Magnetic Resonance Imaging (MRI) is a powerful imaging modality providing exceptional soft-tissue contrast with widespread use in clinical and preclinical applications. Exogenous paramagnetic contrast agents are often used during MRI studies to improve tissue visualization and disease detection. The utility of MRI contrast agents has led to the development of novel MRI contrast agents with improved magnetic properties, specific targeting to disease markers, and responsiveness to physiological conditions in vivo. These new agents are used in preclinical molecular MRI studies to sensitively identify disease, evaluate tissue function, and report on the tissue microenvironment. However, current molecular MRI studies are limited to single agent use despite the existence of situations where two or more agents would provide useful and complementary information. This is primarily due to the inability of contrast enhanced MRI studies to uniquely identify individual agents when two or more agents are used simultaneously.
In this work, we propose using the multi-property quantification of the novel Magnetic Resonance Fingerprinting (MRF) technique as a method for uniquely quantifying the local concentration of two co-administered paramagnetic MRI contrast agents. MRF is a wholly new way to perform quantification of MRI-specific tissue properties and has demonstrated the ability to simultaneously quantify multiple tissue properties with high temporal resolution and robustness to imaging artifacts. First, we describe the Regularly Incremented Phase Encoding-MRF (RIPE-MRF) method for improving the motion resistance of preclinical MRF scans. RIPE-MRF uses a variable acquisition scheme that suppresses the appearance of motion artifacts in the resulting quantitative MRF tissue property maps. Then, we present an extension to the fundamental MRI contrast equations that enables simultaneous calculation of the concentration of two co-administered MRI contrast agents. We term this method Dual Contrast-Magnetic Resonance Fingerprinting (DC-MRF) and show how it enables unambiguous analytical calculation of multiple agent concentrations. This work demonstrates how DC-MRF can be used in multi-agent molecular MRI studies creating numerous opportunities for subvoxel analysis of tissue fractions, MRI-based imaging of genetic expression, and measurement of enzyme activity.