Advertisement

Magnetic Resonance Spectroscopy in HIV-Associated Neurocognitive Disorders: HAND

Chapter
  • 655 Downloads
Part of the Contemporary Clinical Neuroscience book series (CCNE)

Abstract

A significant number of HIV-infected patients develop neurological symptoms ranging from minor cognitive impairment to severe dementia (known HIV-associated dementia, HAD). Without combination antiretroviral therapy (cART) HAD occurs in 20–40 % of HIV positive subjects, with the advent of cART the incident has decreased to 5–10 %, although milder forms of cognitive deficits may occur in 30–50 % of those infected with HIV. It is believed that HIV enters the CNS during the early stages of infection by infected immune cells which initiate an inflammatory cascade which results in neuronal injury and loss. Imaging has been widely used to evaluate the effect of HIV to the brain. Specifically, proton magnetic resonance spectroscopy (1H MRS) is one of the most informative methods employed in patients suffering from HIV-associated neurocognitive disorders (HAND). MRS is able to noninvasively measure metabolic changes pertaining to neuronal injury and inflammation, thus, it can assist in the diagnosis of the disease and measure the severity of injury. In animal models of neuroAIDS, MRS has been proven extremely powerful to assess disease progression and response to treatment. Here we review the literature of preclinical models as well as MRS studies of HIV+ adults and children before and after the advent of cART regiments. In addition, we discuss technical considerations related to the disease and finally talk about future direction in HAND using MRS.

Keywords

AIDS (acquired immune deficiency syndrome) HIV (Human immunodeficiency Virus) NeuroAIDS HAND (HIV-associated neurocognitive disorders) SIV (Simian immunodeficiency virus) Rhesus Macaque Brain MRS (magnetic resonance spectroscopy) MRSI (magnetic resonance spectroscopic imaging) cART (combination antiretroviral therapy) Minocycline Neuroinflammation 

Notes

Acknowledgements

This work was partly funded by NIH grants R21NS059331, R01NS050041, R01NS040237, R01NS37654, R01MH62962, MH59754, MH62512, RR00168, R24 RR016001, N01 AI040101, and P41RR14075. The author wishes to thank Dr. R Gilberto Gonzalez for valuable discussions.

References

  1. 1.
    Worldwide HIV AIDS Statistics (2014) http://www.avert.org/worldwide-hiv-aids-statistics.htm
  2. 2.
    Daar ES, Moudgil T, Meyer RD, Ho DD (1991) Transient high levels of viremia in patients with primary human immunodeficiency virus type 1 infection. N Engl J Med 324(14):961–964PubMedCrossRefGoogle Scholar
  3. 3.
    Gupta KK (1993) Acute immunosuppression with HIV seroconversion. N Engl J Med 328(4):288–289PubMedCrossRefGoogle Scholar
  4. 4.
    Vento S, Di Perri G, Cruciani M, Garofano T, Concia E, Bassetti D (1993) Rapid decline of CD4+ cells after IFN alpha treatment in HIV-1 infection. Lancet 341(8850):958–959PubMedCrossRefGoogle Scholar
  5. 5.
    Navia BA, Cho ES, Petito CK, Price RW (1986) The AIDS dementia complex: II. Neuropathology. Ann Neurol 19(6):525–535PubMedCrossRefGoogle Scholar
  6. 6.
    Navia BA, Jordan BD, Price RW (1986) The AIDS dementia complex: I. Clinical features. Ann Neurol 19(6):517–524PubMedCrossRefGoogle Scholar
  7. 7.
    Price RW, Brew B, Sidtis J, Rosenblum M, Scheck AC, Cleary P (1988) The brain in AIDS: central nervous system HIV-1 infection and AIDS dementia complex. Science 239(4840):586–592PubMedCrossRefGoogle Scholar
  8. 8.
    Gray F, Hurtrel M, Hurtrel B (1993) Early central nervous system changes in human immunodeficiency virus (HIV)-infection. Neuropathol Appl Neurobiol 19(1):3–9PubMedCrossRefGoogle Scholar
  9. 9.
    Vaughan JT, Hetherington HP, Otu JO, Pan JW, Pohost GM (1994) High frequency volume coils for clinical NMR imaging and spectroscopy. Magn Reson Med 32(2):206–218PubMedCrossRefGoogle Scholar
  10. 10.
    Price RW, Brew BJ (1988) The AIDS dementia complex. J Infect Dis 158(5):1079–1083PubMedCrossRefGoogle Scholar
  11. 11.
    Brodt HR, Kamps BS, Gute P, Knupp B, Staszewski S, Helm EB (1997) Changing incidence of AIDS-defining illnesses in the era of antiretroviral combination therapy. AIDS 11(14):1731–1738PubMedCrossRefGoogle Scholar
  12. 12.
    McArthur JC (2004) HIV dementia: an evolving disease. J Neuroimmunol 157(1–2):3–10PubMedCrossRefGoogle Scholar
  13. 13.
    Nath A, Schiess N, Venkatesan A, Rumbaugh J, Sacktor N, McArthur J (2008) Evolution of HIV dementia with HIV infection. Int Rev Psychiatry 20(1):25–31PubMedCrossRefGoogle Scholar
  14. 14.
    Heaton RK, Clifford DB, Franklin DR Jr, Woods SP, Ake C, Vaida F, Ellis RJ, Letendre SL, Marcotte TD, Atkinson JH, Rivera-Mindt M, Vigil OR, Taylor MJ, Collier AC, Marra CM, Gelman BB, McArthur JC, Morgello S, Simpson DM, McCutchan JA, Abramson I, Gamst A, Fennema-Notestine C, Jernigan TL, Wong J, Grant I (2010) HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy: CHARTER Study. Neurology 75(23):2087–2096PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Gannon P, Khan MZ, Kolson DL (2013) Current understanding of HIV-associated neurocognitive disorders pathogenesis. Curr Opin Neurol 24(3):275–283CrossRefGoogle Scholar
  16. 16.
    Sacktor N (2002) The epidemiology of human immunodeficiency virus-associated neurological disease in the era of highly active antiretroviral therapy. J Neurovirol 8(Suppl 2):115–121PubMedCrossRefGoogle Scholar
  17. 17.
    Sacktor N, McDermott MP, Marder K, Schifitto G, Selnes OA, McArthur JC, Stern Y, Albert S, Palumbo D, Kieburtz K, De Marcaida JA, Cohen B, Epstein L (2002) HIV-associated cognitive impairment before and after the advent of combination therapy. J Neurovirol 8(2):136–142PubMedCrossRefGoogle Scholar
  18. 18.
    Ellis RJ, Deutsch R, Heaton RK, Marcotte TD, McCutchan JA, Nelson JA, Abramson I, Thal LJ, Atkinson JH, Wallace MR, Grant I (1997) Neurocognitive impairment is an independent risk factor for death in HIV infection. San Diego HIV Neurobehavioral Research Center Group. Arch Neurol 54(4):416–424PubMedCrossRefGoogle Scholar
  19. 19.
    Liner KJ II, Hall CD, Robertson KR (2008) Effects of antiretroviral therapy on cognitive impairment. Curr HIV/AIDS Rep 5(2):64–71PubMedCrossRefGoogle Scholar
  20. 20.
    Peluso R, Haase A, Stowring L, Edwards M, Ventura P (1985) A Trojan Horse mechanism for the spread of visna virus in monocytes. Virology 147(1):231–236PubMedCrossRefGoogle Scholar
  21. 21.
