The role of perfusion imaging in the management of acute ischemic stroke (AIS) is to establish the degree and extent of reduced regional cerebral blood flow (CBF), and to contribute to the identification of the ischemic penumbra - regions of hypoperfusion that may be salvaged by thrombolytic and/or endovascular recanalization therapies. Dynamic susceptibility contrast enhanced (DSC) techniques have been the main MR perfusion imaging method used in AIS. The initial DEFUSE cohort study suggested that perfusion-diffusion mismatch may predict clinical responses to thrombolytic therapy. Randomized trials (e.g. EPITHET, DIAS), however, have yielded ambiguous findings showing only trends to benefit when using perfusion and diffusion mismatch as a patient selection criterion for thrombolysis. To date, the value for identifying the ischemic penumbra in the management of AIS remains less than firmly established. Arterial spin labeled (ASL) perfusion MRI is an emerging non-contrast MRI method to measure CBF. With the latest implementation using pseudo- continuous ASL (pCASL) and background suppressed 3D GRASE, we recently demonstrated that ASL can be reliably applied for acute stroke imaging, and provides consistent results with DSC perfusion MRI for delineating hypoperfused brain regions. ASL also demonstrates the potential to illustrate collateral blood supply through delayed arterial transit effects as well as the use of vessel-selective ASL. Because ASL is easy, fast and does not require the injection of contrast agents, serial perfusion imaging can be performed to trace the dynamics of reperfusion and correlate with clinical outcomes. The main purpose of this proposal is to further develop, refine and evaluate the clinical utility of ASL for perfusion imaging in AIS In Aim 1, we will improve ASL perfusion quantification by including arterial transit time (ATT) measurement and perform a systematic evaluation of ASL and DSC perfusion MRI.
In Aim 2, we will evaluate the utility of multi-delay ASL and vessel encoded pCASL in determining the state of collateral perfusion in AIS by comparison with the gold standard of digital subtraction angiography.
In Aim 3, we will evaluate the clinical utility of serial ASL perfusion imaging by correlating with clinical outcomes such as reperfusion, hemorrhagic transformation (HT) and DSC measures of blood-brain barrier (BBB) permeability in AIS patients. We hypothesize that ASL hyperperfusion is associated with reperfusion, BBB leakage and is a predictor of HT in AIS patients. The present project capitalizes on the extremely rich clinical resources for AIS neuroimaging and treatments at UCLA. It is a translational project with the goal to develop and validate an entirely noninvasive and quantitative MRI method for routine clinical evaluation of AIS as well as other cerebrovascular disorders.

Public Health Relevance

Stroke is the fourth leading cause of death in the US with more than 137,000 people dying each year from stroke. This project will develop, refine and validate a noninvasive and quantitative MRI method to measure cerebral blood flow in acute stroke patients, and is expected to improve the management and treatment of stroke patients.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS081077-02
Application #
8543780
Study Section
Special Emphasis Panel (ZRG1-DTCS-A (81))
Program Officer
Babcock, Debra J
Project Start
2012-09-15
Project End
2015-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
2
Fiscal Year
2013
Total Cost
$409,264
Indirect Cost
$143,508
Name
University of California Los Angeles
Department
Neurology
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
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Li, Chun-Xia; Patel, Sudeep; Wang, Danny J J et al. (2014) Effect of high dose isoflurane on cerebral blood flow in macaque monkeys. Magn Reson Imaging 32:956-60
Wang, Rui; Yu, Songlin; Alger, Jeffry R et al. (2014) Multi-delay arterial spin labeling perfusion MRI in moyamoya disease--comparison with CT perfusion imaging. Eur Radiol 24:1135-44
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Wang, Danny J J; Alger, Jeffry R; Qiao, Joe X et al. (2013) Multi-delay multi-parametric arterial spin-labeled perfusion MRI in acute ischemic stroke - Comparison with dynamic susceptibility contrast enhanced perfusion imaging. Neuroimage Clin 3:1-7
Yan, Lirong; Salamon, Noriko; Wang, Danny J J (2013) Time-resolved noncontrast enhanced 4-D dynamic magnetic resonance angiography using multibolus TrueFISP-based spin tagging with alternating radiofrequency (TrueSTAR). Magn Reson Med :

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