College of Engineering

Critical technologies are those that respond quickly to an identified need at the appropriate moment. They also significantly advance the industry, often lead to other applications that were not apparent at the beginning of the process, and frequently require a forward jump in our understanding of the underlying science and engineering. Virginia Tech is committed to the pursuit of critical technology research. It is developing an infrastructure and committing resources to the identification and development of critical technologies. The result is a new environment where researchers and ideas can prosper across and between conventional disciplinary lines. At Virginia Tech, this environment is found in the Institute for Critical Technologies and Applied Science. ICTAS encourages a seamless path from fundamental research, through development, to technology transfer, job creation, and technical assistance to business and industry. The research component of the newly established School of Biomedical Engineering and Sciences ( SBES), our pioneering joint venture between Virginia Tech’s Colleges of Engineering and Veterinary Medicine and Wake Forest University’s School of Medicine, is a prominent part of ICTAS. SBES will occupy an entire floor of the first ICTAS building, scheduled for completion in 2008.

With SBES we have a number of visions:

• We will produce students who are experts in their fields. What I mean by this is that the graduate’s knowledge will extend to a particular branch of engineering, such as tissue engineering. Our graduate program will produce qualified engineers who have a strong life science component.

• We are introducing engineering into traditional medical school subjects, such as physiology. By this example, I mean that we are introducing mathematical descriptions of organ-system functions into physiology. The plan is to make this course a two-semester offering of physiology and engineering principles. Think about measuring cardiac output, the flow rate of blood exiting the heart. One current method is to run a catheter up the right atrium into the pulmonary artery, inject a cold saline solution, and measure temperature reduction. There are several assumptions in the analysis that is used for this measurement that can and do lead to large errors. If an engineer learns both the physiology and the engineering principles, we can potentially improve the process by reducing and correcting many of the original assumptions used in the measurement. With improvements, the present tool becomes much more effective and practicing physicians will rely on the results, instead of regarding them a guide that may not be that good a measurement.

• After Wake Forest successfully recruited Dr. Anthony Atala and his research group on regenerative medicine from Harvard’s Medical School in 2004, we decided to increase our emphasis on cell and tissue engineering. We are developing specialty course work that relates the engineering component to regenerative medicine. As researchers attempt to grow replacement parts for the human body, the key is to be able to nourish the stem cells that are used in the scaffolding and to provide the right biochemical messengers. We are looking at team-teaching in this area soon.

• We are planning to grow SBES with three new faculty members annually for the next five years. Two would locate at Virginia Tech and one would join Wake Forest. And with additional resources, we will be able to introduce new courses or purchase time from other departments. For example, the Edward Via College of Osteopathic Medicine, located at Virginia Tech’s Corporate Research Center, provides an excellent opportunity for our College of Engineering to interact with the medical profession.

• As biomedical engineering educators, we also hope to assist the medical profession through student design projects. Our students are often involved in great solutions to problems, and we are able to commercialize designs through an agreement we have with the Carilion Biomedical Institute.

• SBES is also looking at improving the relationship between Wake Forest and Virginia Tech faculty with small grants that provide graduate student funding for a year. During that time, the collaborators with the student must produce a proposal to a funding agency, such as NIH or NSF, for continuation of the work.

Our longer-range goals include solicitation of funding for named professorships in the school, summer clinical rotations, SBES scholarships and assistantships, and a building on each campus.

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. SBES will help create an environment that will attract outstanding researchers from around the world.

Wally Grant, director

Cancer remains a leading cause of death in the United States. Early detection and treatment are critical to improving the survival rate. Yet, an individual’s response to treatment varies considerably, even among cancers of the same histological type. Given these variables, patient assessment becomes a very challenging procedure.

Yue (Joseph) 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 are now studying disease at molecular levels and need the analytical skills of engineers to aid in both discovery and understanding of biological systems, Wang says.

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

In studying 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 one 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,” Wang explains.

This data processing and manipulation typically falls under the computational bioinformatics field, where a number of computational engineers and computer scientists are now working.

Another, newer field, called systems biology or systems biomedicine, is 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.

Molecular data are typically obtained from gene microarrays, which are silicon chips imprinted with DNA and its thousands of genes. The microarrays get ‘washed’ with a solution carrying fluorescent messenger RNA from the biopsied tissue sample of a cancer patient. The RNA molecules then attach to their corresponding DNA genes. The more RNA segments that attach to a gene, the more that gene will glow or fluoresce, which is called gene expression. The expression can then be measured and analyzed.

Wang’s team is also working with similar technology involving protein microarrays to study cancer at an even more precise level. The new field, called proteomics, is expected to help researchers better study the function and control of the molecules involved.

Both technologies yield “vast amounts of data,” Wang explains. His team is developing tools that help eliminate noise and develop analysis algorithms so that the true biological effects can be studied. They are also developing, optimizing, and validating neural network classifiers so that cancer can be more accurately classified and therapy can be personally tailored for optimal response.

“This is important with diseases that are caused not by a single factor, but by multiple factors. Cancer, for example, can be caused by genetic predisposition, with contributing factors, such as diet, environment, and alcohol consumption. Type 2 diabetes requires a systems approach, as it is caused almost entirely by multiple social factors, including diet and lack of exercise.”

