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Original Research

Quantitative analysis of the side-branch orifice after bifurcation stenting using en-face processing of OCT images

a comparison between Xience V and Resolute Integrity stents

Minami, Yoshiyasua; Wang, Zhaod; Aguirre, Aaron D.c; Lee, Stephene; Uemura, Shirof; Soeda, Tsunenaria; Vergallo, Roccoa; Raffel, Owen C.h; Barlis, Peteri; Itoh, Tomonorig; Lee, Hangb; Fujimoto, Jamesd; Jang, Ik-Kyunga,j

Author Information
doi: 10.1097/MCA.0000000000000319



Stenting for coronary bifurcation lesions is associated with a higher incidence of thrombotic events 1. Potential mechanisms underlying these thrombotic complications include incomplete stent apposition (ISA) 2,3 and nonapposed struts crossing the side-branch (SB) orifice 4. A recent study using optical coherence tomography (OCT) demonstrated that, at midterm follow-up, the neointimal coverage of nonapposed side-branch (NASB) struts crossing the orifice was delayed compared with well-apposed struts 5. Thus, the evaluation and management of NASB struts may help prevent thrombotic complications.

Using phantom models and micro-computed tomography (CT) 6,7, several ex-vivo studies have evaluated stent struts around SB orifices. These analyses enabled quantitative evaluation of SB orifices following stent implantation, providing important preliminary information for selecting the optimal stent type and intervention strategy for bifurcation lesions. However, no method has previously enabled the quantitative evaluation of stent struts around SB orifices in clinical cases. Recently, several studies introduced the utility of three-dimensional (3D) reconstruction of OCT images for the assessment of SB orifices 8–10. This 3D methodology might contribute to the optimization of percutaneous coronary intervention (PCI) in bifurcation lesions 11 by, for example, showing the best strut cell for rewiring 12. However, its utility within the realm of qualitative assessment has been limited so far.

In the present study, we introduce an en-face projection OCT processing for the quantitative assessment of SB orifices and examine the accuracy using a phantom model. We then apply this algorithm to clinical cases of bifurcation stenting to assess the impact of stent design and treatment strategies on the SB orifice area free from NASB struts.


Quantification of side-branch orifice in an en-face projection view

To quantitatively evaluate SB orifices, we developed an algorithm using standard cross-sectional OCT data to create en-face projection images (Fig. 1). En-face images provide the user with a direct view into the SB orifice, and therefore they are useful for measuring orifice dimensions and features. OCT images were first normalized to the range 0–1 by the maximum and minimum values of the OCT pullback for convenience of processing. As OCT is performed by helical-scanning a catheter inside the artery, a depth-resolved tissue intensity profile is generated at each angular position, which is also known as an A-line. We projected each two-dimensional cross-sectional image in polar coordinates into one dimension by averaging intensity values along each A-line between the lumen and a depth of 0.5 mm. The lumen boundary was identified by a robust algorithm reported previously 13. By combining all the projected A-line profiles of the stented region into one image, we created an en-face projection image displayed as a function of pullback distance and the angular position. Because the SB regions have accumulated low intensity, they appear as dark holes in the en-face projection view. The exact boundaries of SB can be segmented automatically by extracting the region with a pixel intensity value lower than a predefined threshold (T=0.3) and with an area larger than another threshold (20 pixels). The segmentation was reviewed and corrected manually by examining the SB orifice in the corresponding cross-sectional view and mapping it back to the en-face view.

Fig. 1:
En-face projection view for quantification of side branches. (a, b) OCT images in polar coordinates were projected to one-dimension curves by averaging intensity values along each A-line between the lumen and a depth of 0.5 m. The side-branch regions have low intensities in the projected curve. (c) By combining all the projected A-line profiles of the stented region into one image, an en-face projection image can be created as a function of pullback distance and the angular position. *Guidewire artifact. OCT, optical coherence tomography.

Ex-vivo phantom model

The accuracy of area measurements obtained from en-face views was validated using a bifurcation phantom model with three side holes (Supplementary Fig. 1, Supplemental digital content 1, OCT images were acquired 15 times across each side hole using a commercially available frequency domain (C7-XR OCT Intravascular Imaging System; St. Jude Medical Inc., St. Paul, Minnesota, USA). The side-hole orifice area was measured on the en-face projection image by an independent investigator who was blinded to the actual size of the side holes. The accuracy of the area measurements was evaluated by a linear regression model regressing the actual value on the estimated area measurements and testing departures of the intercept and slope from 0 and 1, respectively. We also examined whether there were any measured area values outside of the 95% prediction interval over the entire range of the experiment.

