Skip to main content

Advertisement

SpringerLink
Log in

Quantitative Diffusion Tensor Imaging Tractography Metrics are Associated with Cognitive Performance Among HIV-Infected Patients

  • Published:
Brain Imaging and Behavior Aims and scope Submit manuscript

Abstract

There have been many studies examining HIV-infection-related alterations of magnetic resonance imaging (MRI) diffusion metrics. However, examining scalar diffusion metrics ignores the orientation aspect of diffusion imaging, which can be captured with tractography. We examined five different tractography metrics obtained from global tractography maps (global tractography FA, average tube length, normalized number of streamtubes, normalized weighted streamtube length, and normalized total number of tubes generated) for differences between HIV positive and negative patients and the association between the metrics and clinical variables of disease severity. We also examined the relationship between these metrics and cognitive performance across a wide range of cognitive domains for the HIV positive and negative patient groups separately. The results demonstrated a significant difference between the groups for global tractography FA (t = 2.13, p = 0.04), but not for any of the other tractography metrics examined (p-value range = 0.39 to 0.95). There were also several significant associations between the tractography metrics and cognitive performance (i.e., tapping rates, switching 1 and 2, verbal interference, mazes; r ≥ 0.42) for HIV infected patients. In particular, associations were noted between tractography metrics, speed of processing, fine motor control/speed, and executive function for the HIV-infected patients. These findings suggest that tractography metrics capture clinically relevant information regarding cognitive performance among HIV infected patients and suggests the importance of subtle white matter changes in examining cognitive performance.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • An, S. F., Ciardi, A., Giometto, B., Scaravilli, T., Gray, F., & Scaravilli, F. (1996). Investigation on the expression of major histocompatibility complex class II and cytokines and detection of HIV-1 DNA within brains of asymptomatic and symptomatic HIV-1-positive patients. Acta Neuropathologica, 91(5), 494–503.

    Article  CAS  PubMed  Google Scholar 

  • Assaf, Y., & Pasternak, O. (2008). Diffusion tensor imaging (DTI)-based white matter mapping in brain research: a review. J Mol Neurosci, 34(1), 51–61.

    Article  CAS  PubMed  Google Scholar 

  • Bell, J. E. (2004). An update on the neuropathology of HIV in the HAART era. Histopathology, 45(6), 549–559.

    Article  CAS  PubMed  Google Scholar 

  • Budka, H., Costanzi, G., Cristina, S., Lechi, A., Parravicini, C., Trabattoni, R., et al. (1987). Brain pathology induced by infection with the human immunodeficiency virus (HIV). A histological, immunocytochemical, and electron microscopical study of 100 autopsy cases. Acta Neuropathologica, 75(2), 185–198.

    Article  CAS  PubMed  Google Scholar 

  • Cherner, M., Cysique, L., Heaton, R. K., Marcotte, T. D., Ellis, R. J., Masliah, E., et al. (2007). Neuropathologic confirmation of definitional criteria for human immunodeficiency virus-associated neurocognitive disorders. J Neurovirol, 13(1), 23–28.

    Article  PubMed  Google Scholar 

  • Cherner, M., Letendre, S., Heaton, R. K., Durelle, J., Marquie-Beck, J., Gragg, B., et al. (2005). Hepatitis C augments cognitive deficits associated with HIV infection and methamphetamine. Neurology, 64(8), 1343–1347.

    CAS  PubMed  Google Scholar 

  • Correia, S., Lee, S. Y., Voorn, T., Tate, D. F., Paul, R. H., Zhang, S., et al. (2008). Quantitative tractography metrics of white matter integrity in diffusion-tensor MRI. Neuroimage, 42(2), 568–581.

    Article  PubMed  Google Scholar 

  • Cossarizza, A. (2008). Apoptosis and HIV infection: about molecules and genes. Current Pharmaceutical Design, 14(3), 237–244.

    Article  CAS  PubMed  Google Scholar 

  • Cysique, L. A., Maruff, P., & Brew, B. J. (2006). The neuropsychological profile of symptomatic AIDS and ADC patients in the pre-HAART era: a meta-analysis. Journal of the International Neuropsychological Society, 12(3), 368–382.

    Article  PubMed  Google Scholar 

  • Davis, L. E., Hjelle, B. L., Miller, V. E., Palmer, D. L., Llewellyn, A. L., Merlin, T. L., et al. (1992). Early viral brain invasion in iatrogenic human immunodeficiency virus infection. Neurology, 42(9), 1736–1739.

    CAS  PubMed  Google Scholar 

  • DeBoy, C. A., Zhang, J., Dike, S., Shats, I., Jones, M., Reich, D. S., et al. (2007). High resolution diffusion tensor imaging of axonal damage in focal inflammatory and demyelinating lesions in rat spinal cord. Brain, 130(Pt 8), 2199–2210.

