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February 20, 2014

Research Notes

Repurposing drugs holds cancer promise

By screening a library of FDA-approved anticancer drugs that previously wouldn’t have been considered as a treatment for a rare type of cancer, University of Pittsburgh Cancer Institute (UPCI) scientists were surprised when they found several potential possibilities to try if the cancer becomes resistant to standard drug treatment.

The discovery, published in Cancer Research, demonstrates that high-throughput screening of FDA-approved drugs can identify new therapies that could be moved rapidly to the clinic.

Said senior author Anette Duensing, pathology faculty member at UPCI: “This is known as ‘drug repurposing,’ and it is an increasingly promising way to speed up the development of treatments for cancers that do not respond well to standard therapies. Drug repurposing builds upon previous research and development efforts, and detailed information about the drug formulation and safety is usually available, meaning that it can be ready for clinical trials much faster than a brand-new drug.”

Duensing and her team ran the screening on 89 drugs previously approved by the FDA in an attempt to find more treatment options for patients with gastrointestinal stromal tumors (GISTs), which are uncommon tumors that begin in the walls of the gastrointestinal tract. According to the American Cancer Society, about 5,000 GIST cases occur each year in the United States with an estimated five-year survival rate of 45 percent in patients with advanced disease.

GISTs are caused by a single gene mutation and can be treated successfully with the targeted therapy drug imatinib, known by the trade name Gleevec. However, about half of the patients treated with Gleevec become resistant to the drug within the first two years of treatment.

After studying how GIST samples responded to various concentrations of the 89 drugs in the laboratory, Duensing and her colleagues identified 37 compounds that showed some anticancer activity in at least one of the concentrations tested. Importantly, they noted that the most promising candidates all belonged to only two major drug classes: inhibitors of gene transcription and so-called topoisomerase II inhibitors. Based on these findings, the research team selected the two most promising compounds for further testing: gene transcription inhibitor mithramycin A, which is in clinical trials to treat Ewing sarcoma, and topoisomerase II inhibitor mitoxantrone, which is used in metastatic breast cancer and leukemia.

Both drugs were highly effective in fighting GISTs in laboratory tests. Moreover, the mechanism of action of each drug was linked to the specific underlying biology of these tumors.

“These are very encouraging results,” said Duensing. “The next step will be moving our findings to clinical exploration to see if the results we found in the lab hold up in patients.”

Additional Pitt co-authors of this study included Sergei Boichuk, Derek J. Lee, Keith R. Mehalek, Kathleen R. Makielski, Danushka S. Seneviratne, Rolando Cuevas,  Joshua A. Parry, Matthew F. Brown, James P. Zewe and Shih-Fan Kuan. Other researchers on the study were from Catholic University in Leuven, Belgium; University of Heidelberg, Germany, and Kochi Medical School, Japan.

The research was supported by the American Cancer Society, The Life Raft Group, GIST Cancer Research Fund and the Howard Hughes Medical Institute.

Researchers gain $1 million for 3-D printing

Additive manufacturing (AM) or 3-D printing represents a transformative method for time-sensitive, on-demand production of complex structures from a digital blueprint. But a research team from the Swanson School of Engineering proposes that by integrating a cellular structure or “latticework” into the digital blueprint, load-bearing AM products can be made more sustainably, with less weight and lower cost while maintaining the necessary structural integrity.

“Developing Topology Optimization Tools That Enable Efficient Design of AM Cellular Structures” was one of 15 projects selected by America Makes, the National Additive Manufacturing Innovation Institute, as part of its second call for AM applied research and development projects. Principal investigator is Albert To, mechanical engineering and materials science faculty member; co-PIs are Kevin P. Chen of electrical and computer engineering and Paul E. Lego Faculty Fellow, and David Schmidt of mechanical engineering and materials science. The $438,000 grant, with an additional $526,000 match from Pitt and corporate partners, is for an 18-month period.