In-vivo study population

All in-vivo study participants were selected from the Massachusetts General Hospital (MGH) OCT Registry. We identified 137 cases of bifurcation lesions, with an SB diameter of at least 2 mm on an angiogram and treated with Xience V [an everolimus-eluting stent (EES); Abbott Vascular, Santa Clara, California, USA] or Resolute Integrity [a zotarolimus-eluting stent (ZES); Medtronic, Minneapolis, Minnesota, USA], from August 2010 to January 2014. We excluded cases of restenosis (n=20), cases treated with two stents (n=12), and those with poor image quality (n=17). Finally, we included 42 EES and 46 ZES cases in the analysis. The registry protocol was approved by each institution’s ethics committee, and all patients provided written informed consent.

In-vivo procedure and optical coherence tomography image acquisition

All treatment strategies were implemented at the discretion of the operators at each institution, including decisions with regard to SB dilatation and/or additional stenting. Patients in whom a stent was implanted in the SB were, however, excluded from our study. Offline quantitative coronary angiography was performed to assess the reference and minimal lumen diameters of the target lesions before and after PCI using dedicated software (CASS version 5.10.1; Pie Medical Imaging BV, Maastricht, the Netherlands). OCT images were acquired at the end of PCI using commercially available frequency domain or time domain (M2/M3 Cardiology Imaging System; LightLab Imaging Inc., Westford, Massachusetts, USA) OCT systems. All images were deidentified, digitally stored, and submitted to the MGH-OCT Registry Laboratory for analysis. Quantitative analysis was carried out for every cross-sectional frame using proprietary software (St. Jude Medical) by independent, experienced investigators 14.

In-vivo quantification of side-branch open area in an en-face projection view

Using the en-face projection algorithm, SB orifice area free from stent struts was evaluated in vivo. The stent struts were automatically detected based on a previous method 15 and corrected manually, if necessary. The open area can be computed from the segmented SB and stent struts using stent-specific information (i.e. strut width) from the manufacturers. For the entire task, custom-designed software was developed in MATLAB (The MathWorks Inc., Natick, Massachusetts, USA) to allow users to visualize, annotate, and review the OCT images of SB and stent struts. The SB orifice area (A) and the area obstructed by struts (B) were calculated on the en-face view (Fig. 2). The percent open area was defined as (A−B)/A*100.

Fig. 2:
Definitions. (Left) A representative image of an en-face OCT reconstruction. *Guidewire artifact. (Right) (A) Orifice area; (B) strut area. %Open area was calculated as [(A)−(B)]/(A)*100. OCT, optical coherence tomography.


The SB orifice width was defined as the length between both corners that divides the SB and the main vessel on the cross-sectional view. All parameters were evaluated from the proximal edge to the distal edge of the SB orifice, which were identified on the longitudinal OCT images.

Statistical methods

If normally distributed according to the Kolmogorov–Smirnov test, categorical data were summarized as counts and proportions (%), and continuous data were summarized as mean±SD. Otherwise, median values with lower and upper quartiles were reported. Mean values were compared using the t-test or one-way ANOVA when the data were normally distributed and using the Mann–Whitney U-test or the Kruskal–Wallis test when the data were not normally distributed. Measurement accuracy of en-face projection views was evaluated by means of a linear regression model. Independent risk factors for the lower %open area (below median; <85.5%) were determined by means of a multivariate logistic model. Statistical significance was defined as P less than 0.05. All statistical analyses were carried out with SPSS version 17.0 (SPSS Inc., Chicago, Illinois, USA).


Measurement accuracy of an en-face projection view

The measurement values of three SB holes (actual area: 3.14, 3.97, 4.91 mm2) in ex-vivo phantom were 3.09±0.22 3.79±0.27, 4.87±0.30 mm2, respectively. The estimated area predicted the value accurately in that the observed intercept was not different from 0 (−0.12434±0.22782, P=0.588) and the slope was not different from 1 (1.00896±0.05596, R2=0.88, P=0.874; Fig. 3).

