American Heart Journal
Volume 152, Issue 4 , Pages 755.e1-755.e4, October 2006

Measurement of the thickness of the fibrous cap by optical coherence tomography

  • Teruyoshi Kume, MD

      Affiliations

    • Department of Cardiology, Kawasaki Medical School, Kurashiki 701-0192, Japan
    • Corresponding Author InformationReprint requests: Teruyoshi Kume, MD, Department of Cardiology, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192, Japan.
    • ,
  • Takashi Akasaka, MD

      Affiliations

    • Department of Cardiology, Wakayama Medical University, Wakayama 641-8509, Japan
    • ,
  • Takahiro Kawamoto, MD

      Affiliations

    • Department of Cardiology, Kawasaki Medical School, Kurashiki 701-0192, Japan
    • ,
  • Hiroyuki Okura, MD

      Affiliations

    • Department of Cardiology, Kawasaki Medical School, Kurashiki 701-0192, Japan
    • ,
  • Nozomi Watanabe, MD

      Affiliations

    • Department of Cardiology, Kawasaki Medical School, Kurashiki 701-0192, Japan
    • ,
  • Eiji Toyota, MD

      Affiliations

    • Department of Cardiology, Kawasaki Medical School, Kurashiki 701-0192, Japan
    • ,
  • Yoji Neishi, MD

      Affiliations

    • Department of Cardiology, Kawasaki Medical School, Kurashiki 701-0192, Japan
    • ,
  • Renan Sukmawan, MD

      Affiliations

    • Department of Cardiology, Kawasaki Medical School, Kurashiki 701-0192, Japan
    • ,
  • Yoshito Sadahira, MD

      Affiliations

    • Department of Pathology, Kawasaki Medical School, Kurashiki 701-0192, Japan
    • ,
  • Kiyoshi Yoshida, MD

      Affiliations

    • Department of Cardiology, Kawasaki Medical School, Kurashiki 701-0192, Japan

Received 14 January 2006; accepted 6 June 2006. published online 04 September 2006.

Article Outline

Background

Identification of the fibrous cap is important because its thickness is a major determinant of plaque vulnerability in lipid-rich plaque. Thus, a high-resolution imaging technique may be a promising method for the identification of the fibrous cap within lipid-rich plaque. The purpose of this study was to investigate the feasibility of using optical coherence tomography (OCT) to measure the thickness of the fibrous cap within lipid-rich plaque.

Methods and Results

We examined 35 lipid-rich plaques from 102 coronary arterial segments of 38 human cadavers (22 men and 16 women; mean ages, 74 ± 7 years). Optical coherence tomography and corresponding histological images were digitized for measurement of the thickness of fibrous cap, and the results between OCT and histological examination were compared. There was good correlation of the thickness of the fibrous cap between OCT and histological examination (y = 0.97x + 28.49; r = 0.90; P < .001). A Bland-Altman test showed good agreement of the thickness of the fibrous cap between OCT and histological examination (mean difference, −24 ± 44 μm).

Conclusions

Optical coherence tomography provides an accurate representation of the thickness of the fibrous cap and may prove useful in assessing plaque vulnerability in lipid-rich plaque.

 

Autopsy studies have identified several histological characteristics of vulnerable plaques that are prone to rupture and cause acute coronary events. These vulnerable plaques possess (1) a thin fibrous cap, (2) a large lipid pool, and (3) activated macrophages near the fibrous cap.1, 2, 3, 4 Especially, the identification of the fibrous cap is important because the thickness of the fibrous cap is a major determinant of plaque vulnerability in lipid-rich plaque.4, 5, 6 Thus, a high-resolution imaging technique may be a promising method for the identification of the fibrous cap within lipid-rich plaque.

Optical coherence tomography (OCT) has recently been proposed as a high-resolution imaging method.7, 8, 9 The resolution of OCT was approximately 10 to 20 μm, which was about 10 times higher than that of intravascular ultrasound.8 This study investigated the feasibility of using OCT to measure the thickness of the fibrous cap within the lipid-rich plaque.

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Methods 

We examined 102 coronary arterial segments from 38 human cadavers (22 men and 16 women; mean ages, 74 ± 7 years). Of these 38 cadavers, 6 had symptomatic cardiovascular disease (16%). The study protocol was approved by the ethics committee of Kawasaki medical school, and written informed consent was obtained from each family. About 5 cm in length of the proximal site of the 3 major coronary arteries, including the left anterior descending coronary artery, left circumflex artery, and right coronary artery, were obtained from the cadaver at autopsy within 3 hours after death. The surrounding soft tissues were dissected from each specimen. Small arterial perforators and the branches were tied off with sutures, and the distal end of the artery was occluded with a large cork. A 7F sheath was sewn into the proximal end of the artery to complete the closed system. Saline (0.9%), which was kept at a temperature of 37°C, was infused through the side arm of the sheath. The pressure inside the coronary artery was maintained at a physiologic level (60-80 mm Hg) with a syringomanometer connected to the infusion.

Optical coherence tomography images 

The intravascular OCT catheter (ImageWire, LightLab Imaging, Westford, MA) was inserted through the diaphragm of the sheath. Serial images of the OCT were obtained using an automatic pullback device at a rate of 0.5 mm/s. The obtained OCT images were processed and analyzed using proprietary software from LightLab Imaging, Inc, for off-line analysis.

Histological examination 

After OCT imaging, each coronary artery was pressure-fixed in 10% neutral buffered formalin. After fixation for 48 hours, standard paraffin embedding was performed. In every 400 μm of the coronary arteries, 2 series of 4-μm-thick sections were cut and stained with hematoxylin-eosin, elastica van Gieson technique. When the lipid was present in ≥2 quadrants within a plaque assessed by histological examination, it was considered a lipid-rich plaque.

