Noninvasive In Vivo Thrombus Imaging in Patients With Ischemic Stroke or Transient Ischemic 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 Whiteley; Joanna M Wardlaw; David E Newby

doi:10.1161/ATVBAHA.122.318204

Noninvasive In Vivo Thrombus Imaging in Patients With Ischemic Stroke or Transient Ischemic 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 Whiteley, Joanna M WardlawDavid E Newby

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

BACKGROUND: 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 a median of 11 (range, 2-21) days from symptom onset. 18F-GP1 uptake (maximum target-to-background ratio) 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 nonstenotic 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 maximum target-to-background ratio, 1.55 [interquartile range, 1.26-1.82]) compared with the contralateral nonculprit carotid artery (maximum target-to-background ratio, 1.22 [1.19-1.6]). In those with brain 18F-GP1 uptake (maximum target-to-background ratio, 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 postmortem 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 noninvasive method of identifying in vivo cerebrovascular thrombosis, which holds major promise in understanding the role and origin of thrombosis in stroke.

REGISTRATION: URL: https://www.

CLINICALTRIALS: gov; Unique identifier: NCT03943966.

Original language	English
Journal	Arteriosclerosis, Thrombosis, and Vascular Biology
Early online date	13 Jul 2023
DOIs	https://doi.org/10.1161/ATVBAHA.122.318204
Publication status	E-pub ahead of print - 13 Jul 2023

Access to Document

10.1161/ATVBAHA.122.318204

ATVBAHA.122.318204Final published version, 556 KBLicence: Creative Commons: Attribution (CC-BY)

2 Active
5 Finished

Incidental coronary calcification on thoracic computed tomography
Williams, M., Mills, N. & Newby, D.
UK-based charities
1/02/21 → 31/01/26
Project: Research
High-Sensitivity Cardiac Troponin Beyond the Acute Coronary Syndrome
Mills, N., Anand, A., Chapman, A., Ferry, A., Newby, D., Strachan, F. & Tsanas, T.
UK-based charities
1/06/20 → 31/05/25
Project: Research
Role and origin of thromboembolism in the pathogenesis of ischaemic stroke
Newby, D.
UK-based charities
1/08/21 → 31/07/24
Project: Research

Edinburgh Imaging Facility
Anne Grant (Manager), Edwin van Beek (Manager) & Scott Semple (Manager)
Deanery of Clinical Sciences
Facility/equipment: Facility
Edinburgh Preclinical Imaging
Carmel Moran (Manager), Adrian Thomson (Manager), Ross J Lennen (Manager), Adriana Tavares (Manager), Carlos J. Alcaide-Corral (Manager), Tim Morgan (Other), Islay Cranston (Other) & Kerry O'Rourke (Other)
Deanery of Clinical Sciences
Facility/equipment: Facility

Cite this

Whittington, B., Tzolos, E., Bing, R., Andrews, J., Lucatelli, C., MacAskill, M. G., Tavares, A. A. S., Clark, T., Mills, N. L., Nash, J., Dey, D., Slomka, P. J., Koglin, N., Stephens, A. W., van Beek, E. J. R., Smith, C., Dweck, M. R., Williams, M. C., Whiteley, W., ... Newby, D. E. (2023). Noninvasive In Vivo Thrombus Imaging in Patients With Ischemic Stroke or Transient Ischemic Attack. Arteriosclerosis, Thrombosis, and Vascular Biology. Advance online publication. https://doi.org/10.1161/ATVBAHA.122.318204

@article{882a53917f0047faa13d71ac0af1a4de,

title = "Noninvasive In Vivo Thrombus Imaging in Patients With Ischemic Stroke or Transient Ischemic Attack",

abstract = "BACKGROUND: 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 a median of 11 (range, 2-21) days from symptom onset. 18F-GP1 uptake (maximum target-to-background ratio) 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 nonstenotic 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 maximum target-to-background ratio, 1.55 [interquartile range, 1.26-1.82]) compared with the contralateral nonculprit carotid artery (maximum target-to-background ratio, 1.22 [1.19-1.6]). In those with brain 18F-GP1 uptake (maximum target-to-background ratio, 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 postmortem 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 noninvasive method of identifying in vivo cerebrovascular thrombosis, which holds major promise in understanding the role and origin of thrombosis in stroke. REGISTRATION: URL: https://www.CLINICALTRIALS: gov; Unique identifier: NCT03943966.",

