Quantitative in Vivo Molecular MRI

Molecular magnetic resonance imaging (MRI) combines chemistry, chemical biology, and imaging techniques to track molecular events non-invasively. Quantitative molecular MRI aims to provide meaningful, reproducible numerical measurements of molecular processes or biochemical targets within the body. In this review, the classifications of molecular MRI probes based on their signal-generating mechanism and functionality are first described. From there, the primary considerations for in vitro characterization and in vivo validation of molecular MRI probes, including how to avoid pitfalls and biases are discussed. Then, recommendations on imaging acquisition protocols and analysis methods to establish quantitative relationships between MRI signal change induced by the probes and the molecular processes of interest are provided. Finally, several representative case studies are highlighted that incorporate these features. Quantitative molecular MRI is a multidisciplinary research area incorporating expertise in chemical biology, inorganic chemistry, molecular probes, imaging physics, drug development, pathobiology, and medicine. The purpose of this review is to provide guidance to chemists developing MR imaging probes and methods in terms of in vitro and in vivo validation to accelerate the translation of these new quantitative tools for non-invasive imaging of biological processes.