Feasibility of Optical Coronary Tomography in Quantitative Measurement of Coronary Arteries With Lipid-Rich Plaque

Abstract

Background: The aim of the present study was to evaluate the feasibility of optical coherence tomography (OCT) for measurement of vessel area in coronary arteries with lipid-rich plaque as compared with intravascular ultrasound (IVUS).

Methods and Results: We investigated 80 coronary artery segments with lipid-rich plaque on OCT and non-attenuated plaque on IVUS. According to the lipid arc on OCT, the plaques were classified into 4 groups: group 1, lipid arc ≤90°; group 2, 90°<lipid arc≤180°; group 3, 180°<lipid arc≤270°; group 4, lipid arc >270°. Vessel circular arcs that could not be identified due to OCT signal attenuation were interpolated using an approximating algorithm. OCT-measured vessel area was well-correlated with IVUS-measured vessel area (R=0.834, P<0.001). On Bland-Altman plot, there was a good agreement between OCT-measured vessel area and IVUS-measured vessel area, although mean difference and limits of agreement increased with increase of lipid arc (mean difference in groups 1–4: –0.21, –0.31, –1.02, and –2.13 mm²; lower limit: –1.49, –3.22, –5.24, and –9.25 mm²; and upper limit: 1.07, 2.60, 3.20, and 4.99 mm²). Intra-observer (R=0.97–0.99, P<0.001) and inter-observer (R=0.97–0.99, P<0.001) reproducibility for OCT measurement of vessel area was excellent.

Conclusions: Like IVUS, OCT can be used to measure vessel area in coronary arteries with lipid-rich plaque. (Circ J 2015; 79: 600–606)

Intravascular optical coherence tomography (OCT) is a light-based imaging technique that can provide high-resolution images of coronary arteries. The spatial resolution of OCT is 10–20 μm, which is approximately 10-fold higher than that of intravascular ultrasound (IVUS).¹ Given that OCT offers excellent contrast between lumen and vessel wall, this technique allows accurate measurement of lumen area.² The shallow penetration depth of OCT (1.5–2 mm), however, limits the measurement of vessel area. Near-infrared light used in OCT is attenuated by lipid.³ Therefore, vessel circumference behind the lipid-rich plaque is not clearly delineated due to shadowing. The unclear vessel circumference is interpolated by interpreter’s inference. Unlike OCT, IVUS has a deep signal penetration (approximately 5 mm), which enables visualization of the entire vessel circumference of coronary arteries.⁴ The measurement of vessel area is essential to assess important features of coronary atherosclerosis such as plaque burden and arterial remodeling.⁵ The aim of the present study was to evaluate the feasibility of OCT for measurement of vessel area in coronary arteries with lipid-rich plaque, as compared with IVUS.

Editorial p 513

Methods

Subjects

We retrospectively screened 100 patients with stable coronary artery disease who underwent OCT and IVUS before any intervention. The target of the present study was non-culprit coronary segment with percent diameter stenosis <70% on angiogram. Then, we identified 80 patients with coronary artery segments that fulfilled the following criteria: (1) de novo coronary plaque; (2) lipid-rich plaque on OCT; and (3) non-attenuated plaque on IVUS. Lipid-rich plaque on OCT was characterized by a signal-poor region with diffuse border.³ Attenuated plaque on IVUS was defined as hypoechoic or mixed atheroma with ultrasound attenuation but without calcification.⁶ Twenty patients with fibrotic plaque, calcification, entire circumferential lipid, intracoronary thrombus, small vessel (lumen diameter <2 mm), large vessel (lumen diameter >4 mm), or poor image quality due to artifacts were excluded. The institutional review board approved the study, and all patients provided written informed consent.

Coronary Angiography

Coronary angiography was performed in the standard manner with a 6-F Judkins guiding catheter. Quantitative coronary angiography (QCA) analysis was performed using a validated automated edge detection algorithm (CAAS-5; Pie Medical, Maastricht, The Netherlands) by an independent investigator (T. Yamano). The reference lumen diameter, minimum lumen diameter, percent diameter stenosis [(1–minimum lumen diameter/reference lumen diameter)×100] were calculated in the view that was the most severe and which was not foreshortened.

