Suitability of Neuroimaging in Diagnosis of Sleep, Fatigue, Perfusion and Metabolite Deficits after Mild Traumatic Brain Injury

The objective of this review is to summarize the findings of promising imaging approaches that may provide mechanistic understanding of mild traumatic brain injury (mTBI). Imaging in mTBI has so far explored brain tissue damage or physiologic changes involving perfusion and metabolite distribution. Clinical manifestations of sleep, visual disturbances and associated fatigue observed in a substantial number of mTBI patients have not been diagnosed at all. Although the association of TBI with sleep disorders is being recognized, the mechanistic relation is far from clear. The association of fatigue and sleep with mTBI raises the question which one comes first. This has been addressed to some extent in this review. Patients with mTBI and persistent post-concussive symptoms have a high incidence of medial temporal lobe injury leading to altered hippocampal, caudate and insular perfusion. The mTBI literature discusses the importance of oxidative stress and BBB disruption. Although SPECT is very sensitive in this regard, various imaging modalities with tools to map perfusion, metabolite and functional deficiencies are showing significant promise. It is a concern that MR spectroscopic abnormalities in mTBI go mostly undetected. We could not find any work that addresses secondary metabolite levels like GABA, Glutamate and so on or explores the whole brain to assess mTBI induced global metabolite abnormalities. Further mechanistic understanding to link sleep and fatigue is necessary. In conclusion, combining tissue biology to model the impact of oxidative stressor and injury localization with tracer imaging and functional connectivity mapping is preferred as well as global perfusion/metabolite measurements. Multi-modal approaches hold more promise than advanced applications of single modalities. Focal surgical procedures as in the placement of neurological shunts or neuroimplants offer excellent templates to study the deficits from static loads in pre-planned locations and may help mechanistic evaluation of mTBI that usually involves dynamic and global loads.

Keywords: Mild TBI; mTBI; Head trauma; Fatigue; Perfusion imaging; SPECT; MRI in TBI; Functional MRI in TBI; MR Spectroscopy in TBI; Metabolite imaging in TBI

Abbreviations: TBI: Traumatic Brain Injuryl; mTBI: Mild Traumatic Brain Injury; SPECT: Single Photon Emission Computed Tomography; PET: Positron Emission Tomography; MRI: Magnetic Resonance Imaging; CT: Computed Tomography; MEG: Magnetoencephalography; DTI: Diffusion Tensor Imaging (Diffusion Tractography); fMRI: Functional MRI; LOC: Loss of Consciousness; PTA: Post Traumatic-Amnesia; GSC: Glasgow Coma Scale; CDC: Center for Disease Control; PCD: Post Concussive Disorder