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 4½ 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.
Patients who present with acute chest symptoms are a frequent clinical problem ( ). This is partly due to the range of acute diagnoses that can be considered. As a result, early triage to decide on adequate management is crucial. This has led to a significant increase in CT utilization ( ), and attempts are now focusing on reducing the number of patients requiring imaging ( ). Essentially, the three most critical diagnoses that clinicians focus on are (a) myocardial ischemia, (b) pulmonary embolism (PE), and (c) aortic dissection or rupture. Although all three diagnoses can now be evaluated using CT, simultaneous evaluation, or a “triple rule-out” CT protocol, it is difficult to entertain due to competing requirements. Because conventional contrast agents are distributed and cleared within minutes ( ), effective multifunctional imaging becomes difficult. Thus, for PE evaluation, the contrast bolus has to be timed to be optimal in the right heart and pulmonary circulation ( ), while for assessment of the aorta and coronary arteries, a greater delay from bolus to imaging is required to reach optimal contrast enhancement in the left heart.
A correctly timed contrast bolus delay is not easy to achieve; even with the aid of a test bolus or bolus detection systems in modern CT scanners, up to 10% of PE studies have suboptimal contrast in the pulmonary arteries ( ). Although one could devise a combined protocol with multiple contrast bolus injections and repeated CT imaging of the relevant field of view, it is likely that the number of suboptimal contrast studies will rise. A single study with optimal, simultaneous enhancement in multiple vascular beds would prevent repeat studies with their incremental x-ray dose with each scan and the nephrotoxicity of repeat contrast administration.
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Materials and methods
Rabbit In Vivo Protocol
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Induction of Pulmonary Embolism
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Thrombolytic Therapy Protocol
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Imaging Protocol
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Contrast Agents
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Image Analysis
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Results
Contrast Agent Comparison
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Thrombolytic Effect Measurements
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Discussion
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