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Structure-specific glial response in a macaque model of neuroAIDS: multivoxel proton magnetic resonance spectroscopic imaging at 3 Tesla

Wu, William E.a; Tal, Assafa; Zhang, Kea; Babb, James S.a; Ratai, Eva-Mariab; González, R. Gilbertob; Gonen, Odeda

doi: 10.1097/01.aids.0000433244.32105.96
Basic Science

Objective: As ∼40% of persons with HIV also suffer neurocognitive decline, we sought to assess metabolic dysfunction in the brains of simian immunodeficiency virus (SIV)-infected rhesus macaques, an advanced animal model, in structures involved in cognitive function. We test the hypothesis that SIV-infection produces proton-magnetic resonance spectroscopic imaging (1H-MRSI)-observed decline in the neuronal marker, N-acetylaspartate (NAA), and elevations in the glial marker, myo-inositol (mI), and associated creatine (Cr) and choline (Cho) in these structures.

Design: Pre- and 4–6 weeks post-SIV infection (with CD8+ T-lymphocyte depletion) was monitored with T2-weighted quantitative MRI and 16 × 16 × 4 multivoxel 1H-MRSI (TE/TR = 33/1400 ms) in the brains of five rhesus macaques.

Methods: Exploiting the high-resolution 1H-MRSI grid, we obtained absolute, cerebrospinal fluid partial volume-corrected NAA, Cr, Cho and mI concentrations from centrum semiovale, caudate nucleus, putamen, thalamus and hippocampus regions.

Results: Pre- to post-infection mean Cr increased in the thalamus: 7.2 ± 0.4 to 8.0 ± 0.8 mmol/l (+11%, P < 0.05); mI increased in the centrum semiovale: 5.1 ± 0.8 to 6.6 ± 0.8 mmol/l, caudate: 5.7 ± 0.7 to 7.3 ± 0.5 mmol/l, thalamus: 6.8 ± 0.8 to 8.5 ± 0.8 mmol/l and hippocampus: 7.7 ± 1.2 to 9.9 ± 0.4 mmol/l (+29%, +27%, +24% and +29%, all P < 0.05). NAA and Cho changes were not significant.

Conclusion: SIV-infection appears to cause brain injury indirectly, through glial activation, while the deep gray matter structures’ neuronal cell bodies are relatively spared. Treatment regimens to reduce gliosis may, therefore, prevent neuronal damage and its associated neurocognitive impairment.

aDepartment of Radiology, New York University School of Medicine, New York, New York

bMassachusetts General Hospital, Athinoula A. Martinos Center for Biomedical Imaging and Neuroradiology Division, Charlestown, Massachusetts, USA.

Correspondence to Oded Gonen, PhD, Department of Radiology, New York University School of Medicine, 660 First Avenue 4-th Floor, New York, New York 10016, USA. Tel: +1 212 263 3532; fax: +1 212 263 7541; e-mail: oded.gonen@med.nyu.edu

Received 5 April, 2013

Revised 25 June, 2013

Accepted 9 July, 2013

© 2013 Lippincott Williams & Wilkins, Inc.