title: Detection of coronary atherosclerotic plaques with superficial proteoglycans and foam cells using real-time intrinsic fluorescence spectroscopy.
abstract: OBJECTIVE
  The protein components of low-density lipoprotein (LDL), oxidized LDL and proteoglycans such as versican contain tryptophan, an amino acid with characteristic fluorescence features at 308 nm excitation wavelength. We hypothesize that intrinsic fluorescence spectroscopy at 308 nm excitation wavelength IFS308, a method suitable for clinical use, can identify coronary artery lesions with superficial foam cells (SFCs) and/or proteoglycans.
  
  
  METHODS
  We subjected 119 human coronary artery specimens to in vitro fluorescence and reflectance spectroscopy. We used 5 basis spectra to model IFS308, and extracted their contributions to each individual IFS308 spectrum. A diagnostic algorithm using the contributions of Total Tryptophan and fibrous cap to IFS308 was built to identify specimens with SFCs and/or proteoglycans in their top 50 μm.
  
  
  RESULTS
  We detected SFCs and/or proteoglycans, such as versican or the glycosaminoglycan hyaluronan, in 24 fibrous cap atheromas or pathologic intimal thickening (PIT) lesions. An algorithm using the contributions of Total Tryptophan and fibrous cap to IFS308 was able to identify these segments with 92% sensitivity and 80% specificity.
  
  
  CONCLUSIONS
  We were able to establish a set of characteristic LDL, oxidized LDL, versican and hyaluronan fluorescence spectra, ready to be used for real-time diagnosis. The IFS(308) technique detects SFCs and/or proteoglycans in fibrous cap atheromas and PIT lesions. SFCs and proteoglycans are histological markers of vulnerable plaques, and this study is a step further in developing an invasive clinical tool to detect the vulnerable atherosclerotic plaque.
authors.affiliation: G. R. Harrison Spectroscopy Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. goangheloiu@drmc.org
authors.forename: George O
authors.initials: GO
authors.lastname: Angheloiu
authors.forename: Abigail S
authors.initials: AS
authors.lastname: Haka
authors.forename: Irene
authors.initials: I
authors.lastname: Georgakoudi
authors.forename: Joseph
authors.initials: J
authors.lastname: Arendt
authors.forename: Markus G
authors.initials: MG
authors.lastname: Müller
authors.forename: Obrad R
authors.initials: OR
authors.lastname: Scepanovic
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Evanko
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Wight
authors.forename: Prasun
authors.initials: P
authors.lastname: Mukherjee
authors.forename: David H
authors.initials: DH
authors.lastname: Waldeck
authors.forename: Ramachandra R
authors.initials: RR
authors.lastname: Dasari
authors.forename: Maryann
authors.initials: M
authors.lastname: Fitzmaurice
authors.forename: John R
authors.initials: JR
authors.lastname: Kramer
authors.forename: Michael S
authors.initials: MS
authors.lastname: Feld
mesh_terms: D000465:Algorithms; D005260:Female; D005487:Foam Cells / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D006820:Hyaluronic Acid / Q000032:analysis; D008077:Lipoproteins, LDL / Q000032:analysis; D008297:Male; D008875:Middle Aged; D058226:Plaque, Atherosclerotic / Q000737:chemistry* / Q000473:pathology; D011509:Proteoglycans / Q000032:analysis* / Q000378:metabolism; D013050:Spectrometry, Fluorescence / Q000379:methods*; D014364:Tryptophan / Q000032:analysis / Q000737:chemistry*; D053675:Versicans / Q000032:analysis
chemical_list: D008077:Lipoproteins, LDL; D011509:Proteoglycans; C099252:oxidized low density lipoprotein; D053675:Versicans; D014364:Tryptophan; D006820:Hyaluronic Acid