Advertisement

Journal of NeuroVirology

, Volume 22, Issue 2, pp 231–239 | Cite as

Longitudinal assessment of fractional anisotropy alterations caused by simian immunodeficiency virus infection: a preliminary diffusion tensor imaging study

  • Zhenchao Tang
  • Enqing DongEmail author
  • Jiaojiao Liu
  • Zhenyu Liu
  • Wenjuan Wei
  • Bo Wang
  • Hongjun LiEmail author
  • Jie TianEmail author
Article

Abstract

Previous diffusion tensor imaging (DTI) studies found that human immunodeficiency virus (HIV) infection led to white matter (WM) microstructure degeneration. Most of the DTI studies were cross-sectional and thus merely investigated only one specific point in the disease. In order to systematically study the WM impairments caused by HIV infection, more longitudinal studies are needed. However, longitudinal studies on HIV patients are very difficult to conduct. To address this question, we employed the simian immunodeficiency virus (SIV)-infected rhesus monkeys model to carry out a longitudinal DTI study. We aimed to longitudinally access the WM abnormalities of SIV-infected rhesus monkeys by studying the fractional anisotropy (FA) alterations with Tract Based Spatial Statistic (TBSS) analysis. Four rhesus monkeys inoculated intravenously with SIVmac239 were utilized in the study. DTI scans and peripheral blood CD4+ and CD8+ T cell counts were acquired prior to virus inoculation (as the baseline) and in the 12th and 24th week postvirus inoculation. Significant FA alterations were found in the two areas of the inferotemporal regions (iTE), respectively located in the ventral subregion of posterior iTE (iTEpv) and the dorsal subregion of iTE (iTEpd). The decreased FA values in iTEpd were found significantly negatively correlated with the elevated peripheral blood CD4+/CD8+ ratios. It might suggest that WM in iTEpd was still impaired even though the immune dysfunction alleviated temporally.

Keywords

Simian immunodeficiency virus Longitudinal study Diffusion tensor imaging Fractional anisotropy Tract-based spatial statistic 

Notes

Acknowledgments

This paper is supported by the National Natural Science Foundation of China under Grant No. 81501549, 81371635, 81571649, 81227901, 61231004, 81171314, and 81571634, the National Basic Research Program of China (973 Program) under Grant 2011CB707700, the Key Research Program of the Chinese Academy of Sciences under Grant No. KGZD-EW-T03, the Natural Science Foundation of Beijing under Grant No. 7132108, the Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support under Grant No. ZYLX201511, and the capital health research and development of special under Grant No. 2011-2018-01. The authors also would like to express their deep appreciation to all anonymous reviewers for their kind comments.

Conflict of interest

The authors declare that they have no conflict of interest. The authors alone are responsible for the content and writing of the paper.

Supplementary material

13365_2015_388_MOESM1_ESM.doc (55 kb)
Table A1 Body temperature and laboratory evaluation values for all the animals. (The serial number of the animals were 130005, 130007, 130010, and 130011. Monkey 130007 died of terminal AIDS in the 13th week) (DOC 55 kb)
13365_2015_388_MOESM2_ESM.doc (260 kb)
Fig. A1 The raw TBSS FA maps of the animals. Red-yellow represents the skeletonized FA maps. (Monkey 130007 died of terminal AIDS in the 13th week) (DOC 259 kb)
13365_2015_388_MOESM3_ESM.doc (50 kb)
Table A2 The Pearson correlation results between the DTI indices and the peripheral blood plasma SIV RNA viral load. (DOC 50 kb)
13365_2015_388_MOESM4_ESM.doc (50 kb)
Table A3 The Pearson correlation results between the DTI indices and the peripheral blood white cell counts. (DOC 50 kb)