    Hickey WF, Hsu BL, Kimura H (1991) T-lymphocyte entry into the central nervous system. J Neurosci Res 28(2):254–260PubMedCrossRefGoogle Scholar
  22. 22.
    Bonwetsch R, Croul S, Richardson MW, Lorenzana C, Valle LD, Sverstiuk AE, Amini S, Morgello S, Khalili K, Rappaport J (1999) Role of HIV-1 Tat and CC chemokine MIP-1alpha in the pathogenesis of HIV associated central nervous system disorders. J Neurovirol 5(6):685–694PubMedCrossRefGoogle Scholar
  23. 23.
    Catani MV, Corasaniti MT, Navarra M, Nistico G, Finazzi-Agro A, Melino G (2000) gp120 induces cell death in human neuroblastoma cells through the CXCR4 and CCR5 chemokine receptors. J Neurochem 74(6):2373–2379PubMedCrossRefGoogle Scholar
  24. 24.
    Cheng J, Nath A, Knudsen B, Hochman S, Geiger JD, Ma M, Magnuson DS (1998) Neuronal excitatory properties of human immunodeficiency virus type 1 Tat protein. Neuroscience 82(1):97–106PubMedCrossRefGoogle Scholar
  25. 25.
    Meucci O, Fatatis A, Simen AA, Bushell TJ, Gray PW, Miller RJ (1998) Chemokines regulate hippocampal neuronal signaling and gp120 neurotoxicity. Proc Natl Acad Sci U S A 95(24):14500–14505PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Nath A (2002) Human immunodeficiency virus (HIV) proteins in neuropathogenesis of HIV dementia. J Infect Dis 186(Suppl 2):S193–S198PubMedCrossRefGoogle Scholar
  27. 27.
    Nath A, Psooy K, Martin C, Knudsen B, Magnuson DS, Haughey N, Geiger JD (1996) Identification of a human immunodeficiency virus type 1 Tat epitope that is neuroexcitatory and neurotoxic. J Virol 70(3):1475–1480PubMedPubMedCentralGoogle Scholar
  28. 28.
    Ohagen A, Ghosh S, He J, Huang K, Chen Y, Yuan M, Osathanondh R, Gartner S, Shi B, Shaw G, Gabuzda D (1999) Apoptosis induced by infection of primary brain cultures with diverse human immunodeficiency virus type 1 isolates: evidence for a role of the envelope. J Virol 73(2):897–906PubMedPubMedCentralGoogle Scholar
  29. 29.
    D’Aversa TG, Eugenin EA, Berman JW (2005) NeuroAIDS: contributions of the human immunodeficiency virus-1 proteins Tat and gp120 as well as CD40 to microglial activation. J Neurosci Res 81(3):436–446PubMedCrossRefGoogle Scholar
  30. 30.
    Crowe S, Zhu T, Muller WA (2003) The contribution of monocyte infection and trafficking to viral persistence, and maintenance of the viral reservoir in HIV infection. J Leukoc Biol 74(5):635–641PubMedCrossRefGoogle Scholar
  31. 31.
    Gartner S (2000) HIV infection and dementia. Science 287(5453):602–604PubMedCrossRefGoogle Scholar
  32. 32.
    Persidsky Y, Gendelman HE (2003) Mononuclear phagocyte immunity and the neuropathogenesis of HIV-1 infection. J Leukoc Biol 74(5):691–701PubMedCrossRefGoogle Scholar
  33. 33.
    Williams KC, Hickey WF (2002) Central nervous system damage, monocytes and macrophages, and neurological disorders in AIDS. Annu Rev Neurosci 25:537–562PubMedCrossRefGoogle Scholar
  34. 34.
    Roy S, Wainberg MA (1988) Role of the mononuclear phagocyte system in the development of acquired immunodeficiency syndrome (AIDS). J Leukoc Biol 43(1):91–97PubMedGoogle Scholar
  35. 35.
    Kaul M, Garden GA, Lipton SA (2001) Pathways to neuronal injury and apoptosis in HIV-associated dementia. Nature 410(6831):988–994PubMedCrossRefGoogle Scholar
  36. 36.
    Kaul M, Zheng J, Okamoto S, Gendelman HE, Lipton SA (2005) HIV-1 infection and AIDS: consequences for the central nervous system. Cell Death Differ 12(Suppl 1):878–892PubMedCrossRefGoogle Scholar
  37. 37.
    Kraft-Terry SD, Buch SJ, Fox HS, Gendelman HE (2009) A coat of many colors: neuroimmune crosstalk in human immunodeficiency virus infection. Neuron 64(1):133–145PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Wiley CA, Soontornniyomkij V, Radhakrishnan L, Masliah E, Mellors J, Hermann SA, Dailey P, Achim CL (1998) Distribution of brain HIV load in AIDS. Brain Pathol 8(2):277–284PubMedCrossRefGoogle Scholar
  39. 39.
    Moore DJ, Masliah E, Rippeth JD, Gonzalez R, Carey CL, Cherner M, Ellis RJ, Achim CL, Marcotte TD, Heaton RK, Grant I (2006) Cortical and subcortical neurodegeneration is associated with HIV neurocognitive impairment. AIDS 20(6):879–887PubMedCrossRefGoogle Scholar
  40. 40.
    Filippi CG, Ulug AM, Ryan E, Ferrando SJ, van Gorp W (2001) Diffusion tensor imaging of patients with HIV and normal-appearing white matter on MR images of the brain. AJNR Am J Neuroradiol 22(2):277–283PubMedGoogle Scholar
  41. 41.
    Bonnet F, Amieva H, Marquant F, Bernard C, Bruyand M, Dauchy FA, Mercie P, Greib C, Richert L, Neau D, Catheline G, Dehail P, Dabis F, Morlat P, Dartigues JF, Chene G (2013) Cognitive disorders in HIV-infected patients: are they HIV-related? AIDS 27(3):391–400PubMedCrossRefGoogle Scholar
  42. 42.
    Ances BM, Ortega M, Vaida F, Heaps J, Paul R (2012) Independent effects of HIV, aging, and HAART on brain volumetric measures. J Acquir Immune Defic Syndr 59(5):469–477PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Pfefferbaum A, Rosenbloom MJ, Sassoon SA, Kemper CA, Deresinski S, Rohlfing T, Sullivan EV (2012) Regional brain structural dysmorphology in human immunodeficiency virus infection: effects of acquired immune deficiency syndrome, alcoholism, and age. Biol Psychiatry 72(5):361–370PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Aylward EH, Henderer JD, McArthur JC, Brettschneider PD, Harris GJ, Barta PE, Pearlson GD (1993) Reduced basal ganglia volume in HIV-1-associated dementia: results from quantitative neuroimaging. Neurology 43(10):2099–2104PubMedCrossRefGoogle Scholar
  45. 45.
    Broderick DF, Wippold FJ II, Clifford DB, Kido D, Wilson BS (1993) White matter lesions and cerebral atrophy on MR images in patients with and without AIDS dementia complex. AJR Am J Roentgenol 161(1):177–181PubMedCrossRefGoogle Scholar
  46. 46.
    Dooneief G, Bello J, Todak G, Mun IK, Marder K, Malouf R, Gorman J, Hilal S, Stern Y, Mayeux R (1992) A prospective controlled study of magnetic resonance imaging of the brain in gay men and parenteral drug users with human immunodeficiency virus infection. Arch Neurol 49(1):38–43PubMedCrossRefGoogle Scholar
  47. 47.
