Advertisement

Brain Imaging in People with HIV

  • Paul M. Thompson
  • Jeffry R. Alger
  • Neda Jahanshad

Abstract

In this short review, we show how brain imaging is used to understand brain changes that may occur in people living with HIV. Before combined antiretroviral therapy (cART) became widely available, people infected with HIV often had progressive brain degeneration, and even fatal infections of the central nervous system, if the virus multiplied unchecked. Since the cART era, the focus of HIV neuroimaging research has changed to understanding brain changes that may occur in people with chronic but stable disease, and what factors may help preserve the brain and resist change. A great deal has been learned about how HIV affects the developing and aging brain from in vivo magnetic resonance imaging (MRI) and its variants—MR spectroscopy, diffusion imaging, and resting-state functional MRI. We review some of these developments, including some new techniques that are helping to understand treatment effects in drug trials, and how the virus and medications may affect brain development in children living with HIV.

Keywords

Neuroimaging HIV HIV-associated dementia (HAD) Prenatal infection Brain development Cognition 

Notes

Acknowledgments

P.T. and N.J. are funded by National Institutes of Health grants NS080655, AG040060, EB008432, MH097268, AG024904, MH085667, and MH089722. J.R.A. was funded by National Institutes of Health grants EB00822 and NS044378 and by NeuroSpectroScopics LLC (after July 1, 2014) (for PT and NJ) R01MH102151 (to J. Ananworanich/P. Thompson) and the 2014 NIH Big Data to Knowledge (BD2K) Initiative under grant U54 EB020403 (to PI Thompson).