    Article  PubMed  Google Scholar 

  • Dewhurst, S., Gelbard, H. A., & Fine, S. M. (1996). Neuropathogenesis of AIDS. Molecular Medicine Today, 2(1), 16–23.

    Article  CAS  PubMed  Google Scholar 

  • Ding, X. Q., Sun, Y., Braabeta, H., Illies, T., Zeumer, H., Lanfermann, H., et al. (2008). Evidence of Rapid Ongoing Brain Development Beyond Two Years of Age Detected by Fiber Tracking. AJNR. American Journal of Neuroradiology, 29(7), 1261–1265.

    Google Scholar 

  • Dubois, J., Dehaene-Lambertz, G., Soares, C., Cointepas, Y., Le Bihan, D., & Hertz-Pannier, L. (2008). Microstructural correlates of infant functional development: example of the visual pathways. J Neurosci, 28(8), 1943–1948.

    Article  CAS  PubMed  Google Scholar 

  • Everall, I. P., Hansen, L. A., & Masliah, E. (2005). The shifting patterns of HIV encephalitis neuropathology. Neurotoxicity Research, 8(1–2), 51–61.

    Article  CAS  PubMed  Google Scholar 

  • Everall, I. P., Luthert, P. J., & Lantos, P. L. (1993). Neuronal number and volume alterations in the neocortex of HIV infected individuals. Journal of Neurology, Neurosurgery and Psychiatry, 56(5), 481–486.

    Article  CAS  Google Scholar 

  • Ferrarese, C., Aliprandi, A., Tremolizzo, L., Stanzani, L., De Micheli, A., Dolara, A., et al. (2001). Increased glutamate in CSF and plasma of patients with HIV dementia. Neurology, 57(4), 671–675.

    CAS  PubMed  Google Scholar 

  • Filippi, C. G., Ulug, A. M., Ryan, E., Ferrando, S. J., & van Gorp, W. (2001). Diffusion tensor imaging of patients with HIV and normal-appearing white matter on MR images of the brain. AJNR. American Journal of Neuroradiology, 22(2), 277–283.

    CAS  PubMed  Google Scholar 

  • Gilmore, J. H., Lin, W., Corouge, I., Vetsa, Y. S., Smith, J. K., Kang, C., et al. (2007). Early Postnatal Development of Corpus Callosum and Corticospinal White Matter Assessed with Quantitative Tractography. AJNR. American Journal of Neuroradiology, 28(9), 1789–1795.

    Google Scholar 

  • Gray, F., Lescs, M. C., Keohane, C., Paraire, F., Marc, B., Durigon, M., et al. (1992). Early brain changes in HIV infection: neuropathological study of 11 HIV seropositive, non-AIDS cases. Journal of Neuropathology and Experimental Neurology, 51(2), 177–185.

    Article  CAS  PubMed  Google Scholar 

  • Haughey, N. J., Nath, A., Mattson, M. P., Slevin, J. T., & Geiger, J. D. (2001). HIV-1 Tat through phosphorylation of NMDA receptors potentiates glutamate excitotoxicity. Journal of Neurochemistry, 78(3), 457–467.

    Article  CAS  PubMed  Google Scholar 

  • Haverkos, H. W. (1998). HIV/AIDS and drug abuse: epidemiology and prevention. Journal of Addictive Diseases, 17(4), 91–103.

    Article  CAS  PubMed  Google Scholar 

  • Heaton, R. K., Marcotte, T. D., Mindt, M. R., Sadek, J., Moore, D. J., Bentley, H., et al. (2004a). The impact of HIV-associated neuropsychological impairment on everyday functioning. Journal of the International Neuropsychological Society, 10(3), 317–331.

    Article  Google Scholar 

  • Heaton, R. K., Walden, M., Taylor, M. J., & Grant, I. (2004b). Revised comprehensive norms for an expanded Halstead-Reitan battery: demographically adjusted neuropsychological norms for African Americans and Caucasian Adults. Lutz: Psychological Assessment Resources, Inc.

    Google Scholar 

  • Hilsabeck, R. C., Castellon, S. A., & Hinkin, C. H. (2005). Neuropsychological aspects of coinfection with HIV and hepatitis C virus. Clinical Infectious Diseases, 41(Suppl 1), S38–44.

    Article  PubMed  Google Scholar 

  • Kellogg, S., McHugh, P., Bell, K., Schluger, J., Schluger, R., LaForge, K., et al. (2003). The Kreek–McHugh–Schluger–Kellog scale: a new, rapid method for quantifying substance abuse and its possible applications. Drug and Alcohol Dependence, 69(2), 137–150.

