OHSU

Image is Everything

petri dish

OHSU Extra, Summer 2014

In the late 1600s, when Antony van Leeuwenhoek decided to examine the plaque between his teeth under his homemade microscope, he discovered what he described as “little living animalcules, very prettily a-moving” – organisms we now call bacteria. This unexpected insight upended the conventional wisdom of the time and led to countless improvements in human health.


Today, OHSU scientists are using state-of-the-art imaging equipment and techniques to illuminate everything from hidden brain cells to early breast cancer, lighting the path to new understanding and new cures. 

 Imaging technology may be revolutionizing biomedical science, but funding is a constant challenge. 

“While our researchers are able to bring in highly competitive federal grants, this funding does not cover the costs of imaging equipment itself, nor the expert staff who make its use possible,” said Dan Dorsa, Ph.D., OHSU’s senior vice president for research. “Philanthropic dollars have been essential to our ability to maintain and expand our cutting-edge imaging capabilities.” 

Private philanthropy has allowed OHSU to assemble some of the world’s most advanced imaging equipment and teams. At OHSU’s Center for Spatial Systems Biomedicine, for example, Joe Gray, Ph.D., and his team are using powerful, one-of-a-kind electron microscopes to study how cancer cells change over time and location in the body. They will use what they learn to create cancer treatments that work faster and help people stay cancer-free for longer. 

The microscopes (including the Titan, pictured on the cover) were furnished to OHSU through an innovative research alliance with Hillsboro-based manufacturer FEI. The collaboration is helping the Gray team understand the structure of cancer cells. Philanthropic investment from the W. M. Keck Foundation, the M.J. Murdock Charitable Trust, and Phil and Penny Knight, among others, made it possible to advance the OHSU-FEI collaboration. Their support also helped to give the sensitive microscopes a new home: a highly-specialized, vibration-free lab in the basement of the new OHSU/OUS Collaborative Life Sciences Building that opened in June. 

“Our new imaging techniques are allowing us to measure features in cells we haven’t seen before. It’s prompting us to ask entirely new kinds of questions and to think differently about new approaches to cancer treatment,” said Dr. Gray. No doubt Leeuwenhoek felt the same way, confronted with the lively “animalcules.” 

Philanthropy is helping OHSU to create an environment in which innovators like Dr. Gray have the resources they need to ask “new kinds of questions” in the service of improving human health. The following are but a few of the fascinating examples of what’s possible when creative thinkers can use powerful technology to reveal what was once hidden from view. 

 

microbubbles

Microbubbles moving through a patient’s bloodstream.

Microbubbles hone in on heart disease

By injecting tiny bubbles into a heart patient's artery and then watching the bubbles' progress on an ultrasound machine, doctors can see how fast blood is circulating and even defects in the heart. Known as microbubble-based myocardial contrast echocardiography (MCE), the procedure was pioneered by Sanjiv Kaul, M.D., co-director of the OHSU Knight Cardiovascular Institute and Ernest C. Swigert Distinguished Professor of Cardiology. MCE represents a major advance in imaging as it allows doctors to detect heart attacks that other methods (like electrocardiograms) often miss. Dr. Kaul developed the procedure over two decades of research. He expects the technology to lead to earlier detection and better treatment of heart conditions. Philanthropists Phil and Penny Knight, Hank Swigert, Ralph Quinsey, John Elorriaga and many others made this research possible.


Brain and ATP

The healthy patient brain pictured left shows normal levels of ATP. The MS patient brain on the right shows lower levels of ATP.

Magnets expose multiple sclerosis

At OHSU's Advanced Imaging Research Center (AIRC), scientists are using powerful magnetic resonance imaging equipment to find more sensitive ways to test potential cures for multiple sclerosis. Researchers Dennis Bourdette, M.D., F.A.A.N., Manoj Sammi, Ph.D., and William Rooney, Ph.D., used imaging technology to test the idea that part of what causes MS is a failure of energy production in the brain cells, which produces a deficit of the chemical adenosine triphosphate (ATP). Using OHSU's 7-Tesla MRI scanner, they were able to compare the ATP levels in brains of healthy patients and those with advanced MS. Their theory was correct: People with MS had 20 percent less ATP. They are now pursuing potential treatments that would boost levels of ATP and energy production within brain cells. The AIRC's capabilities would not be possible without philanthropic support from the W. M. Keck Foundation and a host of individual donors. 

 


brain cells

The image on the left shows an immature, less complex brain cell. The cell on the right is fully mature and features branching dendrites, tiny protrusions that enable communication between brain cells.

Imaging offers new hope for brain-injured preemies 


Stephen A. Back, M.D., Ph.D., the Clyde and Ella Munson Professor of Pediatric Research, made a startling discovery that offers new hope for the most vulnerable patients of all – premature infants. 

Babies born too soon are at high risk of brain injury, due to low blood and oxygen flow to their brains. Doctors once assumed that any damage to the developing brain was permanent. But now, thanks to powerful magnetic resonance imaging technology, Back's team has disproven that assumption. What they found by looking at the brains of premature sheep was that their brain cells were immature – but not gone. Dr. Back's discovery has led to an exciting new line of inquiry: how to help brain cells fully mature. "We now have a much more hopeful scenario," said Back.   

OCT-retina

In this image, OCT reveals the presence of abnormal blood vessels (yellow) under the retina in a case of wet age-related macular degeneration.

Light waves uncover eye disease 

In 1990, OHSU's David Huang, M.D., Ph.D., co-invented an imaging tool called optical coherence tomography (OCT), which has been heralded as the most important diagnostic advance in ophthalmology in more than 100 years. 


OCT is a non-invasive test that uses light waves to take cross-section pictures with micron resolution. Ophthalmologists around the world use OCT to image the retina, the light-sensitive tissue lining the back of the eye. It is essential for managing patients with the most common causes of vision loss: glaucoma, macular degeneration and diabetes. Dr. Huang, a professor of ophthalmology at OHSU Casey Eye Institute, along with several of his colleagues, received the 2012 Champalimaud Vision Award, the largest prize in ophthalmology, for the invention. Dr. Huang is now developing new applications of this remarkable technology, such as imaging blood flow in fine vessels within the eye – a first step to earlier diagnosis of blinding eye diseases. This work received significant support from the Champalimaud Foundation.  


MRI of breast cancer

These images, taken from an MRI of a breast cancer patient, show how frequently water cycles across breast cancer cell membranes. Being able to see this metabolic process in action allows researchers to track how fast a cancer cell is growing.

Metabolic activity reveals cancer's progress 

AIRC researchers Charles Springer, Ph.D., William Rooney, Ph.D., Xin Li, Ph.D. and Wei Huang, Ph.D., are the first in the world to use a technique called dynamic contrast-enhanced (DCE) MRI to measure the speed of a vital metabolic process taking place inside cells in a living human body. This revolutionary method allows researchers to measure how frequently water cycles across a cancer cell membrane, which in turn reveals how fast a cancerous tumor is progressing inside an individual patient. The method also helps determine if the cells are benign or malignant and allows doctors and patients to make better decisions about whether an invasive procedure like a biopsy is truly needed. This technique has shown success with breast, prostate and brain cancers and shows promise for early diagnosis of multiple sclerosis and heart disease. This discovery was made possible by support from the Oregon Opportunity campaign and the W. M. Keck Foundation. 

Left: This petri dish holds small support grids containing breast cancer cells. The new Titan electron microscope (pictured on the cover) allows researchers to view cells at a million times magnification, revealing never-before-seen structures in cancer cells.