title: Reproducibility of the whole-brain N-acetylaspartate level across institutions, MR scanners, and field strengths.
abstract: OBJECTIVE
  Radiologic markers in multicenter trials are often confounded by different instrumentation used. Our goal was to estimate the variance of the global concentration of the neuronal cell marker N-acetylaspartate (NAA) among research centers using MR imaging scanners of different models, from different manufacturers, and of different magnetic field strength.
  
  
  METHODS
  Absolute millimolar amounts of whole-brain NAA (WBNAA) were quantified with nonlocalizing proton MR spectroscopy in the brains of 101 healthy subjects (53 women, 48 men) aged 16-59 years (mean, 34.2 years). Twenty-three were scanned at 1 institute in a 1.5T Siemens Vision; 31 from another institute were studied with a 1.5T Siemens SP63; 36 were scanned at a third institute (24 with a 1.5T Vision, 12 with a 3T Siemens Trio); and 11 were obtained at a fourth institute using a 4T GE Signa 5.x. The NAA amounts were quantified with phantom-replacement and divided by the brain volume, segmented from MR imaging, to yield the concentration, a metric independent of brain size suitable for cross-sectional comparison.
  
  
  RESULTS
  The average WBNAA concentration among institutions was 12.2 +/- 1.2 mmol/L. The subjects' WBNAA distributions did not differ significantly (p > .237) among the 4 centers, regardless of scanner manufacturer, model, or field strength and irrespective of whether adjustments were made for age or sex.
  
  
  CONCLUSIONS
  Absolute quantification against a standard makes the WBNAA concentration insensitive to the MR hardware used to acquire it. This important attribute renders it a robust surrogate marker for multicenter neurologic trials.
authors.affiliation: Department of Radiology, New York University School of Medicine, New York, New York 10016, USA.
authors.forename: B
authors.initials: B
authors.lastname: Benedetti
authors.forename: D J
authors.initials: DJ
authors.lastname: Rigotti
authors.forename: S
authors.initials: S
authors.lastname: Liu
authors.forename: M
authors.initials: M
authors.lastname: Filippi
authors.forename: R I
authors.initials: RI
authors.lastname: Grossman
authors.forename: O
authors.initials: O
authors.lastname: Gonen
mesh_terms: D000293:Adolescent; D000328:Adult; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000032:analysis; D001921:Brain / Q000473:pathology*; D015331:Cohort Studies; D004867:Equipment Design; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000295:instrumentation*; D009682:Magnetic Resonance Spectroscopy / Q000295:instrumentation*; D008297:Male; D008875:Middle Aged; D012015:Reference Standards; D015203:Reproducibility of Results
chemical_list: D001224:Aspartic Acid; C000179:N-acetylaspartate