The long-term objective of this research program is to improve the care of patients suffering from acute ischemic stroke secondary to large vessel occlusion. Acute ischemic stroke affects up to 700,000 people a year in the United States and is the fourth leading cause of death. Approximately 10% of acute ischemic stroke patients present with large vessel occlusion which are associated with high rates of long-term morbidity and mortality. As of 2015, mechanical thrombectomy became standard of care for treatment of acute ischemic stroke from large vessel occlusion. Since then, there has been a significant increase in the use of mechanical thrombectomy for acute stroke treatment. Despite high revascularization rates (~80%), 50% of stroke patients still experience poor neurological outcomes. In addition, 20% of patients are not successfully revascularized due to limitations of current revascularization technologies. Rates of clot fragmentation during mechanical thrombectomy are high with most patients having residual tiny distal emboli in the ischemic territory and up to 10% of patients developing emboli in previously unaffected vascular beds due to fragmentation during clot retrieval. High rates of clot fragmentation and failure to remove the clot resulting in poor neurological outcomes suggest that in order to further advance the field of stroke intervention, we must turn our attention to the science of clot. In this R01 program we will embark on a comprehensive study of the histological, physical and imaging characteristics of clot in acute ischemic stroke with the ultimate goal of studying the efficacy of various revascularization strategies on different clot phenoytpes so that care of acute ischemic stroke patients can be improved. We propose a methodical approach to the study of clot in stroke.
Our first aim i s to characterize the histological characteristics of clots from a large sample of acute ischemic stroke patients from multiple institutions. Data from this registry will then be used to 1) identify clot phenotypes which will be made for further in vitro study and 2) identify histologic characteristics that are more commonly present in clots prone to fragmentation or difficult to remove clots.
Our second aim i s to identify imaging biomarkers to identify difficult clots by performing in vitro imaging of the clot phenotypes identified in the first aim.
Our third aim i s to determine which revascularization techniques are associated with superior outcomes when treating each clot phenotype. This will be performed using an in vitro flow model which replicates the physiological conditions of acute ischemic stroke in humans. If successful, this translational research program will directly improve patient outcomes by helping the stroke community better identify difficult to treat clots and provide data on which revascularization techniques are best suited for clots which are prone to fragmentation or difficult to remove.

Public Health Relevance

Acute ischemic stroke affects up to 800,000 people per year in the United States and is the fourth leading cause of death. Mechanical thrombectomy has become standard of care for acute ischemic stroke secondary to large vessel occlusion and up to 70,000 of these procedures will be performed annually by 2020. Despte best practice, 20% of stroke patients receiving mechanical thrombectomy do not get revascularized and among those who are revasularized, nearly 30% have distal emboli secondary to clot fragmentation. The goal of this project is to identify the histologic characteristics of clots which are more prone to fragmentation or more difficult to remove, develop imaging biomarkers to identify these difficult clots and identify the best thrombectomy techniques to achieve complete revascularization for these clots.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
Project #
Application #
Study Section
Medical Imaging Study Section (MEDI)
Program Officer
Koenig, James I
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Mayo Clinic, Rochester
United States
Zip Code
Brouwer, Patrick A; Brinjikji, Waleed; De Meyer, Simon F (2018) Clot Pathophysiology: Why Is It Clinically Important? Neuroimaging Clin N Am 28:611-623
Fitzgerald, Seán; Rizvi, Asim; Dai, Daying et al. (2018) Acute ischemic stroke secondary to cardiac embolus of a 'foreign body' material after a redo sternotomy for mitral valve replacement: A case report. Interv Neuroradiol :1591019918810538
Brinjikji, Waleed; Duffy, Sharon; Burrows, Anthony et al. (2017) Correlation of imaging and histopathology of thrombi in acute ischemic stroke with etiology and outcome: a systematic review. J Neurointerv Surg 9:529-534