Advanced Neuroimaging Can Guide Interventions in Traumatic Brain Injury

Recent In-Roads in Neuroimaging

The challenge in neuroimaging has been to have an inexpensive and reliable method of discerning TBI from the uninjured and from those with PTSD. The military has made beating this challenge a high priority. Recent research has focused on new ways to use MRI to ferret out more information from the brain. In April 2016, a group under the direction of Gerald Riedy, MD, PhD, at the National Intrepid Center of Excellence, published a paper²⁴ on the findings in 834 military service members who had been exposed to bomb blasts (84%) or lost consciousness with their TBI (63%). Using a high-powered 3 Tesla MRI, they were able to find evidence of white matter T2 weighted hyperintensities in 51.8% of those injured. Assuming all who were exposed to blasts had a brain injury, this technique picked up between 62% and 82% of the mild-to-moderate TBI cases. These data fit with a recent postmortem histopathology study of a small number of service members who had acute or chronic blast exposure-related TBI or impact-related TBI.²⁵ Postmortem analysis showed astroglial scarring at the grey-white matter junctions, along blood vessels, and just below the pial surface. In other words, the axons and white matter were damaged at interfaces between tissue and fluid and between tissues with different densities.

The challenge is to get this highly refined technique to work in the average MRI in the average VA, military hospital, or in the field. That hurdle has yet to be overcome, and when it is, the accuracy will likely be lower than the range of 62%-82% achieved in the research setting.

From the functional MRI research a concept has risen of the “default mode network” (DMN), which is a grouping of structures in the brain that tend to be most synchronously active when the brain is in a resting state. More precisely, these areas are more co-active in-between tasks. For example, changes in the activity and connectivity of the DMN have been found in depression.²⁶ Attempts to use the DMN to identify TBI have had mixed results. In a comparison of 15 patients with TBI with 12 healthy controls, Nathan and colleagues²⁷ found there was high variability in the findings of the patients with TBI, consistent with the variability in the structures and degree of injury that is inherent to TBI. However, increased levels of linked activity were found among the elements of the DMN.

In another study, Raji and colleagues^28,29 analyzed more than 20,000 SPECT scans of patients with TBI and/or PTSD compared with controls and found that quantitative analysis of the DMN allowed a high level of discrimination between the different conditions — with greater than  94% accuracy. Specifically, the DMN is hyperperfused in individuals diagnosed with PTSD and hypoperfused in patients diagnosed with TBI. This work delivered a very strong message: that SPECT can unravel a distressing conundrum for those who treat veterans. The differentiation of TBI and PTSD and the combination of both conditions has been a daunting task for military and veteran services. Indeed, this work was recognized by Discover magazine as one of the top 20 scientific findings of 2015.³⁰

The opportunity exists to radically change the way medicine approaches TBI. The protocol that my colleagues and I elaborated on in this pair of papers^28,29 can be readily applied worldwide. SPECT scanners are available in virtually every major city and most countries. The number of SPECT scanners far outnumbers 3 Tesla MRI machines. SPECT scanners also outnumber positron emission tomography (PET) scanners by 12:1 in the United States and 100:1 in Canada.^31,32 The technological build-up to implement SPECT neuroimaging for TBI diagnostics would be small. Moreover, the software to perform the type of quantitative analysis used by our group is freely available. The initial step is to change the way medicine conceptualizes TBI, as even mild TBI has lasting effects on a person’s life and health.³³ TBI can be accurately diagnosed using neuroimaging and treated with new cutting-edge techniques.³⁴

Please see the next page for a list of references.