References

  1. Anthony IC, Bell JE (2008) The neuropathology of HIV/AIDS. Int Rev Psychiatry 20:15–24CrossRefPubMedGoogle Scholar
  2. Bao R, Zhuang K, Liu J, Wu J, Li J, Wang X, Ho WZ (2014) Lipopolysaccharide induces immune activation and SIV replication in rhesus macaques of Chinese origin. PLoS One 9, e98636CrossRefPubMedPubMedCentralGoogle Scholar
  3. Basser PJ, Mattiello J, LeBihan D (1994) MR diffusion tensor spectroscopy and imaging. Biophys J 66:259–267CrossRefPubMedPubMedCentralGoogle Scholar
  4. Becker JT, Maruca V, Kingsley LA, Sanders JM, Alger JR, Barker PB, Goodkin K, Martin E, Miller EN, Ragin A, Sacktor N, Selnes O, Multicenter ACS (2012) Factors affecting brain structure in men with HIV disease in the post-HAART era. Neuroradiology 54:113–121CrossRefPubMedPubMedCentralGoogle Scholar
  5. Bell JE (1998) The neuropathology of adult HIV infection. Rev Neurol (Paris) 154:816–829Google Scholar
  6. Burudi EM, Fox HS (2001) Simian immunodeficiency virus model of HIV-induced central nervous system dysfunction. Adv Virus Res 56:435–468CrossRefPubMedGoogle Scholar
  7. 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 47:1154–1162CrossRefPubMedPubMedCentralGoogle Scholar
  8. Clifford DB, Ances BM (2013) HIV-associated neurocognitive disorder. Lancet Infect Dis 13:976–986CrossRefPubMedPubMedCentralGoogle Scholar
  9. Correa DG, Zimmermann N, Doring TM, Wilner NV, Leite SC, Cabral RF, Fonseca RP, Bahia PR, Gasparetto EL (2015) Diffusion tensor MR imaging of white matter integrity in HIV-positive patients with planning deficit. NeuroradiologyGoogle Scholar
  10. Ellis R, Langford D, Masliah E (2007) HIV and antiretroviral therapy in the brain: neuronal injury and repair. Nat Rev Neurosci 8:33–44CrossRefPubMedGoogle Scholar
  11. Gelman BB (2015) Neuropathology of HAND with suppressive antiretroviral therapy: encephalitis and neurodegeneration reconsidered. Curr HIV/AIDS Rep 12:272–279CrossRefPubMedPubMedCentralGoogle Scholar
  12. Gold LH, Fox HS, Henriksen SJ, Buchmeier MJ, Weed MR, Taffe MA, Huitron-Resendiz S, Horn TF, Bloom FE (1998) Longitudinal analysis of behavioral, neurophysiological, viral and immunological effects of SIV infection in rhesus monkeys. J Med Primatol 27:104–112CrossRefPubMedGoogle Scholar
  13. Gongvatana A, Schweinsburg BC, Taylor MJ, Theilmann RJ, Letendre SL, Alhassoon OM, Jacobus J, Woods SP, Jernigan TL, Ellis RJ, Frank LR, Grant I, Charter G (2009) White matter tract injury and cognitive impairment in human immunodeficiency virus-infected individuals. J Neurovirol 15:187–195CrossRefPubMedPubMedCentralGoogle Scholar
  14. Gongvatana A, Cohen RA, Correia S, Devlin KN, Miles J, Kang H, Ombao H, Navia B, Laidlaw DH, Tashima KT (2011) Clinical contributors to cerebral white matter integrity in HIV-infected individuals. J Neurovirol 17:477–486CrossRefPubMedPubMedCentralGoogle Scholar
  15. Gosztonyi G, Artigas J, Lamperth L, Webster HD (1994) Human-immunodeficiency-virus (Hiv) distribution in Hiv encephalitis - study of 19 cases with combined Use of in-situ hybridization and immunocytochemistry. J Neuropathol Exp Neurol 53:521–534CrossRefPubMedGoogle Scholar
  16. 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, Group C (2010) HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy: CHARTER study. Neurology 75:2087–2096CrossRefPubMedPubMedCentralGoogle Scholar
  17. 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 Neuropsychiatry Clin Neurosci 23:308–315CrossRefPubMedGoogle Scholar
  18. 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-naive “slow progressors”. J Neurovirol 18:205–212CrossRefPubMedGoogle Scholar
  19. Howell BR, McCormack KM, Grand AP, Sawyer NT, Zhang X, Maestripieri D, Hu X, Sanchez MM (2013) Brain white matter microstructure alterations in adolescent rhesus monkeys exposed to early life stress: associations with high cortisol during infancy. Biol Mood Anxiety Disord 3:21CrossRefPubMedPubMedCentralGoogle Scholar
  20. Howell BR, Godfrey J, Gutman DA, Michopoulos V, Zhang X, Nair G, Hu X, Wilson ME, Sanchez MM (2014) Social subordination stress and serotonin transporter polymorphisms: associations with brain white matter tract integrity and behavior in juvenile female macaques. Cereb Cortex 24:3334–3349CrossRefPubMedPubMedCentralGoogle Scholar
