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Magnetic Resonance Spectroscopy to Assess NeuroInflammation and Neuropathic Pain

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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.

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References

  • 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 21:668–676

    Article  PubMed  CAS  Google Scholar 

  • 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):331–336

    PubMed  CAS  Google Scholar 

  • 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):2687–2694

    Google Scholar 

  • 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 65:121–131

    Article  PubMed  Google Scholar 

  • 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 82:686–692

    Article  PubMed  Google Scholar 

  • 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 63:1734–1736

    Article  PubMed  CAS  Google Scholar 

  • 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 60:370–377

    Article  PubMed  CAS  Google Scholar 

  • Brand A, Richter-Landsberg C, Leibfritz D (1993) Multinuclear NMR studies on the energy metabolism of glial and neuronal cells. Dev Neurosci 15:289–298

    Article  PubMed  CAS  Google Scholar 

  • Brun A, Englund E (1981) Regional pattern of degeneration in Alzheimer’s disease: neuronal loss and histopathological grading. Histopathology 5:549–564

    Article  PubMed  CAS  Google Scholar 

  • 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 56:549–556

    Article  PubMed  CAS  Google Scholar 

  • 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 354:177–180

    Article  PubMed  CAS  Google Scholar 

  • 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 197:525–531

    PubMed  CAS  Google Scholar 

  • Chang L, Ernst T, Poland RE, Jenden DJ (1996) In vivo proton magnetic resonance spectroscopy of the normal aging human brain. Life Sci 58:2049–2056

    Article  PubMed  CAS  Google Scholar 

  • 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 48:836–845

    Article  PubMed  CAS  Google Scholar 

  • 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 42:1105–1114

    Article  PubMed  CAS  Google Scholar 

  • 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 10:521–526

    Article  PubMed  CAS  Google Scholar 

  • 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 52:100–108

    Article  PubMed  CAS  Google Scholar 

  • 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 53:782–789

    Article  PubMed  CAS  Google Scholar 

  • 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 156:716–722

    PubMed  CAS  Google Scholar 

  • 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 17:1638–1648

    Article  PubMed  Google Scholar 

  • 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 8:17–26

    PubMed  CAS  Google Scholar 

  • Chang L, Ernst T, St Hillaire C, Conant K (2004a) Antiretroviral treatment alters relationship between MCP-1 and neurometabolites in HIV patients. Antivir Ther 9:431–440

    PubMed  CAS  Google Scholar 

  • 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 23:1336–1347

    Article  PubMed  CAS  Google Scholar 

  • 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 57:967–974

    Article  PubMed  CAS  Google Scholar 

  • Chang L, Ernst T, Speck O, Grob CS (2005b) Additive effects of HIV and chronic methamphetamine use on brain metabolite abnormalities. Am J Psychiatry 162:361–369

    Article  PubMed  Google Scholar 

  • 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 1:65–76

    Article  CAS  Google Scholar 

  • Chang L, Jiang CS, Ernst T (2009) Effects of age and sex on brain glutamate and other metabolites. Magn Reson Imaging 27:142–145

    Article  PubMed  CAS  Google Scholar 

  • Chang L, Feger U, Ernst T (2012) Neuroimaging. In: Gendelman HE, Ikezu T (eds) Neuroimmune pharmacology. Springer, New York, p l, 827 p

    Google Scholar 

  • 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 23:547–553

    Article  PubMed  CAS  Google Scholar 

  • 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 130:2220–2231

    Article  PubMed  CAS  Google Scholar 

  • 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:e30918

    Article  PubMed  CAS  Google Scholar 

  • Ernst T, Chang L (2008) Adaptation of brain glutamate plus glutamine during abstinence from chronic methamphetamine use. J NeuroImmune Pharm 3:165–172

    Article  Google Scholar 

  • Ernst T, Kreis R, Ross BD (1993) Absolute quantitation of water and metabolites in the human brain. I: compartments and water. J Magn Res B102:1–8

    Google Scholar 

  • Ernst T, Chang L, Melchor R, Mehringer CM (1997) Frontotemporal dementia and early Alzheimer disease: differentiation with frontal lobe H-1 MR spectroscopy. Radiology 203:829–836

    PubMed  CAS  Google Scholar 

  • Ernst T, Chang L, Walot I, Huff K (1998) Physiologic MRI of a tumefactive multiple sclerosis lesion. Neurology 51:1486–1488

    Article  PubMed  CAS  Google Scholar 

  • Ernst T, Chang L, Leonido-Yee M, Speck O (2000) Evidence for long-term neurotoxicity associated with methamphetamine abuse: a 1H MRS study. Neurology 54:1344–1349

