New light on MRI: Contrast boost

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  • Published: Mar 1, 2017
  • Author: David Bradley
  • Channels: MRI Spectroscopy
thumbnail image: New light on MRI: Contrast boost

Linked switch

MRI image of a mouse cancer model, showing strong MRI signals (orange color) appearing only in the cancerous region.

A new technology platform can effectively tune the magnetic resonance imaging (MRI) signals in a scan switch on a contrast-boosting lamp on diseased tissue. Details are published in the journal Nature Materials suggesting that the approach might overcome some of the limitations of MRI contrast agents.

A research team led by Cheon Jinwoo at the Center for Nanomedicine at the Institute for Basic Science in Seoul, Republic of Korea and colleagues at Yonsei University, also in Seoul, and at the University of California, Berkeley, and the Lawrence Berkeley National Laboratory have developed what might be described as a "Nano MRI Lamp." As is common knowledge, MRI is becoming increasingly popular as a non-invasive diagnostic technique. However, while certain tissues are amenable to MRI others require contrast agents to illuminate target areas sufficiently. When typical contrast agents, such as gadolinium agents are administered by injection, this is done with the agent effectively in its "ON", which gives a broad background signal. "We found a new principle to switch the MRI contrast agent "ON" only in the location of the target," explains Cheon.

Enzyme activation

The team's Nano MRI Lamp technology consists of two magnetic materials: a quenching magnetic nanoparticle and the enhancer, the MRI contrast agent. The distance between the two is what facilitates the switching process. When the two materials are separated by a critical distance, more than 7 nanometres, the MRI signal is "ON". But, if they are separated by less than 7 nm the signal is "OFF". The team has dubbed this process magnetic resonance tuning (MRET), which they suggest is analogous to optical sensing technique called fluorescence resonance energy transfer (FRET).

In a proof of principle, the team has used their approach in a cancer diagnosis. They connected the two magnetic materials with a linker that is naturally cleaved by an enzyme that can induce tumour metastasis, MMP-2 (matrix metalloproteinase-2) in mice with cancer. The linker keeps the two materials close to together, the MRI signal is "OFF". However, if cancerous tissue is present, the linkage is broken by the enzyme MMP-2, the two materials can separate and the signal is switched to the "ON" position, but only in tissues containing active MMP2 enzyme. The MRI signal can thus reveal the sites in which MMP-2 is present and so give a clear demarcation of the tumour and any metastases. Moreover, the degree of contrast enhancement, the brightness, in other words, correlates directly with concentration of MMP-2 in the cancerous tissue given enough of the contrast agent.

Diagnostic diversity

"Current contrast agents are like using a flashlight on a sunny day, their effect is limited," Cheon explains. "Instead, this new technology is like using a flashlight at night and therefore more useful."

There are putative applications beyond cancer diagnosis, Cheon suggests, For instance, in principle, the same principle could be exploited by using linkers that are split by other enzymes associated with diseased tissue. It could be used for in vivo diagnostics of a range of pathologies as well as in biomedical research where MRI is a boon.

"Although we still have a long way to go, we established the principle and believe that the MRET and Nano MRI Lamp can serve as a novel sensing principle to augment the exploration of a wide range of biological systems," Cheon adds. The team is now working on developing safer and smarter multitasking contrast agents, which can simultaneously record and interpret multiple biological targets, and eventually allow a better understanding of biological processes and accurate diagnosis of diseases.

Related Links

Nature Mater 2017, online: "Distance-dependent magnetic resonance tuning as a versatile MRI sensing platform for biological targets"

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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