Neuroimage Biomarker of Thalamo-Cortical Network for Outcome Prediction in Mild Taumatic Brain Injury: a Translational Mri Research

Single or repetitive mild traumatic brain injury (mTBI) can lead to acute and chronic neurological dysfunctions, such as headache, sleep disturbances, anxiety, balance problem, and memory impairment. These post-concussion symptoms (PCS) in patients with mTBI are associated with the shearing forces and stretching in white matter during a sudden acceleration and deceleration on patients’ head. Despite PCS can be observed on mTBI patients, there is typically an absence of obvious structural lesions on CT or conventional MRI examination, which has made it difficult to correlate the presenting clinical symptoms with relevant neuroanatomy. The absence of neuroimage evidence therefore limited the recent progression in diagnosis and prognosis of mTBI. It is emergent to implement a proper neuropathological model and a reliable neuroimage biomarker that can elucidate the occurrence of PCS and predict the patient outcomes in the early phase of mTBI. In this project, we hypothesize that the mTBI-caused impairment of thalamo-cortical pathways can be used to elucidate the non-specific PCS and to predict final outcomes after injury. Alterations of thalamo-cortical network will be identified, and a novel approach, the multi-level network analysis, will be developed to unravel the network reorganization and neural plasticity following mTBI. A translational neuroimaging study from rat mTBI models to clinical mTBI patients will be conducted to verify our hypothesis. In Aim 1 (Year 1 – animal study), we will identify the correlate between the acute alteration of thalamo-cortical connectivity and anatomical/behavioral outcomes following a single or repetitive concussive injury. The design of single-impact model is to mimic the concussion caused by a motor vehicle accident, and the repetitive concussion model is used to unravel the accumulation effect after repetitive injury that commonly occurs in contact-sport athletes. In Aim 2 (Year 2 – clinical study), we will determine whether the spectrum of PCS can be correlated to the injury of specific thalamo-cortical pathway. The multi-level network analysis will be applied to extract biomarkers of network reorganization in response to the mTBI. A reliable predication model based on the neuroimage biomarker of thalamo-cortical network for 1-year outcomes after mTBI will be established. The confirmation of the proposed neuropathological model and the outcome prediction model can be used to sieve out the patients with the demand of intensive monitoring and therefore improves the clinical care and treatment of mTBI patients.