Biomolecular MRI reporters: Evolution of new mechanisms

Abstract

Magnetic resonance imaging (MRI) is a powerful technique for observing the function of specific cells and molecules inside living organisms. However, compared to optical microscopy, in which fluorescent protein reporters are available to visualize hundreds of cellular functions ranging from gene expression and chemical signaling to biomechanics, to date relatively few such reporters are available for MRI. Efforts to develop MRI-detectable biomolecules have mainly focused on proteins containing or transporting paramagnetic metals for T1 and T2 relaxation enhancement or large numbers of exchangeable protons for chemical exchange saturation transfer. While these pioneering developments established several key uses of biomolecular MRI, such as imaging of gene expression and functional biosensing, they also revealed that low molecular sensitivity poses a major challenge for broader adoption in biology and medicine. Recently, new classes of biomolecular reporters have been developed based on alternative contrast mechanisms, including enhancement of spin diffusivity, interactions with hyperpolarized nuclei, and modulation of blood flow. These novel reporters promise to improve sensitivity and enable new forms of multiplexed and functional imaging.

Recombinantly expressed gas vesicles as nanoscale contrast agents for ultrasound and hyperpolarized MRI

“…Recombinant expression of Mega GVs in E. coli provides a convenient platform for the simple and rapid production of gas‐filled protein nanostructures for applications in molecular imaging, within which GVs offer unique advantages alongside other emerging nanoscale and protein‐based reporters . In future studies, this expression system could also facilitate the genetic engineering of GV properties.…”

“…Ultrasound contrast is produced by sound wave scattering at interfaces between materials with different density or stiffness. Likewise, MRI is capable of whole‐body imaging with spatial resolution on the order of 100 µm, and uses a variety of contrast mechanisms arising from nuclear spin behavior . Among these mechanisms, hyperpolarized MRI provides particularly high molecular sensitivity using nuclei, such as 129 Xe, prepared with nonequilibrium polarization several orders of magnitude higher than that available under equilibrium conditions .…”

Function, energy and environment orientation in innovation research of rare earth materials

“…Efforts to develop MRI-detectable biomolecules have focused on proteins transporting paramagnetic metals for T 1 and T 2 relaxation enhancement or containing large numbers of exchangeable protons for chemical exchange saturation transfer. While these pioneering developments established several key uses of biomolecular MRI, such as imaging of gene expression and functional biosensing [17].…”

Proteins, air and water: reporter genes for ultrasound and magnetic resonance imaging

“…However, while these technologies continue to improve, they face intrinsic limitations due to their reliance on metal co-factors, and difficulty in being distinguished from background tissue contrast at low concentrations [20]. New contrast mechanisms are therefore needed to help overcome these limitations.…”