Emerging advances of in vivo detection of chronic traumatic encephalopathy and traumatic brain injury

Abstract

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disorder that is of epidemic proportions in contact sports athletes and is linked to subconcussive and concussive repetitive head impacts (RHI). Although postmortem analysis is currently the only confirmatory method to diagnose CTE, there has been progress in early detection techniques of fluid biomarkers as well as in advanced neuroimaging techniques. Specifically, promising new methods of diffusion MRI and radionucleotide PET scans could aid in the early detection of CTE. The authors examine early detection methods focusing on various neuroimaging techniques. Advances in structural and diffusion MRI have demonstrated the ability to measure volumetric and white matter abnormalities associated with CTE. Recent studies using radionucleotides such as flortaucipir and 18F-FDDNP have shown binding patterns that are consistent with the four stages of neurofibrillary tangle (NFT) distribution postmortem. Additional research undertakings focusing on fMRI, MR spectroscopy, susceptibility-weighted imaging, and singlephoton emission CT are also discussed as are advanced MRI methods such as diffusiontensor imaging and arterial spin labeled. Neuroimaging is fast becoming a key instrument in early detection and could prove essential for CTE quantification. This review explores a global approach to in vivo early detection. Limited data of in vivo CTE biomarkers with postmortem confirmation are available. While some data exist, they are limited by selection bias. It is unlikely that a single test will be sufficient to properly diagnosis and distinguish CTE from other neurodegenerative diseases such as Alzheimer disease or Frontotemporal Dementia. However, with a combination of fluid biomarkers, neuroimaging, and genetic testing, early detection may become possible.

Return to Play Following Concussion: Role for Imaging?

“…27 63 73 Recent research delving into spatial memory navigation tasks using fMRI in athletes with SRC demonstrated distinctive brain activation patterns. 18 20 27 63 73 74 75 Although no significant differences in task performance were observed between concussed individuals and neurologically normal controls, fMRI revealed more extensive cortical networks with additional activation outside the study's regions of interest. 27 63 76 The enhanced activation was evident in the parietal cortex, right DLPFC, and right hippocampus.…”

“…[18][19][20][21][22] PET provides a more thorough understanding of the metabolic activity of brain regions and their correlation with the associated neurovascular changes linked to symptomatology through the use of radionucleotide tracer fludeoxyglucose F18 (abbreviated as 18F-FDG) that measures local glucose metabolism in various brain regions. 74,84,85 PET imaging can be combined with CT or MRI for anatomical localization (►Fig. 4 and ►Fig.…”

“…Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease linked to repetitive head impacts. 74,76,79,80,[86][87][88]94 CTE, which occurs predominantly in contact sports and military service, presents a significant challenge because a diagnosis can only be made postmortem at this time. This limitation prevents intervention and comprehensive patient care.…”

“…The emerging role of neuroimaging techniques in the in vivo diagnosis of CTE is a promising development. 74,76,79,94 MRI has revealed significant alterations in brain structure and function among individuals with CTE including changes in brain volume, ventricular enlargement, cerebral atrophy, white matter organization, cortical thinning, and functional connectivity. 74,80,94 These findings are indicative of the neuropathologic changes associated with CTE and provide a potential tool for early diagnosis and intervention.…”

“…79,83 Radionuclide 18F-FDDNP has shown potential in distinguishing CTE from other conditions. 74 The limitation of these methods includes financial coverage, nonspecific binding, and safety concerns. 74 In Shin's 2023 review in the National High School Journal of Science, there is a discussion about the need for personalized models of tau-induced atrophy in CTE, allowing clinicians to understand the trajectory of individual disease processes and intervene accordingly.…”