“We are working with physicians to analyze cancer data from all levels: the entire body, the cellular, the molecular, and the genetic,” he says. “We are seeking to understand how disease starts, how it progresses, and which biomarkers can be used for therapeutic purposes,” he explains. “Not all molecules in the body are responsible for a disease; only a certain subset are. If we can accurately identify the responsible molecules and determine appropriate biomarkers, we can develop rational treatments.” He stresses that, since cancer progression is a process of acquisition of multiple and alternative mutations, molecular imaging must be able to image multiple biomarkers.

Wang, based in Northern Virginia, is a member of Virginia Tech’s Alexandria Research Institute and also serves as an adjunct professor of radiology at Johns Hopkins Medical Institutions. He works with teams that include biologists and physicians from Georgetown University, Johns Hopkins Medical Institutions, the National Institutes of Health, and the Children’s National Medical Center. He is a member of the Virginia Tech– Wake Forest University School of Biomedical Engineering and Science.

In February, Wang was inducted into the College of Fellows of the American Institute for Medical and Biological Engineering (AIMBE) for his contributions to biomedical informatics. AIMBE Fellows represent only two percent of the researchers active in medical and biological engineering.

After blood, bone is the second most transplanted tissue. It is used clinically for spinal fusions, tissue augmentation, and repair of skeletal defects that arise from disease, trauma, or birth defects. Presently, the best clinical outcome is obtained by using donor tissue obtained from other sites in the patient’s body. However, since this procedure means added pain and cost to the patient, and since there may be limited availability of donor tissue, other materials, such as from bone banks and synthetics, are in high demand.

Synthetic biomaterials are one alternative. But as gains are made in biomedical engineering research, we are shifting from biomaterials that replace tissue function toward ones that assist in the healing process, says Aaron Goldstein, assistant professor of chemical engineering at Virginia Tech.

In his laboratory, Goldstein is focusing on the development of an engineered tissue for the repair of bone defects. He is seeding adult stem cells that he obtains from bone marrow onto degradable biomaterials and is growing them in a bioreactor to produce a material suitable for bone repair. By using various stimuli, Goldstein is attempting to direct their growth and differentiation.

“Cells are very sensitive to the conditions of their environment. Therefore, it is important that we not only develop bioreactor strategies to provide adequate supplies of oxygen and nutrients, but also exert beneficial mechanical stimuli. Concurrently, we need to design biomaterial architectures that facilitate cell adhesion, cell to cell communication, and tissue development.”

The process of normal bone healing involves the formation of a cartilaginous callus that bridges the defect. This tissue then calcifies into woven bone, which then is slowly replaced with lamellar bone. When the defect is too large, the bone will not heal without surgical intervention. Goldstein envisions that his material can be implanted into such defects to stimulate healing, and then to be replaced with lamellar bone.

Several existing research labs make up the new consortium: the Industrial Ergonomics and Biomechanics Laboratory, the Locomotion Research Laboratory, and the Musculoskeletal Biomechanics Laboratory. Maury Nussbaum of industrial and systems engineering is the director of the center. Thurmon Lockhart and Kari Babski-Reeves, also of ISE, and Kevin Granata and Michael Madigan of engineering science and mechanics, are the core members.

An unlikely team — an engineer, a dentist, and a veterinarian — builds bone tissue

Oral and pharyngeal cancers rank among the most prevalent worldwide, although they account for only about three percent of all cancers in the United States. Unfortunately, most oral cancers are detected at advanced stages when combinations of surgery and radiation are required, and the most recent studies show the five-year survival rate of 53 percent has not changed in the past 30 years.

If two Virginia Tech researchers, collaborating with the American Dental Association (ADA), are able to successfully construct a tissue engineered composite material for oral reconstructions, these dismal statistics might yield a better outcome.

The repair of the diseased tissue in these cancers often requires reconstruction of the bone, and Brian Love, professor of materials science and engineering and principal investigator on a National Institutes for Health (NIH) grant, believes “substantially better clinical outcomes for all oral constructions could result if a more viable scaffold material were used that was capable of faster and higher quality bone formation.”

Love and the team are looking at amorphous calcium phosphates (ACPs) as inorganic host materials in the rebuilding of tissue. ACPs, in the presence of cells that make bone (called osteoblasts), are believed to “more readily” provide the host material for new bone formation in tissue engineering than other choices, Love explains.

“By constructing tissue engineered composites containing ACPs, living osteoblasts, and donor materials,” Love believes the result could be faster and higher quality bone formation.

By constructing tissue engineered composites containing ACPs, living osteoblasts, and donor materials,” Brian Love believes the result could be faster and higher quality bone formation.

The Paffenbarger Research Center of the ADA is supplying the ACP for the current studies. Aaron Goldstein of Virginia Tech’s Department of Chemical Engineering is a co-principal investigator, and Drago Skrtic of the ADA Paffenbarger Research Center and Peter Shires of Virginia-Maryland Regional College of Veterinary Medicine are collaborating with Love and Goldstein.

In earlier studies, Love recently completed a research leave at the Dental Polymers Group of the National Institute for Standards and Technology working on photopolymers used in dentistry. Goldstein has performed post-doctoral work at Rice University’s Tissue Engineering Laboratories, and has six years of cell culture and tissue engineering experience with bone marrow stromal osteoprogenitor cells here at Virginia Tech. Skrtic has studied ACP precipitation, purification, and incorporation into remineralizing resins for the past 12 years. Shires’ primary research interests are bone defects, osteoarthritis, and surgical repair. He has the facilities to evaluate host tissue responses to the tissue-engineered materials.

