Journal of Neuroimmune Pharmacology

, Volume 8, Issue 3, pp 576–593 | Cite as

Magnetic Resonance Spectroscopy to Assess NeuroInflammation and Neuropathic Pain

  • Linda Chang
  • Sody M. Munsaka
  • Stephanie Kraft-Terry
  • Thomas Ernst
INVITED REVIEW

Abstract

Proton magnetic resonance spectroscopy (1H MRS) has been applied to numerous clinical studies, especially for neurological disorders. This technique can non-invasively evaluate brain metabolites and neurochemicals in selected brain regions and is particularly useful for assessing neuroinflammatory disorders. Neurometabolites assessed with MRS include the neuronal markers N-acetylaspartate (NAA) and glutamate (Glu), as well as the glial marker myo-inositol (MI). Therefore, the concentrations of these metabolites typically correspond to disease severity and often correlate well with clinical variables in the various brain disorders. Neuroinflammation with activated astrocytes and microglia in brain disorders are often associated with elevated MI, and to a lesser extent elevated total creatine (tCr) and choline containing compounds (Cho), which are found in higher concentrations in glia than neurons, while neuronal injury is indicated by lower than normal levels of NAA and Glu. This review summarizes the neurometabolite abnormalities found in MRS studies performed in patients with neuroinflammatory disorders or neuropathic pain, which also may be associated with neuroinflammation. These brain disorders include multiple sclerosis, neuroviral infections (including Human Immunodeficiency virus and Hepatitis C), degenerative brain disorders (including Alzheimer’s disease and Parkinson’s disease), stimulant abuse (including methamphetamine and cocaine) as well as several chronic pain syndromes.

Keywords

Magnetic resonance spectroscopy Neuroinflammation Neuropathic pain 

References

  1. Alexander GM, Perreault MJ, Reichenberger ER, Schwartzman RJ (2007) Changes in immune and glial markers in the CSF of patients with Complex Regional Pain Syndrome. Brain Behav Immun 21:668–676PubMedCrossRefGoogle Scholar
  2. Ashford JW, Adamson M, Beale T, La D, Hernandez B, Noda A, Rosen A, O’Hara R, Fairchild JK, Spielman D, Yesavage JA (2011) MR spectroscopy for assessment of memantine treatment in mild to moderate Alzheimer dementia. J Alzheimers Dis 26(Suppl 3):331–336PubMedGoogle Scholar
  3. Bagory M, Durand-Dubief F, Ibarrola D, Comte JC, Cotton F, Confavreux C, Sappey-Marinier D (2011) Implementation of an absolute brain (1)H-MRS quantification method to assess different tissue alterations in multiple sclerosis. IEEE Trans Biomed Eng 59(10):2687–2694Google Scholar
  4. Banati RB (2003) Neuropathological imaging: in vivo detection of glial activation as a measure of disease and adaptive change in the brain. Br Med Bull 65:121–131PubMedCrossRefGoogle Scholar
  5. Bladowska J, Zimny A, Koltowska A, Szewczyk P, Knysz B, Gasiorowski J, Furdal M, Sasiadek MJ (2013) Evaluation of metabolic changes within the normal appearing gray and white matters in neurologically asymptomatic HIV-1-positive and HCV-positive patients: magnetic resonance spectroscopy and immunologic correlation. Eur J Radiol 82:686–692PubMedCrossRefGoogle Scholar
  6. Blaes F, Schmitz K, Tschernatsch M, Kaps M, Krasenbrink I, Hempelmann G, Brau ME (2004) Autoimmune etiology of complex regional pain syndrome (M. Sudeck). Neurology 63:1734–1736PubMedCrossRefGoogle Scholar
  7. Bokemeyer M, Ding XQ, Goldbecker A, Raab P, Heeren M, Arvanitis D, Tillmann HL, Lanfermann H, Weissenborn K (2011) Evidence for neuroinflammation and neuroprotection in HCV infection-associated encephalopathy. Gut 60:370–377PubMedCrossRefGoogle Scholar
  8. Brand A, Richter-Landsberg C, Leibfritz D (1993) Multinuclear NMR studies on the energy metabolism of glial and neuronal cells. Dev Neurosci 15:289–298PubMedCrossRefGoogle Scholar
