Detection of human immunodeficiency virus induced inflammation and oxidative stress in lenticular nuclei with magnetic resonance spectroscopy despite antiretroviral therapy.
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.
Roc
Anne C
AC
Center for Functional Neuroimaging, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA.
Ances
Beau M
BM
Chawla
Sanjeev
S
Korczykowski
Marc
M
Wolf
Ronald L
RL
Kolson
Dennis L
DL
Detre
John A
JA
Poptani
Harish
H
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*
D015415:Biomarkers; D001224:Aspartic Acid; D019344:Lactic Acid; C000179:N-acetylaspartate; D003401:Creatine; D002794:Choline