Fig. 3:
Accuracy of area measurement on an en-face image. Horizontal axis: estimated area of mimic side-branch orifice in a phantom model; vertical axis: measured area of mimic side-branch orifice on an en-face projection image.

Baseline characteristics of in-vivo assessment

Of the total 88 cases, 31 (17 EES and 14 ZES) were treated with SB dilatation and 57 (25 EES and 32 ZES) were treated with crossover stenting without SB dilatation (Fig. 4). Baseline characteristics are shown in Table 1. All variables other than the clinical presentation in cases without SB dilatation were comparable between patients treated with EES and those treated with ZES. There was no significant difference in the target vessel or medina classification between lesions treated with EES and those treated with ZES (Table 2). In both prequantitative and postquantitative coronary angiography analysis, the minimal lumen diameter was smaller in the EES group than in the ZES group in cases without SB dilatation. The frequency of use of the kissing-balloon technique (KBT) was significantly higher in the EES group than in the ZES group (82.4 vs. 35.7%, P<0.01; Table 2).

Fig. 4:
Study flow chart. DES, drug-eluting stent; EES, everolimus-eluting stent (Xience V); MGH, Massachusetts General Hospital; OCT, optical coherence tomography; ZES, zotarolimus-eluting stent (Resolute Integrity).
Table 1:
Baseline clinical characteristics
Table 2:
Angiographic and procedural characteristics

Comparison between cases treated with the everolimus-eluting stent versus the zotarolimus-eluting stent

The results of quantitative OCT analysis are shown in Table 3 and Fig. 5. On the analysis using en-face views, the %open area was found to be significantly larger in cases treated with EES compared with ZES [89.2% (83.7–91.3) vs. 84.3% (78.9–87.8), P=0.04] in cases without SB dilatation. However, the %open area was not significantly different between the EES group and the ZES group [89.0% (87.8–90.9) vs. 91.4% (86.1–94.0), P=0.33] in cases with SB dilatation. The difference in %open area was statistically significant between SB dilatation and no SB dilatation in the ZES group [91.4% (86.1–94.0) vs. 84.3% (78.9–87.8), P=0.04], whereas the difference was not significant in the EES group (P=0.58). The representative images are shown in Fig. 6. Multivariate analysis showed that the use of ZES was an independent predictor of a smaller %open area [below median; <85.5%, odds ratio 4.85, 95% confidential interval (1.23–19.1), P=0.02], in addition to small orifice width in no SB dilatation (Table 4).

Table 3:
OCT comparison of open area between EES and ZES
Fig. 5:
Comparison of %open area between EES and ZES. Comparison of %open area measured on the en-face view. Gray column: Xience V (EES); white column: Resolute Integrity (ZES); y-axis: percent of open area; *P=0.04 versus ZES with side-branch (SB) dilatation. EES, everolimus-eluting stent; ZES, zotarolimus-eluting stent.
Fig. 6:
Representative cases. (a, c) A case of no SB dilatation with Xience V (EES). No strut was seen at the center of SB orifice (*) in the (a) longitudinal reconstructed view, (b) cross-sectional view, and (c) en-face view. (d, f) A case of no SB dilatation with Resolute Integrity (ZES). Two struts (white arrow) in the SB orifice were visible in the (e) cross-sectional view. The shape of crossing struts was well depicted in the (f) en-face view. (g, i) A case of SB dilatation after main vessel stenting with Resolute Integrity (ZES). Struts were well eliminated from the (i) center of SB orifice. Stent struts crossing the SB orifice were highlighted by gray color in the en-face view. EES, everolimus-eluting stent; SB, side branch; ZES, zotarolimus-eluting stent.
Table 4:
Independent predictors for smaller %open areaa in cases without SB dilatation

Comparison between single-balloon and kissing-balloon dilatation

Different treatment strategies for the treatment of bifurcation lesions have been compared. The %open area of both single-balloon dilatation [91.1% (83.7–93.6)] and kissing-balloon dilatation [89.4% (87.9–91.0)] was significantly larger compared with no SB dilatation cases [85.5% (81.0–89.5), P=0.02, P=0.02, respectively]. No statistically significant difference was seen in %open area between single-balloon dilatation and kissing-balloon dilatation (P=0.78).


