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Published on: June 26, 2013
Factor analysis reveals differences in brain metabolism in macaques with SIV/AIDS and those with SIV-induced
Margaret R Lentz1, Vallent Lee, Susan V Westmoreland
1Department of Neuroradiology/A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA 02129, USA.
Abstract:
MRS has often been used to study metabolic processes in the HIV-infected brain. However, it remains unclear how changes in individual metabolites are related to one another in this context of virus-induced central nervous system dysfunction. We used factor analysis (FA) to identify patterns of metabolite distributions from an MRS study of healthy macaques and those infected with simian immunodeficiency virus (SIV) which were moribund with AIDS. FA summarized the correlations from nine metabolites into three main factors. Factor 3 identified patterns that discern healthy animals from those with SIV/AIDS. Factor 2 was able to differentiate between animals that had encephalitis and those moribund with AIDS but lacking encephalitis. Specifically, Factor 2 was able to distinguish animals with moderate to severe encephalitis from animals with mild or no encephalitis as well as uninfected controls. FA not only confirmed the involvement of neuronal metabolites (N-acetylaspartate and glutamate) in disease severity, but also detected changes in creatine and myo-inositol that have not been observed in the SIV macaque model previously. These results suggest that the divergent pathways of N-acetylaspartate and creatine in this disease may enable the commonly reported ratio N-acetylaspartate/creatine to be a more sensitive marker of disease severity.
Insights
Factor analysis of magnetic resonance spectroscopy (MRS) data revealed distinct metabolic patterns in SIV-infected macaques. These patterns help differentiate healthy animals from those with SIV/AIDS and identify disease severity, including encephalitis.
Area of Science:
- Neuroscience
- Metabolic Imaging
- Primate Models
Background:
- Metabolic processes in the HIV-infected brain are studied using Magnetic Resonance Spectroscopy (MRS).
- Understanding inter-metabolite relationships in virus-induced central nervous system dysfunction remains unclear.
Purpose of the Study:
- To identify patterns of metabolite distributions using factor analysis (FA) in healthy and SIV-infected macaques.
- To correlate metabolic changes with disease progression and central nervous system dysfunction.
Main Methods:
- Magnetic Resonance Spectroscopy (MRS) was employed on healthy and SIV-infected macaques.
- Factor Analysis (FA) was used to analyze correlations among nine metabolites.
- Statistical analysis identified key metabolic factors differentiating disease states.
Main Results:
- FA identified three main factors summarizing metabolite correlations.
- Factor 3 distinguished healthy animals from those with SIV/AIDS.
- Factor 2 differentiated animals with encephalitis from those moribund with AIDS but without encephalitis, and identified disease severity.
- Confirmed involvement of N-acetylaspartate and glutamate; detected novel changes in creatine and myo-inositol.
Conclusions:
- Factor analysis provides a robust method for analyzing complex metabolic data in SIV infection.
- Metabolic profiles identified by FA can serve as biomarkers for disease state and severity.
- The N-acetylaspartate/creatine ratio may be a more sensitive marker for disease severity due to divergent metabolic pathways.
