In medicine, early detection, individual assessment technologies offer hope in the battle against deadly illnesses

By Lynn Nystrom, College of Engineering

Cancer remains a leading cause of death in the United States, but there is good news. The five-year survival rate now stands at 60 percent – far better than a decade ago, or even a few years ago.

A critical key to further improving this cancer survival rate, as well as for other life-threatening illnesses, rests with new technology. A handful of medical specialists argue that it makes sense to use research money to figure out how to diagnose and stop disease at an early stage rather than pour dollars into new drugs that might add only a few months or years onto a patient’s life. Their viewpoint is gaining traction.

With pharmaceutical drugs, an individual’s reaction to medication can vary considerably, even among cancers of the same histological type. And although current technology using early detection methods has helped multitudes of patients, the procedures can be intrusive and uncomfortable, or worse, inaccurate. For example, the current blood test for prostate cancer, called PSA, incorrectly suggests a man has cancer about 70 percent of the time, according to the National Cancer Institute. Given these variables, patient assessment becomes a very challenging procedure.

“And with drug studies, hundreds of patients may be involved. That’s a lot of data. If you’re evaluating a new drug for cancer and you scan 1,000 patients three times, you have 3,000 sets of data. Can you hire a radiologist to look at all that?” asks Chris Wyatt, a faculty member in the Virginia Tech-Wake Forest University School of Biomedical Engineering and Sciences (SBES).

“You can acquire the data, but pulling out the information you want – such as how the lesion is changing – is a difficult, time-consuming process that right now is done manually in many cases. Trained technicians look at the images and outline the lesions by hand,” says Wyatt, who is also a member of the Department of Electrical and Computer Engineering (ECE) at Virginia Tech.

Early detection and individual patient assessment are part of the research agenda for the new collaboration that has Virginia Tech’s College of Engineering partnering with the Wake Forest University School of Medicine, a national leader in cancer care and research. Faculty members participating in the SBES are focusing on imaging and medical physics, as well as biomechanics and cell and tissue engineering.

Enhanced, quicker, and more relevant images

Imaging, which includes the use of radiographs, computed tomography (CT), magnetic resonance imaging, ultrasound, and other techniques by which physicians evaluate an area of the human body that is not normally visible, has the invaluable potential to greatly extend the reach of medical research beyond detecting the anatomical presence of the disease. By employing applied engineering technologies, more intensive study of diseases at the cellular level will be possible. In turn, this greater understanding of the physiology of an illness will lead to more targeted treatments. In the instance of cancer, the importance of targeting tumors cannot be overestimated – as little as one cubic micron of tissue can harbor anywhere from 1,000 to 10,000 tumor cells capable of causing a recurrence of the cancer.

Wyatt is attempting to provide the medical community with enhanced, quicker, and more relevant images of the human body. The benefits could include easier disease detection, lower medical costs, and new treatments. Wyatt is specifically looking at improving imaging for virtual colonoscopies and developing algorithms to replace extensive manual work in brain imaging.

It’s doubtful one could find a patient who would prefer the current, invasive procedure of a colonoscopy to a virtual one. If this early detection comes without the uncomfortable, hours-long process, chances are the percentage of patients getting the test would increase dramatically – probably even more than when newscaster Katie Couric allowed her colonoscopy to be televised.

Wyatt and other researchers in SBES, part of Virginia Tech’s Institute for Critical Technology and Applied Science, are eager to identify the technologies needed for a specific individual’s assessment, including screening, treatment planning, monitoring, and follow-up therapy. To do so, according to Wally Grant, SBES director and professor of engineering science and mechanics, research advances are needed in imaging capabilities that promote earlier detection and targeted, or image guided therapies; sensitivity and resolution of imaging technology to fashion therapy that is tumor-specific; and advanced data management methods, including computer-aided diagnostics and modeling.

A more personalized medicine

Joseph Yue Wang, who currently leads a $5.5 million research effort to improve the outcome for breast cancer patients, dreams of a more personalized medicine in which doctors can precisely determine how a patient’s cancer will behave. Then, based on the expected outcomes, the physician can target a precise treatment plan.

Researchers studying disease at molecular levels need the analytical skills of engineers to aid in both discovery and understanding of biological systems, says Wang, another member of the ECE department and SBES.

“Personalized medicine requires a quantitative-plus-molecular equation, in which computational intelligence tools can play a major role. However, many difficulties need to be overcome before a molecular signature-based, computer-aided diagnosis can be developed. Prognosis and monitoring therapy are among our future tasks,” he says.

