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White matter microstructure among perinatally HIV-infected youth: a diffusion tensor imaging study

  • Manoj K. Sarma
  • Margaret A. Keller
  • Paul M. Macey
  • David E. Michalik
  • Judy Hayes
  • Karin Nielsen-Saines
  • Jaime Deville
  • Joseph A. Church
  • Irwin Walot
  • M. Albert ThomasEmail author
Article
  • 36 Downloads

Abstract

We evaluated white matter microstructure integrity in perinatally HIV-infected (PHIV) youths receiving cART compared to age- and gender-matched healthy youths through DTI metrics using voxel-based morphometry (VBM). We investigated 14 perinatally HIV-infected patients (age 17.9 ± 2.5 years) on cART and 17 healthy youths (HC) (age 18.0 ± 3.0 years) using a 3T MRI scanner. Four DTI-derived metrics were fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). Statistical analysis was done with voxel-based analysis of covariance (ANCOVA), with age and gender as covariates. Region-of-interest secondary analyses in statistically significant regions were also performed. Regional increases in FA in the PHIV youths were found in left middle frontal gyrus, right precuneus, right lingual gyrus, and left supramarginal gyrus. Increased MD was found in the right precentral gyrus while decreased MD was found in the white matter of the right superior parietal lobule and right inferior temporal gyrus/fusiform gyrus. Regions of increased/decreased RD overlapped with regions of increased/decreased MD. Both increased and decreased AD were found in three to four regions respectively. The regional FA, MD, RD, and AD values were consistent with the voxel-based analysis findings. The findings are mostly consistent with previous literature, but increased FA has not been previously reported for perinatally HIV-infected youths. Potentially early and prolonged therapy in our population may have contributed to this new finding. Both toxicity of antiretroviral therapy and indolent infection must be considered as causative factors in the DTI metric changes that we have observed.

Keywords

Brain Human immunodeficiency virus (HIV) Combination anti-retroviral therapy (cART) Diffusion tensor imaging (DTI) Fractional anisotropy (FA) Mean diffusivity (MD) Radial diffusivity (RD) Axial diffusivity (AD) Voxel-based morphometry (VBM) 

Notes

Acknowledgements

We also acknowledge the scientific support of Dr. Rajakumar Nagarajan.

