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Semin Neurol 2017; 37(05): 503-509
DOI: 10.1055/s-0037-1608764
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Magnetic Resonance Spectroscopy as a Biomarker for Chronic Traumatic Encephalopathy

Michael L. Alosco
1   Department of Neurology, Boston University Alzheimer's Disease and CTE Center, Boston University School of Medicine, Boston, Massachusetts
,
Johnny Jarnagin
1   Department of Neurology, Boston University Alzheimer's Disease and CTE Center, Boston University School of Medicine, Boston, Massachusetts
,
Benjamin Rowland
2   Department of Radiology, Center for Clinical Spectroscopy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
,
Huijun Liao
2   Department of Radiology, Center for Clinical Spectroscopy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
,
Robert A. Stern
3   Departments of Neurology, Neurosurgery, and Anatomy and Neurobiology, Boston University Alzheimer's Disease and CTE Center, Boston University School of Medicine, Boston, Massachusetts
,
Alexander Lin
2   Department of Radiology, Center for Clinical Spectroscopy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
› Author Affiliations
Further Information

Publication History

Publication Date:
05 December 2017 (online)

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Abstract

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with exposure to repetitive head impacts (RHI). Currently, CTE can only be diagnosed after death by postmortem, as validated in vivo biomarkers of CTE do not yet exist. Proton magnetic resonance spectroscopy (MRS) measures brain tissue metabolism in vivo and could facilitate a “probable CTE” diagnosis during life. Here, we propose MRS as one potential biomarker for CTE through a review of CTE neuropathology, and the extant literature that has examined the acute and long-term effects of RHI exposure on brain chemistry. There is preliminary empirical support for MRS in the detection of later-life neurological impairment associated with RHI exposure, but further ante- and postmortem research is needed before MRS can be considered a diagnostic biomarker for CTE.

Keywords

MR spectroscopy - chronic traumatic encephalopathy - neurochemistry - metabolism - repetitive head impacts
 

