Grant: Discovery Grants Program - Individual

Molecular imaging is a medical imaging approach that allows visualization and measurements of biochemical processes and molecular targets in living organisms. It provides images of biological processes by using probes (biosensors) that target specific molecules or cells of interest. Advances in the molecular imaging field have the potential to revolutionize modern healthcare, specifically for early disease detection, personalized medicine, and metabolic imaging. Typically, molecular imaging is performed using positron emission tomography (PET) and single-photon emission computed tomography (SPECT) which have extreme sensitivity. These techniques, however, have several significant limitations. Both PET and SPECT utilize ionizing radiation which makes them unsuitable for high-frequency longitudinal studies. Moreover, PET and SPECT have limited spatial resolution and require additional anatomical information from either computed tomography (CT) or magnetic resonance imaging (MRI) for signal localization. Conventional MRI is not suitable for molecular imaging purposes due to the low sensitivity of this imaging modality, albeit it has superior spatial resolution. Recently, however, the development and implementation of the hyperpolarized (HP) Chemical Exchange Saturation Transfer (HyperCEST) MRI technique turned the tables for MRI molecular imaging completely. Utilization of supramolecular macrocycle capable of constant chemical exchange of HP nuclei between the contrast agent and dissolved pool produces signal enhancement uo to nine orders in magnitude. This phenomenon renders HP MRI one of the most promising molecular imaging modalities. Our research program is focused on the basic research and engineering of HyperCEST active contrast agents for HP MRI molecular imaging. This research program pursues three main research objectives: a) the basic functionalization of a HyperCEST active supramolecular cage via creation of cleavable rotaxanes sensitive to pH level; b) the optimization of HyperCEST MRI methods and evaluation of the performance of the functionalized imaging biosensors in vitro; and c) performing a proof-of-concept in vivo imaging of the functionalized MRI biosensors in rat model. Our research program will establish a basic research and engineering bulwark for the future translation of HP MRI imaging biosensors, from in vitro design to the in vivo detection of diseases. HP molecular MRI will become a safer and less expensive molecular imaging technique compared to conventional PET imaging while maintaining similar sensitivity and superior image resolution. This development of a novel molecular imaging approach that combines the high resolution of MRI with the molecular sensitivity of PET, while being safer, more economical, and deployable on existing hospital imaging equipment, will revolutionize the field of molecular imaging.