Funding information

This research was supported by research grants from the National Institute of Neurological Disorders and Stroke (NINDS) 1R21NS08064901A1, 1R21NS09095601A1, and 1R21NS06062001A1.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. Ackermann C, Andronikou S, Laughton B, Kidd M, Dobbels E, Innes S, van Toorn R, Cotton M (2014) White matter signal abnormalities in children with suspected HIV-related neurologic disease on early combination antiretroviral therapy. Pediatr Infect Dis J 33:e207–e212.  https://doi.org/10.1097/INF.0000000000000288 CrossRefPubMedPubMedCentralGoogle Scholar
  2. Ackermann C, Andronikou S, Saleh MG, Laughton B, Alhamud AA, van der Kouwe A, Kidd M, Cotton MF, Meintjes EM (2016) Early antiretroviral therapy in HIV-infected children is associated with diffuse white matter structural abnormality and corpus callosum sparing. AJNR Am J Neuroradiol 37:2363–2369.  https://doi.org/10.3174/ajnr.A4921 CrossRefPubMedPubMedCentralGoogle Scholar
  3. 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 64:529–536CrossRefGoogle Scholar
  4. Ashburner J, Friston KJ (2000) Voxel-based morphometry—the methods. Neuroimage 11:805–821.  https://doi.org/10.1006/nimg.2000.0582 CrossRefPubMedGoogle Scholar
  5. Basser PJ, Pierpaoli C (1996) Microstructural and physiological features of tissues elucidated by quantitative-diffusion-tensor MRI. J Magn Reson B 111:209–219 doi: 10.1.1.162.3203CrossRefGoogle Scholar
  6. Beaulieu C (2002) The basis of anisotropic water diffusion in the nervous system—a technical review. NMR Biomed 15:435–455.  https://doi.org/10.1002/nbm.782 CrossRefPubMedGoogle Scholar
  7. Berger JR, Avison MJ (2001) Diffusion tensor imaging in HIV infection: what is it telling us? AJNR Am J Neuroradiol 22:237–238PubMedGoogle Scholar
  8. 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, HIV MRS Consortium (2004) A multicenter in vivo proton-MRS study of HIV-associated dementia and its relationship to age. Neuroimage 23:1336–1347.  https://doi.org/10.1016/j.neuroimage.2004.07.067 CrossRefPubMedGoogle Scholar
  9. Chang L, Wong V, Nakama H, Watters M, Ramones D, Miller EN, Cloak C, Ernst T (2008) Greater than age-related changes in brain diffusion of HIV patients after 1 year. J NeuroImmune Pharmacol 3:265–274.  https://doi.org/10.1007/s11481-008-9120-8 CrossRefPubMedPubMedCentralGoogle Scholar
  10. Chen Y, An H, Zhu H, Stone T, Smith JK, Hall C, Bullitt E, Shen D, Lin W (2009) White matter abnormalities revealed by diffusion tensor imaging in non-demented and demented HIV+ patients. Neuroimage 47:1154–1162.  https://doi.org/10.1016/j.neuroimage.2009.04.030 CrossRefPubMedPubMedCentralGoogle Scholar
  11. Cho H, Yang DW, Shon YM, Kim BS, Kim YI, Choi YB, Lee KS, Shim YS, Yoon B, Kim W, Ahn KJ (2008) Abnormal integrity of corticocortical tracts in mild cognitive impairment: a diffusion tensor imaging study. J Korean Med Sci 23:477–483.  https://doi.org/10.3346/jkms.2008.23.3.477 CrossRefPubMedPubMedCentralGoogle Scholar
  12. Choe AS, Stepniewska I, Colvin DC, Ding Z, Anderson AW (2012) Validation of diffusion tensor MRI in the central nervous system using light microscopy: quantitative comparison of fiber properties. NMR Biomed 25:900–908.  https://doi.org/10.1002/nbm.1810 CrossRefPubMedPubMedCentralGoogle Scholar
  13. Cohen S, Ter Stege JA, Geurtsen GJ, Scherpbier HJ, Kuijpers TW, Reiss P, Schmand B, Pajkrt D (2015) Poorer cognitive performance in perinatally HIV-infected children versus healthy socioeconomically matched controls. Clin Infect Dis 60:1111–1119.  https://doi.org/10.1093/cid/ciu1144 CrossRefPubMedGoogle Scholar
  14. Cohen S, Caan MW, Mutsaerts HJ, Scherpbier HJ, Kuijpers TW, Reiss P, Majoie CB, Pajkrt D (2016) Cerebral injury in perinatally HIV-infected children compared to matched healthy controls. Neurology 86:19–27.  https://doi.org/10.1212/WNL.0000000000002209 CrossRefPubMedGoogle Scholar
  15. Connolly NC, Riddler SA, Rinaldo CR (2005) Proinflammatory cytokines in HIV disease-a review and rationale for new therapeutic approaches. AIDS Rev 7:168–180.  https://doi.org/10.1371/journal.pone.0170063 CrossRefPubMedGoogle Scholar
  16. Ellis R, Langford D, Masliah E (2007) HIV and antiretroviral therapy in the brain: neuronal injury and repair. Nat Rev Neurosci 8:33–44.  https://doi.org/10.1038/nrn2040 CrossRefPubMedGoogle Scholar
  17. Ellis RJ, Calero P, Stockin MD (2009) HIV infection and the central nervous system: a primer. Neuropsychol Rev 19:144–151.  https://doi.org/10.1007/s11065-009-9094-1 CrossRefPubMedPubMedCentralGoogle Scholar