  21. Kravitz DJ, Saleem KS, Baker CI, Mishkin M (2011) A new neural framework for visuospatial processing. Nat Rev Neurosci 12:217–230CrossRefPubMedPubMedCentralGoogle Scholar
  22. Kravitz DJ, Saleem KS, Baker CI, Ungerleider LG, Mishkin M (2013) The ventral visual pathway: an expanded neural framework for the processing of object quality. Trends Cogn Sci 17:26–49CrossRefPubMedPubMedCentralGoogle Scholar
  23. Kuper M, Rabe K, Esser S, Gizewski ER, Husstedt IW, Maschke M, Obermann M (2011) Structural gray and white matter changes in patients with HIV. J Neurol 258:1066–1075CrossRefPubMedGoogle Scholar
  24. Langford TD, Letendre SL, Marcotte TD, Ellis RJ, McCutchan JA, Grant I, Mallory ME, Hansen LA, Archibald S, Jernigan T, Masliah E, Group H (2002) Severe, demyelinating leukoencephalopathy in AIDS patients on antiretroviral therapy. AIDS 16:1019–1029CrossRefPubMedPubMedCentralGoogle Scholar
  25. Leite SC, Correa DG, Doring TM, Kubo TT, Netto TM, Ferracini R, Ventura N, Bahia PR, Gasparetto EL (2013) Diffusion tensor MRI evaluation of the corona radiata, cingulate gyri, and corpus callosum in HIV patients. J Magn Reson Imaging 38:1488–1493CrossRefPubMedGoogle Scholar
  26. Lentz MR, Kim WK, Lee V, Bazner S, Halpern EF, Venna N, Williams K, Rosenberg ES, Gonzalez RG (2009) Changes in MRS neuronal markers and T cell phenotypes observed during early HIV infection. Neurology 72:1465–1472CrossRefPubMedPubMedCentralGoogle Scholar
  27. Li C, Zhang X, Komery A, Li Y, Novembre FJ, Herndon JG (2011) Longitudinal diffusion tensor imaging and perfusion MRI investigation in a macaque model of neuro-AIDS: a preliminary study. Neuroimage 58:286–292CrossRefPubMedPubMedCentralGoogle Scholar
  28. Masters MC, Ances BM (2014) Role of neuroimaging in HIV-associated neurocognitive disorders. Semin Neurol 34:89–102CrossRefPubMedPubMedCentralGoogle Scholar
  29. McLaren DG, Kosmatka KJ, Oakes TR, Kroenke CD, Kohama SG, Matochik JA, Ingram DK, Johnson SC (2009) A population-average MRI-based atlas collection of the rhesus macaque. Neuroimage 45:52–59CrossRefPubMedPubMedCentralGoogle Scholar
  30. Medana IM, Esiri MM (2003) Axonal damage: a key predictor of outcome in human CNS diseases. Brain 126:515–530CrossRefPubMedGoogle Scholar
  31. Murray EA, Rausch DM, Lendvay J, Sharer LR, Eiden LE (1992) Cognitive and motor impairments associated with SIV infection in rhesus monkeys. Science 255:1246–1249CrossRefPubMedGoogle Scholar
  32. Nir TM, Jahanshad N, Busovaca E, Wendelken L, Nicolas K, Thompson PM, Valcour VG (2014) Mapping white matter integrity in elderly people with HIV. Hum Brain Mapp 35:975–992CrossRefPubMedPubMedCentralGoogle Scholar
  33. Ohyama K, Sugase-Miyamoto Y, Matsumoto N, Sato C, Shidara M (2014) Small effect of upcoming reward outcomes on visual cue-related neuronal activity in macaque area TE during conditional associations. Neurosci Res 88:28–38CrossRefPubMedGoogle Scholar
  34. 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 130:48–64CrossRefPubMedGoogle Scholar
  35. Raja F, Sherriff FE, Morris CS, Bridges LR, Esiri MM (1997) Cerebral white matter damage in HIV infection demonstrated using beta-amyloid precursor protein immunoreactivity. Acta Neuropathol 93:184–189CrossRefPubMedGoogle Scholar
  36. Sainz T, Serrano-Villar S, Diaz L, Gonzalez Tome MI, Gurbindo MD, de Jose MI, Mellado MJ, Ramos JT, Zamora J, Moreno S, Munoz-Fernandez MA (2013) The CD4/CD8 ratio as a marker T-cell activation, senescence and activation/exhaustion in treated HIV-infected children and young adults. AIDS 27:1513–1516CrossRefPubMedGoogle Scholar
  37. Saleem KS, Logothetis NK (2012) A combined MRI and histology atlas of the rhesus monkey brain in stereotaxic coordinates. Academic PressGoogle Scholar
  38. Saracino A, Bruno G, Scudeller L, Volpe A, Caricato P, Ladisa N, Monno L, Angarano G (2014) Chronic inflammation in a long-term cohort of HIV-infected patients according to the normalization of the CD4:CD8 ratio. AIDS Res Hum Retroviruses 30:1178–1184CrossRefPubMedGoogle Scholar