3-D printing utilizes a robotic arm to lay successive layers of materials such as ceramics, metals and polymers to create simple structures or complex parts. To’s research aims to enhance AM by integrating a computer-designed cellular structure into the layering process, allowing for more efficient and sustainable manufacturing.

Said To: “When we design a load-bearing structure, we need to span a certain volume. But we don’t need to create an entirely solid object; we just need to create a framework to maintain its structural integrity. By developing a computational model that allows us to integrate a cellular structure into the designs of AM products, we can reduce weight, maintain load-bearing capacity, and enhance the sustainability of the entire process.”

To says that because AM is so new, current computational tools don’t allow for the optimal design of a complex cellular structure within an AM product. Coupling his research expertise in computational mechanics and materials with companies involved in AM, computational modeling, and materials will enable them to develop more efficient design and optimization of these cellular structures. Corporate partners will include Acutec Precision Machining, Alcoa, ANSYS and ExOne.

“Design of AM cellular structures can be incredibly complicated, and so we need to utilize advanced mechanics theory to create an efficient model that can be used for multiple AM platforms and with various types of materials,” he said. “This also allows for easier recycling of a product because the cellular structure enables the base materials to be broken down into the native powder form used in AM.”

The team will investigate many different kinds of lattice structures, from random patterns to geometric forms like honeycombs, to determine which provides the best structural integrity in AM. He notes that varying the porosity of cellular structures optimizes the weight and mechanical performance of a product, making AM a more valuable tool for aerospace, health care, and military applications such as on-demand manufacturing of replacement parts.

“Every extra pound adds to the cost of manufacturing, transporting and storing a product, and so introducing a cellular matrix helps to reduce these costs while still maintaining a high degree of quality,” he said. “For example, we could create lighter parts for aircraft that would improve fuel efficiency without sacrificing reliability. Or instead of storing complex replacement parts on remote military bases and even the International Space Station, 3-D printers could be used to manufacture a new part without having to transport it from the supplier.

“Additive manufacturing will not replace traditional manufacturing, but it will become a cost-effective, sustainable alternative for many niche applications.”

Ctr. for Medical Innovation  gives awards for biomedical technology

The Center for Medical Innovation (CMI) awarded a total of $82,000 to six research groups through its 2013 round-2 pilot funding program for early stage medical technology research and development. The latest projects to receive funding include a “smart” topical wound gel; a CPR system; an infectious disease detection device, and a prototype instrument for minimally invasive brain surgery.

CMI, a University center housed in the Swanson School, funds early-stage applied technology projects, with the goal of transitioning the work to clinical adoption.

Proposals were evaluated on the basis of scientific merit, technical and clinical relevance, potential health care impact and significance, experience of the investigators, and potential in obtaining further financial investment to translate the particular solution to health care. Funding ranges from $10,000 to $25,000 each.

Said Alan D. Hirschman, CMI executive director, “CMI serves as a critical ‘kickstart’ for biomedical devices that are ready to move to the next level of R&D, and so we’re excited for the potential of these six projects. The CMI leadership team was impressed by the quality of these proposals, which represent some of the most intriguing early-stage interdisciplinary research at Pitt and UPMC.”

The projects are:

  • Award 1: To develop Curostem, a “smart” topical wound gel that incorporates biological and pharmacological materials into a bioengineered polymer gel topically applied to non-healing wounds in all clinical care settings. Research team: Donald P. Taylor, bioengineering faculty, Swanson School; Austin Nuschke (student co-PI), pathology; Alan Wells, bioengineering; Eric Beckman, chemical engineering faculty.
  • Award 2: To develop a rapid point-of-care instrument using isothermal DNA amplification to detect antibiotic-resistant bacteria. Research team: Abhay N. Vats and Kathrin Gassei, both of pediatrics, Children’s Hospital; Alex K. Jones and William Stanchina, electrical and computer engineering faculty.
  • Award 3: To develop a device for use with laparoscopic surgical instruments to eliminate the risk of burns for over 2 million patients annually. Research team: Benjamin T. Ristau, urology resident, UPMC; William W. Clark, mechanical engineering and materials science faculty; Steven G. Docimo, chief medical officer, Children’s Hospital.
  • Award 4: To design, build and test a prototype device for minimally invasive brain surgery that can mitigate most of the tissue trauma generated by surgical devices. Research team: Johnathan A. Engh, neurological surgery, UPMC; Anne M. Robertson, mechanical engineering faculty.
  • Award 5: To continue development of a “smart” CPR system. The grant will fund experimental work and preclinical studies. Research Team: Clifton Callaway and James Menegazzi, emergency medicine, UPMC; William Clark, mechanical engineering and materials science faculty; Matthew Sundermann, graduate student in bioengineering.
  • Award 6: To continue development of an advanced gel for treatment of macular degeneration and other eye diseases. Research team: Yadong Wang, bioengineering faculty; Thomas Friberg, ophthalmology, UPMC.