  9. Brun A, Englund E (1981) Regional pattern of degeneration in Alzheimer’s disease: neuronal loss and histopathological grading. Histopathology 5:549–564PubMedCrossRefGoogle Scholar
  10. Byrnes V, Miller A, Lowry D, Hill E, Weinstein C, Alsop D, Lenkinski R, Afdhal NH (2012) Effects of anti-viral therapy and HCV clearance on cerebral metabolism and cognition. J Hepatol 56:549–556PubMedCrossRefGoogle Scholar
  11. Camicioli RM, Korzan JR, Foster SL, Fisher NJ, Emery DJ, Bastos AC, Hanstock CC (2004) Posterior cingulate metabolic changes occur in Parkinson’s disease patients without dementia. Neurosci Lett 354:177–180PubMedCrossRefGoogle Scholar
  12. Chang L, Miller BL, McBride D, Cornford M, Oropilla G, Buchthal S, Chiang F, Aronow H, Beck CK, Ernst T (1995) Brain lesions in patients with AIDS: H-1 MR spectroscopy. Radiology 197:525–531PubMedGoogle Scholar
  13. Chang L, Ernst T, Poland RE, Jenden DJ (1996) In vivo proton magnetic resonance spectroscopy of the normal aging human brain. Life Sci 58:2049–2056PubMedCrossRefGoogle Scholar
  14. Chang L, Ernst T, Tornatore C, Aronow H, Melchor R, Walot I, Singer E, Cornford M (1997a) Metabolite abnormalities in progressive multifocal leukoencephalopathy by proton magnetic resonance spectroscopy. Neurology 48:836–845PubMedCrossRefGoogle Scholar
  15. Chang L, Mehringer CM, Ernst T, Melchor R, Myers H, Forney D, Satz P (1997b) Neurochemical alterations in asymptomatic abstinent cocaine users: a proton magnetic resonance spectroscopy study. Biol Psychiatry 42:1105–1114PubMedCrossRefGoogle Scholar
  16. Chang L, Ernst T, Grob CS, Poland RE (1999a) Cerebral (1)H MRS alterations in recreational 3, 4-methylenedioxymethamphetamine (MDMA, “ecstasy”) users. J Magn Reson Imaging 10:521–526PubMedCrossRefGoogle Scholar
  17. Chang L, Ernst T, Leonido-Yee M, Walot I, Singer E (1999b) Cerebral metabolite abnormalities correlate with clinical severity of HIV-1 cognitive motor complex. Neurology 52:100–108PubMedCrossRefGoogle Scholar
  18. Chang L, Ernst T, Leonido-Yee M, Witt M, Speck O, Walot I, Miller EN (1999c) Highly active antiretroviral therapy reverses brain metabolite abnormalities in mild HIV dementia. Neurology 53:782–789PubMedCrossRefGoogle Scholar
  19. Chang L, Ernst T, Strickland T, Mehringer CM (1999d) Gender effects on persistent cerebral metabolite changes in the frontal lobes of abstinent cocaine users. Am J Psychiatry 156:716–722PubMedGoogle Scholar
  20. Chang L, Ernst T, Witt MD, Ames N, Gaiefsky M, Miller E (2002) Relationships among brain metabolites, cognitive function, and viral loads in antiretroviral-naive HIV patients. NeuroImage 17:1638–1648PubMedCrossRefGoogle Scholar
  21. Chang L, Ernst T, Witt MD, Ames N, Walot I, Jovicich J, DeSilva M, Trivedi N, Speck O, Miller EN (2003) Persistent brain abnormalities in antiretroviral-naive HIV patients 3 months after HAART. Antivir Ther 8:17–26PubMedGoogle Scholar
  22. Chang L, Ernst T, St Hillaire C, Conant K (2004a) Antiretroviral treatment alters relationship between MCP-1 and neurometabolites in HIV patients. Antivir Ther 9:431–440PubMedGoogle Scholar
  23. Chang L, Lee PL, Yiannoutsos CT, Ernst T, Marra CM, Richards T, Kolson D, Schifitto G, Jarvik JG, Miller EN, Lenkinski R, Gonzalez G, Navia BA (2004b) A multicenter in vivo proton-MRS study of HIV-associated dementia and its relationship to age. NeuroImage 23:1336–1347PubMedCrossRefGoogle Scholar
  24. Chang L, Cloak C, Patterson K, Grob C, Miller EN, Ernst T (2005a) Enlarged striatum in abstinent methamphetamine abusers: a possible compensatory response. Biol Psychiatry 57:967–974PubMedCrossRefGoogle Scholar
  25. Chang L, Ernst T, Speck O, Grob CS (2005b) Additive effects of HIV and chronic methamphetamine use on brain metabolite abnormalities. Am J Psychiatry 162:361–369PubMedCrossRefGoogle Scholar
