Our research aims to translate and evaluate the recently developed pH weighted MRI as a new imaging parameter for characterizing acute human ischemic stroke. Since the 1990s, there has been enormous advancement in stroke therapeutics and imaging, but early intervention is required for successful outcome. For instance, the conventional treatment window for recombinant tissue plasminogen activator (tPA) is within 3 hrs of stroke onset, which significantly limits its clinical applications. On the other hand, could salvageable ischemic tissue be detected, the thrombolytic therapy can be individualized to benefit patients admitted beyond the traditional treatment window. MRI, particularly perfusion and diffusion MRI, may highlight potentially salvageable ischemic tissue for treatment, and is being used as operational penumbra. However, the mismatch model is not optimal; portions of the diffusion lesion can be reversed by early reperfusion, while the perfusion deficit may contain hypoperfused area at no risk of infarction. Consequently, the development of reliable and specific imaging markers for salvageable tissue that complement perfusion and diffusion MRI, will be extremely valuable. pH, a tightly regulated tissue parameter, falls sharply upon metabolic impairment and may potentially serve as a sensitive metabolic marker for ischemic tissue. The proposed work will test whether a recently developed pH weighted MRI technique (amide proton transfer (APT) imaging) can become a new imaging marker for identifying early ischemic tissue. Previously, we have shown that pH weighted imaging provides information complementary to that attained by perfusion and diffusion MRI; the outer boundary of the hypoperfused area showing a decrease in pH without diffusion abnormality may correspond to ischemic penumbra, while the hypoperfused region at normal pH may represent benign oligemia. In addition, the final infarction area was not different from the pH weighted MRI deficit (p=0.84), but significantly different from the perfusion and diffusion MRI (p<0.001) using a permanent animal stroke model. In the proposed research, we will perform a pilot study to translate and evaluate pH weighted MRI for human acute ischemic stroke and our specific aims are: (1) to implement and optimize a fast multi-slice pH weighted MRI on clinical scanners (2) to evaluate pH weighted MRI as a new imaging marker complementary to perfusion and diffusion MRI. We hypothesize the pH weighted MRI will improve the diagnostic value of multi-parametric MRI and assist with image-guided stroke therapy.

Public Health Relevance

Ischemic stroke is a severe neurological disease with profound health and socioeconomic impact. The key for effective stroke therapy is to salvage ischemic tissue before it is irreversibly damaged. We propose to translate and evaluate the recently developed pH weighted MRI as a new imaging marker for human ischemic tissue, which has potential to improve the diagnostic value of MRI and assist with image-guided stroke therapy. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21NS061119-01A1
Application #
7530867
Study Section
Special Emphasis Panel (ZRG1-SBIB-J (90))
Program Officer
Golanov, Eugene V
Project Start
2008-07-01
Project End
2010-06-30
Budget Start
2008-07-01
Budget End
2009-06-30
Support Year
1
Fiscal Year
2008
Total Cost
$214,102
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
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
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
Sun, Phillip Zhe (2012) Simplified quantification of labile proton concentration-weighted chemical exchange rate (k(ws) ) with RF saturation time dependent ratiometric analysis (QUESTRA): normalization of relaxation and RF irradiation spillover effects for improved quantitative Magn Reson Med 67:936-42
Cheung, Jerry S; Wang, Enfeng; Zhang, XiaoAn et al. (2012) Fast radio-frequency enforced steady state (FRESS) spin echo MRI for quantitative T2 mapping: minimizing the apparent repetition time (TR) dependence for fast T2 measurement. NMR Biomed 25:189-94
Sun, Phillip Zhe; Wang, Enfeng; Cheung, Jerry S (2012) Imaging acute ischemic tissue acidosis with pH-sensitive endogenous amide proton transfer (APT) MRI--correction of tissue relaxation and concomitant RF irradiation effects toward mapping quantitative cerebral tissue pH. Neuroimage 60:1-6
Cheung, Jerry S; Wang, Xiaoying; Zhe Sun, Phillip (2011) Magnetic resonance characterization of ischemic tissue metabolism. Open Neuroimag J 5:66-73
Sun, Phillip Zhe; Cheung, Jerry S; Wang, Enfeng et al. (2011) Association between pH-weighted endogenous amide proton chemical exchange saturation transfer MRI and tissue lactic acidosis during acute ischemic stroke. J Cereb Blood Flow Metab 31:1743-50
Sun, Phillip Zhe; Wang, Enfeng; Cheung, Jerry S et al. (2011) Simulation and optimization of pulsed radio frequency irradiation scheme for chemical exchange saturation transfer (CEST) MRI-demonstration of pH-weighted pulsed-amide proton CEST MRI in an animal model of acute cerebral ischemia. Magn Reson Med 66:1042-8
Sun, Phillip Zhe; Cheung, Jerry S; Wang, Enfeng et al. (2011) Fast multislice pH-weighted chemical exchange saturation transfer (CEST) MRI with Unevenly segmented RF irradiation. Magn Reson Med 65:588-94
Singhal, Aneesh B; Hajj-Ali, Rula A; Topcuoglu, Mehmet A et al. (2011) Reversible cerebral vasoconstriction syndromes: analysis of 139 cases. Arch Neurol 68:1005-12

Showing the most recent 10 out of 15 publications