Ischemic stroke continues to be one of leading sources of mortality and morbidity in the U.S. For clinicians who treat acute stroke victims, it is challenging to reliably discriminate salvageable from irreversibly injured tissue as well as to predict which patients are most likely to respond favorably to reperfusion therapy and which patients should have treatment withheld to avoid severe complications. Similar to the diagnostic parameters needed for the workup of acute stroke patients, the specific aims of this project will focus on: (1) the detection of irreversibly damaged tissue (stroke core);(2) the identification of potentially salvageable tissue (at-risk tissue);(3) the detection of leakage from the vascular into the interstitial space and prediction f hemorrhage (hemorrhagic transformation);and (4) the involvement of specific brain regions and their respective functions when assessing stroke severity and predicting outcome. Note that the difference between stroke core and at-risk tissue is often referred to as penumbra. With these four aims in mind, the overarching aim of this project is to collect CT and MR imaging data over a period of 4 years from 60 acute stroke victims (whose scans are performed ?30min apart) and to prospectively compare for the first time at such narrow time interval the ability of CT and MR to identify irreversibly damaged tissue, at-risk-tissue, and tissue that will most likely transform into (symptomatic) hemorrhage. This project will also assess each modality's ability to identify patients who will respond favorably to clot lysis/retrieval (a.k.a., reperfusion therapy) as well a those who will not benefit or who might actually sustain harm from the complications of reperfusion. Other project deliverables include improved MRI acquisition methods;optimized scan protocols for CT and MR in acute stroke;assessment of the role of iterative CT reconstructions in CT perfusion;new and refined outcome predictors;and a fully automated software that can be deployed at stroke centers nationwide (e.g., via NITRC). In summary, the project combines a sophisticated trial design with innovative imaging methods, medical image processing algorithms, and long-standing clinical and technical expertise in stroke imaging. This unique combination will produce invaluable clinical/imaging data from acute stroke patients;new clinical profiles and tools for patient triage;and a quantifiable assessment of the diagnostic strengths and weaknesses of advanced CT and MR methods as well as their clinical yield in acute stroke.

Public Health Relevance

Stroke is the primary source of disability in the United States. Each year, 800,000 patients suffer a new stroke in the U.S., and approximately 90% of these patients do not receive any acute therapy. This is primarily because they present beyond the short treatment window for approved therapies, and clinicians have no aces to imaging markers that can identify salvageable tissue in late time windows. With roughly 500,000 stroke patients potentially qualifying for urgent stroke imaging in the U.S., developing a more objective decision-making process for selecting patients to receive acute therapy would be of tremendous value to public health by lowering patient morbidity and increasing cost savings. This project aims to compare for the first time the diagnostic ability of CT and MR to reliably identify ! irreversibly damaged tissue, at-risk (but potentially salvageable) tissue, and the leakiness of injured vessels in acute stroke patients. It will also assess each modality's ability to identify patients who will respond favorably to clot lysis/retrieval (a.k.a., reperfusion therapy) as well a those patients who would not benefit or who might actually sustain harm from the complications of reperfusion. In addition, this project delivers improved MRI acquisition methods, optimized scan protocols for CT and MR in acute stroke, information about the role of a novel family of CT reconstruction in CT perfusion imaging, as well as predictors that take into account the location of a stroke lesion and its likely impact on a patient's clinical disability.

National Institute of Health (NIH)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Research Project (R01)
Project #
Application #
Study Section
Medical Imaging Study Section (MEDI)
Program Officer
Liu, Guoying
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Stanford University
Schools of Medicine
United States
Zip Code
Sharma, Anuj; Bammer, Roland; Stenger, V Andrew et al. (2015) Low peak power multiband spokes pulses for B1 (+) inhomogeneity-compensated simultaneous multislice excitation in high field MRI. Magn Reson Med 74:747-55
Van, Anh T; Aksoy, Murat; Holdsworth, Samantha J et al. (2015) Slab profile encoding (PEN) for minimizing slab boundary artifact in three-dimensional diffusion-weighted multislab acquisition. Magn Reson Med 73:605-13
Purushotham, Archana; Campbell, Bruce C V; Straka, Matus et al. (2015) Apparent diffusion coefficient threshold for delineation of ischemic core. Int J Stroke 10:348-53
O'Halloran, Rafael; Aksoy, Murat; Aboussouan, Eric et al. (2015) Real-time correction of rigid body motion-induced phase errors for diffusion-weighted steady-state free precession imaging. Magn Reson Med 73:565-76
Inoue, Manabu; Mlynash, Michael; Christensen, Soren et al. (2014) Early diffusion-weighted imaging reversal after endovascular reperfusion is typically transient in patients imaged 3 to 6 hours after onset. Stroke 45:1024-8
Van, Anh T; Holdsworth, Samantha J; Bammer, Roland (2014) In vivo investigation of restricted diffusion in the human brain with optimized oscillating diffusion gradient encoding. Magn Reson Med 71:83-94
Olivot, Jean Marc; Mlynash, Michael; Inoue, Manabu et al. (2014) Hypoperfusion intensity ratio predicts infarct progression and functional outcome in the DEFUSE 2 Cohort. Stroke 45:1018-23
Marks, Michael P; Lansberg, Maarten G; Mlynash, Michael et al. (2014) Effect of collateral blood flow on patients undergoing endovascular therapy for acute ischemic stroke. Stroke 45:1035-9
Aksoy, Didem; Bammer, Roland; Mlynash, Michael et al. (2013) Magnetic resonance imaging profile of blood-brain barrier injury in patients with acute intracerebral hemorrhage. J Am Heart Assoc 2:e000161
Kopeinigg, Daniel; Aksoy, Murat; Forman, Christoph et al. (2013) Prospective optical motion correction for 3D time-of-flight angiography. Magn Reson Med 69:1623-33

Showing the most recent 10 out of 54 publications