Viral evasion discovery points to potential drugs

Some viruses are evading our immune systems by blocking the protein that our cells use as a “check” to block early stages of growth, thereby allowing the deadly viruses to slip in unnoticed.The blocking structure, called a “stem-loop,” is found at the beginning of the virus’s genetic material.

This discovery, published in Science, is the first time researchers have found such an evasion mechanism built directly into the genetic material of a virus.

Said co-author William Klimstra, faculty in the Center for Vaccine Research (CVR): “Knowing how viruses evade the immune system points to a potential target for designing new drugs.

One of the difficult parts of designing antiviral drugs is making sure the drug targets the virus and not the host, or the drug can cause some very serious side effects. It’s an especially tough nut to crack, making this discovery a very productive area of investigation.”

Klimstra and his colleagues at CVR did much of the virus work for the research in the Regional Biocontainment Laboratory, a high-security facility constructed with Pitt and NIH funds.

The researchers studied alphaviruses, a group of viruses that include West Nile, influenza, SARS, yellow fever and polio. These viruses encode their genes directly into RNA, which is genetic material read by a cell’s protein-making machinery.

When the alphavirus’s stem-loop is stable, a key immune system protein called Ifit1 is blocked from binding to the viral RNA, allowing the virus to begin growing in the cell and enabling infection to proceed unchecked.

This builds on several years of research by Klimstra’s team, including their 2005 discovery showing that Ifit1 has antiviral activity against invading RNA viruses.

Additional co-authors  included Christina L. Gardener and Derek W. Trobaugh of CVR, and researchers from Washington University, Osaka University and the University of Texas.

Public health begins HIV research on black men

The Graduate School of Public Health and the Center for Black Equity are partnering on a new research project to study reasons for increased risk of HIV infection among African-American men who have sex with men (MSM).

The project, funded by a $3.2 million grant from the National Institute of Nursing Research at the National Institutes of Health (NIH), will seek to enroll nearly 6,000 African-American MSM who attend Black Gay Pride events in large cities nationwide.

Said Ron Stall, director of the Center for LGBT Health Research at the public health school: “It has become clear in recent years that the major reason that African-American MSM have such high rates of HIV infection is not that these men have high rates of risk-taking behaviors for infection.  Rather, the reason for elevated infection has far more to do with lack of access to HIV testing and medical care.”

Stall and his team plan to recruit men for their study at Black Gay Pride events in Atlanta, Chicago, Houston, Los Angeles, Philadelphia and Washington D.C. Black Gay Pride events have grown to become a social movement in the United States attended by an estimated 300,000 people annually.

The men will be asked questions as part of an anonymous survey that will help researchers understand the barriers and facilitators to HIV testing and care.

In addition to data about HIV risk in this population, the study will generate information about other social determinants that are likely to be important to the overall health of African-American MSM, including depression, substance use, violence victimization and other health problems. Finally, the study will measure specific resiliencies — or the ability to avoid negative health outcomes — that may be important resources for health, even among men who must cope with adverse social environments.

“HIV/AIDS has been a crisis in the African-American MSM community for more than 30 years, and it is past time that we took this epidemic more seriously,” said Stall. “We hope that this study, in collaboration with other research and care efforts, will provide a real contribution to bringing this dangerous epidemic to an end.”