    McArthur JC, Kumar AJ, Johnson DW, Selnes OA, Becker JT, Herman C, Cohen BA, Saah A (1990) Incidental white matter hyperintensities on magnetic resonance imaging in HIV-1 infection. Multicenter AIDS Cohort Study. J Acquir Immune Defic Syndr 3(3):252–259PubMedGoogle Scholar
  48. 48.
    Boska MD, Mosley RL, Nawab M, Nelson JA, Zelivyanskaya M, Poluektova L, Uberti M, Dou H, Lewis TB, Gendelman HE (2004) Advances in neuroimaging for HIV-1 associated neurological dysfunction: clues to the diagnosis, pathogenesis and therapeutic monitoring. Curr HIV Res 2(1):61–78PubMedCrossRefGoogle Scholar
  49. 49.
    Hammoud DA, Endres CJ, Chander AR, Guilarte TR, Wong DF, Sacktor NC, McArthur JC, Pomper MG (2005) Imaging glial cell activation with [11C]-R-PK11195 in patients with AIDS. J Neurovirol 11(4):346–355PubMedCrossRefGoogle Scholar
  50. 50.
    Wiley CA, Lopresti BJ, Becker JT, Boada F, Lopez OL, Mellors J, Meltzer CC, Wisniewski SR, Mathis CA (2006) Positron emission tomography imaging of peripheral benzodiazepine receptor binding in human immunodeficiency virus-infected subjects with and without cognitive impairment. J Neurovirol 12(4):262–271PubMedCrossRefGoogle Scholar
  51. 51.
    Andersen AB, Law I, Krabbe KS, Bruunsgaard H, Ostrowski SR, Ullum H, Hojgaard L, Lebech A, Gerstoft J, Kjaer A (2010) Cerebral FDG-PET scanning abnormalities in optimally treated HIV patients. J Neuroinflammation 7:13PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Chang L, Wang GJ, Volkow ND, Ernst T, Telang F, Logan J, Fowler JS (2008) Decreased brain dopamine transporters are related to cognitive deficits in HIV patients with or without cocaine abuse. Neuroimage 42(2):869–878PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    Ances BM, Christensen JJ, Teshome M, Taylor J, Xiong C, Aldea P, Fagan AM, Holtzman DM, Morris JC, Mintun MA, Clifford DB (2010) Cognitively unimpaired HIV-positive subjects do not have increased 11C-PiB: a case-control study. Neurology 75(2):111–115PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Chang L, Feger U, Ernst TM (2011) Bioimaging. In: The neurology of AIDS, 3rd edn. Oxford University Press, OxfordGoogle Scholar
  55. 55.
    Birken DL, Oldendorf WH (1989) N-Acetyl-L-aspartic acid: a literature review of a compound prominent in 1H-NMR spectroscopic studies of brain. Neurosci Biobehav Rev 13(1):23–31PubMedCrossRefGoogle Scholar
  56. 56.
    Simmons ML, Frondoza CG, Coyle JT (1991) Immunocytochemical localization of N-acetyl-aspartate with monoclonal antibodies. Neuroscience 45(1):37–45PubMedCrossRefGoogle Scholar
  57. 57.
    Moffett JR, Namboodiri MA, Cangro CB, Neale JH (1991) Immunohistochemical localization of N-acetylaspartate in rat brain. Neuroreport 2(3):131–134PubMedCrossRefGoogle Scholar
  58. 58.
    Urenjak J, Williams SR, Gadian DG, Noble M (1993) Proton nuclear magnetic resonance spectroscopy unambiguously identifies different neural cell types. J Neurosci 13(3):981–989PubMedGoogle Scholar
  59. 59.
    Menon DK, Ainsworth JG, Cox IJ, Coker RC, Sargentoni J, Coutts GA, Baudouin CJ, Kocsis AE, Harris JR (1992) Proton MR spectroscopy of the brain in AIDS dementia complex. J Comput Assist Tomogr 16(4):538–542PubMedCrossRefGoogle Scholar
  60. 60.
    Meyerhoff DJ, MacKay S, Bachman L, Poole N, Dillon WP, Weiner MW, Fein G (1993) Reduced brain N-acetylaspartate suggests neuronal loss in cognitively impaired human immunodeficiency virus-seropositive individuals: in vivo 1H magnetic resonance spectroscopic imaging. Neurology 43(3 Pt 1):509–515PubMedCrossRefGoogle Scholar
  61. 61.
    Chong WK, Sweeney B, Wilkinson ID, Paley M, Hall-Craggs MA, Kendall BE, Shepard JK, Beecham M, Miller RF, Weller IV et al (1993) Proton spectroscopy of the brain in HIV infection: correlation with clinical, immunologic, and MR imaging findings. Radiology 188(1):119–124PubMedCrossRefGoogle Scholar
  62. 62.
    Barker PB, Lee RR, McArthur JC (1995) AIDS dementia complex: evaluation with proton MR spectroscopic imaging. Radiology 195(1):58–64PubMedCrossRefGoogle Scholar
  63. 63.
    Meyerhoff DJ, Bloomer C, Cardenas V, Norman D, Weiner MW, Fein G (1999) Elevated subcortical choline metabolites in cognitively and clinically asymptomatic HIV+ patients. Neurology 52(5):995–1003PubMedCrossRefGoogle Scholar
  64. 64.
    Brand A, Richter-Landsberg C, Leibfritz D (1993) Multinuclear NMR studies on the energy metabolism of glial and neuronal cells. Dev Neurosci 15(3–5):289–298PubMedGoogle Scholar
  65. 65.
    Laubenberger J, Haussinger D, Bayer S, Thielemann S, Schneider B, Mundinger A, Hennig J, Langer M (1996) HIV-related metabolic abnormalities in the brain: depiction with proton MR spectroscopy with short echo times. Radiology 199(3):805–810PubMedCrossRefGoogle Scholar
  66. 66.
    Lopez-Villegas D, Lenkinski RE, Frank I (1997) Biochemical changes in the frontal lobe of HIV-infected individuals detected by magnetic resonance spectroscopy. Proc Natl Acad Sci U S A 94(18):9854–9859PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Chang L, Ernst T, Leonido-Yee M, Walot I, Singer E (1999) Cerebral metabolite abnormalities correlate with clinical severity of HIV-1 cognitive motor complex. Neurology 52(1):100–108PubMedCrossRefGoogle Scholar
  68. 68.
    Saunders DE, Howe FA, van den Boogaart A, Griffiths JR, Brown MM (1999) Aging of the adult human brain: in vivo quantitation of metabolite content with proton magnetic resonance spectroscopy. J Magn Reson Imaging 9(5):711–716PubMedCrossRefGoogle Scholar
  69. 69.
    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(3):1638–1648PubMedCrossRefGoogle Scholar
  70. 70.
    Ratai EM, Pilkenton SJ, Greco JB, Lentz MR, Bombardier JP, Turk KW, He J, Joo CG, Lee V, Westmoreland S, Halpern E, Lackner AA, Gonzalez RG (2009) In vivo proton magnetic resonance spectroscopy reveals region specific metabolic responses to SIV infection in the macaque brain. BMC Neurosci 10:63PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Ratai EM, Annamalai L, Burdo T, Joo CG, Bombardier JP, Fell R, Hakimelahi R, He J, Lentz MR, Campbell J, Curran E, Halpern EF, Masliah E, Westmoreland SV, Williams KC, Gonzalez RG (2011) Brain creatine elevation and N-acetylaspartate reduction indicates neuronal dysfunction in the setting of enhanced glial energy metabolism in a macaque model of NeuroAIDS. Magn Reson Med 66(3):625–634PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Sailasuta N, Shriner K, Ross B (2009) Evidence of reduced glutamate in the frontal lobe of HIV-seropositive patients. NMR Biomed 22(3):326–331PubMedCrossRefGoogle Scholar
  73. 73.
