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Updated: Mar 17, 2026
A Magnetic Resonance Imaging Protocol for Stroke Onset Time Estimation in Permanent Cerebral Ischemia
Published on: September 16, 2017
pH-sensitive MRI demarcates graded tissue acidification during acute stroke - pH specificity enhancement with
Yingkun Guo1, Iris Yuwen Zhou1, Suk-Tak Chan1
1Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
Abstract:
pH-sensitive amide proton transfer (APT) MRI provides a surrogate metabolic biomarker that complements the widely-used perfusion and diffusion imaging. However, the endogenous APT MRI is often calculated using the asymmetry analysis (MTRasym), which is susceptible to an inhomogeneous shift due to concomitant semisolid magnetization transfer (MT) and nuclear overhauser (NOE) effects. Although the intact brain tissue has little pH variation, white and gray matter appears distinct in the MTRasym image. Herein we showed that the heterogeneous MTRasym shift not related to pH highly correlates with MT ratio (MTR) and longitudinal relaxation rate (R1w), which can be reasonably corrected using the multiple regression analysis. Because there are relatively small MT and R1w changes during acute stroke, we postulate that magnetization transfer and relaxation-normalized APT (MRAPT) analysis increases MRI specificity to acidosis over the routine MTRasym image, hence facilitates ischemic lesion segmentation. We found significant differences in perfusion, pH and diffusion lesion volumes (P<0.001, ANOVA). Furthermore, MRAPT MRI depicted graded ischemic acidosis, with the most severe acidosis in the diffusion lesion (-1.05±0.29%/s), moderate acidification within the pH/diffusion mismatch (i.e., metabolic penumbra, -0.67±0.27%/s) and little pH change in the perfusion/pH mismatch (i.e., benign oligemia, -0.04±0.14%/s), providing refined stratification of ischemic tissue injury.
Insights
Magnetization transfer and relaxation-normalized amide proton transfer (MRAPT) MRI improves pH sensitivity over standard MTRasym imaging. This technique enhances specificity for acidosis, aiding in the precise segmentation of ischemic stroke lesions.
Area of Science:
- Biomedical Imaging
- Neuroimaging
- Medical Physics
Background:
- Amide proton transfer (APT) MRI offers metabolic insights complementary to perfusion and diffusion imaging.
- Standard MTRasym calculation for APT MRI is prone to artifacts from magnetization transfer (MT) and nuclear Overhauser effects (NOE).
- These artifacts cause heterogeneous shifts in MTRasym, particularly between white and gray matter, unrelated to pH.
Purpose of the Study:
- To develop and validate a corrected APT MRI method (MRAPT) for improved pH specificity in acute stroke.
- To assess the utility of MRAPT for differentiating ischemic tissue injury and facilitating lesion segmentation.
Main Methods:
- Multiple regression analysis was employed to correct MTRasym for MT and R1w influences.
- Magnetization transfer (MT) ratio and longitudinal relaxation rate (R1w) were measured alongside APT MRI.
- MRAPT analysis was compared against routine MTRasym for specificity in detecting acidosis during acute stroke.
Main Results:
- MRAPT analysis demonstrated increased specificity to acidosis compared to MTRasym, particularly in the context of acute stroke.
- Significant differences were observed in perfusion, pH, and diffusion lesion volumes (P<0.001).
- MRAPT MRI revealed graded ischemic acidosis, accurately distinguishing severe acidosis in diffusion lesions, moderate acidification in the metabolic penumbra, and minimal pH changes in benign oligemia.
Conclusions:
- MRAPT analysis effectively corrects for confounding MT and R1w effects, enhancing the pH sensitivity of APT MRI.
- This improved specificity facilitates more accurate ischemic lesion segmentation and characterization.
- MRAPT MRI provides refined stratification of ischemic tissue injury, offering valuable insights into stroke pathophysiology.