  18. Filippi CG, Lin DD, Tsiouris AJ, Watts R, Packard AM, Heier LA, Uluğ AM (2003) Diffusion-tensor MR imaging in children with developmental delay: preliminary findings. Radiology 229:44–50.  https://doi.org/10.1148/radiol.2291020049 CrossRefPubMedGoogle Scholar
  19. Hoare J, Fouche JP, Spottiswoode B, Sorsdahl K, Combrinck M, Stein DJ, Paul RH, Joska JA (2011) White-matter damage in clade C HIV-positive subjects: a diffusion tensor imaging study. J Neuropsychiatr Clin Neurosci 23:308–315.  https://doi.org/10.1176/appi.neuropsych.23.3.308 CrossRefGoogle Scholar
  20. Hoare J, Fouche JP, Spottiswoode B, Donald K, Philipps N, Bezuidenhout H, Mulligan C, Webster V, Oduro C, Schrieff L, Paul R, Zar H, Thomas K, Stein D (2012) A diffusion tensor imaging and neurocognitive study of HIV-positive children who are HAART-naïve “slow progressors”. J Neuro-Oncol 18:205–212.  https://doi.org/10.1007/s13365-012-0099-9 CrossRefGoogle Scholar
  21. Hoare J, Ransford GL, Philipps N, Amos T, Donald KA, Stein DJ (2014) Systematic review of neuroimaging studies in vertically transmitted HIV positive children and adolescents. Metab Brain Dis 29:221–229.  https://doi.org/10.1007/s11011-013-9456-5 CrossRefPubMedGoogle Scholar
  22. Hoare J, Fouche JP, Phillips N, Joska JA, Donald KA, Thomas K, Stein DJ (2015) Clinical associations of white matter damage in cART-treated HIV-positive children in South Africa. J Neuro-Oncol 21:120–128.  https://doi.org/10.1007/s13365-014-0311-1 CrossRefGoogle Scholar
  23. Hoeft F, Barnea-Goraly N, Haas BW, Golarai G, Ng D, Mills D, Korenberg J, Bellugi U, Galaburda A, Reiss AL (2007) More is not always better: increased fractional anisotropy of superior longitudinal fasciculus associated with poor visuospatial abilities in Williams syndrome. J Neurosci 27:11960–11965.  https://doi.org/10.1523/JNEUROSCI.3591-07.2007 CrossRefPubMedGoogle Scholar
  24. Jahanshad N, Couture MC, Prasitsuebsai W, Nir TM, Aurpibul L, Thompson PM, Pruksakaew K, Lerdlum S, Visrutaratna P, Catella S, Desai A, Kerr SJ, Puthanakit T, Paul R, Ananworanich J, Valcour VG, SEARCH 012 and PREDICT Study Groups (2015) Brain imaging and neurodevelopment in HIV-uninfected Thai children born to HIV-infected mothers. Pediatr Infect Dis J 34:e211–e216.  https://doi.org/10.1097/INF.0000000000000774 CrossRefPubMedPubMedCentralGoogle Scholar
  25. Jankiewicz M, Holmes MJ, Taylor PA, Cotton MF, Laughton B, van der Kouwe AJW, Meintjes EM (2017) White matter abnormalities in children with HIV infection and exposure. Front Neuroanat 11:88.  https://doi.org/10.3389/fnana.2017.00088 CrossRefPubMedPubMedCentralGoogle Scholar
  26. Jiang H, van Zijl PC, Kim J, Pearlson GD, Mori S (2006) DtiStudio: resource program for diffusion tensor computation and fiber bundle tracking. Comput Methods Prog Biomed 81:106–116.  https://doi.org/10.1016/j.cmpb.2005.08.004 CrossRefGoogle Scholar
  27. Johann-Liang R, Lin K, Cervia J, Stavola J, Noel G (1998) Neuroimaging findings in children perinatally infected with the human immunodeficiency virus. Pediatr Infect Dis J 17:753–754CrossRefGoogle Scholar
  28. Kolson D (2017) Neurologic complications in persons with HIV infection in the era of antiretroviral therapy. Top Antivir Med 25:97–101PubMedPubMedCentralGoogle Scholar
  29. Laughton B, Cornell M, Boivin M, Van Rie A (2013) Neurodevelopment in perinatally HIV-infected children: a concern for adolescence. J Int AIDS Soc 16:18603.  https://doi.org/10.7448/IAS.16.1.18603 CrossRefPubMedPubMedCentralGoogle Scholar
  30. Lee GM, Gortmaker SL, McIntosh K, Hughes MD, Oleske JM, Pediatric AIDS Clinical Trials Group Protocol 219C Team (2006) Quality of life for children and adolescents: impact of HIV infection and antiretroviral treatment. Pediatrics 117:273–283.  https://doi.org/10.1542/peds.2005-0323 CrossRefPubMedGoogle Scholar
  31. Li Q, Sun J, Guo L, Zang Y, Feng Z, Huang X, Yang H, Lv Y, Huang M, Gong Q (2010) Increased fractional anisotropy in white matter of the right frontal region in children with attention-deficit/hyperactivity disorder: a diffusion tensor imaging study. Neuro Endocrinol Lett 31:747–753PubMedGoogle Scholar
  32. Liner KJ 2nd, Ro MJ, Robertson KR (2010) HIV, antiretroviral therapies, and the brain. Curr HIV/AIDS Rep 7:85–91.  https://doi.org/10.1007/s11904-010-0042-8 CrossRefPubMedGoogle Scholar
  33. Lochner C, Fouché JP, du Plessis S, Spottiswoode B, Seedat S, Fineberg N, Chamberlain SR, Stein DJ (2012) Evidence for fractional anisotropy and mean diffusivity white matter abnormalities in the internal capsule and cingulum in patients with obsessive-compulsive disorder. J Psychiatry Neurosci 37:193–199.  https://doi.org/10.1503/jpn.110059 CrossRefPubMedPubMedCentralGoogle Scholar