    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(5):625–633PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    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(5):1045–1053PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    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(9):1251–1257PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    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(17):1465–1472PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Roc AC, Ances BM, Chawla S, Korczykowski M, Wolf RL, Kolson DL, Detre JA, Poptani H (2007) Detection of human immunodeficiency virus induced inflammation and oxidative stress in lenticular nuclei with magnetic resonance spectroscopy despite antiretroviral therapy. Arch Neurol 64(9):1249–1257PubMedCrossRefGoogle Scholar
  78. 78.
    Lee PL, Yiannoutsos CT, Ernst T, Chang L, Marra CM, Jarvik JG, Richards TL, Kwok EW, Kolson DL, Simpson D, Tang CY, Schifitto G, Ketonen LM, Meyerhoff DJ, Lenkinski RE, Gonzalez RG, Navia BA (2003) A multi-center 1H MRS study of the AIDS dementia complex: validation and preliminary analysis. J Magn Reson Imaging 17(6):625–633PubMedCrossRefGoogle Scholar
  79. 79.
    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 (2004) A multicenter in vivo proton-MRS study of HIV-associated dementia and its relationship to age. Neuroimage 23(4):1336–1347PubMedCrossRefGoogle Scholar
  80. 80.
    Sacktor N, Skolasky RL, Ernst T, Mao X, Selnes O, Pomper MG, Chang L, Zhong K, Shungu DC, Marder K, Shibata D, Schifitto G, Bobo L, Barker PB (2005) A multicenter study of two magnetic resonance spectroscopy techniques in individuals with HIV dementia. J Magn Reson Imaging 21(4):325–333PubMedCrossRefGoogle Scholar
  81. 81.
    Greco JB, Sakaie KE, Aminipour S, Lee PL, Chang LL, He J, Westmoreland S, Lackner AA, Gonzalez RG (2002) Magnetic resonance spectroscopy: an in vivo tool for monitoring cerebral injury in SIV-infected macaques. J Med Primatol 31(4–5):228–236PubMedCrossRefGoogle Scholar
  82. 82.
    Jacobs MA, Horska A, van Zijl PC, Barker PB (2001) Quantitative proton MR spectroscopic imaging of normal human cerebellum and brain stem. Magn Reson Med 46(4):699–705PubMedCrossRefGoogle Scholar
  83. 83.
    Soher BJ, van Zijl PC, Duyn JH, Barker PB (1996) Quantitative proton MR spectroscopic imaging of the human brain. Magn Reson Med 35(3):356–363PubMedCrossRefGoogle Scholar
  84. 84.
    Michaelis T, Merboldt KD, Bruhn H, Hanicke W, Frahm J (1993) Absolute concentrations of metabolites in the adult human brain in vivo: quantification of localized proton MR spectra. Radiology 187(1):219–227PubMedCrossRefGoogle Scholar
  85. 85.
    Barker PB, Soher BJ, Blackband SJ, Chatham JC, Mathews VP, Bryan RN (1993) Quantitation of proton NMR spectra of the human brain using tissue water as an internal concentration reference. NMR Biomed 6(1):89–94PubMedCrossRefGoogle Scholar
  86. 86.
    Christiansen P, Henriksen O, Stubgaard M, Gideon P, Larsson HB (1993) In vivo quantification of brain metabolites by 1H-MRS using water as an internal standard. Magn Reson Imaging 11(1):107–118PubMedCrossRefGoogle Scholar
  87. 87.
    Ernst T, Kreis R, Ross BD (1993) Absolute quantitation of water and metabolites in the human brain; Part I: Compartments and water. J Magn Res B102:1–8CrossRefGoogle Scholar
  88. 88.
    Tofts PS, Wray S (1988) A critical assessment of methods of measuring metabolite concentrations by NMR spectroscopy. NMR Biomed 1(1):1–10PubMedCrossRefGoogle Scholar
  89. 89.
    Hennig J, Pfister H, Ernst T, Ott D (1992) Direct absolute quantification of metabolites in the human brain with in vivo localized proton spectroscopy. NMR Biomed 5(4):193–199PubMedCrossRefGoogle Scholar
  90. 90.
    Toggas SM, Masliah E, Rockenstein EM, Rall GF, Abraham CR, Mucke L (1994) Central nervous system damage produced by expression of the HIV-1 coat protein gp120 in transgenic mice. Nature 367(6459):188–193PubMedCrossRefGoogle Scholar
  91. 91.
    Persidsky Y, Limoges J, McComb R, Bock P, Baldwin T, Tyor W, Patil A, Nottet HS, Epstein L, Gelbard H, Flanagan E, Reinhard J, Pirruccello SJ, Gendelman HE (1996) Human immunodeficiency virus encephalitis in SCID mice. Am J Pathol 149(3):1027–1053PubMedPubMedCentralGoogle Scholar
  92. 92.
    Persidsky Y, Buttini M, Limoges J, Bock P, Gendelman HE (1997) An analysis of HIV-1-associated inflammatory products in brain tissue of humans and SCID mice with HIV-1 encephalitis. J Neurovirol 3(6):401–416PubMedCrossRefGoogle Scholar
  93. 93.
    Persidsky Y, Gendelman HE (2002) Murine models for human immunodeficiency virus type 1-associated dementia: the development of new treatment testing paradigms. J Neurovirol 8(Suppl 2):49–52PubMedCrossRefGoogle Scholar
  94. 94.
    Zink WE, Anderson E, Boyle J, Hock L, Rodriguez-Sierra J, Xiong H, Gendelman HE, Persidsky Y (2002) Impaired spatial cognition and synaptic potentiation in a murine model of human immunodeficiency virus type 1 encephalitis. J Neurosci 22(6):2096–2105PubMedGoogle Scholar
  95. 95.
    Jacobson S, Henriksen SJ, Prospero-Garcia O, Phillips TR, Elder JH, Young WG, Bloom FE, Fox HS (1997) Cortical neuronal cytoskeletal changes associated with FIV infection. J Neurovirol 3(4):283–289PubMedCrossRefGoogle Scholar
  96. 96.
    Podell M, Oglesbee M, Mathes L, Krakowka S, Olmstead R, Lafrado L (1993) AIDS-associated encephalopathy with experimental feline immunodeficiency virus infection. J Acquir Immune Defic Syndr 6(7):758–771PubMedGoogle Scholar
  97. 97.
    Phillips TR, Prospero-Garcia O, Wheeler DW, Wagaman PC, Lerner DL, Fox HS, Whalen LR, Bloom FE, Elder JH, Henriksen SJ (1996) Neurologic dysfunctions caused by a molecular clone of feline immunodeficiency virus, FIV-PPR. J Neurovirol 2(6):388–396PubMedCrossRefGoogle Scholar
  98. 98.
    Silvotti L, Corradi A, Brandi G, Cabassi A, Bendinelli M, Magnan M, Piedimonte G (1997) FIV induced encephalopathy: early brain lesions in the absence of viral replication in monocyte/macrophages. A pathogenetic model. Vet Immunol Immunopathol 55(4):263–271PubMedCrossRefGoogle Scholar
  99. 99.