This project is being funded by NIH.

Bio course duplicates success in 70 colleges

Graham Hatfull, biology faculty member, is simultaneously studying “phages” (short for viruses called bacteriophages) and ways to improve science education on college campuses nationwide.

Hatfull’s success developing a “phage-hunting” course that’s applicable for freshmen education at a range of institutions is chronicled in a study published in mBio from the American Society for Microbiology.

Hatfull, the Eberly Family Professor of Biotechnology in the Kenneth P. Dietrich School of Arts and Sciences, began enlisting undergraduate students in his ongoing hunt for novel phages in 2001. The following year, he was named one of 20 Howard Hughes Medical Institute Professors tasked with developing creative, nationally applicable science education programs and putting them into practice.

For the next several years, with the help of others, Hatfull created a course intended to attract freshman college students to science. Called Science Education Alliance Phage Hunters Advancing Genomics and Evolutionary Science (SEA-PHAGES), the course, formalized in 2008 at Pitt, now is being taught at 70-plus colleges and universities around the country.

To date, SEA-PHAGES students have found 3,000 new bacteriophages (all catalogued in Pitt’s mycobacteriophage database ( and have been listed as co-authors on 10 scientific journal articles. The students get to name their own phages, which gives them a sense of ownership over their contributions to phage research.

SEA-PHAGES graduates are more likely to continue in the sciences. The study published in mBio analyzes the progress of more than 4,800 students who went through SEA-PHAGES over five years. The students followed the course at a range of institutions — from research universities to colleges granting associate’s degrees. SEA-PHAGES students consider themselves better educated than students who undertook intensive summer research programs and were more likely than their peers to stay involved in science. Some stay involved by becoming undergraduate teaching assistants for the next group of phage-hunters.

While there are many phages, not much is known about them. As a practical matter, the discovery and genetic profiling of new bacteriophages will shed light on what information their genes encode and what individual genes do, enabling a better understanding of their role in the environment, where they substantially impact carbon turnover rates and their role in bacterial pathogenesis —how bacteria make us ill.

SEA-PHAGES also differentiates itself from other courses by introducing students to research methods and approaches, experiment design and data interpretation in the context of a specific project (the phage hunt) rather than in generalities, allowing them to see exactly how abstract knowledge applies to authentic research.

The two-semester course begins with students digging in the dirt, then isolating phages from their soil samples. What happens next essentially is practicing microbiology as students grow a stock of phages to work with and examine them under an electron microscope, looking at their form and structure. Semester two is all about sequencing and studying their phage’s genome, using the tools of bioinformatics and computational biology.

Said Hatfull: “They use complicated math to predict the location of genes, the organization of the genome, and to figure out what the genes do. Then they examine how the genome of their phage is related to the other genomes out there.”

The study, “A Broadly Implementable Research Course in Phage Discovery and Genomics for First-Year Undergraduate Students,” was supported by the Howard Hughes Medical Institute.

Call frequency predicts hospitalization

A comprehensive analysis of patient telephone records at an inflammatory bowel disease (IBD) clinic revealed that 15 percent of patients account for half of all calls to the clinic. Forty-two percent of frequent-caller patients also were seen in the emergency department or hospitalized within the following year.

The results, which can help doctors identify patients with the most severe disease and those at risk of potentially avoidable high-cost medical interventions, were published in Clinical Gastroenterology and Hepatology.

Inflammatory bowel diseases (Crohn’s disease and ulcerative colitis) are chronic lifelong conditions that affect the gastrointestinal tract of up to 2 million Americans, the majority of whom are diagnosed as young adults. Telephone communication in IBD care is common, and involves reporting clinical status, treatment, reassurance and completion of health care forms and insurance authorization. Yet, until now, there has been limited information on telephone activity volume or the reasons for calls in the care of chronic illness, including IBD.

