Improving the detection sensitivity of pH-weighted amide proton transfer MRI in acute stroke patients using extrapolated semisolid magnetization transfer reference signals

Purpose: To quantify amide protein transfer (APT) effects in acidic ischemic lesions and assess the spatial-temporal relationship among diffusion, perfusion, and pH deficits in acute stroke patients. Methods: Thirty acute stroke patients were scanned at 3T. Quantitative APT (APT^#) effects in acidic ischemic lesions were measured using an extrapolated semisolid magnetization transfer reference signal technique and compared with commonly used MTR_asym(3.5ppm) or APT-weighted parameters. Results: The APT^# images showed clear pH deficits in the ischemic lesion, whereas the MTR_asym(3.5ppm) signals were slightly hypointense. The APT^# contrast between acidic ischemic lesions and normal tissue in acute stroke patients was more than three times larger than MTR_asym(3.5ppm) contrast (-1.45±0.40% for APT^# versus -0.39±0.52% for MTR_asym(3.5ppm), P<4.6 × 10^-4). Hypoperfused and acidic areas without an apparent diffusion coefficient abnormality were observed and assigned to an ischemic acidosis penumbra. Hypoperfused areas at normal pH were also observed and assigned to benign oligemia. Hyperintense APT signals were observed in a hemorrhage area in one case. Conclusions: The quantitative APT study using the extrapolated semisolid magnetization transfer reference signal approach enhances APT MRI sensitivity to pH compared with conventional APT-weighted MRI, allowing more reliable delineation of an ischemic acidosis in the penumbra.