An unmet clinical need: The history of thrombus imaging

Abstract

Robust thrombus imaging is an unresolved clinical unmet need dating back to the mid 1970s. While early molecular imaging approaches began with nuclear SPECT imaging, contrast agents for virtually all biomedical imaging modalities have been demonstrated in vivo with unique strengths and common weaknesses. Two primary molecular imaging targets have been pursued for thrombus imaging: platelets and fibrin. Some common issues noted over 40 years ago persist today. Acute thrombus is readily imaged with all probes and modalities, but aged thrombus remains a challenge. Similarly, anti-coagulation continues to interfere with and often negate thrombus imaging efficacy, but heparin is clinically required in patients suspected of pulmonary embolism, deep venous thrombosis or coronary ruptured plaque prior to confirmatory diagnostic studies have been executed and interpreted. These fundamental issues can be overcome, but an innovative departure from the prior approaches will be needed.

Keywords: Thrombus; biomedical imaging; fibrin; platelet.

Figure 1

Acoustic enhancement of canine femoral artery thrombus, targeted with biotinylated anti-fibrin antibody, before (A) and after (B) exposure to targeted perfluorocarbon emulsion. Pre-contrast the acute arterial thrombus is poorly visualized with a 7.5-MHz linear-array, focused transducer. The transmural electrode (yellow arrow) and the wall boundaries of the femoral artery are clearly delineated. Post contrast the thrombus is easily recognized (red arrows before and after) exposure. Reproduced with permission Reference.

Figure 2

A White light image of canine femoral artery with recovered segmented thrombus, following recovery, formed as described in Figure 1 with electrical current to draw platelets toward anodal needle tip to propagate clot. B Ultrasound imaging obtained in vivo in the canine femoral artery prior to excision showing thrombus. C Ex vivo T1-weighted MRI image (1.5T) of excised artery in beaker of buffer. These data present the first demonstration of in vivo targeting of thrombus with a dual modality US–MR perfluorocarbon nanoparticle in canines showing close correspondence between the light, ultrasound, and MR images.

Figure 3

(A) CT blood pool signal in rabbits following IV injection of NanoK. CT scan imaging parameters were thickness 0.8, increment 0.8, kV 90, mAs 1500, resolution HIGH, collimation 4 × 0.75, pitch 0.35, rotation time 1.5 seconds, FOV 75 mm. Inset The concentration of bismuth (ICP) in blood vs time post-injection. Note that the background signal is at baseline in less than 30 minutes; (B, C) targeting in situ clot (thrombus) in rabbits; (D) 2 weeks clearance profile of bismuth from mice. Reproduced with permission.