  34. Loy DN, Kim JH, Xie M, Schmidt RE, Trinkaus K, Song SK (2007) Diffusion tensor imaging predicts hyperacute spinal cord injury severity. J Neurotrauma 24:979–990.  https://doi.org/10.1089/neu.2006.0253 CrossRefPubMedGoogle Scholar
  35. Marra CM, Zhao Y, Clifford DB, Letendre S, Evans S, Henry K, Ellis RJ, Rodriguez B, Coombs RW, Schifitto G, McArthur JC, Robertson K, AIDS Clinical Trials Group 736 Study Team (2009) Impact of combination antiretroviral therapy on cerebrospinal fluid HIV RNA and neurocognitive performance. AIDS 23:1359–1366.  https://doi.org/10.1097/QAD.0b013e32832c4152 CrossRefPubMedPubMedCentralGoogle Scholar
  36. Metwalli NS, Benatar M, Nair G, Usher S, Hu X, Carew JD (2010) Utility of axial and radial diffusivity from diffusion tensor MRI as markers of neurodegeneration in amyotrophic lateral sclerosis. Brain Res 1348:156–164.  https://doi.org/10.1016/j.brainres.2010.05.067 CrossRefPubMedGoogle Scholar
  37. Moore RD, Chaisson RE (1999) Natural history of HIV infection in the era of combination antiretroviral therapy. AIDS 13:1933–1942.  https://doi.org/10.1097/00002030-199910010-00017 CrossRefPubMedGoogle Scholar
  38. Mori S, Crain BJ, Chacko VP, van Zijl PC (1999) Three-dimensional tracking of axonal projections in the brain by magnetic resonance imaging. Ann Neurol 45:265–269 doi: N/ACrossRefGoogle Scholar
  39. Musielak KA, Fine JG (2016) An updated systematic review of neuroimaging studies of children and adolescents with perinatally acquired HIV. J Pediatr Neuropsychol 2:34–49.  https://doi.org/10.1007/s40817-015-0009-1 CrossRefGoogle Scholar
  40. Nagarajan R, Sarma MK, Thomas MA, Chang L, Natha U, Wright M, Hayes J, Nielsen-Saines K, Michalik DE, Deville J, Church JA, Mason K, Critton-Mastandrea T, Nazarian S, Jing J, Keller MA (2012) Neuropsychological function and cerebral metabolites in HIV-infected youth. J NeuroImmune Pharmacol 7:981–990.  https://doi.org/10.1007/s11481-012-9407-7 CrossRefPubMedPubMedCentralGoogle Scholar
  41. Palella FJ Jr, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, Aschman DJ, Holmberg SD (1998) Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N Engl J Med 338:853–860.  https://doi.org/10.1056/NEJM199803263381301 CrossRefPubMedGoogle Scholar
  42. Patel K, Hernán MA, Williams PL, Seeger JD, McIntosh K, Van Dyke RB, Seage GR 3rd, Pediatric AIDS Clinical Trials Group 219/219C Study Team (2008) Long-term effectiveness of highly active antiretroviral therapy on the survival of children and adolescents with HIV infection: a 10-year follow-up study. Clin Infect Dis 46:507–515.  https://doi.org/10.1086/526524 CrossRefPubMedGoogle Scholar
  43. Pfefferbaum A, Rosenbloom MJ, Adalsteinsson E, Sullivan EV (2007) Diffusion tensor imaging with quantitative fibre tracking in HIV infection and alcoholism comorbidity: synergistic white matter damage. Brain 130:48–64.  https://doi.org/10.1093/brain/awl242 CrossRefPubMedGoogle Scholar
  44. Pierpaoli C, Jezzard P, Basser PJ, Barnett A, Di Chiro G (1996) Diffusion tensor MR imaging of human brain. Radiology 201:637–648.  https://doi.org/10.1148/radiology.201.3.8939209 CrossRefPubMedGoogle Scholar
  45. Pomara N, Crandall DT, Choi SJ, Johnson G, Lim KO (2001) White matter abnormalities in HIV-1 infection: a diffusion tensor imaging study. Psychiatry Res 106:15–24.  https://doi.org/10.1016/S0925-4927(00)00082-2 CrossRefPubMedGoogle Scholar
  46. Ragin AB, Wu Y, Storey P, Cohen BA, Edelman RR, Epstein LG (2006) Monocyte chemoattractant protein-1 correlates with subcortical brain injury in HIV infection. Neurology 66:1255–1257.  https://doi.org/10.1212/01.wnl.0000208433.34723.65 CrossRefPubMedPubMedCentralGoogle Scholar
  47. Robertson KR, Su Z, Margolis DM, Krambrink A, Havlir DV, Evans S, Skiest DJ, A5170 Study Team (2010) Neurocognitive effects of treatment interruption in stable HIV positive patients in an observational cohort. Neurology 74:1260–1266.  https://doi.org/10.1212/WNL.0b013e3181d9ed09 CrossRefPubMedPubMedCentralGoogle Scholar
  48. Robertson K, Liner J, Meeker RB (2012) Antiretroviral neurotoxicity. J Neuro-Oncol 18:388–399.  https://doi.org/10.1007/s13365-012-0120-3 CrossRefGoogle Scholar
  49. Roosendaal SD, Geurts JJ, Vrenken H, Hulst HE, Cover KS, Castelijns JA, Pouwels PJ, Barkhof F (2009) Regional DTI differences in multiple sclerosis patients. Neuroimage 44:1397–1403.  https://doi.org/10.1016/j.neuroimage.2008.10.026 CrossRefPubMedGoogle Scholar
