Thromboembolic diseases such as myocardial infarction, stroke, and pulmonary embolism (PE) are major causes of morbidity and mortality worldwide [1
]. Imaging is forefront in identifying thrombus. Currently, thrombus imaging relies on different modalities depending on the vascular territory. Carotid ultrasound is used to search for carotid thrombus, transesophageal echocardiography (TEE) searches for cardiac chamber clot, ultrasound searches for deep vein thrombosis (DVT), and CT has become the gold standard for PE detection. Despite the success of these techniques, there continues to be a strong push for a molecular imaging solution for thrombus detection and monitoring.
Molecular imaging of thrombosis has several motivations. First, there are certain vascular territories that are underserved. For instance, despite best imaging efforts some 30% to 40% of ischemic strokes are “cryptogenic,” that is, of indefinite cause, or in other words, the source of the thromboembolism is never identified [2
]. Underlying sources of cryptogenic stroke include atherosclerosis in the aortic arch [3
], intracranial arteries (eg, moderate stenosis) [4
], or vertebral artery stenosis thought to be unrelated to the stroke [5
]; or patent foramen ovale, which allows venous thrombus to embolize to the brain [6
]. Plaque rupture in the arch or other major vessels, in particular, is thought to be a major source of cryptogenic strokes [7
] but can be difficult to detect with routine methods.
There is also the added molecular specificity. Current clinical imaging methods detect the thrombus indirectly. For instance, in the ascending aorta, in the absence of mobile thrombus, conventional imaging identifies gross vessel wall thickening and cannot distinguish stable atherosclerotic plaque from plaque with associated thrombus. Recent TEE clinical trial data showed that the presence of thickened vessel wall in the aortic arch was not predictive of ischemic stroke [16
], although ulcerated
aortic arch plaques are associated with cryptogenic stroke [7
]. A thrombus-targeted molecular imaging approach could potentially identify clot in the presence of atherosclerotic plaque. Depending on the choice of imaging target, it may be possible to distinguish active, forming clots from older constituted thrombi. By targeting activated platelets or enzymes upregulated in the clotting cascade (eg, thrombin, factor XIII), it may be possible to visualize fresh thrombus.
Finally, there is a desire for a “one stop shopping” approach where a single modality could be used to identify thrombus throughout the body. For instance, in stroke follow-up, multiple examinations are required to search for the source of the embolus.