Said senior author David Binion, visiting faculty member in medicine, clinical and translational science and co-director of the IBD Center in the School of Medicine: “Telephone surveillance and the use of Big Data allowed us to find red flags identifying patients at risk of high-cost medical interventions, such as emergency department use and/or hospitalization. These findings can help to identify disease severity and teach us how to take better care of our patients.”

Researchers tracked more than 50,000 phone calls over a period of two years, from more than 3,000 patients. The researchers assessed associations between clinical factors and logged telephone encounters, and between patterns of telephone calls and future visits to the emergency room or hospitalization.

Calls were categorized into five groups:

  • Problem/follow-up (incoming calls from patients), representing 52 percent of all calls.
  • Resolution/plan (outgoing calls to patients), representing 25 percent of all calls.
  • Refill requests/pharmacy contacts, representing 12 percent of all calls.
  • Insurance authorization, representing 10 percent of all calls.
  • Completion of forms or record requests, representing 1 percent of all calls.

Researchers also measured telephone encounters logged into electronic medical records in consented subjects from a prospective IBD research registry. Patients calling more than 10 times per year were considered high telephone encounters.

Results showed that:

  • Telephone calls are predictors of how likely patients are to enter the emergency room: clusters of phone calls over time were highly predictive of who ended up in the hospital over the course of the next year.
  • Frequent telephone calls correlated with poorly controlled inflammation of IBD and patients with a high degree of pain and difficulty coping.

“We believe we will ultimately be able to use this information to prevent hospitalization, since we now have better insight into the heterogeneous factors which are getting our patients into trouble,” added Binion.

“Our next step is to set up an intervention trial, where patterns of telephone activity will be used as an early warning strategy to identify at-risk patients. Perhaps the most important aspect of the study was its simplicity and generalizability, as records of telephone communication in health care are an important part of electronic health records available throughout the U.S.

Drug that stabilizes mood could treat liver disease

Opening up a can of worms is a good way to start hunting for new drugs, recommend researchers from the School of Medicine and Children’s Hospital.

In a study published in the Public Library of Science One, they used a primitive worm model to show that a drug typically used to treat agitation in schizophrenia and dementia has potential as a treatment for a-1 antitrypsin (AT) deficiency, an inherited disease that causes severe liver scarring.

In the classic form of AT deficiency, which affects 1 in 3,000 live births, a gene mutation leads to production of an abnormal protein, dubbed ATZ, that unlike its normal counterpart is prone to clumping, explained David H. Perlmutter, Vira I. Heinz Endowed Chair in pediatrics.

Said Perlmutter: “These protein aggregates accumulate in liver cells and eventually lead to scarring of the organ or to tumor formation. If we could find a drug that slows or stops this process, we might be able to prevent the need for liver transplantation in these patients.”

To find that drug, Perlmutter’s team worked with Stephen Pak in pediatrics and Gary Silverman, Twenty-five Club Professor of Pediatrics, Cell Biology and Physiology, who developed a model of AT deficiency in Caenorhabditis elegans, or C. elegans, a harmless microscopic worm or nematode typically found in soil. Previous experiments conducted by Pak and Silverman, in which more than 2,000 compounds were screened, showed that fluphenazine, a drug approved for human use as a mood stabilizer, could reduce ATZ accumulation in the worm, so the team studied it further.

Worms that produce ATZ die sooner than normal ones, which typically have a life span of fewer than 20 days. Those that were exposed to fluphenazine, however, had lower burdens of ATZ and lived more than a day longer than untreated animals. The lifespan of normal worms was unchanged by fluphenazine exposure. The researchers also labeled with fluorescent markers intracellular structures called autophagosomes, which help clear abnormal proteins out of the cell in a process called autophagy. Fluphenazine exposure was associated with a greater presence of autophagosomes, suggesting that increased autophagy led to reduced ATZ accumulation.

Follow-up experiments showed that fluphenazine reduced ATZ accumulation in several mammalian-cell line models of AT deficiency, Silverman said.