  50. Rorden C, Karnath HO, Bonilha L (2007) Improving lesion-symptom mapping. J Cogn Neurosci 19:1081–1088.  https://doi.org/10.1162/jocn.2007.19.7.1081 CrossRefPubMedGoogle Scholar
  51. Sarma MK, Nagarajan R, Keller MA, Kumar R, Nielsen-Saines K, Michalik DE, Deville J, Church JA, Thomas MA (2013) Regional brain gray and white matter changes in perinatally HIV-infected adolescents. Neuroimage Clin 4:29–34.  https://doi.org/10.1016/j.nicl.2013.10.012 CrossRefPubMedPubMedCentralGoogle Scholar
  52. Song SK, Sun SW, Ramsbottom MJ, Chang C, Russell J, Cross AH (2002) Dysmyelination revealed through MRI as increased radial (but unchanged axial) diffusion of water. Neuroimage 17:1429–1436.  https://doi.org/10.1006/nimg.2002.1267 CrossRefPubMedGoogle Scholar
  53. Song SK, Yoshino J, Le TQ, Lin SJ, Sun SW, Cross AH, Armstrong RC (2005) Demyelination increases radial diffusivity in corpus callosum of mouse brain. Neuroimage 26:132–140.  https://doi.org/10.1016/j.neuroimage.2005.01.028 CrossRefPubMedGoogle Scholar
  54. Stebbins GT, Smith CA, Bartt RE, Kessler HA, Adeyemi OM, Martin E, Cox JL, Bammer R, Moseley ME (2007) HIV-associated alterations in normal-appearing white matter: a voxel-wise diffusion tensor imaging study. J Acquir Immune Defic Syndr 46:564–573.  https://doi.org/10.1097/QAI.0b013e318159d807 CrossRefPubMedGoogle Scholar
  55. Stubbe-Drger B, Deppe M, Mohammadi S, Keller SS, Kugel H, Gregor N, Evers S, Young P, Ringelstein EB, Arendt G, Knecht S, Husstedt IW, German Competence Network HIV/AIDS (2012) Early microstructural white matter changes in patients with HIV: a diffusion tensor imaging study. BMC Neurol 12:23.  https://doi.org/10.1186/1471-2377-12-23 CrossRefPubMedPubMedCentralGoogle Scholar
  56. Thomason ME, Thompson PM (2011) Diffusion imaging, white matter and psychopathology. Annu Rev Clin Psychol 7:63–85.  https://doi.org/10.1146/annurev-clinpsy-032210-104507 CrossRefPubMedGoogle Scholar
  57. Thurnher MM, Castillo M, Stadler A, Rieger A, Schmid B, Sundgren PC (2005) Diffusion-tensor MR imaging of the brain in human immunodeficiency virus-positive patients. AJNR Am J Neuroradiol 26:2275–2281PubMedGoogle Scholar
  58. Uban KA, Herting MM, Williams PL, Ajmera T, Gautam P, Huo Y, Malee KM, Yogev R, Csernansky JG, Wang L, Nichols SL, Sowell ER, Pediatric HIVAIDS Cohort and the Pediatric Imaging, Neurocognition, and Genetics Studies (2015) White matter microstructure among youth with perinatally acquired HIV is associated with disease severity. AIDS 29:1035–1044.  https://doi.org/10.1097/QAD.0000000000000648 CrossRefPubMedPubMedCentralGoogle Scholar
  59. Wang Y, Wang Q, Haldar JP, Yeh FC, Xie M, Sun P, Tu TW, Trinkaus K, Klein RS, Cross AH, Song SK (2011) Quantification of increased cellularity during inflammatory demyelination. Brain 134:3587–3598.  https://doi.org/10.1093/brain/awr307 CrossRefPubMedCentralGoogle Scholar
  60. Whitehead N, Potterton J, Coovadia A (2014) The neurodevelopment of HIV-infected infants on HAART compared to HIV-exposed but uninfected infants. AIDS Care 26:497–504.  https://doi.org/10.1080/09540121.2013.841828 CrossRefPubMedGoogle Scholar
  61. Winston A, Puls R, Kerr SJ, Duncombe C, Li P, Gill JM, Ramautarsing R, Taylor-Robinson SD, Emery S, Cooper DA, ALTAIR Study Group (2015) Differences in the direction of change of cerebral function parameters are evident over three years in HIV-infected individuals electively commencing initial cART. PLoS One 10:e0118608.  https://doi.org/10.1371/journal.pone.0118608 CrossRefPubMedPubMedCentralGoogle Scholar
  62. Wood SP, Moore DJ, Weber E, Grant I (2009) Cognitive neuropsychology of HIV-associated neurocognitive disorders. Neuropsychol Rev 19:152–168.  https://doi.org/10.1007/s11065-009-9102-5 CrossRefGoogle Scholar
  63. Wozniak JR, Lim KO (2006) Advances in white matter imaging: a review of in vivo magnetic resonance methodologies and their applicability to the study of development and aging. Neurosci Biobehav Rev 30:762–774.  https://doi.org/10.1016/j.neubiorev.2006.06.003 CrossRefPubMedPubMedCentralGoogle Scholar
  64. Wright PW, Heaps JM, Shimony JS, Thomas JB, Ances BM (2012) The effects of HIV and combination antiretroviral therapy on white matter integrity. AIDS 26:1501–1508.  https://doi.org/10.1097/QAD.0b013e3283550bec CrossRefPubMedPubMedCentralGoogle Scholar
  65. Wu Y, Storey P, Cohen BA, Epstein LG, Edelman RR, Ragin AB (2006) Diffusion alterations in corpus callosum of patients with HIV. AJNR Am J Neuroradiol 27:656–660 https://www.fil.ion.ucl.ac.uk/spm/software/spm12/ PubMedPubMedCentralGoogle Scholar

