Noninvasive Thrombus Imaging in Patients With Ischemic Stroke

BACKGROUND: Determining the source of thromboembolism in patients with acute ischemic stroke remains challenging because current diagnostic approaches rely largely on circumstantial and inferential associations rather than direct identification of the cause of stroke. Fluorine-18 GP1 ([ 18 F]GP1) is a novel radiotracer that binds with high affinity and specificity to activated glycoprotein IIb/IIIa receptors on activated platelets. We aimed to determine whether hybrid [ 18 F]GP1 positron emission tomography (PET) and computed tomography angiography could identify in vivo cardiovascular thromboembolism in patients with acute ischemic stroke and provide a mechanism-based assessment of stroke etiology. METHODS: In a single-center prospective observational cohort study, 100 patients presenting with acute ischemic stroke underwent hybrid [ 18 F]GP1 PET/computed tomography angiography within 21 days of symptom onset in addition to standard-of-care stroke investigations. Stroke etiology was classified using the causative classification system by an expert stroke physician blinded to [ 18 F]GP1 PET findings. In parallel, [ 18 F]GP1 PET/computed tomography angiography images were analyzed independently by readers who were blinded to all clinical data and causative classification system classification. We assessed whether [ 18 F]GP1 PET/computed tomography angiography could identify the source of in vivo cardiovascular thromboembolism, influence stroke classification, and predict recurrent cerebrovascular events. RESULTS: Cardiovascular [ 18 F]GP1 uptake indicative of thrombosis was identified in nearly two-thirds (n=63) of participants, changing stroke classification in over a quarter (n=26) of patients. In those with stroke of undetermined cause, the source of thrombus was identified in 18 of 41 (44%) participants, which included nonstenotic carotid atherothrombosis, native cardiac valve thrombosis, and paradoxical thromboembolism. During a median follow-up of 613 (interquartile interval, 251–788) days, recurrent stroke or transient ischemic attack occurred in 14 patients, 13 (93%) of whom had cardiovascular [ 18 F]GP1 uptake at baseline. Cardiovascular [ 18 F]GP1 uptake was associated with a 10.4-fold increased risk of recurrent events (95% CI, 1.35–79.40; P =0.024). CONCLUSIONS: Noninvasive thrombosis imaging is a novel technique that enables direct in vivo identification of thrombus formation and frequently reveals the source of thromboembolism in patients with acute ischemic stroke. This approach represents a shift from inference-based to mechanism-based stroke classification with potential implications for targeted prevention strategies and better patient outcomes. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique Identifier: NCT05636748.