Long-term quantitative imaging of oxygen levels via an injectable MRI agent

Quantitative measurement of oxygen levels would be highly useful in the oncology clinic, as hypoxia confers resistance to radiotherapy, impedes the action of chemotherapeutics, and promotes metastasis. However, no method of measuring oxygen in tissues has yet been introduced that meets clinical needs. Current approaches are either invasive, only useful in superficial tissues, or require specialized, expensive equipment not available in most medical centers.

A research group at MIT has recently introduced a creative solution to this challenge: an injectable MRI agent that forms a depot. This unusual strategy ensures that a sufficient concentration of the oxygen-responsive component, decamethyltetrasiloxane (DMTSO), is present within the region in which oxygen levels are to be imaged. The team, led by Michael Cima, a materials scientist, encapsulated this compound into polydimethylsiloxane (PDMS) microparticles at a 7:3 ratio so that it would be retained for long periods. Tissue oxygen concentrations can be calculated by correlation with a calibration curve generated by imaging DMTSO:PDMS exposed directly to varying concentrations of oxygen. In this study, the ability of the DMTSO:PDMS depot to detect oxygen level variation in vivo was determined by imaging rats whose calf muscles had been injected with the microparticles while they breathed air containing varying proportions of oxygen.

Injectable O2-sensing MRI agent
Oxygen tension (pseudocolored) extracted from the MR signal from a DMTSO/PDMS depot overlaid on anatomical images (coronal slices of the leg).

While the paper argues the advantages of depot MR agents, including a consistent concentration for repeated measurements, and demonstrates the biocompatibility of their material up to one month, an injected depot may not be as clinically translatable as an agent that could be cleared from the body, such as a nanoparticle. Whether DMTSO could be incorporated into a smaller agent is not discussed, perhaps because of the difficulty of inducing a sufficient concentration of nanoparticles to accumulate within the anatomical region of interest.

Liu et al., Solid MRI contrast agents for long-term, quantitative in vivo oxygen sensing, Proc Natl Acad Sci 2014; published online April 21.