Demonstration of pH imaging in acute stroke with endogenous ratiometric chemical exchange saturation transfer magnetic resonance imaging at 2 ppm

pH change is often considered a hallmark of metabolic disruption in diseases such as ischemic stroke and cancer. Chemical exchange saturation transfer (CEST) MRI, particularly amide proton transfer (APT), has emerged as a noninvasive pH imaging approach. However, there are changes in multipool CEST effects besides APT MRI. Our study investigated radiofrequency (RF) amplitude-based ratiometric CEST pH imaging in acute stroke. Briefly, adult male Wistar rats underwent CEST MRI under two RF saturation (B-1) levels of 0.75 and 1.5 mu T following middle cerebral artery occlusion. Magnetization transfer (MT), direct water saturation, CEST at 2 ppm (CEST@2 ppm), amine (2.75 ppm), and APT (3.5 ppm) effects were resolved with the multipool Lorentzian fitting approach. The ratiometric analysis was measured in the ischemic lesion and the contralateral normal area, which was also correlated with pH-specific MT and the relaxation normalized APT (MRAPT) index. MT, amine CEST effect, and their respective ratiometric indices did not show significant changes in ischemic regions (p > 0.05), as expected. Whereas APT decreased in the ischemic lesion for B-1 of 1.5 mu T (p < 0.01), the correlation between the amide ratio with MRAPT index was moderate (r = 0.52, p = 0.02). By comparison, the ischemic tissue showed a significantly increased CEST@2 ppm for both saturation levels from the contralateral normal area (p <= 0.01). Importantly, the CEST@2 ppm ratio decreased in the ischemic lesion (p < 0.01), which highly correlated with the MRAPT index (r = 0.93, p < 0.001). To summarize, our study demonstrated the feasibility of endogenous CEST@2 ppm ratiometric imaging of pH upon acute stroke, promising to detect pH changes in metabolic diseases.