Optical detection of structural changes in human carotid atherosclerotic plaque

Background: Arterial bifurcations are commonly the sites of developing atherosclerotic plaque that lead to arterial occlusions and plaque rupture (myocardial infarctions and strokes). Laser induced fluorescence (LIF) spectroscopy provides an effective nondestructive method supplying spectral information on extracellular matrix (ECM) protein composition, specifically collagen and elastin. Purpose: To investigate regional differences in the ECM proteins -- collagen I, III and elastin in unstable plaque by analyzing data from laser-induced fluorescence spectroscopy of human carotid endarterectomy specimens. Methods: Gels of ECM protein extracts (elastin, collagen types I & III) were measured as reference spectra and internal thoracic artery segments (extra tissue from bypass surgery) were used as tissue controls. Arterial segments and the endarterectomy specimens (n=21) were cut into 5mm cross-sectional rings. Ten fluorescence spectra per sampling area were then recorded at 5 sites per ring with argon laser excitation (357nm) with a penetration depth of 200 μm. Spectra were normalized to maximum intensity and analyzed using multiple regression analysis. Tissue rings were fixed in formalin (within 3 hours of surgery), sectioned and stained with H&E or Movat's Pentachrome for histological analysis. Spectroscopy data were correlated with immunohistology (staining for elastin, collagen types I, III and IV). Results: Quantitative fluorescence for the thoracic arteries revealed a dominant elastin component on the luminal side -- confirmed with immunohistology and known artery structure. Carotid endarterectomy specimens by comparison had a significant decrease in elastin signature and increased collagen type I and III. Arterial spectra were markedly different between the thoracic and carotid specimens. There was also a significant elevation (p<0.05) of collagen type I distal to the bifurcation compared to proximal tissue in the carotid specimens. Conclusion: Fluorescence spectroscopy is an effective method for evaluating ECM (collagen and elastin) associated with vascular remodeling despite the considerable variability in the plaque structure. Consistent regional differences were detected in the carotid specimens.

[1]  M Fitzmaurice,et al.  Laser induced fluorescence spectroscopy of normal and atherosclerotic human aorta using 306–310 nm excitation , 1990, Lasers in surgery and medicine.

[2]  R. Ross.  Atherosclerosis is an inflammatory disease , 1999 .

[3]  C. Chiang,et al.  Autofluorescence spectroscopy for in vivo diagnosis of DMBA-induced hamster buccal pouch pre-cancers and cancers. , 2003, Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology.

[4]  Nirmala Ramanujam,et al.  FLUORESCENCE SPECTROSCOPY IN VIVO 1 Fluorescence Spectroscopy In Vivo , 2000 .

[5]  Koh Arakawa,et al.  Fluorescence Analysis of Biochemical Constituents Identifies Atherosclerotic Plaque With a Thin Fibrous Cap , 2002, Arteriosclerosis, thrombosis, and vascular biology.

[6]  Constantinos Pitris,et al.  Optical imaging of the cervix , 2003, Cancer.

[7]  W S Grundfest,et al.  Discrimination of Human Coronary Artery Atherosclerotic Lipid-Rich Lesions by Time-Resolved Laser-Induced Fluorescence Spectroscopy , 2001, Arteriosclerosis, thrombosis, and vascular biology.

[8]  Maria Drangova,et al.  Optical Detection of Triggered Atherosclerotic Plaque Disruption by Fluorescence Emission Analysis¶ , 2000 .

[9]  M J Berry,et al.  Laser‐Induced Autofluorescence of Human Arteries , 1988, Circulation research.

[10]  V. Fuster,et al.  Clinical Imaging of the High-Risk or Vulnerable Atherosclerotic Plaque , 2001, Circulation research.

[11]  P. Libby.  Inflammation in atherosclerosis , 2002, Nature.

[12]  S. Jimi,et al.  Nonenzymatic glycation and extractability of collagen in human atherosclerotic plaques. , 1995, Atherosclerosis.

[13]  J Tulip,et al.  Laser‐induced fluorescence: III. Quantitative analysis of atherosclerotic plaque content , 1995, Lasers in surgery and medicine.

[14]  K. Seung,et al.  Visualization of coronary atherosclerotic plaques in patients using optical coherence tomography: comparison with intravascular ultrasound. , 2002, Journal of the American College of Cardiology.

[15]  Alexander Christov,et al.  In Vivo Optical Analysis of Quantitative Changes in Collagen and Elastin During Arterial Remodeling¶ , 2005, Photochemistry and photobiology.

[16]  W D Wagner,et al.  A definition of advanced types of atherosclerotic lesions and a histological classification of atherosclerosis. A report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association. , 1995, Arteriosclerosis, thrombosis, and vascular biology.

[17]  Laura Marcu,et al.  Photobleaching of Arterial Fluorescent Compounds: Characterization of Elastin, Collagen and Cholesterol Time‐resolved Spectra during Prolonged Ultraviolet Irradiation , 1999, Photochemistry and photobiology.

[18]  A. Lafont,et al.  Basic aspects of plaque vulnerability , 2003, Heart.

[19]  P. Bernstein,et al.  Noninvasive detection of macular pigments in the human eye. , 2004, Journal of biomedical optics.

[20]  W S Grundfest,et al.  Time-resolved Fluorescence Spectra of Arterial Fluorescent Compounds: Reconstruction with the Laguerre Expansion Technique , 2000, Photochemistry and photobiology.