Early tPA thrombolysis is critical for ischemic stroke treatment, known as """"""""time is brain"""""""". However, very few patients present for treatment within 3 hours of the stroke onset, the narrow therapeutic window of tPA. Because ischemic tissue injury is heterogeneous, imaging plays a crucial role in stroke patient management. Perfusion and diffusion (PWI and DWI) MRI have proven clinically useful as an imaging approximation to the ischemic tissue prior to infarction (penumbra). The rationale is that PWI identifies hypoperfused tissue while DWI defines the severely damaged ischemic core. As such, the PWI/DWI mismatch identifies the ischemic penumbra, and has been adopted in multiple trials to select patients for tPA therapy. Additionally, variant DWI- based paradigms, including MR angiogram (MRA)/DWI and clinical/DWI have been chosen to overcome the technical challenges of PWI to more practically guide tPA therapy in clinic. However, it is now recognized that the approximation of the DWI lesion as ischemic core is oversimplified. As noted in the recommendation for imaging of acute ischemic stroke from American Heart Association in both 2009 and 2013, """"""""DWI is not a simple indicator of irreversible infarction but a complex variable that requires more study."""""""" Our proposal to develop kurtosis MRI as a means to augment the standard DWI is thus directly responsive to this call. We have recently established kurtosis MRI for imaging acute stroke. We demonstrated that kurtosis MRI detects the most severely damaged ischemic tissue within the conventional DWI lesion. Importantly, using a transient filament animal stroke model, we showed that kurtosis MRI defines the irreversibly damaged ischemic core while the DWI lesion without kurtosis abnormality recovers upon reperfusion. A key step before we can translate the new kurtosis MRI and guide tPA therapy in acute stroke patients is to evaluate it in an embolic stroke model that more reasonably mimics human stroke. Our central hypothesis is that kurtosis MRI is an ischemic core-specific index, which can overcome the limitation of conventional DWI for imaging acute stroke. Specifically, our proposal will use histology to verify that kurtosis MRI defines more severely injured ischemic tissue (Aim 1), determine kurtosis lesion response to tPA therapy in experimental stroke models (Aim 2), and translate and evaluate kurtosis MRI in the acute stroke clinical setting (Aim 3). The success of our proposal will establish the biologica significance of kurtosis MRI, and establish DKI in the acute stroke clinical setting for future larger scale clinical studies.

Public Health Relevance

Ongoing efforts to develop imaging-guided stroke treatment are hindered by the limitations of the standard DWI. Our proposal aims to evaluate kurtosis as a new MRI index of more severely injured ischemic tissue. Kurtosis MRI will be evaluated in experimental stroke models prior to clinical translation to refine the standard DWI in imaging acute stroke patients.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21NS085574-02
Application #
8730739
Study Section
Medical Imaging Study Section (MEDI)
Program Officer
Babcock, Debra J
Project Start
2013-09-15
Project End
2015-08-31
Budget Start
2014-09-01
Budget End
2015-08-31
Support Year
2
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199
Yin, Jianzhong; Sun, Haizhen; Wang, Zhiyun et al. (2018) Diffusion Kurtosis Imaging of Acute Infarction: Comparison with Routine Diffusion and Follow-up MR Imaging. Radiology 287:651-657
Wu, Yin; Zhou, Iris Y; Igarashi, Takahiro et al. (2018) A generalized ratiometric chemical exchange saturation transfer (CEST) MRI approach for mapping renal pH using iopamidol. Magn Reson Med 79:1553-1558
Wu, Yin; Zhou, Iris Yuwen; Lu, Dongshuang et al. (2018) pH-sensitive amide proton transfer effect dominates the magnetization transfer asymmetry contrast during acute ischemia-quantification of multipool contribution to in vivo CEST MRI. Magn Reson Med 79:1602-1608
Zhou, Iris Yuwen; Wang, Enfeng; Cheung, Jerry S et al. (2017) Quantitative chemical exchange saturation transfer (CEST) MRI of glioma using Image Downsampling Expedited Adaptive Least-squares (IDEAL) fitting. Sci Rep 7:84
Yuwen Zhou, Iris; Wang, Enfeng; Cheung, Jerry S et al. (2017) Direct saturation-corrected chemical exchange saturation transfer MRI of glioma: Simplified decoupling of amide proton transfer and nuclear overhauser effect contrasts. Magn Reson Med 78:2307-2314
Wu, Yin; Kim, Jinsuh; Chan, Suk-Tak et al. (2016) Comparison of image sensitivity between conventional tensor-based and fast diffusion kurtosis imaging protocols in a rodent model of acute ischemic stroke. NMR Biomed 29:625-30
Hirai, Kelsi K; Groisser, Benjamin N; Copen, William A et al. (2016) Comparing prognostic strength of acute corticospinal tract injury measured by a new diffusion tensor imaging based template approach versus common approaches. J Neurosci Methods 257:204-13
Guo, Yingkun; Zhou, Iris Yuwen; Chan, Suk-Tak et al. (2016) pH-sensitive MRI demarcates graded tissue acidification during acute stroke - pH specificity enhancement with magnetization transfer and relaxation-normalized amide proton transfer (APT) MRI. Neuroimage 141:242-249
Lima, Fabricio O; Silva, Gisele S; Furie, Karen L et al. (2016) Field Assessment Stroke Triage for Emergency Destination: A Simple and Accurate Prehospital Scale to Detect Large Vessel Occlusion Strokes. Stroke 47:1997-2002
Zhou, Iris Yuwen; Fuss, Taylor L; Igarashi, Takahiro et al. (2016) Tissue Characterization with Quantitative High-Resolution Magic Angle Spinning Chemical Exchange Saturation Transfer Z-Spectroscopy. Anal Chem 88:10379-10383

Showing the most recent 10 out of 13 publications