As the interdisciplinary research team better understands how bone-making cells respond to ACP, their next challenge will be to assess these re-growth characteristics in vivo.

Several neurologically based afflictions, such as Huntington’s, Parkinson’s, and Alzheimer diseases, have been correlated to a higher than normal presence of a specific type of enzymes, called transglutaminases (TGase) in the human body. TGases, whose function is to catalyze covalent bonds among proteins, are commonly found in several different human tissues.

In the presence of unusually high levels of these enzymes, some proteins tend to form denser clusters than normal in vivo. If the aggregates grow in size, it can lead to a build-up of insoluble plaques that can block neurovascular transport and cause neural cell death.

“If higher TGase concentrations in cerebrospinal fluid and in the brain lead to protein agglomeration, then their inhibition could reduce symptoms, delay the onset of agglomeration, and maintain viable neural cell health, extending the quality of life for those afflicted,” hypothesizes Brian Love, a professor of materials science and engineering (MSE) at Virginia Tech.

Love, who focuses his research on tissue and cell engineering, and Elena Fernandez Burguera, a post-doctoral research associate, are evaluating specific therapies to fight the abnormally high TGase binding. Based upon the prior work of several others who are conducting clinical trials, Love and Burguera are developing an in-vitro model to evaluate the ability of several inhibitors to block protein aggregation by TGases.

“Our goal is to find the safest and most effective inhibitors that prevent the agglomeration-based cross linking found throughout these neurological disorders.” Brian Love

Based on the work of other scientists, “several compounds show some positive effects,” Love says. These include creatine, cystamine hydrochloride, and a few others. “The development of an inhibition protocol may help test the efficacy of other inhibitors, as well,” the engineer adds.

They are looking at the enzymatic binding of protein-bound polystyrene particles as models. Groups of particles are dispersed in calcium-rich aqueous solutions containing TGases. Once mixed, the particle binding begins. The bigger agglomerates attempt to settle out of the solution, and Love and Burguera track particle sedimentation.

The tracking method, called Z-axis Translating Laser Light Scattering (ZATLLS), is unique to Virginia Tech and based on key concepts in transport phenomena. It has been used to gauge how other complex fluids, such as paints and sealants, are dispersed. Now Love and Burguera are resolving when protein coated particles are effectively dispersed in vitro and under what conditions that they are unstable enough to agglomerate.

They track in-situ sedimentation of protein coated particles exposed to transglutaminase, both in the presence of and without transglutaminase inhibitors. “We can use ZATLLS to resolve whether inhibitors prevent agglomeration of protein coated particles by TGase if the inhibitors lower the particle sedimentation velocity,” Love says. “Our goal is to find the safest and most effective inhibitors that prevent the agglomeration-based cross linking found throughout these neurological disorders.”

Watching all the Cells Go By

Kathleen Meehan is member of a team of researchers from across campus that is pursuing methods to detect biochemical changes within living cells. These changes can be used to monitor cell function and determine how the cell reacts to the presence of toxins, drugs, and normal intercellular biosignals. She is leading the efforts to use optical detection techniques for the live-cell monitors. The team is developing biosensors for applications ranging from monitoring the health of wastewater treatment bacteria to tracking the path of disease-causing viruses through an organism.

Nondestructive live-cell monitoring is important in many research efforts for both efficiency and accuracy. Current methods often involve killing the sample cells in order to monitor and to measure the chemicals that represent the activity being studied.

Meehan is a faculty member in the Bradley Department of Electrical and Computer Engineering.

When a person suffers from burn injuries and needs a skin graft, physicians must be able to assess the flow of blood through capillaries and living tissue in the affected areas. A number of medical procedures to accomplish this currently exist, but they have associated problems.

However, a microsensor used by the engineering profession is showing promise as a measurement technique in the biomedical field. Virginia Tech’s Elaine Scott and her colleagues have adapted this microsensor — used in heat transfer research — to a device that can measure the flow of blood. The primary advantage to a patient is that the procedure becomes non-invasive — the sensor can record its findings without probing inside the body.

Based on a prototype that her colleague, Tom Diller, originally developed, Scott and Diller received a two-year $350,000 grant from the National Institutes of Health ( NIH). They hope to develop an easy-to-use, non-invasive, absolute thermal blood perfusion measurement system for a wide variety of applications.

Scott, a professor of mechanical engineering (ME), is an expert in the field of heat transfer, a fundamental area of mechanical engineering that affects all energy transforming devices from electronic circuits to jet engines. She has developed an inverse technique for estimating unsteady heat fluxes from surface temperature measurements, which she has applied in situations ranging from aerospace surfaces in high-speed flows to this most recent area of blood-flow estimates in bioengineering.

This project began some 10 years ago when she teamed with Diller, who was developing a non-invasive probe that, among other uses, might detect the presence of a tumor in the human body.

They built a prototype that is designed to determine blood perfusion, the measurement of the volume of blood at the capillary level. Changes in blood perfusion are associated with a variety of pathologic processes. As blood flows through the body, its functions include the removal of waste products and the transportation of oxygen and nutrients. Thus, there is a wide range of blood perfusion in human tissue.