For any single disease, thousands of genes and proteins that interact with each other are studied and tested. Proteins, the basic building blocks of cells, are also involved in cellular function and control. A single cell can contain 1 billion molecules capable of interacting with each other. These numbers produce “vast amounts of data that need to be interpreted and analyzed so that the components involved with diseases can be isolated and identified,” says Wang, who currently participates in two National Institutes of Health (NIH) Center of Excellence projects, one Department of Defense Center of Excellence project, and one NIH Cancer Bioinformatics Grid project.

The data processing and manipulation Wang is referring to typically falls under the bioinformatics field, where a number of computational engineers and computer scientists are now working.

A newer field, called systems biology, is also emerging. It requires modeling and systems engineering skills based on a solid mathematical and theoretical background, Wang says. The completion of the human genome project, in which every gene in the human body was identified and mapped, has provided a foundation for the field. A frequently used metaphor is that the genome project provided a location map, but the roads and traffic patterns remain unknown. Wang, based in Northern Virginia, is also an affiliated faculty member of the Johns Hopkins Medical Institutions. He works with teams that include biologists and physicians from Georgetown University, Johns Hopkins Medical Institutions, NIH, and the Children’s National Medical Center. He is on the Institute for Scientific Information list of the 200 most cited authors.

SBES engineers like Wang are hoping to provide physicians with the tools to determine such things as which cancers identified through screening should be treated and which are best left untreated. They should also be able to help identify individuals who are at risk for specific cancers and require routine testing or lifestyle modification. And they should be able to assess treatment using biological, chemical, and genetic markers in addition to anatomical measures to provide improved results and reduce fatalities.

If a suite of advanced detection tools allows the accurate assessment of specific forms of cancer cells, of which there are thousands, physicians will be better able to determine when treatment is necessary and provide more sophisticated approaches to monitor treatment and to introduce follow-up therapy.

Strengthening the SBES faculty’s emphasis on imaging was the recruitment of Ge Wang, Virginia Tech’s Samuel Reynolds Pritchard Chaired Professor of Engineering. He produced the first paper in the area of spiral cone-beam CT, now in the mainstream of medical CT research. In 2004, he authored the first paper in the area of bioluminescence tomography, an emerging modality for molecular imaging. More than 1,000 citations are attributed to Ge Wang and his group’s pioneering efforts in imaging research. Wang joined Tech from his position as director of the University of Iowa’s Center for X-Ray and Optical Tomography in the Department of Radiology.

Ge Wang is the founding editor-in-chief of the International Journal of Biomedical Imaging, and since receiving his Ph.D. in 1992 has attracted more than $8 million in research initiatives as a principal investigator (PI) and another $20 million as a co-PI or a co-investigator.

“The partnership between Wake Forest and Virginia Tech will result in visionary research that will advance discovery in human tissue engineering and related critical technologies,” says Richard Benson, dean of Virginia Tech’s College of Engineering. “SBES is helping to create an environment that will continue to attract outstanding researchers like Dr. Wang from around the world.”

Detail of an illustration by Charles Wood. View the illustration at a larger size.

Imaging has the invaluable potential to greatly extend the reach of medical research beyond detecting the anatomical presence of the disease.


This microCT scanner is a dedicated small animal imaging system. The scanner provides detailed images of an anatomy that are relevant to a wide variety of disease models. Photo by John McCormick. You can view the complete photo at a larger size.


A portion of a Rick Griffiths photo showing Chris Wyatt's work on the virtual colonoscopy project. You can view the complete photo at a larger size.

Illustration by Charles Wood

For any single disease, thousands of genes and proteins that interact with each other are studied and tested.


This thumbnail photo shows Cindy Hatfield, assistant professor, small animal clinical sciences, Virginia-Maryland Regional College of Veterinary Medicine. Also shown in the complete photo is Christopher Wyatt, assistant professor of electrical and computer engineering. Photo by John McCormick.

Yue (Joseph) Wang demonstrates the protein array analyzer in the Center for Genetic Medicine at Children's National Medical Center. You can view the complete photo at a larger size. Photo by Michael Kiernan.

Illustration by Brittany Bowman. View the illustration at a larger size

Protein Array Analysis, called "proteomics," is similar to gene array analysis, but at a more defined level. Yue Wang and a team of biologists and clinicians are incorporating proteomics in their fights against cancer, diabetes, and other diseases. Photo by Michael Kiernan.

Gene analysis in the Center for Genetic Medicine at Children's National Medical Center. You can view the complete photo at a larger size. Photo by Michael Kiernan.

 

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