  39. Sarma MK, Nagarajan R, Keller MA, Kumar R, Nielsen-Saines K, Michalik DE, Deville J, Church JA, Thomas MA (2014) Regional brain gray and white matter changes in perinatally HIV-infected adolescents. Neuroimage Clin 4:29–34CrossRefPubMedPubMedCentralGoogle Scholar
  40. Schouten J, Cinque P, Gisslen M, Reiss P, Portegies P (2011) HIV-1 infection and cognitive impairment in the cART era: a review. AIDS 25:561–575CrossRefPubMedGoogle Scholar
  41. Serrano-Villar S, Gutierrez C, Vallejo A, Hernandez-Novoa B, Diaz L, Abad Fernandez M, Madrid N, Dronda F, Zamora J, Munoz-Fernandez MA, Moreno S (2013) The CD4/CD8 ratio in HIV-infected subjects is independently associated with T-cell activation despite long-term viral suppression. J Infect 66:57–66CrossRefPubMedGoogle Scholar
  42. Sewards TV (2011a) Adolf Hopf’s 1954 myeloarchitectonic parcellation of the human temporal lobe: a review and assessment. Brain Res Bull 86:298–313CrossRefPubMedGoogle Scholar
  43. Sewards TV (2011b) Neural structures and mechanisms involved in scene recognition: a review and interpretation. Neuropsychologia 49:277–298CrossRefPubMedGoogle Scholar
  44. Smith SM (2002) Fast robust automated brain extraction. Hum Brain Mapp 17:143–155CrossRefPubMedGoogle Scholar
  45. Smith SM, Jenkinson M, Woolrich MW, Beckmann CF, Behrens TE, Johansen-Berg H, Bannister PR, De Luca M, Drobnjak I, Flitney DE, Niazy RK, Saunders J, Vickers J, Zhang Y, De Stefano N, Brady JM, Matthews PM (2004) Advances in functional and structural MR image analysis and implementation as FSL. Neuroimage 23(Suppl 1):S208–S219CrossRefPubMedGoogle Scholar
  46. Smith SM, Jenkinson M, Johansen-Berg H, Rueckert D, Nichols TE, Mackay CE, Watkins KE, Ciccarelli O, Cader MZ, Matthews PM, Behrens TE (2006) Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data. Neuroimage 31:1487–1505CrossRefPubMedGoogle Scholar
  47. 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 HA (2012) Early microstructural white matter changes in patients with HIV: a diffusion tensor imaging study. BMC Neurol 12:23CrossRefPubMedPubMedCentralGoogle Scholar
  48. Sun SW, Liang HF, Trinkaus K, Cross AH, Armstrong RC, Song SK (2006) Noninvasive detection of cuprizone induced axonal damage and demyelination in the mouse corpus callosum. Magn Reson Med 55:302–308CrossRefPubMedGoogle Scholar
  49. Thornhill J, Inshaw J, Oomeer S, Kaleebu P, Cooper D, Ramjee G, Schechter M, Tambussi G, Fox J, Miro JM, Weber J, Babiker A, Porter K, Fidler S (2014) Enhanced normalisation of CD4/CD8 ratio with early antiretroviral therapy in primary HIV infection. J Int AIDS Soc 17:19480CrossRefPubMedPubMedCentralGoogle Scholar
  50. Williams R, Bokhari S, Silverstein P, Pinson D, Kumar A, Buch S (2008) Nonhuman primate models of NeuroAIDS. J Neurovirol 14:292–300CrossRefPubMedPubMedCentralGoogle Scholar
  51. Winkler AM, Ridgway GR, Webster MA, Smith SM, Nichols TE (2014) Permutation inference for the general linear model. Neuroimage 92:381–397CrossRefPubMedPubMedCentralGoogle Scholar
  52. Woolrich MW, Jbabdi S, Patenaude B, Chappell M, Makni S, Behrens T, Beckmann C, Jenkinson M, Smith SM (2009) Bayesian analysis of neuroimaging data in FSL. Neuroimage 45:S173–S186CrossRefPubMedGoogle Scholar
  53. Wright PW, Heaps JM, Shimony JS, Thomas JB, Ances BM (2012) The effects of HIV and combination antiretroviral therapy on white matter integrity. AIDS 26:1501–1508CrossRefPubMedPubMedCentralGoogle Scholar
  54. 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 27:656–660PubMedPubMedCentralGoogle Scholar
  55. Zhu T, Zhong J, Hu R, Tivarus M, Ekholm S, Harezlak J, Ombao H, Navia B, Cohen R, Schifitto G (2013) Patterns of white matter injury in HIV infection after partial immune reconstitution: a DTI tract-based spatial statistics study. J Neurovirol 19:10–23CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Journal of NeuroVirology, Inc. 2015

Authors and Affiliations

  1. 1.School of Mechanical, Electrical & Information EngineeringShandong UniversityWeihaiChina
  2. 2.Beijing YouAn HospitalCapital Medical UniversityBeijingChina
  3. 3.Key Laboratory of Molecular ImagingInstitute of Automation, Chinese Academy of SciencesBeijingChina
  4. 4.School of AutomationHarbin University of Science and TechnologyHarbinChina

Personalised recommendations