OCT

Isosorbide dinitrate (2 mg) was injected into the coronary artery before OCT image acquisition. OCT was performed using ILUMIEN^TM (St. Jude Medical, St. Paul, MN, USA) as reported previously.^7–11 In short, following automatic calibration, an OCT catheter was advanced to the distal portion of the coronary artery over a 0.014-in conventional angioplasty guidewire. After the catheter placement, pre-heated contrast media at 37℃ was flushed through the guiding catheter at a rate of 3–4 ml/s for approximately 3–4 s via an injector pump. When a blood-free image was observed, the OCT imaging core was pulled back over a longitudinal distance up to 50 mm at a rate of 20 mm/s using standalone electronic control of the pullback motor. OCT images (100frames/s) were stored digitally for analysis.

OCT analysis was performed using dedicated off-line review systems (St. Jude Medical). The OCT images were analyzed by an experienced investigator (T. Yamaguchi) to compare with IVUS findings. Recalibration was done before OCT analysis. Plaque characterization was performed using previously validated criteria.^12–16 Lipid core was characterized by a diffusely bordered, signal-poor region. On visual screening, 1 candidate cross-section (frame) was selected for measurement of maximum lipid arc. The lipid arc was measured with a protractor centered in the center of the lumen. According to the lipid arc, the plaques were classified into 4 groups: group 1, lipid arc ≤90°; group 2, 90°<lipid arc≤180°; group 3, 180°<lipid arc≤270°; group 4, lipid arc >270°. Lumen and external elastic membrane (vessel) areas were measured in the frame with maximum lipid arc (Figure 1). In group 1, vessel circular arcs that could not be identified due to signal attenuation caused by lipid tissue were interpolated by referring to identifiable vessel circumference. In groups 2–4, it was interpolated using an approximating algorithm that estimates a center of the vessel through 3 points on the identifiable vessel circumference (Figure 2). Re-measurements of the lumen and vessel areas were performed by another investigator (Y.I.) to assess inter- and intra-observer reproducibility. Both investigators were blinded to the IVUS findings.

Figure 1.

Representative optical coherence tomography and intravascular ultrasound. (A) Group 1, lipid arc=70°; (B) group 2, lipid arc=137°; (C) group 3, lipid arc=205°; (D) group 4, lipid arc=280°.

Figure 2.

Approximating algorithm of vessel circumference. Three points (x, y, z) are placed on the visible circular arc. The central point (x) is connected with the other 2 points (y and z) by straight lines. Through the mid-point of each straight line, a perpendicular line is drawn. Intersection of the 2 perpendicular lines is assumed to be the center of the circle. This is the circular approximation.

IVUS

Isosorbide dinitrate (2 mg) was injected into the coronary artery before IVUS image acquisition. IVUS was performed using Atlantis SR Pro^TM (Boston Scientific, Maple Grove, MN, USA), which consisted of a 40-MHz transducer. The IVUS catheter was advanced to the distal portion of the coronary artery over a 0.014-in conventional angioplasty guidewire and withdrawn to the aorto-ostial junction at a rate of 0.5 mm/s using a motorized pullback device. IVUS images (30frames/s) were stored digitally for analysis.

IVUS analysis was performed using validated planimetry software (EchoPlaque, INDEC Systems, Mountain View, CA, USA). The IVUS images were analyzed by an experienced investigator (Y.S.) to compare with OCT findings. An IVUS frame corresponding to the analyzed OCT frame was identified using the distances from 2 landmarks, such as side branches or calcifications. Lumen area, vessel area, plaque area (vessel-lumen), and plaque burden (plaque/vessel×100) were measured according to the American College of Cardiology Clinical Expert Consensus Document on Standards for Acquisition, Measurement, and Reporting of Intravascular Ultrasound Studies (Figure 1).⁴ Subsequently, re-measurements of those areas were performed by another investigator (T.K.) to assess inter- and intra-observer reproducibility. Both investigators were blinded to the OCT findings.

