Skip to main content
SpringerLink
Log in

Brain Imaging in People with HIV

  • Chapter
Global Virology I - Identifying and Investigating Viral Diseases

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.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  8. Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. 1991;82(4):239–59.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed Central  PubMed  Google Scholar 

  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.

    Article  PubMed Central  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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.

    Article  PubMed Central  PubMed  Google Scholar 

  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.

    Article  PubMed Central  PubMed  Google Scholar 

  17. Stoodley CJ. The cerebellum and cognition: evidence from functional imaging studies. Cerebellum. 2012;11(2):352–65.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed Central  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed Central  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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.

    Article  PubMed Central  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed Central  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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.

    Article  PubMed Central  PubMed  Google Scholar 

  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.

    Article  PubMed Central  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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.

    Article  PubMed Central  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Alger JR. The diffusion tensor imaging toolbox. J Neurosci. 2012;32(22):7418–28.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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.

    Article  PubMed Central  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  35. Jahanshad N, Rajagopalan P, Thompson PM. Neuroimaging, nutrition, and iron-related genes. Cell Mol Life Sci. 2013;70(23):4449–61.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed Central  PubMed  Google Scholar 

  39. Jahanshad et al., 2015

    Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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. 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.

    Article  PubMed Central  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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.

    PubMed Central  PubMed  Google Scholar 

  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.

    Article  PubMed Central  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed Central  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

Download references

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).

Author information

Authors and Affiliations

  1. Imaging Genetics Center, Institute for Neuroimaging and Informatics, Keck School of Medicine of USC, 4676 Admiralty Way, Suite 400, Marina del Rey, CA, 90292, USA

    Paul M. Thompson Ph.D.

  2. Department of Neurology, Keck USC School of Medicine, Los Angeles, CA, USA

    Paul M. Thompson Ph.D. & Neda Jahanshad

  3. Department of Radiology, Keck USC School of Medicine, Los Angeles, CA, USA

    Paul M. Thompson Ph.D.

  4. Department of Ophthalmology, Keck USC School of Medicine, Los Angeles, CA, USA

    Paul M. Thompson Ph.D.

  5. Department of Pediatrics, Keck USC School of Medicine, Los Angeles, CA, USA

    Paul M. Thompson Ph.D.

  6. Department of Psychiatry, Keck USC School of Medicine, Los Angeles, CA, USA

    Paul M. Thompson Ph.D.

  7. Department of Engineering, Keck USC School of Medicine, Los Angeles, CA, USA

    Paul M. Thompson Ph.D.

  8. UCLA Geffen School of Medicine, Los Angeles, CA, USA

    Jeffry R. Alger

  9. NeuroSpectroScopics LLC, Sherman Oaks, CA, USA

    Jeffry R. Alger

  10. IImaging Genetics Center, Mary and Mary Stevens Institute for Neuroimaging and Informatics, Keck School of Medicine of USC, 4676 Admiralty Way, Suite 400, Marina del Rey, CA, 90292, USA

    Neda Jahanshad

Authors
  1. Paul M. Thompson Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jeffry R. Alger
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Neda Jahanshad
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Paul M. Thompson Ph.D. .

Editor information

Editors and Affiliations

  1. Division of Infectious Diseases and International Medicine, USF Morsani College of Medicine, Tampa, Florida, USA

    Paul Shapshak

  2. Infectious Diseases and International He, USF Morsani College of Medicine, Tampa, Florida, USA

    John T. Sinnott

  3. Division of Infectious Diseases and Inte, USF Morsani College of Medicine, Tampa, Florida, USA

    Charurut Somboonwit

  4. C.W. Bill Young Center for Biodefense & Emerging Infectious Diseases, NIH-NIAID Div. Clinical Research, Frederick, Maryland, USA

    Jens H. Kuhn

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer Science+Business Media New York

About this chapter

Cite this chapter

Thompson, P.M., Alger, J.R., Jahanshad, N. (2015). Brain Imaging in People with HIV. In: Shapshak, P., Sinnott, J., Somboonwit, C., Kuhn, J. (eds) Global Virology I - Identifying and Investigating Viral Diseases. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-2410-3_28

Download citation

Publish with us

Policies and ethics

Search

Navigation