“Future directions for this research could include the effects of various drugs on perfusion, the ability to monitor diabetic conditions, and the ability to monitor perfusion in donor organs prior to transplantation.”
Elaine Scott

Scott and Diller’s probe measures surface temperature and heat flux fluctuations. An air supply connected to the microsensor cools it and the underlying tissue through the process of convection, thus eliciting a temperature response from the tissue. Altered perfusion flows can indicate a problem. The needs for this tool extend far beyond testing the viability of skin for a graft. For example, tumors are known to have an altered perfusion.

As Scott explains, the medical community currently uses invasive probes or laser doppler to measure blood perfusion. However, these probes have limitations due to inconsistencies in readings or to their invasiveness.

Working on the NIH grant with Scott and Diller is Otto Lance of the Virginia-Maryland Regional College of Veterinary Medicine. Four ME students, undergraduates Ian Campbell and Patricia Rickets, and graduate students Ashvinikumar Mudaliar and Caroline Comas, are also on the team.

Now, at the end of the first year of testing, the heat sensitive probe’s recorded measured perfusion differences have been evaluated against existing methods and found to show “good sensitivity and repeatability,” Scott says.

“Future directions for this research could include the effects of various drugs on perfusion, the ability to monitor diabetic conditions, and the ability to monitor perfusion in donor organs prior to transplantation,” Scott adds.

Feeding Quantum Dots to Bacteria

Kathleen Meehan is working on the development of quantum dots as intracellular probes. Quantum dots are nanometer-sized pieces of semiconductor material. They are introducing the dots into the fluid around the cells and attempting to trigger
the cells into ingesting the dots.

“We are looking at how the optical properties of quantum dots are influenced by the chemical composition of the cells. The intensity of the light they emit should be a function of the chemicals inside the cell,” Meehan says.

The quantum dot sensors will be used in collaboration with Virginia Tech biologists Jill Sible and John Tyson, who are studying the chemical reaction pathways for cell apoptosis, which is the natural process of cell death. The hope is to make the quantum dots sensitive to specific chemicals so that the researchers can detect when the chemicals appear in the cell.

A well-respected researcher who is now chief of an immunology laboratory of the National Institutes of Health(NIH) has rocked the boat for the experts in the understanding of the autoimmune system.

NIH’s Polly Matzinger has developed the “danger model,” suggesting that the immune system is more concerned with damage detected on the basis of a biological cell’s death than with the introduction of foreign invaders, such as viruses. If Matzinger is correct, then decades of scientific and medical diagnostic thinking could be in jeopardy.

As immunologists consider the relatively new concept, a new NIH grant, awarded to Amy Bell of electrical and computer engineering (ECE) and Karen Duca, a research assistant professor at the Virginia Bioinformatics Institute (VBI), both of Virginia Tech, could answer some of the questions about the human body’s responses to viruses. Viruses cause a number of diseases, from the common cold, to herpes, to AIDS. Even some types of cancer have been linked to viruses.

Prior to Matzinger’s model, the common assumption was that the body’s cells recognize substances or germs that do not come from within the body. The recognition triggers the immune system’s attempt to eliminate the invader. What the immune system actually does, according to Matzinger, is discriminate between things that are dangerous and things that are not. And it does this by defining anything that does damage as dangerous. Through this selectivity process, the immune system does not respond to things that don’t do damage.

Examples she uses to support her thesis that the body recognizes some invading substances are not dangerous include the development of a fetus during a woman’s pregnancy and the production of milk by lactating women.

So the question remains: Do we really know what a body’s host cell does when a virus infects it?

Bell and Duca’s collaboration is an attempt to profile the host-virus system using the electrical engineering concepts of signal and image processing. As Duca, a biophysicist, introduces viruses into cells in a laboratory dish, she infects only the cell’s center. Then, she and Bell, who is also currently associated with VBI as one of its faculty fellows, study the response as the virus moves outward. Their method differs from conventional laboratory studies of viruses that generally involve infecting the entire dish at once.

As the virus moves out from the center in its attempt to infect other healthy cells, Duca identifies and stains relevant markers from the virus and the host. Under ultraviolet lighting, the chemical stains become fluorescent, allowing Bell and Duca to capture images of the laboratory dish at regular time intervals as the infection progresses. The images then provide Bell and Duca with information about innate immune responses to viruses.

Using the NIH support of almost $400,000, Bell plans to next remove the noise from these low-resolution images, creating what she calls a clean immuno-fluorescent intensity signal. The noise she refers to is not audible to the human ear. From an electrical engineering standpoint, noise in this example includes the spurious artifacts that appear in the image due to the microscope’s uneven source illumination. Noise can also result from the spectral overlap of the fluorescent markers that Duca uses.

Also, since the microscope cannot capture the entire laboratory dish at once, multiple sub-images must be taken quickly, then reassembled in the proper matrix. The “montage” artifact arises from the microscope’s uneven illumination, which is brighter in the center and dissipates nearer the edges of the dish for each sub-image.

To compensate for this artifact or noise, Bell’s lab has developed “a method to remove the grid created by assembling the montage of sub-images. Our method — based on a model we developed that reflects the physics of fluorescent microscopy — also estimates and corrects the effect of the microscope’s uneven illumination and the markers’ spectral overlap,” Bell explains.