    Prospero-Garcia O, Herold N, Waters AK, Phillips TR, Elder JH, Henriksen SJ (1994) Intraventricular administration of a FIV-envelope protein induces sleep architecture changes in rats. Brain Res 659(1–2):254–258PubMedCrossRefGoogle Scholar
  100. 100.
    Poli A, Abramo F, Di Iorio C, Cantile C, Carli MA, Pollera C, Vago L, Tosoni A, Costanzi G (1997) Neuropathology in cats experimentally infected with feline immunodeficiency virus: a morphological, immunocytochemical and morphometric study. J Neurovirol 3(5):361–368PubMedCrossRefGoogle Scholar
  101. 101.
    Podell M, March PA, Buck WR, Mathes LE (2000) The feline model of neuroAIDS: understanding the progression towards AIDS dementia. J Psychopharmacol 14(3):205–213PubMedCrossRefGoogle Scholar
  102. 102.
    Podell M, Maruyama K, Smith M, Hayes KA, Buck WR, Ruehlmann DS, Mathes LE (1999) Frontal lobe neuronal injury correlates to altered function in FIV-infected cats. J Acquir Immune Defic Syndr 22(1):10–18PubMedCrossRefGoogle Scholar
  103. 103.
    Desrosiers RC (1990) The simian immunodeficiency viruses. Annu Rev Immunol 8:557–578PubMedCrossRefGoogle Scholar
  104. 104.
    Zink MC, Amedee AM, Mankowski JL, Craig L, Didier P, Carter DL, Munoz A, Murphey-Corb M, Clements JE (1997) Pathogenesis of SIV encephalitis. Selection and replication of neurovirulent SIV. Am J Pathol 151(3):793–803PubMedPubMedCentralGoogle Scholar
  105. 105.
    Zink MC, Spelman JP, Robinson RB, Clements JE (1998) SIV infection of macaques—modeling the progression to AIDS dementia. J Neurovirol 4(3):249–259PubMedCrossRefGoogle Scholar
  106. 106.
    Murray EA, Rausch DM, Lendvay J, Sharer LR, Eiden LE (1992) Cognitive and motor impairments associated with SIV infection in rhesus monkeys. Science 255(5049):1246–1249PubMedCrossRefGoogle Scholar
  107. 107.
    Burudi EME, Fox HS (2001) Simian immunodeficiency virus model of HIV-induced central nervous system dysfunction. Adv Virus Res 56:435–468PubMedCrossRefGoogle Scholar
  108. 108.
    Bruce-Keller AJ, Chauhan A, Dimayuga FO, Gee J, Keller JN, Nath A (2003) Synaptic transport of human immunodeficiency virus-Tat protein causes neurotoxicity and gliosis in rat brain. J Neurosci 23(23):8417–8422PubMedGoogle Scholar
  109. 109.
    Okamoto S, Kang YJ, Brechtel CW, Siviglia E, Russo R, Clemente A, Harrop A, McKercher S, Kaul M, Lipton SA (2007) HIV/gp120 decreases adult neural progenitor cell proliferation via checkpoint kinase-mediated cell-cycle withdrawal and G1 arrest. Cell Stem Cell 1(2):230–236PubMedCrossRefGoogle Scholar
  110. 110.
    Zelivyanskaya ML, Nelson JA, Poluektova L, Uberti M, Mellon M, Gendelman HE, Boska MD (2003) Tracking superparamagnetic iron oxide labeled monocytes in brain by high-field magnetic resonance imaging. J Neurosci Res 73(3):284–295PubMedCrossRefGoogle Scholar
  111. 111.
    Nelson JA, Dou H, Ellison B, Uberti M, Xiong H, Anderson E, Mellon M, Gelbard HA, Boska M, Gendelman HE (2005) Coregistration of quantitative proton magnetic resonance spectroscopic imaging with neuropathological and neurophysiological analyses defines the extent of neuronal impairments in murine human immunodeficiency virus type-1 encephalitis. J Neurosci Res 80(4):562–575PubMedCrossRefGoogle Scholar
  112. 112.
    Phipps AJ, Hayes KA, Buck WR, Podell M, Mathes LE (2000) Neurophysiologic and immunologic abnormalities associated with feline immunodeficiency virus molecular clone FIV-PPR DNA inoculation. J Acquir Immune Defic Syndr 23(1):8–16PubMedCrossRefGoogle Scholar
  113. 113.
    Podell M, Hayes K, Oglesbee M, Mathes L (1997) Progressive encephalopathy associated with CD4/CD8 inversion in adult FIV-infected cats. J Acquir Immune Defic Syndr Hum Retrovirol 15(5):332–340PubMedCrossRefGoogle Scholar
  114. 114.
    Belman AL (1997) Pediatric neuro-AIDS. Update. Neuroimaging Clin N Am 7(3):593–613PubMedGoogle Scholar
  115. 115.
    Johnston JB, Silva C, Hiebert T, Buist R, Dawood MR, Peeling J, Power C (2002) Neurovirulence depends on virus input titer in brain in feline immunodeficiency virus infection: evidence for activation of innate immunity and neuronal injury. J Neurovirol 8(5):420–431PubMedCrossRefGoogle Scholar
  116. 116.
    Reimann KA, Tenner-Racz K, Racz P, Montefiori DC, Yasutomi Y, Lin W, Ransil BJ, Letvin NL (1994) Immunopathogenic events in acute infection of rhesus monkeys with simian immunodeficiency virus of macaques. J Virol 68(4):2362–2370PubMedPubMedCentralGoogle Scholar
  117. 117.
    Staprans SI, Dailey PJ, Rosenthal A, Horton C, Grant RM, Lerche N, Feinberg MB (1999) Simian immunodeficiency virus disease course is predicted by the extent of virus replication during primary infection. J Virol 73(6):4829–4839PubMedPubMedCentralGoogle Scholar
  118. 118.
    Greco JB, Westmoreland SV, Ratai EM, Lentz MR, Sakaie K, He J, Sehgal PK, Masliah E, Lackner AA, Gonzalez RG (2004) In vivo 1H MRS of brain injury and repair during acute SIV infection in the macaque model of neuroAIDS. Magn Reson Med 51(6):1108–1114PubMedCrossRefGoogle Scholar
  119. 119.
    Chakrabarti L, Hurtrel M, Maire MA, Vazeux R, Dormont D, Montagnier L, Hurtrel B (1991) Early viral replication in the brain of SIV-infected rhesus monkeys. Am J Pathol 139(6):1273–1280PubMedPubMedCentralGoogle Scholar
  120. 120.
    Sharer LR, Baskin GB, Cho ES, Murphey-Corb M, Blumberg BM, Epstein LG (1988) Comparison of simian immunodeficiency virus and human immunodeficiency virus encephalitides in the immature host. Ann Neurol 23(Suppl):S108–S112PubMedCrossRefGoogle Scholar
  121. 121.
    Simon MA, Chalifoux LV, Ringler DJ (1992) Pathologic features of SIV-induced disease and the association of macrophage infection with disease evolution. AIDS Res Hum Retroviruses 8(3):327–337PubMedCrossRefGoogle Scholar
  122. 122.
    Fox HS, Weed MR, Huitron-Resendiz S, Baig J, Horn TFW, Dailey PJ, Bischofberger N, Henriksen SJ (2000) Antiretroviral treatment normalizes neurophysiological but not movement abnormalities in simian immunodeficiency virus-infected monkeys. J Clin Invest 106(1):37–45PubMedPubMedCentralCrossRefGoogle Scholar
  123. 123.
