James R. Stone, MD, PhD, assistant professor departments of radiology and neurosurgery, University of Virginia

Responsible for 2.1 million injuries and 50,000 deaths annually in the U.S., traumatic brain injury (TBI) is the leading cause of death in individuals under the age of 35. The incidence among deployed soldiers is also high, with one study suggesting as many as 300,000 Iraq and Afghanistan veterans have some form of TBI.

One of the challenges associated with TBI, which has been identified as a major public health problem, is obtaining a prompt and accurate diagnosis. Existing clinical imaging methods for detecting TBI—CT and MRI—are usually confined to a hospital setting and provide information concerning gross changes to brain structure. Although emerging methods using functional and diffusion MRI have shown promise in improving capabilities for detecting TBI, there remains a clear disconnect between changes known to occur in TBI and those which clinicians are currently able to detect with imaging.

To address these issues, researchers at the University of Virginia Health System, in partnership with federal laboratories and supported by $6 million Department of Defense (DoD) grants, are exploring two potential imaging approaches to improve diagnosis.

The first project—development of a handheld, battle-ready ultrasound system capable of measuring tissue stiffness—builds on earlier laboratory research examining the viscoelastic properties of injured tissues, James Stone, MD, PhD, assistant professor of radiology and medical imaging at the University of Virginia School of Medicine in Charlottesville, told Health Imaging News.

Several years ago, Stone and colleagues demonstrated measurable changes in tissue stiffness after experimental TBI by correlating microscopic evidence of tissue injury with direct measurements of tissue stiffness using a laboratory tissue indenter device. Although it's known that tissues can be disrupted following TBI, this study demonstrated this alteration occurs in a physically measurable fashion, Stone explained. “This established the theoretical basis for the next stage—developing a noninvasive diagnostic tool that might detect elastography changes associated with TBI.”

Stone’s research parallels other efforts in breast and liver ultrasound to develop elastography. However, Stone’s proof-of-concept hinges on exploring whether ultrasound is capable of detecting tissue stiffness associated with TBI and migrating elastography functionality to a rugged, handheld ultrasound system that combat medics could use to acquire the appropriate data.

The other research project, launched last year, involves the development of PET probes for improved diagnosis of TBI in settings where advanced imaging is available. Stone and colleagues are focusing on probes to assess hypoxia, inflammation, neutrophil infiltration, apoptosis and necrosis to determine if they may help diagnose TBI.

Although the DoD ultrasound grant emphasizes a battlefield-ready system to measure tissue stiffness, Stone envisions stateside applications as well. For example, an EMT might use the portable system on soccer or football sidelines to determine whether a player who sustained a blow to the head requires immediate follow-up.

If the research team successfully develops the new diagnostic techniques, they could help physicians better diagnose TBI, says Greg Helm, MD, PhD, professor of clinical neurological surgery and biomedical engineering at the UVA School of Medicine. Improved diagnosis could equip clinicians with better tools to optimize management and refine prognosis. Furthermore, precisely identifying injury may allow physicians to more effectively evaluate promising therapies for the treatment of TBI.