Stroke is the number 1 cause of disability in the United States and a global public health problem. Globally, approximately 15 million people suffer a stroke each year, leading to 5 million deaths and another 5 million patients who suffer permanent disability from their stroke. Strokes that are caused by blockage of large blood vessels supplying blood to the brain are typically the most disabling. Over the last 5 years, there have been major breakthroughs in acute stroke therapy for this type of stroke. In 2015, multiple trials demonstrated a profound benefit from endovascular stroke therapy for patients with a large vessel ischemic stroke who present in the early time-window (within 6 hours after symptom onset). This success was followed by the DEFUSE 3 and DAWN trials showing a very strong benefit from endovascular therapy in the delayed time-window (6-24 hours after symptom onset). These therapies have now become standard of care at specialty hospitals (comprehensive stroke centers) across the country. Despite this new highly effective therapy, stroke-related disability continues to be substantial for patients with large-vessel occlusions, because of brain damage that occurs in the time-period before patients receive endovascular therapy that restores blood flow to the brain. The time period before blood flow is restored can be long (several hours) especially if patients need to be transferred from a community hospital that does not have the capability to provide endovascular therapy to a comprehensive stroke center that does. Because of this delay, significant brain damage can occur between the time that a patient initially presents to a hospital and the time that blood flow is restored. To address this problem, we need to conduct clinical trials of therapies that protect the brain in the crucial time-period before blood flow is restored. In order to conduct such trials, we first need tools to identify patients who are most likely to benefit from treatments that protect the brain and tools that can be used to determine if the treatments are effective. The overall aim of this project is to develop these tools. We will achieve this aim using both an existing imaging dataset and using new data that we will obtain from patients who are being transferred from a community hospital to a comprehensive stroke center for endovascular therapy. To identify patients who will likely benefit from treatments that protect the brain, we will develop a CT-based tool that visualizes how much brain damage a patient is likely to sustain during transport. To be able to determine if a treatment is effective at protecting the brain, we will develop a CT-based tool that can accurately measure the amount of brain damage (infarct volume) that is already present prior to transport.

Public Health Relevance

To reduce the public health burden of stroke, the number one cause of disability in the United States, we need treatments to protect the brain in the crucial time-period before blood flow to the brain can be restored. In order to test treatments that protect the brain in clinical trials, we need methods to identify patients who are most likely to benefit from them and methods to determine if the treatments are effective. In this project, we will develop both.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
2R01NS075209-06
Application #
9740290
Study Section
Acute Neural Injury and Epilepsy Study Section (ANIE)
Program Officer
Moy, Claudia S
Project Start
2011-09-01
Project End
2024-04-30
Budget Start
2019-05-15
Budget End
2020-04-30
Support Year
6
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Stanford University
Department
Neurology
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
Demeestere, Jelle; Scheldeman, Lauranne; Cornelissen, Sandra A et al. (2018) Alberta Stroke Program Early CT Score Versus Computed Tomographic Perfusion to Predict Functional Outcome After Successful Reperfusion in Acute Ischemic Stroke. Stroke 49:2361-2367
Demeestere, Jelle; Albers, Gregory W; Lansberg, Maarten et al. (2018) Response by Demeestere et al to Letter Regarding Article, ""Alberta Stroke Program Early CT Score Versus Computed Tomographic Perfusion to Predict Functional Outcome After Successful Reperfusion in Acute Ischemic Stroke"". Stroke :STROKEAHA118023955
Tsai, Jenny P; Mlynash, Michael; Christensen, Soren et al. (2018) Time From Imaging to Endovascular Reperfusion Predicts Outcome in Acute Stroke. Stroke 49:952-957
Lansberg, Maarten G; Christensen, Soren; Kemp, Stephanie et al. (2017) Computed tomographic perfusion to Predict Response to Recanalization in ischemic stroke. Ann Neurol 81:849-856
Lemmens, Robin; Hamilton, Scott A; Liebeskind, David S et al. (2016) Effect of endovascular reperfusion in relation to site of arterial occlusion. Neurology 86:762-70
Kasasbeh, Aimen S; Christensen, Søren; Straka, Matus et al. (2016) Optimal Computed Tomographic Perfusion Scan Duration for Assessment of Acute Stroke Lesion Volumes. Stroke 47:2966-2971
Lansberg, Maarten G; Bhat, Ninad S; Yeatts, Sharon D et al. (2016) Power of an Adaptive Trial Design for Endovascular Stroke Studies: Simulations Using IMS (Interventional Management of Stroke) III Data. Stroke 47:2931-2937
Mishra, Nishant K; Christensen, Søren; Wouters, Anke et al. (2015) Reperfusion of very low cerebral blood volume lesion predicts parenchymal hematoma after endovascular therapy. Stroke 46:1245-9
Lansberg, Maarten G; Cereda, Carlo W; Mlynash, Michael et al. (2015) Response to endovascular reperfusion is not time-dependent in patients with salvageable tissue. Neurology 85:708-14
Mishra, Nishant K; Albers, Gregory W; Christensen, Søren et al. (2014) Comparison of magnetic resonance imaging mismatch criteria to select patients for endovascular stroke therapy. Stroke 45:1369-74