Statistical Analysis

Statistical analysis was performed using Dr SPSS II for Windows version 11.01J (SPSS Japan, Tokyo, Japan) and MedCalc for Windows, version 12.3.0.0 (MedCalc Software, Mariakerke, Belgium). Categorical variables are presented as absolute numbers and percentages. Continuous variables are presented as mean±SD. The relationships between the OCT and IVUS measurements were investigated using a simple regression analysis. The agreements between the measurements were analyzed using Bland-Altman plot, which showed the differences of each pair of measurements vs. their means with reference lines for the mean difference of all paired measurements. The limits of agreement were defined as mean±1.96 SD of the absolute difference. P<0.05 was considered statistically significant.

Results

Patient Characteristics

Patient characteristics are summarized in Table 1. Mean percent diameter stenosis on coronary angiography was 45±12%. Plaque burden on IVUS was 55±16%.

Table 1. Patient Characteristics

Characteristics	Mean±SD or n (%)
Age (years)	66±10
Male gender	62 (78)
Coronary risk factors
Hypertension	62 (78)
Dyslipidemia	59 (74)
Diabetes mellitus	29 (36)
Current smoker	44 (55)
Vessels
LAD	49 (61)
LCX	6 (8)
RCA	25 (31)
Quantitative coronary angiography
Reference vessel diameter (mm)	3.07±0.64
Minimum lumen diameter (mm)	1.69±0.55
Diameter stenosis (%)	45±12
IVUS measurements
Lumen area (mm2)	6.14±2.33
Vessel area (mm2)	14.28±4.13
Plaque area (mm2)	8.14±3.71
Plaque burden (%)	55±16

IVUS, intravascular ultrasound; LAD, left anterior descending coronary artery; LCX, left circumflex coronary artery; RCA, right coronary artery.

OCT vs. IVUS Measurement

OCT-measured lumen area was well-correlated with IVUS-measured lumen area (R=0.979, P<0.001; Figure 3A). Also, OCT-measured vessel area was well-correlated with IVUS-measured vessel area (R=0.834, P<0.001; Figure 3B). The number of plaques in groups 1–4 was 12, 23, 28, and 17, respectively. On Bland-Altman plot there was an excellent agreement between OCT-measure lumen area and IVUS-measured lumen area in groups 1–4 (Figure 4). In addition, there was good agreement between OCT-measured vessel area and IVUS-measured vessel area, although mean difference and limits of agreement increased with increase of lipid arc (mean difference in groups 1–4: –0.21, –0.31, –1.02, and –2.13 mm², respectively; lower limit: –1.49, –3.22, –5.24, and –9.25 mm², respectively; and upper limit: 1.07, 2.60, 3.20, and 4.99 mm², respectively; Figure 5).

Figure 3.

Regression analysis for measurements of lumen and vessel areas. There was a direct correlation for measurements of (A) lumen and (B) vessel areas between optical coherence tomography (OCT) and intravascular ultrasound (IVUS).

Figure 4.

Bland-Altman analysis for measurement of lumen area. There was (A–D) excellent agreement for measurements of lumen area between optical coherence tomography (OCT) and intravascular ultrasound (IVUS) in groups 1–4.

Figure 5.

Bland-Altman analysis for measurement of vessel area. There was (A–D) good agreement for measurements of vessel area between optical coherence tomography (OCT) and intravascular ultrasound (IVUS) in groups 1–4.

Intra- and Inter-Observer Reproducibility

Intra- and inter-observer reproducibility for measurements of lumen and vessel area were excellent in both OCT (Table 2) and IVUS (Table 3).