The main findings of this study are as follows: (i) the quantitative evaluation of an SB orifice by en-face projection processing of OCT images was validated using a bifurcation phantom model, and (ii) in-vivo application of the en-face projection processing demonstrated differences in %open area among stent types and treatment strategies. In the no SB dilatation case, the Xience V stent provides a larger %open area compared with the Resolute Integrity stent. A significant difference in the %open area between cases with and without SB dilatation was demonstrated in the Resolute Integrity stent.

Risk for thrombotic complications after percutaneous coronary intervention for bifurcation lesions

Bifurcation lesions remain a challenging subset in PCI because of procedural complexity, and they are associated with worse clinical outcomes, including a higher incidence of stent thrombosis 1. Several pathological studies 4,16 have demonstrated that ISA and uncovered struts crossing the SB orifice can serve as a nidus for stent thrombosis. Indeed, a recent OCT study demonstrated both ISA and NASB struts were not well covered by the neointima in the chronic phase, in contrast to well-apposed struts 5. The incidence of ISA and the percentage of uncovered struts are significantly lower with current generation drug-eluting stents (DESs) compared with first-generation DESs 17,18. However, SB orifices and NASB struts had not previously been well evaluated in vivo because of lack of a diagnostic modality.

Assessment of stent struts around the side-branch orifice in ex-vivo models

Several ex-vivo studies have attempted to quantitatively evaluate stent struts around the SB orifice. Ormiston et al.6 investigated the area of SB orifice obstructed by the residual struts after crush stenting using micro-computed tomographic imaging of a bench-top model. They demonstrated that the obstruction area was dependent on the stenting/ballooning strategy and the stent cell size. Mortier et al.7 evaluated the SB orifice after provisional stenting using a dedicated finite element simulation model. They assessed the SB orifice en face and compared orifice area stenosis due to the remaining struts among different ballooning techniques and stent types. They reported that the modified KBT (two-step dilatation) was better than simultaneous KBT (one-step dilatation), and the results were similar among three stent types [Integrity (Medtronic), Omega (Boston Scientific, Natick, Massachusetts, USA), and Multi-link 8 (Abbott Vascular, Santa Clara, California, USA)]. Another study also reported that the characteristics of the stent platform affected the orifice area free from strut after SB dilatation 19. These studies indicate that quantitative evaluation of the SB orifice and NASB struts in vivo might give new insight into optimal strategies for bifurcation treatment.

In-vivo assessment of side-branch orifice area free from nonapposed strut

To quantitatively evaluate the SB orifice area after stenting in vivo, we developed an algorithm and reconstructed raw OCT digital data into en-face projection images. We demonstrated the accuracy of area measurement on the en-face projection images using a bifurcation phantom model, although important differences exist between a mimic side hole in a phantom model and an SB orifice in a human coronary artery (e.g. angulation between the main vessel and the side branch 10, variation in shape, and border irregularity). Next, we applied the algorithm to actual cases of bifurcation lesion stenting to examine the impact of stent design and treatment strategies on the SB orifice area free from nonapposed struts in vivo, as previous ex-vivo have studies examined. To the best of our knowledge, this is the first study that quantitatively evaluates SB orifices after stenting in consecutive bifurcation cases.

Stent cell design and orifice area free from nonapposed strut

In this study, the %open area in cases with no SB dilatation was significantly larger in the EES group compared with the ZES group, which was confirmed by multivariate analysis. In the provisional approach for bifurcation lesions, if the angiographic results of both the main vessel and the SB are satisfactory after initial stent placement, the SB orifice would not be further dilated 20. Therefore, the SB orifice remains jailed by the struts of stent within the main vessel. In those cases, the number of crossing struts should depend on the stent cell design itself, and the relative position and size between stent struts and the SB orifice. Xience V is a cobalt–chromium-based, open-cell design DES with a narrower strut thickness (81 μm), covered by a 7.8 μm fluoropolymer coating. The Resolute Integrity stent is an open-cell, cobalt–chromium-based DES with a 91 μm strut thickness and a 6 μm polymer. The platform is made with a continuous sinusoid technology, with laser fusion of the adjacent crown 21. We believe that the difference in %open area between the two stents in cases without SB dilatation was mainly caused by these differences in mechanical performance.

