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

Beth Whittington, Evangelos Tzolos, Rong Bing, Jack Andrews, Christophe Lucatelli, Mark G Macaskill, Adriana A S Tavares, Tim Clark, Nicholas L Mills, Jennifer Nash, Damini Dey, Piotr J Slomka, Norman Koglin, Andrew W. Stephens, Edwin J R van Beek, Colin Smith, Marc R Dweck, Michelle C Williams, William N Whiteley, Joanna M. WardlawDavid E Newby

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Background and Purpose. 18F-GP1 is a novel positron-emitting radiotracer that is highly specific for activated platelets and thrombus. In a proof-of-concept study, we aimed to determine its potential clinical application in establishing the role and origin of thrombus in ischemic stroke.
Methods. Eleven patients with recent ischemic stroke (n=9) or transient ischemic attack (n=2) underwent 18F-GP1 positron emission tomography and computed tomography angiography at median of 11 (range 2-21) days from symptom onset. 18F-GP1 uptake (maximum target-to-background ratio, TBRmax) was assessed in the carotid arteries and brain.
Results. 18F-GP1 uptake was identified in 10 of 11 patients: 4 in the carotid arteries only, 3 in the brain only and 3 in both the brain and carotid arteries. In those with carotid uptake, 4 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. 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 diffuse uptake within some of the infarcted brain tissue reflecting parenchymal petechial hemorrhage.
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.
Original languageEnglish
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Early online date13 Jul 2023
DOIs
Publication statusE-pub ahead of print - 13 Jul 2023

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