As Bell and Duca are able to develop their composite images, they will be able to mathematically produce a quantitative description of the spreading of the virus as well as the host-virus interaction. “The immunofluorescent intensity signals (IIS) depict how the virus and host are interacting over time, from the point of origin to the point of infection,” Bell says.

Ultimately, the interdisciplinary team hopes their efforts will provide a quantitative method that derives a characteristic profile or fingerprint from the IIS of any host-virus system. If their method can achieve results in hours instead of days, their techniques could be used in clinical and field settings to quickly identify known viruses, or to map unknown viruses to existing profiles to better predict their behavior and start appropriate treatment.

Ultimately, their work should contribute to what starts an immune response. And as NIH’s Matzinger says, knowing what initiates an immune response will affect and, researchers hope,improve medical treatment.

Developing clothes to monitor health

Computer engineering professors Mark Jones and Tom Martin are developing clothes that can monitor chronic illness through body temperature, blood pressure, heart rates, breathing, and even the way we walk. They dream of garments that can trigger paralyzed limbs to move and that can smooth the motions of patients with Parkinson’s disease or multiple sclerosis.

Their team, working in the e-Textile Laboratory, is merging computers and clothing. They are integrating ultra-fine, detergent-proof wiring into the very weave of the fabric and attaching the necessary miniature processors, sensors, and actuators. The prototype clothing will eventually monitor vital signs and motion for monitoring health and preventing falls. The fabric feels like a soft burlap and is quite comfortable.

Chris Wyatt is an electrical engineer who is attempting to provide the medical community with better, quicker, and more relevant images of the human body. The side effects are not bad either — lower medical costs, new treatments, and earlier disease detection.

Today, doctors and researchers can view the body’s hard and soft tissues through X-ray, ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI) technology. With MRI and positron emission tomography (PET) scans, viewing cellular activity is also possible.

But these viewing techniques can be enhanced. Wyatt is specifically looking at improving imaging for virtual colonoscopies; developing algorithms to replace extensive manual work in brain imaging; and developing image-guided polypectomy technology.

As an example of the impact that smarter imaging techniques could have, consider the pharmaceutical industry and its drug trials. “Drug studies involve many hundreds of patients; 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? 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,” Wyatt, a faculty member in the Virginia Tech– Wake Forest University School of Biomedical Engineering and Sciences, explains.

In brain imaging, Wyatt is concentrating on improving the medical understanding of addiction through modeling techniques. Wyatt is working with the Wake Forest University School of Medicine’s Center for the Neurobehavorial Study of Alcohol (CNSA) to develop algorithms that increase the medical understanding of neurological structures beyond what is currently provided by state-of-the-art MRIs. Wyatt hopes to produce an MRI brain template for two species of macaque monkeys and verify his results using the animals in ongoing studies of alcohol abuse and alcoholism.

“Monkeys are a unique tool for alcoholism research because several aspects of their alcohol consumption closely mimic those of humans,” Wyatt says. “Using monkey models and magnetic resonance imaging, it is possible to design complex studies to understand the neurological mechanisms of alcoholism without the confounding factors problematic in human research. However, current neuroimage analysis tools were designed for use on human data and do not provide the same level of accuracy and robustness when applied to monkey data,” he explains. Wyatt’s goal is to develop a comprehensive set of tools for the analysis of monkey images.

If Wyatt is able to improve medicine’s understanding of the biological mechanisms of addiction, then he will also increase the knowledge about the influence of risk factors and the effects on the body. “As many of these mechanisms are primarily located in the brain, understanding the neurological effects of alcohol and related factors is a key aspect of alcoholism research. This knowledge is critical to diagnosis, treatment, and prevention of alcoholism,” Wyatt says.

Computer-aided diagnosis could also improve the quality of evaluations. “The problem with evaluating all these images manually is that you use different people at different skill levels at different times of the day. People inherently introduce inconsistencies, whereas computers are more consistent and reliable if programmed correctly.”

Wyatt is also pursing imaging advancements in the detection and treatment of colon cancer. “About 50 percent of today’s colon cancer cases could have been prevented with early detection of polyps. Doctors have the screening methods, but compliance is a problem. Colonoscopies are not fun. If we can do the initial screening with more comfortable imaging instead of scoping, we can get higher compliance and detect more cases early,” he says.

He is working to extend the virtual colonoscopy technology to image-guided polypectomy. “The polyps still need to be surgically removed, but patients who already know they have polyps are much more amenable to enduring a scope. A well-trained endoscopist, if there is no problem with insertion, is very fast and very good. Sometimes, though, the polyps can hide in a fold and finding them can be difficult. If we can use virtual colonoscopy to help guide the endoscope to the polyps, we can help the endoscopists become even better and faster.”

While earning his Ph.D. at the Wake Forest University School of Medicine, Wyatt worked in its Virtual Colonoscopy Laboratory, which uses CT data to image the colon.

“My efforts are in connecting prior information to analyze the data we get from different imaging,” he says. The prior information encompasses anatomy, physiology, and imaging experience. “Physicians and radiologists use prior knowledge of the organs and prior experience in reading images,” he explains. “When they look at an image, even if it’s not a good image, they impose their knowledge to extract usable information. We've been working for some time to develop algorithms to incorporate this kind of knowledge into the operating systems of imaging equipment.”