Table 2. Reproducibility of Intravascular Ultrasound

	Measurement 1 (mm2)	Measurement 2 (mm2)	Linear regression		Absolute difference (mm2)	Limits of agreement† (mm2)
			R	P-value		Lower	Upper
Intra-observer
Lumen area
Group 1	8.04±2.31	7.97±2.33	0.98	<0.001	0.06±0.31	0.67	−0.55
Group 2	6.20±2.08	6.21±2.07	0.99	<0.001	0.00±0.09	0.18	−0.18
Group 3	5.74±2.08	5.76±2.06	0.99	<0.001	−0.02±0.10	0.18	−0.22
Group 4	5.39±2.53	5.38±2.49	0.99	<0.001	0.01±0.11	0.23	−0.21
Vessel area
Group 1	12.52±2.65	12.47±2.87	0.97	<0.001	0.05±0.50	1.03	−0.93
Group 2	11.75±3.49	12.01±3.62	0.99	<0.001	−0.26±0.44	0.60	−1.12
Group 3	15.79±3.84	15.82±3.71	0.97	<0.001	−0.03±0.67	1.28	−1.34
Group 4	16.49±4.12	16.68±4.09	0.99	<0.001	−0.19±0.41	0.61	−0.99
Inter-observer
Lumen area
Group 1	8.04±2.31	8.04±2.22	0.99	<0.001	0.00±0.20	0.39	−0.39
Group 2	6.20±2.08	6.19±2.05	0.99	<0.001	0.01±0.13	0.26	−0.24
Group 3	5.74±2.08	5.78±2.09	0.99	<0.001	−0.04±0.21	0.37	−0.45
Group 4	5.39±2.53	5.44±2.45	0.99	<0.001	−0.05±0.21	0.36	−0.46
Vessel area
Group 1	12.52±2.65	12.59±2.90	0.98	<0.001	−0.07±0.49	0.89	−1.03
Group 2	11.75±3.49	11.91±3.47	0.97	<0.001	−0.16±0.63	1.07	−1.39
Group 3	15.79±3.84	15.87±3.81	0.99	<0.001	−0.08±0.44	0.78	−0.94
Group 4	16.49±4.12	16.75±4.01	0.98	<0.001	−0.26±0.62	0.96	−1.48

^†Bland-Altman limits of agreement defined as mean±1.96 SD of absolute difference.

Table 3. Reproducibility of Optical Coherence Tomography

	Measurement 1 (mm2)	Measurement 2 (mm2)	Linear regression		Absolute difference (mm2)	Limits of agreement† (mm2)
			R	P-value		Lower	Upper
Intra-observer
Lumen area
Group 1	7.73±2.36	7.73±2.37	0.99	<0.001	0.01±0.03	0.07	−0.05
Group 2	5.88±2.27	5.88±2.27	0.99	<0.001	0.00±0.01	0.02	−0.02
Group 3	5.55±2.20	5.56±2.18	0.99	<0.001	−0.01±0.02	0.03	−0.05
Group 4	5.09±2.56	5.09±2.56	0.99	<0.001	0.00±0.01	0.02	−0.02
Vessel area
Group 1	12.31±2.93	12.71±2.59	0.93	<0.001	−0.40±0.80	1.17	−1.97
Group 2	11.48±3.68	12.14±3.65	0.90	<0.001	−0.66±1.16	1.61	−2.93
Group 3	14.76±3.46	15.30±3.31	0.79	<0.001	−0.55±1.59	2.57	−3.67
Group 4	14.34±4.64	15.07±4.46	0.56	<0.001	−0.73±3.21	5.56	−7.02
Inter-observer
Lumen area
Group 1	7.73±2.36	7.73±2.38	0.99	<0.001	0.01±0.05	0.11	−0.09
Group 2	5.88±2.27	5.88±2.26	0.99	<0.001	0.00±0.03	0.06	−0.06
Group 3	5.55±2.20	5.56±2.19	0.99	<0.001	0.00±0.02	0.04	−0.04
Group 4	5.09±2.56	5.08±2.57	0.99	<0.001	0.01±0.02	0.05	−0.03
Vessel area
Group 1	12.31±2.93	12.23±3.17	0.92	<0.001	0.08±0.88	1.80	−1.64
Group 2	11.48±3.68	11.40±4.01	0.85	<0.001	0.09±1.51	3.05	−2.87
Group 3	14.76±3.46	15.85±3.16	0.57	<0.001	−1.09±2.30	3.42	−5.60
Group 4	14.34±4.63	16.33±4.24	0.45	0.002	−1.98±3.49	4.86	−8.82

^†Bland-Altman limits of agreement defined as mean±1.96 SD of absolute difference.

Discussion

The main findings of the present study were as follows: (1) OCT-measured vessel area was well-correlated with IVUS-measured vessel area; (2) there was a good agreement between OCT-measured vessel area and IVUS-measured vessel area, although mean difference and limits of agreement increased with increase of lipid arc; and (3) intra- and inter-observer reproducibility for measurement of vessel area was excellent for both OCT and IVUS. OCT might be a feasible tool for measuring vessel area in coronary arteries with lipid-rich plaque.

