title: Imaging of Glial Cell Activation and White Matter Integrity in Brains of Active and Recently Retired National Football League Players.
abstract: OBJECTIVE
  Microglia, the resident immune cells of the central nervous system, play an important role in the brain's response to injury and neurodegenerative processes. It has been proposed that prolonged microglial activation occurs after single and repeated traumatic brain injury, possibly through sports-related concussive and subconcussive injuries. Limited in vivo brain imaging studies months to years after individuals experience a single moderate to severe traumatic brain injury suggest widespread persistent microglial activation, but there has been little study of persistent glial cell activity in brains of athletes with sports-related traumatic brain injury.
  
  
  OBJECTIVE
  To measure translocator protein 18 kDa (TSPO), a marker of activated glial cell response, in a cohort of National Football League (NFL) players and control participants, and to report measures of white matter integrity.
  
  
  METHODS
  This cross-sectional, case-control study included young active (n = 4) or former (n = 10) NFL players recruited from across the United States, and 16 age-, sex-, highest educational level-, and body mass index-matched control participants. This study was conducted at an academic research institution in Baltimore, Maryland, from January 29, 2015, to February 18, 2016.
  
  
  METHODS
  Positron emission tomography-based regional measures of TSPO using [11C]DPA-713, diffusion tensor imaging measures of regional white matter integrity, regional volumes on structural magnetic resonance imaging, and neuropsychological performance.
  
  
  RESULTS
  The mean (SD) ages of the 14 NFL participants and 16 control participants were 31.3 (6.1) years and 27.6 (4.9) years, respectively. Players reported a mean (SD) of 7.0 (6.4) years (range, 1-21 years) since the last self-reported concussion. Using [11C]DPA-713 positron emission tomographic data from 12 active or former NFL players and 11 matched control participants, the NFL players showed higher total distribution volume in 8 of the 12 brain regions examined (P < .004). We also observed limited change in white matter fractional anisotropy and mean diffusivity in 13 players compared with 15 control participants. In contrast, these young players did not differ from control participants in regional brain volumes or in neuropsychological performance.
  
  
  CONCLUSIONS
  The results suggest that localized brain injury and repair, indicated by higher TSPO signal and white matter changes, may be associated with NFL play. Further study is needed to confirm these findings and to determine whether TSPO signal and white matter changes in young NFL athletes are related to later onset of neuropsychiatric symptoms.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins Medical Institutions, Baltimore, Maryland2Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Coughlin
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Yuchuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Il
authors.initials: I
authors.lastname: Minn
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Bienko
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Emily B
authors.initials: EB
authors.lastname: Ambinder
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Xin
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Peters
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: John W
authors.initials: JW
authors.lastname: Dougherty
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Melin
authors.initials: M
authors.lastname: Vranesic
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Soo Min
authors.initials: SM
authors.lastname: Koo
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Hye-Hyun
authors.initials: HH
authors.lastname: Ahn
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Merton
authors.initials: M
authors.lastname: Lee
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Chris
authors.initials: C
authors.lastname: Cottrell
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Haris I
authors.initials: HI
authors.lastname: Sair
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Akira
authors.initials: A
authors.lastname: Sawa
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins Medical Institutions, Baltimore, Maryland3Department of Neurology, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Munro
authors.affiliation: Concussion Legacy Foundation, Waltham, Massachusetts5Alzheimer's Disease and CTE Center, Boston University School of Medicine, Boston, Massachusetts.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Nowinski
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Dannals
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Constantine G
authors.initials: CG
authors.lastname: Lyketsos
authors.affiliation: School of Chemistry, University of Sydney, New South Wales, Australia7Discipline of Medical Radiation Sciences, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Kassiou
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Gwenn
authors.initials: G
authors.lastname: Smith
authors.affiliation: Department of Biostatistics, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Brian
authors.initials: B
authors.lastname: Caffo
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Susumu
authors.initials: S
authors.lastname: Mori
authors.affiliation: Department of Environmental and Occupational Health, Florida International University, Miami10Program in Cognitive Neuroscience and Imaging, Florida International University, Miami.
authors.forename: Tomas R
authors.initials: TR
authors.lastname: Guilarte
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins Medical Institutions, Baltimore, Maryland2Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Martin G
authors.initials: MG
authors.lastname: Pomper
mesh_terms: D000081:Acetamides / Q000493:pharmacokinetics; D000328:Adult; D056352:Athletes; D001924:Brain Concussion / Q000150:complications / Q000000981:diagnostic imaging* / Q000209:etiology; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D016022:Case-Control Studies; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005538:Football / Q000293:injuries; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography; D011720:Pyrazoles / Q000493:pharmacokinetics; D011743:Pyrimidines / Q000493:pharmacokinetics; D018079:Receptors, GABA / Q000378:metabolism*; D012179:Retirement; D014481:United States; D066127:White Matter / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000378:metabolism*; D055815:Young Adult
chemical_list: D000081:Acetamides; D002250:Carbon Radioisotopes; C507091:N,N-diethyl-2-(2-(4-methoxyphenyl)-5,7-dimethyl-pyrazolo(1,5-a)pyrimidin-3-yl)-acetamide; D011720:Pyrazoles; D011743:Pyrimidines; D018079:Receptors, GABA; C499229:TSPO protein, human