    Williams K, Westmoreland S, Greco J, Ratai E, Lentz M, Kim WK, Fuller RA, Kim JP, Autissier P, Sehgal PK, Schinazi RF, Bischofberger N, Piatak M, Lifson JD, Masliah E, Gonzalez RG (2005) Magnetic resonance spectroscopy reveals that activated monocytes contribute to neuronal injury in SIV neuroAIDS. J Clin Invest 115(9):2534–2545PubMedPubMedCentralCrossRefGoogle Scholar
  124. 124.
    Altfeld M, Rosenberg ES, Shankarappa R, Mukherjee JS, Hecht FM, Eldridge RL, Addo MM, Poon SH, Phillips MN, Robbins GK, Sax PE, Boswell S, Kahn JO, Brander C, Goulder PJ, Levy JA, Mullins JI, Walker BD (2001) Cellular immune responses and viral diversity in individuals treated during acute and early HIV-1 infection. J Exp Med 193(2):169–180PubMedPubMedCentralCrossRefGoogle Scholar
  125. 125.
    Rosenberg E, Cotton D (1997) Primary HIV infection and the acute retroviral syndrome. AIDS Clin Care 9(3):19, 23–25PubMedGoogle Scholar
  126. 126.
    McArthur JC, Hoover DR, Bacellar H, Miller EN, Cohen BA, Becker JT, Graham NM, McArthur JH, Selnes OA, Jacobson LP et al (1993) Dementia in AIDS patients: incidence and risk factors. Multicenter AIDS Cohort Study. Neurology 43(11):2245–2252PubMedCrossRefGoogle Scholar
  127. 127.
    Lentz MR, Kim JP, Westmoreland SV, Greco JB, Fuller RA, Ratai EM, He J, Sehgal PK, Halpern EF, Lackner AA, Masliah E, Gonzalez RG (2005) Quantitative neuropathologic correlates of changes in ratio of N-acetylaspartate to creatine in macaque brain. Radiology 235(2):461–468PubMedCrossRefGoogle Scholar
  128. 128.
    Blusztajn JK, Wurtman RJ (1983) Choline and cholinergic neurons. Science 221(4611):614–620PubMedCrossRefGoogle Scholar
  129. 129.
    Kim JP, Lentz MR, Westmoreland SV, Greco JB, Ratai EM, Halpern E, Lackner AA, Masliah E, Gonzalez RG (2005) Relationships between astrogliosis and 1H MR spectroscopic measures of brain choline/creatine and myo-inositol/creatine in a primate model. AJNR Am J Neuroradiol 26(4):752–759PubMedGoogle Scholar
  130. 130.
    Fuller RA, Westmoreland SV, Ratai E, Greco JB, Kim JP, Lentz MR, He J, Sehgal PK, Masliah E, Halpern E, Lackner AA, Gonzalez RG (2004) A prospective longitudinal in vivo 1H MR spectroscopy study of the SIV/macaque model of neuroAIDS. BMC Neurosci 5(1):10PubMedPubMedCentralCrossRefGoogle Scholar
  131. 131.
    Westmoreland SV, Halpern E, Lackner AA (1998) Simian immunodeficiency virus encephalitis in rhesus macaques is associated with rapid disease progression. J Neurovirol 4(3):260–268PubMedCrossRefGoogle Scholar
  132. 132.
    Zink MC, Suryanarayana K, Mankowski JL, Shen A, Piatak M Jr, Spelman JP, Carter DL, Adams RJ, Lifson JD, Clements JE (1999) High viral load in the cerebrospinal fluid and brain correlates with severity of simian immunodeficiency virus encephalitis. J Virol 73(12):10480–10488PubMedPubMedCentralGoogle Scholar
  133. 133.
    Zink M, Clements J (2000) A rapid, reproducible model of AIDS and encephelitis in SIV infected macaques demonstrates the role of viral load in CNS disease. NeuroAIDS 3(5):online—OctoberGoogle Scholar
  134. 134.
    Zink MC, Clements JE (2002) A novel simian immunodeficiency virus model that provides insight into mechanisms of human immunodeficiency virus central nervous system disease. J Neurovirol 8(Suppl 2):42–48PubMedCrossRefGoogle Scholar
  135. 135.
    Weed MR, Hienz RD, Brady JV, Adams RJ, Mankowski JL, Clements JE, Zink MC (2003) Central nervous system correlates of behavioral deficits following simian immunodeficiency virus infection. J Neurovirol 9(4):452–464PubMedCrossRefGoogle Scholar
  136. 136.
    Schmitz JE, Kuroda MJ, Santra S, Sasseville VG, Simon MA, Lifton MA, Racz P, Tenner-Racz K, Dalesandro M, Scallon BJ, Ghrayeb J, Forman MA, Montefiori DC, Rieber EP, Letvin NL, Reimann KA (1999) Control of viremia in simian immunodeficiency virus infection by CD8+ lymphocytes. Science 283(5403):857–860PubMedCrossRefGoogle Scholar
  137. 137.
    Schmitz JE, Simon MA, Kuroda MJ, Lifton MA, Ollert MW, Vogel CW, Racz P, Tenner-Racz K, Scallon BJ, Dalesandro M, Ghrayeb J, Rieber EP, Sasseville VG, Reimann KA (1999) A nonhuman primate model for the selective elimination of CD8+ lymphocytes using a mouse-human chimeric monoclonal antibody. Am J Pathol 154(6):1923–1932PubMedPubMedCentralCrossRefGoogle Scholar
  138. 138.
    Williams K, Alvarez X, Lackner AA (2001) Central nervous system perivascular cells are immunoregulatory cells that connect the CNS with the peripheral immune system. Glia 36(2):156–164PubMedCrossRefGoogle Scholar
  139. 139.
    Domercq M, Matute C (2004) Neuroprotection by tetracyclines. Trends Pharmacol Sci 25(12):609–612PubMedCrossRefGoogle Scholar
  140. 140.
    Baptiste DC, Fehlings MG (2006) Pharmacological approaches to repair the injured spinal cord. J Neurotrauma 23(3–4):318–334PubMedCrossRefGoogle Scholar
  141. 141.
    Stirling DP, Koochesfahani KM, Steeves JD, Tetzlaff W (2005) Minocycline as a neuroprotective agent. Neuroscientist 11(4):308–322PubMedCrossRefGoogle Scholar
  142. 142.
    Tikka T, Fiebich BL, Goldsteins G, Keinanen R, Koistinaho J (2001) Minocycline, a tetracycline derivative, is neuroprotective against excitotoxicity by inhibiting activation and proliferation of microglia. J Neurosci 21(8):2580–2588PubMedGoogle Scholar
  143. 143.
    Lin S, Zhang Y, Dodel R, Farlow MR, Paul SM, Du Y (2001) Minocycline blocks nitric oxide-induced neurotoxicity by inhibition p38 MAP kinase in rat cerebellar granule neurons. Neurosci Lett 315(1–2):61–64PubMedCrossRefGoogle Scholar
  144. 144.
    Si Q, Cosenza M, Kim MO, Zhao ML, Brownlee M, Goldstein H, Lee S (2004) A novel action of minocycline: inhibition of human immunodeficiency virus type 1 infection in microglia. J Neurovirol 10(5):284–292PubMedCrossRefGoogle Scholar
  145. 145.
    Dutta K, Mishra MK, Nazmi A, Kumawat KL, Basu A (2010) Minocycline differentially modulates macrophage mediated peripheral immune response following Japanese encephalitis virus infection. Immunobiology 215(11):884–893PubMedCrossRefGoogle Scholar
  146. 146.
