Send to

Choose Destination

Magnetic Resonance Imaging Application in the Area of Mild and Acute Traumatic Brain Injury: Implications for Diagnostic Markers?.


Toth A.


In: Kobeissy FH1, editor.


Brain Neurotrauma: Molecular, Neuropsychological, and Rehabilitation Aspects. Boca Raton (FL): CRC Press/Taylor & Francis; 2015. Chapter 24.
Frontiers in Neuroengineering.

Author information

Psychoproteomics and Nanotechnology Research Center Department of Psychiatry University of Florida Gainsville, Florida, USA


Mild traumatic brain injury (mTBI) causes brain damage generally invisible for conventional imaging methods. Its diagnosis mostly relies on the patient’s history, subjective complaints and neuropsychological status. Long-term complication development is just scarcely linked to these clinical factors. Imaging markers would contribute not only to the diagnosis and prognosis of mTBI, but to the understanding of its pathomechanisms as well. Advanced Magnetic Resonance Imaging (MRI) methods offer new insights to the background of mTBI. The microscopic scale white matter disease following mTBI can be evaluated by Diffusion Tensor Imaging (DTI) and Susceptibility Weighted Imaging (SWI). It’s possible to detect subtle atrophy using advanced volumetric analyses of submillimeter resolution images, while biochemical aspects can be assessed by MR spectroscopy. Functional MRI (fMRI) provides information of altered and compensational brain activity due to injury. Further advanced MRI techniques and perspectives are discussed as well in the chapter. Mild traumatic brain injury is a special field calling for advanced imaging methods, first of all magnetic resonance imaging (MRI) methods. The numerous definitions for mTBI and inconsistent nomenclature (e.g., concussion, minor head injury, minor brain injury, minor head trauma) show that the confinement of this clinical category is challenging. Diagnoses are mostly based on symptoms and self-reported history, yet no generally deployable objective marker exists; however, recent attempts for both imaging and biomarkers are promising. The most widely accepted criteria for mTBI are blunt trauma, Glasgow Coma Scale of 13–15, brief period (<30 minutes) of loss of consciousness, and brief period (<24 hours) of posttraumatic amnesia (Carroll et al., 2004; Mild Traumatic Brain Injury Committee, 1993). Inclusion of cases in which computed tomography (CT) scans show trauma-related pathology is debated; mostly these cases are excluded (i.e., mTBI is considered to be CT scan–negative). Indeed, CT scans are normal in about 90% of the cases fulfilling the aforementioned criteria; this fact is somewhat paradoxical considering the sometimes alarming neuropsychological signs and symptoms of these patients. The categorization of CT-positive mTBI cases as “complicated mTBI” (e.g., finding of focal contusion) seems to be useful because these cases generally deserve extra attention acutely; however, focal lesions may not predict the outcome 3 months after injury (Lannsjo et al., 2013). Clinical variables together with age may be stronger predictors for outcome (Jacobs et al., 2010). Beyond the issues with definitions and diagnostic criteria, the greater problem from a clinical point of view is that the severity of the complaints or neuropsychological deficits at admission are only very scarcely linked to the prognosis and true severity of the injury. This means that, for example, loss of consciousness or the length of posttraumatic amnesia is not necessarily associated with the actual mechanical force suffered or the chance of developing persistent posttraumatic complaints. It is important to keep in mind that mTBI can be interpreted as “mild” only when compared with moderate or severe TBI, which is known to be life-threatening. In itself, mTBI is also potentially dangerous because in 10%–30% of cases it may lead to serious long-term complications significantly worsening life quality and disabling work or social interactions (see the following section). Additionally, considering its extremely high incidence (up to 500/100,000), mTBI deserves to be called a public health problem. Long-term complications may include such persisting acute symptoms as headache, dizziness, nausea, or concentration/memory problems, although new complaints may also develop in time such as depression, sleeping disorders, or anxiety. Patients suffering from repetitive mTBIs are especially exposed to long-term complications. This makes the decision of letting one return to work or return to play (in case of sports concussion) really serious. Still, without enough objective information of mTBI-related mechanisms, the background of long-term complications is not fully understood. It is debated whether these complications are a result of psychological or organic factors. Because mTBI-related pathomechanisms remain elusive, therapeutic possibilities are also going to be limited. Presently, the only widely accepted treatment is rest, both physical and cognitive. Medications used merely serve as symptomatic treatment and their use is generally based on local anecdotal evidence (Meehan, 2011). One reason why identification of the details of related mechanisms has been held up is that, generally, histopathological examination is not possible. Human histopathological observations are very scarce and are from the rare cases of mTBI accompanying fatal conditions. The vast majority of histological information and data about pathomechanism have been obtained from animal (mostly rodent) mTBI models (for an overview on neuropathology in mTBI, see Bigler and Maxwell, 2012). These models allow an infinite range of controlled observations on different elements of brain injury and have provided irreplaceable findings. However, all mTBI animal models suffer from the problem that mTBI can only be interpreted truthfully at the level of the human brain’s complexity. Most of the neuropsychological deficits characterizing this condition are hardly transposable to animals. For example, a mainstay element of the mTBI definition is posttraumatic amnesia. To be simplistic, mTBI, grossly, is the damage of a theoretical fraction of the human brain that an animal does not even have. These concerns regarding mTBI diagnosis, prognosis evaluation, and pathomechanism have together called for noninvasive, highly sensitive contemporary imaging tools. Among these are single photon emission computed tomography, positron emission tomography, and MRI, the latter of which has become the most widely applied in mTBI studies because it is the most accessible, multimodal, and the least harmful because no ionizing radiation is used and, generally, no contrast agent has to be administered. Multimodality in MRI means that this method, depending on actual acquisition parameters, can provide different insights to the complex pathology of the damaged brain, from detailed microstructural to functional components. Unlike classic neuroradiological scan evaluation, assessment of advanced MRI data is based often on quantitative and statistical methods. This means that although visible images are created, the true information is held in the underlying numbers that allow objective, often group-wise analytical processes. One of the most promising methods of the field is diffusion tensor imaging (DTI) that is able to detect change in water microcompartments due to microstructural pathology as axonal deformation and swelling. Focal microscopic bleeds developing as part of diffusion axonal imaging are most successfully detectable by susceptibility-weighted imaging (SWI), a method exploiting the magnetic property of iron. Recent efforts seem to validate the clinical importance of these methods (see the following section). High-resolution, three-dimensional, T1-weighted images allow precise volumetric analyses to be performed shedding light on subtle changes in the brain macrostructure because of, for example, edematic and atrophic mechanisms after injury. Beyond the advanced investigation of brain structure, magnetic resonance spectroscopy (MRS) offers information of the metabolic state of the brain by measuring specific magnetic signals from mainly the 1H nuclei in different metabolites. Getting to the functional level, the effect of injury on brain functions such as perception or cognitive tasks (memory and concentration functions are typically affected) can be investigated by functional MRI (fMRI). The following sections provide a brief overview of the benefits and also challenges of using these methods in the mTBI field.

© 2015 by Taylor & Francis Group, LLC.

Support Center