Copyright information

© Journal of NeuroVirology, Inc. 2019

Authors and Affiliations

  • Manoj K. Sarma
    • 1
  • Margaret A. Keller
    • 2
    • 3
  • Paul M. Macey
    • 4
    • 5
  • David E. Michalik
    • 6
  • Judy Hayes
    • 2
  • Karin Nielsen-Saines
    • 7
  • Jaime Deville
    • 7
  • Joseph A. Church
    • 8
  • Irwin Walot
    • 9
  • M. Albert Thomas
    • 1
    Email author return OK on get
  1. 1.Radiological Sciences, David Geffen School of MedicineUCLALos AngelesUSA
  2. 2.Pediatrics, Los Angeles County Harbor-UCLA Medical CenterTorranceUSA
  3. 3.Los Angeles Biomedical Research Institute at Harbor-UCLA Medical CenterTorranceUSA
  4. 4.Brain Research InstituteUCLA School of MedicineLos AngelesUSA
  5. 5.UCLA School of NursingLos AngelesUSA
  6. 6.Infectious Diseases-PediatricsMiller Children’s Hospital of Long BeachLong BeachUSA
  7. 7.Pediatrics, David Geffen School of MedicineUCLALos AngelesUSA
  8. 8.Pediatrics, Keck School of Medicine, Children’s Hospital Los AngelesUniversity of Southern CaliforniaLos AngelesUSA
  9. 9.Radiology, Los Angeles County Harbor-UCLA Medical CenterTorranceUSA

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