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Developing Next Generation MRI Contrast Agents
Developing Next Generation MRI Contrast Agents

Great social, technological, or scientific breakthroughs rarely happen in a vacuum. Rather, they require collaborative environments where ideas and resources can be freely exchanged. Research Triangle in North Carolina, Route 128 in Boston, and Silicon Valley are the three most-often cited U.S. examples of this kind of entrepreneurial hothouse. The anchor universities and spinoff companies in those three regions have flourished because of these creative synergies.

Oregon’s best shot at replicating this model is the partnership between PSU and Oregon Health and Science University. As already described in this Quarterly Review, these two schools form the core of the Innovation Quadrant, which has a distinctly life science flavor. Co-located classrooms, shared research laboratories, and even a joint School of Public Health are all evidence of this close connection.

However, nothing links two educational institutions together more closely than shared faculty. PSU and OHSU are still in the early stages of developing this mechanism for partnership. One of the early pioneers in this experiment is Dr. Mark Woods, who holds joint appointments as Associate Professor of Chemistry at PSU and Associate Scientist in the Advanced Imaging Research Center (AIRC) at OHSU. Drawing on the resources of both universities, Dr. Woods focuses his research on the development of novel, more effective magnetic resonance imaging (MRI) contrast agents that improve the quality of images in general and target specific diseases in particular.

The use of MRI as an investigative and diagnostic tool in medical and scientific settings has become commonplace in the three and a half decades since the technology first became commercially available. Its applications include the diagnosis of some types of cancer, detection of cardiovascular disease, the characterization of liver and pancreatic disorders, and the study of brain activity.

“When we use magnetic resonance imaging in all of these applications,” Dr. Woods said, “what we’re measuring, in a sense, is the water that makes up over 60% of our bodies.”

During an MRI scan, radio waves transmitted in the presence of a strong magnetic field temporarily knock the atomic nuclei of water molecules in human tissues out of their natural positions. As the nuclei realign, they send out additional radio signals, which can be detected by scanners in the machine, analyzed by a computer and converted into an image. The brighter areas of the scan indicate places where nuclei take longer to return to their natural positions; these tend to correlate with areas where something is amiss.

“The purpose of MRI contrast agents is to accelerate the slowdown of nuclei,” Dr. Woods explained. “By hastening the slowdown you can increase the contrast between the brighter and darker areas of the scan, which helps radiologists identify tumors, brain activity, liver damage, or other potential health issues. And while that’s great, there are a lot of problems with contrast agents we still need to overcome.”

According to Dr. Woods, contrast agents work best in scans performed by low magnetic field machines. In these cases, scientists working in labs can increase the effectiveness of contrast agents between 20 and 30 percent. The problem is that low field machines produce poorer quality images, even when contrast agents are applied, and contrast agents, even those enhanced in the lab, lose all effectiveness in high field scans. A second problem Dr. Woods is working on is one of scale. The molecular structures of current clinical contrast agents are far too large to detect disease biomarkers that may only be present at the nanoscale.

“So the challenge we’re working on is how to improve contrast agents at the low field level, to get them to the point where they can detect something as minute as a disease biomarker. At the same time we’re trying to develop a contrast agent that can perform as effectively at high magnetic fields as low fields. It’s work that takes me back and forth between my lab here at PSU and the Advanced Imaging Resource Center [at OHSU].”

Dr. Woods notes that there are other imaging technologies available to the medical and scientific communities already capable of detecting nanoscale disease biomarkers in the human body. Single Photon Emission Computed Tomography (SPECT) and Positron Emission Tomography (PET) scans are the two most common. There are, however, disadvantages to these modalities. Both require the application of radioactive substances to diagnose and treat illnesses. Both produce images of far lower resolution than MRI scans. And neither provides radiologists the anatomical information that is inherent with MRI scans.

“We don’t yet have the technology to dig as deep as radiologists can with nuclear medicine,” Dr. Woods said. “But we know MRI is a better tool on many different levels. That’s why I think the work we’re doing is important. If we can get the combination of effectiveness at the high field and the ability of the contrast agents to perform at the scale of disease biomarkers, we’ll be able to really change the way imaging is done in research fields and perhaps even see these agents working in preclinical settings.”

Dr. Woods is hard at work on achieving those breakthroughs. He is currently collaborating with OHSU biomedical engineer Dr. John Muschler on developing MRI contrast agents capable of detecting bladder cancer, the sixth most common form of cancer. Affecting more than 200,000 people per year in the U.S. alone, bladder cancer, which usually affects older adults, can be difficult to detect, and even more difficult to treat depending on a patient’s age. Dr. Woods’ goal is to develop a contrast agent capable of identifying diseased tissue at an early stage before harsh and invasive treatment methods are required.

As OHSU’s top research priority, the battle against cancer is sure to be a recurring theme in future news from Portland. Faculty members like Dr. Mark Woods, who serve as ambassadors between OHSU and PSU, increase the likelihood that PSU’s scientists and engineers will also play a significant role in these major breakthroughs, just as the Innovation Quadrant itself increases the visibility of Portland’s contributions to the solution of society’s grand challenges.