  26. Chang L, Cloak C, Yakupov R, Ernst T (2006) Combined and independent effects of chronic marijuana use and HIV on brain metabolites. J NeuroImmune Pharm 1:65–76CrossRefGoogle Scholar
  27. Chang L, Jiang CS, Ernst T (2009) Effects of age and sex on brain glutamate and other metabolites. Magn Reson Imaging 27:142–145PubMedCrossRefGoogle Scholar
  28. Chang L, Feger U, Ernst T (2012) Neuroimaging. In: Gendelman HE, Ikezu T (eds) Neuroimmune pharmacology. Springer, New York, p l, 827 pGoogle Scholar
  29. Chassain C, Bielicki G, Keller C, Renou JP, Durif F (2010) Metabolic changes detected in vivo by 1H MRS in the MPTP-intoxicated mouse. NMR Biomed 23:547–553PubMedCrossRefGoogle Scholar
  30. Ciccarelli O, Wheeler-Kingshott CA, McLean MA, Cercignani M, Wimpey K, Miller DH, Thompson AJ (2007) Spinal cord spectroscopy and diffusion-based tractography to assess acute disability in multiple sclerosis. Brain 130:2220–2231PubMedCrossRefGoogle Scholar
  31. Emir UE, Tuite PJ, Oz G (2012) Elevated pontine and putamenal GABA levels in mild-moderate Parkinson disease detected by 7 tesla proton MRS. PLoS One 7:e30918PubMedCrossRefGoogle Scholar
  32. Ernst T, Chang L (2008) Adaptation of brain glutamate plus glutamine during abstinence from chronic methamphetamine use. J NeuroImmune Pharm 3:165–172CrossRefGoogle Scholar
  33. Ernst T, Kreis R, Ross BD (1993) Absolute quantitation of water and metabolites in the human brain. I: compartments and water. J Magn Res B102:1–8Google Scholar
  34. Ernst T, Chang L, Melchor R, Mehringer CM (1997) Frontotemporal dementia and early Alzheimer disease: differentiation with frontal lobe H-1 MR spectroscopy. Radiology 203:829–836PubMedGoogle Scholar
  35. Ernst T, Chang L, Walot I, Huff K (1998) Physiologic MRI of a tumefactive multiple sclerosis lesion. Neurology 51:1486–1488PubMedCrossRefGoogle Scholar
  36. Ernst T, Chang L, Leonido-Yee M, Speck O (2000) Evidence for long-term neurotoxicity associated with methamphetamine abuse: a 1H MRS study. Neurology 54:1344–1349PubMedCrossRefGoogle Scholar
  37. Ernst T, Jiang CS, Nakama H, Buchthal S, Chang L (2010) Lower brain glutamate is associated with cognitive deficits in HIV patients: a new mechanism for HIV-associated neurocognitive disorder. J Magn Reson Imaging 32:1045–1053PubMedCrossRefGoogle Scholar
  38. Fernando MS, O’Brien JT, Perry RH, English P, Forster G, McMeekin W, Slade JY, Golkhar A, Matthews FE, Barber R, Kalaria RN, Ince PG (2004) Comparison of the pathology of cerebral white matter with post-mortem magnetic resonance imaging (MRI) in the elderly brain. Neuropathol Appl Neurobiol 30:385–395PubMedCrossRefGoogle Scholar
  39. Foerster BR, Petrou M, Edden RA, Sundgren PC, Schmidt-Wilcke T, Lowe SE, Harte SE, Clauw DJ, Harris RE (2012) Reduced insular gamma-aminobutyric acid in fibromyalgia. Arthritis Rheum 64:579–583PubMedCrossRefGoogle Scholar
  40. Forton DM, Allsop JM, Main J, Foster GR, Thomas HC, Taylor-Robinson SD (2001) Evidence for a cerebral effect of the hepatitis C virus. Lancet 358:38–39PubMedCrossRefGoogle Scholar
  41. Forton DM, Thomas HC, Murphy CA, Allsop JM, Foster GR, Main J, Wesnes KA, Taylor-Robinson SD (2002) Hepatitis C and cognitive impairment in a cohort of patients with mild liver disease. Hepatology 35:433–439PubMedCrossRefGoogle Scholar
  42. Forton DM, Thomas HC, Taylor-Robinson SD (2004) Central nervous system involvement in hepatitis C virus infection. Metab Brain Dis 19:383–391PubMedCrossRefGoogle Scholar
  43. Forton DM, Hamilton G, Allsop JM, Grover VP, Wesnes K, O’Sullivan C, Thomas HC, Taylor-Robinson SD (2008) Cerebral immune activation in chronic hepatitis C infection: a magnetic resonance spectroscopy study. J Hepatol 49:316–322PubMedCrossRefGoogle Scholar
