September 5, 2014
At this time, we have a poor understanding of mechanisms behind concussion and traumatic brain injury (TBI) in athletes and soldiers, and few means for intervening to reduce their occurrence, manage their treatment/rehabilitation, and optimize long-term outcomes for individuals with concussion or TBI. In order to adequately address the challenges associated with concussion in current and retired athletes and TBI in military veterans, we need to develop (1) biomarkers of injury and prognosis, (2) new methods for treatment and monitoring treatment efficacy, and (3) techniques for understanding the interaction of brain injury with brain development and long-term outcomes for athletes and soldiers. Without properly assessing (via technologically advanced tools), treating and managing these injuries, athletes and soldiers will have poor future prognosis, and their careers will be shortened, leaving a potentially significant cost burden to society at large.
Our understanding of brain injuries, such as concussion and TBI, has increased significantly within the past decade parallel to the increased attention given to injured athletes on high school, collegiate and professional sports teams and veterans returning from overseas conflicts. These patients have focused the research community’s efforts into further understanding the pathophysiological underpinnings of the injury as well as its both short-term and long-term effects. Widespread media coverage and several high-profile cases have raised the issue of possible severe and devastating long-term consequences of repetitive sports-related brain trauma that may involve the acquisition of a “tau-opathy” as well as an increased risk for developing neurodegenerative diseases associated with repetitive concussive and sub-concussive blows. A parallel issue has arisen with military veterans given an increased incidence in individuals with mild TBI of negative outcomes such as addiction, post-traumatic stress disorder, depression and suicide.
Although the problem is significant for both the athletic and military communities, in the discussion that follows, we will focus on the athletic community given brain-based research has the chance to start early in the course of trauma onset and dissociate it from brain development. Many military veterans prepare for future military involvement through contact sports, and will have an increased likelihood of sports-based injury before enlisting in the military.
If athletics-based concussion is, indeed, a complex pathophysiological process affecting the brain, proper imaging based diagnostic tools must be standardized, clinically validated and implemented in practice to directly assess this complex pathophysiology. This mission is critically important in light of the fact that conventional neuroimaging techniques (i.e. harmful CT and costly MRI scans) and neuropsychological tests fail to adequately detect the subtle structural, neurometabolic, and functional disruptions affecting the concussed brain. Additionally, the diagnostic value of conventional applications of CT and MRI in concussion is quite poor with findings being generally negative. Therefore, CT and MRI examination in the case of concussion places undue financial strain on the healthcare system and the family of the individual undergoing the examinations.
Recently, with advances in brain imaging hardware, pulse sequences and analytical techniques, newer MRI methods have demonstrated the ability to detect and localize several pathologic and pathophysiologic consequences of concussion. These advanced MR technologies include: susceptibility weighted imaging (SWI) to detect micro-hemorrhage; MR spectroscopy (MRS) to detect metabolic alterations; diffusion tensor imaging (DTI) to detect edema and axonal injury; perfusion weighted imaging (PWI) and arterial spin labeling (ASL) to measure cerebral blood flow in brain tissue; and functional MRI (fMRI) to measure local changes in blood oxygen level in response to neuronal activity. Having a number of imaging biomarkers, all of which are obtained in a single scanning session (or multiple sessions as from longitudinal study) affords great advantages, including: (1) enhanced sensitivity; (2) ability to understand differential sensitivity of these biomarkers and the link between biomarkers and clinical deficits in concussed brain; (3) improved clinical management resulting from more precise prognostication of brain injuries; and (4) enhanced power of clinical intervention in concussed patients.
To move this field forward, consolidated efforts of leading MR researchers from multiple institutions are needed to standardize operational procedures and brain imaging protocols from both a research and clinical perspectives.
Our key objectives:
- Consolidation of leading brain science/brain imaging experts and efforts aimed at identification of imaging “biomarkers” of concussion and athletes at risk for traumatic concussion;
- Development of advanced MR imaging techniques to measure physiological and neuropsychological alterations after concussion;
- Development and validation of advanced MR assessment tools aimed at detecting “pathophysiological biomarkers” of sports-related concussion;
- Development of a standardized, MR-evidenced based and platform independent Operational Manual for acquisition and processing brain imaging data;
- Synthesis of multi-modal neuroimaging measures to provide quantitative metrics of neural health that can be used longitudinally;
- Integration of neuroimaging measures with mathematical metrics of behavior to aid medical intervention and prognosis assessment;
- Development of model-based assessment, prediction, and management based on imaging in the nervous system;
- Creation of longitudinal benchmark data related brain imaging measures for prognostication of long-term deficits induced by concussive blows;
- Establishment of partnership with MRI vendors, pharmaceutical and other companies as a critical component for research on neurological structure, function and treatment brain injured patients;
- Secure funding for development of residency programs and fellowships for medical professionals in charge of treatment of concussed athletes;
- Endowed faculty, postdoctoral fellow, medical residents or graduate training lines in one or more of the core consortium’s initiatives associated with MR assessment and management of concussion;
- Demonstration of proof-of-concept and production of solid imaging data necessary to support large-scale funding request from major private and federal funding entities, including NFL, NIH, NHL, NSF, DOD and VA.