“We found when we gave this drug for three weeks to mice with the disease, autophagy is activated, the abnormal protein load is diminished and liver scarring is reversed. It’s truly amazing,” he said. “And because fluphenazine is already being safely prescribed for other conditions, it should be easier to bring it to clinical trials for AT deficiency.”

The project also reveals the power of the worm model to rapidly screen drug candidates, Perlmutter noted.

“This is the first extensive investigation of a drug that was discovered through the C. elegans screening method,” he said. “It’s remarkable that you can take a completely unbiased, high-content screen using a primitive organism and end up identifying a drug that reduces the accumulation of an abnormal protein in mammalian cell lines and a living mouse. It’s proof-of-principle of this research pipeline. Furthermore, this drug is very similar pharmacologically to carbamazepine, another mood stabilizer that we found to enhance autophagy and reverse liver fibrosis in the mouse model of a-1 antitrypsin deficiency.”

Other co-authors in medicine included Jie Li, Linda P. O’Reilly, Joshua A. Benson, Yan Wang, Tunda Hidvegi, Pamela Hale, Christine Dippold, and Michael Ewing.

The project was funded by the U.S. Public Health Service and the Hartwell Foundation.

Uninsured have fewer hospital transfers

Uninsured patients with a variety of common medical diagnoses are significantly less likely to be transferred between hospitals for treatment, according to a study led by researchers at the School of Medicine. They also found that women, insured or not, are less likely to be transferred between hospitals. The findings, in the Annals of Internal Medicine, suggest that non-medical factors, including patients’ sex and insurance coverage, may influence care decisions and lead to potential health disparities.

Said Janel Hanmer, medicine faculty member and lead author of the study: “Federal law requires hospitals and physicians to care for and stabilize any patient with an emergency medical condition, regardless of the patient’s ability to pay. While there’s been persistent concern about patients being transferred between hospital emergency rooms for non-medical reasons, our study is one of the first to look at inter-hospital transfers among patients who have already been admitted to the hospital.”

The researchers used data from the 2010 Nationwide Inpatient Sample (NIS), the largest all-payer inpatient care database in the United States, to examine the relationship between a patient’s insurance coverage and the hospital transfers for five common medical diagnoses: biliary tract disease, chest pain, pneumonia, sepsis and skin infection.

The data covered 315,748 hospitalized patients, ages 18-64, who were discharged from 1,051 hospitals across the country.

The researchers were surprised to find that uninsured hospitalized patients were 20-40 percent less likely to be transferred to another hospital for four of the five diagnoses when compared with privately insured patients, even after adjusting for demographic factors and severity of illness. Additionally, women were significantly less likely to be transferred than men for all five diagnoses, with transfer rates of women occurring 35-40 percent less often than for men. The transfer rate for all patients between hospitals was 2-5 percent, depending on the diagnosis.

“We hypothesized that uninsured patients would be more likely to be transferred as hospitals tried to punt these unprofitable cases to other hospitals in the area. Our study showed this did not happen,” said Hanmer. “Instead, we found that uninsured patients (and women) were substantially less likely to be transferred, suggesting that perhaps both the uninsured and women are not being transferred when they should be.”

The data used in the study lacked detail necessary to determine if the differences seen were due to clinical differences, patient preference, physician referral patterns or receiving hospital screening practices.

Still, said Hanmer, the study is cause for concern and future investigation into the outcomes of transferred patients. “If we presume that transfer between hospitals results in greater access to advanced treatments, then it’s evident that the uninsured and women face a serious health care disparity,” she noted. “Alternatively, privately insured patients and men may be at risk of greater exposure to more costly procedures and excessive treatments.”

Collaborators on the study included researchers at the universities of Iowa and Toronto.

The research was funded by the Department of Veterans Affairs, the National Heart, Lung and Blood Institute and NIH.

Low vitamin D could result in severe preeclampsia

Women who are deficient in vitamin D in the first 26 weeks of pregnancy may be at risk of developing severe preeclampsia, a potentially life-threatening disorder diagnosed by an increase in blood pressure and protein in the urine, according to Graduate School of Public Health research.

