Neurochemical Aftermath of Repetitive Mild Traumatic Brain Injury

IMPORTANCE: Evidence is accumulating that repeated mild traumatic brain injury (mTBI) incidents can lead to persistent, long-term debilitating symptoms and in some cases a progressive neurodegenerative condition referred to as chronic traumatic encephalopathy. However, to our knowledge, there are no objective tools to examine to which degree persistent symptoms after mTBI are caused by neuronal injury. OBJECTIVE: To determine whether persistent symptoms after mTBI are associated with brain injury as evaluated by cerebrospinal fluid biochemical markers for axonal damage and other aspects of central nervous system injury. DESIGN, SETTINGS, AND PARTICIPANTS: A multicenter cross-sectional study involving professional Swedish ice hockey players who have had repeated mTBI, had postconcussion symptoms for more than 3 months, and fulfilled the criteria for postconcussion syndrome (PCS) according to the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) matched with neurologically healthy control individuals. The participants were enrolled between January 2014 and February 2016. The players were also assessed with Rivermead Post Concussion Symptoms Questionnaire and magnetic resonance imaging. MAIN OUTCOMES AND MEASURES: Neurofilament light protein, total tau, glial fibrillary acidic protein, amyloid β, phosphorylated tau, and neurogranin concentrations in cerebrospinal fluid. RESULTS: A total of 31 participants (16 men with PCS; median age, 31 years; range, 22-53 years; and 15 control individuals [11 men and 4 women]; median age, 25 years; range, 21-35 years) were assessed. Of 16 players with PCS, 9 had PCS symptoms for more than 1 year, while the remaining 7 returned to play within a year. Neurofilament light proteins were significantly increased in players with PCS for more than 1 year (median, 410 pg/mL; range, 230-1440 pg/mL) compared with players whose PCS resolved within 1 year (median, 210 pg/mL; range, 140-460 pg/mL) as well as control individuals (median 238 pg/mL, range 128-526 pg/mL; P = .04 and P = .02, respectively). Furthermore, neurofilament light protein concentrations correlated with Rivermead Post Concussion Symptoms Questionnaire scores and lifetime concussion events (ρ = 0.58, P = .02 and ρ = 0.52, P = .04, respectively). Overall, players with PCS had significantly lower cerebrospinal fluid amyloid-β levels compared with control individuals (median, 1094 pg/mL; range, 845-1305 pg/mL; P = .05). CONCLUSIONS AND RELEVANCE: Increased cerebrospinal fluid neurofilament light proteins and reduced amyloid β were observed in patients with PCS, suggestive of axonal white matter injury and amyloid deposition. Measurement of these biomarkers may be an objective tool to assess the degree of central nervous system injury in individuals with PCS and to distinguish individuals who are at risk of developing chronic traumatic encephalopathy

Attenuation correction in quantitative SPECT of cerebral blood flow: a Monte Carlo study

Monte Carlo simulation has been used to produce projections from a voxel-based brain phantom, simulating a 99mTc-HMPAO single photon emission computed tomography (SPECT) brain investigation. For comparison, projections free from the effects of attenuation and scattering were also simulated, giving ideal transaxial images after reconstruction. Three methods of attenuation correction were studied: (a) a pre-processing method, (b) a post-processing uniform method and (c) a post-processing non-uniform method using a density map. The accuracy of these methods was estimated by comparison of the reconstructed images with the ideal images using the normalized mean square error, NMSE, and quantitative values of the regional cerebral blood flow, rCBF. A minimum NMSE was achieved for the effective linear attenuation coefficient mu(eff) = 0.07 (0.09) cm(-1) for the uniform(pre) method, the effective mass attenuation coefficient mu(eff)/rho = 0.08 (0.10) cm2 g(-1) for the uniform(post) method and mu(eff)/rho = 0.12 (0.13) cm2 g(-1) for the non-uniform(post) method. Values in parentheses represent the case of dual-window scatter correction. The non-uniform(post) method performed better, as measured by the NMSE, both with and without scatter correction. Furthermore, the non-uniform(post) method gave, on average, more accurate rCBF values. Although the difference in rCBF accuracy was small between the various methods, the same method should be used for patient studies as for the reference material

Dual-window scatter correction and energy window setting in cerebral blood flow SPECT: a Monte Carlo study

The image quality in SPECT studies of the regional cerebral blood flow (rCBF) performed with 99mTc-HMPAO is degraded by scattered photons. The finite energy resolution of the gamma camera makes the detection of scattered photons unavoidable, and this is observed in the image as an impaired contrast between grey and white matter structures. In this work, a Monte Carlo simulated SPECT study of a realistic voxel-based brain phantom was used to evaluate the resulting contrast-to-noise ratio for a number of energy window settings, with and without the dual-window scatter correction. Values of the scaling factor k, used to obtain the fraction of scattered photons in the photopeak window, were estimated for each energy window. The use of a narrower, asymmetric, energy discrimination window improved the contrast, with a subsequent increase in statistical noise due to the lower number of counts. The photopeak-window setting giving the best contrast-to-noise ratio was found to be the same whether or not scatter correction was applied. Its value was 17% centred at 142 keV. At the optimum photopeak-window setting, the contrast was improved by using scatter correction, but the contrast-to-noise ratio was made worse