author = "Beth Whittington and Evangelos Tzolos and Rong Bing and Jack Andrews and Christophe Lucatelli and MacAskill, {Mark G} and Tavares, {Adriana A S} and Tim Clark and Mills, {Nicholas L} and Jennifer Nash and Damini Dey and Slomka, {Piotr J} and Norman Koglin and Stephens, {Andrew W} and {van Beek}, {Edwin J R} and Colin Smith and Dweck, {Marc R} and Williams, {Michelle C} and William Whiteley and Wardlaw, {Joanna M} and Newby, {David E}",

note = "Sources of Funding B. Whittington (FS/CRTF/21/24129), E. Tzolos (FS/CRTF/20/24086), N.L. Mills (CH/F/21/90010 and RG/20/10/34966), M.C. Williams (FS/ ICRF/20/26002, FS/11/014, and CH/09/002), D.E. Newby (CH/09/002, RG/16/10/32375, and RE/18/5/34216), and M.R. Dweck (FS/14/78/31020) are supported by the British Heart Foundation. D.E. Newby is the recipient of a Welcome Trust Senior Investigator Award (WT103782AIA). E.J.R. van Beek is supported by the Scottish Imaging Network: a Platform of Scientific Excellence. M.R. Dweck is supported by the Sir Jules Thorn Biomedical Research Award 2015 (15/JTA). FusionQuant analysis tools and P.J. Slomka are supported by the National Institutes of Health (NIH) National Heart, Lung, and Blood Institute (NHLBI) grant 5R01HL135557. D. Dey is supported by the NIH NHLBI grant 1R01HL148787-01A1. W. Whiteley is supported by the Chief Scientist{\textquoteright}s Office, Alzheimer{\textquoteright}s Society. J.M. Wardlaw is supported by the UK Dementia Research Institute, which receives its funding from DRI, Ltd, funded by the UK Medical Research Council, Alzheimer{\textquoteright}s Society and Alzheimer{\textquoteright}s Research UK. The Ed- inburgh Clinical Research Facilities, Edinburgh Imaging Facility, and Edinburgh Clinical Trials Unit are supported by the National Health Service Research Scot- land through the National Health Service Lothian Health Board. For the purpose of open access, the author has applied a Creative Commons Attribution (CC-BY) licence to any author accepted manuscript version arising from this submission.",

year = "2023",

month = jul,

day = "13",

doi = "10.1161/ATVBAHA.122.318204",

language = "English",

journal = "Arteriosclerosis, Thrombosis, and Vascular Biology",

issn = "1079-5642",

publisher = "Lippincott Williams & Wilkins",

}

Whittington, B, Tzolos, E, Bing, R, Andrews, J, Lucatelli, C , MacAskill, MG , Tavares, AAS, Clark, T, Mills, NL, Nash, J, Dey, D, Slomka, PJ, Koglin, N, Stephens, AW, van Beek, EJR , Smith, C , Dweck, MR , Williams, MC , Whiteley, W , Wardlaw, JM & Newby, DE 2023, 'Noninvasive In Vivo Thrombus Imaging in Patients With Ischemic Stroke or Transient Ischemic Attack', Arteriosclerosis, Thrombosis, and Vascular Biology. https://doi.org/10.1161/ATVBAHA.122.318204

TY - JOUR

T1 - Noninvasive In Vivo Thrombus Imaging in Patients With Ischemic Stroke or Transient Ischemic Attack