  44. Frederick BD, Lyoo IK, Satlin A, Ahn KH, Kim MJ, Yurgelun-Todd DA, Cohen BM, Renshaw PF (2004) In vivo proton magnetic resonance spectroscopy of the temporal lobe in Alzheimer’s disease. Prog Neuro-Psychopharmacol Biol Psychiatry 28:1313–1322CrossRefGoogle Scholar
  45. Fukui S, Matsuno M, Inubushi T, Nosaka S (2006) N-Acetylaspartate concentrations in the thalami of neuropathic pain patients and healthy comparison subjects measured with (1)H-MRS. Magn Reson Imaging 24:75–79PubMedCrossRefGoogle Scholar
  46. Garvey LJ, Pavese N, Ramlackhansingh A, Thomson E, Allsop JM, Politis M, Kulasegaram R, Main J, Brooks DJ, Taylor-Robinson SD, Winston A (2012) Acute HCV/HIV coinfection is associated with cognitive dysfunction and cerebral metabolite disturbance, but not increased microglial cell activation. PLoS One 7:e38980PubMedCrossRefGoogle Scholar
  47. Gerstner GE, Gracely RH, Deebajah A, Ichesco E, Quintero A, Clauw DJ, Sundgren PC (2012) Posterior insular molecular changes in myofascial pain. J Dent Res 91:485–490PubMedCrossRefGoogle Scholar
  48. Geurts JJ, Reuling IE, Vrenken H, Uitdehaag BM, Polman CH, Castelijns JA, Barkhof F, Pouwels PJ (2006) MR spectroscopic evidence for thalamic and hippocampal, but not cortical, damage in multiple sclerosis. Magn Reson Med 55:478–483PubMedCrossRefGoogle Scholar
  49. Griffith HR, den Hollander JA, Stewart CC, Evanochko WT, Buchthal SD, Harrell LE, Zamrini EY, Brockington JC, Marson DC (2007) Elevated brain scyllo-inositol concentrations in patients with Alzheimer’s disease. NMR Biomed 20:709–716PubMedCrossRefGoogle Scholar
  50. Griffith HR, den Hollander JA, Okonkwo OC, O’Brien T, Watts RL, Marson DC (2008a) Brain metabolism differs in Alzheimer’s disease and Parkinson’s disease dementia. Alzheimers Dement 4:421–427PubMedCrossRefGoogle Scholar
  51. Griffith HR, den Hollander JA, Okonkwo OC, O’Brien T, Watts RL, Marson DC (2008b) Brain N-acetylaspartate is reduced in Parkinson disease with dementia. Alzheimer Dis Assoc Disord 22:54–60PubMedCrossRefGoogle Scholar
  52. Griffith HR, Okonkwo OC, O’Brien T, Hollander JA (2008c) Reduced brain glutamate in patients with Parkinson’s disease. NMR Biomed 21:381–387PubMedCrossRefGoogle Scholar
  53. Grover VP, Pavese N, Koh SB, Wylezinska M, Saxby BK, Gerhard A, Forton DM, Brooks DJ, Thomas HC, Taylor-Robinson SD (2012) Cerebral microglial activation in patients with hepatitis C: in vivo evidence of neuroinflammation. J Viral Hepat 19:e89–e96PubMedCrossRefGoogle Scholar
  54. Gu T, Ma XX, Xu YH, Xiu JJ, Li CF (2008) Metabolite concentration ratios in thalami of patients with migraine and trigeminal neuralgia measured with 1H-MRS. Neurol Res 30:229–233PubMedCrossRefGoogle Scholar
  55. Gustafsson MC, Dahlqvist O, Jaworski J, Lundberg P, Landtblom AM (2007) Low choline concentrations in normal-appearing white matter of patients with multiple sclerosis and normal MR imaging brain scans. AJNR Am J Neuroradiol 28:1306–1312PubMedCrossRefGoogle Scholar
  56. Hardy J, Allsop D (1991) Amyloid deposition as the central event in the aetiology of Alzheimer’s disease. Trends Pharmacol Sci 12:383–388PubMedCrossRefGoogle Scholar
  57. Harezlak J, Buchthal S, Taylor M, Schifitto G, Zhong J, Daar E, Alger J, Singer E, Campbell T, Yiannoutsos C, Cohen R, Navia B (2011) Persistence of HIV-associated cognitive impairment, inflammation, and neuronal injury in era of highly active antiretroviral treatment. AIDS 25:625–633PubMedCrossRefGoogle Scholar
  58. Harris RE, Clauw DJ (2012) Imaging central neurochemical alterations in chronic pain with proton magnetic resonance spectroscopy. Neurosci Lett 520:192–196PubMedCrossRefGoogle Scholar
  59. Harris RE, Sundgren PC, Pang Y, Hsu M, Petrou M, Kim SH, McLean SA, Gracely RH, Clauw DJ (2008) Dynamic levels of glutamate within the insula are associated with improvements in multiple pain domains in fibromyalgia. Arthritis Rheum 58:903–907PubMedCrossRefGoogle Scholar
