title: In vivo detection of macrophages in a rabbit atherosclerotic model by time-resolved laser-induced fluorescence spectroscopy.
abstract: Accumulation of numerous macrophages in the fibrous cap is a key identifying feature of plaque inflammation and vulnerability. This study investigates the use of time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) as a potential tool for detection of macrophage foam cells in the intima of atherosclerotic plaques. Experiments were conducted in vivo on 14 New Zealand rabbits (6 control, 8 hypercholesterolemic) following aortotomy to expose the intimal luminal surface of the aorta. Tissue autofluorescence was induced with a nitrogen pulse laser (337 nm, 1 ns). Lesions were histologically classified by the percent of collagen or macrophage foam cells as well as thickness of the intima. Using parameters derived from the time-resolved fluorescence emission of plaques, we determined that intima rich in macrophage foam cells can be distinguished from intima rich in collagen with high sensitivity (>85%) and specificity (>95%). This study demonstrates, for the first time, that a time-resolved fluorescence-based technique can differentiate and demark macrophage content versus collagen content in vivo. Our results suggest that TR-LIFS technique can be used in clinical applications for identification of inflammatory cells important in plaque formation and rupture.
authors.affiliation: Biophotonics Research & Technology Development, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. lmarcu@bmsrs.usc.edu
authors.forename: Laura
authors.initials: L
authors.lastname: Marcu
authors.forename: Qiyin
authors.initials: Q
authors.lastname: Fang
authors.forename: Javier A
authors.initials: JA
authors.lastname: Jo
authors.forename: Thanassis
authors.initials: T
authors.lastname: Papaioannou
authors.forename: Amir
authors.initials: A
authors.lastname: Dorafshar
authors.forename: Todd
authors.initials: T
authors.lastname: Reil
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Qiao
authors.forename: J Dennis
authors.initials: JD
authors.lastname: Baker
authors.forename: Julie A
authors.initials: JA
authors.lastname: Freischlag
authors.forename: Michael C
authors.initials: MC
authors.lastname: Fishbein
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000276:immunology* / Q000473:pathology*; D004195:Disease Models, Animal; D007091:Image Processing, Computer-Assisted / Q000295:instrumentation / Q000379:methods; D007834:Lasers; D008264:Macrophages / Q000473:pathology*; D008297:Male; D008856:Microscopy, Fluorescence / Q000295:instrumentation* / Q000379:methods*; D011817:Rabbits