    Article  PubMed  Google Scholar 

  • Kim, A. Y., & Lauer, G. M. (2007). Pathogenesis of HIV-HCV Coinfection. Current Infectious Disease Reports, 9(4), 331–337.

    Article  PubMed  Google Scholar 

  • Lin, W., Weinberg, E. M., Tai, A. W., Peng, L. F., Brockman, M. A., Kim, K. A., et al. (2008). HIV increases HCV replication in a TGF-beta1-dependent manner. Gastroenterology, 134(3), 803–811.

    Article  CAS  PubMed  Google Scholar 

  • Lipton, S. A. (1991). HIV-related neurotoxicity. Brain Pathology, 1(3), 193–199.

    Article  CAS  PubMed  Google Scholar 

  • Louboutin, J. P., Agrawal, L., Reyes, B. A., Van Bockstaele, E. J., & Strayer, D. S. (2007). Protecting neurons from HIV-1 gp120-induced oxidant stress using both localized intracerebral and generalized intraventricular administration of antioxidant enzymes delivered by SV40-derived vectors. Gene Therapy, 14(23), 1650–1661.

    Article  CAS  PubMed  Google Scholar 

  • Masliah, E., Heaton, R. K., Marcotte, T. D., Ellis, R. J., Wiley, C. A., Mallory, M., et al. (1997). Dendritic injury is a pathological substrate for human immunodeficiency virus-related cognitive disorders. HNRC Group. The HIV Neurobehavioral Research Center. Annals of Neurology, 42(6), 963–972.

    Article  CAS  PubMed  Google Scholar 

  • McArthur, J. C., McDermott, M. P., McClernon, D., St Hillaire, C., Conant, K., Marder, K., et al. (2004). Attenuated central nervous system infection in advanced HIV/AIDS with combination antiretroviral therapy. Archives of Neurology, 61(11), 1687–1696.

    Article  PubMed  Google Scholar 

  • Paul, R. H., Lawrence, J., Williams, L. M., Richard, C. C., Cooper, N., & Gordon, E. (2005). Preliminary validity of “integneuro”: a new computerized battery of neurocognitive tests. International Journal of Neuroscience, 115(11), 1549–1567.

    Article  PubMed  Google Scholar 

  • Perry, W., Hilsabeck, R., & Hassanein, T. (2008). Cognitive dysfunction in chronic hepatitis C: a reviewq. Digestive Diseases and Sciences, 53, 307–321.

    Article  PubMed  Google Scholar 

  • Pfefferbaum, A., Rosenbloom, M. J., Adalsteinsson, E., & Sullivan, E. V. (2007). Diffusion tensor imaging with quantitative fibre tracking in HIV infection and alcoholism comorbidity: synergistic white matter damage. Brain, 130(Pt 1), 48–64.

    PubMed  Google Scholar 

  • Pomara, N., Crandall, D. T., Choi, S. J., Johnson, G., & Lim, K. O. (2001). White matter abnormalities in HIV-1 infection: a diffusion tensor imaging study. Psychiatry Research, 106(1), 15–24.

    Article  CAS  PubMed  Google Scholar 

  • Power, C., Kong, P. A., Crawford, T. O., Wesselingh, S., Glass, J. D., McArthur, J. C., et al. (1993). Cerebral white matter changes in acquired immunodeficiency syndrome dementia: alterations of the blood-brain barrier. Annals of Neurology, 34(3), 339–350.

    Article  CAS  PubMed  Google Scholar 

  • Ragin, A. B., Storey, P., Cohen, B. A., Edelman, R. R., & Epstein, L. G. (2004). Disease burden in HIV-associated cognitive impairment: a study of whole brain imaging measures. Neurology, 63(12), 2293–2297.

    CAS  PubMed  Google Scholar 

  • Ragin, A. B., Wu, Y., Storey, P., Cohen, B. A., Edelman, R. R., & Epstein, L. G. (2005). Diffusion tensor imaging of subcortical brain injury in patients infected with human immunodeficiency virus. Journal of Neurovirology, 11(3), 292–298.

    Article  PubMed  Google Scholar 

  • Samet, J. H., Walley, A. Y., & Bridden, C. (2007). Illicit drugs, alcohol, and addiction in human immunodeficiency virus. Panminerva Medica, 49(2), 67–77.

    CAS  PubMed  Google Scholar 

  • Schlosser, R. G., Nenadic, I., Wagner, G., Gullmar, D., von Consbruch, K., Kohler, S., et al. (2007). White matter abnormalities and brain activation in schizophrenia: a combined DTI and fMRI study. Schizophrenia Research, 89(1–3), 1–11.

