Measurement of Collagen and Smooth Muscle Cell Content in Atherosclerotic Plaques Using Polarization-Sensitive Optical Coherence Tomography
Seemantini K. Nadkarni, PhD*, ,*,
Mark C. Pierce, PhD*,,
B. Hyle Park, PhD*,,
Johannes F. de Boer, PhD*,,
Peter Whittaker, PhD||,
Brett E. Bouma, PhD*,,
Jason E. Bressner, BS*,,
Elkan Halpern, PhD ,
Stuart L. Houser, MD and
Guillermo J. Tearney, MD, PhD*,,
* Department of Dermatology
Department of Radiology
Department of Pathology
Wellman Center for Photomedicine, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts
|| Department of Emergency Medicine and Department of Anesthesiology, University of Massachusetts Medical School, Worcester, Massachusetts
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Figure 1 Collagen Birefringence in Atherosclerotic Plaques
(A and E) Optical coherence tomography images of fibrous plaques. (B) Polarization-sensitive optical coherence tomography (PSOCT) image of fibrous plaque showing high birefringence as seen by the rapid transition of the image from black to white corresponding to 0° to 180° phase retardation. (C) Picrosirius red (PSR)-stained histology section showing orange-red fibers (thicker fibers) under polarized light microscopy. (D and H) Trichrome stained histology images. (F) PSOCT image of fibrous plaque showing black region corresponding to low birefringence below the luminal surface. (G) Corresponding PSR-stained histology section showing yellow-green (thinner fibers) under polarized light microscopy. Scale bars = 500 µm.
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Figure 3 Birefringence in an NCFA
(A) Optical coherence tomography image of a necrotic core fibroatheroma (NCFA). (B) Corresponding PSOCT image showing birefringence within the fibrous cap overlying a region of the lipid pool. Cholesterol crystals shown by arrows appear birefringent below the fibrous cap. (C) Corresponding PSR-stained image of the NCFA showing collagen birefringence within the fibrous cap. (D) Trichrome-stained histology. Scale bars = 500 µm. Abbreviations as in Figure 1.
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Figure 5 SMC Birefringence in Atherosclerotic Plaques
(A) Optical coherence tomography image of a fibrous plaque. (B) Corresponding PSOCT image showing high birefringence. (C) Corresponding PSR-stained section shows low collagen content in the plaque under polarized light microscopy. (D) Corresponding histology section stained for alpha-smooth muscle actin shows numerous smooth muscle cells (SMCs) within the fibrous plaque. Scale bars = 500 µm. Abbreviations as in Figure 1.
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Figure 6 Relation Between SMC Content and PSOCT Birefringence
High positive correlation between  and intimal smooth muscle cell (SMC) content is demonstrated in plaques with low (<50%) collagen content (r = 0.74, p < 0.001). The dotted lines show 95% prediction intervals. Abbreviations as in Figure 1.
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, angles averaged over the width of the central region of interest (500 x 200 µm) in the 2 PSOCT images shown in Figures 1B and 1F are plotted as a function of depth. Least-squares fits over a depth of 200 µm for each plot show that PSOCT birefringence measured as the slope as the phase retardation plot is higher (
= 0.04°/µm) for the plaque with depleted collagen (displayed in Figs. 1E to 1H). Abbreviations as in Figure 1.