References

  1. 1.
    Neuenburg JK, Brodt HR, Herndier BG, Bickel M, Bacchetti P, Price RW, et al. HIV-related neuropathology, 1985 to 1999: rising prevalence of HIV encephalopathy in the era of highly active antiretroviral therapy. J Acquir Immune Defic Syndr. 2002;31(2):171–7.PubMedCrossRefGoogle Scholar
  2. 2.
    Levy RM, Mills CM, Posin JP, Moore SG, Rosenblum ML, Bredesen DE. The efficacy and clinical impact of brain imaging in neurologically symptomatic AIDS patients: a prospective CT/MRI study. J Acquir Immune Defic Syndr. 1990;3(5):461–71.PubMedCrossRefGoogle Scholar
  3. 3.
    An SF, Groves M, Gray F, Scaravilli F. Early entry and widespread cellular involvement of HIV-1 DNA in brains of HIV-1 positive asymptomatic individuals. J Neuropathol Exp Neurol. 1999;58(11):1156–62.PubMedCrossRefGoogle Scholar
  4. 4.
    Gray F, Scaravilli F, Everall I, Chretien F, An S, Boche D, et al. Neuropathology of early HIV-1 infection. Brain Pathol. 1996;6(1):1–15.PubMedCrossRefGoogle Scholar
  5. 5.
    Hestad K, McArthur JH, Dal Pan GJ, Selnes OA, Nance-Sproson TE, Aylward E, et al. Regional brain atrophy in HIV-1 infection: association with specific neuropsychological test performance. Acta Neurol Scand. 1993;88(2):112–8.PubMedCrossRefGoogle Scholar
  6. 6.
    Sacktor N, McDermott MP, Marder K, Schifitto G, Selnes OA, McArthur JC, et al. HIV-associated cognitive impairment before and after the advent of combination therapy. J Neurovirol. 2002;8(2):136–42.PubMedCrossRefGoogle Scholar
  7. 7.
    Thompson PM, Hayashi KM, de Zubicaray G, Janke AL, Rose SE, Semple J, et al. Dynamics of gray matter loss in Alzheimer’s disease. J Neurosci. 2003;23(3):994–1005.PubMedGoogle Scholar
  8. 8.
    Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. 1991;82(4):239–59.PubMedCrossRefGoogle Scholar
  9. 9.
    Jack Jr CR, Knopman DS, Jagust WJ, Petersen RC, Weiner MW, Aisen PS, et al. Tracking pathophysiological processes in Alzheimer’s disease: an updated hypothetical model of dynamic biomarkers. Lancet Neurol. 2013;12(2):207–16.PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Jack Jr CR, Knopman DS, Jagust WJ, Shaw LM, Aisen PS, Weiner MW, et al. Hypothetical model of dynamic biomarkers of the Alzheimer’s pathological cascade. Lancet Neurol. 2010;9(1):119–28.PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Fjell AM, Walhovd KB. New tools for the study of Alzheimer’s disease: what are biomarkers and morphometric markers teaching us? Neuroscientist. 2011;17(5):592–605.PubMedCrossRefGoogle Scholar
  12. 12.
    Ances BM, Vaida F, Yeh MJ, Liang CL, Buxton RB, Letendre S, et al. HIV infection and aging independently affect brain function as measured by functional magnetic resonance imaging. J Infect Dis. 2010;201(3):336–40.PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    Scott JC, Woods SP, Carey CL, Weber E, Bondi MW, Grant I. Neurocognitive consequences of HIV infection in older adults: an evaluation of the “cortical” hypothesis. AIDS Behav. 2011;15(6):1187–96.PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Thompson PM, Dutton RA, Hayashi KM, Toga AW, Lopez OL, Aizenstein HJ, et al. Thinning of the cerebral cortex visualized in HIV/AIDS reflects CD4+ T lymphocyte decline. Proc Natl Acad Sci U S A. 2005;102(43):15647–52.PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Chiang MC, Dutton RA, Hayashi KM, Lopez OL, Aizenstein HJ, Toga AW, et al. 3D pattern of brain atrophy in HIV/AIDS visualized using tensor-based morphometry. Neuroimage. 2007;34(1):44–60.PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Becker JT, Sanders J, Madsen SK, Ragin A, Kingsley L, Maruca V, et al. Subcortical brain atrophy persists even in HAART-regulated HIV disease. Brain Imaging Behav. 2011;5(2):77–85.PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Stoodley CJ. The cerebellum and cognition: evidence from functional imaging studies. Cerebellum. 2012;11(2):352–65.PubMedCrossRefGoogle Scholar
  18. 18.
    Klunder AD, Chiang MC, Dutton RA, Lee SE, Toga AW, Lopez OL, et al. Mapping cerebellar degeneration in HIV/AIDS. Neuroreport. 2008;19(17):1655–9.PubMedCentralPubMedCrossRefGoogle Scholar
  19. 19.
    Valcour VG, Sacktor NC, Paul RH, Watters MR, Selnes OA, Shiramizu BT, et al. Insulin resistance is associated with cognition among HIV-1-infected patients: the Hawaii aging with HIV cohort. J Acquir Immune Defic Syndr. 2006;43(4):405–10.PubMedCrossRefGoogle Scholar
  20. 20.
