By Rob Mitchum // May 16, 2014
The public perception of concussions has changed dramatically in the last few years. What was once considered a minor injury by some, merely a case of “getting your bell rung,” recent findings in football players, soldiers, and other concussion-sufferers about the long-term effects of these injuries have raised awareness and fear about head trauma. Unfortunately, the “milder” form of traumatic brain injuries (known by the acronym mTBI) is difficult to detect using standard imaging procedures, such as MRI and CAT scans. But as University of Chicago radiologist Michael Vannier explained in his Research Computing Center talk May 8th, computational methods may soon provide new biomarkers and diagnostics for physicians to treat patients with head injuries.
Vannier believes that the solution may lie in a specialized form of MRI scans, called diffusion MRI. Traditional MRI measures the excitation of hydrogen atoms stimulated by a magnetic field, producing slices of images that doctors use to find tumors, strokes, and other damage. In diffusion MRI, the scanner tracks the diffusion of water through tissue, revealing more information about the architecture of the brain, heart, or other organs. The same equipment can be used for both scans; diffusion MRI simply requires a different protocol.
However, diffusion MRI is more commonly used for research, such as the Human Connectome Project, instead of clinical purposes. The method excels at tracing the paths of the brain’s white matter, the often long neuronal projections sheathed in myelin. For many of the basic uses of MRI, this level of detail is not necessary. But as more neurological conditions — including autism, multiple sclerosis, and traumatic brain injury — are linked to damage or differences in white matter, diffusion MRI is gaining steam as a diagnostic technique. Surgeons are also increasingly using the method to help plan for delicate procedures such as removing tumors or placing brain-stimulation electrodes, mapping the important tracts of the brain so that they are not damaged during surgery.
Traumatic brain injuries are usually categorized as one of three levels: mild, moderate, and severe. Not only are these diagnoses somewhat vague, they also provide little guidance as to what clinical course of treatment a patient should receive, Vannier said. Often, after a concussion, no brain damage can be detected on a traditional scan. But diffusion MRI may allow physicians to see the axonal damage and other diffuse brain injuries that better define the severity of a head trauma.
“With these diffuse injuries, what we would like to have is a method so that we can visualize brain injuries, because most people survive these injuries,” Vannier said. “But the ordinary techniques that we would use would not find anything abnormal.”
To create a more precise diagnostic scale for traumatic brain injury, researchers will need to find imaging biomarkers that predict the future course of the damage closer to the time of injury. But validating new biomarkers is an arduous process, Vannier said, requiring a strong body of evidence, reproducibility, and predictive value. Meeting these requirements means setting up large, coordinated studies involving multiple hospitals using standardized methods — no easy task.
Fortunately, similar efforts to find neuroimaging biomarkers for other conditions provide guidance for the traumatic brain injury community. Projects underway for acute stroke, Alzheimer’s disease, brain cancers, and autism have figured out how to create the national infrastructure, data repositories, analysis methods, and software development necessary for a successful search. In 2012, the largest yet coordinated project to study traumatic brain injury in this manner launched as FITBIR, short for Federal Interagency Traumatic Brain Injury Research. FITBIR partners include the NFL, NCAA, and the Department of Defense, groups with a highly vested interest in creating more knowledge about diagnosing and treating these injuries.
However, the promise of this project comes at a depressing time for the traumatic brain injury field, as a recent meeting concluded that not a single phase 3 randomized controlled trials of drugs, devices, and procedures for treating TBI has produce a proven treatment to date. However, the report pointed to experimental issues such as low robustness, insensitive measures, and the heterogeneity of patients as contributors to this failure.
“Have we been giving new therapies a fair chance? Or have we just discarded all kinds of useful therapies because the trials were so ineffectively administered?”, Vannier asked.
Vannier’s own research hopes to avoid repeating these mistakes, creating standardized protocols and data analysis pipelines (built with Kyle Chard of the Computation Institute) for multi-center studies of using diffusion MRI for traumatic brain injury diagnosis. A 2013 workshop organized by Vannier helped establish priorities for the field, creating a roadmap to develop the biomarkers that the injury sorely needs to bring clarity for a currently cloudy disorder.
[Vannier’s introduction on diffusion MRI for TBI at the 2013 workshop.]