Dual contrast CEST MRI for pH-weighted imaging in stroke

Purpose: pH enhanced (pH(enh)) CEST imaging combines the pH sensitivity from amide and guanidino signals, but the saturation parameters have not been optimized. We propose pH(dual) as a variant of pH(enh) that suppresses background signal variations, while enhancing pH sensitivity and potential for imaging ischemic brain injury of stroke.Methods: Simulation and in vivo rodent stroke experiments of pH(enh) MRI were performed with varied RF saturation powers for both amide and guanidino protons to optimize the contrast between lesion/normal tissues, while simultaneously minimizing signal variations across different types of normal tissues. In acute stroke, contrast and volume ratio measured by pHdual imaging were compared with an amide-CEST approach, and perfusion and diffusion MRI.Results: Simulation experiments indicated that amide and guanidino CEST signals exhibit unique sensitivities across different pH ranges, with pH(enh) producing greater sensitivity over a broader pH regime. The pH(enh) data of rodent stroke brain demonstrated that the lesion/normal tissue contrast was maximized for an RF saturation power pair of 0.5 mu T at 2.0 ppm and 1.0 mu T at 3.6 ppm, whereas an optimal contrast-to-variation ratio (CVR) was obtained with a 0.7 mu T saturation at 2.0 ppm and 0.8 mu T at 3.6 ppm. In acute stroke, CVR optimized pHenh (i.e., pH(dual)) achieved a higher sensitivity than the three-point amide-CEST approach, and distinct patterns of lesion tissue compared to diffusion and perfusion MRI.Conclusion: pH(dual) MRI improves the sensitivity of pH-weighted imaging and will be a valuable tool for assessing tissue viability in stroke.