    Becker JT, Maruca V, Kingsley LA, Sanders JM, Alger JR, Barker PB, et al. Factors affecting brain structure in men with HIV disease in the post-HAART era. Neuroradiology. 2011;54(2):113–21.PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    Nakamoto BK, Jahanshad N, McMurtray A, Kallianpur KJ, Chow DC, Valcour VG, et al. Cerebrovascular risk factors and brain microstructural abnormalities on diffusion tensor images in HIV-infected individuals. J Neurovirol. 2012;18(4):303–12.PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Jernigan TL, Archibald SL, Fennema-Notestine C, Taylor MJ, Theilmann RJ, Julaton MD, et al. Clinical factors related to brain structure in HIV: the CHARTER study. J Neurovirol. 2011;17(3):248–57.PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Thompson PM, Dutton RA, Hayashi KM, Lu A, Lee SE, Lee JY, et al. 3D mapping of ventricular and corpus callosum abnormalities in HIV/AIDS. Neuroimage. 2006;31(1):12–23.PubMedCrossRefGoogle Scholar
  24. 24.
    Wang Y, Zhang J, Gutman B, Chan TF, Becker JT, Aizenstein HJ, et al. Multivariate tensor-based morphometry on surfaces: application to mapping ventricular abnormalities in HIV/AIDS. Neuroimage. 2010;49(3):2141–57.PubMedCentralPubMedCrossRefGoogle Scholar
  25. 25.
    Cohen RA, Harezlak J, Schifitto G, Hana G, Clark U, Gongvatana A, et al. Effects of nadir CD4 count and duration of human immunodeficiency virus infection on brain volumes in the highly active antiretroviral therapy era. J Neurovirol. 2010;16(1):25–32.PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26.
    Nir TM, Jahanshad N, Busovaca E, Wendelken L, Nicolas K, Thompson PM, et al. Mapping white matter integrity in elderly people with HIV. Hum Brain Mapp. 2014;35(3):975–92.PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.
    Gongvatana A, Cohen RA, Correia S, Devlin KN, Miles J, Kang H, et al. Clinical contributors to cerebral white matter integrity in HIV-infected individuals. J Neurovirol. 2011;17(5):477–86.PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    Lopez-Villegas D, Lenkinski RE, Frank I. Biochemical changes in the frontal lobe of HIV-infected individuals detected by magnetic resonance spectroscopy. Proc Natl Acad Sci U S A. 1997;94(18):9854–9.PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29.
    Harezlak J, Cohen R, Gongvatana A, Taylor M, Buchthal S, Schifitto G, et al. Predictors of CNS injury as measured by proton magnetic resonance spectroscopy in the setting of chronic HIV infection and CART. J Neurovirol. 2014;20(3):294–303.PubMedCentralPubMedCrossRefGoogle Scholar
  30. 30.
    Hua X, Boyle CP, Harezlak J, Tate DF, Yiannoutsos CT, Cohen R, et al. Disrupted cerebral metabolite levels and lower nadir CD4+ counts are linked to brain volume deficits in 210 HIV-infected patients on stable treatment. Neuroimage Clin. 2013;3:132–42.PubMedCentralPubMedCrossRefGoogle Scholar
  31. 31.
    Sailasuta N, Ross W, Ananworanich J, Chalermchai T, DeGruttola V, Lerdlum S, et al. Change in brain magnetic resonance spectroscopy after treatment during acute HIV infection. PLoS One. 2012;7(11):e49272.PubMedCentralPubMedCrossRefGoogle Scholar
  32. 32.
    Alger JR. The diffusion tensor imaging toolbox. J Neurosci. 2012;32(22):7418–28.PubMedCentralPubMedCrossRefGoogle Scholar
  33. 33.
    Jahanshad N, Valcour VG, Nir TM, Kohannim O, Busovaca E, Nicolas K, et al. Disrupted brain networks in the aging HIV+ population. Brain Connect. 2012;2(6):335–44.PubMedCentralPubMedCrossRefGoogle Scholar
  34. 34.
    Jahanshad N, Kohannim O, Hibar DP, Stein JL, McMahon KL, de Zubicaray GI, et al. Brain structure in healthy adults is related to serum transferrin and the H63D polymorphism in the HFE gene. Proc Natl Acad Sci U S A. 2012;109(14):E851–9.PubMedCentralPubMedCrossRefGoogle Scholar
  35. 35.
    Jahanshad N, Rajagopalan P, Thompson PM. Neuroimaging, nutrition, and iron-related genes. Cell Mol Life Sci. 2013;70(23):4449–61.PubMedCentralPubMedCrossRefGoogle Scholar
  36. 36.
    Hoare J, Ransford GL, Phillips N, Amos T, Donald K, Stein DJ. Systematic review of neuroimaging studies in vertically transmitted HIV positive children and adolescents. Metab Brain Dis. 2013;29(2):221–9.PubMedCrossRefGoogle Scholar
  37. 37.
    Smith R, Chernoff M, Williams PL, Malee KM, Sirois PA, Kammerer B, et al. Impact of HIV severity on cognitive and adaptive functioning during childhood and adolescence. Pediatr Infect Dis J. 2012;31(6):592–8.PubMedCrossRefGoogle Scholar
  38. 38.
    Puthanakit T, Ananworanich J, Vonthanak S, Kosalaraksa P, Hansudewechakul R, van der Lugt J, et al. Cognitive function and neurodevelopmental outcomes in HIV-infected Children older than 1 year of age randomized to early versus deferred antiretroviral therapy: the PREDICT neurodevelopmental study. Pediatr Infect Dis J. 2013;32(5):501–8.PubMedCentralPubMedCrossRefGoogle Scholar