  • References

  • 1 McKee AC, Cairns NJ, Dickson DW. , et al; TBI/CTE group. The first NINDS/NIBIB consensus meeting to define neuropathological criteria for the diagnosis of chronic traumatic encephalopathy. Acta Neuropathol 2016; 131 (01) 75-86
    CrossrefPubMedGoogle Scholar
  • 2 Bieniek KF, Ross OA, Cormier KA. , et al. Chronic traumatic encephalopathy pathology in a neurodegenerative disorders brain bank. Acta Neuropathol 2015; 130 (06) 877-889
    CrossrefPubMedGoogle Scholar
  • 3 McKee AC, Stern RA, Nowinski CJ. , et al. The spectrum of disease in chronic traumatic encephalopathy. Brain 2013; 136 (Pt 1): 43-64
    CrossrefPubMedGoogle Scholar
  • 4 Stein TD, Alvarez VE, McKee AC. Concussion in chronic traumatic encephalopathy. Curr Pain Headache Rep 2015; 19 (10) 47
    CrossrefPubMedGoogle Scholar
  • 5 Stein TD, Alvarez VE, McKee AC. Chronic traumatic encephalopathy: a spectrum of neuropathological changes following repetitive brain trauma in athletes and military personnel. Alzheimers Res Ther 2014; 6 (01) 4
    CrossrefPubMedGoogle Scholar
  • 6 McKee AC, Cantu RC, Nowinski CJ. , et al. Chronic traumatic encephalopathy in athletes: progressive tauopathy after repetitive head injury. J Neuropathol Exp Neurol 2009; 68 (07) 709-735
    CrossrefPubMedGoogle Scholar
  • 7 Stern RA, Daneshvar DH, Baugh CM. , et al. Clinical presentation of chronic traumatic encephalopathy. Neurology 2013; 81 (13) 1122-1129
    CrossrefPubMedGoogle Scholar
  • 8 Montenigro PH, Baugh CM, Daneshvar DH. , et al. Clinical subtypes of chronic traumatic encephalopathy: literature review and proposed research diagnostic criteria for traumatic encephalopathy syndrome. Alzheimers Res Ther 2014; 6 (05) 68
    CrossrefPubMedGoogle Scholar
  • 9 Alosco ML, Mez J, Kowall NW. , et al. Cognitive reserve as a modifier of clinical expression in chronic traumatic encephalopathy: a preliminary examination. J Neuropsychiatry Clin Neurosci 2017; 29 (01) 6-12
    CrossrefPubMedGoogle Scholar
  • 10 Wang H, Tan L, Wang H-F. , et al. Magnetic resonance spectroscopy in Alzheimer's disease: systematic review and meta-analysis. J Alzheimers Dis 2015; 46 (04) 1049-1070
    CrossrefPubMedGoogle Scholar
  • 11 Watson R, Blamire AM, O'Brien JT. Magnetic resonance imaging in Lewy body dementias. Dement Geriatr Cogn Disord 2009; 28 (06) 493-506
    CrossrefPubMedGoogle Scholar
  • 12 Coulthard E, Firbank M, English P. , et al. Proton magnetic resonance spectroscopy in frontotemporal dementia. J Neurol 2006; 253 (07) 861-868
    CrossrefPubMedGoogle Scholar
  • 13 Mihara M, Hattori N, Abe K, Sakoda S, Sawada T. Magnetic resonance spectroscopic study of Alzheimer's disease and frontotemporal dementia/Pick complex. Neuroreport 2006; 17 (04) 413-416
    CrossrefPubMedGoogle Scholar
  • 14 Griffith HR, Stewart CC, den Hollander JA. Proton magnetic resonance spectroscopy in dementias and mild cognitive impairment. Int Rev Neurobiol 2009; 84: 105-131
    PubMedGoogle Scholar
  • 15 Gardner A, Iverson GL, Stanwell P. A systematic review of proton magnetic resonance spectroscopy findings in sport-related concussion. J Neurotrauma 2014; 31 (01) 1-18
    CrossrefPubMedGoogle Scholar
  • 16 Koerte IK, Lin AP, Willems A. , et al. A review of neuroimaging findings in repetitive brain trauma. Brain Pathol 2015; 25 (03) 318-349
    CrossrefPubMedGoogle Scholar
  • 17 Ng TS, Lin AP, Koerte IK. , et al. Neuroimaging in repetitive brain trauma. Alzheimers Res Ther 2014; 6 (01) 10
    CrossrefPubMedGoogle Scholar
  • 18 Henry LC, Tremblay S, Leclerc S. , et al. Metabolic changes in concussed American football players during the acute and chronic post-injury phases. BMC Neurol 2011; 11: 105
    CrossrefPubMedGoogle Scholar
  • 19 Vagnozzi R, Signoretti S, Cristofori L. , et al. Assessment of metabolic brain damage and recovery following mild traumatic brain injury: a multicentre, proton magnetic resonance spectroscopic study in concussed patients. Brain 2010; 133 (11) 3232-3242
    CrossrefPubMedGoogle Scholar
  • 20 Vagnozzi R, Signoretti S, Tavazzi B. , et al. Temporal window of metabolic brain vulnerability to concussion: a pilot 1H-magnetic resonance spectroscopic study in concussed athletes--part III. Neurosurgery 2008; 62 (06) 1286-1295 , discussion 1295–1296
    PubMedGoogle Scholar
  • 21 Johnson B, Gay M, Zhang K. , et al. The use of magnetic resonance spectroscopy in the subacute evaluation of athletes recovering from single and multiple mild traumatic brain injury. J Neurotrauma 2012; 29 (13) 2297-2304
    CrossrefPubMedGoogle Scholar
  • 22 Lin AP, Liao HJ, Merugumala SK, Prabhu SP, Meehan III WP, Ross BD. Metabolic imaging of mild traumatic brain injury. Brain Imaging Behav 2012; 6 (02) 208-223
    CrossrefPubMedGoogle Scholar
  • 23 Duarte JM, Lei H, Mlynárik V, Gruetter R. The neurochemical profile quantified by in vivo 1H NMR spectroscopy. Neuroimage 2012; 61 (02) 342-362
    CrossrefPubMedGoogle Scholar
