title: Detection of liquid phase cholesteryl ester in carotid atherosclerosis by 1H-MR spectroscopy in humans.
abstract: OBJECTIVE
  This study hypothesized that (1)H magnetic resonance spectroscopy ((1)H-MRS) can identify carotid plaque cholesteryl ester in vivo in humans.
  
  
  BACKGROUND
  Liquid phase cholesteryl ester comprises a major fraction of atherosclerotic plaque, and its abundance is associated with plaque rupture and atherothrombosis. A noninvasive imaging technique to detect liquid cholesteryl ester that has been applied ex vivo is now demonstrated in vivo.
  
  
  METHODS
  (1)H-MRS scans were obtained of carotid plaques of 35 subjects at 3.0 T. Turbo spin echo, black blood, T1-weighted images were acquired for localization. Spectra were acquired using a 2-dimensional point resolved spectroscopy sequence: repetition time/echo time = 1,100/30 ms, 5-mm slice thickness, 8 × 8-cm field of view, 16 × 16 matrix size, and 13-min acquisition time. Saturation bands were placed around the artery. Resonance of methylene protons and allylic methylene protons were assigned to 1.2 ppm and 2.0 ppm. The 2.0:1.2 ppm ratio was calculated to reflect the ratio of the fatty acid composition of plaque cholesteryl ester to that of triglycerides of perivascular tissue. We obtained spectra of lipid standards as a reference.
  
  
  RESULTS
  Our (1)H-MRS data showed typical spectra of cholesteryl ester mixed with triglycerides, with intense resonance from methylene (1.2 ppm) and allylic methylene (2.0 ppm) protons. The average 2.0:1.2 ppm ratio was 0.10 ± 0.03. The 2.0:1.2 ppm ratio correlated with the plaque tissue volume to perivascular tissue volume ratio (Spearman rho = 0.55, p = 0.02), suggesting that more (1)H-MRS signal was obtained from cholesteryl ester when the (1)H-MRS voxel comprised more plaque tissue. Repeat (1)H-MRS scans in 4 subjects showed an intraclass correlation coefficient of 0.92 (95% prediction intervals: 0.40 to 0.99), indicating good reproducibility. Seventeen of the 35 (1)H-MRS spectra were of adequate quality for analysis.
  
  
  CONCLUSIONS
  In vivo image-guided (1)H-MRS for detection of liquid phase cholesteryl ester in carotid atherosclerotic plaques in humans is feasible.
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Raphaël
authors.initials: R
authors.lastname: Duivenvoorden
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Diederik
authors.initials: D
authors.lastname: van Wijk
authors.affiliation: Merck Research Laboratories, West Point, Pennsylvania.
authors.forename: Michael
authors.initials: M
authors.lastname: Klimas
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: John J P
authors.initials: JJ
authors.lastname: Kastelein
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Erik S G
authors.initials: ES
authors.lastname: Stroes
authors.affiliation: Department of Radiology, Academic Medical Center, Amsterdam, the Netherlands. Electronic address: a.j.nederveen@amc.uva.nl.
authors.forename: Aart J
authors.initials: AJ
authors.lastname: Nederveen
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000032:analysis; D002339:Carotid Arteries / Q000737:chemistry* / Q000473:pathology; D002340:Carotid Artery Diseases / Q000175:diagnosis* / Q000378:metabolism; D002788:Cholesterol Esters / Q000032:analysis*; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D058226:Plaque, Atherosclerotic; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D014280:Triglycerides / Q000032:analysis
chemical_list: D015415:Biomarkers; D002788:Cholesterol Esters; D014280:Triglycerides
keywords: (1)H magnetic resonance spectroscopy; (1)H-MRS; MRI; TE; TR; atherosclerosis; cholesterol; echo time; magnetic resonance imaging; magnetic resonance spectroscopy; repetition time