Identification of the fibrous cap 

According to the histological definition, there were 35 lipid-rich plaques from 102 coronary arteries. The thickness of the fibrous cap was measured at the thinnest part of each plaque. Histological images were digitized in the computer to measure the thickness of the fibrous cap. Corresponding OCT images were selected, and the thickness of the fibrous cap were compared between OCT and histological examination. In OCT images, lipid-rich plaques were characterized by signal-poor regions with diffuse borders,7, 9 and the fibrous cap was defined as the minimum distance from the coronary artery lumen to inner border of lipid pool.

Each set of OCT images and histological examinations were analyzed by 2 independent observers. The analyses were compared to study the interobserver variability. Blinded analyses were repeated by the first observer after an interval of at least 4 weeks. The measurements were compared to study the intraobserver variability.

Statistics 

Values are expressed as mean ± SD. The accuracy of OCT measurements compared with histological measurements was assessed with 2 different analyses: (1) linear regression and (2) Bland-Altman analysis of agreement.10 The latter analysis was used to compare the mean difference and SD between the values from OCT and histological examination. The mean difference in measurements represents the bias of OCT relative to histology; the SD indicates a measure of precision of value from OCT compared with that from the histological examination. In these analyses, a value of P < .05 was considered significant.

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Results 

Measurement of the thickness of the fibrous cap 

The thickness of the fibrous cap measured by histological examination ranged from 10 to 450 μm (mean, 138 μm). The thickness of the fibrous cap measured by OCT ranged from 10 to 430 μm (mean, 163 μm). Representative OCT image and corresponding histological image of the fibrous cap within the lipid-rich plaque are shown in Figure 1. There was good correlation of the thickness of the fibrous cap between OCT and histological examination (y = 0.97x + 28.49; r = 0.90; P < .001) (Figure 2). A Bland-Altman test showed good agreement of the thickness of the fibrous cap between OCT and histological examination (mean difference, −24 ± 44 μm).

  • View full-size image.
  • Figure 1. 

    A, Representative example of OCT image. B, Histological examination of corresponding coronary arterial cross-section with elastica van Gieson stain. Arrow indicates fibrous cap; L, lipid core. Scale bar, 1 mm.

  • View full-size image.
  • Figure 2. 

    Comparison of the thickness of the fibrous cap measured by OCT versus histological examination (left panel). Bland-Altman test for OCT vs histological examination in measurement of the thickness of the fibrous cap (right panel).

Reproducibility of measurements using OCT 

For measurements of the thickness of the fibrous cap by OCT, both intraobserver (13 ± 41 μm) and interobserver (20 ± 59 μm) differences were low. Correlation coefficients were high for repeated measurements by the same observer (r = 0.92) and measurements by 2 different observers (r = 0.88).

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Discussion 

In this study, the accuracy of OCT for measuring the thickness of the fibrous cap was tested against histological examinations and was found to be acceptable according to both the correlation study and Bland-Altman analysis. Considering the resolution of OCT, which was 10 μm, the bias of the OCT on the thickness of the fibrous cap was quite acceptable. Recently, OCT has been proposed as a high-resolution intravascular imaging method, providing accurate evaluation of not only coronary arterial plaque but also thrombus.7, 9, 11, 12, 13, 14 Jang et al15 have already reported that the thickness of the fibrous cap assessed by OCT was significantly different between the acute coronary syndrome group and stable angina pectoris group in the living human being. In addition, Cilingiroglu et al16 reported that there was a good correlation in the thickness of the fibrous cap of the apolipoprotein E knockout mice between OCT and histological examination. However, the comparison in the thickness of the fibrous cap from human cadaver between OCT and histological examination has not been examined. To the best of our knowledge, this is the first report to analyze the concordance in the thickness of the fibrous cap from human cadaver between OCT and histological examination.

Many of the determinants of plaque vulnerability are structural abnormalities. Especially, the thickness of the fibrous cap covering the lipid core is related to plaque vulnerability.5, 6, 17, 18 Although, the “vulnerable” value of the thickness of the fibrous cap is a matter of dispute, it has been documented that plaque is prone to rupture when the thickness of the fibrous cap becomes <65 μm.4 Therefore, OCT may prove useful in discriminating vulnerable plaque in lipid-rich plaque.

Limitations 

Measurements during OCT and histological examination were carried out strictly on corresponding sites at the same distance from the side branches used as anatomical landmarks. Any discrepancy related to differences in the measurement position for OCT and histological examination might influence the results.

Optical coherence tomography examinations overestimated the results compared with histological examination. This might be due to a shrinkage artifact in the processing of histological specimens in spite of the use of pressure fixation. However, it has been reported that in vessels with <50% luminal cross-sectional narrowing, histological fixation and processing changed the size of luminal cross-sectional area but did not change absolute wall area.19 Therefore, the effect of histological fixation and processing was not so significant in the measurement of thickness of the fibrous cap.

In this study, we analyzed coronary arteries from cadavers. If OCT is to be used in vivo, heart motion artifacts might represent a potential limitation. Furthermore, it is necessary to establish a blood-free environment for OCT light penetration to the vessel wall.

Conclusions 

Optical coherence tomography provides an accurate representation of the thickness of the fibrous cap and may prove useful in assessing plaque vulnerability in lipid-rich plaque.

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The authors gratefully acknowledge the excellent assistance of all medical personnel in the catheterization laboratory.

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PII: S0002-8703(06)00628-4

doi:10.1016/j.ahj.2006.06.030

American Heart Journal
Volume 152, Issue 4 , Pages 755.e1-755.e4, October 2006

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