In Virginia Tech’s Musculoskeletal Biomechanics Laboratory, a research volunteer somewhere between the ages of 55 and 65 is strapped in an upper body harness and asked to lean forward while standing on a long platform. Suddenly, a graduate student releases a rope and the volunteer pitches forward, then instinctively takes a step to recover her balance.

As sadistic as this sounds, the student’s motives are aimed at a worthy goal — learning how to prevent often injurious or even fatal falls among older adults. The volunteer suffers only that scary falling feeling. If she doesn't recover her balance, a harness rope attached to the ceiling arrests her fall before she hits the “trip platform.”

This experiment is overseen by Michael Madigan, an assistant professor of engineering science and mechanics and co-director of the lab, who won a two-year grant from the Center for Disease Control’s National Institute of Occupational Safety and Health (NIOSH) to study the role that muscle strength plays in helping older adults recover from tripping.

“One-in-three people over 65 fall at least once a year, and the older we become, the more often we tend to fall,” Madigan says. “There’s data that indicates that about 50 percent of all falls among the elderly are the result of trips.” The majority of falls are either falls forward, commonly caused by trips, or falls backward, commonly caused by slips. Thurmon Lockhart of industrial and systems engineering is studying falls from slips in his Locomotion Research Laboratory.

As the elderly segment of the U.S. population swells in numbers, fall-related injuries are becoming an issue of growing concern. The National Council on Aging, which in March 2005 announced a national action plan for preventing falls, has released some somber statistics: in 2002 about 12,800 people over 65 died from accidental falls and 1.64 million were treated in emergency departments (EDs) for non-fatal falls.

“Or put another way,” the council’s March 9 announcement states, “every hour one older adult died and 183 were treated in EDs for fall-related injuries.”

In his NIOSH-funded research, Madigan is investigating a suspected culprit in these falls. “There’s a good deal of evidence that age-related muscle strength reduction is a primary cause of falls among older adults,” Madigan says, “but recent studies have cast doubt on this theory.”

One mystery Madigan and his students intend to solve is what happens during attempted trip recovery. “A significant number of falls occur even though people of all ages are able to take a step after tripping to recover their balance,” he notes. “But do older people have to use a larger portion of their strength in an attempt to recover? Answering this question will help us determine if muscle strength really is important, or if there are other major causes we need to focus on.”

Madigan’s NIOSH project is in full swing, with two categories of test subjects — college students and people aged 55 to 65 — braving the trip platform.

When a test subject of any age trips and then attempts balance recovery (while secured by the harness), the biomechanics of the event are measured and recorded by a motion analysis system and a series of scales. The motion analysis system consists of infrared markers and a set of video cameras that record the motion of a subject’s body. The scales measure shifts in body weight as the subject first leans forward and then takes a step to recover balance.

“The data recorded by the motion analysis system and the scales is used to create a biomechanical computer model that will show how muscles in the lower body are working,” Madigan says.

After being analyzed on the trip platform, a subject is put on a machine that measures the muscle strength involved in trip recovery by simulating the same knee angles and forward velocities the subject experienced on the platform.

The result should be a precise measurement of the muscle strength exerted by each test subject. Madigan will use the college students’ data to establish baseline measurements, against which he will evaluate the data from experiments with the older subjects.

Madigan and his graduate students then will attempt to find out how much decreased joint muscle strength in older ankles, knees, and hips contributes to an inability to recover balance after tripping. They also hope to learn more about the role muscle strength plays in the overall tendency to trip and fall.

If muscle strength — or the lack of it — proves to be a primary factor in trips and falls, Madigan believes the information can be used to develop specific prevention strategies, such as special weight training and exercise regimens or footwear design modifications.

While working on his Ph.D. at Virginia Commonwealth University, Madigan won a Student Dissertation Grant from the International Society of Biomechanics to study the role of muscle fatigue in musculoskeletal injury. “At that time, I focused my research in the area of sports biomechanics,” he says. “I began studying the subject of falls after coming to Virginia Tech in 2001. Now my research goal is to help prevent falls.”

In addition to studying falls among older people, Madigan is investigating falls in occupational settings with Maury Nussbaum, an associate professor of industrial and systems engineering and Madigan’s mentor on the “trips” project. Funded by another NIOSH grant, the researchers are examining the role muscle fatigue plays in falls from heights among people working in the construction industry.

Let’s make a wager. Two vehicles are side-by-side at a stoplight. In one car — say a Mustang — is a 20-year-old revving the engine while he cranks the stereo up to an obnoxious decibel level. In the other car — perhaps a Lexus — is a 70-year-old quietly paying close attention to the traffic signal.

Statistically, which of these drivers would you bet is more likely to have an accident before returning home?

If you bet on the noisy, impatient adolescent, you’re wrong. The National Highway Traffic Safety Administration reports that drivers aged 65 and older have more crashes per vehicle mile traveled than either young or middle-aged drivers.

Automakers and engineers are beginning to pay more attention to older drivers, and with good reason.

Aging poses unique driver safety issues, and the consumer base of older drivers is increasing significantly as the general population ages. By 2020, an estimated 50 million people over 65 will be eligible to drive in the United States — and almost half of those will be 75 or older.