AU - Whittington, Beth

AU - Tzolos, Evangelos

AU - Bing, Rong

AU - Andrews, Jack

AU - Lucatelli, Christophe

AU - MacAskill, Mark G

AU - Tavares, Adriana A S

AU - Clark, Tim

AU - Mills, Nicholas L

AU - Nash, Jennifer

AU - Dey, Damini

AU - Slomka, Piotr J

AU - Koglin, Norman

AU - Stephens, Andrew W

AU - van Beek, Edwin J R

AU - Smith, Colin

AU - Dweck, Marc R

AU - Williams, Michelle C

AU - Whiteley, William

AU - Wardlaw, Joanna M

AU - Newby, David E

N1 - Sources of Funding B. Whittington (FS/CRTF/21/24129), E. Tzolos (FS/CRTF/20/24086), N.L. Mills (CH/F/21/90010 and RG/20/10/34966), M.C. Williams (FS/ ICRF/20/26002, FS/11/014, and CH/09/002), D.E. Newby (CH/09/002, RG/16/10/32375, and RE/18/5/34216), and M.R. Dweck (FS/14/78/31020) are supported by the British Heart Foundation. D.E. Newby is the recipient of a Welcome Trust Senior Investigator Award (WT103782AIA). E.J.R. van Beek is supported by the Scottish Imaging Network: a Platform of Scientific Excellence. M.R. Dweck is supported by the Sir Jules Thorn Biomedical Research Award 2015 (15/JTA). FusionQuant analysis tools and P.J. Slomka are supported by the National Institutes of Health (NIH) National Heart, Lung, and Blood Institute (NHLBI) grant 5R01HL135557. D. Dey is supported by the NIH NHLBI grant 1R01HL148787-01A1. W. Whiteley is supported by the Chief Scientist’s Office, Alzheimer’s Society. J.M. Wardlaw is supported by the UK Dementia Research Institute, which receives its funding from DRI, Ltd, funded by the UK Medical Research Council, Alzheimer’s Society and Alzheimer’s Research UK. The Ed- inburgh Clinical Research Facilities, Edinburgh Imaging Facility, and Edinburgh Clinical Trials Unit are supported by the National Health Service Research Scot- land through the National Health Service Lothian Health Board. For the purpose of open access, the author has applied a Creative Commons Attribution (CC-BY) licence to any author accepted manuscript version arising from this submission.

PY - 2023/7/13

Y1 - 2023/7/13

N2 - BACKGROUND: 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 a median of 11 (range, 2-21) days from symptom onset. 18F-GP1 uptake (maximum target-to-background ratio) 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 nonstenotic 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 maximum target-to-background ratio, 1.55 [interquartile range, 1.26-1.82]) compared with the contralateral nonculprit carotid artery (maximum target-to-background ratio, 1.22 [1.19-1.6]). In those with brain 18F-GP1 uptake (maximum target-to-background ratio, 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 postmortem 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 noninvasive method of identifying in vivo cerebrovascular thrombosis, which holds major promise in understanding the role and origin of thrombosis in stroke. REGISTRATION: URL: https://www.CLINICALTRIALS: gov; Unique identifier: NCT03943966.

AB - BACKGROUND: 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 a median of 11 (range, 2-21) days from symptom onset. 18F-GP1 uptake (maximum target-to-background ratio) 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 nonstenotic 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 maximum target-to-background ratio, 1.55 [interquartile range, 1.26-1.82]) compared with the contralateral nonculprit carotid artery (maximum target-to-background ratio, 1.22 [1.19-1.6]). In those with brain 18F-GP1 uptake (maximum target-to-background ratio, 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 postmortem 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 noninvasive method of identifying in vivo cerebrovascular thrombosis, which holds major promise in understanding the role and origin of thrombosis in stroke. REGISTRATION: URL: https://www.CLINICALTRIALS: gov; Unique identifier: NCT03943966.

U2 - 10.1161/ATVBAHA.122.318204

DO - 10.1161/ATVBAHA.122.318204

M3 - Article

C2 - 37439259

SN - 1079-5642

JO - Arteriosclerosis, Thrombosis, and Vascular Biology

JF - Arteriosclerosis, Thrombosis, and Vascular Biology

ER -

Noninvasive In Vivo Thrombus Imaging in Patients With Ischemic Stroke or Transient Ischemic Attack

Abstract / Description of output

Access to Document

Fingerprint

Projects

Incidental coronary calcification on thoracic computed tomography

High-Sensitivity Cardiac Troponin Beyond the Acute Coronary Syndrome

Role and origin of thromboembolism in the pathogenesis of ischaemic stroke

Equipment

Edinburgh Imaging Facility

Edinburgh Preclinical Imaging

Cite this