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Detection of Human Immunodeficiency Virus–Induced Inflammation and Oxidative Stress in Lenticular Nuclei With Magnetic Resonance Spectroscopy Despite Antiretroviral Therapy
Anne C. Roc, PhD;
Beau M. Ances, MD, PhD;
Sanjeev Chawla, PhD;
Marc Korczykowski, MS;
Ronald L. Wolf, MD;
Dennis L. Kolson, MD, PhD;
John A. Detre, MD;
Harish Poptani, PhD
Arch Neurol. 2007;64:(doi:10.1001/archneur.64.9.noc60125).
Background Single-voxel magnetic resonance spectroscopy measurements of N-acetyl aspartate, choline, and creatine (Cr) are affected in patients with human immunodeficiency virus (HIV) and neurocognitive impairment. However, these metabolic markers are often normalized in affected central nervous system regions, such as the lenticular nuclei, after initiation of highly active antiretroviral therapy (HAART).
Objective To examine whether lactate (Lac), a marker of inflammation and anaerobic glycolysis, and lipid, an indicator of cell membrane turnover resulting from oxidative stress, could serve as surrogate biomarkers within the lenticular nuclei of HIV-positive patients with different degrees of neurocognitive impairment.
Design Three-tesla 2-dimensional–chemical shift imaging magnetic resonance spectroscopy at echo times of 30 milliseconds and 135 milliseconds was performed in voxels overlapping the lenticular nuclei of seronegative controls and a spectrum of HIV-positive patients (neurocognitively normal, mildly impaired, or moderately to severely impaired).
Setting University of Pennsylvania, Philadelphia.
Participants Ten seronegative controls and 45 HIV-positive patients with different degrees of neurocognitive impairment (15 neurocognitively normal patients, 12 mildly impaired patients, and 18 moderately to severely impaired patients).
Main Outcome Measures In vivo 2-dimensional–chemical shift imaging magnetic resonance spectroscopy analysis of N-acetyl aspartate:Cr, choline:Cr, Lac:Cr, and (lipid + Lac):Cr ratios among the various groups. In addition, the effect of the degree of HAART central nervous system penetration (high vs low) on these ratios was studied.
Results No significant lenticular nuclei atrophy was detected with volumes similar across all of the groups. Both N-acetyl aspartate:Cr and choline:Cr ratios were similar across all of the groups at either echo time. In contrast, the Lac:Cr ratio was significantly greater in HIV-positive patients with moderate to severe impairment compared with seronegative controls. The (lipid + Lac):Cr ratio was significantly elevated within each HIV-positive subgroup compared with seronegative controls. Within HIV-positive patients receiving HAART, the degree of central nervous system penetration (high vs low) did not affect metabolic ratios.
Conclusions As seen with 2-dimensional–chemical shift imaging magnetic resonance spectroscopy, HIV induces inflammation and oxidative stress in HIV-positive patients despite HAART. Lipid and Lac are more sensitive inflammatory biomarkers that may be used to differentiate HIV-positive subgroups. However, no significant difference in efficacy, as measured by metabolic ratios, exists for high– vs low–central nervous system–penetrating HAART.
Author Affiliations: Center for Functional Neuroimaging (Drs Roc and Detre and Mr Korczykowski) and Departments of Radiology (Drs Chawla, Wolf, Detre, and Poptani) and Neurology (Drs Kolson and Detre), Hospital of the University of Pennsylvania, Philadelphia; and Departments of Neuroscience and Radiology, University of California, San Diego (Dr Ances).
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New Techniques for Imaging Human Immunodeficiency Virus–Associated Cognitive Impairment in the Era of Highly Active Antiretroviral Therapy
Martin G. Pomper and Ned Sacktor
Arch Neurol. 2007;64(9):1233-1235.
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New Techniques for Imaging Human Immunodeficiency Virus Associated Cognitive Impairment in the Era of Highly Active Antiretroviral Therapy
Pomper and Sacktor
Arch Neurol 2007;64:1233-1235.
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