    Zink MC, Uhrlaub J, DeWitt J, Voelker T, Bullock B, Mankowski J, Tarwater P, Clements J, Barber S (2005) Neuroprotective and anti-human immunodeficiency virus activity of minocycline. JAMA 293(16):2003–2011PubMedCrossRefGoogle Scholar
  147. 147.
    Ratai EM, Bombardier JP, Joo CG, Annamalai L, Burdo TH, Campbell J, Fell R, Hakimelahi R, He J, Autissier P, Lentz MR, Halpern EF, Masliah E, Williams KC, Westmoreland SV, Gonzalez RG (2010) Proton magnetic resonance spectroscopy reveals neuroprotection by oral minocycline in a nonhuman primate model of accelerated NeuroAIDS. PLoS One 5(5):e10523PubMedPubMedCentralCrossRefGoogle Scholar
  148. 148.
    Ratai EM, Fell R, He J, Piatak M, Lifson JD, Burdo TH, Campbell J, Autissier P, Annamalai L, Masliah E, Westmoreland SV, Williams KC, Gilberto Gonzalez R (2012) Reduction of brain virus by minocycline and combination anti-retroviral therapy produces neuronal protection in a primate model of AIDS. In: ISMRM 20th Annual Meeting & Exhibition, MelbourneGoogle Scholar
  149. 149.
    Campbell JH, Burdo TH, Autissier P, Bombardier JP, Westmoreland SV, Soulas C, Gonzalez RG, Ratai EM, Williams KC (2011) Minocycline inhibition of monocyte activation correlates with neuronal protection in SIV NeuroAIDS. PLoS One 6(4):e18688PubMedPubMedCentralCrossRefGoogle Scholar
  150. 150.
    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(3):220–229PubMedPubMedCentralCrossRefGoogle Scholar
  151. 151.
    Sailasuta N, Ross W, Ananworanich J, Chalermchai T, DeGruttola V, Lerdlum S, Pothisri M, Busovaca E, Ratto-Kim S, Jagodzinski L, Spudich S, Michael N, Kim JH, Valcour V (2012) Change in brain magnetic resonance spectroscopy after treatment during acute HIV infection. PLoS One 7(11):e49272PubMedPubMedCentralCrossRefGoogle Scholar
  152. 152.
    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) Central nervous system viral invasion and inflammation during acute HIV infection. J Infect Dis 206(2):275–282PubMedPubMedCentralCrossRefGoogle Scholar
  153. 153.
    Peluso MJ, Meyerhoff DJ, Price RW, Peterson J, Lee E, Young AC, Walter R, Fuchs D, Brew BJ, Cinque P, Robertson K, Hagberg L, Zetterberg H, Gisslen M, Spudich S (2013) Cerebrospinal fluid and neuroimaging biomarker abnormalities suggest early neurological injury in a subset of individuals during primary HIV infection. J Infect Dis 207(11):1703–1712PubMedPubMedCentralCrossRefGoogle Scholar
  154. 154.
    Masters MC, Ances BM (2014) Role of neuroimaging in HIV-associated neurocognitive disorders. Semin Neurol 34(1):89–102PubMedPubMedCentralCrossRefGoogle Scholar
  155. 155.
    Menon DK, Baudouin CJ, Tomlinson D, Hoyle C (1990) Proton MR spectroscopy and imaging of the brain in AIDS: evidence of neuronal loss in regions that appear normal with imaging. J Comput Assist Tomogr 14(6):882–885PubMedCrossRefGoogle Scholar
  156. 156.
    Salvan AM, Vion-Dury J, Confort-Gouny S, Nicoli F, Lamoureux S, Cozzone PJ (1997) Brain proton magnetic resonance spectroscopy in HIV-related encephalopathy: identification of evolving metabolic patterns in relation to dementia and therapy. AIDS Res Hum Retroviruses 13(12):1055–1066PubMedCrossRefGoogle Scholar
  157. 157.
    Tracey I, Carr CA, Guimaraes AR, Worth JL, Navia BA, Gonzalez RG (1996) Brain choline-containing compounds are elevated in HIV-positive patients before the onset of AIDS dementia complex: a proton magnetic resonance spectroscopic study. Neurology 46(3):783–788PubMedCrossRefGoogle Scholar
  158. 158.
    Marcus CD, Taylor-Robinson SD, Sargentoni J, Ainsworth JG, Frize G, Easterbrook PJ, Shaunak S, Bryant DJ (1998) 1H MR spectroscopy of the brain in HIV-1-seropositive subjects: evidence for diffuse metabolic abnormalities. Metab Brain Dis 13(2):123–136PubMedCrossRefGoogle Scholar
  159. 159.
    Moller HE, Vermathen P, Lentschig MG, Schuierer G, Schwarz S, Wiedermann D, Evers S, Husstedt IW (1999) Metabolic characterization of AIDS dementia complex by spectroscopic imaging. J Magn Reson Imaging 9(1):10–18PubMedCrossRefGoogle Scholar
  160. 160.
    von Giesen HJ, Wittsack HJ, Wenserski F, Koller H, Hefter H, Arendt G (2001) Basal ganglia metabolite abnormalities in minor motor disorders associated with human immunodeficiency virus type 1. Arch Neurol 58(8):1281–1286CrossRefGoogle Scholar
  161. 161.
    Anthony IC, Ramage SN, Carnie FW, Simmonds P, Bell JE (2005) Influence of HAART on HIV-related CNS disease and neuroinflammation. J Neuropathol Exp Neurol 64(6):529–536PubMedCrossRefGoogle Scholar
  162. 162.
    Anthony IC, Bell JE (2008) The neuropathology of HIV/AIDS. Int Rev Psychiatry 20(1):15–24PubMedCrossRefGoogle Scholar
  163. 163.
    Chang L, Ernst T, Leonido-Yee M, Witt M, Speck O, Walot I, Miller EN (1999) Highly active antiretroviral therapy reverses brain metabolite abnormalities in mild HIV dementia. Neurology 53(4):782–789PubMedCrossRefGoogle Scholar
  164. 164.
    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(14):1877–1886PubMedCrossRefGoogle Scholar
  165. 165.
    Schifitto G, Yiannoutsos CT, Ernst T, Navia BA, Nath A, Sacktor N, Anderson C, Marra CM, Clifford DB (2009) Selegiline and oxidative stress in HIV-associated cognitive impairment. Neurology 73(23):1975–1981PubMedPubMedCentralCrossRefGoogle Scholar
  166. 166.
    Pfefferbaum A, Adalsteinsson E, Sullivan EV (2005) Cortical NAA deficits in HIV infection without dementia: influence of alcoholism comorbidity. Neuropsychopharmacology 30(7):1392–1399PubMedGoogle Scholar
  167. 167.
    Chang L, Ernst T, Speck O, Grob CS (2005) Additive effects of HIV and chronic methamphetamine use on brain metabolite abnormalities. Am J Psychiatry 162(2):361–369PubMedPubMedCentralCrossRefGoogle Scholar
  168. 168.
    Marra CM, Zhao Y, Clifford DB, Letendre S, Evans S, Henry K, Ellis RJ, Rodriguez B, Coombs RW, Schifitto G, McArthur JC, Robertson K (2009) Impact of combination antiretroviral therapy on cerebrospinal fluid HIV RNA and neurocognitive performance. AIDS 23(11):1359–1366PubMedPubMedCentralCrossRefGoogle Scholar
  169. 169.