Accuracy of OCT

Intravascular OCT provides accurate quantitative measurements with excellent reproducibility due to its extraordinarily high resolution.^17,18 A phantom model showed that the areas measured with OCT were equal to the actual areas, while the areas measured with IVUS were 8% greater than the actual areas.² In the clinical setting, QCA underestimated coronary lumen diameter (relative reference, −5%) and IVUS overestimated it (relative reference, 9%) in comparison with OCT.² Those data form the basis of quantitative OCT and IVUS measurements.

OCT Limited Penetration Depth

Penetration depth is a term that defines how deeply within tissue it is possible to obtain useable image data. The high resolution of OCT comes at the expense of penetration depth. Near-infrared light with wavelengths ranging from 1,250 to 1,350 nm allows for the creation of OCT images at a microscopic level but limits penetration depth to within 1.5–2.0 mm. The penetration depth is dependent on tissue type. The near-infrared light is attenuated more rapidly by lipid compared with fibrotic or fibrocalcific tissue.¹⁹ The predominant forms of attenuation are scattering and absorption. Shallow penetration depth is a critical limitation of the current OCT systems for measuring exact vessel area.

Interpolation of Vessel Contour

IVUS has a deeper penetration depth than OCT, but signal attenuation can occur with IVUS as well. Calcified tissue blocks the ultrasound signal and reflects it back toward to the transducer. Necrotic core attenuates the signal and precludes visualization of vessel structure behind the plaque. In addition, guidewires and stent struts cause acoustic shadowing, which obscures vessel circumference. Interpolation of the vessel circular arc that is not identified due to signal attenuation, is performed to measure vessel area even in IVUS.²⁰

Clinical Implication of Vessel Area Measurement

Measurements of lumen and vessel area allow us to estimate plaque burden and arterial remodeling. Positive remodeling of the coronary arteries is frequently observed in the culprit lesions in acute coronary syndromes, and it is considered to be a feature of vulnerable plaque.²¹ An IVUS trial showed that a plaque burden ≥70% was an independent predictor of adverse coronary events at 3-year follow-up (hazard ratio, 5.03; 95% CI: 2.51–10.11; P<0.001).²² Moreover, several pharmacologic intervention studies have used the decrease of plaque burden assessed on IVUS as a surrogate marker of the reduction of clinical risk.²³ The accurate measurement of vessel area on intravascular imaging is helpful to assess the instability and development of coronary atherosclerosis.

In addition, measurement of vessel diameter with OCT is important for percutaneous coronary intervention (PCI) guidance in daily clinical practice.^24,25 Reference segments for PCI often have mild or moderate plaque, which prevent visualization of vessel circumference on OCT. The approximating algorithm used in the present study enables estimation of the reference vessel diameter and facilitates choice of the appropriate balloon/stent size for PCI.

Study Limitations

The present study had several limitations. First, the approximating algorithm of vessel circumference cannot be used in coronary arteries with entirely circumferential lipid. Second, the approximating algorithm assumes that everything is a precise circle. If this algorithm was applied to an oval vessel, the calculated vessel area would be larger or smaller than the actual vessel area. Third, the agreement between OCT-measured vessel area and IVUS-measured vessel area may be lower in the coronary artery with positive remodeling compared to negative remodeling, because the coronary artery with positive remodeling is often accompanied by much more lipid-rich plaque. Fourth, the longitudinal resolution in OCT and IVUS is limited. This may have biased the identification of corresponding cross-sections between OCT and IVUS. Fifth, the influence of coronary pulsation on vessel area was not assessed. Corresponding OCT and IVUS were not necessarily acquired during the same phase of the cardiac cycle, because the pullback speed is different between the 2 techniques. Finally, rapid injection of contrast media for OCT increases shear stress, which could induce vasoconstriction. A potential difference in vascular tonus between OCT and IVUS cannot be excluded.

Conclusions

Like IVUS, OCT can be used to measure vessel area in coronary arteries with lipid-rich plaque.

Disclosures

Funding Sources: None. Conflict of Interest: Dr Kubo has received lecture fees from St. Jude Medical. Dr Akasaka has received lecture fees from St. Jude Medical. All other authors report that they have no relationships relevant to the contents of this paper to disclose.

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