Side-branch dilatation and orifice area free from nonapposed strut

Unlike the results in cases without SB dilatation, the %open area was similar between the two stents after SB dilatation. In EES cases, the %open area in cases with SB dilatation was not significantly different from that in those without SB dilatation, indicating that sufficient open area was already achieved without SB dilatation and that additional balloon dilatation of the SB did not further improve the open area. However, the %open area was significantly larger in cases with SB dilatation than in those without SB dilatation in the ZES group, whereas we need further studies to evaluate the importance of SB dilatation in cases treated with ZES.

In contrast to our results, Burzotta et al.19 demonstrated with a virtual simulation model that the %open area after SB dilatation varied among stent types. They reported that the %open area after KBT was better with EES (90.6%) than with Cypher stents (Cordis; Johnson & Johnson, Warren, New Jersey, USA; 84.7%) but was worse with TAXUS Liberte (Boston Scientific; 98.3%) and Endeavor Resolute (Medtronic; 97.2%). Therefore, the %open area after SB dilatation might also be affected by stent design. However, they simulated only a single case for each stent type in a silicon phantom model, without any variety in vessel morphology. Thus, their findings need to be confirmed in a larger number of cases in vivo.

As for the dilatation strategies, we did not find an advantage of KBT over the single-balloon technique with respect to %open area. Foin et al.22 also demonstrated comparable results of SB orifice area free from strut between KBT and single ballooning in a micro-CT computational model.

Clinical implications and future issues

To date, there has been no clinical study that has demonstrated the impact of NASB on long-term clinical outcomes. This is partly because of the lack of a diagnostic modality to quantitatively assess NASB despite development in the field of intracoronary image reconstruction. The recent development of 3D OCT image reconstruction has enabled us to qualitatively evaluate the anatomical structure of bifurcation lesions and struts around the SB orifice after implantation of bioresorbable vascular scaffolds or stents 8–10. These might contribute to the optimization of PCI in bifurcation lesions 11. In addition, a combination of 3D angiography and OCT images obtained using a dedicated software was reported to more accurately measure the SB orifice area by taking into account the angle between the main branch and the SB 23. However, these methods could not quantitatively evaluate stent struts around the SB orifice. In the present study, we report the differences in open area within the SB orifice among different stent types and strategies using a novel approach. This method can be applied to standard intravascular OCT data and is therefore widely applicable with existing clinical OCT systems. We believe that our method should provide information to better understand the mechanisms of restenosis and stent thrombosis at previously treated bifurcation lesions, and will therefore lead to better strategies with optimal stent design and techniques to prevent these complications.


Several limitations should be noted. First, this is not a randomized study but rather a retrospective analysis with limited number of cases from a registry database. Therefore, some underlying differences in patient or procedural characteristics might have affected the results. Second, we did not take into account the SB angulation and plaque burden, as this algorithm is not 3D. In future development, these features may be incorporated. Third, we applied our method in only two cases of left main disease because of the limited utilization of OCT for them in our registry. Fourth, most EES cases with SB dilatation were dilated by KBT. Thus, the results of open area should be interpreted with caution. Finally, because of the small number of cases, we could not examine the impact of %open area on clinical outcomes. Further studies with larger cohorts will be needed to evaluate the clinical impact of our findings.


The accuracy of SB orifice measurements obtained using an en-face image processing algorithm was demonstrated. This novel approach could quantitatively evaluate the area of NASB obstructing the SB orifice after bifurcation stenting in vivo. The SB orifice %open area was larger in the EES group compared with the ZES group after no SB dilatation. However, after SB balloon dilatation, the SB orifice %open area was significantly improved in the ZES group.


The authors thank all the investigators and supporting staff at all sites of the MGH-OCT Registry for their contributions. They also thank Iris A. McNulty, RN, Shankha Mukhopadhyay, MS, and James Chan, MS, for exceptional work in the core laboratory and Russell Joye, AS, for his editorial assistance.

A. Aguirre received support from the American Heart Association (14FTF20380185). Z. Wang and J. Fujimoto are supported in part by NIH R01-CA075289-17. This study was also supported by Michael and Kathryn Park and Gill and Allan Gray.

Conflicts of interest

This study was partly funded by Medtronic Inc. J. Fujimoto receives royalties for intellectual property owned by MIT and licensed to St. Jude Medical. I. Jang reports grants from Medtronic Inc., during the conduct of the study; grants from St. Jude Medical, grants from Boston Scientific, outside the submitted work. For the remaining authors there are no conflicts of interest.


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bifurcation lesion; drug-eluting stent; optical coherence tomography

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