title: pH-sensitive MRI demarcates graded tissue acidification during acute stroke - pH specificity enhancement with magnetization transfer and relaxation-normalized amide proton transfer (APT) MRI.
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.
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
authors.forename: Yingkun
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
authors.forename: Iris Yuwen
authors.initials: IY
authors.lastname: Zhou
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
authors.forename: Suk-Tak
authors.initials: ST
authors.lastname: Chan
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA; China-America Joint Neuroscience Institute, Xuanwu Hospital, Capital Medical University, Beijing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Neuroprotection Research Laboratory, Department of Radiology and Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
authors.forename: Emiri T
authors.initials: ET
authors.lastname: Mandeville
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Igarashi
authors.affiliation: Neuroprotection Research Laboratory, Department of Radiology and Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
authors.forename: Eng H
authors.initials: EH
authors.lastname: Lo
authors.affiliation: China-America Joint Neuroscience Institute, Xuanwu Hospital, Capital Medical University, Beijing, China.
authors.forename: Xunming
authors.initials: X
authors.lastname: Ji
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA; China-America Joint Neuroscience Institute, Xuanwu Hospital, Capital Medical University, Beijing, China; Neuroprotection Research Laboratory, Department of Radiology and Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA. Electronic address: pzhesun@mgh.harvard.edu.
authors.forename: Phillip Zhe
authors.initials: PZ
authors.lastname: Sun
mesh_terms: D000465:Algorithms; D000577:Amides / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000737:chemistry; D001921:Brain / Q000000981:diagnostic imaging*; D001923:Brain Chemistry; D006863:Hydrogen-Ion Concentration; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D060526:Magnetic Fields; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D011522:Protons; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D020521:Stroke / Q000000981:diagnostic imaging* / Q000378:metabolism*
chemical_list: D000577:Amides; D015415:Biomarkers; D011522:Protons