title: A prospective longitudinal in vivo 1H MR spectroscopy study of the SIV/macaque model of neuroAIDS.
abstract: BACKGROUND
  The neurological complications of HIV infection remain poorly understood. Clinically, in vivo 1H magnetic resonance spectroscopy (MRS) demonstrates brain injury caused by HIV infection even when the MRI is normal. Our goal was to undertsand the dynamics of cerebral injury by performing a longitudinal in vivo 1H MRS study of the SIV/macaque model of neuroAIDS.
  
  
  RESULTS
  Eight rhesus macaques were infected with SIVmac251 and serially imaged with MRI and 1H MRS to terminal AIDS or the endpoint of 2 years. During acute infection, there were stereotypical brain MRS changes, dominated by a significant elevation of the Cho/Cr ratio in the frontal cortex. Subsequently, brain metabolic patterns diverged between animals. There was an elevation of basal ganglia Cho/Cr four weeks post-inoculation in 2 animals that developed SIV encephalitis (p = 0.022). Metabolite ratios averaged across all 8 animals were not significantly different from baseline at any time point after 2 weeks post inoculation. However, linear regression analysis on all 8 animals revealed a positive correlation between a change in frontal lobe Cho/Cr and plasma viral load (P < 0.001, R = 0.80), and a negative correlation between NAA/Cr in the basal ganglia and the plasma viral load (P < 0.02, R = -0.73). No MRI abnormalities were detected at any time.
  
  
  CONCLUSIONS
  After infection with SIV, macaque brain metabolism changes in a complex manner that is dependent on brain region, host factors and viral load. An elevation of basal ganglia Cho/Cr 4 weeks after SIV infection may be marker of a propensity to develop SIV encephalitis. Elevations of Cho/Cr, often observed in CNS inflammation, were associated with increased plasma viral load during acute and chronic infection. Evidence of neuronal injury in the basal ganglia was associated with increased plasma viral load in the chronic stage of infection. These observations support the use of drugs capable of controlling the viral replication and trafficking of virus into the CNS, and may help explain the reduction in incidence of HIV-associated dementia in the era of HAART despite the inability of most of those drugs to effectively enter the CNS.
authors.affiliation: Massachusetts General Hospital NMR Center and Neuroradiology Division, Harvard Medical School, Charlestown, MA, USA. fullerra@umdnj.edu
authors.forename: Robert A
authors.initials: RA
authors.lastname: Fuller
authors.forename: Susan V
authors.initials: SV
authors.lastname: Westmoreland
authors.forename: Eva
authors.initials: E
authors.lastname: Ratai
authors.forename: Jane B
authors.initials: JB
authors.lastname: Greco
authors.forename: John P
authors.initials: JP
authors.lastname: Kim
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Lentz
authors.forename: Julian
authors.initials: J
authors.lastname: He
authors.forename: Prabhat K
authors.initials: PK
authors.lastname: Sehgal
authors.forename: Eliezer
authors.initials: E
authors.lastname: Masliah
authors.forename: Elkan
authors.initials: E
authors.lastname: Halpern
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Lackner
authors.forename: R Gilberto
authors.initials: RG
authors.lastname: González
mesh_terms: D015526:AIDS Dementia Complex / Q000150:complications / Q000175:diagnosis* / Q000473:pathology; D000208:Acute Disease; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002794:Choline / Q000097:blood / Q000378:metabolism; D002908:Chronic Disease; D003401:Creatine / Q000097:blood / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D007294:Inositol / Q000097:blood / Q000378:metabolism; D008137:Longitudinal Studies; D008253:Macaca mulatta; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D011237:Predictive Value of Tests; D011446:Prospective Studies; D016097:Simian Acquired Immunodeficiency Syndrome / Q000150:complications / Q000378:metabolism* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000472:pathogenicity*; D015996:Survival Rate; D019562:Viral Load
chemical_list: D001224:Aspartic Acid; D007294:Inositol; C000179:N-acetylaspartate; D003401:Creatine; D002794:Choline