Losses in visual perception, cognition, and psychomotor (movement produced by action of the mind) functionality are all believed to adversely affect driving ability, says Thurmon Lockhart, an assistant professor in the Grado Department of Industrial and Systems Engineering. With sponsorship from Toyota Motor Corp., Lockhart has been studying the visual perceptions of older drivers.
“Vision is the most critical safety factor for drivers of all ages,” Lockhart notes. “In fact, vision is responsible for up to 95 percent of the sensory information we use while driving.”

As we age and the lens of our eyes become less flexible, we suffer degradation of the accommodative process — the ability of the eye to adjust its refractive power in order to see objects clearly at various distances. This loss of accommodation, also called “presbyopia,” can reduce driving performance and increase the risk of automobile accidents.

Obviously, drivers need to clearly see what’s going on outside their vehicles. But another critical factor is a driver’s visual perception of the vehicle control panel, and this has been the focus of Lockhart’s research for Toyota. “Presbyopia can pose real safety problems for elderly drivers who find it difficult to read instrumentation and dashboard control panel displays, like the ‘door ajar’ symbol,” he says.

“The automobile industry is moving toward active safety technology, such as crash avoidance systems,” Lockhart says. “The new generation of safety systems must help drivers without distracting or confusing them, and this human-machine interface will be especially important for the elderly.”

“This study is aimed at exploring the design attributes and parameters of in-vehicle displays that are needed to accommodate older drivers, especially at night.”
Thurmon Lockhart

Lockhart’s research has been conducted with the help of two groups of volunteers — Virginia Tech students and people aged 65 and older. As the volunteers looked at a control panel simulator in Lockhart’s laboratory, their retinal focus and sensitivity were measured and analyzed. During the experiments, Lockhart and his graduate students changed a number of parameters, including the distance between the test subjects and the control panel, the colors of lights used in the display, and the types and sizes of letters and symbols displayed.

In addition to measuring sharpness and sensitivity of vision, the research team tested the volunteers’ ability to process and react to the changing visual information.

“This study is aimed at exploring the design attributes and parameters of in-vehicle displays that are needed to accommodate older drivers, especially at night,” Lockhart says. “If the design of a vehicle’s control panel provides optimal visual accommodation, the driver can process information much more efficiently and safely.”

The major finding of Lockhart’s research so far offers guidance to automakers in the matter of control panel display colors. “Younger drivers don’t show any performance difference with regard to color,” he says. “But older drivers do tend to perform better at night when displays are in blue. This could be because blue light refracts more while passing through the lens of the eye.”

Future analysis of data from the experiments should help Lockhart determine optimal guidelines for the distance between drivers and control panel displays and the most effective size for display letters and symbols.

“Our goal is to find ways to enhance the comfort and safety of our older drivers,” says Lockhart.

He also is involved in another type of research that could make the world a safer place for older adults. In his Locomotion Research Laboratory, with funding from organizations, including the Whitaker Foundation and the National Institutes of Health, he has been studying why and how older people slip and fall.

“Fifty percent of people over 75 will either die or be forced to enter institutional care because of falls, and I want to find out why these falls happen,” Lockhart says. “We need to understand more about the mechanics involved in being older. It’s important that we not simply accept the folklore about aging and injuries, but try to learn how to prevent those injuries.”

SBES Interim Director

SBES Core Faculty – Virginia Tech

SBES Affiliate Faculty - Virginia Tech

SBES Core Faculty – Wake Forest

SBES Affilliate Faculty - Wake Forest

Centers and Labs

SBES is the partnership of the two eminent educational institutions. Virginia Tech’s highly acclaimed engineering college has long been the university’s educational centerpiece. Since 1987, when U.S. News & World Report starting ranking the top undergraduate engineering programs, and later, the graduate schools, Virginia Tech’s College of Engineering has consistently appeared in the magazine’s listings. The college had already vaulted from the bottom 10 percent in research expenditures to the top 10 percent of all accredited engineering schools between 1965 and 1985, and has remained in this position ever since. Today, the National Science Foundation lists the college among the top 15 for research expenditures. Wake Forest University Baptist Medical Center gained nearly $10 million in funding from the National Institutes of Health (NIH) for the fiscal year that ended on Sept. 30, 2004, reaching $114,768,124 and ranking 36th overall among 125 American medical schools.

The idea to partner the two schools that reside in neighboring states developed through a joint effort of several faculty members. They include Wally Grant, a professor of engineering science and mechanics, and Elaine Scott, a professor of mechanical engineering and the director of Virginia Tech’s Center for Biomedical Engineering, both at Virginia Tech; and Peter Santago, chair of Wake Forest’s Department of Medical Engineering and an alumnus of Virginia Tech’s Department of Electrical and Computer Engineering, and C. Douglas Maynard, M.D., former chair of the radiology department, also of Wake Forest. The four met in 2001, and it led to the involvement of others at each university. By 2004, the two schools officially celebrated the establishment of the academic program and the completion of an interactive video classroom that helps to make the academic exchange possible. Scott became the first acting SBES director, and Santago became the associate SBES director. Scott stepped down in 2005 and Grant is the new acting SBES director.