In one of the largest studies to date, researchers examined blood samples collected from 700 pregnant women who later developed preeclampsia, in an effort to examine a woman’s vitamin D status during pregnancy and her risk of developing preeclampsia. The full study, funded by NIH, is available online in Epidemiology.

Said lead author Lisa Bodnar, faculty member in public health’s Department of Epidemiology: “For decades, vitamin D was known as a nutrient that was important only for bone health. Over the past 10 to 15 years, scientists have learned that vitamin D has diverse functions in the body beyond maintaining the skeleton, including actions that may be important for maintaining a healthy pregnancy.”

Bodnar and her colleagues also studied blood samples from 3,000 mothers who did not develop preeclampsia. The samples were collected between 1959 and 1965 at 12 U.S. sites enrolled in the Collaborative Perinatal Project. The blood was well-preserved, and researchers were able to test for vitamin D levels decades later.

Scientists controlled for factors that could have affected a woman’s vitamin D status, including race, pre-pregnancy body mass index, number of previous pregnancies, smoking, diet, physical activity and sunlight exposure, which is the body’s primary source of vitamin D.

The researchers found that vitamin D sufficiency was associated with a 40 percent reduction in risk of severe preeclampsia. But there was no relationship between vitamin D and mild preeclampsia. The overall risk of severe preeclampsia in the women sampled was 0.6 percent, regardless of vitamin D status.

“If our results hold true in a modern sample of pregnant women,” said Bodnar, “then further exploring the role of vitamin D in reducing the risk of preeclampsia would be warranted. Until then, women shouldn’t automatically take vitamin D supplements during pregnancy as a result of these findings.”

Additional Pitt co-authors included Hyagriv N. Simhan, Janet M. Catov, James M. Roberts and Jill C. Diesel, along with a researcher from McGill University.

GE/NFL give award for brain imaging research

General Electric and the NFL have awarded one of their inaugural Head Health Initiative grants to a joint Pitt-UPMC effort in which researchers will assess whether a powerful imaging technology can identify concussion and subsequent recovery in a newly injured athlete in order to safely return him or her to play.

The $300,000 grant includes an option to apply for additional funding after the opening six months of the study. About 1.7 million Americans sustain concussions every year.

High definition fiber-tracking (HDFT), developed by a team led by Walter Schneider, faculty member in psychology and neurological surgery and a senior scientist at the Learning Research and Development Center, will be tested in a one-year study to see if it could become the first imaging technique to accurately and consistently aid in determining a diagnosis of concussion and injury prognosis.

The proposal, among 402 submitted internationally, was one of 15 winners.

The project will study 50 or more athletes ages 13-28 who sustained a head injury within seven days of seeking care at the UPMC Sports Medicine concussion program. In addition to undergoing examination-room assessments, vestibular and ocular evaluations and neurocognitive testing, patients will have an HDFT scan.

There are billions of neural connections in 40 major fiber tracts in the human brain, comprising the information cables of the mind, explained Schneider. Conventional imaging is not able to show these cables or to pick up the subtle damage that can be caused by a mild traumatic brain injury. HDFT, however, uses advanced computational means to process data from sophisticated magnetic resonance imaging (MRI) machines, revealing these brain pathways and spots where the tracts might be disrupted.

Said Schneider:“This imaging technology allows us to see fiber loss and tract breaks, which has not been possible before. HDFT could provide an objective way of identifying and quantifying damage, as well as a way to monitor healing. Concussion patients may find it a relief to be able to point to a specific cause for symptoms that otherwise might seem inexplicable.”

The researchers will also determine whether HDFT imaging findings align with functional impairment and symptoms in patients. For example, the HDFT findings might show that there is damage to a memory tract in the brain that corresponds to functional impairment in memory performance. As the athlete recovers, investigators may see the evidence of this in both functional and HDFT findings.

The project will involve others from the Schneider lab and the UPMC concussion program.


The University Times Research Notes column reports on funding awarded to Pitt researchers as well as findings arising from University research.

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