title: Detection of human immunodeficiency virus induced inflammation and oxidative stress in lenticular nuclei with magnetic resonance spectroscopy despite antiretroviral therapy.
abstract: 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.
  
  
  METHODS
  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).
  
  
  METHODS
  University of Pennsylvania, Philadelphia.
  
  
  METHODS
  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).
  
  
  METHODS
  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.
authors.affiliation: Center for Functional Neuroimaging, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Anne C
authors.initials: AC
authors.lastname: Roc
authors.forename: Beau M
authors.initials: BM
authors.lastname: Ances
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Chawla
authors.forename: Marc
authors.initials: M
authors.lastname: Korczykowski
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Wolf
authors.forename: Dennis L
authors.initials: DL
authors.lastname: Kolson
authors.forename: John A
authors.initials: JA
authors.lastname: Detre
authors.forename: Harish
authors.initials: H
authors.lastname: Poptani
mesh_terms: D015526:AIDS Dementia Complex / Q000378:metabolism / Q000473:pathology; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001284:Atrophy; D015415:Biomarkers; D002794:Choline / Q000378:metabolism; D003342:Corpus Striatum / Q000473:pathology*; D003401:Creatine / Q000378:metabolism; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D019344:Lactic Acid / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009483:Neuropsychological Tests; D018384:Oxidative Stress / Q000502:physiology*
chemical_list: D015415:Biomarkers; D001224:Aspartic Acid; D019344:Lactic Acid; C000179:N-acetylaspartate; D003401:Creatine; D002794:Choline