  • 24 Govindaraju V, Young K, Maudsley AA. Proton NMR chemical shifts and coupling constants for brain metabolites. NMR Biomed 2000; 13 (03) 129-153
    CrossrefPubMedGoogle Scholar
  • 25 Magistretti PJ, Pellerin L. Cellular mechanisms of brain energy metabolism and their relevance to functional brain imaging. Philos Trans R Soc Lond B Biol Sci 1999; 354 (1387): 1155-1163
    CrossrefPubMedGoogle Scholar
  • 26 Ramadan S, Lin A, Stanwell P. Glutamate and glutamine: a review of in vivo MRS in the human brain. NMR Biomed 2013; 26 (12) 1630-1646
    CrossrefPubMedGoogle Scholar
  • 27 Chang L, Ernst T, Poland RE, Jenden DJ. In vivo proton magnetic resonance spectroscopy of the normal aging human brain. Life Sci 1996; 58 (22) 2049-2056
    CrossrefPubMedGoogle Scholar
  • 28 Mueller SG, Schuff N, Weiner MW. Evaluation of treatment effects in Alzheimer's and other neurodegenerative diseases by MRI and MRS. NMR Biomed 2006; 19 (06) 655-668
    CrossrefPubMedGoogle Scholar
  • 29 Ashwal S, Holshouser B, Tong K. , et al. Proton spectroscopy detected myoinositol in children with traumatic brain injury. Pediatr Res 2004; 56 (04) 630-638
    CrossrefPubMedGoogle Scholar
  • 30 Kierans AS, Kirov II, Gonen O. , et al. Myoinositol and glutamate complex neurometabolite abnormality after mild traumatic brain injury. Neurology 2014; 82 (06) 521-528
    CrossrefPubMedGoogle Scholar
  • 31 Duffy SL, Lagopoulos J, Hickie IB. , et al. Glutathione relates to neuropsychological functioning in mild cognitive impairment. Alzheimers Dement 2014; 10 (01) 67-75
    CrossrefPubMedGoogle Scholar
  • 32 Blaylock RL, Maroon J. Immunoexcitotoxicity as a central mechanism in chronic traumatic encephalopathy-A unifying hypothesis. Surg Neurol Int 2011; 2: 107
    CrossrefPubMedGoogle Scholar
  • 33 Murray ME, Przybelski SA, Lesnick TG. , et al. Early Alzheimer's disease neuropathology detected by proton MR spectroscopy. J Neurosci 2014; 34 (49) 16247-16255
    CrossrefPubMedGoogle Scholar
  • 34 Kantarci K, Knopman DS, Dickson DW. , et al. Alzheimer disease: postmortem neuropathologic correlates of antemortem 1H MR spectroscopy metabolite measurements. Radiology 2008; 248 (01) 210-220
    CrossrefPubMedGoogle Scholar
  • 35 Alosco ML, Rowland B, Tripodis Y, Liao HJ, Chua A, Martin B. . et al. Repetitive head impact exposure and later-life neurochemistry: a magnetic resonance spectroscopy investigation in symptomatic former NFL players. Paper presented at: 25th Annual Meeting of the International Society of Magnetic Resonance in Medicine; April 26, 2017; Honolulu, Hawaii
    PubMedGoogle Scholar
  • 36 Chamard E, Théoret H, Skopelja EN, Forwell LA, Johnson AM, Echlin PS. A prospective study of physician-observed concussion during a varsity university hockey season: metabolic changes in ice hockey players. Part 4 of 4. Neurosurg Focus 2012; 33 (6, E4): E4 , 1–7
    PubMedGoogle Scholar
  • 37 Davie CA, Pirtosek Z, Barker GJ, Kingsley DP, Miller PH, Lees AJ. Magnetic resonance spectroscopic study of parkinsonism related to boxing. J Neurol Neurosurg Psychiatry 1995; 58 (06) 688-691
    CrossrefPubMedGoogle Scholar
  • 38 Hetherington HP, Hamid H, Kulas J. , et al. MRSI of the medial temporal lobe at 7 T in explosive blast mild traumatic brain injury. Magn Reson Med 2014; 71 (04) 1358-1367
    CrossrefPubMedGoogle Scholar
  • 39 Koerte IK, Lin AP, Muehlmann M. , et al. Altered neurochemistry in former professional soccer players without a history of concussion. J Neurotrauma 2015; 32 (17) 1287-1293
    CrossrefPubMedGoogle Scholar
  • 40 Lin AP, Ramadan S, Stern RA. , et al. Changes in the neurochemistry of athletes with repetitive brain trauma: preliminary results using localized correlated spectroscopy. Alzheimers Res Ther 2015; 7 (01) 13
    CrossrefPubMedGoogle Scholar
  • 41 Mayer AR, Ling JM, Dodd AB, Gasparovic C, Klimaj SD, Meier TB. A longitudinal assessment of structural and chemical alterations in mixed martial arts fighters. J Neurotrauma 2015; 32: 1759-1767
    CrossrefPubMedGoogle Scholar
  • 42 Poole VN, Breedlove EL, Shenk TE. , et al. Sub-concussive hit characteristics predict deviant brain metabolism in football athletes. Dev Neuropsychol 2015; 40 (01) 12-17
    CrossrefPubMedGoogle Scholar
  • 43 Poole VN, Abbas K, Shenk TE. , et al. MR spectroscopic evidence of brain injury in the non-diagnosed collision sport athlete. Dev Neuropsychol 2014; 39 (06) 459-473
    CrossrefPubMedGoogle Scholar
  • 44 Tremblay S, De Beaumont L, Henry LC. , et al. Sports concussions and aging: a neuroimaging investigation. Cereb Cortex 2013; 23 (05) 1159-1166
    CrossrefPubMedGoogle Scholar
  • 45 Ramadan S, Andronesi OC, Stanwell P, Lin AP, Sorensen AG, Mountford CE. Use of in vivo two-dimensional MR spectroscopy to compare the biochemistry of the human brain to that of glioblastoma. Radiology 2011; 259 (02) 540-549
    CrossrefPubMedGoogle Scholar
  • 46 Thomas MA, Yue K, Binesh N. , et al. Localized two-dimensional shift correlated MR spectroscopy of human brain. Magn Reson Med 2001; 46 (01) 58-67
    CrossrefPubMedGoogle Scholar