    Article  PubMed  CAS  Google Scholar 

  • 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 32:1045–1053

    Article  PubMed  Google Scholar 

  • 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 30:385–395

    Article  PubMed  CAS  Google Scholar 

  • 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 64:579–583

    Article  PubMed  CAS  Google Scholar 

  • 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 358:38–39

    Article  PubMed  CAS  Google Scholar 

  • 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 35:433–439

    Article  PubMed  Google Scholar 

  • Forton DM, Thomas HC, Taylor-Robinson SD (2004) Central nervous system involvement in hepatitis C virus infection. Metab Brain Dis 19:383–391

    Article  PubMed  Google Scholar 

  • 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 49:316–322

    Article  PubMed  CAS  Google Scholar 

  • 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 28:1313–1322

    Article  CAS  Google Scholar 

  • 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 24:75–79

    Article  PubMed  CAS  Google Scholar 

  • 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:e38980

    Article  PubMed  CAS  Google Scholar 

  • 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 91:485–490

    Article  PubMed  CAS  Google Scholar 

  • 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 55:478–483

    Article  PubMed  CAS  Google Scholar 

  • 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 20:709–716

    Article  PubMed  CAS  Google Scholar 

  • 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 4:421–427

    Article  PubMed  CAS  Google Scholar 

  • 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 22:54–60

    Article  PubMed  CAS  Google Scholar 

  • Griffith HR, Okonkwo OC, O’Brien T, Hollander JA (2008c) Reduced brain glutamate in patients with Parkinson’s disease. NMR Biomed 21:381–387

    Article  PubMed  CAS  Google Scholar 

  • 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–e96

    Article  PubMed  CAS  Google Scholar 

  • 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 30:229–233

    Article  PubMed  CAS  Google Scholar 

  • 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 28:1306–1312

    Article  PubMed  CAS  Google Scholar 

  • Hardy J, Allsop D (1991) Amyloid deposition as the central event in the aetiology of Alzheimer’s disease. Trends Pharmacol Sci 12:383–388

    Article  PubMed  CAS  Google Scholar 

  • 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 25:625–633

    Article  PubMed  CAS  Google Scholar 

  • Harris RE, Clauw DJ (2012) Imaging central neurochemical alterations in chronic pain with proton magnetic resonance spectroscopy. Neurosci Lett 520:192–196

    Article  PubMed  CAS  Google Scholar 

  • 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 58:903–907

    Article  PubMed  CAS  Google Scholar 

  • 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 50:190–195

    Article  PubMed  CAS  Google Scholar 

  • 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 66:520–523

    Article  PubMed  CAS  Google Scholar 

  • Jansen JF, Backes WH, Nicolay K, Kooi ME (2006) 1H MR spectroscopy of the brain: absolute quantification of metabolites. Radiology 240:318–332

    Article  PubMed  Google Scholar 

  • 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 72:1735–1740

    Article  PubMed  CAS  Google Scholar 

  • 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 20:757–762

    Article  PubMed  CAS  Google Scholar 

  • 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 80:1330–1336

    Article  PubMed  CAS  Google Scholar 

  • 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 80:39–46

    Article  PubMed  Google Scholar 

  • 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 20:26–31

    Article  PubMed  CAS  Google Scholar 

  • 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 42:1578–1585

    Article  PubMed  CAS  Google Scholar 

  • Latremoliere A, Woolf CJ (2009) Central sensitization: a generator of pain hypersensitivity by central neural plasticity. J Pain 10:895–926

    Article  PubMed  Google Scholar 

  • 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 72:1465–1472

    Article  PubMed  CAS  Google Scholar 

  • 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 17:220–229

    Article  PubMed  CAS  Google Scholar 

  • 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 17:63–69

    Article  PubMed  CAS  Google Scholar 

  • 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 45:1481–1487

    Article  PubMed  CAS  Google Scholar 

  • 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 182:3855–3865

    Article  PubMed  CAS  Google Scholar 

  • 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 31:180–184

    Article  PubMed  CAS  Google Scholar 

  • 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 41:801–808

    Article  PubMed  Google Scholar 

  • 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 275:18495–18502

    Article  PubMed  CAS  Google Scholar 

  • 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 4:405–419

    Article  PubMed  CAS  Google Scholar 

  • 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 187:433–437

    PubMed  CAS  Google Scholar 

  • Moats RA, Ernst T, Shonk TK, Ross BD (1994) Abnormal cerebral metabolite concentrations in patients with probable Alzheimer disease. Magn Reson Med 32:110–115

