PA during a 90-minute interval using liposomal iohexol contrast.

Figure 6

These series of images demonstrate near-complete clot resolution of a right lower lobe embolus (bold arrow) in response to t-PA during a 240-minute interval using liposomal iohexol contrast. It should be noted that no additional contrast was administered during this time period.