Non-invasive in vivo thrombus imaging in patients with ischaemic stroke or transient ischaemic attack

Abstract

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): British Heart Foundation Life Molecular Imaging provide reagents for GP1 production free of charge. Background and Purpose 18F-GP1 is a novel positron-emitting radiotracer that has high and specific binding affinity for the activated glycoprotein IIb/IIIa receptor, a key receptor in platelet activation and thrombus formation. Preliminary studies 18F-GP1 demonstrated excellent in vivo binding properties which enabled detection of intravascular thrombosis in a range of conditions including coronary thrombosis, left ventricular thrombus, pulmonary thromboembolism, and deep vein thrombosis. In a pilot proof-of-concept study, we aimed to determine its potential clinical application in establishing the role and origin of thrombus in stroke . Methods Autoradiography of 18F-GP1 uptake was performed on post-mortem samples of infarcted brain tissue following an acute ischaemic stroke and from control brain tissue without stroke. Eleven patients with recent ischaemic stroke (n=9) or transient ischaemic attack (n=2) underwent 18F-GP1 positron emission tomography and computed tomography angiography at median of 11 (absolute range 2–21) days from symptom onset. 18F-GP1 uptake (quantified by maximum target-to-background ratio, TBRmax) was assessed in the carotid arteries and brain. Results Ex vivo autoradiography of post-mortem infarcted brain tissue showed focal uptake corresponding to intraluminal thrombus within the culprit vessel and downstream microvasculature. There was also evidence of lower diffuse uptake within some of the infarcted brain tissue reflecting microthrombi within regions of reperfusion haemorrhage. In vivo 18F-GP1 uptake was identified in 9 of 11 patients: 3 in the carotid arteries only, 3 in the brain only and 3 in both the brain and carotid arteries. In those with carotid uptake, 3 participants had >50% stenosis and 3 had non-stenotic disease. One case had bilateral stenotic disease (>70%) but only the culprit carotid artery demonstrated 18F-GP1 uptake. The average uptake was higher in the culprit (median TBRmax 1.55 [interquartile range 1.26–1.82]) compared with the contralateral non-culprit carotid artery (TBRmax 1.22 [1.19–1.6]). In those with brain 18F-GP1 uptake (TBRmax 6.45 [4.89–7.65]), areas of acute infarction on computed tomography correlated with brain 18F-GP1 uptake in 6 cases. There was no brain 18F-GP1 uptake in the 7 cases without CT-defined acute cerebral infarction. Conclusions 18F-GP1 positron emission tomography and computed tomography angiography is a novel non-invasive method of identifying in vivo cerebrovascular thrombosis which holds major promise in understanding the role and origin of thrombosis in stroke.