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PRECLINICAL STUDY

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, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts
Department of Radiology, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts
Department of Pathology, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts
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.

Manuscript received August 3, 2006; revised manuscript received October 31, 2006, accepted November 27, 2006.

^_* Reprint requests and correspondence: Dr. Seemantini K. Nadkarni, Harvard Medical School, Massachusetts General Hospital and Wellman Center for Photomedicine, 40 Blossom Street, BAR 718, Boston, Massachusetts 02114. (Email: snadkarni{at}hms.harvard.edu).

Objectives: The purpose of this study was to investigate the measurement of collagen and smooth muscle cell (SMC) content in atherosclerotic plaques using polarization-sensitive optical coherence tomography (PSOCT).

Background: A method capable of evaluating plaque collagen content and SMC density can provide a measure of the mechanical fidelity of the fibrous cap and can enable the identification of high-risk lesions. Optical coherence tomography has been demonstrated to provide cross-sectional images of tissue microstructure with a resolution of 10 µm. A recently developed technique, PSOCT measures birefringence, a material property that is elevated in tissues such as collagen and SMCs.

Methods: We acquired PSOCT images of 87 aortic plaques obtained from 20 human cadavers. Spatially averaged PSOCT birefringence, , was measured and compared with plaque collagen and SMC content, quantified morphometrically by picrosirius red and smooth muscle actin staining at the corresponding locations.

Results: There was a high positive correlation between PSOCT measurements of and total collagen content in all plaques (r = 0.67, p < 0.001) and in fibrous caps of necrotic core fibroatheromas (r = 0.68, p < 0.001). Polarization-sensitive optical coherence tomography measurements of demonstrated a strong positive correlation with thick collagen fiber content (r = 0.76, p < 0.001) and SMC density (r = 0.74, p < 0.01).

Conclusions: Our results demonstrate that PSOCT enables the measurement of birefringence in plaques and in fibrous caps of necrotic core fibroatheromas. Given its potential to evaluate collagen content, collagen fiber thickness, and SMC density, we anticipate that PSOCT will significantly improve our ability to evaluate plaque stability in patients.

Abbreviations and Acronyms   FA = fibroatheroma   FC = fibrocalcific   NCFA = necrotic core fibroatheroma   OCT = optical coherence tomography   PSOCT = polarization-sensitive optical coherence tomography   ROI = region of interest   PSR = picrosirius red   SMC = smooth muscle cell

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