  60. Inglese M, Li BS, Rusinek H, Babb JS, Grossman RI, Gonen O (2003) Diffusely elevated cerebral choline and creatine in relapsing-remitting multiple sclerosis. Magn Reson Med 50:190–195PubMedCrossRefGoogle Scholar
  61. Iranzo A, Moreno A, Pujol J, Marti-Fabregas J, Domingo P, Molet J, Ris J, Cadafalch J (1999) Proton magnetic resonance spectroscopy pattern of progressive multifocal leukoencephalopathy in AIDS. J Neurol Neurosurg Psychiatry 66:520–523PubMedCrossRefGoogle Scholar
  62. Jansen JF, Backes WH, Nicolay K, Kooi ME (2006) 1H MR spectroscopy of the brain: absolute quantification of metabolites. Radiology 240:318–332PubMedCrossRefGoogle Scholar
  63. Jessen F, Gur O, Block W, Ende G, Frolich L, Hammen T, Wiltfang J, Kucinski T, Jahn H, Heun R, Maier W, Kolsch H, Kornhuber J, Traber F (2009) A multicenter (1)H-MRS study of the medial temporal lobe in AD and MCI. Neurology 72:1735–1740PubMedCrossRefGoogle Scholar
  64. Kickler N, Krack P, Fraix V, Lebas JF, Lamalle L, Durif F, Krainik A, Remy C, Segebarth C, Pollak P (2007) Glutamate measurement in Parkinson’s disease using MRS at 3 T field strength. NMR Biomed 20:757–762PubMedCrossRefGoogle Scholar
  65. Kirov II, Patil V, Babb JS, Rusinek H, Herbert J, Gonen O (2009) MR spectroscopy indicates diffuse multiple sclerosis activity during remission. J Neurol Neurosurg Psychiatry 80:1330–1336PubMedCrossRefGoogle Scholar
  66. Kirov II, Tal A, Babb JS, Herbert J, Gonen O (2013) Serial proton MR spectroscopy of gray and white matter in relapsing-remitting MS. Neurology 80:39–46PubMedCrossRefGoogle Scholar
  67. Kish SJ, Rajput A, Gilbert J, Rozdilsky B, Chang LJ, Shannak K, Hornykiewicz O (1986) Elevated gamma-aminobutyric acid level in striatal but not extrastriatal brain regions in Parkinson’s disease: correlation with striatal dopamine loss. Ann Neurol 20:26–31PubMedCrossRefGoogle Scholar
  68. Klunk WE, Panchalingam K, Moossy J, McClure RJ, Pettegrew JW (1992) N-acetyl-L-aspartate and other amino acid metabolites in Alzheimer’s disease brain: a preliminary proton nuclear magnetic resonance study. Neurology 42:1578–1585PubMedCrossRefGoogle Scholar
  69. Latremoliere A, Woolf CJ (2009) Central sensitization: a generator of pain hypersensitivity by central neural plasticity. J Pain 10:895–926PubMedCrossRefGoogle Scholar
  70. Lentz MR, Kim WK, Lee V, Bazner S, Halpern EF, Venna N, Williams K, Rosenberg ES, Gonzalez RG (2009) Changes in MRS neuronal markers and T cell phenotypes observed during early HIV infection. Neurology 72:1465–1472PubMedCrossRefGoogle Scholar
  71. Lentz MR, Kim WK, Kim H, Soulas C, Lee V, Venna N, Halpern EF, Rosenberg ES, Williams K, Gonzalez RG (2011) Alterations in brain metabolism during the first year of HIV infection. J Neurovirol 17:220–229PubMedCrossRefGoogle Scholar
  72. Letendre SL, Zheng JC, Kaul M, Yiannoutsos CT, Ellis RJ, Taylor MJ, Marquie-Beck J, Navia B (2011) Chemokines in cerebrospinal fluid correlate with cerebral metabolite patterns in HIV-infected individuals. J Neurovirol 17:63–69PubMedCrossRefGoogle Scholar
  73. Li SJ, Wang Y, Pankiewicz J, Stein EA (1999) Neurochemical adaptation to cocaine abuse: reduction of N-acetyl aspartate in thalamus of human cocaine abusers. Biol Psychiatry 45:1481–1487PubMedCrossRefGoogle Scholar
  74. Liu J, Gong N, Huang X, Reynolds AD, Mosley RL, Gendelman HE (2009) Neuromodulatory activities of CD4+CD25+ regulatory T cells in a murine model of HIV-1-associated neurodegeneration. J Immunol 182:3855–3865PubMedCrossRefGoogle Scholar
  75. Marliani AF, Clementi V, Albini Riccioli L, Agati R, Carpenzano M, Salvi F, Leonardi M (2010) Quantitative cervical spinal cord 3T proton MR spectroscopy in multiple sclerosis. AJNR Am J Neuroradiol 31:180–184PubMedCrossRefGoogle Scholar