    Article  PubMed  Google Scholar 

  • Schmierer, K., Wheeler-Kingshott, C. A., Boulby, P. A., Scaravilli, F., Altmann, D. R., Barker, G. J., et al. (2007). Diffusion tensor imaging of post mortem multiple sclerosis brain. Neuroimage, 35(2), 467–477.

    Article  PubMed  Google Scholar 

  • Silverstein, S. M., Berten, S., Olson, P., Paul, R., Willams, L. M., Cooper, N., et al. (2007). Development and validation of a World-Wide-Web-based neurocognitive assessment battery: WebNeuro. Behavior Research Methods, 39(4), 940–949.

    PubMed  Google Scholar 

  • Skranes, J., Vangberg, T. R., Kulseng, S., Indredavik, M. S., Evensen, K. A., Martinussen, M., et al. (2007). Clinical findings and white matter abnormalities seen on diffusion tensor imaging in adolescents with very low birth weight. Brain, 130(Pt 3), 654–666.

    Article  CAS  PubMed  Google Scholar 

  • Smit, C., van den Berg, C., Geskus, R., Berkhout, B., Coutinho, R., & Prins, M. (2008). Risk of hepatitis-related mortality increased among hepatitis C virus/HIV-coinfected drug users compared with drug users infected only with hepatitis C virus: a 20-year prospective study. Journal of Acquired Immune Deficiency Syndromes, 47(2), 221–225.

    Article  PubMed  Google Scholar 

  • Sulkowski, M. S., Mehta, S. H., Torbenson, M. S., Higgins, Y., Brinkley, S. C., de Oca, R. M., et al. (2007). Rapid fibrosis progression among HIV/hepatitis C virus-co-infected adults. AIDS, 21(16), 2209–2216.

    Article  PubMed  Google Scholar 

  • von Giesen, H. J., Heintges, T., Abbasi-Boroudjeni, N., Kucukkoylu, S., Koller, H., Haslinger, B. A., et al. (2004). Psychomotor slowing in hepatitis C and HIV infection. J Acquir Immune Defic Syndr, 35(2), 131–137.

    Article  Google Scholar 

  • Wilde, E. A., McCauley, S. R., Hunter, J. V., Bigler, E. D., Chu, Z., Wang, Z. J., et al. (2008). Diffusion tensor imaging of acute mild traumatic brain injury in adolescents. Neurology, 70(12), 948–955.

    Article  CAS  PubMed  Google Scholar 

  • Zhang, S., Demiralp, C., & Laidlaw, D. (2003). Visualizing diffusion tensor MR images using streamtubes and streamsurfaces. IEEE Transactions on Visualization and Computer Graphics, 9(4), 454–462.

    Article  Google Scholar 

Download references

Acknowledgements

This manuscript was supported in part by the following grants: K23-MH073416 (DFT), K23-MH065857 (RP), and P30-AG013846 (DFT).

Author information

Authors and Affiliations

  1. Departments of Radiology and Psychiatry, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    David F. Tate & Jared Conley

  2. Department of Neurology, Boston University Medical Center Alzheimer’s Disease Center, Boston University Medical School, Boston, MA, USA

    David F. Tate

  3. Department of Psychology, University of Missouri at St. Louis, St. Louis, MO, USA

    Robert H. Paul

  4. Center for AIDS Research, The Miriam Hospital, Providence, RI, USA

    Kathryn Coop, Lynn E. Taylor, Timothy Flanigan & Karen Tashima

  5. Department of Computer Science and Engineering, Mississippi State University, Starkville, MS, USA

    Song Zhang

  6. Department of Computer Science, Brown University, Providence, RI, USA

    Wenjin Zhou & David H. Laidlaw

  7. Department of Medicine, The Warren Alpert Medical School at Brown University, Providence, RI, USA

    Lynn E. Taylor, Timothy Flanigan & Karen Tashima

  8. Department of Medicine, Tufts New England Medical Center, Boston, MA, USA

    Bradford Navia

  9. Department of Psychiatry and Behavioral Medicine, The Warren Alpert School of Medicine at Brown University, Providence, RI, USA

    Ronald Cohen

Authors
  1. David F. Tate
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jared Conley
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Robert H. Paul
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kathryn Coop
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Song Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Wenjin Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. David H. Laidlaw
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Lynn E. Taylor
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Timothy Flanigan
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Bradford Navia
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Ronald Cohen
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Karen Tashima
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to David F. Tate.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tate, D.F., Conley, J., Paul, R.H. et al. Quantitative Diffusion Tensor Imaging Tractography Metrics are Associated with Cognitive Performance Among HIV-Infected Patients. Brain Imaging and Behavior 4, 68–79 (2010). https://doi.org/10.1007/s11682-009-9086-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11682-009-9086-z

Keywords

Search

Navigation