Magnetic-susceptibility-dependent ratiometric probes for enhancing quantitative MRI

In magnetic resonance imaging (MRI), quantitative measurements of analytes are hindered by difficulties in distinguishing the MRI signals of activation of the probe by the analyte from those of the accumulation of the intact probe. Here we show that imaging sensitivity and quantitation can be enhanced by ratiometric MRI probes with a high relaxivity-ratio change (more than 2.5-fold at 7 T) via magnetic-susceptibility-dependent magnetic resonance tuning. Specifically, polymeric probes that incorporate paramagnetic Mn-porphyrin and superparamagnetic iron oxide nanoparticles inducing opposite changes in the longitudinal and transverse magnetic relaxivities responded to analyte concentration independently of probe concentration. In mice, the probes allowed for quantitative real-time dynamic imaging of H₂O₂, H₂S or pH in subcutaneous tumours, in livers with drug-induced injury and in orthotropic gliomas. The ratiometric MRI probes may be advantageously used to obtain molecular insight into pathological processes and to circumvent interference from dynamic changes in probe concentration within the body while providing anatomical information.