  76. McAndrews MP, Farcnik K, Carlen P, Damyanovich A, Mrkonjic M, Jones S, Heathcote EJ (2005) Prevalence and significance of neurocognitive dysfunction in hepatitis C in the absence of correlated risk factors. Hepatology 41:801–808PubMedCrossRefGoogle Scholar
  77. McLaurin J, Golomb R, Jurewicz A, Antel JP, Fraser PE (2000) Inositol stereoisomers stabilize an oligomeric aggregate of Alzheimer amyloid beta peptide and inhibit abeta -induced toxicity. J Biol Chem 275:18495–18502PubMedCrossRefGoogle Scholar
  78. Meyerhoff DJ, Bloomer C, Schuff N, Ezekiel F, Norman D, Clark W, Weiner MW, Fein G (1999) Cortical metabolite alterations in abstinent cocaine and cocaine/alcohol-dependent subjects: proton magnetic resonance spectroscopic imaging. Addict Biol 4:405–419PubMedCrossRefGoogle Scholar
  79. Miller BL, Moats RA, Shonk T, Ernst T, Woolley S, Ross BD (1993) Alzheimer disease: depiction of increased cerebral myo-inositol with proton MR spectroscopy. Radiology 187:433–437PubMedGoogle Scholar
  80. Moats RA, Ernst T, Shonk TK, Ross BD (1994) Abnormal cerebral metabolite concentrations in patients with probable Alzheimer disease. Magn Reson Med 32:110–115PubMedCrossRefGoogle Scholar
  81. Mogi M, Harada M, Riederer P, Narabayashi H, Fujita K, Nagatsu T (1994) Tumor necrosis factor-alpha (TNF-alpha) increases both in the brain and in the cerebrospinal fluid from parkinsonian patients. Neurosci Lett 165:208–210PubMedCrossRefGoogle Scholar
  82. Mohamed MA, Barker PB, Skolasky RL, Selnes OA, Moxley RT, Pomper MG, Sacktor NC (2010) Brain metabolism and cognitive impairment in HIV infection: a 3-T magnetic resonance spectroscopy study. Magn Reson Imaging 28:1251–1257PubMedCrossRefGoogle Scholar
  83. Mullins PG, Rowland LM, Jung RE, Sibbitt WL Jr (2005) A novel technique to study the brain’s response to pain: proton magnetic resonance spectroscopy. NeuroImage 26:642–646PubMedCrossRefGoogle Scholar
  84. Nie K, Zhang Y, Huang B, Wang L, Zhao J, Huang Z, Gan R (2013) Marked N-acetylaspartate and choline metabolite changes in Parkinson’s disease patients with mild cognitive impairment. Parkinsonism Relat Disord 19:329–334PubMedCrossRefGoogle Scholar
  85. Nordahl TE, Salo R, Possin K, Gibson DR, Flynn N, Leamon M, Galloway GP, Pfefferbaum A, Spielman DM, Adalsteinsson E, Sullivan EV (2002) Low N-acetyl-aspartate and high choline in the anterior cingulum of recently abstinent methamphetamine-dependent subjects: a preliminary proton MRS study. Magnetic resonance spectroscopy. Psychiatry Res 116:43–52PubMedCrossRefGoogle Scholar
  86. O’Neill J, Schuff N, Marks WJ Jr, Feiwell R, Aminoff MJ, Weiner MW (2002) Quantitative 1H magnetic resonance spectroscopy and MRI of Parkinson’s disease. Mov Disord 17:917–927PubMedCrossRefGoogle Scholar
  87. Oz G, Terpstra M, Tkac I, Aia P, Lowary J, Tuite PJ, Gruetter R (2006) Proton MRS of the unilateral substantia nigra in the human brain at 4 tesla: detection of high GABA concentrations. Magn Reson Med 55:296–301PubMedCrossRefGoogle Scholar
  88. Pattany PM, Yezierski RP, Widerstrom-Noga EG, Bowen BC, Martinez-Arizala A, Garcia BR, Quencer RM (2002) Proton magnetic resonance spectroscopy of the thalamus in patients with chronic neuropathic pain after spinal cord injury. AJNR Am J Neuroradiol 23:901–905PubMedGoogle Scholar
  89. Pattullo V, McAndrews MP, Damyanovich A, Heathcote EJ (2011) Influence of hepatitis C virus on neurocognitive function in patients free from other risk factors: validation from therapeutic outcomes. Liver Int 31:1028–1038PubMedCrossRefGoogle Scholar
  90. Penner J, Rupsingh R, Smith M, Wells JL, Borrie MJ, Bartha R (2010) Increased glutamate in the hippocampus after galantamine treatment for Alzheimer disease. Prog Neuro-Psychopharmacol Biol Psychiatry 34:104–110CrossRefGoogle Scholar