    Article  PubMed  CAS  Google Scholar 

  • 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 165:208–210

    Article  PubMed  CAS  Google Scholar 

  • 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 28:1251–1257

    Article  PubMed  CAS  Google Scholar 

  • 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 26:642–646

    Article  PubMed  Google Scholar 

  • 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 19:329–334

    Article  PubMed  Google Scholar 

  • 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 116:43–52

    Article  PubMed  CAS  Google Scholar 

  • 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 17:917–927

    Article  PubMed  Google Scholar 

  • 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 55:296–301

    Article  PubMed  CAS  Google Scholar 

  • 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 23:901–905

    PubMed  Google Scholar 

  • 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 31:1028–1038

    Article  PubMed  Google Scholar 

  • 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 34:104–110

    Article  CAS  Google Scholar 

  • 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 24:274–279

    Article  PubMed  CAS  Google Scholar 

  • 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 50:550–554

    Article  PubMed  CAS  Google Scholar 

  • 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 23:231–237

    PubMed  Google Scholar 

  • 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 78:1383–1389

    Article  PubMed  CAS  Google Scholar 

  • Rupsingh R, Borrie M, Smith M, Wells JL, Bartha R (2011) Reduced hippocampal glutamate in Alzheimer disease. Neurobiol Aging 32:802–810

    Article  PubMed  CAS  Google Scholar 

  • 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 113:133–138

    Article  PubMed  Google Scholar 

  • 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 21:1877–1886

    Article  PubMed  CAS  Google Scholar 

  • 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 11:356–364

    Article  PubMed  CAS  Google Scholar 

  • 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 260:132–138

    Article  PubMed  CAS  Google Scholar 

  • 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 31:980–981

    Article  PubMed  Google Scholar 

  • 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 128:1016–1025

    Article  PubMed  Google Scholar 

  • 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 88:28–35

    Article  PubMed  CAS  Google Scholar 

  • 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):101–106

    PubMed  Google Scholar 

  • 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 13:150–159

    Article  PubMed  CAS  Google Scholar 

  • 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 278:44405–44411

    Article  PubMed  CAS  Google Scholar 

  • 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 

  • 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 40:168–173

    Article  PubMed  Google Scholar 

  • 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 53:256–266

    Article  PubMed  CAS  Google Scholar 

  • 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 41:845–851

    Article  PubMed  Google Scholar 

  • 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 154:204–212

    Article  PubMed  CAS  Google Scholar 

  • 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 91:401–415

    Article  PubMed  CAS  Google Scholar 

  • 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 32:6665–6669

    Article  PubMed  CAS  Google Scholar 

  • Yamamoto BK, Moszczynska A, Gudelsky GA (2010) Amphetamine toxicities: classical and emerging mechanisms. Ann N Y Acad Sci 1187:101–121

    Article  PubMed  CAS  Google Scholar 

  • 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 174:171–176

    Article  PubMed  CAS  Google Scholar 

  • 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 3:200–203

    Article  PubMed  Google Scholar 

  • 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 19:533–542

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We thank Dr. Steven Buchthal who generated the MR spectra shown in the figures in this manuscript.

Funding

This work was supported by the National Institute on Drug Abuse (K24-DA016170), the National Institute on Neurological Disorders and Strokes (U54-NS056883) and the National Institutes on Minority Health and Health Disparities (G12 MD007601).

Disclosure Statements

The authors have no actual or potential conflicts of interest.

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Authors and Affiliations

  1. Department of Medicine, John A. Burns School of Medicine, University of Hawai’i at Manoa, Neuroscience and Magnetic Resonance Research Program, The Queen’s Medical Center, 1356 Lusitana Street, UH Tower 7th Floor, Honolulu, HI, 96813, USA

    Linda Chang, Sody M. Munsaka & Thomas Ernst

  2. Department of Biology, University of Hawai’i at Manoa, Honolulu, HI, USA

    Stephanie Kraft-Terry

  3. Department of Medicine, John A. Burns School of Medicine, The Queen’s Medical Center, University Tower 7th floor, 1356 Lusitana Street, Honolulu, HI, 96813, USA

    Linda Chang

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  1. Linda Chang
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  2. Sody M. Munsaka
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  3. Stephanie Kraft-Terry
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  4. Thomas Ernst
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Correspondence to Linda Chang.

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Chang, L., Munsaka, S.M., Kraft-Terry, S. et al. Magnetic Resonance Spectroscopy to Assess NeuroInflammation and Neuropathic Pain. J Neuroimmune Pharmacol 8, 576–593 (2013). https://doi.org/10.1007/s11481-013-9460-x

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  • DOI: https://doi.org/10.1007/s11481-013-9460-x

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