    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(4):356–364PubMedCrossRefGoogle Scholar
  170. 170.
    Keller MA, Venkatraman TN, Thomas A, Deveikis A, LoPresti C, Hayes J, Berman N, Walot I, Padilla S, Johnston-Jones J, Ernst T, Chang L (2004) Altered neurometabolite development in HIV-infected children: correlation with neuropsychological tests. Neurology 62(10):1810–1817PubMedCrossRefGoogle Scholar
  171. 171.
    Mbugua K, Holmes MJ, Hess AT, Little F, Cotton MF, Dobbels E, van der Kouwe AJ, Laughton B, Meintjes EM (2014) Effects of ART timing and HIV progression on neuro-metabolite levels in basal ganglia at age 5 years. In: 20th Annual Meeting of the Organization for Human Brain Mapping, Hamburg, GermanyGoogle Scholar
  172. 172.
    Holmes MJ, Mbugua K, Little F, Cotton MF, van der Kouwe AJ, Laughton B, Meintjes EM (2014) A longitudinal study of the effects of HIV exposure on metabolite levels in the Midfrontal Gray Matter in children: at 5 and 7 years. In: 20th Annual AIDS conference, Melbourne, AustraliaGoogle Scholar
  173. 173.
    Banakar S, Thomas MA, Deveikis A, Watzl JQ, Hayes J, Keller MA (2008) Two-dimensional 1H MR spectroscopy of the brain in human immunodeficiency virus (HIV)-infected children. J Magn Reson Imaging 27(4):710–717PubMedCrossRefGoogle Scholar
  174. 174.
    Thomas MA, Yue K, Binesh N, Davanzo P, Kumar A, Siegel B, Frye M, Curran J, Lufkin R, Martin P, Guze B (2001) Localized two-dimensional shift correlated MR spectroscopy of human brain. Magn Reson Med 46(1):58–67PubMedCrossRefGoogle Scholar
  175. 175.
    Trabesinger AH, Boesiger P (2001) Improved selectivity of double quantum coherence filtering for the detection of glutathione in the human brain in vivo. Magn Reson Med 45(4):708–710PubMedCrossRefGoogle Scholar
  176. 176.
    Trabesinger AH, Weber OM, Duc CO, Boesiger P (1999) Detection of glutathione in the human brain in vivo by means of double quantum coherence filtering. Magn Reson Med 42(2):283–289PubMedCrossRefGoogle Scholar
  177. 177.
    Terpstra M, Henry PG, Gruetter R (2003) Measurement of reduced glutathione (GSH) in human brain using LCModel analysis of difference-edited spectra. Magn Reson Med 50(1):19–23PubMedCrossRefGoogle Scholar
  178. 178.
    Terpstra M, Marjanska M, Henry PG, Tkac I, Gruetter R (2006) Detection of an antioxidant profile in the human brain in vivo via double editing with MEGA-PRESS. Magn Reson Med 56(6):1192–1199PubMedCrossRefGoogle Scholar
  179. 179.
    Srinivas A, Dias BF (2008) Antioxidants in HIV positive children. Indian J Pediatr 75(4):347–350PubMedCrossRefGoogle Scholar
  180. 180.
    Markovic I, Clouse KA (2004) Recent advances in understanding the molecular mechanisms of HIV-1 entry and fusion: revisiting current targets and considering new options for therapeutic intervention. Curr HIV Res 2(3):223–234PubMedCrossRefGoogle Scholar
  181. 181.
    Provencher SW (1993) Estimation of metabolite concentrations from localized in vivo proton NMR spectra. Magn Reson Med 30(6):672–679PubMedCrossRefGoogle Scholar
  182. 182.
    Tkac I, Oz G, Adriany G, Ugurbil K, Gruetter R (2009) In vivo 1H NMR spectroscopy of the human brain at high magnetic fields: metabolite quantification at 4T vs. 7T. Magn Reson Med 62(4):868–879PubMedPubMedCentralCrossRefGoogle Scholar
  183. 183.
    Ratai EM, Pilkenton S, He J, Fell R, Bombardier JP, Joo CG, Lentz MR, Kim WK, Burdo TH, Autissier P, Annamalai L, Curran E, O’Neil SP, Westmoreland SV, Williams KC, Masliah E, Gilberto Gonzalez R (2011) CD8+ lymphocyte depletion without SIV infection does not produce metabolic changes or pathological abnormalities in the rhesus macaque brain. J Med Primatol 40(5):300–309PubMedPubMedCentralCrossRefGoogle Scholar
  184. 184.
    Gonen O, Liu S, Goelman G, Ratai EM, Pilkenton S, Lentz MR, Gonzalez RG (2008) Proton MR spectroscopic imaging of rhesus macaque brain in vivo at 7T. Magn Reson Med 59(4):692–699PubMedPubMedCentralCrossRefGoogle Scholar
  185. 185.
    Caruso PA, Johnson J, Thibert R, Rapalino O, Rincon S, Ratai EM (2013) The use of magnetic resonance spectroscopy in the evaluation of epilepsy. Neuroimaging Clin N Am 23(3):407–424PubMedCrossRefGoogle Scholar
  186. 186.
    Hess AT, Tisdall MD, Andronesi OC, Meintjes EM, van der Kouwe AJ (2011) Real-time motion and B0 corrected single voxel spectroscopy using volumetric navigators. Magn Reson Med 66(2):314–323PubMedPubMedCentralCrossRefGoogle Scholar
  187. 187.
    Tisdall MD, Hess AT, Reuter M, Meintjes EM, Fischl B, van der Kouwe AJ (2012) Volumetric navigators for prospective motion correction and selective reacquisition in neuroanatomical MRI. Magn Reson Med 68(2):389–399PubMedCrossRefGoogle Scholar
  188. 188.
    Bogner W, Hess AT, Gagoski B, Tisdall MD, van der Kouwe AJ, Trattnig S, Rosen B, Andronesi OC (2013) Real-time motion- and B-correction for LASER-localized spiral-accelerated 3D-MRSI of the brain at 3T. Neuroimage 88C:22–31Google Scholar
  189. 189.
    Kuperman JM, Brown TT, Ahmadi ME, Erhart MJ, White NS, Roddey JC, Shankaranarayanan A, Han ET, Rettmann D, Dale AM (2011) Prospective motion correction improves diagnostic utility of pediatric MRI scans. Pediatr Radiol 41(12):1578–1582PubMedPubMedCentralCrossRefGoogle Scholar
  190. 190.
    Brown TT, Kuperman JM, Erhart M, White NS, Roddey JC, Shankaranarayanan A, Han ET, Rettmann D, Dale AM (2010) Prospective motion correction of high-resolution magnetic resonance imaging data in children. Neuroimage 53(1):139–145PubMedPubMedCentralCrossRefGoogle Scholar
  191. 191.
    Andrews-Shigaki BC, Armstrong BS, Zaitsev M, Ernst T (2011) Prospective motion correction for magnetic resonance spectroscopy using single camera Retro-Grate reflector optical tracking. J Magn Reson Imaging 33(2):498–504PubMedPubMedCentralCrossRefGoogle Scholar
  192. 192.
    Keating B, Ernst T (2012) Real-time dynamic frequency and shim correction for single-voxel magnetic resonance spectroscopy. Magn Reson Med 68(5):1339–1345PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Department of Radiology, Neuroradiology DivisionMassachusetts General Hospital, Harvard Medical School and Athinuola A. Martinos Center for Biomedical ImagingBostonUSA

Personalised recommendations