MRI biomarkers in mild traumatic brain injury.

In this issue of Neurology®, Huang et al. describe a higher prevalence of cerebral microbleeds in patients with mild traumatic brain injury (mTBI) in comparison to healthy controls using susceptibility-weighted MRI. They could also link these observations to neuropsychological deficits as measured by the digit span score, in comparison to patients with mTBI without microbleeds. This report aligns with a variety of recent publications dealing with advanced MRI techniques for the detection of microstructural cerebral changes in mTBI, sports-related concussion in general, and repetitive concussive head trauma as in boxing. However, Bigler and Deibert recently lamented the lack of sufficient and objective in vitro biomarkers in the field of mTBI in contrast to severe craniocerebral trauma. Therefore, subtle imaging findings must be both characterized and evaluated for their relevance to clinical severity and long-term prognosis. Susceptibility-weighted imaging (SWI) permits the detection of cerebral microhemorrhages at an almost microscopic level, especially at high-fieldstrength MRI. In brain trauma, the overlying cortex moves at a different speed relative to subcortical white matter, with the consequence of shear forces and axonal and vessel stretching leading to microbleeds at the corticomedullary boundary. On one hand, microbleeds in the context of cerebral trauma may represent an epiphenomenon of brain damage or the “tip of the iceberg,” because axonal damage may also occur without hemorrhage. On the other hand, cerebral microhemorrhages are found with a prevalence from 10% to 40% in communitydwelling populations depending on the age. In addition, they are found in a variety of vascular diseases, such as CNS vasculitis, cerebral amyloid angiopathy, and hypertensive encephalopathy. Another magnetic resonance technique, diffusion tensor imaging (DTI), can evaluate microstructural changes in mTBI. In this setting, DTI yields quantitative parameters of tissue integrity of the cerebral white matter. These measures, e.g., the fractional anisotropy, can be fed into statistical models to test their influence on performances in neuropsychological tests and thereby investigate their clinical relevance. In recent studies, DTI was a sensitive tool with high diagnostic accuracy. The present findings by Huang et al. deserve greater attention for practical and academic reasons. First, their method appears robust, readily available, and observer-independent, so it has greater potential to be integrated into daily clinical routine. Also, their method has a high specificity, making the approach more conservative. Moreover, they could relate their observations to neuropsychological deficits, making it an ideal candidate to monitor patients with moderate to severe traumatic brain injury (TBI). The observed deficits in memory retrieval were associated with a lobar distribution of subcortical microbleeds. This raises a potential link to pathologies mediated by polymorphisms of APO. The APO e4 genotype appears to mediate not only memory deficits after TBI but also links the development of later dementia to TBI. Finally, the APO e4 genotype was associated with microhemorrhages in the same distribution, i.e., lobar in nontraumatized individuals. Huang et al. found that microbleeds in these locations discriminated TBI patients with memory deficits from those without. These microbleeds might not only indicate the severity of TBI but also the individual vulnerability to TBI or associated late consequences. If so, this might be related to genetic factors such as APO e4. Therefore, the current work indicates that SWI warrants further evaluation, not only as a diagnostic marker but also as a prognostic marker in mTBI. A recent study by Lui et al. provided Class III evidence that classification algorithms using a variety of magnetic resonance features, including conventional brain imaging, magnetic field correlation, and multifeature analysis, may accurately define patients with mTBI. The microstructural in vivo evaluation of mTBI is of growing interest, not only because of the increasing popularity of contact sports, but also for advisory opinions regarding the clinical and forensic consequences of accidental trauma, assaults, and interpersonal violence. Advanced magnetic resonance