  91. Rami L, Gomez-Anson B, Bosch B, Sanchez-Valle R, Monte GC, Villar A, Molinuevo JL (2007) Cortical brain metabolism as measured by proton spectroscopy is related to memory performance in patients with amnestic mild cognitive impairment and Alzheimer’s disease. Dement Geriatr Cogn Disord 24:274–279PubMedCrossRefGoogle Scholar
  92. Reneman L, Majoie CB, Schmand B, van den Brink W, den Heeten GJ (2001) Prefrontal N-acetylaspartate is strongly associated with memory performance in (abstinent) ecstasy users: preliminary report. Biol Psychiatry 50:550–554PubMedCrossRefGoogle Scholar
  93. Reneman L, Majoie CB, Flick H, den Heeten GJ (2002) Reduced N-acetylaspartate levels in the frontal cortex of 3,4-methylenedioxymethamphetamine (Ecstasy) users: preliminary results. AJNR Am J Neuroradiol 23:231–237PubMedGoogle Scholar
  94. Rigotti DJ, Inglese M, Kirov II, Gorynski E, Perry NN, Babb JS, Herbert J, Grossman RI, Gonen O (2012) Two-year serial whole-brain N-acetyl-L-aspartate in patients with relapsing-remitting multiple sclerosis. Neurology 78:1383–1389PubMedCrossRefGoogle Scholar
  95. Rupsingh R, Borrie M, Smith M, Wells JL, Bartha R (2011) Reduced hippocampal glutamate in Alzheimer disease. Neurobiol Aging 32:802–810PubMedCrossRefGoogle Scholar
  96. Salo R, Buonocore MH, Leamon M, Natsuaki Y, Waters C, Moore CD, Galloway GP, Nordahl TE (2011) Extended findings of brain metabolite normalization in MA-dependent subjects across sustained abstinence: a proton MRS study. Drug Alcohol Depend 113:133–138PubMedCrossRefGoogle Scholar
  97. Schifitto G, Navia BA, Yiannoutsos CT, Marra CM, Chang L, Ernst T, Jarvik JG, Miller EN, Singer EJ, Ellis RJ, Kolson DL, Simpson D, Nath A, Berger J, Shriver SL, Millar LL, Colquhoun D, Lenkinski R, Gonzalez RG, Lipton SA (2007) Memantine and HIV-associated cognitive impairment: a neuropsychological and proton magnetic resonance spectroscopy study. AIDS 21:1877–1886PubMedCrossRefGoogle Scholar
  98. Schweinsburg BC, Taylor MJ, Alhassoon OM, Gonzalez R, Brown GG, Ellis RJ, Letendre S, Videen JS, McCutchan JA, Patterson TL, Grant I (2005) Brain mitochondrial injury in human immunodeficiency virus-seropositive (HIV+) individuals taking nucleoside reverse transcriptase inhibitors. J Neurovirol 11:356–364PubMedCrossRefGoogle Scholar
  99. Shinno H, Inagaki T, Miyaoka T, Okazaki S, Kawamukai T, Utani E, Inami Y, Horiguchi J (2007) A decrease in N-acetylaspartate and an increase in myoinositol in the anterior cingulate gyrus are associated with behavioral and psychological symptoms in Alzheimer’s disease. J Neurol Sci 260:132–138PubMedCrossRefGoogle Scholar
  100. Sorensen L, Siddall PJ, Trenell MI, Yue DK (2008) Differences in metabolites in pain-processing brain regions in patients with diabetes and painful neuropathy. Diabetes Care 31:980–981PubMedCrossRefGoogle Scholar
  101. Srinivasan R, Sailasuta N, Hurd R, Nelson S, Pelletier D (2005) Evidence of elevated glutamate in multiple sclerosis using magnetic resonance spectroscopy at 3 T. Brain 128:1016–1025PubMedCrossRefGoogle Scholar
  102. Sung YH, Cho SC, Hwang J, Kim SJ, Kim H, Bae S, Kim N, Chang KH, Daniels M, Renshaw PF, Lyoo IK (2007) Relationship between N-acetyl-aspartate in gray and white matter of abstinent methamphetamine abusers and their history of drug abuse: a proton magnetic resonance spectroscopy study. Drug Alcohol Depend 88:28–35PubMedCrossRefGoogle Scholar
  103. Tarasow E, Wiercinska-Drapalo A, Jaroszewicz J, Orzechowska-Bobkiewicz A, Dzienis W, Prokopowicz D, Walecki J (2004) Antiretroviral therapy and its influence on the stage of brain damage in patients with HIV - 1H MRS evaluation. Med Sci Monit 10(Suppl 3):101–106PubMedGoogle Scholar
  104. Taylor MJ, Schweinsburg BC, Alhassoon OM, Gongvatana A, Brown GG, Young-Casey C, Letendre SL, Grant I (2007) Effects of human immunodeficiency virus and methamphetamine on cerebral metabolites measured with magnetic resonance spectroscopy. J Neurovirol 13:150–159PubMedCrossRefGoogle Scholar