Today, SBES is focusing on imaging and medical physics, as well as biomechanics and cell and tissue engineering. Imaging has the invaluable potential to greatly extend the reach of medical research beyond detecting the anatomical presence of the disease. Employing applied engineering technologies to treatment will allow more intensive study of diseases at the cellular level. A 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 may harbor as many as 1,000 to 10,000 tumor cells capable of causing a recurrence of the cancer.

This collaboration between engineering and medicine underscores SBES’ distinctive efforts. SBES provides an exceptional environment for research activities that will take place in both Blacksburg, Va., and Winston-Salem, N.C. Engineering faculty and graduate students will team with medical school faculty and students, both at Wake Forest University’s School of Medicine and the Virginia-Maryland Regional College of Veterinary Medicine. And an educational component involving the graduate programs of both universities will provide educational and research opportunities, enabling students to contribute to the advancement of these technologies.

The SBES graduate programs allow students to earn M.S. and Ph.D. degrees in biomedical engineering, a joint M.D./Ph.D. program through the WFU School of Medicine, and a joint D.V.M./Ph.D. program through the VMRCVM. Students may take classes on either campus or by distance learning while residing on their home campus.

Some of the key aspects of the collaboration include:

Virginia Tech College of Engineering faculty members who are fostering a growing biomedical engineering program;
The Virginia-Maryland Regional College of Veterinary Medicine, which houses a Center for Comparative Oncology;
The Wake Forest University’s School of Medicine medical team, whose top priority is cancer research (including The Comprehensive Cancer Center, ranked among the best treatment facilities in the country);
One of the largest non-human primate facilities in the U.S. at Wake Forest’s School of Medicine;
Strong imaging programs at both Wake Forest’s School of Medicine and at Virginia Tech;
Center for Injury Biomechanics at Virginia Tech;
Industrial Ergonomics and Biomechanics Laboratory at Virginia Tech;
Virginia Bioinformatics Institute at Virginia Tech;
Carilion Biomedical Engineering Institute;
Wake Forest University’s Institute for Regenerative Medicine;
Wake Forest University’s School of Medicine’s genomics center.

I hope you will enjoy reading the following pages that highlight some of the research activities that are affiliated with SBES.

Richard Benson
Dean of Engineering

Until recently, few would consider Virginia Tech a critical player in resolving some of the issues of patient-specific medical assessment. Thanks to the university's singular collaboration with Wake Forest University's School of Medicine, that perception is about to undergo a dramatic change.The new partnership between Virginia Tech's highly acclaimed College of Engineering and Wake Forest University, whose Baptist Hospital is traditionally ranked as one of America's top 50 hospitals, creates a unique enterprise, the School of Biomedical Engineering and Science (SBES). Faculty members in the Virginia-Maryland Regional College of Veterinary Medicine (VMRCVM) were also among the initial collaborators. The timing of the partnerships propitious, coinciding with the formation of a new institute within the National Institutes for Health.This institute is focusing on bioengineering and biomedical imaging, two areas that will substantially improve upon monitoring therapy during the course of medical treatment.

Virginia Tech's Department of Computer Science began an effort to build a faculty group in bioinformatics in1999. The department was motivated by the desire to create a critical mass of faculty members who diversified theirresearch portfolios through the addition of National Institutes of Health (NIH) funding. The department also wanted tobecome a leading force in the deep and continuing interaction between computer science and the life sciences duringthe proclaimed 'Century of Biology.'

The department's bioinformatics initiative was launched through a joint proposal by the department andthe Virginia Bioinformatics Institute (VBI) to the state's Commonwealth Technology Research Fund. Throughthis proposal the department has hired five faculty members in bioinformatics. The bioinformatics groupcurrently contains six core faculty, at least seven strongly affiliated faculty, and three VBI faculty with tenuredappointments in the department. Within five years of the creation of this initiative, the faculty is responsible for more than $10 million in ongoing, funded interdisciplinary bioinformatics work.

Algorithms: Vicky Choi, Lenny Heath, Eunice Santos, Joao Setubal, Cliff Shaffer, Layne Watson
Algorithms and the Mathematical Foundations of Computer Science: Vicky Choi, Lenny Heath, Madhay Marathe, Eunice Santos, Joao Setubal, Cliff Shaffer, Layne Watson
Computational Structural Biology: Alexey Onufriev, Adrian Sandu
Computational Systems Biology: T.M. Murali
Data Mining: Naren Ramakrishnan
Genomics: Lenny Heath, T.M. Murali, Naren Ramakrishnan, Joao Setubal, Liqing Zhang
Human Computer Interaction, Visualization: Chris North
Image Processing: Roger Ehrich, Layne Watson
Information Retrieval: Roger Ehrich
High Performance Computing: Adrian Sandu, Eunice Santos, Layne Watson
Optimization: Layne Watson
Simulation: Chris Barrett

Dean: Richard C. Benson
Editor and Writer: Lynn Nystrom
Art Director and Designer: Barbara Corbett
Photo Editor and Lead Photographer: Michael Kiernan
Photographers: Michael Kiernan and Rick Griffi ths
Contributors: Richard Lovegrove, Elizabeth Crumbley,
Karen Gilbert, and Shari Mueller

Virginia Tech does not discriminate against employees, students, or applicants for admission or employment on the basis of race, gender, disability, age, veteran status, national origin, religion, sexual orientation, or political affi liation. Anyone having questions concerning discrimination should contact the Office for Equal Opportunity.