  39. 39.
    Jahanshad et al., 2015Google Scholar
  40. 40.
    Thompson PM, Giedd JN, Woods RP, MacDonald D, Evans AC, Toga AW. Growth patterns in the developing brain detected by using continuum mechanical tensor maps. Nature. 2000;404(6774):190–3.PubMedCrossRefGoogle Scholar
  41. 41.
    Gogtay N, Giedd JN, Lusk L, Hayashi KM, Greenstein D, Vaituzis AC, et al. Dynamic mapping of human cortical development during childhood through early adulthood. Proc Natl Acad Sci U S A. 2004;101(21):8174–9.PubMedCentralPubMedCrossRefGoogle Scholar
  42. 42.
    Ortega M, Heaps JM, Joska J, Vaida F, Seedat S, Stein DJ, et al. HIV clades B and C are associated with reduced brain volumetrics. J Neurovirol. 2013;19(5):479–87.PubMedCrossRefGoogle Scholar
  43. 43.
    Stein JL, Medland SE, Vasquez AA, Hibar DP, Senstad RE, Winkler AM, et al. Identification of common variants associated with human hippocampal and intracranial volumes. Nat Genet. 2012;44(5):552–61.PubMedCentralPubMedCrossRefGoogle Scholar
  44. 44.
    Hibar DP, ENIGMA_Consortium. Common genetic variants affect brain structure: a genome-wide screen of 29,000 brain scans. Nature 2014 (submitted).Google Scholar
  45. 45.
    Tate DF, Sampat M, Harezlak J, Fiecas M, Hogan J, Dewey J, et al. Regional areas and widths of the midsagittal corpus callosum among HIV-infected patients on stable antiretroviral therapies. J Neurovirol. 2011;17(4):368–79.PubMedCentralPubMedCrossRefGoogle Scholar
  46. 46.
    Heaton RK, Clifford DB, Franklin Jr DR, Woods SP, Ake C, Vaida F, et al. HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy: CHARTER Study. Neurology. 2010;75(23):2087–96.PubMedCentralPubMedCrossRefGoogle Scholar
  47. 47.
    Thompson PM, Stein JL, Medland SE, Hibar DP, Vasquez AA, Renteria ME, et al. The ENIGMA Consortium: large-scale collaborative analyses of neuroimaging and genetic data. Brain Imaging Behav. 2014;8(2):153–82.PubMedCentralPubMedGoogle Scholar
  48. 48.
    Levine AJ, Service S, Miller EN, Reynolds SM, Singer EJ, Shapshak P, et al. Genome-wide association study of neurocognitive impairment and dementia in HIV-infected adults. Am J Med Genet B Neuropsychiatr Genet. 2012;159B(6):669–83.PubMedCentralPubMedCrossRefGoogle Scholar
  49. 49.
    Thompson PM, Hayashi KM, Simon SL, Geaga JA, Hong MS, Sui Y, et al. Structural abnormalities in the brains of human subjects who use methamphetamine. J Neurosci. 2004;24(26):6028–36.PubMedCrossRefGoogle Scholar
  50. 50.
    Lu LH, Johnson A, O’Hare ED, Bookheimer SY, Smith LM, O’Connor MJ, et al. Effects of prenatal methamphetamine exposure on verbal memory revealed with functional magnetic resonance imaging. J Dev Behav Pediatr. 2009;30(3):185–92.PubMedCentralPubMedCrossRefGoogle Scholar
  51. 51.
    Bae SC, Lyoo IK, Sung YH, Yoo J, Chung A, Yoon SJ, et al. Increased white matter hyperintensities in male methamphetamine abusers. Drug Alcohol Depend. 2006;81(1):83–8.PubMedCrossRefGoogle Scholar
  52. 52.
    Chang L, Ernst T, Speck O, Grob CS. Additive effects of HIV and chronic methamphetamine use on brain metabolite abnormalities. Am J Psychiatry. 2005;162(2):361–9.PubMedCrossRefGoogle Scholar
  53. 53.
    Jernigan TL, Gamst AC, Archibald SL, Fennema-Notestine C, Mindt MR, Marcotte TD, et al. Effects of methamphetamine dependence and HIV infection on cerebral morphology. Am J Psychiatry. 2005;162(8):1461–72.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Paul M. Thompson
    • 1
    • 2
    • 3
    • 4
    • 5
    • 6
    • 7
  • Jeffry R. Alger
    • 8
    • 9
  • Neda Jahanshad
    • 2
    • 10
  1. 1.Imaging Genetics Center, Institute for Neuroimaging and InformaticsKeck School of Medicine of USCMarina del ReyUSA
  2. 2.Department of NeurologyKeck USC School of MedicineLos AngelesUSA
  3. 3.Department of RadiologyKeck USC School of MedicineLos AngelesUSA
  4. 4.Department of OphthalmologyKeck USC School of MedicineLos AngelesUSA
  5. 5.Department of PediatricsKeck USC School of MedicineLos AngelesUSA
  6. 6.Department of PsychiatryKeck USC School of MedicineLos AngelesUSA
  7. 7.Department of EngineeringKeck USC School of MedicineLos AngelesUSA
  8. 8.UCLA Geffen School of MedicineLos AngelesUSA
  9. 9.NeuroSpectroScopics LLCSherman OaksUSA
  10. 10.IImaging Genetics Center, Mary and Mary Stevens Institute for Neuroimaging and InformaticsKeck School of Medicine of USCMarina del ReyUSA

Personalised recommendations