  105. Tofaris GK, Razzaq A, Ghetti B, Lilley KS, Spillantini MG (2003) Ubiquitination of alpha-synuclein in Lewy bodies is a pathological event not associated with impairment of proteasome function. J Biol Chem 278:44405–44411PubMedCrossRefGoogle Scholar
  106. Valcour V, Chalermchai T, Sailasuta N, Marovich M, Lerdlum S, Suttichom D, Suwanwela NC, Jagodzinski L, Michael N, Spudich S, van Griensven F, de Souza M, Kim J, Ananworanich J (2012) CNS viral invasion and inflammation during acute HIV. J Infect Dis 206(2):275–282.Google Scholar
  107. van der Voorn JP, Pouwels PJ, Vermeulen RJ, Barkhof F, van der Knaap MS (2009) Quantitative MR imaging and spectroscopy in congenital cytomegalovirus infection and periventricular leukomalacia suggests a comparable neuropathological substrate of the cerebral white matter lesions. Neuropediatrics 40:168–173PubMedCrossRefGoogle Scholar
  108. Vrenken H, Barkhof F, Uitdehaag BM, Castelijns JA, Polman CH, Pouwels PJ (2005) MR spectroscopic evidence for glial increase but not for neuro-axonal damage in MS normal-appearing white matter. Magn Reson Med 53:256–266PubMedCrossRefGoogle Scholar
  109. Weissenborn K, Krause J, Bokemeyer M, Hecker H, Schuler A, Ennen JC, Ahl B, Manns MP, Boker KW (2004) Hepatitis C virus infection affects the brain-evidence from psychometric studies and magnetic resonance spectroscopy. J Hepatol 41:845–851PubMedCrossRefGoogle Scholar
  110. Widerstrom-Noga E, Pattany PM, Cruz-Almeida Y, Felix ER, Perez S, Cardenas DD, Martinez-Arizala A (2013) Metabolite concentrations in the anterior cingulate cortex predict high neuropathic pain impact after spinal cord injury. Pain 154:204–212PubMedCrossRefGoogle Scholar
  111. Williams DW, Eugenin EA, Calderon TM, Berman JW (2012) Monocyte maturation, HIV susceptibility, and transmigration across the blood brain barrier are critical in HIV neuropathogenesis. J Leukoc Biol 91:401–415PubMedCrossRefGoogle Scholar
  112. Wood ET, Ronen I, Techawiboonwong A, Jones CK, Barker PB, Calabresi P, Harrison D, Reich DS (2012) Investigating axonal damage in multiple sclerosis by diffusion tensor spectroscopy. J Neurosci 32:6665–6669PubMedCrossRefGoogle Scholar
  113. Yamamoto BK, Moszczynska A, Gudelsky GA (2010) Amphetamine toxicities: classical and emerging mechanisms. Ann N Y Acad Sci 1187:101–121PubMedCrossRefGoogle Scholar
  114. Yang S, Salmeron BJ, Ross TJ, Xi ZX, Stein EA, Yang Y (2009) Lower glutamate levels in rostral anterior cingulate of chronic cocaine users - A (1)H-MRS study using TE-averaged PRESS at 3 T with an optimized quantification strategy. Psychiatry Res 174:171–176PubMedCrossRefGoogle Scholar
  115. Yoon JH, Bang OY, Kim HS (2007) Progressive multifocal leukoencephalopathy in AIDS: proton MR spectroscopy patterns of asynchronous lesions confirmed by serial diffusion-weighted imaging and apparent diffusion coefficient mapping. J Clin Neurol 3:200–203PubMedCrossRefGoogle Scholar
  116. Zhang W, Wang T, Pei Z, Miller DS, Wu X, Block ML, Wilson B, Zhou Y, Hong JS, Zhang J (2005) Aggregated alpha-synuclein activates microglia: a process leading to disease progression in Parkinson’s disease. FASEB J 19:533–542PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Linda Chang
    • 1
    • 3
  • Sody M. Munsaka
    • 1
  • Stephanie Kraft-Terry
    • 2
  • Thomas Ernst
    • 1
  1. 1.Department of Medicine, John A. Burns School of Medicine, University of Hawai’i at Manoa, Neuroscience and Magnetic Resonance Research ProgramThe Queen’s Medical CenterHonoluluUSA
  2. 2.Department of BiologyUniversity of Hawai’i at ManoaHonoluluUSA
  3. 3.Department of Medicine, John A. Burns School of MedicineThe Queen’s Medical CenterHonoluluUSA

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