MRI implant: Monitoring oxygen levels

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  • Published: May 1, 2014
  • Author: David Bradley
  • Channels: MRI Spectroscopy
thumbnail image: MRI implant: Monitoring oxygen levels

Local oxygen

The MRI sensor, made of two forms of silicone, can be shaped into cylinders of different sizes and implanted in the body. Credit: Cima et al

A solid device that can be implanted in the body could be used to monitor oxygen levels in the body over the course of several seeks by scanning with magnetic resonance imaging (MRI) has been developed for a wide range of medical diagnostics applications.

Cancer cells thrive even when their oxygen supply is low, unlike health cells. Moreover, those tumours that grow in a low-oxygen environments also tend to be more resistant to chemotherapy and other forms of treatment and can spread, or metastasise, more aggressively to other parts of the body. It would therefore be rather important to be able to measure the oxygen levels in a given tumour in order to allow oncologists to make appropriate treatment decisions for their patients. Unfortunately, there is no reliable and non-invasive technology available to allow them to monitor oxygen levels as such a localised level. However, a new sensor developed by a research led by Michael Cima of Massachusetts Institute of Technology (MIT) could change all that.

Cima and his colleagues, Vincent Liu, Christophoros Vassiliou, Syed Imaad, have developed an injectable device, a solid MRI contrast agent for long-term quantitative oxygen monitoring. They suggest that using this kind of technology could allow oncologists to better determine the appropriate radiation dose needed to treat a given cancer and to see whether the treatment is effective. They report details in the journal Proceedings of the National Academy of Sciences.

Decision injection

"In cases where you are trying to make therapeutic decisions, you want to have some numbers that you can fall back on, explains graduate student Liu, who is lead author on the paper and works as part of Cima's team at the Koch Institute for Integrative Cancer Research. Targeted MRI contrast agents have been developed before for monitoring specific metabolites and biomarkers. However, they have limited utility in ongoing clinical studies for serial imaging because their concentration does not remain constant after they are first injected. The team's new solid contrast agent is comprised of a silicone polymeric matrix - polydimethylsiloxane (PDMS) - that circumvents this concentration problem by providing structural support for a second, responsive agent, also based on silicone, dodecamethylpentasiloxane (DDMPS), to provide the MRI signal. The hydrophobic DDMPS dissolves in PDMS, creating a "swollen polymer", which can be formed into an implantable solid just 1.5 millimetres in diameter. This structure can be injected into the tumour site during biopsy. Alternatively, smaller particles (tens of micrometres long) can be injected through a needle and they then aggregate in the site to form a solid mass. The DDMPS can absorb oxygen from its surroundings which shifts the magnetic resonance signals associated with its protons. The degree to which this occurs reflects the local oxygen levels.

This is the first MRI sensor of any kind that can remain in the body for an extended period of time. The team tested structural stability in laboratory rats and showed that the molecular device remains functional for at least one month. This is ten times as long as liquid siloxane remains stable at an injection site. Conventional MRI contrast agents are, of course, designed to be used once for a particular scan and then to degrade in the body and be excreted. Such agents are commonly used to reveal the presence of diseased or damaged tissues, including tumours. But have no use in monitoring over the course of several weeks and longer. With the new MIT sensor, oncologists could track the size and shape of a tumour to predict how it might respond to radiation treatment and then to observe whether or not it does so.

Oxygen damage

Radiotherapy initiates DNA damage in cancer cells, but oxygen must be present for the effects of the ionising radiation to lead to a lethal cascade of chemical changes at the cellular level. An insight into how much oxygen is likely to be present in a tumour would therefore provide the radiologist with much needed knowledge about possible response as well hinting at the possibility of metastasis. Low-oxygen tumours tend to spread more rapidly.

Ralph Weissleder, director of the Massachusetts General Hospital Center for Molecular Imaging Research, is enthusiastic about the new MRI sensor. "The cancer field certainly needs something like this," he says. "The ways we currently have to measure oxygen tension are fairly cumbersome and not quantitative, so no one really uses them."

The same type of contrast agent might also be used to monitoring restricted blood flow in patients with diabetes, where blood circulation in the extremities is often compromised or in accident victims with serious injuries. The team is also now working on extending the range of stimuli to which such sensors might respond to include pH or other factors for which continual monitoring in the body over the course of weeks might be useful.

Related Links

Proc Natl Acad Sci, 2014, online: "Solid MRI contrast agents for long-term, quantitative in vivo oxygen sensing"

Article by David Bradley

The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.

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